1

ROOM ENGINEERING DESIGN

WHITE

Author: Ph. Celso Tapia Sánchez

First edition December 2019

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INDEX
PROLOGUE (P.4)
I .- INTRODUCTION (P18)
II .- INTERNATIONAL STANDARDS FOR CLEAN ROOMS (P.47)
III .- THE DESIGN OF CLEAN ROOMS FOR THE MICROELECTRONICS
INDUSTRY (P.62)
IV .- THE DESIGN OF CLEAN ROOMS FOR THE PHARMACEUTICAL INDUSTRY
(P.79)
V .- PHARMACEUTICAL INDUSTRY VALIDATION AND QUALIFICATION (P.108)
VI .- CLEAM ROOM CRITICAL PATIENTS UNIT (UPC) (P.122)
VII .- GENERAL HISTORY OF INFECTIOUS AND IMMUNODEPRESSED
ISOLATES (P.136)
VIII .- FLUID MECHANICS CONCEPTS APPLIED TO CLEAN ROOM (P.149)
IX .- DEVELOPMENT OF P&ID INSTRUMENTATION DIAGRAMS IN CLEAN
ROOMS (P.179)
X .- CONTROL SEQUENCES FOR CLEAN ROOM HVAC SYSTEMS (P.201)
XI .- VAV AND CAV AIR SYSTEMS (P.230)
XII .- HOSPITAL HVAC DESIGN (P.238)
XIII .- CONDENSATION SYSTEMS FOR CLEAN ROOM HVAC SYSTEMS (P.288)
XIV . -ADVANCED AIR HANDLING UNIT SYSTEMS CONFIGURATIONS (P.348)
XV .- ANALYSIS OF CONTROL SYSTEMS FOR HANDLING UNITS IN TROPICAL
AREAS (P.387)
XVI .- UTAS CONFIGURATIONS FOR PHARMACEUTICAL APPLICATIONS (P.405)
XVII .- CONCLUSIONS (P.422)
CLEAN ROOM APPLICATION VIDEOS (P.432)
UMAS SELECTION SOFTWARE

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Dedication
It is difficult to generate a special dedication, because many names come to mind, which were part
of my training, but starting with my grandmother Amanda for the love she gave me when I was little.
To my parents for the patience they had when I lived with them.

To my wife Andrea for the love and the wait of not being able to dedicate time to the family,
especially my two children, who sometimes do not understand what goes through their father's head.

But there are two people to whom I want to mention in a very special way, my dear mother-in-law,
who always gave me her support in the most difficult moments of life.

But there is a man who inserted me into this mysterious world of Air Conditioning, my friend and
first Boss, Mr. Rubén Cespedes, who I was lucky enough to work with twice. I always remember the
three months I was in training at his company and he taught me more than a teacher, more like a
father.

And finally, I hope it serves all those who are future generations, my dear grandson, Tomas Tapia
Sánchez, who knows that since he was born he has been my constant concern.

Celso Tapia

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FOREWORD
In 1945 the need to test filters in gas masks against particles and biological
materials led to the development of counters for particles dispersed in the
environment. The final step, the development of the HEPA filter, took place at
SANDIA laboratories for the Atomic Energy Commission after World War II.
Nuclear particles that would have been fatal to personnel were isolated in
process areas with HEPA filters while allowing air to circulate through them.
Willis Whitfield pioneered the field of cleaning to perform clean work in
confined spaces. Finally the space age with its cleanliness requirements
promoted pollution control technology. In the 60s, documents such as FED STD
209a, NASA SP-5045, “Contamination Control Handbook”, NASA SP-4074,
“Clean Room Technology”, NASA SP-5045, “contamination control principles”
and “AF-TO-” were written. 00-25-203, “Contamination control of aerospace
facilities, US Air Force.” These documents contain principles that are still
relevant today. ISO/TC209 14644-1 is the international designation for
cleanroom cleanliness and incorporates the metric units used in other parts of the
world. Therefore, it is essential to have a certified air conditioning and
ventilation system that guarantees a safe environment for the patient, workers
and visitors.
Among the sites that require greater precision, calculation, evaluation and strict
control of environmental conditions within the HVAC sector is the
pharmaceutical industry. Extraction equipment, ducts, filters, diffusers, among
other systems, must be chosen carefully and based on the elements established
by the applicable regulations, so that the processes are optimal, the products are
of quality, and the personnel remains safe. .

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The pharmaceutical industry is one of the sectors that requires the strictest air
controls in the indoor environment of production areas. The IPSE Regulations
establish the minimum requirements that must be met in the manufacturing
process of medicines marketed in the country, in addition to the specifications
that some products require, such as specific conditions of temperature, humidity
and air quality to be manufactured.
HVAC systems within the pharmaceutical industry are considered critical, as are
purified water and compressed air systems, because they are in direct contact
with the product. Each laboratory has defined methods to carry out the so-called
“good manufacturing practices” (GMP) throughout the production process,
which sometimes usually exceed the minimum requirements of the standard. In
this way, HVAC systems are not exempt from rigorous monitoring and
mandatory requirements when carrying out system validation.
Design
Deciding which HVAC system is correct when designing and installing depends
largely on how the production areas will be classified, which is done based on
the type of medication that you want to manufacture. Basically, there are two
groups of medications: sterile and non-sterile. For each group, the IPSE
standard, in its appendix A (normative), classifies production areas according to
the degree of asepsis necessary for their manufacturing.
Within the group of sterile medications, we can find, among others, all injectable
medications. In the group of non-sterile medications, there are, as
pharmaceutical forms, tablets, capsules, syrups, suspensions, emulsions,
ointments, creams, gels, among others.

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The engineer in charge of designing the HVAC system within this industry must
carry out a preliminary investigation, focused on the type of medication that is to
be manufactured and the classification that corresponds to the area where
production is to be carried out, before beginning to develop calculations or
estimates; This will help select the equipment needed to integrate the system.
In itself, the correct design of the HVAC system is of utmost importance; first,
because it must comply with what is specified in current regulations; second,
because, when the equipment is finally installed, the system itself should not
generate cross contamination, and third, because within the air handling units
and within the ducts there should be no growth of fungi, yeast, bacteria or any
other type. of contamination that compromises the quality of the product or the
safety of personnel.
Cross contamination is one of the most important aspects to avoid in the
pharmaceutical industry. All manufacturing procedures, from receiving raw
materials to obtaining the final product, are designed to avoid cross
contamination; Even the architecture of the plant is designed to meet the same
objective.
Precision . Exact temperature, pressure and humidity ranges are vital to the
result.
One of the most common questions that arise when starting to design the critical
HVAC system for pharmaceutical production areas is determining whether or
not the air that is supplied to the areas can be returned. Logically, it is known
that by returning a certain amount of air, quite considerable energy savings are
achieved. Unfortunately, returns are not always allowed, although, if the same
product is manufactured within the areas and high volume dust is not produced,
it is possible to return it. However, if the products

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manufactured are diverse or a large amount of dust is produced, it is convenient

to extract the air with other equipment independent of the injection and
discharge it into the atmosphere, but not before filtering it to eliminate any
contaminant toxic to the environment.
In the IPSE there are four classifications that, according to the manufacturing
process, define the characteristics that must be met, such as the maximum
number of total particles per cubic meter of air, the maximum number of viable
particles (CFU, colony forming units ) allowed, both in dynamic conditions and
in static conditions, with a particle size of 0.5 and 5 μ m, as well as the
monitoring frequency. The minimum differential pressures that must exist
between areas, whether of the same classification or different, and the direction
of flow that the air must have are also defined. In addition to this, the minimum
air changes per hour and the temperature and relative humidity ranges within the
areas, as well as the necessary entry clothing.
The HVAC system must be designed to meet these requirements. While they are
quite demanding, they are not impossible. The important thing is to correctly
understand the requirements for each classification.
Filtration
A very significant characteristic of HVAC systems within the pharmaceutical
industry is the filtering, both of the air that enters the areas, and of the
extractions and collection of dust. The type of filter, its efficiency or whether it
is terminal, that is, placed at ceiling level, are described in the subindex.
The HVAC system must be designed and integrated in such a way as to comply
with the required area classification in accordance with Appendix A
(Regulatory). Those corresponding to ISO class 5, 6 and 7 must have, at least,
99.97% HEPA terminal filters of 0.3 μ m.

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In the case of ISO-8 class, they must have at least 95% efficiency filters and for
ISO-9 class they must have at least 85% efficiency filters.
The terminal filters mentioned in the standard for ISO classes 5, 6 and 7, in
addition to the efficiency already defined, must have an airtight cabinet, and the
accessories must be installed in a way that facilitates the integrity tests carried
out on the filters. filtered periodically by the validation department. It is
advisable that the filter have a gel seal on its perimeter to achieve airtightness
between the filter and the cabinet; This will provide an acceptable particle count.
The integrity tests carried out on the HEPA terminal filters, with 99.97 percent
efficiency, are done to guarantee that the filters are not broken or have
manufacturing defects. As particle counting in ISO-5 class is continuous during
the applied filling process for injectable medicines, it is of utmost importance to
ensure that the filters trap contaminating particles on their surface.
Within the components of the HVAC system, such as air handlers, air filters
must also be placed in stages; commonly there are three. An air handler that will
serve an ISO-Class 8 production area for non-sterile medications will have
pleated filters with 35 percent efficiency in the first stage; This is to prevent the
accumulation of dust inside the unit and to serve as a protector for the next
filtering stage. In the second filtering stage, filters with 65 to 70 percent
efficiency are usually placed as pre-filters, which will help protect the third
stage, which will finally give the 95 percent efficiency required by the standard.
Some laboratories sometimes require 99.97 percent efficient HEPA filters to be
installed in the third stage, instead of one of the

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95 percent; this, in order to guarantee a particle count much lower than the
minimum specified by the standard; therefore, the 95 percent filter is placed in
the second stage. This is also allowed by the authorities.
During extractions, care must be taken to ensure that the air discharged into the
atmosphere does not contain medication residues. For this, the air must be
filtered with an efficiency similar to that of injection to avoid, as already
mentioned, the passage of contaminants into the environment.
It is necessary to remember that there is a very varied number of medications
that can be toxic, such as hormonal ones, which can cause considerable effects
on the human body if subjected to prolonged exposure. It is important to
mention that the extraction discharge ducts and dust collectors must be
constantly monitored through easily accessible sampling ports.
Filters should be changed according to a validated maintenance schedule. There
must be a standard operating procedure that defines how and when it should be
carried out. The standard requires that differential pressure gauges be installed in
all equipment that contains filters, whose reading must be recorded weekly to
prevent the filters from collapsing if they are too saturated. Dirty filters should
not be thrown away; They must be removed carefully, without shaking them, to
finally take them to confinement.

air changes
The calculation of the amount of air to be supplied must be carried out
respecting the air changes per hour specified in the standard.

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A calculation of sensitive and latent thermal loads must also be carried out, both
indoors and outdoors, in summer and winter; consider the number of people
working per shift, the number of motors belonging to the production equipment,
the incidence of solar radiation on the exterior walls (when applicable) and the
heat generated by the product when it is manufactured at high temperatures.
Of the two results obtained, whether due to changes or thermal loads, the greater
should always be taken; Otherwise, there would be a risk of complying with the
established changes, but falling short in the cooling or heating capacity of the
equipment, and that they never provide the desired temperature.
Air tightness . The better the door seal, the higher the differential pressure and
the lower the air changes per hour.
Flow directions
The directions of the air flow of the infiltrations through the doors are defined
by considering whether the area is negative or positive, according to its
classification, or if too much dust is generated within the areas, such as in the
weighing or mixing areas.
The doors used within the pharmaceutical industry have a perimeter seal that
allows a fixed pressure to be maintained as long as they are kept closed. If the
amount of air to be supplied and the amount of infiltration air that enters or
leaves through the doors is known, it is possible to calculate the return or
extraction air flow rate, as appropriate. For example, if you want to know the
amount of air to be supplied to a particular room and you also want to know the
amount of air that can be returned, the first thing you need to know is the
volume of the room in question. So, if you have a value of 30 cubic meters, the
next thing is to multiply it by the air changes per hour defined by the standard,
according to the classification; for the purposes of this

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For example, a minimum of 10 changes per hour will be used. The result of
these data would be 300 m³/h, which indicates the air flow to be supplied to the
area to comply with the changes. Now, if there is also an air infiltration of 100
m³/h through the door cracks, the result would be 400 m³/h of total air supplied.
In summary, the amount of air that will come out through the injection diffuser
will be 300 m³/h and the amount of air through the return grille will be 400 m³/h;
Thus, the material balance or volumetric flow is fulfilled.
On the other hand, if you had not only one room, but ten, the calculations would
have to be developed for each of them and finally add the total amount of air,
which will indicate the amount of air that the handling unit or the unit would
have to move. extraction equipment. The infiltration air flow is calculated based
on the area of air passage through the door slots, with respect to a passage speed.
Differential pressures
According to ISO 14.644-1 , given classification corresponds to a pressure
differential; The better the seal on the doors, the greater the pressure differential.
If the doors are not pharmaceutical grade, the lack of seal can be compensated
for by increasing air changes per hour; This will raise the differential pressure
with respect to the adjacent area; However, if there is very high pressure, it will
be difficult to open or keep the doors closed.
To know if the corresponding minimum differential pressures are being met,
boards must be located within the areas where it is possible to place differential
pressure gauges for each door in each area. Readings should be taken daily to
rule out any problems related to the performance of the HVAC system.
Temperature and humidity control

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Temperature control is achieved by forcing air through cooling coils, either
direct expansion (refrigerant gas) or through a hydronic chilled or hot water
system.
Although the standard calls for maintaining a temperature range of 18 to 25
degrees Celsius for all classifications, it does not mean that a constant
temperature of 18 degrees Celsius in summer or 25 degrees in winter must be
maintained, unless the conditions of manufacturing of the product so require. It
is then possible to maintain a temperature of, for example, 22 °C, ± 2 degrees, to
avoid excessive energy consumption and favor working conditions for
production operators.
In the case of warehouses, whether for raw materials or finished products, the
temperature conditions must guarantee the adequate quality of the product. Most
medications and supplies indicate on their labels that they should be stored in a
cool, dry place at less than 30 degrees Celsius. Inside the warehouses it must be
checked that, during the time the medicine is in storage, the interior air never
exceeds 30 degrees.
Storage areas must be designed and constructed to ensure good storage
practices; They must comply with the conditions of cleanliness, temperature and
relative humidity required by the type of inputs or products, and carry out their
control, monitoring and verification.
Controlling relative humidity is more complex, since there are different internal
and external factors that complicate it. Although the range varies between 30
and 65 percent, which seems quite wide, the simple fact that it is raining outside
considerably modifies indoor conditions if the fresh air coming from outside is
significant. They exist in the

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market dehumidifying equipment or steam humidifiers, which can be installed
to control this variable. The most used equipment to dehumidify the air that
enters the areas is the desiccant wheel, based on silica gel, where reactivation is
carried out with hot air.
Temperature and relative humidity must be constantly monitored and
documented before manufacturing a batch and during the manufacturing
process.
Equipment
• Air-handling unit
Although there are different manufacturers of air handling units, it is important
that the unit installed is pharmaceutical grade, due to the characteristics they
present; For example, it is recommended that the modules be made of 2-inch
extracted aluminum profiles, joined by cast aluminum corners. Double-wall
panels, galvanized steel, aluminum or stainless steel sheets, 2 inches thick,
completely coated with weatherproof paint should also be used if they are placed
outdoors. Each module has completely smooth interior surfaces to facilitate
cleaning and maintenance tasks, and prevent microbiological growth. The doors
are constructed, like the panels, with a hermetic seal and in one piece. Inspection
windows must be constructed of double polycarbonate, with an internal fixing
system. Hinges and locks must be constructed with materials that avoid thermal
bridges, with differential pressure gauges in each filter section. In sum, the unit
must be able to withstand a pressure of between 6 and 8 inches of water column
to ensure that it meets the allowable leakage limit.

• Extraction units and dust collectors

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The extraction units have a similar construction to the air supply units, except
that they only have the centrifugal extraction fan and the filter section. The
filters in these units should be located before the exhaust fan to avoid medication
fouling in the motor or in the fan itself.
Dust collectors fulfill the specific function of vacuuming the dust generated
during the manufacture of a medicine; However, as it is part of an HVAC
system, it has to meet the characteristics of pharmaceutical grade equipment.
Production areas in which dust is generated (sampling, weighing, mixing or
other process) must have dust extraction and collection systems that, by design,
avoid cross contamination and the environment.
The first thing to know before designing a dust collection system for the
pharmaceutical industry are the characteristics of the dust generated during
production; for example, the size and density of the dust particles, whether it is
hygroscopic or toxic, such as hormonal or penicillin, to which some people are
allergic; In this case, the system must have a method of safely changing (bag-in
bag-out) filters located in the dust collector or may use a highly explosive active
ingredient.
• Ducts
Injection, return or extraction ducts are commonly constructed of galvanized
sheet of the caliber corresponding to the dimensions of the duct, except in those
systems where another type of material is specified. Only exposed ductwork
within manufacturing areas will be stainless steel.

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Some pharmaceutical laboratories tend to prefer TDC (Transverse Duct
Connections) flanged type ducts for the following reasons:
1. Economic savings: being more rigid, it allows the use of thinner sheet gauges
2. Energy savings: due to the use of gaskets between flanges
The calculation of flanged ducts allows the use of smaller gauges thanks to the
rigidity obtained with TDC type flanges; According to studies carried out,
material savings are approximately 30 percent. For example, with a 2-inch water
column pressure system, in a duct measuring 38 inches x 20 inches and 4 feet
long, if a zeta-clip is used, a 22 gauge is required, equivalent to 23.2 kilograms
of sheet; On the other hand, if TDC type flanged duct is used, 24 gauge is
required, equivalent to 16.5 kilograms of sheet.
The design of these ducts allows them to be quickly connected, without
generating noise due to hammering. The rigidity of the TDC type duct also
allows the distance between supports to be extended. The quick connection
system of the duct sections only requires 8 screws and clips, in addition to
facilitating maintenance and cleaning tasks. These savings are important because
specialized pharmaceutical-grade equipment is typically priced higher than
commercial-grade equipment.
A seal that is resistant to environmental conditions and, above all, prevents the
growth of fungi, yeast or bacteria must be applied to all duct joints. Once the
ducts are installed, tightness tests must be carried out to ensure that there is only
a minimum allowable leak, in accordance with the design pressure.
Air distribution
Air distribution is carried out by means of diffusers placed on the ceiling, while
air return or extraction is carried out with grilles located 30 centimeters above
floor level. The objective of

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This is achieving a sweep of the production area with the supply air, trapping
the suspended particles and directing them towards the grilles so that they are
finally captured by the equipment filter.
An important characteristic of these accessories is that they must be placed flush
with the ceiling or wall, avoiding edges on the fastening frames where dust can
accumulate. The materials can be aluminum if they are installed in warehouses;
In the case of critical or aseptic areas, the diffusers and grilles can be made of
stainless steel so that they can be cleaned periodically with sanitizer.
HVAC System Air Balancing
All HVAC systems in the industry must be balanced by dampers to ensure that
the required amount of air passes through the diffusers or return grilles.
However, in the pharmaceutical industry this procedure is very important, since
not only are the necessary flow rates obtained, but a good air balance is used to
obtain differential pressures and air flow directions that will avoid cross
contamination, as requires the standard.
Control and automation
Although a specific type of control of the critical HVAC system is not
mentioned, it is clear that temperature and humidity conditions must be
maintained and monitored, as well as differential pressures and air flow
directions in production areas. The control of these conditions can be carried out
in a simple way or, if desired, it is possible to use a central control that keeps the
system balanced when the doors are left open for long periods of time and the
differential pressures do not recover during the following 20 seconds; If this
were to occur and the system was unable to compensate for pressure losses, an
audiovisual alarm would be issued to correct the problem as far as possible.

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Installing variable frequency drives on equipment motors makes it easier to
balance the air system and also maintains a constant flow, even when the air
filters become saturated.
Validation
Validation is an essential element for GMP compliance, allowing the
functionality of the HVAC system to be demonstrated. This is a set of
qualifications carried out by specialists in the sector. Qualification is defined as
the performance of specific tests based on scientific knowledge to demonstrate
that equipment, critical systems, facilities, personnel and suppliers meet the
previously established requirements, and must be concluded before validating
the processes.
• Recommended evaluations
Of design. It is the documented evidence that demonstrates that the proposed
design of facilities, systems and equipment is suitable for the intended purpose.
Of installation. It is documented evidence that facilities, systems and equipment
have been installed in accordance with previously established design
specifications.
Of operation. It is the documented evidence that demonstrates that equipment,
facilities and systems operate consistently, in accordance with established design
specifications.
Performance. It is documented evidence that facilities, systems, and equipment
perform in compliance with previously established acceptance criteria.
In itself, the design, operation and maintenance of a critical HVAC system for
the pharmaceutical sector is a challenge, as it must be constantly monitored and
validated to allow the work carried out there to continue.

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INTRODUCTION
The clean room is a modern phenomenon. Although the roots of clean design and
management go back more than 100 years and are rooted in infection control in hospitals, the
need for a clean environment for industrial manufacturing is a requirement of modern society.
The use of clean rooms is diverse and shown in Table 1.1 is a selection of products that are
now being made clean rooms, or that require pollution control facilities. It can be seen that the
clean room requirement can be broadly divided into two. The first is that inanimate particles
are a problem and where their presence, even in submicron sizes, can prevent a product from
functioning or reduce its useful life. The second group requires the absence of particles
carrying microorganisms whose growth in the product (or in a hospitalized patient) could lead
to human infection. It can also be seen that many of the examples given are recent innovations
and this list will certainly be added to in the future, with there being a considerable increase in
demand for these types of rooms.
Table 1.1
Electronics Computers LCD screens, LED screens
Semiconductors Production of integrated circuits used in computer memory
and control

Micromechanics Gyroscopes, Miniature Bearings

Optical lenses Photographic film, laser equipment

Biotechnology Production of antibiotics, genetic engineering.

Pharmacy Sterile pharmaceuticals

Medical devices Heart valves, cardiac bypass systems

Food and drink Disease-free food and drink

Hospitable Isolation of contagious patients, operating rooms

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THE HISTORY OF CLEAN ROOMS
It is clear that the first clean rooms were in hospitals. The work of Pasteur, Koch, Lister and
other pioneering microbiologists and surgeons more than a hundred years ago established that
bacteria cause wound infections. Therefore, it was deduced that the removal of bacteria from
the hospital and, in particular, the operating room should prevent infection. This was the
scientific basis of the first clean rooms. Lister substantially reduced infection in his operating
room at the Royal Infirmary, Glasgow, by using an antiseptic solution (carbolic acid) on the
surgeon's instruments, wounds and hands. He attempted to prevent airborne infections by
spraying carbolic acid into the air. However, their attempts at "cleaning" were accomplished
by antiseptics and progress toward modern clean rooms was through the path leading to the
adoption of aseptic techniques, ie. sterilization of the wound, instruments and the use of
surgical gloves, masks and gowns. These latter techniques remain the basis of many clean
room techniques today.
Although the clean rooms of yesteryear had similarities to modern chambers, a major
omission was positive ventilation by filtered air. The use of ventilation, albeit the natural type,
to reduce bacterial infection had been advocated by the likes of Florence Nightingale and
mechanical ventilation was provided in the hospital designed for Crimea by Brunel in 1855.
However, artificial ventilation was rare until around the 1960s.
Figure 1 .1 shows that ventilation was used to achieve the comfort and hygiene of many
designs advocated at the time, and later, for hospital ventilation.
Not clearly distinguishing between the two, it was only towards the end of World War II that
ventilation in hospitals was being clearly advocated for pollution control. The problems of
airborne infection of people in crowded situations that occurred in times of war, e.g. e.g.
Submarines, bomb shelters and army barracks were studied. Room ventilation with respect to
infection, the invention of bacterial plaque sampling, and particle aerodynamics were studied
during World War II. Much of the early postwar work was carried out in operating rooms and
burn rooms, and by the early 1960s most of the principles dictating the performance of
conventional turbulent-ventilated rooms were known, e.g. example, the

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airflow patterns with respect to the type and placement of air diffusers and exhaust
extractions; the effect of a temperature difference between the incoming and ambient air; the
effect of air supply volume on dilution of air pollution; Air filter efficiency and control air
movement between areas. Knowledge had advanced well enough for a guide to the design of
an operating theater ventilation system to be included in a United Kingdom, Medical
Research Council Report published in 1962. It was also established that people were the
source of airborne bacteria, which disperse on the skin, and that open-weave cotton clothing
did little to prevent dispersion.
Directional Airflow is key to efficiently removing air pollution from a hospital.
Sir John Simon, who wrote in 1864 that ventilation must 'flow from inlet to outlet' and that
this could only be achieved by an artificial supply system by which "the currents are
decisively regulated". The Royal Victoria Hospital in Belfast, Northern Ireland, was built at
the end of the previous century, with a ventilation system intended to achieve this, but the
understanding of moving air was insufficient to produce the desired result.
Bourdillon and Colebrook's work, published in 1946, described a brewing station in which
there were 20 air changes per hour of filtered air, where the room was pressurized relative to
the outside areas. They also discussed the piston effect in which air forms layers that push
down very slowly to cause draft and that push dirty air in front of them as they go. They
discussed the possibility of using 60 or more air changes per hour and reported that laboratory
tests gave a 'sudden, disappearing bacterial cloud'. They did not go further with this idea, due
to the high cost of supplying large quantities of air in a hospital.

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FIGURE 1 .1. Hospital room ventilation in the 1920s. A patient can inhale fresh air from
the funnel. The dirty air on the ground was extracted through another funnel.

Similar advances were being made in the engineering industries. The development of the first
clean rooms for industrial manufacturing largely began during World War II in the United
States and the United Kingdom primarily in an attempt to improve the quality and reliability
of instrumentation used in weapons, tanks and aircraft.
It was warned that the cleanliness of the production environment had to be improved or items
such as pump sights and precision bearings would malfunction. At that time clean rooms were
built that copied the design and practices of the operating room. Anyway, it was soon realized
that "bacteria-free" was not the same as "particle-free."
Therefore, great effort was made to ensure that materials and surfaces did not generate
particles, but it was not fully appreciated that the dispersion into the air of large quantities of
particles by machines and people had to be removed by large quantities of air. pure.

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The peaceful and war uses of the nuclear reaction, as well as biological and chemical
products. War research was the driving force for the production of high-efficiency particulate
air (HEPA) filters that were necessary to contain dangerous microbial or radioactive
contaminants, their availability allowed clean rooms to be supplied with air and low levels of
pollution in the air.
Rooms with large volumes of well-filtered air supplied by ceiling diffusers were built between
1955 and the early 1960s, much of the impetus for the construction of such rooms being the
requirement to build inertial guidance systems.
CLEAN ROOMS
What is a clean room?
It is clear that a clean room is a room that is clean. However, a clean room now has a special
meaning and is defined in Federal Rule 209E as:
`A room in which the concentration of particles in the air is controlled and which contains one
or more clean zones.
And in ISO 14644-1:
“A room in which the concentration of particles in the air is controlled, and which is
constructed and used in such a way as to minimize the introduction, generation and retention
of particles within the room and in which other relevant parameters, e.g. Temperature,
humidity and pressure are controlled as necessary.”
CLASSIFICATION OF CLEAN ROOMS
Definition of Clean Rooms : Federal Standard 209E defines a clean room as a room in which
the concentration of particles in the air is controlled to specific limits. British Standard BS
5295 defines a clean room as a room with particle contamination control, designed and used
in such a way as to minimize the introduction, generation and retention of particles within the
room, and in which the temperature, humidity , airflow patterns, air movement and pressure
are controlled. Other relevant parameters such as temperature, humidity and pressure are
controlled according to specifications and in ISO 14644-1 as: “A room in which the
concentration of

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particles in the air is controlled, and which is prepared and used in a way that minimizes the
introduction, generation and retention of particles inside the room and in which other particles
and relevant parameters, such as temperature, humidity and pressure, are controlled. as
necessary".
Classification of Clean Rooms: Clean rooms are classified according to the cleanliness of
the air. The most applied method is that indicated in the versions of US FEDERAL
STANDARD 209 up to edition “E” Table 1.2. Table 1.2 shows the simplified cleanroom class
classification according to US FEDERAL STANDARD 209E. The most easily understood
and universally applied method is that suggested by Federal Standard 209E, in which the
number of particles equal to or greater than 0.5 microns measured in a cubic foot of air
designates the class number.

Table 1.2.a. Limit class according to US Federal Standard 209E for clean rooms

For example, a class 100,000 clean room limits the concentration of air particles equal to or
greater than 0.5 microns to 100,000 particles in a cubic foot of air, in the English system the
class indicates the number of particles per cubic foot.

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Table 1.2.B. Class and particles per m3

LIMIT CLASS OF CLEAN ROOMS

ACCORDING TO ISO14644-1
In the standard classification ISO 14644-1"Classification of Air Cleanliness" is based on the
formula.

where:
Cn =Maximum permitted number of particles per cubic meter equal to or greater than the
specified particle size, rounded to the nearest whole number.
N =It is the ISO class number, which must be a multiple of 0.1 and must be 9 or less.
D = is the particle size in micrometers.

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Size ofj particle measured (um) cillas in

(I lefteach mi )
class
0.1pm 0.3pm 0.5pm 5 pm
0.2 p.m.
1 1.240 265 106 35.3
10 12.400 2.650 1.060 353
100 26.500 10.600 3.530
1000 35.300 247
10000 353.000 2.470
100000 3.350.000 24.700

APPLICATIONS OF CLEAN ROOMS

Clean Rooms for Different Industries.
The more susceptible the product is to contamination, the stricter the standard will be. The
table below shows a selection of products that are now being manufactured in clean rooms, or
that require contamination control facilities.
Many industries and institutions use laboratories and clean rooms. In figure 1.2 you can see
the demand for clean rooms:

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% of clean room manufacturing

■ Hospitals ■ Meals ■ Automobiles

■ Aerospace ■ Semiconductor suppliers ■ Medical services

■ ■ Pharmaceutical laboratories ■ Semiconductors

Electronics
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Fig 1.2 Distribution of clean rooms according to the type of industry .

Application Considerations
Hospitals. Clean rooms in hospitals are essential for controlling bacteria that can cause
infections in patients undergoing therapy or recovery. Hospital infections are among the top
ten causes of death in the United States. The minimum purity of the air entering the
operating room is 95%, with a particle filter of up to 0.3 microns. A filter suitable for a
surgery room costs around USD 250, and a surgery room requires a bank of filters, (33%
pre-filter and 66% or 95% filter).
Pharmaceutical industry.
The two most used standards concerning clean rooms for the pharmaceutical industry are
the European Union Guide to Good Manufacturing Practice (EU

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GGMP) and the Federal Drug Association (FDA) in the United States. The FDA guidelines
only specify a minimum of 230 changes per hour for controlled areas without specifically
specifying it. For example, an ISO 7 clean room is controlled to allow no more than 10,000
particles of 0.5 microns or larger per cubic foot of air volume. Cleanroom particle counting
is periodically performed to maintain the room sterile.
CLASSES OF CLEAN ROOMS.
They are clean rooms with turbulent air flow and laminar air flow.
Unidirectional airflow rooms . Laminar air flow is used when low concentrations of
particles and bacteria in the air are required.
This air flow pattern is in one direction, usually horizontal or vertical Figure 2 at a uniform
speed between 0.3 and 0.45 meters per second and throughout the entire space. Classes 100
and lower have unidirectional or laminar airflow arrangements.

Figure 2. Flow Lines in Clean Rooms (a) unidirectional and (b) non-unidirectional

Turbulent air flow . It is non-unidirectional because it has varying speed, multi-pass

circulation, or non-parallel flow direction. Conventional flow in class 1000, 10000, 100,000
rooms have non-unidirectional or mixed arrangements. Figure 2b is a diagram of a simple
ventilated clean room

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conventionally. A typical turbulent airflow room such as offices, warehouses, etc., would
have between 2 and 10 air changes per hour; A clean room would have between 20 and 60.
This additional air supply is provided to dilute to an acceptable concentration.
Types of clean areas
Clean areas can be divided into four main types. These are shown in a diagram that is
formed from Figures 3-6 and are as follows:
1. Conventional . These clean rooms are also known as turbulently ventilated or non-
unidirectional, flowing and distinguished by their air supply method. As can be seen in
Figure 3, this is of the conventional type, the air is supplied by air diffusers or filters on the
ceiling.
2. Unidirectional flow. This was previously known as laminar flow. As can be seen from
Figure 4, clean air is supplied from a high efficiency filter bank and passes unidirectionally
through the room.
3. Mixed flow . As shown in Figure 5, this type of clean room is conventionally ventilated,
but where the product is exposed to contamination, a unidirectional flow cabinet or
workstation is used.
4. Isolators or microenvironments . These are used within a clean room to give
maximum level of protection against contamination. In Figure 6, the isolator is shown to
have a unidirectional air supply, but this may be a conventional turbulent flow type.

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FIGURE 3 Conventional (non-unidirectional) airflow cleaning paths.

FIGURE 4, Laminar air flow, unidirectional

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FIGURE 5, Mixed flow

FIGURE 6, Isolators or microenvironments

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Conventionally Ventilated Clean Rooms Shown in Figure 7 is a diagram of a simple

conventionally ventilated clean room. The general ventilation method used in this type of clean
room is similar to that found in offices, shops, etc., as the air is supplied by an air conditioning
plant through diffusers in the ceiling. However, a clean room differs from an ordinary
ventilated room in several ways:
1) Greater air supply : an office or store will be supplied with sufficient air to achieve
comfort conditions; this may be in the region of 2 to 10 air changes per hour. A typical
conventionally ventilated clean room is likely to have between 20 and 60 air changes per hour.
This additional air supply is provided primarily to dilute the contamination produced in the
room to an acceptable concentration.

FIGURE 7, Conventional clean room ventilation

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2) High efficiency filters : a clean room uses much more efficient filters than those used in
offices, etc. Clean room filters would typically be greater than 99.97% efficient at removing
particles larger than 0.3 microns from the room air supply.
These filters are known as high-efficiency particulate air (HEPA) filters, although ultra-low
particulate air (ULPA) filters, which have higher efficiency, are used in areas of
microelectronic manufacturing.

3) Terminal Air Filters – High-efficiency filters used in clean rooms are installed at air
discharge points in the room. In air conditioning systems used in offices, etc. The filters will be
placed directly after the ventilation floor, but particles can be induced into the air supply ducts
or leave the duct surfaces and therefore pass into the room.
4) Room pressurization and passage grilles – To ensure that air does not pass from adjacent
dirtier areas into the clean room, the clean room is positively pressurized with respect to these
dirtier areas. This is done by extracting less air from the room than it is supplied, or by
extracting the supplied air in zones. To achieve the correct pressure and allow designed air
movement from the cleanest to the least clean rooms in a suite, vents or dampers are usually
seen at a low level on walls or doors.
Another indication of a clean room is the type of surface finish. The room will be built with
materials that do not generate particles and are easy to clean. Surfaces will be constructed in
such a way that they are accessible for cleaning and do not harbor dirt in crevices, for example.
openwork floors and recessed lighting.
Cleanliness in the air of a conventionally ventilated clean room depends on the quantity and
quality of the air supplied to the room and the efficiency of the mixing of the air.

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air. Generally speaking, a clean room will have sufficient air supply to achieve good mixing
and the air quality of the room will depend on the air supply quantity and quality. It is
important to understand that conventional cleaning of a ventilated clean room depends on the
volume of air supplied per unit of time and not the rate of air change.
Cleanliness also depends on the generation of contamination within the room. that is, the
machinery and people who work in the room. With more people in the clean room, more
pollution is generated in the air.
A typical type of vertical flow clean room is shown in Figure 8. It can be seen that the air is
supplied from a full bank of high efficiency filters located in the ceiling and this flows
vertically through the room and exits through open grill floors. The air shown in the figure
flows through the entire floor area, but it is common to find rooms in which the air returns
through grilles that are distributed across the floor. If the floor area is not too large, the grates
can alternatively be placed at a lower level on the walls. The exhaust air is recirculated, mixed
with some fresh makeup air, and supplied to the room through high-efficiency filters in the
ceiling of the room.

Fig. 8, Vertical unidirectional flow clean room

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Cabinet and containment rooms
Figure 9 shows an example of a containment room that could be used to work with
microorganisms that are dangerous to the health of the personnel who work there, or to anyone
who passes by the room. It can be seen that clean air is supplied to the room, but more air must
be removed from the room so that the room becomes negative pressure and air will always
flow into the room.
The air that is extracted must be filtered through a high-efficiency HEPA filter before being
discharged outside or inside this room, there will be a safety cabinet in which the
microorganisms are located.

Fig. 9 Containment room

In a room where there is not a very high risk, a Class I or Class II cabinet is generally used. In
a high risk area a Class III cabinet would be used, as shown in Figure 10(a), 10(b) and 10(c),
where is a schematic representation of these three types of cabinets showing their principles. of
air flow and insulation. If handling in the cabinet requires clean conditions, then a Class II
cabinet will be used, as this type is designed to provide a flow that filters air over the product,
while ensuring that the air flow is within the cabinet. cabinet.
To ensure satisfactory operation of a Class II enclosure, routine attention must be paid to
airflow balance and, if especially clean conditions are not necessary, a Class I Enclosure may
be chosen for its more airflow balance. stable.

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Other features that can be seen in such rooms are the use of an airlock to allow people to enter
and exit the room. A pass-through autoclave may be available to allow sterilization of
contaminated material.
Other containment rooms may be of a higher or lower level, depending on the toxic, chemical
or microbiological hazard of the room. Less dangerous rooms do not use an airlock or pass-
through autoclave and a Class I Cabinet is necessary to create a negative pressure in the room.
In rooms in which the danger is high, a Class III cabinet type is advisable, the which should
provide a shower area between the airlock and the room. It is particularly dangerous in
situations, where personnel would wear air-filtering suits.

SUPPLY OF LIQUIDS AND GASES FOR CLEANING

To ensure that the product produced in the room is free of particles and microbes,
contamination, it is necessary to ensure that not only that the air is free of contamination.
Because other gases and liquids supplied to the room must also be free of contamination.
In pharmaceutical clean rooms there is a requirement for large quantities of water used to
prepare pharmaceutical products and in semiconductor manufacturing areas pure water is used
to wash silicon wafers during semiconductor manufacturing.
It also requires the supply of various gases and these must be provided with low levels of
contamination.

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Figure 10, Type of Cabinets

Class I biological safety cabinets

Definition: Class I biological safety cabinets provide minimal protection to the operator, but
are not designed to maintain sample sterility.
These are extraction cabins with an open front inside which the operator can carry out
manipulations of low or moderate risk biological agents. The air flowing from the room into
the cabin minimizes the escape of aerosols that may form in the working chamber and is
expelled after passing through a HEPA filter.
Application: protection of the operator and the environment against biological agents of low
and moderate risk, with the sterility of the samples not being guaranteed.

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Fig 11, Biological Cabinet Type I

Class II biological safety cabinets

Definition: CSB Class II, in addition to providing the same level of user protection offered by
Class I, also protects the sterility of the material inside. In other words, in addition to the front
air inlet that protects the operator, there is also the existence of Laminar Flow and a Class 100
inside the working chamber to protect the samples.
In Class II Type A cabins, of the air entering through the front, which as we say constitutes the
barrier that prevents the exit of any particle from the working chamber, 70% is recirculated in
the form of filtered FL to protect the samples from contamination. external and/or crossed and
the remaining 30% is expelled from the top, after HEPA filtration, thus also guaranteeing the
protection of the environment, to maintain the front air inlet.
In Class II Type B cabins, the operation is basically the same with one exception: the
percentages are inverted, that is, 70% of the air is expelled, with the remaining 30% being
recirculated. In practice, these cabins are in disuse because although the protection of the
operator is absolutely guaranteed with the excellent frontal barrier created by the expulsion of
70% of the air, this is detrimental to the laminar FL for the protection of the sample that only
has of the remaining 30% of the air.
Furthermore, it may happen that the flow of potentially contaminated incoming air, being so
large with respect to the flow of recirculated air in the form of laminar flow,

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create interference with it. With the current technology available, it is proven that the 30%
expulsion carried out by Class II Type A cabins is sufficient to create a frontal barrier speed
always greater than 0.4 m/sec, which is what regulations establish such as the European
EN12469 so that the user's protection is guaranteed, while with 70% of recirculating air, an FL
completely adequate for the sterility of the sample can be created, avoiding interference
between both flow rates.
For this reason, it can be said that Class II type A CSBs are the most widely used today,
guaranteeing both the protection of the operator, the samples and the environment.
Application: Protection of the operator, sample and environment from all types of low and
moderate risk biological agents.

Fig 12, Biological Cabinet Type II

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Class III biological safety cabinet
Definition: Class III biological safety cabinets are completely closed systems, whose interior is
only accessed through ports with gloves, thus guaranteeing complete protection of the operator
and the environment and therefore being suitable for the handling of group 4 pathogens.
They have an interlock that allows the introduction of samples and material into the working
chamber without breaking its tightness.
Both the inlet and outlet air are filtered with HEPA, so the protection of the environment is
guaranteed and to a certain extent also the protection of the sample since it is only in contact
with HEPA filtered or sterile air. However, since there is no laminar flow but air entry in a
turbulent regime, the protection of the sample is not as complete as in the case of Class II,
since cross contamination may occur between the different samples present in the chamber.
Application: protection of the operator and the environment against all types of pathogens.

Fig 13, Biological Cabinet Type III

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PARTICULATE CONTROL
Figure 14 shows the relationship between cleanroom airflow requirements vs. cleanroom class
as specified under Federal Standard 209E.
The curves show the range between ideal conditions, standard conditions and compromised
conditions.
In an 8-foot-high room, a particle in the 50-micron range might take 60 seconds to settle, while
a one-micron particle might take 15 hours to settle. The fundamentals of clean room design are
to control the concentration of airborne particles, which are controlled by controlling the
sources.
External Sources . These sources include general air pollution and dust storms. External
pollution is mainly brought in through the air conditioning system. This can be easily achieved
by supplying more air than is returned, thus pressurizing the room, the overpressure must be
greater than 10 Pascals.
Internal Sources . The internal generation is the one that comes from construction elements
such as walls, floors, false ceilings; of the equipment and most importantly, of the operators.
The internal generation of building elements can be minimized by using hard surfaces, the
internal generation of operators can be minimized with appropriate clothing to cover the body
and street clothing.
A typically clothed cleanroom operator will generate approximately 10,000 particles of 0.5
microns or larger per hour per cubic foot (352,800 particles/h per cubic meter of air volume).

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Figure 14. Airflow vs Clean Room Class

METHODOLOGY AND DESIGN CONSIDERATIONS OF A CLEAN ROOM.

To design air conditioning systems for clean rooms, the following general aspects must be
taken into account:
a. Identify the type of industry or application where the project will be carried out.
b. Define the purpose of the project (prevention of condensation, material stagnation, etc.)
c. Identify the internal temperature and humidity conditions of the space.
d. Use external dry bulb temperature and relative humidity or wet bulb data and design for the
most extreme conditions that may occur in a period of no less than 24 hours.
e. Establish control levels and tolerances.
f. Carry out an exhaustive process for calculating internal and external thermal loads and
humidity.

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g. Space conditions (area and volume)
h. Design applying mixed dehumidification process.
i. Select equipment and components
Ventilation and makeup air . Ventilation and make-up air volumes are dictated by the
amount required to maintain indoor air quality, air replacement and building pressurization this
ensures that carbon dioxide and oxygen remain in balance, and that formaldehyde and other
vapors are generated. by building materials and furniture are diluted, and that air changes occur
with sufficient frequency to minimize the risk of a high concentration of air pollution inside
the building.
Air flow. According to ASHRAE Handbook 1999, HVAC Applications, US Federal Standard
209E does not specify speed requirements. The figure of 90 fpm (0.45 m/s) is still widely used
in clean rooms. The air flow design in clean rooms follows as shown in Table 4.

Table 4 Speed and changes per hour for clean rooms, N=non-unidirectional. U=
unidirectional.

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All measured values must be positioned within the measured average with plus or minus 20%.
The common advantage in designing a clean room with unidirectional airflow is to simply set
the filter velocity to 90 fpm, and then different percentages of ceiling cover for different
classification levels.
Pressurization . Rooms in a clean facility should be maintained at static pressures greater than
or greater than atmospheric to prevent wind infiltration. Positive differential pressures must be
maintained between rooms to ensure air flows from the cleanest space to the least clean space.
The only exception to using a negative differential pressure is when dealing with specific
materials where government agencies require the room to be at a negative pressure.
One of the most important parameters in HVAC design for a clean room is the pressure
differential in the room. The following pressure differentials are often used.

Table 5. Pressure differential between clean rooms in wc= Inches water column. Pa=
Pascals

Recovery time. Recovery time is inversely proportional to the air exchange rate. The recovery
time of a higher class (say from ISO 8 to ISO 7) can be estimated using the following formula:

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For example, the time for an ISO 7 to recover from a stop condition from a level 100,000 to an
operational level 100, assuming 30 changes per hour is approximately 0.083 hours i.e. 5 min, if
the change rate is doubled to 60 , only 2.5 min is required. If an ISO 6 room must recover from
an ISO 8 condition with the same air change rate, twice as much time is required. However an
ISO 6 has at least twice as many air changes and so the recovery time is approximately the
same. It is notable that the recovery time for an ISO 5 zone is almost instantaneous since the
entire zone is covered by a supply of particle-free air and it is not a dilution process but a
displacement process. It is obvious that most clean rooms can be recovered in a reasonably
short time.
6.5 Temperature and Humidity. Temperature control is required to provide stable conditions
for:

Table 6. Some typical standard applications. T=temperature. RH= relative humidity

Because process failure can be directly tied to controlling the humidity level in the surrounding
environment, it is vital to know the type of conditioning, how to choose equipment, and how to
effectively use the equipment to control humidity in the area. of process.

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Clean room controls . Although ISO 1 through ISO 5 cleanrooms use unidirectional flow
designs, most pharmaceutical cleanrooms rely on the dilution principle to control their
particles. For well-mixed air at any given time, the particle concentration x can be expressed in
the following equation, assuming that there is no infiltration since the room is pressurized:
dx = ( SX) * V *dt + g*dt
Where, s = concentration of particles in the supply air in particles per cubic foot. v = is the
supply air flow rate in terms of the number of changes per hour. g = is the internal generation
of particles per cubic foot per hour. x = is the concentration in the room or return air in
particles per cubic foot. Assuming that the initial concentration in the room is x0 and
neglecting the variation of g with time t, the differential equation above can be solved as:

When time t increases and the system reaches steady state the final concentration simply
becomes:

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II.- INTERNATIONAL STANDARDS FOR CLEAN ROOMS

INTRODUCTION
This chapter discusses the standards, norms, orders, practices and recommendations that are available
internationally and should be considered when designing a clean room.
These standards are presented in this chapter in three groups, namely:

• General engineering standards

• Pharmaceutical or bio contamination standards, and
• Containment standards
Current standards related to these older groups are described, along with a number of other useful
older standards. However, it should be noted that Clean Room Standards are being developed for
international use by International Standards.
Organization (ISO), and for use within the European Union by the European Committee for
Standardization (CEN). Information about this work in progress is also provided in this chapter.
In addition to information on standards, there is a list of references to monographs, standards, and
guidelines given in this chapter, as well as a list of abbreviations and addresses of sources for
documents discussed in this chapter.
The objective of this chapter is, therefore, to describe well-known and established standards and to
inform the reader about upcoming international standards, which should be considered when
designing clean rooms.
CLEANING STANDARDS
When referring to standards, practices, and technical orders in this chapter, the word standard is used
as a general term for words of a similar meaning. In some cases there is an official national or
international standard, while in other cases, authorities have only presented a recommendation,
specification or guide. There are also internal rules or orders.

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however, it will be used internationally, as in the case of US military technical orders.
Who produces clean room standards?
Pollution control standards, until the 1990s, were written primarily for use in countries where they
were written and much work was done by national standards organizations in the United States,
European countries, and Japan (see list at End of this chapter).
National pollution control societies, of which there were 16 in 1998, also carried out the important
work of drafting standards. Its confederation, the International Confederation of Pollution Control
Societies (ICCCS), aims to promote international cleanroom standards. ICCCS is also a liaison partner
in ISO Work.
However, some international organizations such as ISO, FIP and WHO (see end of chapter for an
explanation of abbreviations), and European organizations such as Eurovent and PIC, which covered a
dozen countries, also wrote standards on clean rooms at that time. Recently, much work has been done
on European standards by CEN in the European Union and by ISO for global standards. Within a few
years, this work by CEN and ISO will completely change the structure of major pollution control
standards.
International development of clean room standards
Hospitals at the beginning of the year 1940 knew about contamination problems from an early date.
Microorganisms have been known since the 19th century to cause infections.
Between the 1940s and 1960s, studies were conducted in hospitals to demonstrate the relationship
between microorganisms and airborne infections.
Standards for hospitals were written in the early 1960s.

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CLEANING STANDARDS - INFLUENCE FACTORS
Contaminants and other factors to consider
Since the first Federal Standard 209, the most studied contamination in clean rooms is airborne
particles. In the following years, many other contaminants, which were considered factors that can
damage the product/process/operator.
The importance of these factors depends on the specific cleanroom demands and a cleanroom designer
must know which of these contaminants should be considered.
Table 7 serves as a checklist.
Federal Rule 209 and other national standards consider only the total number of particles in the air;
nothing else. For microbiological contaminants, pharmaceutical standards (Good Manufacturing
Practice Guides) as well as ISO biocontamination control standards should be consulted.

Table 7 List of possible 'contaminants' in a clean room.

Particulate and gaseous contaminants

Cleanliness of the air and surfaces of the working place (dead and
living particles, inert and toxic particles)

Environmental factors of other types

Temperature of the air Humidity noise
of the air Light intensity Radiation
Vibrations Ionization
Electromagnetics, EMD Electrostatics, ESD

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Cleaning of contaminating particles
The most measured and discussed pollutants are particles. They can be very different: alive or dead,
inert or toxic, small or large, white or black, solid or liquid, rough or shiny. There is also a very large
size range, from 1000 ppm to 0.001 ppm, and they can have very different morphological and surface
properties, which complicates their counting.
A good knowledge of existing test methods and their limitations, as well as an appreciation of
appropriate sampling techniques at very low concentrations and statistical interpretation, is necessary
to properly determine the clean room class. This issue is discussed in Federal Rule 209E.
For the last 20 years, most classes of clean rooms have been based on the measurement of dead,
airborne particles of a size, 0.5 pm or -> 5 pm. Federal Standard 209E considers five particle sizes:
0.1 ppm; > 0.2 ppm; 0.3ppm; 0.5 ppm and >5 0 ppm.
Also considered are 'ultrafine', which are defined as <0.02 ppm, and large or 'macro' particles, which
are defined as, 5 ppm. This form of classification is also used by CEN and ISO in their air
classification work.
Clean room classes for microorganisms (pharmaceutical or bio-cleaning classes) also include
microbe-carrying particles for reference. The determination of live microorganisms in the clean room
environment is generally complex and time-consuming (1-3 days) and has certain limitations that
influence the count. Today there is an IES RP 023 on microbial measurements and ISO / CEN have
issued a draft standard on measurement of microorganisms in the air, on surfaces, in liquids and on
textiles.
The relationship between inanimate and living particles has not been sufficiently studied and this topic
is discussed later in this chapter. Federal Rule 209E states that there is no stable relationship. The new
European Union Guide to GMP gives class figures for inanimate and living particles, but in different
tables.

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The dangerous nature of hazardous chemical aerosols must be known and occupational aspects taken
into account. Threshold limit values (TLVs) are used here instead of classes. Not only toxic products
should be considered, but also allergic products, hormones, etc., as they are harmful to personnel and
products produced nearby.
Relationship between class and design materials
To properly design, build and maintain a clean room, we must know the relationship between design,
material, operators, etc. and 'class'. Greater cleaning requires certain design concepts and better
materials for the internal surfaces of a room, as well as greater cleaning frequency, better clean room
attire, better room changing, etc. Long experience has shown that there is a correlation, even though
cleanliness often refers only to air cleanliness and air supply volumes.
This relationship between the materials used in the room and the operators with respect to clean room
classes is given or emphasized only in some clean room standards.
Clean rooms and classified rooms
In the early 1960s, the term "white room" was used to describe a room with a low level of dust and
controlled temperature, humidity, etc. The walls and ceiling were often painted white. Thus the term
"clean room" was adopted.
The 209E standard published in 1992 provides a brief definition as follows: `A room in which the
concentration of airborne particles is controlled and contains one or more clean zones. This is an
important design statement because it highlights the fact that a clean room can have multiple clean
zones and recognizes the concept of mini and micro environments in a clean room, which were
formally developed in the 1990s.
The ISO 14644-1 clean room classification standard defines both a clean room and a clean zone. More
details are mentioned in the definition and defines a clean room as:

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A room in which the numerical concentration of particles in the air is controlled and which is
constructed and used in such a way as to minimize the introduction, generation and retention of
particles within the room and in which other relevant parameters, e.g.
Temperature, humidity and pressure are controlled as necessary.
Clean rooms may have 'one or more clean zones', protecting a critical area. The environment for a
clean process does not necessarily have to be a clean room, but can often be a clean area in a less
clean room. These clean zones can be provided by clean benches, workstations, environments and
insulators, the standards of which must also be considered by the designer.
In the definitions above, "control" is the key word. The word "clean" is a bit misleading, as poorer
clean rooms may not be very clean, their cleanliness spanning seven magnitudes (FS 209E) or nine
magnitudes (ISO 146644-1). In the less clean rooms (such as in the hydraulic industry) the clean
rooms are not very clean, but are only controlled.
Contaminants other than particles and microorganisms must be considered. Because of this, the term
'controlled room' would be better. The term however, 'clean room' has been used for a long time and
the terms 'clean room' and 'clean zone' are used as a general term in this chapter.
The designer must refer to a condition or mode, of which there are three (usually one referring to the
operating condition). Typically the designer will design a clean room with only one condition, but
may need to refer to another condition.
1. When the clean room has just been built and is ready for equipment installation.
2. When all the equipment is installed and ready to operate, but without contaminating people's
influence.
3. When the room is operational and both the equipment is working and the staff are working.
The main classification standards call these three conditions 'as built', at rest' and 'operational'

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The agreed definition of these conditions is given in the new ISO standard and below in the relevant
section.
It is normal for the contractor installing the ventilation system to be required to provide a clean room
in an 'as built' condition. To ensure that this clean room can achieve the correct classification in the
'operational' condition, it is normal to design and build the clean room at least one class better in the
'as built' condition, intended.
Table 8, A comparison of the major cleanroom engineering classes in the world.

USES ISO Japan France (iermany UK Australia

209E 14644-1 B 9920 X44101 VDI 2083 BS 5295 AS 1386
1992 1997 1989 1981 1990 1989 1989

ISO Class 1 1
w- 1 ISO Class 2 2 0
M1
1 N-~
ISO Class 3 3 1 c 0.035
10 M2 TSO Class 4 4 2 d 0.35
100 JVi •2 5 4000 3 L. F 3.5
ISO Class5
Wq-g
YO'
1000 ISO Class 6 6 — 4 G, Il 35
Ws 4
'YO •
10000 Ws e
ISO Class 7 7 400 000 5 J. 350
100 000 w- ISO Class 8 8 4 000 000 6 K 3500
Mf
ISO Class 9 7 YO..

A comparison of the classes given in some of these various standards, as well as the ISO/CEN
(European Committee for Standardization) standard, is shown in Table 8.

Federal Standard 209E, and its first four editions

Federal Standard 209 was published in 1963, revised in 1966 (209A), in 1973 (20913), in 1987
(209C), in 1988 (209D), and in 1992 (209E). FS 209B was a mix of information, advice and
regulations. He was very useful for his time, helping people enter the new field of pollution control
and building clean rooms. Only seven pages were mandatory, while the 26 pages of its appendix was
'Non-mandatory guidance information'. The revision of version B took 14 years. Version C was
printed in 1987 with printing errors and a corrected version D was published, therefore within a year.
In Table 9 it is

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show clean room classifications found in FS 209 prior to version 209E. Although this classification is
replaced, it is still used internationally and is the most common of all methods used to describe
cleanroom cleaning. This is the naming method used in this book, although the equivalent ISO
classification is also given.
Table 9, Federal Rule 209 Class Limits (A through D).

Federal Standard 209-version E

A much changed version E was published in 1992, with a more precise title: "Airborne particle
cleaning classes for clean rooms and clean areas." Version E differs from previous editions in that:

• Clean room classes are metric;

• It has seven cleaning classes: MI-M7;
• Gives a method of measuring the cleanliness of the air;
• Requires a plan to monitor air cleanliness;
• It gives a rationale for the statistical rules used;
• Ultrafine particles are considered, that is, particles <0.02 g;
• Considers ISO and anisokinetic sampling;
• Describes sequential sampling for low particle concentrations.
Federal Standard 209E has a table, reproduced in Table 10, that provides clean room class limits in
terms of particulate concentration, both in metric units and in the original English units. This table
does not necessarily represent the size distribution, to be found in any particular situation.

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Table 10, Federal Standard 209E Airborne Particulate Cleanliness Classes.

Class Limits
(J.
Yo p.m 0.2 um 0.3um 0.5um 5um

Class name Volume units Volume units Volume units Volume units Volume units

YEA English (m' (1-) (m3) (m) (m)) (ft 3 ) (m') (ft 3 ) (m3 (ft 3 )
H
) )
Ml 350 9.91 75.7 2.14 30.9 0.875 10.0 0.283 — —
Ml. 5 1 I 240 35.0 265 7.50 106 3.00 35.3 LOO - -or —
M2 3 500 99.1 757 2J.4 309 8.75 100 2.83 — —
M2.5 10 12 400 350 2650 75.0 1 060 30.0 353 10.0 — —
M3 35000 991 7570 214 3090 87.5 1 000 28.3 — —
M3.5 100 — — 26 500 750 10 600 300 3 530 100 — —
M4 — — 75700 2 140 30900 875 10 000 283 — —
M4.5 1000 — — — — — — 35 300 1 000 247 7.00
M5 — — — — — — 100 000 2 830 618 17.5
M5.5 10000 — —— -— — — — 353000 10000 2 470 70.0

M6 — — — — — — 1 000 000 28300 6180 175

M6.5
M7
100000
— —. — — — — 3 350 000
10000000
1 OU [JOO
283000
24 700
61 800
700
1750
— - — — — —

BIOCONTAMINATION AND PHARMACEUTICAL CLASSES

Production of sterile pharmaceuticals, the development of clean room standards for the
pharmaceutical industry began during the 1960s to counteract contamination problems from sterile
pharmaceuticals, products that had caused illness and death in patients. They had realized that since
only a small sample of the drugs could be analyzed, a final sterility test could never determine the
safety of the sterile products. Therefore, it was necessary to rely on manufacturing, that is, good
manufacturing practices (GMP). These standards are known as good manufacturing practice guides
(GGMP). They drew on experience from the then new FS 209, BS 5295 and other engineering
standards, as well as experience in pharmaceutical manufacturing. The goal of GGMPs is to carefully
specify the appropriate method of manufacturing sterile products by eliminating microbes and
particulate contamination and therefore create the right quality assurance (QA).

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GMP guidelines largely address good manufacturing methods, but may also specify building design,
construction material, personnel care, etc. They can also give figures for types of cleanroom cleaning:
particles, microorganisms, as well as the type of air filters and the number of air changes per hour.
The different GMP guides, produced by different countries, are more indicative than legal and
consider that there is more than one way to achieve what is recommended. To verify that the GMP is
being applied correctly, each country has a government and inspectors, who will interpret the
generally expressed statements of the guidelines.
A pharmaceutical manufacturer must also comply with the GMP guidelines of the countries
receiving your products. GMP guidelines are intended for the pharmaceutical industry, but the
methods used to resolve quality control problems are generally useful. In addition to the
recommendations mentioned
Above, the methods for qualifying equipment and validating processes are applicable to other
industries such as food and microelectronics. GMP guidelines should
Therefore, it will be studied in other industries with quality problems.
Determining 'critical zones' in the room is important and a key factor in risk analysis, such as Hazard
Analysis Critical Control Points (HACCP). This method is considered in the new ISO
biocontamination standards.
In 1963, the Food and Drug Administration (FDA) published the first GMP in the United States.
Three years later, a Swedish regulation was made official and three years later, in 1969, the first
guideline from the World Health Organization (WHO) was published. An important guide was
published by the Europeans
pharmaceutical inspection convention (PIC) in 1972, and revised in 1983, 1989, 1992
and 1995 (document PH 5/92). This PIC GMP guideline is accepted in most Western countries.
European countries, in some Eastern European countries, and in Australia.
In 1989, a guide known as the EEC Guide to Good Manufacturing Practice for Medical Products '
was produced by the Commission of the European Communities.
Reprinted in 1992 with new annexes, it came into legal use and replaced all

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GMP guides produced in CEE countries. This version is now revised with a new clean room
classification method. Annex 1 of the EU GMP was valid from 1 January 1997.
In early 1992, Russia issued its first GMP, LD 64-125-91, as the first GMP issued in Eastern Europe.
The most used GMP guides for clean rooms are the following:

• PIC: GMP and Guidelines 1995 Valid in European countries outside the EU and Australia.
• FDAcGMP, 1987 Valid for the United States.
•EUGGMP 1997 Valid for the EU area.

Table 11, Comparison of the main pharmacy GMP guidelines regarding working conditions and
classes (classification given according to FS 209E).

PIC GMP EU-GMP FDA Transfer of classes, all

GMP 1992 1987 operational

Condition At rest Operational Operational 209D 209E ISO

Grade A 100 100 Critical area 100 M3.5 ISO 5

Grade B 100 10 000 — 100 M3.5 ISO 5
Grade C 10 000 100 000 — 10 000 M5.5 ISO 7
Grade D 100 000 — Controlled area 100 000 M6.5 ISO 8

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Table 12, EU GMP Guide 1997. Air Particle Classification System for Sterile Product
Manufacturing

(a) To achieve B air grades, the number of air changes must be related to the size of the room and the
equipment, personnel present in the room. The air system must be provided with appropriate filters
such as HEPA for grade A
(b) At rest it should be received in the state without anyone entering the room, after the 15-20 minute
'cleaning' period.
(c) Appropriate alert and action limits should be established for particulate and microbiology results.
If these limits are exceeded, operating procedures must prescribe corrective action.

The maximum concentration of microorganisms that should be found in the different grades of clean
rooms in the operational state is given in Table 13.

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Table 13, The values of the EU GMP Guide (1997) for microbiological monitoring in the
operational state, for the manufacture of sterile products.

The EU GMP guide does not provide information on how to measure microorganisms. Test methods
will be found in the upcoming ISO biocontamination control standards and IEST RP 023.
Manufacturing operations in the EU GMP guide are divided into two categories: those where the
preparation is sealed in its final container and terminally sterilized, and those that must be prepared
aseptically at some or all stages. The guide suggests the following use of clean rooms:
Terminally sterilized products
Degree Operation examples

TO Filling of products, when unusually at risk

c
Preparation of solutions, when unusually at risk. Product filling.

d
Preparation of solutions and components for subsequent filling

Remarks : The preparation of most products should be carried out at least in grade D environment,
when there is unusual risk, grade C environment should be used.

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Aseptic preparations
Degree Operation examples

TO An aseptic preparation and filling.

c Preparation of solutions to be filtered.

d Handling of components after washing.

Remarks: After washing, the components should be handled at least in D grade environment.
Handling of sterile starting material should normally be done (see GGMP) in a Grade A environment
with a Grade B background. The preparation of solutions that must be sterile filtered during the
process, must be done in a grade C environment; unfiltered, the preparation of materials and products
must be carried out in grade A environment with a grade B background. Handling and filling of
aseptically prepared products should be done in a Grade A environment with a Grade B background.
Preparation and filling of sterile ointments, creams, suspensions and emulsions should be done in a
Grade A environment, with a Grade B background, when the product is exposed and not subsequently
filtered. Special conditions are specified in the GGMP when insulators or blow-fill seal, where
machines are used.

Other biofouling class standards

Methods for counting airborne microbes were developed in the 1940s and automatic, optical counting
of dust particles in the 1960s. Microbial methods are time-consuming compared to optical or discrete
particle counters (OPC or DPC) and require skilled technicians. Therefore, it would be convenient if a
relationship could be established between dead and live particles in the air.
The methods could be used for quick indications, it is known that for a given room, parallel, tests can
indicate an approximate relationship, but there are many factors that must be considered and the
figures should not be transferred to a different clean room or factory.
In 1993, the IEST in the United States issued a RP 023 on 'Microorganisms in clean rooms'. Provides
methods and describes devices for measuring microorganisms

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in the air and on surfaces, but does not discuss the classification of clean rooms. Disinfectants and
their influence on microbial count measurements are also discussed.
The ISO standard also provides information on methods for the determination of microorganisms in
air, liquids and on surfaces (including textiles). It has three main parts:
ISO 14698-1: Biocontamination control; General principles
ISO 14698-2: Evaluation and interpretation of biocontamination data.
ISO 14698-3: Surface biocontamination control

Biological risks, and the measures directed at them, are classified into four classes. Four laboratories
are used with risk levels from BL 1 to BL 4 (see Table 14).
Table 14, The four BL 1-BL 4 classes of biosafety laboratories.
BL 1 Standard normal laboratory , Ordinary biochemistry laboratories, school and university laboratories
BL 2 Special training and routines to prevent laboratory infections . Diagnostic laboratories, Appropriate waste
management, Health laboratories
BL 3 Special laboratory with negative pressure, Special security laboratories, Air locks for people and materials
Tuberculosis laboratories, Autoclave in the room, All work carried out in a security cabinet, Special decontamination of
waste
BL 4 Special laboratories with total separation between humans, high-risk laboratories and microorganisms in all
aspects, negative pressure, sterilization

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III.- THE DESIGN OF CLEAN ROOMS FOR THE

MICROELECTRONICS INDUSTRY
INTRODUCTION
The technology of clean room design had its conception in medicine/pharmacy, facility development,
and was born in the rush to expand the science of World War II weaponry and warfare. His
adolescence shaped the needs of the race in space and he eventually reached adulthood in time to meet
the challenge of manufacturing in the Lilliputian world of microelectronics, where micron-sized
particles are like car-sized rocks. and impurities of the order of parts per billion that can be crucial.
The demands of creating an environment that provides the near-perfect conditions required in the
manufacturing processes of this world of microelectronics were, and are, strict and include areas that
are vital to manufacturing success. Maximizing Product quality and performance requires strict
control and coordination between the manufacturing facility, tooling, process and operation, but all of
this will largely depend on the strict environmental control offered by advanced clean room
technology.
Pollution control engineering, along with its related equipment, materials and skills, has become so
advanced that the facility and its environmental control should no longer be the limiting factor. If this
is so, where is the challenge in designing clean rooms for microelectronics manufacturing? Obviously,
the goal of clean room environmental control is to provide a contamination-free space in which to
manufacture a contamination-free product. Following approved procedures should produce the desired
result, but contamination has occurred unexpectedly, sometimes without any signs indicating its
origin. The clean room, manufacturing process, equipment and method of operation are all equally
possible sources of contamination.
While the technology was still in its youth, the immediate assumption was, and usually justifiably so,
that the clean room had failed. Currently
Cleanrooms are of a much higher standard and have controls and monitors by which their cleanroom
operating condition can be quickly assessed. If it turns out that, operating correctly, the process,
process equipment and operation can then be examined for each shift.

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The world of environmental control has truly expanded, because, to be recognized as a common
pollution control engineer, one must now accept the challenge of including ownership and
responsibility. You must also participate in the evaluation of handling equipment.
MANUFACTURING OF SEMICONDUCTOR CIRCUITS
Semiconductor circuit manufacturers have become large users of clean rooms.
These clean rooms are designed to maintain temperature, humidity, particulate, static and pressure
levels. This is due to the fact that these factors, as well as static forces, can directly affect or even
compromise the final product, and because these finite electronic manufacturing operations are so
expensive, there is simply no room for error in budgeting.
The reason is that manufacturing operations take place almost at the molecular level, the level and
physics of the device's operation depending on the purity of the materials in atomic percentages
measured in parts per billion. These levels are unknown in any other human endeavor.
First germanium and then silicon became the wonder elements of the 20th century. This is because
they are semiconductors of electricity. Semiconductors derive their name from their ability to
sometimes conduct an electrical current and sometimes not. This is controlled by their internal
structure at the atomic level and by the circuitry into which they are inserted. Certain atomic elements
can be added to the structure during manufacturing that allows these effects to take place. While there
are many categories of devices described (taken at a discrete device level), the functions performed
are: voltage amplification, switching, resistivity, and induction.
Combined with diodes and transistors, these form the basis of semiconductor circuits. To give
perspective to those unfamiliar with the process, the following is a brief summary, along with the
levels of contamination control required, of the manufacturing steps used in the manufacturing of
semiconductor circuits. Large scale integration (VLSI) and complementary metal oxide
semiconductor (CMOS) processes on silicon are used as an illustrative example.
Common practice divides IC manufacturing into three phases:

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Materials, wafer manufacturing and assembly and testing.
Materials
Starting with silica sand, the process is as shown in Table 15.
During the sequence, most operations take place in an ordinary factory environment.
Protection against contamination is provided, for the most part, by doing processing within sealed
systems. Preparation of the charge for the Czochralski, however, the extractor, as well as the cleaning
of the crucible, must be carried out in a well-controlled clean room (minimum standard ISO 5 (class
100). Any contamination introduced during that step will enter the ingot and cause the process to fail
to make a single crystal or cause unacceptable electrical properties to develop.
The last part of the process also requires a clean environment (the minimum standard is ISO 5 (Class
100)) to allow the equipment to produce the required finish, thickness, taper and flatness.
Additionally, great care must be taken to avoid leaving mobile ions or doping elements on the surface.
Subsequent operations at high temperatures distribute them in the crystal structure and destroy the
desired electricity.
This is a very simplified description of the entire process, completely ignoring that many tests,
cleaning steps and process adjustments are required to produce material of the required purity, crystal
size, orientation, uniformity.
There are many other systems in use today, involving multi-metal semiconductors, silicon (or other
semiconductors) deposited on glass, sapphire, diamond, etc. These systems do not negate any
requirement for proper pollution control.

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Table 15

Design public service distribution systems to:

1. Provide easy access for fixing equipment without the need to close under the system or clean
room.
2. Provide adequate flow rates to avoid stagnation and collection of impurities.
3. Avoid pressure fluctuation during operation. Even small variations can have disastrous effects on
the product. It is true not only in supply, but in extraction (exhaust) as well. Refers to all process
public service supply systems:

• supply and extraction of gases (exhaust)

• fluid supply and drainage
• Electrical supply and ground connection.

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4. Periodically provide connection points and shut-off valves for all gases and liquids (except
deionized water) so that a connection can be made without danger of contaminating active process
lines; They are virtually impossible to clean once contaminated. Deionized water systems must be
provided with insulated valves and sterilization connections to:

• make a new connection

• perform sterilization
• testing to ensure sterility and purity specifications
• open the system.
Design for vibrations and electromagnetic interference.
These usually become very critical. Both have some of the same origins and design for control, for
one of these you must start, very early, with site selection. Before adopting any site, testing and
analysis should be done for seismic activity, soil conditions, proximity to railways, highways, airport
landing and take-off roads, adjacent industry.
Large rotating electrical machinery in the vicinity produces ground vibrational excitation and an
electromagnetic field effect.
Power lines in the vicinity not only produce electromagnetic fields, but can also excite some structures
and elements that mechanically vibrate at some multiple (or fraction) of the base frequency.
All of these and others should be carefully evaluated by experts familiar with the needs of the
microelectronics industry before making a decision to proceed.
It is certainly necessary to establish parameters for the design of foundations, columns, spacing of
structural elements, etc.
Define how the clean room will be built, the success of the CLEAN ROOM project will depend
largely on what is put on paper and how it is built. One feature, often overlooked, but certainly within
the designer's purview, is the designation of when and how housekeeping controls should be applied
during the construction phase. This is possibly the most important instruction the designer can give, as
it largely determines the amount of dirt incorporated, which can impair future operations. Dirt,
incorporated during construction, will enter the process during

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operation and can determine the success or failure of the clean room. It is recommended that the
procedures be applied as soon as the building is "dry", ie. before any installation that is, before public
service systems or equipment are installed. Cleaning should include: vacuuming (with a brush) of
each surface, wet washing with free rinse, non-ionic detergent, rinsing with deionized water and a
final cleaning with 'tape cloth' before turning on the installation. Following that procedure should
allow the specified conditions to be met within seconds of powering on the system.
DESIGN FEATURES
Design
Semiconductor clean room design has evolved over several years. A clean room design is shown in
Figure 15 and has been popular for several years.

Fig 15, Vertical flow in a semiconductor clean room

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The clean room tunnel can be designed to provide different air standards. Unidirectional air can be
supplied from 100% coverage of
filters on the roof or from one-way flow working systems; In systems that are not required to be of the
highest quality, the supply air can be supplied by less than 100% filter in the ceiling.
Several designs of this type have been used. Two typical Designs are shown in Figure 16 (a) and (b).
These are designs that have been used in the past but are still applicable. in manufacturing areas or
laboratories where there are fewer cutting-edge components produced.
To achieve lower standards appropriate for less stringent pollution control areas is shown
schematically in Figure 17.
If this method is to be used, Table 16 can be used. Table 16 is published in IEST Recommended
Practice 012, although the room classification nomenclature has been changed to that used in this
book. Please note that the values used in this table are only a guide and are considered by some
authorities to be inappropriate for clean rooms used in non-semiconductor manufacturing industries.
If a supply air plenum is used in the clean room design, then the unfiltered air in the plenum will be at
a higher pressure than the air in the clean room.

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Fig 16, semi conductor clean room design

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Fig.17, Reduced roof filter coverage.

Table 16, values of speeds and hourly renewals in clean rooms

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Physical Barrier
An environment uses a physical barrier (usually a plastic film, plastic sheet, or glass) to
isolate the susceptible or critical part of the manufacturing process from the rest of the
room. The critical manufacturing area is kept within the environment and has large amounts
of top quality air from the rest of the room.
A diagram of Air Supply Design using a more traditional ventilation method is shown in
Figure 18(a). In this design, large amounts of unidirectional airflow are provided to those
parts of the room where production personnel move wafers from one machine to another
machine and in smaller amounts of air.
A diagram of the air supply design used with mini environments is shown in Figure 18 (b),
where the highest quality of the environment is provided within a main environment and a
lower quality of the environment is provided in the area where it is located. the production
staff.
The total air supply volume can be much less when using minienvironments. It can also be
seen that this type of system lends itself to automation and the use of robots: that may or
may not be desirable.
In addition to using an ambient environment to isolate the area where the silicon wafers are
exposed, wafers can also be transported between processing machines on engineered
carriers that interact with the machines through a standard mechanical interface.

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A plan of a semiconductor production area that would be used for VLSI-CMOS or more critical
product manufacturing and is designed for use with minienvironments is shown in Figure 18.
Typical requirements for cleaning the air within the area would be similar to the following:
1. An environment where the wafers are fully exposed: ISO 3 (Class 1) or better.
2. An area where wafers are protected in closed containers and boxes, above ISO 6 (class 1000).
3. Machine-technical engineering area-ISO 6 to ISO 7 (Class 1000 to
Class 10000).
4. Adjacent areas outside standard clean room envelope air conditioning.
In Figure 19, the areas where the wafers are exposed are insulated by rigid plastic or glass walls and
provided with a unidirectional air supply that will give ISO 3 (Class 1), or better, conditions. These
environments are shown in the dark. The darker gray area represents the area where production
personnel move, the wafers that are protected in containers and closed boxes; this may be ISO 6
(Class 1000). The lighter gray area is the service area where technicians gain access to services and
machines; this can be ISO 6 to 7 (class 1000 to 10000).

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Fig.18 A comparison of SMIF isolation and a more traditional approach

(a) traditional type of ventilation
(b) Environment with SMIF technology

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Fig.19, Wafer fabrication area designed for a SMIF/minienvironment system.

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Airflow direction
In most cases, for maximum control of product cleanliness, the air flow should be vertically
downward and should meet ISO 3 (Class 1) or a better cleanliness specification as it flows into the
product. Obviously, vertical flow over the product is not possible in an evaporator, reactor or
diffusion oven. In those special cases, filter blower units, scavenge air vanes, etc. should be tested.
In any event, such specialized treatments must be qualified by extensive testing prior to adoption.
Some special environmental chambers that use horizontal airflow or airflow at 45 degrees to the
horizontal have been quite successful in reducing the number of particles reaching the product in
some production equipment. Such equipment, if available, may be worth investigating.
ULPA filters are 99.9995% more efficient when tested at manufacturing particles 0.1 micrometer in
size, and tested, certified at the same facility, it is recommended that they should be used to ISO 3
(Class 1) or an even lower rating. To allow maximum flexibility and minimum record keeping of
what type of filter goes where and because the cost differential between 99.00% and 99.9995%
efficient filters is small for the given convenience, it is recommended that the same type of filters
be used. Top grade throughout the clean room.
Air must exit the room through perforated panel floors with integral air. The floor covering must be
made of a high-pressure laminate conductor and the system must be grounded. ISO Classes 3-5
(Classes 1-100) will require 100% coverage by perforated panels, while ISO Classes 6 and 7
(Classes 1000 and 10000) require only 50% or less coverage of perforated panels.
An alternative and acceptable solution for airflow design for ISO 6 and 7 (Classes 1000 and 10000)
is to use classic turbulent ventilation, the return vents are in walls or islands and close to floor level.
This may or may not pose a problem for routing return air to air recirculation systems, depending
on the overall design. With this system, perhaps, you abandon some of the inherent flexibility of the
total vertical flow return system through the floor.

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Airflow amount
ISO classes 3-5 (classes 1-100) should be designed between 0.3 and 0.5 m/s depending on the flow
through the respective clean zones. It is important to observe the effect of airflow through critical
production equipment interface locations. There are times when a reduction in airflow can cause a
significant decrease in particle size, or a level or reduction in machine interference (cooling). ISO
Classes 6, ISO 7 and ISO 8 (Classes 1000,10 000 and 100 000) must be designed for 50,30 and 18
ft/min (0.25, 0.15 and 0.09 m/s) flow through them. Primary control is achieved by providing an
equivalent filter/solid panels on the floor. After installation and commissioning, filter adjustment,
perforated panel dampers will be used to adjust the direction and amount of air flow.
Moving air recirculation system
A drawing of a typical air movement system used to recirculate air passing through floor louvers to
high-efficiency air filters is shown in Figure 20. This system must have the following
characteristics and requirements:
1 .- Fan type: should be an axial vane type with an optimal attenuator transition type in both the
cone and the outlet. The motor must be external to the air stream.
2 .- Structural support for fans should be outside of wafer manufacturing with separate
foundations, detuned column support and maximum isolator design, so that transmitted (structural)
vibrations are kept to a minimum and not within the range of 0 - 200Hz.
3 .- The fan chamber must be lined with perforated stainless steel sound attenuators filled with
high-density polypropylene fiberglass batting. This attenuation must be carried beyond the fan
chamber so that at least one 90 degree bend of the air path on the upstream and downstream side is
treated in this manner.
4 .-The fan coils - air ducts - floor perforations - filter - pre-filtering system must be designed to
produce a system pressure drop of no more than 2.0 inches of pressure (500 pa) with clean filters
installed.

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5 .- Fans and motors should be away from the wafer manufacturing area so that motor EMI does
not interfere with the sensitive manufacturing process and inspection equipment. The allowed
proximity varies directly according to the square of the power.
6 . Because all air ducts are so large, they require rotating vanes and, depending on the design,
sound attenuating treatment.
In general, the goal is to keep the air velocity horizontally above the filters at less than 1000 ft/min
(5 m/s). As an example, for a room 100 feet (30 m) wide, with air supplied from both sides, the
plenum should be a minimum of 5 feet (1.5 m) deep. The air speed, then, would be a maximum of
1000 ft/min (5 m/s) on the sides, decreasing to 100 ft/min (0.5 m/s), in the center.
7 . The cooling coils must be mounted upstream of the fans. Direct digital control is preferred with
(electronic) temperature sensors located after the fans.
The cooling system should be of the dual-function type, with the cooling coils controlling sensible
heat only.

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Fig 20, air recirculation system

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IV THE DESIGN OF CLEAN ROOMS FOR INDUSTRY

PHARMACEUTICAL
INTRODUCTION
This chapter considers the design, construction and commissioning of a pharmaceutical
product in a clean zone Chapter 2 of this book provides a bibliography of available
standards, other chapters provide the reader with information on the key components that
will be incorporated within the Clean pharmaceutical area in general. It is, therefore,
proposed to use the information contained in these sections and develop further
characteristics and requirements of sterile pharmaceutical products, rarely found a single
clean room.
Rather there are room suites, which integrate various grades or classes of rooms to
accommodate different parts of the manufacturing process. It is also possible, particularly in
the production of sterile pharmaceutical products by an aseptic process, that isolators should
be used as an alternative or complementary solution to the clean area design.
The relationship of the clean pharmaceutical area within a total Quality Assurance. The
program is important to understand in the design and function of the pharmaceutical
industry.
The manufacturing area forms an important part of good pharmaceutical manufacturing
practices (GPMP), these being the requirements established by government agencies and
contained in various GMP Guides (see Chapter 5). Provision of clean areas may not provide
all the appropriate conditions required, like other quality aspects.
The assurance associated with labor practices is also very important. However, cleaning is
the area element that is an essential and difficult part of the GMP Guidelines.
Also important is the fact that the facility represents a significant capital investment.
The problems associated with the design of clean areas for the manufacture of
pharmaceutical products largely depend on the diversity of requirements of the
pharmaceutical industry.

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If your requirements are not understood then it will not be possible to provide suitable clean
areas. Therefore, it is necessary to consider what occurs in
the clean areas and how this affects the design in terms of room layout.

TYPES OF PHARMACEUTICAL PROCESSES

There are many different types of products produced in pharmaceutical manufacturing.
For the purposes of this chapter, they can first be divided into:
"Injectables: those products that are injected into a person.
"Topical: those that are applied to the outside of the human body.
"Oral: those that are ingested.
Generally speaking, injectables require much higher quality environmental conditions for
production than topicals or orals, as the human body can cope with less bacterial
contamination from the bloodstream than on the skin and in the stomach. Eye drops are an
exception to this general rule since the eye is generally more susceptible to infection than the
skin.
Injectables
In the context of clean area layout and environmental requirements, sterile injectable
The products are can be divided into three classes, ie.

• Productswatery
• Productsfreeze-dried
• Productspowdered
Aqueous Preparation Preparation of injectables in water (or as an emulsion) falls into two
main areas, i.e. aseptic production and terminal product sterilization production. If the
product is thermostable, it will normally be terminally sterilized.

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Therefore, these products will have little bacteriological risk for the patient. However, if the
injectable material cannot be terminally sterilized because it is unstable, as, for example,
with human hormones and vaccines, then the product must be assembled aseptically. This
means that the liquid is filtered free of microorganisms and filled into a sterile container in a
clean area that is as free of microorganisms as reasonably possible.
Aseptic production is therefore the most demanding process in pharmaceutical
manufacturing and difficult to do well. Class 100 conditions are required in critical areas
where the product is exposed and this would generally be achieved by providing a one-way
flow system or isolator within a conventionally ventilated room.
Freeze drying If a pharmaceutical product is unstable in solution, then it can be lyophilized
(lyophilized). The product is composed of a solution that is filtered free of bacteria and
dispensed into sterile containers (usually vials or ampoules). The containers are then taken to
the freeze dryer and the water is removed by the freeze drying process. They are then
removed from the freeze dryer and covered or closed. They are not terminally sterilized, but
no microbial growth will occur in the dry powder.
Dust filling
In this process, the product is delivered in powder form to the filling and dispensing room,
by machine, into containers and closed containers. Antibiotics are very often filled in this
way. Terminal sterilization is not carried out.
The dust will not support the growth of bacteria and if the dust is an antibiotic, the
opportunity is reduced even further. However, they are likely to be considered aseptic
products by regulatory authorities.
The production of dust-filled products has two special problems. Air humidity must be kept
low to ensure that the powder flow and powder filling can rise to clouds of particles which,
if the product has high power, will cause personnel contamination problems. Therefore,
special consideration must be given to extract systems for filling machinery, containment
cabinets or isolators and special air, motion control schemes. Many authorities consider that,
if construction is required for the production of these biologically active powders, at least a
dedicated facility that is effectively isolated from other production areas.

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Topics
These products are applied to the outside of the body. Most of these products
It will be applied as creams, ointments and oils on the skin. Also contained within the
category of topicals are ocular preparations that are aqueous solutions or ointments.
Finally, it is advisable to place implants, which are placed under the skin, in this category.
Because the product is applied to the skin, the need for sterility is less than in injectables.
However, this should be taken as a generalization, as eye solutions and some creams,
ointments and oils should be sterile.
Non-sterile products do not require the best environmental conditions. Rooms that are class
100,000 would generally be acceptable but the preparation of eye and other sterile products,
depending on their production method, will require an environment, similar to that used for
the production of aseptic or terminally sterile injectables.
Implants have special contamination control problems. Because they are placed in the body,
they must be produced sterile but due to their high biological level
activity that must occur in containment areas to prevent them from reaching employees in
significant concentrations. This can be achieved, for example, in 'Class II' or 'Class III'
workstations (see Chapter 1) or in containment isolators.

Oral products
These products include bottles containing liquids, as well as tablets and capsules. Oral
products are not normally sterilized, but depend on the quality of the raw materials and, in
the case of aqueous liquids and creams, preservatives are frequently added to prevent the
development of any bacterial contamination in the container.
Most of these products are also produced in closed systems where the raw material enters at
one end and the finished product exits at the other end.

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The problem with these products, especially tablets and capsules containing powders, is one
of cross-contamination between products or between products and people.
While they are of interest in the general pharmaceutical production scenario, they do not
typically require tightly controlled clean rooms.
FACILITY DESIGN
Design objectives
The design objectives of a set of pharmaceutical clean rooms, within a factory, in a facility,
can be summarized as follows:

• Exclusion of the external environment to the set of clean rooms

• Elimination or dilution of contamination derived from the manufacturing process
• Elimination or dilution of contamination derived from personnel working in the area
• Containment of hazards derived from the product
• Control of cross contamination from product to product
• Personnel protection
• Control and management of material flow through process steps by means of design
and configuration
• Control and management of personnel movement by optimizing the agreement and
connection of individual rooms
• General security of the operation by controlling the entry and exit of personnel and
materials
• Optimal comfort conditions for staff
• Special environmental conditions for products, e.g. low RH for powder filling
• Housing plant and process equipment to ensure safe and easy use, as well as good
access for maintenance
• Effective monitoring of room conditions
• All of these functions are important, and a set of clean rooms should be designed so
that they overlap and function well. The later parts of this chapter will develop these
objectives in more detail.

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Use of guides and standards
It is clear from Chapter 2 of this book that there is no single definitive standard or guideline
that can be applied to the design and operation of a clean pharmaceutical area, designers and
the user have at their disposal a variety of clean room specification documents, such as
Federal Standard 209 and various national guidelines for GMP, as well as guides on
insulator design (see Chapter 2). Therefore, it is essential that the designer develop a clear
technical and performance specification with the user that will describe the design,
validation and operation of a facility and process such that the product and regulatory
demands are met. The appropriate regulatory authorities should be involved at an early stage
as a step towards achieving their essential final approval of the facilities.
It is the opinion of the writer that generally available clean room standards provide such an
effective framework, provided they are not considered absolute. The problem of treating
such standards as absolutes will become clear as the various clean room functions and
environmental parameters are described.
Design methodology
A pharmaceutical processing room has more functions than purely environmental cleaning,
it is necessary to analyze all the requirements and develop the solution in an organized
manner
A simplified stepwise approach can be summarized as follows:

• Analyze production stages

• Prepare process flow charts
• Define activities associated with rooms
• Define environmental quality requirements
• Quantify production, process and space requirements
• Prepare room association diagrams
• Define accommodation needs
• Develop designs and schematics
• Prepare designs and specifications
• "Undertake the detailed design and construction process

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Depending on the physical size, scale and complexity of a facility, these steps can be carried
out at various levels of detail. It is important to clearly define the responsibilities of all
parties involved and ensure that the experience is appropriate for those responsible. The
material generated during the design process can be used in conversations with the
regulatory authority and to help a designer who is not familiar with the particular problem of
a given factory, to effectively understand the philosophies, principles and conditions that are
being developed to the new installation.
Clean room layout
In pharmaceutical manufacturing, clean rooms are constructed as a set of rooms that have
defined functions. These are illustrated in Figures 21 and 22.
In Figure 21 we can see a typical set of clean rooms designed to meet the requirements of
producing an injectable product that can be terminally sterilized. Staff working in this
manufacturing would enter the set of clean rooms through the 'clean changing area'. In this
room, you remove your factory clothing, wash your hands, and put on appropriate clean
room clothing. Raw materials and components, such as containers, would enter through their
corresponding entry locks. In these airlocks, procedures are used to decrease contamination
that can come from outside into the clean rooms. Solutions are prepared in the "solution
preparation" room for transfer, directly or indirectly, by pipes or moving containers, to the
filling operation in the "clean filling" room. The primary containers and closures would be
prepared and washed in the "component preparation" room and transferred manually to the
filling stage or by using a conveyor system. Containers are filled and packed below the one-
way flow cleaning zone in the "clean fill" room. Filled and packaged, the product containers
leave the clean room through the terminal sterilization autoclave. At the end of a work
period, staff would exit the suite through the locker room where the protective clean room
suite would be removed.

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Fig 21, Typical set of rooms for terminally sterilized injectables

Figure 22 shows a typical set of clean rooms configured for the production of a product,
employing an aseptic filling technique. The differences in process requirements relate to the
following key variations: Rooms are separated into clean and aseptic rooms. The barriers
between them are created by the oven, autoclave and transfer hatch for items entering the
aseptic suite, and through the separation of the "solution preparation" and "aseptic filling"
rooms. A separate, more accurate wardrobe control is provided for the aseptic set, due to the
differences between the environmental control of clean and aseptic sets. Additionally, the
isolator can be used in place of the one-way flow workstation.

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Figure 22, Typical set of rooms for aseptic filling

ENVIRONMENTAL CLEANING
The correct quality of cleaning of the internal environment is generally the difficult
requirement to achieve and is determined by:

• The amount of pollution released into the room.

• The quality of the air supplied to the room.
• The amount and method of supply of ambient air, i.e. conventional/turbulent
ventilation or unidirectional flow, or a combination of both.

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• The amount of contamination entering from areas adjacent to the room. When
isolators are used, many of the same considerations are required, but contamination
entry from outside the insulated volume is generally minimized.
These requirements are considered on the back:
Generation and Release of Pollution
Contamination can come from:

• Staff
• Process equipment
• Surfaces
The most important contaminant in a pharmaceutical clean room is bacteria and
most, if not all of these, come from the people in the room. It is therefore useful to know the
number of people expected to work in the premises, as this will have a direct impact, taking
into account the amount of air required to dilute and eliminate airborne dispersion of
contamination from their bodies. . The effectiveness of your clean room clothing will have a
direct relationship to the contamination dispersed by people in the room and hence the
amount of air.
The type of clothing will also influence the cooling load, as the more effective the clothing is
in preventing dispersion, the less air is exchanged through the clothing, therefore the warmer
the staff will be and are likely to be. requires lower ambient temperatures.
Process equipment is a major source of particulate contamination.
Cost effective design.
Cleanroom surfaces can be sources of contamination due to surface dislodgement caused by
lack of cleanliness and durability.
Entry through faulty HEPA filter systems
Within one-way devices and room air supply terminals, a HEPA filter is widely used.
These filters are unlikely to have such high particle removal,
such as those commonly used in the most demanding parts of the microelectronics industry.
The reason for this is threefold, firstly, bacteria

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They do not normally occur in the air as single-celled organisms, but are transported as skin
particles and have an average size in air of approximately 10 to 15 microns. Second,
particles due to their low deposition rate are unlikely to access airborne containers in
sufficient quantities to be a problem for patients. Finally it is very
It is difficult for small particles to cause harm to patients. HEPA filters with efficiency of
approximately 99.97% at particle sizes around 0.5 microns are more than adequate.
HEPA filters must pass, after manufacture, an approved test at the factory, however, a filter
element is good at the time of manufacture, its ultimate effectiveness will depend on the care
with which it is handled and the quality of the hardware. of installation.
Effective housings or enclosures shall be provided for the filter, and where the filter is
installed in the housing the entire system tested by an in-situ test, such as cold or hot
generated oil test or other approved artificial aerosol test. A proven high efficiency filter and
frame produced by a reputable manufacturer are very likely to ensure a satisfactory
conclusion.

Elimination of contamination in a room by displacement or dilution ventilation

The accepted options for ventilating an entire room to remove unwanted contamination are
unidirectional flow systems or turbulent airflow, or a mixture of both. As discussed above, it
is common in pharmaceutical clean rooms to find that in a mixed flow solution, the general
room area is ventilated by conventional turbulent flow, the system and unidirectional flow
units are used to protect the areas where the product is directly exposed to contamination,
that is. The container is open. A typical clean room is shown in figure 23.

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This type of mixed solution is generated by considering:

• Economy, since less air is required.

• The complex nature of pharmaceutical cleanroom suites makes it difficult to return
the large volumes of air required in a complete unidirectional system. This is
particularly difficult if perforated floors cannot be used due to the possibility of glass
or fluids falling to the floor.
• Relative room pressure control requirements. Unidirectional flow rooms are
normally supplied by individual air conditioning plants. This can make pressure
balance between rooms more difficult to achieve.
• Segregation. Users often require that critical manufacturing operations be clearly
viewed as segregated from the rest of the room. This is easily done by using a
localized one-way flow system.
If the amount of contamination released into the air of a clean room is known, it is possible,
in a conventional flow system, to estimate the required air supply volume and therefore
obtain the required standard of contamination in the air. However, information on the
dispersion rate of personnel and especially machinery is difficult to obtain. Therefore it is
normal to use the quantities of air that appear in the Standards or Guides for good
manufacturing, practices based on experience.
It should also be recognized that the type of air supply devices, i.e. grilles or diffusers, will
influence the movement of air in a room with conventional ventilation and, therefore, its
cleanliness. Where there are many types of air supply devices available, but based on their
method of action they can be divided into two types. These are :

• Egg crate or perforated plate type that provides a downward jet of air flow.
• Various types of vane or swirl diffusers that provide good ambient air induction.

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Fig.23 Clean zone of vertical flow over autoclave discharge and vial filling machine.
General ambient environment controlled by a conventional turbulent airflow system
with low level return air. Curtains raised to show the equipment.
These two types of air supply devices give air movement of the type shown in Figures 24
and 25. The perforated box, or discharge type device will produce a jet stream of air beneath
it. This stream of air will carry pollution around its edges, but overall the air quality under
the diffuser will be good. The blade type of device is designed to entrain room air and mix it
with the incoming supply air; The air quality throughout the room will therefore be
reasonably constant. Therefore, it may appear that it is better to install dump-type air devices
and place critical operations under them. However, conditions outside this area should be
poorer and it is not unusual to find critical operations moving away from the designed
position. It is therefore the authors' belief that the

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Air supply devices give the best mixing and therefore constant air pollution throughout the
room should be used with unidirectional flow to improve local air conditions.
Air movement induced by blade diffuser.

Fig.24 Air movement induced by blade diffuser.

Fig.25 Air movement induced by the discharge air supply.

Calculation of air supply volume requires knowledge of the following:
• Minimum air change rates to meet appropriate clean room standards for removal of
internal contamination.
• Internal heat gain.
• Volume of air required to pressurize the suite.

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Experience indicates that a modern manufacturing facility, used for the production of
injectables, will contain process equipment that releases heat to space that will require 25 to
35 air changes per hour for cooling; this is significantly higher than the minimum levels
cited in cleanroom standards and much more than that required pressurizing the room.
Rooms should be designed so that the manufacturing process, and the environment, can be
monitored effectively. To achieve the objectives of the GMP Guidelines, it is important that
there is no variation in environmental conditions that could give unsatisfactory results and
therefore lead to product contamination. Therefore, it is necessary for the user to be able to
monitor the conditions in the room. These conditions, therefore, must be defined in room
validation and routinely maintained during manufacturing.
It is prudent to provide more complex installations with a variety of monitors to assist with
troubleshooting. For example, airflow measurement and pressure switches provide valuable
information about system performance. Failures of elements such as fans, filters and
controls, etc. They will change the pressure in the room.
The provision of unidirectional flow devices would normally be left to a specialist supplier,
However, when specifying unidirectional flow devices or cabinets, it is essential to either
write a specification or apply accepted clean air device standards.
The most frequent problems encountered with unidirectional clean air flow are filter seal
penetrations, cabinet shell leaks, airflow imbalance (in its Type II class), and the inability to
incorporate facilities to perform Convenient testing of filtration system integrity and
performance monitoring.

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Isolators and barrier devices
In recent years, isolator and barrier technology has been successfully applied to
pharmaceutical products.
Historically, isolators were used in the nuclear industry to handle and store radioactive
isotopes and therefore protect operators.
It is also used in veterinary research where it was used to keep animals germ-free. In
pharmaceutical manufacturing they were initially used to provide clean conditions in the
microbiological laboratory, where sterility testing of the final product was carried out. These
cleaning conditions had to be at least as good, if not better, than what was required in the
manufacturing area to ensure that 'false positives', that is, bacterial contamination arising in
the laboratory, did not cause the rejection of a lot. Isolators can be used to protect either the
product from contamination, or the personnel from potent compounds, or in some
applications, such as parenteral cytotoxic products, they can protect both.
The development of a multiplicity of applications has meant that the original relatively
simple design of an isolator has evolved and these evolved isolators are often referred to as
barrier technology.
The use of barrier technology has largely grown from the requirement to increase both
personnel and product protection, but there may also be advantages gained through reducing
the cost of providing and maintaining the manufacturing environment, in In the case of
aseptic filling of pharmaceuticals, it is common for the total installation and process costs for
an isolator application to be 70% to 90% of a traditional clean room system. However,
greater cost savings can be realized in operating costs where sometimes a 40% to 50%
reduction can be achieved. In such cases, savings can come from:
• A reduction in the amount of air needed to maintain cleanliness or asepsis
• A reduction in the amount of subdivision space used in manufacturing;
• A reduction in the quality of the garment and the number of times it is cleaned,

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• A reduction in the amount of monitoring for particles and microorganisms;
• A reduction in the area of critical surfaces requiring cleaning and disinfection;
• An increase in flexibility in personnel deployment;
• Better utilization of equipment.
Conventional filling of aseptic products is normally performed under unidirectional flow. In
this situation it is normal for staff to enter and work within the workstation under this one-
way pattern and therefore, high quality clean room garments should be worn, to ensure that
none of their bacteria reaches the product. It is also necessary to ensure that the air trapped
in the workstation from the surrounding room will have a low concentration of bacteria.
An isolator can exclude bacteria from both staff and the surrounding space, therefore
allowing a reduction in the quality of clothing and room air.
Due to the effectiveness of isolators in excluding bacteria, cleaning standards can be relaxed
not only in the area surrounding the isolator, but also in air movement, control measures
used to minimize air movement between the production room and its surroundings. This
relaxation of air movement control can, in turn, lead to a more simplified design of the
cleaning room and its air handling systems.
In some circumstances, it is possible to reduce the time required to construct a new
manufacturing facility with insulators. However, greater time savings can be achieved by
upgrading a facility by adding an isolator, rather than upgrading the entire manufacturing
facility.

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Typical Insulator Designs and Applications
The formulation, filling and quality control of sterile pharmaceutical products can employ
flexible or rigid isolation systems that can be used as linked networks or separate modules.
The range of size and complexity of insulators is large and continually grows as specific
process applications are developed. Many of the more complex systems must be designed
and manufactured as process engineering projects, rather than standard equipment
procurement tasks, to ensure that particular requirements are adequately defined, designed
and manufactured. Assembled, tested and put into operation. The design of insulators is
mainly influenced by:

• Whether the requirement is to protect the product, or personnel, or both; this

will determine whether the isolators should be positively or negatively pressurized,
with respect to the room it is in;
• The type of transfer system required for the entry and exit of materials into and out
of the isolator;
• The technique used to perform manipulations within the insulator;
• Whether rigid or flexible walls should be used.
Maximum protection of the product or process within an isolator will be achieved through
the use of a positively pressurized isolator. Internal pressures of the order of 20 to 70 Pa,
compared to the environment, are typical. Special care must be taken to ensure that
overpressurization is maintained when gloves or half suits are worn, as when a leak occurs it
is often traced back to this source. Where hazard containment is required, a negative
pressure system would be selected. Where an isolator is required to provide combined
product protection and containment, a decision must be made on the pressurization required.
Where asepsis must be maintained, a positive pressure would normally be selected and
special care would be taken in the selection of transfer system.
The type of transfer device selected for transferring items into and out of an isolator
operation will have a major influence on the ability of that system to maintain a defined
level of internal cleanliness or to contain a specific hazard.

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Most insulator applications require some human manipulation capability. Other than when
using robots or remote manipulators, this capability is achieved through the use of glove
ports or half suits. These two techniques have a major influence on the isolator, as they have
radically different ergonomic attributes and require completely different isolator designs to
accommodate them.
It is clear that rigid and flexible wall devices are fundamentally different in terms of their
durability, configuration, and manufacturing techniques. Generally flexible film, insulators
are simpler shapes and cannot easily accommodate complex air handling systems, fans and
air ducts.
To further emphasize and revise some of the objectives identified above, the designs used in
different applications are discussed and shown below.
Sterility tests . For many years, barrier technology has been a valuable tool for providing
clean conditions in the bacteriology laboratory to test the sterility of the final product. For
this application, flexible film and rigid wall devices have been used, successfully used in
clean room and non-clean room conditions in the microbiological laboratory.
These insulators are used to carry out manipulations with a bacteriological agent. Any
failure in the safety of the isolator will appear as growth in the bacteriological environment
and therefore the effectiveness of barrier technology, operating in conjunction with
disinfection techniques and transfer systems such as interlocking transfer ports, has been
demonstrated. Therefore, they can be confidently applied to high-quality aseptic processing
with the expectation of consistently high-quality aseptic.
Sterility testing requires strict control of microbial contamination from outside the controlled
environment, but not particulate contamination released by the process itself. Therefore, a
positive pressure isolator in a controlled environment, the use of non-unidirectional air flow
is satisfactory. Flexible film devices using half-suit manipulation techniques are frequently
used in these applications.

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An example of an isolator used in sterility testing is shown in Figure 26. Subdivision and
dispensing of potent compounds. As pharmaceutical products contain increasingly powerful
active ingredients, and as health, safety and environment

Fig 26, isolator used in sterility testing

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An example of a system used for drying and handling bulk powder is shown in Figure 27 .
In addition to providing an aseptic environment for bulk powder handling, it also provides
containment of the potent compound and a nitrogen environment to allow the use of
flammable solvents. It is a rigid positive pressure device, located in a CE Grade D clean
room (this is approximately equivalent to ISO 8 or Class 100000). Cleanliness of the internal
nitrogen environment is maintained. Using non-unidirectional air flow. The manipulations
are accomplished with gloves.

Fig 27, Specialized isolator for the processing and handling of potent drugs.

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Design
0 Considerations for the Surrounding Environment
Having taken all of the above as issues into account and determining the type and nature of
the barrier technology used and the quality of the surrounding environment, it is important to
consider the wide range of issues related to the quality of the surrounding environment. It is
not sufficient to consider only whether the environment should be classified in terms of a
clean room standard or an equivalent GMP microbiological requirement. It is necessary to
consider, in a much more exhaustive way, all the attributes of the installation in which the
insulator is placed, since this can have a great influence on the type of the surrounding
environment. Below, we identify some of the key themes to illustrate that the topic is more
than just a cleanroom cleaning classification.
The size of the manufacturing space is clearly significant in relation to the physicality, cost
of creating it, the energy to maintain the conditions, and the efforts to produce some
appropriate level of quality monitoring of that environment.
However, experience with isolator applications generally shows that the total
accommodation area will not be significantly reduced by the use of isolators or barrier
technology. Where you can gain an advantage is in
reduced complexity and subdivision of spaces. If a group of discrete isolators accommodate
different process steps, adjacent zones can be placed within a single space and great
advantages can be obtained in terms of communication, flexibility of people, circulation of
shared space, ventilation and air conditioning.
The layout of a set of rooms used in traditional aseptic production is shown in Figure 28. A
simpler design used with insulators, shown in Figure 29, is one such possible design.
Consideration should be given to the quality of construction and materials used to create the
facility, and a step from building high quality pharmaceutical clean rooms to good one.
Quality packaging department type construction can show significant cost and
construction time advantages. As mentioned above, simplified and less demanding space

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Environmental
1 requirements mean that HVAC systems are less demanding in performance
and can be much simpler in terms of zonal control of air volume, temperature and ambient
pressurization. These problems reduce both capital and operating costs.

Fig 28, Conceptual configuration of a traditional cytotoxic parenteral formulation for

clean rooms and ease of filling.

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2

Fig 29, Conceptual configuration of a cytotoxic parenteral formulation and ease of

filling using isolators for the formulation, filling and external decontamination process
steps.

Operational Issues/Revenue Costs

The other major advantage that can be gained from placing an effective isolator application
within the minimum necessary environment or environment is the cost of maintaining and
managing the surrounding environment.
Reductions can be obtained in the effort and, therefore, in the associated cost, in cleaning
and disinfection as well as the monitoring of particles and microbiological contamination.
By eliminating the need to heat and cool large amounts of air needed for cleaning or asepsis
maintenance to that required to satisfy occupant comfort, significant energy savings can be
achieved. Revenue costs associated with personnel control, particularly

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The
3 change of clothes is significantly reduced due to the simplified space with reduced
subdivision.
Room pressurization and air movement control
The entry of air contamination from outside the clean room is a common problem, although
good design can limit this. This can occur when outside air pollution is induced through a
poorly detailed fabric in the clean room. Gaps in fabrics should therefore be kept to a
minimum and the room pressurized to minimize or prevent this problem. Room
pressurization is discussed below.
Contamination entry can also occur when personnel, equipment and material are transported
through poorly designed airlocks and changing areas; This may be surface or air pollution.
Pharmaceutical cleanroom suites consist of several clean rooms within which different steps
of the manufacturing process are carried out. As product materials and packaging
components are carried through their processes and into different rooms, increasing
standards of environmental control are required until the stage of filling the product and
closing and sealing the container is reached (see Figures 21 and 22).
The highest quality condition is required here. As the sealed product moves through labeling
and inspection, less stringent environmental conditions are required. These different
standards of environmental control are achieved through different air supply rates and the
use of unidirectional flow units or isolators in critical areas.
To ensure that these different conditions are maintained in each clean room, Clean Room,
pharmaceutical good manufacturing practice standards and guidelines require that rooms be
maintained at different pressures. This is to prevent undesirable flow of air from a lower
grade area to a higher grade area, thus reducing the possibility of contamination transfer.
Experience, particularly with complex pharmaceutical processing suites involving many
rooms, shows that achieving a relative ambient pressure sensitive regime and its subsequent
maintenance presents some major design, commissioning and operational problems.
Within the standards established for clean rooms there is a consensus opinion that the
pressure difference between clean rooms should be

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of 410-15 Pa. This is a level that is easily achievable, easy to monitor, and appears to prevent
the transfer of contamination. This is worth keeping in mind that although clean room
guidelines may specify a differential
pressure of 10 or 15 Pa, this requirement is just a means to an end. If there is no adverse
airflow between rooms in the suite the pressure difference is not important.
However, this argument may not be understood and, therefore, not accepted by the user or
regulatory authorities. An exactly similar problem occurs in relation to insulators.
However, in this case because the controlled environment is small, the displacement, the
effect of gloves is important and must be taken into account when selecting and calculating
the qualifying differential pressure. Typical pressure differentials for insulators are 15-60.
In some situations, the clean room exhaust may be in an adjacent exterior hallway reached
through an airlock or changeover area and perhaps in an area of a lower pressure level than
the room. Therefore, the limitations of the construction to accommodate such static
pressures must be taken into account, as well as the capacity of the air handling system in
generating the required overpressure. Excess differential pressure of more than 30 Pa can
cause 'hissing' through door cracks and may give slight difficulties
when manually opening and closing swing doors.
Process equipment crossing ambient pressure limits can cause a problem, this can be
illustrated by considering a tunnel process where a component is washed, sterilized and
filled as it passes from a component preparation area to an aseptic filling room. . The
pressure differential will cause air to flow between the two areas joined by the tunnel. This
airflow can change the heating characteristics and therefore the efficiency of the hot air
furnace and can even cause hot spots and damage to the tunnel.
Fluctuation in pressure differential will cause changes in airflow quantities, which in turn
can lead to changes in efficiency and difficulties validating the system.

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Because
5 the tunnel crosses boundaries between areas of different pressures, it is necessary to
restrict the flow through the tunnel using some type of masking. If this is not done, excessive
air will be required to be supplied to the highest pressure area. Even with a well-masked
tunnel an adequate amount must be added to the air supply; this can be calculated from
equation (1) given later in this section.
Two methods by which clean rooms within a suite can be pressurized relative to each other
are available and are known as the 'closed door' and 'open door' solutions.
The open door approach has been developed and has particular value where airlocks are

TERMINAL
FILTERS

PRESSURE

LOW LEVEL
EXTRACT

AIR LEAKAGE
PATHS

Fig 30, closed door applied to the clean room assembly.

inconvenient or impractical to provide, e.g. hospital operating rooms. An example of a
'closed door' solution applied to a clean room assembly is shown in Figure 30.

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Diagrams
6 of the 'open door' solution applied to the design given in Figure 21 are shown in
Figure 31(a) - (c ). Figure 31(a) shows the expected airflow within the suite when all doors
are closed and Figure 31(b) and (c) shows the airflow through the suite when the doors of
the suite are closed. clean filling area were opened. Due to lack of space it is not possible to
illustrate the effect of opening the remaining doors in the suite. However, calculations show
that the air flow in the suite must be in the right direction, i.e. From clean to less clean areas,
this solution to air movement.
The air supply volume required to ensure that air movement will always be in the correct
direction throughout the assembly is approximately 0.69 m3/s towards the filling room and
approximately 0.63 m3/s to the preparation room of the solution. These volumes are those
necessary for air.

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7

Fig. 31 Airflow through the suite: (a) doors closed; (b) open door between filling room
and equipment and component preparation room; (c) Open door between filling room
and changing area.

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V.-INDUSTRY
8 VALIDATION AND QUALIFICATION
PHARMACEUTICAL
Introduction
The qualification of equipment in the pharmaceutical industry is an essential part of the
quality assurance required by law. This chapter provides an overview of how validation and
qualification are integrated into the GMP environment (1) and describes the general
qualification procedure with the key stages DQ(2), IQ(3), OQ( 4) and PQ(5). The main point
is the qualification of the team. The validation of computerized systems is briefly addressed.
In principle, the white paper is aimed at those interested, who have not yet had contact with
this topic.
In principle, it is addressed to those interested, who have not yet had contact with this topic.
History
In order to guarantee the safety of consumers, medicines are subject to a strict official
control process throughout their useful life. In order to comply with the official standard of
continuously producing products with the same quality, quality control systems have been
used in the pharmaceutical industry since the 1960s. This is what is known as Good
Manufacturing Practices.
Good manufacturing practices
Good practices reproduce each of the phases of the useful life cycle of a medicine, from
development to marketing, through testing and manufacturing.

1 Good Manufacturing Practice, 2 Design Qualification, 3 Installation Qualification, 4 Operational Qualification, 5 Process Execution Qualification

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The9 concept of Good Manufacturing Practices (GMP) was established by the FDA (Food
and Drug Administration). The GMP Guide is internationally recognized and is made up of a
collection of codes and complementary documents.
The first GMP were published in 1968 by the World Health Organization (WHO).
Over the years, additional good practices were introduced, such as Good Laboratory
Practices or Good Clinical Practices.
Good Manufacturing Practices (GMP) were originally conceived to be applied with
medicines; However, today, its use has extended to the food and cosmetic industry.
GMP publications from different organizations
The authorities responsible for the approval and control of medicines, the FDA (in the US).
USA) and the EMA (in the EU) at the national level, as well as the PIC/S (Pharmaceutical
Inspection Convention/Scheme) and the ICH (International Conference on Harmonisation)
at the international level, have published GMP guides. The PIC/S is an international
organization that is responsible for the approval of official inspections by all parties.
The ICH is striving to achieve a code accepted and standardized by the USA. USA, Japan
and the European Union. The table below shows an overview of the documents to consider
regarding GMP and GLP. Integrity is not guaranteed.

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Organization Code Qualification Content

EMA GMP Guide to Good Manufacturing Practices parts 1 and II GMP requirements for medicines and active ingredients:
validated processes, continuous stability controls , risk
management
Annex 11 Computerized systems

Annex 15 Qualification and validation

Annex 20 Quality Risk Management

ZLG Aide mémoire 07121105 Qualification and validation inspection in

Detailed explanations from the inspectors ' point of view
manufacturing and quality control of pharmaceutical products

FDA CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED

Title 21 CFR Part 210 GMP requirements for medicines and active ingredients
PHARMACEUTICALS
Title 21 CFR Part 211
Guidance for Industry Process Validation: General Principles and Practices Final Guidance for Industry
and FDA Staff
WHO WHO, Annex 2 Annex 2: WHO good manufacturing practices for pharmaceutical products: main Minimum GMP requirements worldwide
principles

ICH ICH, QiA Stability Testing of New Drug Substances and Products Harmonized directives for the USA. USA, Japan and the
European Union
ICH, Q7A
Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients

ICH, Q8A Pharmaceutical Development

ICH, Q9A Quality Risk Management

PIC/S PI 006-3 RECOMMENDATIONS ON VALIDATION MASTER PLAN INSTALLATION AND Orientation

OPERATIONAL QUALIFICATION NON-STERILE PROCESS VALIDATION
CLEANING VALIDATION

PS/INF11/2015 GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL PRODUCTS Identical to Annex 15 of the European GMP
ANNEX 15
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US GMP (Current Good Manufacturing Practice (cGMP)) USA They are contained in the
Code of Federal Regulations (Code of Federal Regulations) 21 CFR part 210 (drugs) and 21
CFR part 211 (active ingredients), so they are legally binding on manufacturers and
importers. The GMPs are subject to an annual review (hence they are current).
Similarly, in Europe there are also two EU GMP Guides. Part I is aimed at drug
manufacturers and part 2 at active ingredient manufacturers.
Part I of the European Union Good Manufacturing Practice Guide comprises 9 chapters that
formulate the basic requirements for quality control in the development and manufacturing
process, as well as in relation to personnel, premises and equipment and quality controls.
Another fundamental requirement of the two GMP Guides is the continuous performance of
stability controls on the active ingredients and finished medicines. These stability checks
can be carried out in climatic chambers from the company BINDER GmbH.
"The basic GMP requirements are as follows: (i) all manufacturing processes are clearly
defined, systematically reviewed based on experience gained, and capable of consistently
producing medicines of the quality required [...] (ii) critical steps in manufacturing
processes and significant process changes are validated."
Validation
Validation serves as a quality control method and is an important component of GMP. The
definition according to the European Union can be found in the EU GMP Guidelines:
"Obtaining evidence, in accordance with Good Manufacturing Practice, that any procedure,
process, equipment, material, activity or system actually produces the intended result (see
also qualification)."Guide to Good Manufacturing Practice, Part I
The FDA previously defined validation as:

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"A documented program that provides a high degree of assurance that a specific process,
method, or system will consistently reproduce a result that meets pre-established acceptance
criteria."
The FDA's current view requires that manufacturers have a thorough understanding of the
process: "Process validation:
The collection and evaluation of data, from the process design stage through commercial
production, which establishes scientific evidence that a process is capable of consistently
delivering quality products."
Process validation – The collection and evaluation of data from process design to
commercial production, which establishes scientific evidence that a process is capable of
consistently producing a quality product.
The purpose of the definitions is for the pharmaceutical manufacturer to completely master
all quality-relevant processes, know their risks and strive to maintain their (validated) status
in force. The GMP requires validation to be carried out, but in no case does it indicate in
detail how and what needs to be validated.
Annex 15 helps with validation: qualification and validation with key definitions and
clarifications on the process and types of validation. In addition, a risk assessment is also
necessary to establish the scope and scope of the validation. You will find more details on
risk assessment in Annex 20: Search quality risk management and its content corresponds to
the ICH Q9 Guideline Quality risk management.

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From the point of view of validation activities, it follows that the concept of validation, on
the one hand, is used as a generic term and, on the other hand, describes other permanent
validation activities such as, for example, the validation of processes or the validation of
computerized systems. To refer to premises, equipment and personnel, the term
qualification is used exclusively. Although there is no unified linguistic regulation in the EU
GMP, over the years it has been established that "qualification" is used for everything that is
physical and validation for developments, methods and processes. The procedure in the case
of validation and qualification is similar.
Before proceeding with any validation activity, the Validation Master Plan or PMV must be
prepared. This main document includes company data, describes the validation project and
designates the responsible persons. In addition, the validation policy and general procedures
involved in validation are also included. In order to document all validation activities in
accordance with GMP, the Validation Master Plan includes the corresponding validation
protocols and reports. The time course is also reflected in the Validation Plan.
References to existing documents, such as standards and GMP documentation, are
permitted.
Validation types
Wherever possible, prospective validation should be carried out, i.e. before production itself
begins.
Prospective validation refers to existing facilities and processes, so physical and analytical
process data from batches already manufactured are considered. We speak of concurrent
validation when, at the time of starting production, the complete validation has already been
completed.
Qualification
The definition of qualification matches the definition of validation:
"Operation by which it is verified that a piece of equipment functions correctly and actually
produces the expected results. The term validation is sometimes expanded to include the
concept of qualification. ".Guide to Good Manufacturing Practices, part IO, also:
"Operation by which it is verified that equipment works correctly and

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actually produces the intended results. Qualification is part of validation, but separate
qualification stages do not constitute process validation." Good Manufacturing Practices
Guide, Part I
Annex 15 specifies what needs to be qualified and how qualification and validation are
related.
"The equipment, facilities, services and systems used for process validation must be
qualified. Analytical methods will be validated for their intended use. "The personnel
involved in validation must be properly trained."
Annex 15 of the EU Good Manufacturing Practice Guide

Qualification is a process that is divided into four stages:

• Design Qualification (DQ)
Documented verification that the proposed design of facilities, systems and equipment is
suitable for its intended purpose.
• Installation Qualification (IQ)
Documented verification that facilities, systems and equipment, as installed or modified,
comply with the approved design and manufacturer's recommendations.
• Operational Qualification (OQ)
Documented verification that facilities, systems and equipment, as installed or modified,
operate as desired over all intended operating ranges.
• Process Execution Qualification (PQ)
Documented verification that systems and equipment can operate effectively and
reproducibly in accordance with the approved process method and product specifications.

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The following diagram explains the qualification process and the way in which each of its
elements is related to the rest.

Above all grading activities is the grading plan. In this, unlike the validation plan, the
qualification measures to be carried out are described in detail. The responsible persons are
defined, as well as the tests to be carried out and, together with the risk assessment, the
acceptance criteria are included, that is, the parameters to be verified, the critical
characteristics for quality and the operational situations. On the part of the authorities and
the GMP, no regulations have been established that indicate the scope of the qualification.
Each of the stages of the qualification must be authorized before starting and will end with
the recapitulation, in writing, of the results of the qualification in the corresponding reports.
It is common to group the plan and the qualification report in the same document.
Qualification stages
In the Design Qualification (DQ) phase, the specifications and specifications are prepared.
The DQ is composed, in turn, of the User Requirement Specification (URS), the Functional
Design Specification (FDS) and the Design Specification (DS).
}D}Q in detail: The URS or user specification describes the requirements that the
equipment or installation must meet. The user specification has

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to be prepared by the contractor and will also take into account the requirements of the
GMP. The user specification (URS) is the basis for the qualification of the execution of the
process. In the next stage, based on the URS, the specification sheet (Functional Design
Specification) is prepared. This specifies the technical functions with which the user's
requirements will be met. It serves as a basis for choosing suppliers. The FDS is verified
through performance qualification. In the next stage, the design specification (project
specification) is created based on the specification document. This includes detailed data
about the equipment or installation to be acquired, including all modifications, accessories
and necessary documentation. The proof that the design specification has been met is the
qualification of the installation. In the case of certain complex equipment such as e.g. For
example, incubators or climatic chambers for stability controls, the project specification can
be integrated into the specifications. Design qualification is the most important element of
qualification since, in addition to specifications, plans, protocols and qualification reports
for IQ, OQ and PQ are also prepared. The DQ ends with the ordering of the
system/equipment.

The Factory Acceptance Test (FAT) is carried out by the manufacturer, who provides
documentary evidence that the equipment or system has been manufactured and operates
according to its specifications. Once the FAT has been successfully carried out, the
equipment or system is delivered to the customer by the manufacturer, thus receiving the
delivery release. After delivery

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properly, a Site Acceptance Test (SAT) is usually performed at the customer's facility,
which must again demonstrate that the equipment is operating within specifications. It is
strongly recommended that both FAT and SAT be carried out, especially on complex
systems. In the case of having standard equipment, e.g. For example, a climatic test
chamber or an incubator, the FAT can be dispensed with and the SAT can be carried out in
combination with the qualification of the installation.

The installation qualification (IQ) is documentary proof that the equipment or system has
been delivered without damage, complete and in accordance with the previously specified
documentation. After carrying out a visual inspection, the equipment or, where applicable,
the system, will be installed in accordance with the manufacturer's instructions.
Users will be duly instructed on its handling. During installation qualification, the sensors
will be calibrated and adjusted, if this was not done successfully during the plant acceptance
test.
All activities carried out will be documented in a report, the release of which will be the
precondition to be met for the subsequent qualification of the operation.

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The performance qualification (OQ) is documentary evidence that the system or equipment
is operating correctly according to specifications.
For example, in the case of a climatic test chamber, certain setpoint values for the
temperature and relative humidity of the air are entered and the actual values achieved are
documented. Furthermore, if previously specified in the qualification plan, it is possible to
verify the temperature distribution, the activation of the temperature alarm, as well as the
recovery time after closing the door. It is usually carried out in a vacuum.
At this stage of qualification, Standard Operating Procedures (SOPs) for users, maintenance
plans and log books must be present. In addition, the deadlines and modifications in which a
requalification of the system must be carried out are also determined.
The performance qualification will be concluded when those responsible present the release
of the qualification report.
Typically, performance qualification is carried out immediately after installation
qualification.

As the last qualification activity, the Process Execution Qualification (PQ) is performed.
This represents documented proof that the equipment, in its state of load and under
operating conditions, is capable of achieving the expected results in a reproducible manner.
In the case of stability controls, the temperature distribution in different load states is of
great interest. Depending on the risk assessment, there may be another part of the process
execution qualification, known as "Worst Case" conditions. These operating conditions,
different from ideal conditions, can show to what extent product quality is affected.

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In this case, written documentation is also needed. The equipment/system will be considered
qualified at the time the responsible persons release the final report.
As a general rule, during qualification we will proceed following the principle of "as much
as is necessary, with as little as possible" in order to save and not consume too many
resources. In order to reduce the effort to a minimum when preparing the qualification
documentation, there is the possibility of using documents that have already been prepared.
For standard equipment, such as climate test chambers, standardized manufacturer
qualification documentation can be included in the company's own documentation. For
equipment used in regulated environments, BINDER GmbH offers qualification
documentation for IQ, OQ and PQ, which is tailored to customer needs.
These documents describe how to proceed and include checklists and conclusive
summaries.

Validation of computerized systems

Computerized systems for electronic data collection, measurement and standard control are
used as standard in the pharmaceutical industry. Annex 11 of the European Union GMP
Guide explicitly requires that software must be validated and IT infrastructure must be
qualified, provided that information processing is involved in the relevant qualification
stages.
In USA In the US, this requirement is stipulated in CFR title 21 part 820. Furthermore, part
11 regulates the treatment of electronic signatures. As with Schedule 11, there is an FDA
support for industry and FDA employees describing the transfer. For example, BINDER
GmbH's climatic test chambers, used for stability checks in the quality control process, can
be connected to software suitable for data collection and equipment control.
The procedure to validate/qualify the computer system is the same as to qualify the
equipment or facilities.
Validated system

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The successful completion of the qualification, validation of computerized systems, as well
as the validation of cleaning and analytical methods is the basis for validating the (entire)
manufacturing process, of which the system/equipment is a part, like an everything.
Validation is not a single action: it is about maintaining the validation state.
Trends
A novelty in the GMP Guides in Europe and the USA. USA It is the requirement to
maintain a continuous validation state, instead of implementing revalidation on a regular
basis, which is known in English as Ongoing Process Verification. This new approach
allows applying the consideration of the life cycle of the manufacturing process to that of
process validation, that is, a global consideration of all phases, from planning to
declassification.
In this way, the tendency is revealed that, from the authorities' side, less value is given to the
obstinate application of formalisms, preferring much more the application of scientific
principles. In equipment qualification, this translates as the repetition of quality-relevant,
planned and logical tests in order for the equipment or system to maintain a qualifying state.
Final conclusion
The user in regulated spaces is not exempt from the validation of processes critical to
quality. In order to satisfy the validation requirement, it will be necessary to make a certain
effort that will vary depending on the complexity of the object to be validated. This will
generate costs and consume resources in the company. However, the rule of having to plan a
process with documentation, evaluate it and verify it continuously also brings advantages:
precision when planning and evaluating costs can lead to cost savings, which will avoid
"surprises." " later in operation. Maintaining consistent product quality eliminates costly
product recall campaigns and improves customer satisfaction.
Exhibit
Sources:
WHO, Annex 2 WHO good manufacturing practices for pharmaceutical products: main
principles

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1
Ministry of Health, Social Services and Equality: Guide to Good Manufacturing Practices
part I and II
Ministry of Health, Social Services and Equality: Annex 11 on the Guide to Good
Manufacturing Practices of the European Union, Computerized Systems
Ministry of Health, Social Services and Equality: final version of Annex 15 of the EU Good
Manufacturing Practice Guide: Qualification and validation
Aide mémoire 07121105 Qualification and validation inspection in pharmaceutical
manufacturing and quality controls
Federal Central Authority for health protection in relation to medicines and medical devices
(ZLG)
ICH, Q1A, Stability Testing of New Drug Substances and Products
ICH, Q7A Good Manufacturing Practice Guide for Active Pharmaceutical Ingredients
ICH, Q8A Pharmaceutical Development
ICH, Q9A Quality Risk Management
ICH, Q10A Pharmaceutical Quality System
FDA, Guidance for Industry: Process Validation: General Principles and Practices
General Principles of Software Validation; Final Guidance for Industry and FDA Staff
FDA, General Principles of Software Validation; Final Guidance for Industry and FDA
Staff
PIC/S: GUIDE TO GOOD MANUFACTURING PRACTICE FOR MEDICINAL
PRODUCTS ANNEX 15 *
PIC/S, PI 006-3:RECOMMENDATIONS ON VALIDATION MASTER PLAN
INSTALLATION AND OPERATIONAL QUALIFICATION NON-STERILE PROCESS
VALIDATION CLEANING VALIDATION

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VI.- CLEAM ROOM CRITICAL PATIENTS UNIT (UPC)
Introduction
Although the most important thing in the design of clean rooms should be hospital centers,
where IPSE, ASHRAE, ISO regulations, etc., are the most demanding. In practice this is not
the case, it is more common to find good designs in the development of pharmaceutical
laboratories than in a critical patient unit (CCU) of a hospital.
Isolation rooms (immunosuppressed and infectious) are a real need in hospitals. Over the
last few years this need has become more evident and has been increasing. Episodes such as
the recent cases of Ebola highlight this situation.
Isolated environments, laboratories, boxes, are critical environments and special precautions
must be taken in their ventilation conditions, filtration levels, pressure control (positive or
negative) and monitoring for the safety of patients and staff.
People can suffer and even die as they are exposed to diseases that they did not have when
they come to a hospital. There are often things that hospital design engineers could have
done to prevent the germs found in these healthcare facilities.
These diseases cause organisms to enter the building through the air supply, feed on
moisture, to produce, breed in installed reservoirs, and move air pollutants through the
ventilation system ducts. That
includes fungi, molds, bacteria, inorganic and organic that cause many problems, from
annoying to fatal colds and pneumonia. Legionnaires' disease received its name from the
1976 incident in Philadelphia where 34 members of the American Legion attending a
convention died from that, previously unnamed pneumonia. After much investigation, it was
determined that the bacteria was distributed through the air conditioning system.
In this era of antibiotics, infections are too often acquired in a hospital setting, where they
are not considered important. It is commonly accepted that patients will sometimes suffer
from infections while in hospital "So what! One shot of antibiotic penicillin and that little
rash or fever is gone, right? “, quite true, since, in the United States twenty thousand
(20,000) people die each year as a direct result of nosocomial infections.

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Sixty thousand (60,000) others die, where nosocomial infections are a contributing factor.
Engineering, architectural, or medical firms have placed very little emphasis on designing
facilities for maximum infection control. Often, those who built the facility did so with
criteria that were more related to
Cost, energy efficiency, sustainability and aesthetics, ease of service or asepsis. It is no
longer enough for hospital engineers and planners to blindly accept that | What they design
is the best for patient care.
Controlled environment
There has been growing concern in the medical sector and the community regarding the
dangerous effects of poor indoor air quality on people's health leading to increased
incidence of health-related symptoms such as headache, dizziness, eye and throat infection,
fatigue, memory loss, etc. The terminology 'Indoor Air Quality' refers to the nature of the
conditioned (heated/cooled) air that circulates throughout the space. This refers not only to
comfort, which is affected by temperature, humidity, odor, but also to the harmful chemical
and biological contaminants present in the conditioned space.
The basic differences between an air-conditioned controlled environment for hospitals to
take care of the above are the factors mentioned and that for other types of buildings are
derived from:
1. The need to restrict air movement within and between different departments.
2. Specific requirements for ventilation and filtration to dilute and remove contamination in
the form of odor, airborne microorganisms and viruses, and hazardous chemical and
radioactive substances.
3. The different temperature and humidity requirements for various areas; and
4. The design sophistication necessary to allow precision in the control of environmental
conditions.
The heating, ventilation and air conditioning (HVAC) system and indoor air quality studies
have shown that patients who have controlled environments have a faster recovery than
those who do not.

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Patients with thyrotoxicosis do not tolerate humid heat in high temperature conditions. A
cool, dry environment promotes heat loss through radiation and evaporation from the skin
and can save the patient's life. On the contrary, patients with burns need more heat in the
environment and high relative humidity. A room for burn victims should have temperature
controls that allow the room temperature to be adjusted up to 32°C dry bulb and the relative
humidity up to 95%.
The most important definitions in UPC rooms are the following according to ASHRAE 170:
Infection Control Risk Assessment (ICRA): determination of the potential risk of
transmission of various infectious agents in the facility, a classification of those risks, and a
list of practices required to mitigate those risks during construction or renewal.
Nursing facilities: facilities that provide care,
treatment and resident service areas (including skilled nursing, subacute care, and other
facilities for Alzheimer's and other types of dementia).
Immunocompromised patients: patients whose immune mechanisms are deficient due to
immunological disorders (e.g. e.g., human immunodeficiency virus [HIV] infection or
congenital immunodeficiency syndrome), chronic diseases (e.g. diabetes, cancer,
emphysema, or heart failure), or immunosuppressive therapy (e.g. (e.g., radiation, cytotoxic
chemotherapy, anti-rejection drugs, or steroids) (see Centers for Disease Control and
Prevention (CDC) [2003] in Informational Appendix B).
High-risk immunocompromised patients: Patients who are at highest risk for infections
caused by airborne or waterborne microorganisms. These patients include, but are not
limited to, allogeneic stem cell transplant patients and intensive chemotherapy patients.
Inpatient: A patient whose stay in a health care facility is expected to require twenty-four
hours or more of patient care.

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Airborne Infection Isolation Room: A room that is designed in accordance with the
requirements of this standard and intended to provide isolation for airborne infections.
Protective Environment (PE) Room: A patient room designed in accordance with this
standard and intended to protect a high-risk immunocompromised patient from pathogens.
Invasive Imaging Procedure Room – A room in which radiographic imaging is used and
in which instruments or devices are inserted into patients through the skin or body orifices
under sterile conditions for diagnosis and/or treatment.
Triage: The process of determining the severity of illness or injuries in patients so that
those with the most urgent illnesses or injuries can be treated immediately and those with
less serious injuries can be treated later or in another area.
To provide comfortable conditions in the hospital, the HVAC systems installed are made up
of the following main components: -
1. Compressor 2. Capacitor 3. Evaporator 4. Pumps and cooling towers 5. Air treatment
units 6. Air system distribution (ducts, structures / diffusers).
Recommended design conditions, ventilation and pressure requirements for comfort and
cross contamination.
The control of critical areas is indicated in Table 17 in accordance with ASHRAE
Standards 170 (table 7-1, ASHRAE 170 2013)

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Table 17 Environmental conditions of clean rooms at UPC

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Pressure All Room Air... . ,

Recirculated Air
_ . __ Relationship to Minimum Minimum Exhausted , r RH(k), Design Temperature (1),
1- unction ot Space by Means of . .
Adjacent Areas Outdoor ach Total ach Directly „ 1.). % °F/°C
,tn_ Outdoors
. (j) Room Units (a)
(n)
SURGERY AND CRITICAL CARE
Classes B and C operating rooms, (m), (n), (o) Positive 4 20 N/R No 30-60 68-75/20-24
Operating/surgical cystoscopic rooms, (m), (n) (o) Positive 4 20 N/R No 30-60 68-75/20-24
Delivery room (Caesarean) (in), (n), (o) Positive 4 20 N/R No 30-60 68-75/20-24
Substerile service area N/R 2 6 N/R No N/R N/R
Recovery room N/R 2 6 N/R No 30-60 70-75/21-24
Critical and intensive care Positive 2 6 N/R No 30-60 70-75/21-24
Wound intensive care (bum unit) Positive 2 6 N/R No 40-60 70-75/21-24

Newborn intensive care Positive 2 6 N/R No 30-60 70-75/21-24

Treatment room ( p) N/R 2 6 N/R N/R 30-60 70-75/21-24
Trauma room (crisis or shock) (c) Positive 3 15 N/R No 30-60 70-75/2 1-24
Medical/anesthesia gas storage (r) Negative N/R 8 Forks N/R N/R N/R
Laser eye room Positive 3 15 N/R No 30-60 70-75/2 1-24
ER waiting rooms (q) Negative 2 12 Forks N/R max 65 70-75/2 1-24

Triage Negative 2 12 Forks N/R max 60 70-75/21-24

ER decontamination Negative 2 12 Forks No N/R N/R
Radiology waiting rooms (q) Negative 2 12 Forks N/R max 60 70-75/21-24
Class A Operating/Procedure room (o), (d) Positive 3 15 N/R No 30-60 70-75/21—24
INPATIENT NURSING
Patient room(s) N/R 2 6 N/R N/R max 60 70-75/21-24
Toilet room Negative N/R 10 Forks No N/R N/R
Newborn nursery suite N/R 2 6 N/R No 30-60 72-78/22-26

Protective environment room (f), (n), (t) Positive 2 12 N/R No max 60 70-75/21-24
All room (e), (n\ (u) Negative 2 12 Forks No max 60 70-75/21-24
All isolation anteroom (t) (u) N/R N/R 10 Forks No N/R N/R
Labor/delivery/recovery. / postpartum (LDRP) (s) N/R 2 6 N/R N/R max 60 70-75/21-24
Labor/delivery/recovery (LDR) (s) N/R 2 6 N/R NR max 60 70-75/2 1-24

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All Room Air Air Recirculated by
Pressure Minimum Minimum Exhausted
Function of Space Means of Room I'nits RH(K), % Design Temperature (1), °F/°C
Relationship to Outdoor ach Total ach Directly to Outdoors (a)
Adjacent Areas (n) (j)
Corridor N/R N/R 2 N/R NR N/R N/R
SKILLED NURSING FACILITY

Resident room N/R 2 2 N/R NR N/R 70-75/21-24

Resi de nt g atheri ng. activity /di n i ng N/R 4 4 N/R NR N/R 70-75/21-24
physical therapy Negative 2 6 NR NR N/R 70-75/21-24
Occupational therapy N/R 2 6 NR N/R NR 70-75/21-24
Bathing room Negative N/R 10 Forks NR N/R 70-75/21-24

RADIOLOGY (v)
X-ray (diagnosis and treatment) N/R 2 6 NR N/R max 60 72-78/22-26
X-ray (surgery/critical care and catheterization) Positive 3 15 NR No max 60 70-75/21-24
Darkroom (g) Negative 2 10 Forks No N/R N/R
DIAGNOSTIC AND TREATMENT

Bronchoscopy, sputum collection. 2 12 Forks No NR 68-73/20-23

and pentamidine administration (n)
Laboratory, general (v) Negative 2 6 NR No NR 70-75/21-24
Laboratory, bacteriology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, biochemistry (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, cytology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, glasswashing Negative 2 10 Forks No N/R N/R
Laboratory, histology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, microbiology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, nuclear medicine (v) Negative 2 6 Forks No NR 70-75/21-24
Laboratory, pathology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, serology (v) Negative 2 6 Forks No N/R 70-75/21-24
Laboratory, sterilizing Negative 2 10 Forks No N/R 70-75/21-24
Laboratory, media transfer (v) Positive 2 4 NR No N/R 70-75/21-24
Autopsy room (n) Negative 2 12 Forks No N/R 68-75/20-24
Nonrefrigerated body-holding room (h) Negative N/R 10 Forks No N/R 70-75/21-24
Pharmacy ( b) Positive 2 4 N/R NR N/R N/R
Nott: N/R no requirement

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Pressure All Room Air
Air Recirculated by
Minimum Minimum Exhausted RII (k), % Design Temperature (1). °F/°C
Function of Space Relationship to Adjacent Means of Room Units
Outdoor ach Total ach Directly to Outdoors
Areas (n) (a)
(j)

Examination room N/R 2 6 N/R NR max 60 70-75/21-24

Medication room Positive 2 4 N/R NR max 60 70-75/21-24
Endoscopy Positive 2 15 N/R No 30-60 68-73/20-23
Endoscope cleaning Negative 2 10 Forks No N/R N/R

Treatment room N/R 2 6 N/R N/R max 60 70-75/21-24

Hydrotherapy Negative 2 6 N/R N/R N/R 72-80/22-27
physical therapy Negative 2 6 N/R NR Max 65 72-80/22-27
STERILIZING

Sterilizer equipment room Negative N/R 10 Forks No N/R N/R

CENTRAL MEDICAL AND SURGICAL SUPPLY

Soiled or decontamination room Negative 2 6 Forks No N/R 72-78/22-26

Clean workroom Positive 2 4 N/R No max 60 72-78/22-26

Sterile storage Positive 2 4 N/R NR max 60 72-78/22-26

SERVICE

Food preparation center (i) N/R 2 10 N/R No N/R 72-78/22-26

Warewashing Negative N/R 10 Forks No N/R N/R
Dietary storage N/R N/R 2 N/R No N/R 72-78/22-26
Laundry, general Negative 2 10 Forks No N/R N/R
Soiled linen sorting and storage Negative N/R 10 Forks No N/R N/R
Clean linen storage Positive N/R 2 N/R NR N/R 72-78/22-26

Linen and trash chute room Negative N/R 10 Forks No N/R N/R
Bedpan room Negative N/R 10 Forks No N/R N/R
bathroom Negative N/R 10 Forks No N/R 72-78/22-26
Janitor's closet Negative N/R 10 Forks No N/R N/R
SUPPORT SPACE

Soiled workroom or soiled holding Negative 2 10 Forks No N/R N/R

Clean workroom or clean holding Positive 2 4 N/R NR N/R N/R

Hazardous material storage Negative 2 10 Forks No N/R N/R

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Table 7-1 Notes:

a. Recirculating room HVAC units (with heating or cooling coils) are acceptable to achieve the required air change rates. Because of the cleaning difficulty and the potential for buildup of contaminants tion, recirculating room
units shall not be used in areas marked “No." Isolation and intensive care unit rooms may be ventilated by reheat induction units in which only the primary air supplied from a central system passes through the reheat unit.
Gravity-type heating or cooling units, such as radiators or convectors, shall not be used in operating rooms and other special care areas.
b. Pharmacy compounding areas may have additional air change and filtering requirements beyond the minimum of this table depending on the type of pharmacy, the regulatory requirements (which may include adoption of USP
797), the associated level of risk of the work (sec USP 797) , and the equipment used in the spaces.
c. The term trauma room as used here is a first aid room and/or emergency room used for general initial treatment of accident victims. The operating room within the trauma center that is rou tinely used for emergency surgery is
considered to be an operating room by this Standard.
d. Pressure relationships need not be maintained when the room is unoccupied.
e. Some isolation rooms may be provided with a separate anteroom, but an ante room is not required by this standard.
f. Protective environment rooms are those used for high-risk immunocompromised patients. Such rooms are positively pressurized relative to all adjoining spaces to protect the patient.
g. Exception regarding: All air need not be exhausted if darkroom equipment has a scavenging exhaust duct attached and meets NIOSH ventilation standards . OSHA, and local employee exposure limits. ’ 3
h. A nonrefrigerated body-holding room is applicable only to facilities that do not perform autopsies on-site and use the space for short periods while waiting for the body to be transferred.
i. Minimum total air changes per hour (ach ) shall be that required to provide proper makeup air to kitchen exhaust systems as specified in ANSUASHRAE Standard 154.4 In some cases, excess exfil tration or infiltration to or
from exit corridors compromises the exit corridor restrictions of NFPA 90A,5 the pressure requirements of NFPA 96.6 or the maximum defined in the table. During operation ation, a reduction to the number of air changes to any
extent required for odor control shall be permitted when the space is not in use. (See AIA [2006] in Informative .Annex B: Bibliography.)
j. In some areas with potential contamination and/or odor problems, exhaust air shall be discharged directly to the outdoors and not recirculated to other areas. Individual circumstances may require spe cial consideration for air
exhausted to the outdoors, for example, intensive care units in which patients with pulmonary infection are treated and rooms for bum patients. To satisfy exhaust needs, with Constant replacement air from the outdoors is
necessary when the system is in operation.
k. The RH ranges listed are the minimum and maximum limits where control is specifically needed.
l. Systems shall be capable of maintaining the rooms within the range during normal operation. Lower or higher temperature shall be permitted when patients' comfort and/or medical conditions require those conditions.
m. National Institute for Occupational Safety and Health (NIOSH) criteria documents regarding occupational exposure to waste anesthetic gases and vapors, and control of occupational exposure to nitrous oxide indicate a need for
both local exhaust (scavenging) systems and general ventilation of the areas in which the respective gases are used. Refer to NFPA 99 for other requirements.®
n. If monitoring device alarms are installed, allowances shall be made to prevent nuisance alarms. Short term excursions from required pressure relationships shall be allowed while doors are moving or temporarily open. Simple
visual methods such as smoke trail, ball-in-tube, or flutterstrip shall be permitted for verification of airflow direction. Recirculating devices with HEPA filters shall be per committed in existing facilities as interim, supplemental
environmental controls to meet requirements for the control of airborne infectious agents. The design of either portable or fixed systems should prevent stagnation and short circuiting of airflow. The design of such systems shall
also allow for easy access for scheduled preventive maintenance and cleaning.
o. Surgeons or surgical procedures may require room temperatures, ventilation rates, humidity ranges, and/or air distribution methods that exceed the minimum indicated ranges.
p. Treatment rooms used for bronchoscopy shall be treated as bronchoscopy rooms. Treatment rooms used for procedures with nitrous oxide shall contain provisions for exhausting anesthetic waste gases.
q. In a recirculating ventilation system, HEPA filters shall be permitted instead of exhausting the air from these spaces to the outdoors provided the return air passes through the HEPA filters before it is
introduced into any other spaces. This requirement applies only to waiting rooms programmed to hold patients awaiting chest x-rays for diagnosis of respiratory disease.
r. See NFPA 99 for further requirements.®
s. For patient rooms, labor/delivery/recovery rooms, and labor/delivery/recovery/postpartum rooms, four total ach shall be permitted when supplemental heating and or cooling systems (radiant heating and cooling, baseboard
heating, etc.) are used.
t. The protective environment airflow design specifications protect the patient from common environmental airborne infectious microbes (ie, Aspergillus spores). Recirculation HEPA filters shall be permitted to increase the
equivalent room air exchanges; However, the outdoor air changes are still required. Constant volume airflow is required for consistent ventilation for the protected environment ment. If the design criteria indicate that All is
necessary for protective environment patients, an anteroom should be provided. Rooms with reversible airflow provisions for the purpose of switching between protective environment and All functions shall not be permitted.
u. The All room described in this standard shall be used for isolating the airborne spread of infectious diseases, such as chickenpox, chickenpox, or tuberculosis. The design of All rooms shall include the pro vision for normal
patient care during periods not requiring isolation precautions. Supplemental recirculating devices using HEPA filters shall be permitted in the patient room to increase the equivalent room air exchanges; However, the outdoor
air changes are still required. All rooms that are retrofitted from standard patient rooms from which it is impractical to exhaust directly outside may be received culated with air from the All room, provided that the air first passes
through a HEPA filter. HEPA filtered exhaust air from All rooms may mix with exhaust air that serves non-AII spaces prior to being discharged directly outdoors. Rooms with reversible airflow provisions for the purpose of
switching between protective environment and All functions shall not be permitted. See the guidelines in Informative Annex B: Bibliography for more information.
White Rooms 1 Digital bro. Prepared by e
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(I) Air intake/air extraction
(A) Air intake
The final quality of the air depends on the supply. This is critical as the location of an air
intake is selected, for the best air available is not the most economical. Outdoor air intakes
must be located to attract the best quality air. They should be away from vehicle exhaust,
sewage extraction and any other polluting source, since birds and vermin like to nest in air
intakes.
Birds are an important source of Aspergillus, one of the most common causes of infection in
immunocompromised patients. Insects due to animal dirt and even then cleaning must be
done.
Aspergillus is a genus of about six hundred fungi (molds), and is ubiquitous. Fungi can be
classified into two basic morphological forms: yeasts and hyphae. Aspergillus is a
filamentous fungus (made up of chains of cells, called hyphae).
The exterior air intake grilles must have a surface designed to prevent the entry of rainwater.
These outlets should be located as far away as possible (in directionally different exposures
whenever possible), but not less than 9 m from the exhaust outlet, ventilation outlets of the
hospital or adjacent buildings, extractions from surgical wards, cooling towers, chimneys of
pipes.
The bottom of outside air intakes serving central systems should be located as high as
practical (3.6 m is recommended) but not less than 1.8 m above ground level or if installed
on the roof, 0.9 m above roof level.
(B) exhaust outlets
These exhausts must be located a minimum of 3 m, above ground level and away from
doors, occupied areas and operable windows. Preferred location for exhaust outlets that are
at ceiling level projecting upward or horizontally away from outdoor intakes. Care should
be taken when locating highly contaminated exhausts (e.g. e.g., from engines, fumes from
hoods, biological safety cabinets, kitchen hoods and paint booths). Prevailing winds,
adjacent buildings and discharge rates must be taken into account.

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(II) Air Handling Unit (AHU)
The main components of an AHU are direct or indirect driven centrifugal fan,
cooling/heating coils, condensate or drain pans and humidifier etc. As the air passes through
various sections, it is susceptible to various types of infections.
(A) Heating and cooling coils
Higher efficiency coil and fin designs have been developed for better heat exchange, but
they also trap much more dirt.
While doing their job, the coils draw moisture out of the air. The particles contained in the
air pass over the coils, depositing some particles in the humidity of the coils. Even in the
best of systems, some contamination will stick to the batteries.
In those that are not the best, particles will accumulate and mold and mold will grow until
no air can pass through the coils. This buildup will serve as a reservoir and release germs
into the airstream.
Periodic cleaning is necessary to remove these contaminants, the frequency and methods are
dependent on the quality of the incoming air, the design of the coil and the quality of the
desired air conditioning.
(B) Drain pan
Condensate removed by the coils is removed from the air handler through drain pans. If not
drained properly, water logging takes place and can lead to bacterial growth. Spray foam
insulation on the inside surface of drain pans is becoming common. This is a very unhealthy
practice because an even surface and consistent tone is impossible with a spray foam.
(C) coil housing
The interior sections if not resistant to corrosion, can generate rust and are prone to absorb
moisture which will lead to bacterial growth. Sometimes bare metal needs to be cleaned and
painted, preferably with epoxy paint. Any rusted metal should be repaired and the cause of
the rust, such as excess moisture, corrected.

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(D) AHU insulation
Often AHU plenums are insulated from the inside using fiberglass to reduce noise, several
studies have shown that fiberglass is not suitable for use in the airstream. It absorbs
moisture, has an irregular surface that traps dirt, is impossible to clean, and releases
inorganic respirations. As a result, bacteria and molds thrive on the fiberglass and can even
be transported to the patient on the fiberglass fiber.
(III) Air filtration
To prevent the flow of air containing infectious particles, air filtration is provided in air
handling units that filters particles, pathogens and water droplets, carried into the air, either
from coils and humidifiers or through leaks in the low pressure side of the unit through
critical care areas such as operating rooms, ICU, emergency and recovery areas there is
normally three-stage filtration.
Prefilters (BS-6540): These are first stage filters having an efficiency of 70% down to 10
microns. These filters are washable and installed at the entrance of the air stream.
Fine filters (BS-6540-part-I): second stage filters having an efficiency of 99% down to 5
microns. Pressure drop under dirty conditions should not exceed 20 mm ca and the initial
drop should be between 6.5 to 8.5 mm ca These filters are washable.
Hepa filters: with an efficiency of 99.97% up to 0.3 Microns used for operating rooms and
ICUs. These are special high flow types with more media to handle higher air quality (DOP
tested to Federal Standard 209).
The filter media is microfiber glass paper to provide the required filtering efficiency. For
specifically hospital applications, the pressure drop under saturated conditions should not
exceed 50 mm.ca.
(IV) Duct system
The function of the duct is to transmit air between two points, namely AHU and the space to
be conditioned. It also brings air from the room to the air conditioner.
The air conditioning duct system works like the respiratory system of a hospital. Over time
contaminants such as dust, dirt, fibers, dander, smoke particles accumulate in the duct
system and makes it ideal

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for breeding ground for mold, spores, pollen, bacteria and other microbes. Every time the
air conditioning is turned on from now on, these diseases that cause many problems are
spread and recirculated through the interiors, affecting the health and comfort of the people
present.
Duct cleaning has been vital and complex. In aspects of hospital infection control. To
mitigate these problems, robotic air duct cleaning systems have recently had improvements
that include the following:
Duct cleaning system
• Heavy duty vacuum machine is connected to the duct to collect harmful
contaminants and dust etc.
• Compressed air expels dirt into a vacuum.
• Motorized brush system mechanically cleans the duct from the inside.
• Once the duct system has been cleaned, all access holes are sealed
It has been seen that a clean duct, in addition to improving IAQ indoor air quality, also
gives you substantial energy savings.
(V) conditioned space
In addition to the contribution of the HVAC system, airflow in infection in a conditioned
space is also a factor namely: wet walls, interior finishes, furniture, tiles, carpets, cleaning
and disinfecting agents, floor tiles and assistants, etc. Chemical contaminants, odors and
fungi are the main health hazards in indoor environments. This causes allergies and
respiratory diseases High incidence of diseases due to allergies, asthma, fatigue, headache,
cold.
The disorders are a result of poor indoor air quality.
Ozone generators
Ozone generators provide an easy-to-use solution to reduce or eliminate odors, pollutants,
VOCs and mildew. This is not a filter or a deodorant. Does not mask the smell of
contaminants. It oxidizes contaminants and structurally alters chemical compounds. The
result of oxidation is carbon dioxide and moisture.

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Mounted in full AHU, it continuously injects the controlled and regulated amount of ozone
into the air system. The released ozone combines with the air stream in the air supply duct
and reaches the space. It is present in the interior space in moments of low concentration.
When it encounters chemical pollutants, it oxidizes them almost instantly and keeps the
indoor air free of chemical pollutants like VOCs as it interferes with the metabolism of
fungal cell multiplication, which results in the reduction of fungus along which it is
responsible for the range of indoor-related allergies.
Conclusion
The designer engineer of a hospital can no longer remain inactive in the infection control
effort of the hospital center. Hospitals must make progress in reducing nosocomial
infections, everyone will have to participate, there are so many reasons for nosocomial
infections.
HVAC engineers have the challenge of improving the indoor air quality of healthcare
facilities, in addition to installation costs and energy consumption. Aggressively addressing
the problem requires joint efforts with doctors, nurses, architects, BIM modelers,
environmental engineers, HVAC control engineers and Government entities, where
committed professionals are required.

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VII.- GENERAL BACKGROUND OF INFECTIOUS AND IMMUNODEPRESSED
ISOLATES
Within a Hospital there are two large groups of isolates, those who are infectious and those
who are immunosuppressed. It is made clear that ASHRAE Standard 170 establishes HVAC
design criteria for Clinic and Hospital rooms.
INFECTIOUS
Precautions and isolations in infectious pathology
They have been designed in order to prevent the spread of microorganisms between the
patient, hospital staff, visitors and equipment.
Hospital isolation precautions seek to:

• Break the chain of transmission of the infectious agent

• Reduce the incidence of nosocomial infection
• Prevent and/or control outbreaks
• Rationalize resource use
• Maintain quality in care at the Hospital de los Santos Reyes
CHARACTERISTICS OF PRECAUTIONS
STANDARD PRECAUTIONS
The most important. These are precautions designed for the care of all admitted patients,
regardless of their diagnosis or presumed infection status.
TRANSMISSION-BASED PRECAUTIONS
This second group is designed for the care of specific patients, in whom the existence of
colonization or infection with epidemiologically important pathogens is known or
suspected.
The indication for "isolation" is made by the doctor, as part of the "treatment orders." It is
the doctor's responsibility to leave this indication in writing and preferably also
communicate it verbally to the supervisor, as well as notify the reference Preventive
Service.

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7 precautions have been grouped into four:
These
1 .-Airborne precautions
2 .-Drop transmission precautions
3 .-Contact transmission precautions
4 .- Protective precautions. Reverse isolation
These types of precautions include, in addition to standard precautions, the following:

• Single room
• Knowledge throughout the health group through appropriate signage (posters in the
room, record in the Medical History).
• The patient, family, and visitors should be instructed about the objectives of the
precautions we apply to the patient.
• Visits will be limited to the maximum, there should never be more than one family
member on each shift
• Depending on the type of precautions, the specific measures indicated in this
protocol reflected in the corresponding sections will be taken.
• If the patient has to go to another area of the hospital, a surgical mask will be placed
on them and the staff who will come into contact with the patient will be informed
of the rules (gown, gloves, hand washing, face masks...). according to the
specifications for each type of insulation.
Single room : mandatory for airborne diseases and reverse isolation. In cases of
transmission by contact or droplets, it is recommended (in these cases, if a single room is
not available, the distance between one patient and another must be at least one meter). In
cases of airborne transmission, the room should have a negative pressure system.
STANDARD PRECAUTIONS
Hand washing: should always be done after touching blood, body fluids and contaminated
material, whether or not you are wearing gloves. See hand washing protocol.

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Use8 of gloves: Non-sterile gloves should be used when touching blood, body fluids,
secretions, excretions and contaminated material. Also when you are going to touch a non-
intact mucosa or skin. Change gloves between procedures with the same patient after
contact with material that could contain a high concentration of microorganisms. Wash your
hands immediately after removing gloves.
Use of a mask, eye protectors, face shields: when any procedure is to be performed on the
patient that may generate splashes of blood, secretions and excretions.
Wear a gown (clean, non-sterile) to protect the skin and prevent staining of clothing. After
removing the gown, wash your hands.
Patient Care Equipment: Handle used equipment that is soiled with blood, body fluids,
secretions, and excretions with care to avoid exposure to skin and mucous membranes, as
well as clothing that may contaminate other patients in the environment.
Occupational Health: be extremely careful with sharp and sharp objects. Never recap used
needles. Dispose of all sharp and sharp material in appropriate containers that should be
placed near the area where these instruments are used.
Environmental control: the hospital must have appropriate procedures for cleaning
environmental surfaces.
Linen: handle, transport and process contaminated linen avoiding contact with the skin.
Place uncontrollable patients in a single room.

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9
SPECIFIC INSULATION PRECAUTIONS
GENERAL RULES FOR INSULATION PRECAUTIONS
RESPIRATORY PATIENT
TRANSMISSION ROOM PROTECTION GLOVES COAT TRANSFER

PARTICULATE Standard Standard RESPIRATOR

AIR INDIVIDUAL RESPIRATOR precautions precautions OF PARTICLES
INDIVIDUAL (if SURGICAL Standard Standard SURGICAL
DROPS possible) MASK precautions precautions MASK

INDIVIDUAL
CONTACT (if possible) YEAH YEAH

SURGICAL SURGICAL
REVERSE INDIVIDUAL YEAH YEAH
MASK MASK

1. In cases of airborne transmission, the room should have a negative pressure system.
2. A particulate respirator will only be used in cases of airborne transmission. In other
cases (droplet isolation, reverse isolation or whenever necessary based on standard
precautions) use surgical masks.
AIR TRANSMISSION PRECAUTIONS
It is defined as the isolation that must be achieved when the dissemination of particles
smaller than five microns remain suspended in the air for long periods of time, and are thus
inhaled by a susceptible host.
Due to the risk it poses, it is required to use high-efficiency face masks (particulate
respirators).
Examples: Pulmonary Tuberculosis, Measles, Chickenpox.
Specifications:
• Isolated room with negative air pressure, closed door and open windows if no such
system exists.
• High efficiency face masks, particulate respirator. Discard it when leaving the room.

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• Limited patient transportation and, if necessary, place a surgical mask.
• Beat only if there is a risk of splashing.
• Strict hand washing when in contact with the patient or their fluids.
• Personnel not immune to measles or chickenpox should not enter the room of
patients with these pathologies. If they have to do so, they should put on a high-
efficiency respirator.
PRECAUTIONS FOR DROP TRANSMISSION
This transmission occurs when particles larger than five microns, generated when speaking,
coughing or sneezing, remain suspended in the air, up to one meter away when speaking,
and up to 4 meters when coughing or sneezing.
Examples: invasive disease due to Hemophilus, Meningococcus, Diphtheria, Whooping
Cough, Scarlet Fever, Mycoplasma Pneumonia, Influenza, Rubella.
Specifications:
• Isolated room. Patients with the same germ can share the same room.
• Wash hands before and after touching the patient.
• Place the patient at a distance of no less than one meter from the others.
patients. If not possible, single room.
• Surgical mask: to be less than one meter from the patient or to perform any
procedure. IB. Throw it away when leaving the room.
• Patient transportation should be limited, but if necessary, put a mask on and explain
to the patient the reason for this measure.
• Gloves and gown are worn if there is a risk of splash.
CONTACT PRECAUTIONS
It will be applied to patients in whom a serious, easily transmissible disease is known or
suspected through direct contact with the patient or through indirect contact with surfaces or
utensils used in the patient's care.
Examples: patients infected or colonized by ARMS, ABRIM. Enteric diseases due to
Clostridium Dificile, and in incontinent patients due to E. Coli, Shigella, Hepatitis A and
Rotavirus. Respiratory syncytital virus in children. Skin infections such as Impetigo,
Pediculosis, Scabies, disseminated Herpes Zoster or in immunosuppressed patients.

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Specifications:

• The use of gloves, surgical mask and gown is recommended when having direct
contact with the patient. Discard mask and gloves before leaving the room. Remove
your robe before leaving the room.
• Hand washing is absolutely necessary before and after touching the patient.
• Patient transportation should be limited. Put on a surgical mask.
• Patient care team: when possible this will be dedicated to a single patient. If this is
not possible, clean and disinfect or sterilize it properly before using it on another
patient.
• Material for clinical use such as thermometers, sphygmomanometers, stethoscopes,
etc. It will be for the exclusive use of these patients, and if possible they will remain
inside the room.
REVERSE OR PROTECTIVE INSULATION
It tries to protect immunosuppressed patients from infections and febrile patients from
possible superinfections.
Specifications:

• Handwashing.
• Single room.
• Putting on a gown, cap, surgical mask and leggings before entering the room, for
anyone who comes into contact with the patient. The mask, leggings and hat will be
discarded before leaving the room. The robe will be left inside the room.
• Patient transportation should be limited, but if necessary, put a mask on and explain
to the patient the reason for this measure.
• Clean the stethoscope before and after use, and try to
individualize a tension sleeve.
• It should be applied to all patients with severe neutropenia (< 500
neutrophils) until this figure recovers and the clinical evolution is favorable.
NOTE: some infections require taking several types of precautions simultaneously. For
example: RAMS (contact and droplets), Adenovirus Pneumonia in children (contact and
Droplets), Chickenpox (airborne and contact).

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HVAC Design Data Ashrae 170-2017, Infectious Rooms Airborne
Infection Isolation Room

1 .-Maintain continuous negative air pressure 2.54 Pa

2 .-Ensure well-sealed/leak-free rooms

3 .- Design temperature 21-24°C

4 .- Hour changes of 12 ACH, 2 ACH of minimum outside air

5 .-Calculate ACH based on exhaust flow.

6 .-If it is not occupied, the pressure ratio is maintained and the minimum is 6 ACH

7 .-Switching controls for reversible airflow (pressure ratio) will not be permitted.

8 .-Automatic closing devices on exit doors.

9 .- Direct exhaust air outside, away from the inlet

10 .-When the room has a previous room: the room is negative to the previous room, the
previous room is negative to the corridor
11 .- Monitoring device between the room and the corridor alarm when pressurization is
not maintained.
12 .- Escape grilles located on the ceiling or on the wall at the head of the patient's bed.

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Fig 32; HVAC diagram for infectious rooms

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IMMUNODEPRESSED
The diagnosis of the immunocompromised patient is relatively new. Beginning in the 1950s,
knowledge of primary immunodeficiencies began; From the sixties onwards, there was an
improvement in treatment (from chemotherapy to intravenous gamma globulin as a
replacement treatment, more powerful and effective antibiotics, to bone marrow transplant)
and the diagnosis of neoplastic and lung pathologies, especially leukemias. and lymphomas,
and the appearance of AIDS in the eighties has conditioned the knowledge of serious
infectious and opportunistic diseases, caused by microorganisms such as Pneumocystis
carinii, Asperguillus, Herpes zoster virus, Cytomegalovirus, etc., and by common
pathogenic microorganisms that In these patients they are more aggressive and develop
resistance to antibiotic therapy, such as methicillin-resistant Staphylococcus aureus, etc.
Pulmonary complications are the main cause of morbidity and mortality in patients with
primary and secondary immunodeficiencies. Its usual clinical presentation with pulmonary
infiltrates poses a challenge in diagnosis, since radiological findings and clinical symptoms
are usually nonspecific and the spectrum of diseases is broad, including infectious and non-
infectious processes.
To reach an etiological diagnosis, it is necessary to use invasive techniques such as
fiberoptic bronchoscopy, as well as non-invasive techniques such as computed tomography
(CT), since a delay in diagnosis increases mortality. Fiberoptic bronchoscopy allows us to
identify germs or even exclude infections. CT allows lesions to be defined more precisely
and to demonstrate lesions that have not been observed in conventional radiology. Initial
treatment includes the use of broad-spectrum antibiotics, as well as other anti-infectives,
subsequently adjusting to the results obtained with the diagnostic techniques performed.
Despite diagnostic and therapeutic advances, the prognosis of these immunodeficient
patients with pulmonary complications is poor.
The most common clinical presentation of immunocompromised patients is recurrent or
persistent pneumonia. These patients usually present radiological evidence of recurrent or
persistent pulmonary condensations, associated with typical symptoms of infection such as
fever and tachypnea. These radiological images are usually pulmonary infiltrates that persist
after correct antibiotic treatment, which can be found bilaterally in one or more lobes, and
which are often associated with other radiological findings such as

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hyperinflation or situs inversus; In any case, the diagnosis of persistent or recurrent
pneumonia is extensive and includes more entities than immunodeficiency.
The immunocompromised patient is unable to correctly overcome an infection by a "usual"
respiratory pathogen for the majority of immunocompetent children; For example, RSV,
chickenpox, influenza, parainfluenza or measles infections have a torpid evolution,
presenting severe or sometimes fatal pneumonia in these children. If they become infected
by opportunistic germs, such as varicella zoster virus or Pneumocystis carinii, or infections
fungal infections, the results are devastating in the immunocompromised, especially in those
with bone marrow transplants, in cases of AIDS, in cancer patients with chemotherapy
treatments, in cases of T cell deficiencies, in agamma globulinemia, in those treated with
high doses of corticosteroids or in cases of suppurative pneumonia caused by Hemophilus
influenza or Staphylococus aureus in children with humoral deficiency.
The clinical course of opportunistic infections varies depending on the immune status.
of the patient.
MOST FREQUENT PULMONARY PATHOGENS IN IMMUNOCOMPROMISED
PATIENTS
Lung infection varies according to the nosological entity that causes the immunodeficiency
state in children with organ or bone marrow transplants, with AIDS, with oncological
treatments or primary immunodeficiencies; They will be associated with different specific
pathogens for each entity and type of immunodeficiency they present.
Oncology patients
They have a high risk of suffering from pneumonia due to chemotherapy treatment that
induces neutropenia and secondary cellular immunodeficiency, therefore they are more
likely to develop viral pneumonia due to RSV, Adenovirus, Enterovirus, fungal pneumonia
(Aspergillus, Mucor, Rhizopus), Candida and due to Pneumocystis carinii and
Varicellazoster, so they must perform chemoprophylaxis for Pneumocystis carinii while the
chemotherapy treatment lasts.
These children should also be considered for pneumonia due to Toxoplasma, Cryptocus
neoformans and tuberculosis.

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Bone marrow and solid organ transplants
Pulmonary complications depend on the moment in which they occur after the transplant.
Immediately afterwards they are in a state of neutropenia, presenting a high risk of suffering
from bacterial pneumonia due to Staphylococus aureus or Pseudomonas aeruginosa, due to
Candida and Aspergillus fungi and due to Herpesvirus. After a few months after performing
the transplant, from one month to 4 months, there is the possibility of graft versus host
disease appearing, which is treated with high-dose corticosteroids or cyclosporine, and
pneumonia may appear.
by cytomegalovirus, adenovirus, Aspergillus, Mucor, herpesvirus, Epstein virus
- Barr, Pneumocystis carinii. After 4 months after the transplant, chronic graft-versus-host
disease and a poor humoral response may appear, and during this period pneumonia due to
Varicellazoster virus, gram-positive capsulated bacteria and Pneumocystis carinii infections
may occur.
Primary immunodeficiencies
In patients with common variable immunodeficiency and agammaglobulinemia, recurrent
bacterial pneumonia occurs, usually due to capsule germs, and rarely, pneumonia due to
Pneumocystis carinii occurs.
Children with immunodeficiencies due to T cells, severe combined immunodeficiency, etc.,
are at greater risk of suffering from the same type of opportunistic diseases as AIDS
patients, as well as persistent and recurrent infections due to Candida albicans. Patients with
chronic granulomatous disease suffer from lung infections due to fungi (Aspergillus,
Staphylococus aureus).
Most staphylococcal diseases involve direct tissue invasion and cause skin and soft tissue
infections, pneumonia, endocarditis, or osteomyelitis. Some strains produce a toxin that can
cause toxic shock syndrome, scalded skin syndrome, or food poisoning.
Children with primary immunodeficiencies always present serious pulmonary
complications: bronchiectasis, empyema, lung abscesses, etc.

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AIDS
There is an extensive list of lung infections associated with AIDS, including those due to
Pneumocystis carinii, Cytomegalovirus, and both typical and atypical mycobacteria.

HVAC design data Ashrae 170-2013, in immunocompromised rooms

Airborne infection isolation room

1 .-12 ACH, 2 ACH outside air minimum, ACH for positive room supply airflow

2 .-Positive pressure .01 "wc. 2.5 pa

3 .-Switching controls for reversible airflow (pressure ratio) will not be permitted.
4 .-Design temperature 21-24 °C

5 .- Maintain continuous positive air pressure

6 .- Ensure well-sealed/leak-free rooms

7 .- When the ward has a previous room: the patient's room is positive to the previous
room, the previous room is positive to the corridor.

8 .-Monitoring device between the room and the corridor alarm when pressurization is not
maintained.

9 .-Supply of diffusers located at the head of the patient's bed.

10 .-Exhaust grilles located near the door of the patient's room.

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Fig 33; HVAC scheme for immunosuppressed rooms

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V 9III.- FLUID MECHANICS CONCEPTS APPLIED TO CLEAN ROOM
Introduction
According to fluid mechanics, the Bernoulli equation is what governs the flow balance in
clean rooms, it states the following:
P1 / DA + V1 ² /2 + Z1 *g = P2 / DA + V2 ² /2 + Z1 *g (Eq.1)

SA = INJECTION

RA = RETURN

EA = EXTRACTION

DV = EXFILTRATION/ INFILTRATION

Fig 34, Pressure Balance Diagram

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P1 0 isthe pressure in room 1
P2 isthe pressure in room 2
DA is the density of air, which at sea level is considered to be 1.2 kg/m3
V 1 is the inlet air speedof the door of access
V 2isthe exit air speed ofthe door ofaccess
In this case z1 and z2, which is the reference level, are equal, that is, z1 = z2, therefore they
cancel out, leaving the equation as follows:

P1 / DA + V1 ² /2 = P2 / DA + V2 ² /2 (Eq.2)
If we leave the equation based on pressure and consider that:
Q = flow rate = v1 A1 = v2 * A2, therefore:
V1 = Q/A1 (Eq.3)
V2 = Q/A2 (Eq.4)

P1/DA – P2 /DA = V2 ² /2 - V1 ² /2
(P1 – P2)/ DA = V2 ² /2 - V1 ² /2
( P1- P2 ) / DA = ( V2 ² --V1 ²)/ 2
DP = (V2 ² - V1 ²) * DA/ 2 (Eq.5)
If equation 3 and 4 are replaced in equation 5 we obtain:

DP = ( (Q /A1 ) ² - ( Q/A2 ) ² ) * DA /2 (Eq.6)

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1 this ASHRAE equation, he obtained the following equation to obtain the leak
From
flow rate in a clean room:

It is important to note that the leak area is a very complex value to determine, but for
practical purposes ASHRAE recommends a range of the order of 0.045 m2 to 0.1 m2. The
other option that catalogs generally have, for clean room doors, include their estimated
leakage area.
To the extent that the leak area is less than 0.045 m2, the differential pressure inside the
clean rooms becomes very complicated to manage.
Diff (Pressure) = cte *Q² / (Af )² (Eq.7)
That is, to the extent that the leak area tends to zero, the pressure differential tends to
infinity, therefore the pressure differential is very difficult to control when the flow areas
are very small. Furthermore, if we look at equation 7, the leakage area is found to the square
power.

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Example 1
A laboratory room has two rooms in a pressure cascade, see figure 34, in room 1, there is a
pressure of 25 pascals and in the second room a pressure of 15 pascals.
The injection flow rate in the first room turns out to be 4,000 m3/h and for the second room
3,000 m3/h, the leak area of the door is estimated at 0.045 m2. Determine the return flows
in both rooms to maintain the necessary balance:
Step 1
You must determine the leak rate, from room 1 to room 2:
Q = 840 * AF * root (DP) ( l/s)
Q = 840 * 0.045 m2 * root (25-15) = 119.5 l/s = 430.3 m3/h
Step 2
You must carry out the flow balance in enclosure 1
Flow in = Flow out
Injection flow 1 = Return flow 1 + Exfiltration flow
Return flow 1 = Injection flow rate 1 – Exfiltration flow rate
Return flow 1 = 4,000 m3/h - 430.3 = 3,569.7 m3/h
Step 3
You must carry out the flow balance in enclosure 1
Flow in = Flow out
Injection flow rate 2 + Infiltration = Return flow 2
Return flow 2 = Injection flow 2 + Infiltration
Return flow 2 = 3,000 m3/h + 430.3 = 3,430.3 m3/h
Therefore the return flows are room 1 = 3,569.7 m3/h. room 2 = 3,430.3 m3/h

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Positive pressure in a clean room
According to what was seen in the previous chapters, this is defined by the type of
application or sector where I am working. Figure 35 shows if the room is pressurized:

POSITIVE PRESSURE BETWEEN TWO POINTS

ASHRAE FORMULA

Scenario 1: Room Pressurized

SA - (EA+RA) = AV = >Q > 0

Fig 35, positive pressure between two points

It is very common in pharmaceutical laboratories to find a pressure cascade system.
Especially in injectable rooms (class A room), where the clean room has internal pressures
of the order of 45 pascals in relation to the grade B environment.
If we see it in a room for immunocompromised patients, the pressure is of the order of 25
pascals in relation to the nearest airlock.

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Negative pressure in a clean room
According to what was seen in the previous chapters, this is defined by the type of
application or sector where I am working. Figure 35 shows if the room is depressurized.

NEGATIVE PRESSURE BETWEEN TWO POINTS ASHRAE FORMULA

Scenario 3: Room Depressurized

SA - (EA+RA) = AV = >Q < 0

Fig 36, negative pressure between two points

It is very common in pharmaceutical laboratories to find a pressure sink system. Especially
in locks where it is required to maintain, in some cases, negative pressures, where the clean
room has internal pressures of the order of less than 25 pascals.
If we see it in an infectious ward, the pressure is of the order of less than 12.5 pascals in
relation to the nearest airlock.

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neutral pressure
There is also the option of having two areas in different room classifications, but with the
same internal pressure. Therefore, the pressure differential is canceled, see figure 37.
NEUTRAL ROOM BETWEEN TWO POINTS
ASHRAE FORMULA

Scenario 2: Room Unpressurized

SA - (EA+RA) = AV = >Q = 0

Fig 37, negative pressure between two points

In this example, it is very normal to find it in pharmaceutical laboratories where two grade
A and B environments are available, but their internal pressures tend to be equal, therefore,
the leak flow is zero.
In the case of a surgical ward, the ward area may have the same room classification as the
scrubbing area. Therefore there is no leakage flow either.

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Importance of locks in the balance of pressures and containment of
particulate matter
The locks constitute the “borders” that allow class changes between areas, or an area and
circulation, preventing the pollution that is produced when opening the doors of the area
from passing directly from the dirty area to the clean one.
Physically they are rooms, which receive the same air treatment of the areas to which they
lead. Most of the time they have a specific function, acting as input/output of materials, or
personnel.
In order to emphasize the prevention of pollution, the circulation of people and materials
must be constituted in different locks, even being able to use boxes or tray passes when the
size of the materials allows it.
When we need to contain a process or control cross contamination, pressures play a
fundamental role, allowing air flows to be directed correctly according to the specified
requirement for a certain product or process. It is in this aspect that the main role of airlocks
comes into play.
A differential pressure value between areas is not always required, but the direction of the
air flow in a certain direction must simply be guaranteed, considering a minimum
differential, between 2 to 5 Pa. For example in the case of products that are found in
qualified, unclassified (CNC) areas. In this aspect, the airlock can contribute to the
prevention of pollution when the pressure drops to zero due to the opening of one of the
doors, maintaining the border on the closed door, with an adequate speed for the transport of
the particles. It is essential in these cases to consider some type of alarm, whether audible,
visual or interlocking, that prevents the simultaneous opening of the doors.
It is well known that in the pharmaceutical industry differential pressures play a very
important role in preventing contamination, and air locks are an effective obstacle to this
end.
But there is often a misconception of the limits and consequences of results outside the
specified ranges. The air locks allow working with lower differentials, and therefore lower
injection flow in the area, in addition to allowing better balancing of the installation.

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Considering that the locks must be of the same hygienic classification as the areas to which
they allow access, a high, although not excessive, air renewal rate must be contemplated,
allowing rapid recovery of the condition in the resting state.
Types of airlocks and air directionality
There are basically three configurations of locks:
Waterfall Type:
This type of lock is commonly used for cases in which there are classification requirements,
but not process containment, or vice versa, when there is a class requirement, but not
containment. The direction of air flow is considered in a single direction, towards the
interior of the room in the case of containment or towards the exterior for clean areas.

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Bubble Type:
This type of lock is used for non-contaminated operations; it is a pressurized space in such a
way that the direction of air flow is outward, generating a positive pressure from the lock to
the areas it connects. The same classification should be considered at the lock as in the
cleaner area you enter.

Sump Type:
This type of airlock is recommended for contaminated operations; in this case the air flow
will be towards the inside of the airlock, generating a depression in it.

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We must bear in mind that a lock is a “passage” place, so when opening one of the doors the
pressure drop is inevitably zero, and this presupposes possible contamination, if the
openings are not made under the specific procedures. . On the other hand, as a result of this
abrupt drop in the differential, special attention must be paid to the direction of air flow in
the closed door, and it must be designed in such a way that there is no possibility of
reversing the design direction.
It is therefore essential to have knowledge of the pressure requirement from the beginning
of the project stage.

Below is a clean room, with multiple rooms and also the control system for several locks,
with their pressure differentials and interlocks.

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Supply exhaust Retu in

air AIT air
Valve Valve Valve

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Example of flow balance

There is a white room like the one shown in the following figure:

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The areas with their most important characteristics are the following:
Zone Description ISO classification RH
Classification Classification QTS KW VR Tlocal °C Te °C HUMIDITY HUMIDITY INJ FLOW FLOW R/H m3/h FLOW
GMPs FED STD 209 E m3 INT. % EXT.% QT m3/h DESIGN m3/h

1 SOLVENT 5 b CLASS 100 30 30 22 35 40 60 75

2 LOCK 2 5 c CLASS 10,000 5 25 22 35 40 60 45
3 PACKAGING 8 d CLASS 100,000 3 100 24 35 40 60 25
4 BONE CEMENT 7 c CLASS 10,000 7 45 20 35 40 60 45
5 LOCK 1 7 c CLASS 10,000 2 25 20 35 40 60 45
6 STORE 8 d CLASS 100,000 4 120 24 35 40 60 25
7 LOCK 3 9 S/C 1,5 15 24 35 40 60 25

On the other hand, the Bone cement Manufacturing area has a dust extraction of 800 m3/h and the Solvent area has a Type II Biosafety Booth, with
an extraction in the room of 400 m3/.

FLOW IN OUT FLOW

Zone Description Classification Classification Classification INJ FLOW FLOW EXFILTR. RETURN EXT. EXTRACC. EXTRACC.
I GMPs FED STD 209 E M3/H INFILT. M3/H M3/H M3/H BATHROOM GENER. M3/H POWDER M3/H
1 SOLVENT 5 b CLASS 100 4.479 M3/H 400
2 LOCK 2 5 c CLASS 10,000 1.125
3 PACKAGING 8 d CLASS 100,000 2.500
4 BONE CEMENT 7 c CLASS 10,000 2.025 800
5 LOCK 1 7 c CLASS 10,000 1.125
6 STORE 8 d CLASS 100,000 3.000
7 LOCK 3 9 S/C S/C 375

For calculation purposes, all doors have a creepage area of 0.045 m2, as shown in the following table.

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DOOR Description Area Higher Lower Differential Flow

Leakage m2 pressure Pa pressure Pa Pa Leakage
P1 LOCK 1 / BONE CEMENT 0,045 m3/h
P2 LOCK 1/WAREHOUSE 0,045
P3 PACKAGING/WAREHOUSE 0,045
P4 SOLVENT/LOCK 2 0,045
P5 LOCK 2/WAREHOUSE 0,045
P6 WAREHOUSE/LOCK 3 0,045
P7 LOCK 3/HALLWAY 0,045
Based on the above determine:
a.- How many handling units are required and under what classification they should work
b.- According to the number of handling units, obtain the injection flow, return flow and extraction flow in m3/h, required by each zone.
c.- Make a signal control diagram
d.- Make the P&D Control Diagrams based on the results obtained.

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Development a.- Obtain the injection flow rate required by each zone, based on what is needed per thermal load and per hour renewals,
resulting in the following:
Zone Description Classificatio Classificatio Classification VR HUMIDITY EXT. RH INJ FLOW FLOW R/H FLOW
nI n QTS KW Tlocal °C Te °C
FED STD 209 m3 INT. % HUMIDITY QT m3/h m3/h DESIGN m3/h
GMPs E % 60
1 SOLVENT 5 b CLASS 100 15 30 22 35 40 75 4.479 2250 4.479
2 LOCK 2 5 c CLASS 10,000 3 25 22 35 40 60 45 896 1125 1.125
3 PACKAGING 8 d CLASS 3 100 24 35 40 60 25 896 2500 2.500
4 BONE CEMENT 7 c 100,000
CLASS 10,000 4 45 20 35 40 60 45 1.194 2025 2.025
5 LOCK 1 7 c CLASS 10,000 2 25 20 35 40 60 45 597 1125 1.125
6 STORE 8 d CLASS 4 120 24 35 40 60 25 1.194 3000 3.000
7 LOCK 3 9 S/C 100,000 0,9 15 24 35 40 60 25 269 375 375

Remember the following: a1.- Injection flow rate by Thermal Load

The following formula is used

Vi = Qs *860 / ( ( 1 -F ) *da * cpa * (T local – T injection) )

Qs = sensible thermal load kw

F = bay pass factor

Da = density of air 1.2 kg /m3 (sea level)

Cpa = Specific heat of air = 0.24 Kcal /kg °C

Note: In all UPC applications (critical patient unit, thermal loads are not required to be calculated, they are removed only for hourly renewals) The return flow is obtained by flow balance and in the case of non-critical areas it is approximately 80% of the
injection flow.

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a2.- Flow rate due to hourly renewals

The calculation of injection per hourly renewal is widely used in hospital and pharmaceutical applications and its expression is very simple:

Vi = R/H * VR

R/H = Hourly renewals are obtained by tables, shown below

VR = Room volume m3

Note 1: Remember that in the case of clean rooms, you should always choose the highest flow rate between the ones that are calculated by thermal load and by renovations.

Note 2: The flow rate due to thermal load in critical patient rooms, where 100% outside air is required, is always greater than that due to thermal load.

Note 3: In the case of laboratories, the flow rate due to thermal load is always higher, mainly due to the loads dissipated by the equipment.

b.- Obtain the leakage flows through each door, as indicated in the following table:
Zone Description Area Higher Pressure Differential Flow
Leakage pressure Pa minor Pa Da Leakage m3/h
P1 LOCK 1 / BONE CEMENT m20,045 15 10 5 304
P2 LOCK 1/WAREHOUSE 0,045 15 10 5 304
P3 PACKAGING/WAREHOUSE 0,045 15 10 5 304
P4 SOLVENT/LOCK 2 0,045 25 15 10 430
P5 LOCK 2/WAREHOUSE 0,045 15 10 5 304
P6 WAREHOUSE/LOCK 3 0,045 10 3 7 360
P7 LOCK 3/HALLWAY 0,045 3 0 3 236

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c.- Carry out flow balances, taking into consideration that there must be a balance between the flow that enters and the flow that leaves:
Incoming flows; air injection, air infiltration

Outgoing flows; exfiltration, return, bath extraction, general extraction, equipment extraction, dust extraction and air return

FLOW IN OUT FLOW

Zone Description IS lasing Classificatio Classification INJ FLOW FLOW EXFILTR. RETURN EXT. EXTRACC. EXTRACC.
n FED STD 209 INFILT. BATHROO GENER. POWDER
M3/H M3/H M3/H
GMPs E M3/H M M3/H M3/H M3/H
1 SOLVENT 5 b CLASS 100 4.479 0 430 3649 0 400 0
2 LOCK 2 5 c CLASS 10,000 1.125 430 304 1251 0 0 0
3 PACKAGING 8 d CLASS 2.500 0 304 2196 0 0 0
4 BONE CEMENT 7 c 100,000
CLASS 10,000 2.025 304 0 0 1529 800
5 LOCK 1 7 c CLASS 10,000 1.125 0 609 516 0 0 0
6 STORE 8 d CLASS 3.000 913 360 3553 0 0 0
100,000
7 LOCK 3 9 S/C S/C 375 360 236 499 0 0 0

d.- The UMAS must be selected according to the type of room classification, only room classifications C and D can be combined according to GMPs,
but zones A and Zone B must be with independent equipment.
In areas where there is dust extraction, such as in the case of tablet manufacturing, there can be no return.
The UMAS are separated by classifications below:

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UMA-01
Zone Description ISO classification Classification Classification INJ FLOW FLOW EXFILTR. RETURN EXT. EXTRACC. EXTRACC.
GMPs FED STD 209 E M3/H INFILT. M3/H M3/H M3/H BATHROOM GENER. M3/H POWDER M3/H
M3/H
1 SOLVENT 5b CLASS 100 4.479 0 430 3.649 0 400 0

INJECTION FLOW 4.479 m3/h

RETURN FLOW 3.649 m3/h
EXTERNAL FLOW 830 m3/h
EXTRACTION FLOW 400 m3/h

UMA-02
Zone Description ISO classification Classification Classification INJ FLOW FLOW EXFILTR. RETURN EXT. EXTRACC. EXTRACC.
GMPs FED STD 209 E M3/H INFILT. M3/H M3/H M3/H BATHROOM GENER. M3/H POWDER M3/H
M3/H
2 LOCK 2 5c CLASS 10,000 1.125 430 304 1.251 0 0 0
3 PACKAGING 8d CLASS 100,000 2.500 0 304 2.196 0 0 0
4 BONE CEMENT 7c CLASS 10,000 2.025 304 0 0 1.529 800
5 LOCK 1 7c CLASS 10,000 1.125 0 609 516 0 0 0
6 STORE 8d CLASS 100,000 3.000 913 360 3.553 0 0 0
7 LOCK 3 9 S/C S/C 375 360 236 499 0 0 0
10.150 2.007 1.813 8.015 0 1.529 800

INJECTION FLOW 10.150 m3/h

RETURN FLOW 8.015 m3/h
EXTERNAL FLOW 2.135 m3/h
EXTRACTION FLOW 1.529 m3/h
DUST EXTRACTION FLOW 800 m3/h

Therefore, only two UMAS should be selected.

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e.- The type of UMA configuration must be selected, based on ASHRAE Regulations, a relationship is obtained between the injection flow
rate per hourly renewal and that obtained by Thermal Load.
R = Air flow rate per hour renewals / air flow rate per thermal load according to the , with this the configuration of
following schemes:

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The configurations are as follows:

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For the exercise you obtain:

UMA 01

INJECTION FLOW PER R/H 2250M3/H

INJECTION FLOW THERMAL LOAD 4.479M3/H
RH/QT RELATIONSHIP 0,5
TYPE 1

UMA 02

INJECTION FLOW PER R/H 10.150M3/H

INJECTION FLOW THERMAL LOAD 5.047M3/H
RH/QT RELATIONSHIP 2,0
TYPE 1

f.- With all the data obtained, a ventilation flow diagram is

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made, which is as follows:

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The data for each one must be obtained from the previous tables:

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g.- The diagram of input and output signals, variables to control including access control is as follows:

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h.- The P&D control diagrams of each of the UMAS are the following:
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IX.- DEVELOPMENT OF P&D INSTRUMENTATION DIAGRAMS IN CLEAN
ROOMS .
Introduction
In instrumentation and control, a special system of symbols is used in order to transmit
information in an easier and more specific way. This is essential in the design, selection,
operation and maintenance of control systems. A system of symbols has been standardized
by the ISA (Instrumentalists Society of America). The following information is from the
standard: ANSI/ISA- S5.1-1984 (R 1992). The needs of various users for their processes are
different. The standard recognizes these needs, providing alternative methods of symbolism.
Several examples are maintained by adding the information or simplifying the symbolism,
as desired.
In any industrial process, and in our particular case of HVAC systems, applied to clean
rooms, as well as to manufacturers and installers of air conditioning equipment (hot water
boilers, UMAS Handling Units, hot and cold water pumps, pressure control systems,
temperature, etc.), we often find installations of considerable size and with a multitude of
elements, materials and instruments that make up said installation.
In order to identify these equipment and instruments in a simple way and to also have an
idea of the design conditions of any engineering project, we use a tool that is commonly
known by the acronym P&ID.
Definition
A P&ID is what is defined as a piping and instrumentation diagram (DTI) also known in the
English language as piping and instrumentation diagram/drawing (P&ID) and is a diagram
that shows the process flow in the pipes, as well as the equipment. installed and instruments.
Another possible name used to refer to a P&ID is PFD, a simplified form of English
(Process flow diagram), although this is a less used form.
These diagrams are made up of a series of symbols that will allow us to identify all the
components that make up a process, such as pipes, number of pipe lines and their
dimensions, valves, controls, alarms, equipment, levels, pressure switches, drains, purges,
pumps. , etc.

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The standard symbol instrument used in these diagrams is generally based on ISA S5.1.
Instrumentation and Automation Systems of society.
Use
This symbol standard is used in both the chemical and petrochemical industries,
metallurgical industries, air conditioning industries, energy generators, and in many other
industrial processes.
In addition to these symbols, different types of lines and circles are used to indicate how the
different elements of the process and the functions of each instrument are interconnected.
Instrumentation lines

______________ Connection to process, or mechanical link or power supply of

instruments.
pneumatic signal
Electrical signal

Electrical signal (alternative)

- ------and- —
Capillary tube

Guided sound or electromagnetic signal (includes heat, radio,

~U~~_ nuclear, light)

_ „ Unguided sound or electromagnetic signal

b Software or data connection

. . ■ Mechanical connection
Hydraulic signal

The “Tag numbers”

“Tag numbers” are numbers and letters found within the circles that appear next to an
instrument and that identify the type and function of the device. These circles make up the
control loops of an instrument, device or equipment and are interconnected with the
instrumentation lines seen in the previous table.

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Each of these ties will have a coding in order to have a clear identification of them.

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Instrument identification

Variable to
control 1- letter: Measured or modifying
variable
For
example;
TO. Analysis
E: Voltage
F: Flow
I: Current
J: Power
L Level
Q: Pressure
S: Speed, Frequency
T: Temperature
V- Vibration

These are the most common, although there are many others that appear in table 1.1.
The acronyms come from the English name of each of the instruments' functions.

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Detail of each
loop element
2nd
and 3rd letters: Output, data presentation or modifier function.

For example,

A: Alarm
C: Controller E: Primary Sensor
H: High I : Indicator
L: Low P: Pressure
R: Recorder
S: Switch
T: Transmitter
V: Valve
7- Actuator

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So then 6we have these examples:
1.-

Designates a Temperature Controller with Indication capacity associated with control loop No. 60.

SWITH DIFFERENTIAL
PRESSURE
E 1 FLOW CONTROL
CONSTANT FLOW CONTROL

VARIABLE FLOW CONTROL

SPEED CONTROL

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Depending on how the circles of each instrument are represented, they give us one or
another information:

1. Operator accessible
1.1 Shared viewing
1.2 Shared viewing and control
1.3 Access to the communications network
1.4 Operator interface in the communications network

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2. Auxiliary interface
2.1 panel mounted
2.2 manual station

3. Not normally accessible to the operator

3.1 Controller
3.2 Field-installed shared display
3.3 Calculation, signal conditioning in shared controller
In addition to these there are also symbols used for computers (computers) and symbols for
logical and sequential control.
Symbols for valves.
This way the most commonly used valves are represented:

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Symbology for actuators.

Manual Diaphragm

Motor Solenoid

Below are the following examples:

Example 3

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Example 4

Example 5

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Example 6

With this information, although very summarized, of what a P&ID is, surely that graph or
diagram that we see so often in engineering projects and reminds us of a hieroglyph will no
longer seem so strange and intelligible to us.
Now we will surely know how to better interpret the information it offers us and know
better the instrumentation, design, functions and ultimately all the elements of the industrial
process that is represented to us.
Below, various examples of P&ID control are presented, aimed at clean room HVAC
systems, with the objective of analyzing based on what is explained in this chapter.
Based on the above: a.- You must identify the nomenclature of the plan
b.- The number of control loops and what each one controls
c.- Explain if the system is a ventilation or hydraulic P&ID diagram
d.- Indicate if the UMAS are recirculated air or 100% outside air.

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Table 1.1. Table of instruments and functions letters.

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Problem 7

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Problem 7

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Problem 7

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Problem 7

210 m?h 140 m/h 140 m?h 30 m^h 140 m?h

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Problem 7

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Problem 7

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Problem 7

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Problem 7

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| Nomenclature (according to ISA standard)

Tag Description Pl Pressure Indicator - Manometer

AU Status Auto - Automatic Status Fll Pressure Transmitter 4 ind/heat - Pressure Transmitter with Indicator
BU Disarm, Breakdown
Break Down - PR Pressure Rupture - Vacuum Breaker
C.T. Conductivity Meter Transmitter - Conductivity transmitter P.T. Pressure Transmitter - Pressure Transmitter
IS Voltage Switch - Current Switch Ql Quantity Indicator - Quantity Indicator (Energy)

THAT Voltage Switch Alarm - Current Switch Alarm Q.T. Quantity Transmiter - Quantity (Energy) Transmitter
re riow Control - Flow Control R.A. Rupture Disc Alarm - Rupture Disc Alarm
FCAI Flow Control, Alarm & Indicator - Flow Indicator with Control RD Rupture Disc - Rupture Disc

FCV Flow Control Valve - 1 Gate Valve R.S. Rupture Disc Switch - Rupture Disc Sensor
F.D. Frequency Drive - Frequency Variator HE Speed Control - Speed Control
FlCV Fire Control Damper/ Valve - Fire Damper SC Al Speed Control, Alarm & Indicator - Speed Control Alarm with Indicator
h H^nd ■ Manual SW Start Order

H.C. Humidity Control - Humidity Control S.T. Status On-Off - Tin On-Off
H.T. Humidity Transmitter - Humidity Transmitter - Temperature Control
RC Temperature Control

HICA Humidity Transmitter, Control & Alarm - Humidity Transmitter Control and Alarm TCV Temperature Control Valve - 1 Gate Temperature Control Valve
Humidity & Temperature Transmitter - Temperature and Humidity Probe YOU Temperature Indicator - Thermometer

M Engine - Engine 1IC Temperature Indicator & Control - Thermometer with Control
M.N. Status Manual - Status Manual TICA Temperature Indicator, Control & Alarm - Thermometer with Control and Alarm
PC Pressure Control - Pressure Control YOU Temperature Transmitter ■ Temperature Transmitter
PDC Pressure Differential Control - Differential Pressure Control AND Position - Position
PDS Pressure Differential Switch - Differential Pressure Probe ALRE Position Alarm - Position Alarm
ADY
PDT Pressure Differential Transmitter - Pressure Transmitter Y.S. Position Sensor

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X.-CONTROL SEQUENCES FOR CLEAN ROOM HVAC SYSTEMS

Learning objectives

1. Learn to correctly create an operating sequence.

2. Recognize the importance of the sequence of operation as it relates to design, specifications
and construction.
3. Understand how the sequence of operation continues to update from commissioning and
during the long-term operation of the building.

The sequence of operation is one of the most important design aspects of any HVAC system.
Without proper sequencing, the system could operate out of control or stop working altogether.
When approached methodically, the process can be broken down into smaller segments. We will
look at the steps required to successfully create an operating sequence using variable air volume
(VAV) for a single zone of an air handling unit serving a multi-cleanroom space. These same
steps can be applied to any team.

Before the designer can begin to actually create the sequence of operation, some information
must be gathered. That data collection and brainstorming process can be broken down into the
following main steps:

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Step 1: Create a system flowchart . By creating a flowchart, the designer can identify the
components of the system. Those are the components that must be controlled to achieve the
desired operational results. The general sequence can be written with a subsection for each of the
main components of the air handling unit. One section may deal with fan control, another with
temperature control, and various safety devices and accessories may be detailed separately.

Figure 38: A schematic diagram shows the control components of the example air handling
unit (AHU). Courtesy of: JBA Consulting Engineers

Figure 38 shows the main components of the air handling unit (AHU) that we are considering for
our example. This unit has an air extractor, outside and supply air flow measurement stations,
mixing box, pre-filter, final filter, hot water coil, cold water coil and supply fan. The flow
diagram should also identify the air flow path and piping connections. It is not necessary to
include the air flow velocity and water flow rate data, as

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that this information must be included in the equipment use plans. If desired, flow rates can be
included, or the diagrams can be left more generic. The latter allows the use of the same diagram
for multiple similarly configured units. Include all inputs and all variables that must be controlled.
Components other than inputs or controlled variables should be omitted to maintain a simple
diagram that is easy to read.

Step 2: Classify the purpose of the team . One of the first questions to ask before proceeding is:
“What is the purpose of the system?” Often the purpose is to heat or cool to a temperature of
comfort for human occupants. Sometimes the purpose is to maintain acceptable temperatures for
a process (for example, a data center). Perhaps the system needs to maintain pressure
relationships for a particular space or group of spaces. The designer must also identify any other
equipment that is affected by the sequence. A makeup air unit, for example, must be interlocked
with the exhaust fan(s) that create the need for that makeup air unit. Keep in mind that a system
can have multiple purposes. An AHU may be designed to condition a space during normal
operation and also to function as a smoke control system during a fire.

Step 3: Identify the necessary inputs and outputs . It was noted earlier that the flowchart
should include entries for the controlled variables. Inputs are the readings that go into the building
management system (BMS). These include elements such as spatial sensors, air temperature
sensors, static or differential pressure sensors, etc. In developing this list of input devices, the
designer should consider which inputs are already available for use in the control system. Are any
of the required input devices included as part of the equipment or have they already been
specified for other purposes? At this time additional devices must be indicated and specified in
the construction documents. Outputs should also be considered at this time to prepare the
complete list of points. The outputs are the signals from the BMS system for the controlled
variable.

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Step 4: Detail the system functions required by the regulations . Energy codes (such as
ASHRAE 90.1) are becoming stricter and increasingly demanding more efficient systems.
Identifying these requirements in advance helps ensure that the system will comply with
applicable energy savings regulations. Control requirements, isolation dampers, demand-
controlled ventilation, economizers, superheat limitations, dead zone, and supply air temperature
reset are examples of requirements in operating zone regulations that, where appropriate, should
be incorporated. to the sequence. It is important to recognize the requirements and exceptions for
your particular project location.
Other building, mechanical and fire code requirements should also be reviewed at this time. For
example, regulations may require that a unit be turned off if smoke is detected. Additional control
requirements may come into play if the equipment has a smoke control feature.
HVAC features and equipment required by regulations should be identified early in the design
process. This is one of the reasons why it makes sense to develop the sequence of controls early
in the design process. Doing so allows for a complete and exhaustive coordination initiative as the
design progresses.

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Step 5: Confirm owners' performance requirements and expectations. After identifying the
minimum functions that regulations require of the unit, the designer should confirm whether the
owner has specific operating requirements and should understand how the owner intends to use
the equipment. These requirements can be identified in the project owner's requirements or in a
request for proposal that explains the scope of the project. If a project owner requirements
document has not been developed, the designer should consult with the owner to verify the
intended use of the systems. The team should discuss what desired system features might conflict
with overall proper operation and regulatory requirements. The system should be reviewed to
locate any additional components needed to accommodate the owner's desired operation.

Figure 39: This graph of an example building management system (BMS) shows several
points. The graphical outline presents a summary of the unit's status in a clean and simple
format. Courtesy of: ABS Systems Inc.

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The sequence of operation must be adapted to the mode of operation of the building, as well as
the experience of the facility's maintenance personnel. Sequences developed for a large casino
resort that has a full-time, highly experienced in-house maintenance staff may be more complex
than those developed for a small office building without a dedicated maintenance staff. Sequences
should always be as simple as possible while still meeting performance requirements.
Unnecessarily complex control sequences can overwhelm even the most experienced operator, as
they are more difficult to use and maintain. A lack of understanding on the part of the operator or
the need to take control will often result in the building being operated differently than the
designer intended.
Once that information has been gathered, the designer can begin to actually create the sequence of
operation. This will be the baseline upon which the requirements for the control sequence will be
identified and further developed.

POINT DESCRIPTION To the A.O. GAVE DO TAG

AHU-01
SUPPLY FAN MANUAL MODE 1 H-001
SUPPLY FAN AUTOMATIC MODE 1 AU-002
SUPPLY FAN START ORDER 1 SO-003
SUPPLY FAN STATUS 1 ST-004
SUPPLY FAN FAULT 1 BD-005
SUPPLY VENTILATED EAR PRESSURE 1 PDT-006
DELIVERY FLOW 1 FC-007
DIRTY G-4 FILTER 1 PDS-008
DIRTY F-9 FILTER 1 PDS-009
TEMPERATURE AND HUMIDITY IN RETURN 1 HTT-010
COOLING BATTERY VALVE 1 TCV-011
HEAT BATTERY VALVE 1 TCV-012
DIRTY G-4 FILTER 1 PDS-014
RETURN DUCT PRESSURE 1 PDT-015
RETURN FLOW 1 FC-016
MANUAL MODE RETURN FAN 1 H-018
AUTOMATIC RETURN FAN MODE 1 AU-019
RETURN FAN START ORDER 1 SO-020
RETURN FAN STATUS 1 ST-021
RETURN FAN FAILURE 1 BD-022

Table 18: A list of points is shown for the air handling unit example. All desired inputs and
outputs must be listed and classified. Courtesy of: JBA Consulting Engineers

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Step 6: Make a list of points . The information collected in the previous steps allows the creation
of a list of points. The point list identifies all inputs and outputs that are controlled or monitored
by the BMS system. A matrix similar to Table 18 is often the best method for identifying these
points. The matrix must identify all inputs and outputs for the controlled system. Points can be
classified as digital or analog. The digital inputs and outputs are a simple on/off condition (0 or
1). The analog inputs and outputs represent a value within a range that corresponds to a change in
voltage (for example, from 2 to 10 VDC) or amperage (from 4 to 20 mA) or, in the era of
pneumatic controls , to a change in air pressure. A dirty filter alarm from a differential pressure
switch is an example of a digital input to the controller. The chilled water valve position is an
analog output as it is modulated from the 0% to 100% open position. The system must be
designed to allow for expansion and must be able to handle at least 125% of the number of points
currently specified. Allocations must also be made for virtual points. These are points that are
calculated or passed through the controls system rather than physical hard-wired points.
Step 3 may need to be revisited as the list of points develops. The designer may realize that he or
she does not have all the input and output devices necessary to achieve adequate control of the
system. It is best to identify these changes during the design phase so that they do not become
costly changes in the field.
Monitoring capability and alarms should also be reviewed at this time. These points provide
additional information to the operator and allow them to monitor system performance. This can
be valuable information, but an excessive number of points can be overwhelming, costly and may
not bring real benefits to the operator. Controls should be simple as much as possible. The
operator must have all the necessary information at a glance, additional information becomes
“noise” and distracts the operator, preventing him from focusing on the important points. Almost
any security within a system can be monitored and trended. The designer must ask himself
whether or not each of the points are really necessary for each particular system.
The storage capacity of the system must also be specified. The length of time the data should be
retained should be identified (for example, 30, 60, or 90 days). The frequency of trends must also
be evaluated. Is it necessary to take samples and record readings every 15 seconds or every 15
minutes? The

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Trending hundreds of points every few seconds can lead to network performance issues.
Consider best practices for the specific region you are working in. In some areas, control
specifications may be performance based and in that case the temperature control contractor will
be responsible for providing all hardware components and points necessary to achieve the
designed sequence of operation. Other geographic regions or particular projects may require the
designer to specify the exact details and bullet points for all system components to be provided by
the controlling contractor.

Step 7: Identify setpoints . Setpoints are the values that the system attempts to maintain during
operation. Space temperature is a common example of a set point. The space sensor or thermostat
is the input device that measures the current temperature in the space. The control system
contrasts the actual state with the set point value. Setpoints are not limited to temperature. The
duct static pressure sensor that controls the fan speed will also have a set point. Similarly, a set
point must be identified for the carbon dioxide (CO2) sensor that serves as input to the demand-
controlled ventilation strategy.

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Step 8: Analyze actions and functional responses. Initiation and functional response are the key
aspects of the sequence of functioning. It's probably what comes to most people's minds when
they hear the term “operating sequence.” It is best to analyze them as a numbered list.
Let's look at temperature control for our example. The space temperature sensor is the input
device. It measures the temperature of the space and sends the value to the system brain. In
autonomous equipment, this will probably be an equipment controller with pre-established
control sequences. In larger and more complex systems, that value is reported to a BMS system.
The BMS system acts as the brain of the operation and evaluates whether the measured value is
within the operational parameters, at the set point. Assume the system is operating in cooling
mode with the cooling water control valve partially open and the heating coil coil valve fully
closed. If the value is above the set point, then the space temperature will be higher than desired.
The cold water control valve opening must be modulated to provide additional cooling and reduce
space temperature.

The sequence of operation should concisely list these evaluations and how the system should
respond. Recommended descriptions for the last example may be similar to the following:

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Figure 40: Air treatment units in redundant format connected to a common source and a
return duct. The sequence defines the positions of the control gates and the power-on
sequence of the units. Courtesy of: JBA Consulting Engineers

In cooling mode, the set point will be 75ºF ± 1ºF (adjustable). If the space temperature rises
above the cooling set point, the system will first modulate the cold water control valve from 0%
to 100% open according to proportional, integral and derivative (PID) control and flow. supply
fan air flow will be kept at the minimum position. The supply fan speed will be modulated from
minimum to 100% of design airflow if the control valve position is opened more than 70%
(adjustable). If the space temperature drops below the cooling set point, the system will modulate
the cold water control valve and close it according to the PID control. If the control valve opens
less than or equal to 50% (adjustable), the supply fan speed will reset to the minimum supply air
flow rate.

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The designer has to systematically work out all the ways that the system might need to modulate.
You need to consider all the modes in which the system must operate and which components of
the system must operate differently in those modes. Think about the exhaust and supply fans in
our system. Our example assumes that the exhaust fan air handling unit also functions as a fume
extractor. The fans and dampers will operate differently in smoke control mode than in normal
operation. The sequence of operation must specifically identify the requirements for each of these
modes.

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LIST OF CONTROL POINTS

Systems Outputs Syste s Inputs System Software Control
Binary Analog Binary
m Analog Alarm Processing Application Function
System Component Point ID command Position % Status temperature Pressure Humidity flow Current Totalization Conductivity ORP Percent Data Comm Line Equipment Status Low Limit High Limit Lead Lag StartStop

Supply Fan

On-off
StartStop
Status Aut
Statue Hand
VFD Control Panel

Return Fan

On-of
StartStop
Auto Status
Statue Hand
VFD Control Panel

Relief Fan

On-of
StarStop
Auto Status
Statue Hand
VFD Control Panel

Exhaust Fan

On-off
StartStop
Auto Status
Statue Hand
VFD Control Panel

Glycol Energy Recovery Pump

On-of
StartStop
Auto Status
Statue Hand

Outside Air Temperature

Outside Air Hu miditv
Mixed Air Temperature
Heat Recovery coi 1 Temperature
Preheat Coil Temperature
Chilled Water Coil Temperature
Supply Air Temperature
Supply Air Humidity
Space Temperature
Space Humidity
Pre Filter Status
Freeze stat Status
Duct Mounted Smoke Detector Status
Stat c Pressure sensor

Room Digital Book

Outside Air Damper Position
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ez
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Mixed Air Damper Position

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Table 19: During the design stage, a matrix can be used to write the various modes of
operation. The designer can use this brainstorming exercise to help write the actual
control sequence.
Let us remember that the normal operating mode can also have several other modes associated
with it. In our example, we have economizer operation and recirculation operation. A matrix
like the snippet shown in Table 19 is an easy way to identify the parameters needed for
different modes of operation. Although this matrix will not always be included in the
construction documents, it provides the designer with a general summary that helps him or her
develop a written sequence of operation. The various analog and digital inputs and outputs
should, in some way, be clearly identified in the construction documents with the
corresponding control sequence that has been designed.

Step 9: Identify failure situations. At some point, system components will fail. Although
quality products help reduce the frequency of failures, they are inevitable. If the designer plans
for these failures in the sequence of operation, then they can reduce the resulting operational
impact when a failure occurs. Once again, we must be careful not to oversize. The strength
requirements for a typical office building will be substantially different than those for a data
center. Personal safety requirements must also be considered.
Failure considerations should focus on both the input devices and the controlled components
of the system. Failure of a static pressure sensor in the supply duct could result in improper
speed control of the supply fan variable frequency drive. If the value measured on this sensor
varies significantly from the expected value, a false measurement could have been received.
The operating sequence may specify that this reading be ignored if the value is percentage-
wise outside the expected value. Some input devices may also integrate a function into the
sensor to detect invalid readings.

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Figure 41: Frequency converter is used in air extractors. The sequence jointly modulates the
speed of the fans to maintain a differential pressure within the space. Courtesy of: JBA
Consulting Engineers
Let's consider a low static pressure sensor reading. A sequence that identifies the failure of this
component can reset the power fan to some set speed that keeps the system running and
provides at least some capacity until the maintenance team can properly address the problem.
A system that does not anticipate that failure will continue to control the system using the
erroneous static pressure measurement. This system will likely increase the speed of the
supply fan until the system eventually shuts down due to high static pressure if a high static
pressure set point was considered in the original checklist. This typically requires a manual
reboot and the system will have a longer downtime than a system that does incorporate
failsafes. This is an important consideration for systems where environmental conditions are
critical or where safety could be compromised.

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Let us now consider the failure of a controlled device such as a control valve actuator. Failure
of this device will result in loss of space temperature control. The importance of a failsafe
position for this actuator can be debated, but in a warm climate using an open spring return
actuator for a cooling water coil may be considered. Even if the system no longer has precise
control, this arrangement errs on the side of caution and will overcool the space until the
system can be repaired. This could be more important for cooling equipment serving
telecommunications rooms, data centers or other process loads where a loss of cooling has
significant consequences.

A power fan motor failure in a system with a single power fan has no true fail-safe position.
However, a system with multiple motors and supply fans could respond to this failure situation
without reducing the supply air flow. This is an excellent example of how the development of
an operating sequence can result in changes to the hardware components specified for the
system. The impact of feed fan motor failure may have been overlooked prior to this stage of
design.
Step 10: Review the sequence . At this point, the designer has completed the first step in
developing the operating sequence. A successful sequence is iterative and often requires
revisiting previous steps. It has been mentioned above that a designer might start writing the
actual functional responses of the system and realize that it does not have all the required input
and output devices. This may require an update to the initially developed flowchart. The
operating sequence development process may also identify features or options that were not
originally specified. Now is the time to adjust and fine-tune those specifications.
The best way to review the sequence of operation is to go through each of the actions and
responses. Decompose the system by identifying situations to which the sequence of operation
cannot adequately respond. Rewrite the sequence as necessary to address these scenarios. Ask
a colleague to review the sequence to make sure the purpose of the sequence is clear to
everyone.

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In complex systems, it analyzes how individual equipment interacts with the sequence of
operation of other equipment. A multi-zone VAV system will have an operating sequence for
the individual terminal units and for the central air handling unit. These sequences must be
coordinated to ensure that they work in harmony for maximum operating efficiency. The
correct functioning of one depends on the other.

Start up
Functional testing during commissioning helps ensure that the built project operates in
accordance with the design objective. Testing relies heavily on the designer's sequence of
operation. The equipment should not be expected to perform functions that were not required
by the sequence.
Discrepancies observed during the project start-up phase should be reviewed with the
designer. It may be necessary to update the operating sequence based on data collected during
functional testing. See the static pressure sensor example mentioned above. During start-up is
the appropriate time to verify whether fail-safe strategies are working as expected. The goal is
to keep the system running. The implementation of this feature should be tested by those
responsible for commissioning and the team should modify the setpoints as necessary to
achieve the desired results.

Commissioning is the last opportunity to evaluate the sequence before handing the project
over to the owner. The designer should participate in the commissioning process and review
the final commissioning report. The sequence may need to be modified based on observations
during the commissioning period. Changes this late in the project schedule could have major
implications for costs and planning. That said, the designer should not rely on the
commissioning process to compensate for a lack of adequate foresight during the design phase.

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Functioning

The building operator must have full knowledge of the sequence of operation. This ensures
that the facilities maintenance group operates the equipment consistent with the design
objectives by recognizing all the benefits of the implemented system. The building operator
can take control of the supply air temperature if there are complaints about the temperature of
a space. Said operator must understand the consequences that his taking control has on energy
efficiency. Identify the root causes of operational deficiencies and resolve problems at the
source.
Although the designer must consider operational needs during the design phase, those specific
details may not always be available. The sequence may need to be readjusted based on the
evolution of the building's operation over time. The sequence of operation should be
considered as a living document that is maintained continuously throughout the life of the
system. If this is done, knowledge can be transferred seamlessly within the operations group.
Understanding the control logic for existing equipment is important for designers working on
building renovations or tenant improvements within an existing space. Without this
knowledge, the new design could work against the base system rather than being coordinated
with it.
An update sequence also becomes a testbed for how the system should work. The sequence for
existing equipment can be modified to optimize energy efficiency and improve adaptation to
the evolved functional and operational requirements of buildings. Retrofitting and energy
audits are great ways to identify deficiencies in the control sequence of existing equipment.
Existing equipment without a well-defined operating sequence could be a good target for
energy optimization.
HVAC systems use a large amount of energy in commercial buildings. Developing a well-
thought-out operating sequence helps minimize the energy consumption of these systems.
Additionally, it allows the system to meet the criteria for which it was designed. The designer
must develop the sequence to a level of detail that is appropriate for the project at hand and
maximizes the success of that particular project.

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Although it is not uncommon to see sequences included in project specification manuals, the
best place to include this information is usually directly on the construction drawings. Keeping
the sequence of operations closely tied to team schedules, plans, and control schemes increases
information transparency throughout the project history. This arrangement has its advantages,
since the project specifications manual is not always available in the field and is often
separated from the plans.
The steps described can be translated for almost any system regardless of size and complexity.
What you need to remember is that the sequence of operation cannot be written in a hurry once
the project is ready and just before it is delivered. An effective operating sequence begins early
in the design process, when systems are being developed and equipment is being selected.
Doing so allows the designer to develop the most effective system.

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HVAC CONTROL AND MONITORING SYSTEM
MONITORING AND CONTROL OF HVAC VARIABLES
This may be direct through the communication bus with the equipment card or through link
points such as the following:
Start / Stop , this work is within the scope of the electrical contractor who must deliver this
point to the terminal board.
Operating Status , this may be through Flow Switch, current sensor or auxiliary contact,
supplied and connected by controls.
Selector Status is an auxiliary contact module that the electrical contractor will add to the
automatic mode of the selector and that is delivered to terminal blocks.
Filter Status , this will be through a Pressure Differential in each filtering stage and will be
installed and connected by the controls specialty.
Damper Modulation and Water Valve , the servomotor will be supplied and installed by
climate specialty and electrically connected by controls specialty. The actuator must be
supplied to work with 220 V.
Thermal Failure , this work is within the scope of the electrical contractor who must
deliver this point to the terminal board.
Temperature, Humidity and Pressure Sensors will be supplied and connected by the
controls area. The Temperature, Humidity and Pressure parameters are generally defined by
the Project Design Criteria.
UMAS
The Air Handlers will have a single controller, which will contain the following monitoring
and control parameters:
UMAS
• Start/Stop
• Operating Status
• Pre Filter Status
• Filter Status
• High Efficiency Filter Status

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• Ice Water Valve
• Hot Water Valve
• Air return temperature
• Air injection temperature
• Ambient Humidity
• Start/Stop Humidistat
• Operating Status
• Humidistat
• Zone Pressure Sensor
• Frequency Inverter
• Thermal Failure
• Ice Water Valve
• Hot Water Valve
• Return Temperature
• Injection Temperature
• Thermal Failure
The UMAS must be associated with a temperature and pressure sensor in the area that
makes them operate when the set-point level is registered by the centralized control.
In the case of UMAS that serve more than one enclosure, Multizone UMAS, these will be
associated with an Air Injection temperature sensor or pressure sensor, which makes them
operate when the set-point level is registered by the centralized control. .
CHILLER
For Chiller type equipment, communication based on protocol has been considered, of
which the permitted ones are LonTalk, BACnet MS/TP or Modbus/RTU.

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RECIRCULATOR PUMPS
Both cold and hot water pumps will have the following reading and control variables:
• Start/Stop
• Selector State
• Operating Status
• Thermal Failure
• Frequency Variator: this will be controlled through a local Differential Pressure
Transmitter. Applies only to the hot and cold water supply pumps of the secondary circuits.
FANS AND EXTRACTORS
Extraction (VEX and EX) and air injection (VIN) equipment must have at least the
following control points:
• Start/Stop
• Selector State
• Operating Status
• Filter Status (VIN)
Furthermore, those equipment whose power is small, such as the bathroom fan, its control
will be associated with the room's lighting switch.
The extraction fans located in underground parking spaces must be associated with a
monoxide sensor for each one, which will operate when the level reaches a pre-established
value. These sensors must come with their approval certificate and be first-hand.
BOILERS
These units will be controlled through discrete signals and must have an exclusive
controller, considering the following delivery data:
• Start/Stop.

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• Operating Status
• Return Temperature
• Injection Temperature.
• Gas Pressure
• Water Pressure.
It is the responsibility of the thermal contractor to modify the water and/or gas pipes to take
readings from the different sensors considered.
Below is an example of signals used in different types of drive units.
This means that each configuration of handling units is different.

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Below are some examples of surgical ward control and MRI:

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Conditioning installation for operating room with

unidirectional ceiling

to:
*
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Conditioning facility for MRI departments

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XI. VARIABLE AIR FLOW (VAV) AND CONSTANT AIR FLOW (CAV) SYSTEMS
In the design of a clean room, it is normal to use variable air volume (VAV ) systems and
constant air volume (CAV ) systems. The main difference between the two is that one
maintains the temperature constant to the extent that it modulates the air flow, through the
movement of the dampers of the dampers, in each of the rooms in question. And the other
maintains the constant volume in each room, as the flow of hot and cold water is modified
in the motorized valves of each of the hot and cold coils.
In Clean Rooms and in the pharmaceutical sector, it is required to manage conditions of
pressure, temperature, relative humidity and energy efficiency. The design of heating,
ventilation, and air conditioning (HVAC) systems has a significant impact on both, and
working with a qualified engineering firm has a positive impact on the bottom line.
A key decision in HVAC design is selecting an appropriate air handling configuration:
constant air volume (CAV) or variable air volume (VAV). Each option has advantages and
disadvantages, and using the correct configuration improves comfort and efficiency.
Constant air volume systems
CAV systems maintain a constant airflow, as the name implies, and the desired indoor
conditions are achieved by adjusting the temperature of the air supply. For example, when a
building requires higher cooling output on a higher summer day, the CAV system supplies
cooler air. In chilled water systems, the cooling effect depends on the flow of cold water
delivered to the fan coil unit. In turn, the water flow controller works according to the
thermostat settings.
CAV systems can be single-zone or multi-zone, although they are best suited for single-
zone applications where the load experiences minimal change over time. Some examples
are infectious wards, hospitalization, etc. Multi-zone CAV systems require duct heating to
supply different air temperatures for individual zones, reducing their energy efficiency.
The operation of a multi-zone CAV system can best be described with an example.
Consider the following design conditions:

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An indoor air handling unit (AHU) serves three zones (A, B and C).
Each of the three zones has a dedicated thermostat.
The AHU draws cold water from a chiller with a cooling tower.
Air duct heaters are attached to the main branches that serve individual zones.
Thermostats are set at 55°F (A), 68°F (B), and 72°F (C).
The AHU supplies cold air at 55°F.
Once the supply air enters the duct system, it can only be heated and not cooled. Therefore,
it must be supplied at the lowest of the three required temperatures: 55°F for zone A in this
case. After zone A is served, the airflow can be heated to the temperatures required for other
zones: 68°F for zone B and 72°F for zone C.
Although the operating principle is simple, it has efficiency limitations. Some cooling
output is wasted when reheating the air for zones B and C, and duct heaters also consume
energy.
Variable air volume systems
As you might guess, VAV systems keep the air temperature constant and instead adjust the
airflow based on the load. VAV systems can have single-zone, multi-zone, or dual-duct
configurations. Just as CAV is the preferred choice in single-zone systems, VAV is
recommended for multi-zone systems.
Dual duct VAV systems have separate ducts for hot and cold air, and each zone has a
plenum where its airflow is mixed. The ratio of hot and cold air depends on the desired
temperature for each particular zone. This HVAC configuration is the most expensive in
terms of installation, operation and maintenance.
Multi-zone systems have VAV boxes that control the airflow supplied to individual zones.
Unlike CAV, the flow of cold water supplied to the fan coil unit remains constant. VAV
systems reach their full potential in applications where there are multiple zones with
variable load. Some examples are shopping malls, hotels, and office buildings.

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VAV boxes have a similar function to the duct heaters used in a CAV system. Instead of
reheating the air according to the needs of each individual zone, the airflow is controlled
while keeping the temperature constant.
Basic calculations in CAV and VAV design
The HVAC design process involves complex calculations and energy modeling. However,
the equations that describe the system's operations are simple. This section describes how
the temperature and airflow are adjusted depending on the load.
The starting point is the sensible heat gain equation, which is fundamental in HVAC
systems:
Q = 1.08 x CFM x ΔT
Where:
Q = Load of the room or zone served (BTU / hour)
CFM = air flow in cubic feet per minute
ΔT = Difference between ambient temperature and supply air temperature
Example 1 - VAV System
Suppose a room has a load (Q) of 10,000 BTU/hr, with an indoor temperature of 75°F and a
supply air temperature of 55°F. In this case, the difference is 20°F. To calculate the required
airflow, the sensible heat equation can be rearranged:
Q = 1.08 x CFM x ΔT
CFM = Q ÷ (1.08 x ΔT )
CFM = 10,000 BTU/h ÷ (1.08 x 20°F) = 463 cfm
In this case, the VAV system would have to adjust the airflow to 463 cfm for the
corresponding zone. Let's look at the effect when the load is increased to 12,000 BTU/h.
CFM = 12,000 BTU/h ÷ (1.08 x 20°F) = 555 cfm
The 20°F temperature difference remains constant under a 12,000 BTU/hr load, while
increasing airflow to 555 cfm.

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Example 2 - CAV System
In this case, the cooling load and ambient temperature are the same as used in the previous
example: 10,000 BTU/h and 75°F. However, the airflow is fixed at 500 cfm and the air
supply temperature is adjusted. The sensible heat equation would be rearranged as follows:
ΔT = Q ÷ (1.08 x CFM)

ΔT = 10,000 BTU/h ÷ (1.08 x 500 cfm)

ΔT = 18.52°F

The supply air must be 18.52°F below ambient temperature, which is equivalent to 56.48°F.
Repeating the calculation for 12,000 BTU/h, the following result is achieved:
ΔT = Q ÷ (1.08 x CFM)

ΔT = 12,000 BTU/h ÷ (1.08 x 500 cfm)

ΔT = 22.22°F

In this case, the required supply air temperature is 52.78°F.

Example 3, mixing VAC with VAV
According to what is shown in figure 42, where there is a mixture between a constant air
flow system with a constant volume flow. These rooms are part of a pharmaceutical
laboratory and contain CD grade rooms.
According to what is shown in figure 42, it is a combined system between a VAC and VAV
system, the most important points are the following:

• Control loop (0501), G4 filter pressure differential

• Control loop (0502), filter pressure differential F9
• Control loop (0501 A), Air injection fan, with frequency converter, includes
pressure transmitter, which controls the speed of the fan, as the static pressure
changes during a work cycle.
• Control loops (001, 002,003, 004, 005 and 006) Temperature transmitters control
the passage of water flow in the hot and cold water coils. From the AHU-05
Handling Unit. For supplying air to rooms 025; 026;027; 028; 029 and 030.

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• Control loop 0507: 0508; 0509; 0510; 0511; 0512, differential pressure transmitter.
They control the differential pressure in the different rooms. For rooms 025;
026;027; 028; 029 and 030.
• Control loop 007, temperature control, has the control loops associated with the cold
water and hot water valves. Associated with the temperature transmitters in all
rooms.

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Figure 42, Mixing VAV and CAV systems

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In the case of Hospitals , in general the infectious and immunocompromised wards, use this
type of equipment, by way of knowledge we have:
Infectious Rooms
Each group of these rooms will be attended by an exclusive UMA for this purpose.
- The UMA will only have an air supply module, without heat recovery.
- The extraction will be carried out using independent equipment for each room (including
your bathroom). Logically, each room will have its extraction duct exclusively for it. The
extraction grilles located in the room and in the bathroom will be equipped with HEPA
filters.
- These rooms will be in depression with respect to the hallway (minimum 10 Pa). The
control system will act on the air regulators of the delivery ducts and the frequency
converters of the individual extraction equipment to achieve this objective. Next to the room
there will be a visual panel that will provide the negative differential pressure reading
between the room and the hallway at all times. If the depression were lost, an alarm signal
would be given.
- In the delivery ducts, in addition to the watertight closing gates, overpressure shutters will
be installed to ensure the absence of unwanted air flows in the event of gate failure.
- The arrangement of diffusers and grilles in the room will comply with the provisions of
the ASHRAE 170 standard and its addenda.

Immunocompromised Rooms:
Each group of these rooms will be attended by an exclusive UMA for this purpose.
- These rooms must be overpressurized with respect to the hallway (minimum 10 Pa). The
control system will act on the duct air regulators to achieve this. Next to the room there will
be a visual panel that will provide a positive differential pressure reading between the room
and the hallway at all times. If the overpressure was lost, an alarm signal would be given.

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- In the ducts, in addition to the watertight closing gates, overpressure shutters will be
installed to ensure the absence of unwanted air flows in the event of gate failure.
- The arrangement of diffusers and grilles in the room will comply with the provisions of
the ASHRAE 170 standard and its addenda.

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XII.- HOSPITAL HVAC DESIGN
The development of hospital projects in the HVAC discipline is very complicated to carry
out if you do not have extensive experience in health centers.
It is important to highlight that air conditioning systems must be coordinated with other
specialties such as clinical gases, fire network, fire detection, weak currents, centralized
control systems, pneumatic mail, electricity, sanitary and other specialties.
Air conditioning systems in hospitals
An effective air conditioning system controls the risk of acquired infections in a
hospital
Hospitals, clinics and other medical facilities, their facilities pose several unique challenges
that are not present in traditional HVAC situations.
As such, it is important for HVAC designers, engineers, installers, maintenance personnel,
and other professionals to become familiar with HVAC system installations.
Not only may the comfort of doctors be on the line, but patients may be at risk from a poor,
malfunctioning HVAC system. Here is a brief introduction to HVAC systems for medical
facilities and how a hospital critical patient room should be designed.

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ROLE OF HVAC SYSTEMS IN INFECTION CONTROL
Hospital-acquired infections (HAIs, also known as nosocomial infections) have a significant
impact on patient care. Death rates from HAIs are significant and affect the overall cost of
healthcare.
In the United States, HAIs occur in an estimated 4% to 5% of hospitalized patients; at an
estimated annual cost close to $7 billion dollars. It is generally accepted that 80 to 90% of
HAIs are transmitted by direct contact, with 10% to 20% resulting from airborne
transmission (representing 0.4% to 1% of admitted patients).

1. Contact, both direct and indirect, is the most common mode of transmission in
healthcare, facilities, and other indoor environments.
HVAC systems have little impact on this mode of transmission.
2. Droplet transmission is characterized by the spread of microorganisms from an infected
person over short ranges (3–6 feet). The aerodynamics of this result in microbes contained
in fluids falling from the air quickly.
3. Airborne transmission involves the spread of microbes through droplet nuclei beyond
short ranges, such as through an HVAC system.

HVAC systems can affect the distribution patterns of airborne particles by dilution or
concentrations, moving them into or out of the breathing areas of susceptible people, or
accelerating or slowing the growth rate of airborne microbes. Improperly operated and
maintained HVAC systems can even become a reservoir for microorganisms.

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1.- ROOM INSULATION
If your doctor wants you to be kept away or isolated from other patients while you receive medical care, you
may be in a special hospital room, called an isolation room, to keep you separated from other people.
HOW TO DEAL WITH ROOM ISOLATION

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CODES/STANDARDS, REFERENCES AND GUIDELINES
I CODES

International Mechanical Code (IMC)

Standard
ANSI / ASHRAE / ASHE Standard 170 - Ventilation of
health facilities (2017)
NFPA 101

GUIDELINES

Facility Guidelines Institute (FGI) Guidelines (2014) - for ventilation refers to ASHRAE Standard 170 - 2017

Guidelines for Environmental Infection Control in Health-Care Facilities", Recommendations of CDC (centers for Disease Control &
Prevention) and the Healthcare Infection Control Practices Advisory Committee ( HICPAC), 2014

Types of isolation Critical Patient Unit

TYPES OF ISOLATION ROOMS

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What is an airborne infection (AII) isolation room?
• These rooms are for patients who have an airborne disease.
• In this type of infection, the patient is the source of infection.
• The ventilation system functions as one of multiple levels of the infection control system.
• The purpose is to contain infectious microbes generated by the patient within the room, to prevent the
spread of infection to other patients and staff.

CONSIDERATIONS IN DESIGNING AN ISOLATION ROOM

• AIR TERMINALS
It is recommended that the injection diffuser in the case of infectious patients be in front of the bed and the
extraction grill at the head of the bed. With the idea that no person's health or visits can be contaminated.
In the case of immunosuppressed patients, it is recommended that the injection diffuser be at the head of the
bed and the extraction grid in front of the bed. With the idea that no microorganisms enter from the
hallways.
• FILTRATION SYSTEM
The terminal filters for injection in immunosuppressed patients must be 99.97% efficient and do not require
a HEPA filter in extraction.
The terminal injection filters in the infectious ones must be 95% efficient and if a HEPA filter is required in
the extraction, 99.97%.
• EXTRACTION SYSTEM
It is advisable to use centrifugal extractors with a frequency converter, for a better balance of flow rates.

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• All exhaust air will be sent through a vertical duct
• The power of the extraction fan must be sufficient to extract air from all isolated rooms.
• The air must be discharged at a height of 3 meters above the ceiling level

• MONITORING DEVICE
It is necessary to use pressure differential in the corridor and connect its hoses between the room, lock and
corridor.
• All isolated rooms shall have a permanently installed device and/or mechanism, to constantly monitor
differential air pressure:
-Between the room (when occupied by patients with suspected infection or illness).
• The corridor or adjacent spaces of the room, whether or not there is an anteroom
• A local visual means shall be provided to always indicate that the differential is negative
• A minimum of 0.01” in.ac or 2.5 pa should be achieved.

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• REQUIREMENTS OF A LOCK
In both infectious and immunocompromised isolation rooms, use airlocks to separate areas with greater
contamination.
It is recommended for all isolation rooms.

Below is a table of the Ashrae 170, to see where the design data is obtained from.

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The following figure shows a room of infectious isolates:

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Below is an example of an infectious isolate room.

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ALL ROOM WITHOUT BEFORE ROOM

Considering a room with dimensions:

Length : 10ft
Width: 10ft
And height: 10 ft
Volume of the room will become :10*10*10 = 1000ft3

FORMULA FOR ROOM AIR CHANGES PER HOUR (ACH)

ACH = (60*CFM)/VOLUME

CFM = (ACH * VOLUME)/60

WE HAVE MIN ACH : 12 as per ashrae standard 170.

CFM = (12*1000)760

= 200CFM

Another example is the following:

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What is a PE protection environment?

These rooms are intended for patients with a weakened immune system.
These patients need protection from airborne infectious agents.
In this case, it is the patient who must protect himself from infectious microbes.
Also protection against opportunistic organisms that are not a threat to healthy people.

In the case of protected or immunosuppressed rooms, the following applies:

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Protective isolation room

Room supply and extraction design considerations
The same requirements as the infectious room (AII) except:

• Location of supply diffusers and exhaust grilles.

ASHRAE Standard 170 “Supply diffusers should be above the patient's bed... The diffuser design will limit the air velocity to the patient bed, to
reduce patient discomfort
ASHRAE Standard 170 “The return/exhaust exhaust grille should be located near the patient door.”
• The SA air supply must be from the Air Handling Unit (AHU) that has filtration to the required code:
Minimum MERV 7 prefilters and HEPA final filters (ASHRAE) or MERV 14 final filters with terminal HEPA filter. See following diagram:

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Supply/Exhaust Tracking Pairs

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AII/PE combination rooms

• These rooms are for patients who suffer from a weakened immune system and also have a contagious disease.
• The ventilation problems involved are the combination of room AII and PE

Airborne infectious combinations

ALL insulation/PE protective environment rooms
PE requirements govern supply diffuser and exhaust with grill locations: o ASHRAE Standard 170 “Supply diffusers
must be above patient bed o ASHRAE Standard 170 “Return/exhaust to grill must be located near the patient's door."
Two permanently installed monitoring devices required o One between AII/PE room and lock room o One between lock
room and corridor

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Airborne infectious combinations

Isolation/Protective Environment Rooms

• For immunocompromised patients with an airborne infectious disease.

• CDC and ASHRAE 170 allow two options: positive or negative airlock

Positive Case

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Supply/Exhaust Tracking Pairs

negative case

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Supply/Exhaust Tracking Pairs

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Contact isolation rooms

They are for patients with communicable diseases, that is not in the air.
Contact isolation

• Patients admitted to these rooms do not have an airborne communicable disease.

• Examples of such cases are:
-Diarrhea
–Wound drainage
–Body lice, etc.

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HOSPITAL SURGICAL BLOCKS

Where are there clean rooms in a Hospital?
In hospitals we cannot speak exclusively of “white rooms” or clean, since there are areas or spaces that group together premises with
these characteristics, for example:

• surgical block
• obstetric block
• Intensive care units (ICU), pediatric and neonatal
• Special and isolation boxes
• Burn Units
• Sterilization rooms
• Preparation of cytostatic and sterile
• vascular radiology
• Endoscopy
• Microbiology Laboratory
Other important clean rooms:

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Regarding what the ISO 14.644-1 Standard indicates, the following international table is available:

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Zoning according to risk

Differentiated areas of patient care, according to the risk of contracting infection:
A.-Low risk areas: administrative sections, areas external to the surgical block (BQ), etc.
B.- Moderate risk areas; regular patient care units. Transfer and patient passage areas
C.- High risk areas, isolation and intensive care units.
D.- Very high risk areas, for example, the operating room itself and the ante-operating room.

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WHAT IS UNDERSTOOD BY A SURGICAL BLOCK

Space that groups the operating rooms and the necessary support spaces

Below are single and double aisle BQs.

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Single aisle surgical block

PROFESSIONALS
PATIENTS

SUPPLIES
DIRTY

Operating rooms

White Zone

Pre-anesthesia /
ante-operative
medical work
room room
Gray zone

Patient access

Small surgery Revival

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Examples of flows inside a pavilion

Circuits for the configuration of: (a) double aisle and (b) single aisle

SURGICAL BLOCK
It is recommended that the number of operating rooms per surgical block is not excessive; eight,
operating rooms make it difficult to maintain discipline and air conditioning. more

The surgical block or surgical area must be independent from the general circulations of the hospital. The use of airlocks2
with interlocking automatic doors is recommended for access to the surgical block.
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Classification of Pavilions based on Standard ISO 14.644-1 and UNE 100.713

operating JOINS EN ISO 14644-

UNE 100713:2005 Operating room name Type of intervention
room type 1:2000

Organ transplants, cardiac surgery, vascular

High-tech operating rooms Special
TO Class I ISO class 5 surgery, orthopedic surgery with implants,
surgery.
neurosurgery, ..

Conventional and emergency surgery

b Class I ISO class 7 Conventional operating rooms
Rest of surgical operations.

Ambulatory surgery.
c Class I ISO class 8 Ambulatory surgery operating room
Delivery rooms.

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Hour renewals based on class type

Type of Temperature
operating room
Minimum driven air flow Movements/hour (MH)
Humidity
Pressure Filters

18°C-26°C
A class Minimum 30 45- 55% humidity F5/F9/H14
2400 m-/hour
1200 mYhour (outside air)
+20Pa to +25Pa
Class B Minimum 20
229C-26°C
45- 55% humidity F5/F9/H13

Class C 1200 mYhour (outside air) Minimum 15

Ventilation flow, hourly air movements, temperatures, pressure and filters indicated for operating rooms

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Below is an example of a surgical block:

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Resolution
Press Pas Pressure Diff. Cte
Sector TYPE OF PAVILION volume e Iny flow. Variation
Time renewals ure Pressure Fu area m2 calculation Extraction flow Flow rate ratio
Da m3/h Flow m3/h
Da Da
PAVILION 1 organ transplant

PAVILION! 0 roared card aca

PAVILION 3 G conventional roar

PAVILION 4 G roared convendona

PAVILIO 0 orthopedic roar
N5
PAVILION6 Ambulatory g roar

PAVILION? Q roared ambu atocia

PAVILION 8 Ambulatory g roar

AISLE 120 20

Determine for each pavilion

a.- Injection and extraction flow, exfiltration
b.- For the Central Hallway, determine

Infiltrad ones ma/h Outlet flow through diffusers either m3/h

Injection ma/h Flow rate of extraction grates EITHER m3/h

Extraction m3,h
Extiltration ma/h
Pue rus outlet flow ma/h

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c.- Exfiltration flow rate for doors 1 and 2

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Resolution
Sector TYPE OF PAVILION Volume m3 Diff. Pressure Cte Extraction
Pressure Variation
Hour renewals Pas Pressure Da Pa Iny flow. m3/h Fu area m2 calculation flow Flow rate %
Da Flow m3/h
PAVILION 1 Organ transplant 54 30 25 10 15 1620 0,046 355.407 596 1.024 63
PAVILION 2 Heart surgery 54 30 25 10 15 1620 0,046 355407 596 1.024 63
PAVILION 3 Conventional surgery 48 20 20 10 10 960 0,046 236.938 487 473 49
PAVILION 4 Conventional surgery 50 20 20 10 10 1.000 0,045 236938 487 513 51
PAVILION 5 Orthopedic surgery 54 30 25 10 15 1620 0,046 355.407 596 1.024 63
PAVILION 6 Ambulatory surgery 54 15 20 10 10 810 0,046 236938 48? 323 40
PAVILION 7 Ambulatory surgery 54 15 20 10 10 810 0,046 236938 487 323 40
PAVILION 8 Ambulatory surgery 54 15 20 10 10 810 0,046 236938 487 323 40
AISLE 120 20 10 3 7 2400 0,046 165.856 407 6.215

REMEMBER THAT

INJECTION FLOW + INFILTRATION FLOW = EXFILTRATION FLOW + EXTRACTION FLOW + RETURN FLOW

Balance of flows Central Hall

leakage area 0,046 m2
Infiltration 4.222 m3/h Outlet flow through diffusers 600 m3/h
Injection 2.400 m3/h Extraction grating flow 1.5S4 m3/h
Extraction 6.215 m3/h
Exfiltration 407 m3/h
Door outlet flow 204 m3/h

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Below are some flow balances for different clean rooms:

1 .- OPERATING ROOMS
OPERATING ROOM 01-02-03

INJECTION FLOW 2.220 m3/h

INTERNAL PRESSURE 25 pascals
CLEAN HALL PRESSURE 12,5 pascals
PRESSURE DIFERENCIAL 12,5 pascals
DOOR 01
HEIGHT H 2m
WIDTH A1 0,35 m
WIDTH A2 1,26 m
GUY DOUBLE HINGE
DOOR 02
HEIGHT H 2m
WIDTH H 1,14 m
GUY SIMPLE VISAGRA
LEAK AREA 01 0,03 m2
LEAK AREA 02 0,02 m2
EXFILTRATION FLOW 01 (ve01) 368 m3/h
EXFILTRATION FLOW 02 (ve02) 252 m3/h
EXTRACTION FLOW 1.600 M3/H

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DOOR TYPE 1
VI 01 = Injection flow

VE1
MATERL
ESTER VE 01 = Extraction flow Ws 3,175 mm

ve01 = flow rate 1/8“ = 1175 mm 1/8"= 3,175

door 01 exfiltration
AF = ( (2*H*3.175/1000}+ ( 1* A*3.175/1 000} r A*6.35/1000))

ve02 = flow rate

AFT door exfiltration 02
AF2

—= 1/4" = 6.35mm

—% DOOR TYPE 2
1/8" = 3.175mm

VI1=VE01+ ve1 + ve2 To the A2

VE 01 = VI 01 -ve1-ve2 1/8* s 3.175 mm

1/8" = 3.175mm
1/8" s 3.175 mm

rTeTArsFRoot^DpT
T/s
Af = Leakage area = (0.045-0.13) 1/4“ s 6.35 mm

m2
AF = (| 3'H*3.175/1000) * ( 1* {AH A2)*3.175/1000) ♦ 1 *( A1+A2)* 6.35/1000) )
Dp = Pressure differential (pascals)

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2 .- CLEAN HALLWAY
INJECTION FLOW 900m3/h
INTERNAL PRESSURE 12,5 pascals
VILLAGE HALL PRESSURE 0pascals
PRESSURE DIFERENCIAL 12,5 pascals
DOOR 02
AMOUNT 3
HEIGHT H 2m
WIDTH H 1,14 m
GUY SIMPLE VISAGRA
DOOR 03
AMOUNT 2
HEIGHT H 2m
WIDTH H 0,87 m
GUY SIMPLE VISAGRA
LEAK AREA 01 0,02 m2
LEAK AREA 02 0,02 m2
EXFILTRATION FLOW 01 (ve02) 673m3/h
EXFILTRATION FLOW 01 (ve03) 504m3/h
EXTRACTION FLOW 2.077 M3/H

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3 .- RECOVERY ROOM
RECOVERY ROOM

INJECTION FLOW 1.592,0 m3/h

INTERNAL PRESSURE 25 pascals
VILLAGE HALL PRESSURE 12,5 pascals
PRESSURE DIFERENCIAL 12,5 pascals

UNIT FLOW INFILTRATIONS 368

TOTAL INFILTRATION FLOW 1.103 m
PATIENT BATHROOM AREA 6 m2
SEPTIC ZONE AREA 3,2 m2
TOILET ROOM AREA 5,26 m2
EXTR FLOW 01 270 m3/h
EXTR FLOW 02 144 m3/h
EXTR FLOW 03 237 m3/h
GENERAL EXTRACTION FLOW (VE) 2.044 m3/h

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4 .- STERILIZATION
CALCULATION OF LEAK FLOWS

Sterilization area

Door number Area of highest pressure at lowest pressure LEAK AREA Higher pressure Lower pressure Differential Flow Symbology
m2 Da Da Da leak m3/h
P1 CEYE/SLOCK 0,02098675 20 10 10 201 vex2/vinf2
P2 CEYE/SUB CEYE 0,02098675 20 15 5 142 vex1/vinf1
P3 LOCK / CORRIDOR 0,02098675 10 0 10 201 vex4/vinf4
P4 LOCK/ PREWASH 0,02098675 10 -2,5 12,5 224 vex3/vinf3
P5 HALLWAY/AUTOKEYS 0,02098675 0 -2,5 2,5 100 vinf 05

CEYE INJECTION FLOW (VI01) 1.800 m3/h

INJECTION FLOW SUB CEYE (VI04) 570 m3/h
LOCK INJECTION FLOW (VI02) 225 m3/h BY CALCULATION IT SHOULD BE
CORRECTED
PRE-WASHED INJECTION FLOW (VI03) 324 m3/h
AUTOCLAVE INJECTION FLOW (VI05) 279 m3/h
3.198
EXTRACTION FLOW CEYE VE01 1.457 m3/h
EXTRACTION FLOW SUB CEYE VE03 712 m3/h
CORRECTED INJECTION FLOW LOCK (VE02) 224 m3/h additional flow differential -1 m3/h

PRE-WASHED EXTRACTION FLOW (Vcamp) 548 m3/h

AUTOCLAVE EXTRACTION FLOW 379 m3/h
3.097

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SUB CEYE BALANCE

CEYE BALANCE
vinf 1 = vex1
VI01=VE01+vex1+vex2
VI04 + vinfl = VE03
EMERGENCY VE 01 = VI01 - vex1 -
RECEPTION
vex2
AUTOCLAVE BALANCE MATERIAL
STERILE

VI05 + v inf05 = VE 04

WASHING MACHINE
THERMO DISINFECTOR DELIVERY
MATERIAL
STERILE

LOCK BALANCE

vex 2 = vinf 02

VI02 + vinf02 = vex4 + vex 3

VI02 = vex4 + vex 3 ■ vinf02

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5 .- IMMUNODEPRESSED ROOM
Door number Area of highest pressure at lowest pressure LEAK AREA Higher pressure Lower pressure Differential Flow Symbology
m2 Da Da Da leak m3/h
P1 isolated/bath 0,024 15 -1,5 16,5 299 v1
P2 isolated/sluice 0,020 15 10 5 134 v2
P3 lock/hallway 0,020 10 0 10 192 v3
P4 isolated room/hallway 0,025 15 0 15 297 v4

INJECTION FLOW INMUDEPRESSED ROOM (VI01) 900 VE01 170m3/h

LOCK INJECTION FLOW (VI02) 162 VE02 105m3/h
BATH EXTRACTION FLOW (VE03) 180
BATHROOM
AREA
CTE 12,5L/S M2
BATHROOM 4
AREA
VE03 18 m3/h
0

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6 .- OPERATING ROOM 4
Door number Area of highest pressure at lowest pressure LEAK AREA Higher pressure Lower pressure Differential Flow Symbology
m2 Da Da Da leak m3/h
P1 Lock/corridor 0,021 14 0 14 237v1
P2 Operating room/airlock 0,058 25 14 11 581v2
P3 Operating room/white area 0,021 25 20 5 142v3
P4 White area/hallway 0,021 20 0 20 284v5
P5 Sub Ceye/ hallway 0,021 20 0 20 284v4

VI01 OPERATING ROOM INJECTION FLOW 1.464 m3/h PAVILION BALANCE

CEYE VI02 SUB INJECTION FLOW 498 m3/h
INJECTION FLOW WHITE AREA VI03 702 m3/h
VI01=VEX01+V3+v2
INJECTION FLOW OF LOCK VI04 183 m3/h

VEX01 = VI01 -v2-v3

VEX01 OPERATING ROOM EXTRACTION FLOW 741 m3/h
SUB EXTRACTION FLOW CEYE VEX02 214 m3/h
WHITE AREA EXTRACTION FLOW VEX03 560 m3/h LOCK BALANCE
EXTRACTION FLOW OF LOCK VEX04 527 m3/h

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VI0
1

PAVILION
BALANCE
TRANSFER
VI01 = VEX01 + v3 +
QI CKD v2
GINEcdlFLUI
DO YOU VEX01 = VI01 - v2 -
| 14 dc •
COPY v3
—Ve4 VEX04 VEX LOCK BALANCE
25 pa 01
VI04 + v2 = VEX04 +
v1
VIO
2 VEX04 = VI04 + v2 -
20 pa
WHITE AREA
BALANCE

VI03 + v3 = VEX03 + v4
HANDWASHING VI0
SUB - CEYE VEX03 = VI03 + v3 -v4
3
REGA
ERIAL SUB CEYE
DRESSING BALANCE
TERIL 20 pa ROOM
VEX 20 pa
03 VI02 = VEX02 + v5
VEX0
2 WHITE AREA VEX02= VI02 - v5

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XIII.- CONDENSATION SYSTEM FOR CLEAN ROOM HVAC

SYSTEMS AND MULTI-PURPOSE MACHINES

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INITIAL THEORY
Introduction
When we refer to the term “producing cold” it is not entirely accurate and may be used
inappropriately, since it involves transferring heat energy from a cold source to a hot source.
To do this, an external energy supply is required since this phenomenon does not occur
naturally and spontaneously as Clausius mentioned in one of his statements of the second
principle of thermodynamics.
This chapter aims to give an overview of compression refrigeration machines both in terms
of operation and efficiency.
Theoretical bases
In order to understand air conditioning installations in detail, we must have two theoretical
visions:

• View from the point of view of the air conditioning equipment

• Vision from the point of view outside the equipment – thermal needs of the
local
Vision from the inside point of view:
The fundamental principle, expressed in common language, is that “it doesn't get cold, it
gets hot.” Thus, to transport heat from a low-temperature body to a high-temperature body
(in our context, to cool), it is necessary to provide energy.
For this, a cooling fluid intervenes and goes through a series of thermodynamic
transformations. This thermodynamic cycle avoids continuous replenishments of the
refrigerant gas. Each refrigerant has a defined and different behavior.
For the production of cold with industrial applications, we find two systems:

• The compression refrigeration cycle (example: electric chillers)

• The absorption refrigeration cycle (example: absorption chillers)
Compression cycle
To understand the refrigeration cycle it is necessary to understand each of the components
and their operation. There are 4 main teams:

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• Compressor
• Condenser
• Expansion
• Evaporator
Depending on the stage where the refrigerant fluid is located, we will have particular
conditions of pressure, temperature and state of the fluid. The change of state and pressure
are the essential keys to carrying out the transfer of heat from a cold source to a hot source.

2.1.1.1 Notions of enthalpy diagram

The enthalpic diagram or Mollier diagram is one of the essential elements for understanding
a cold cycle. Each refrigerant has a specific diagram allowing its physical state to be
established based on its pressure.
The X axis shows the enthalpy of the fluid (h), corresponding to the amount of energy
contained in one kilogram of refrigerant. The Y axis corresponds to the fluid pressure (P).
The bell establishes the state of the fluid, where outside that curve the refrigerant is in a
saturated state and cannot change state. The rest of the curves show different parameters of
which we highlight the temperature (isothermal) and the volume (isochorus).

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Description of the refrigeration cycle
Compression
Compression is carried out by means of the compressor. The function of this element is to
take the refrigerant fluid from low pressure to high pressure, compressing the gas.
Normally, the compressor uses electrical energy and compression is carried out
mechanically. It is essential that the fluid is in a gaseous state before compression, since
many of this equipment is very sensitive to liquid shock (compression of a liquid), which
can damage the equipment.
On the other hand, since it is a mechanical compression, it is very important to have a
constant lubrication system that ensures the correct functioning of the equipment.

Condensation
The fluid in the gaseous state is under high pressure, and passes through an exchanger called
a condenser. In this exchanger, the refrigerant fluid transfers the heat energy accumulated in
the evaporator and due to the effect of compression to the external medium (commonly
called a hot source). The effect of giving up that heat energy produces the condensation of
the fluid, taking it to a liquid state at high pressure. This heat transferred to the external
environment can in some cases be recovered to preheat water or air.

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Figure 5 Moliere condensation cycle diagram

The refrigerant fluid is sub-cooled in order to ensure complete change from vapor to liquid.
Figure 4 Condenser diagram

provided by
the refrigerant
in H
condenser

This subcooling is usually between 4 and 7°C. Unlike overheating, it does not require
particular vigilance since it does not represent any type of threat to the components of the
refrigeration circuit.
The heat transfer fluid can be:

• Air
• Water (geothermal, towers)
Expansion:
The refrigerant fluid in a liquid state and high pressure is expanded in order to reduce that
pressure to low pressure. This decrease in pressure is essential to obtain a refrigerant fluid in
favorable conditions to capture the heat energy in the evaporator.

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Figure 6 Expansion scheme

Figure 7 Moliere expansion cycle diagram

Pressurized

Axle

liquid and
Expansion Liquid Steam
bp

Enthalpy
Axis

Liquid

Evaporation:

The fluid in a liquid and vapor state is introduced into an exchanger (evaporator) where it
will be charged with heat energy from the fluid (water or air) that needs to be cooled (cold
source). This heating of the refrigerant causes its evaporation, going from the liquid state
with vapor to a low pressure gaseous state.

Overheating must be caused at the evaporator outlet in order to guarantee that the refrigerant
is completely in a gaseous state to protect the compressor from possible liquid shocks. This
superheat temperature is controlled to avoid possible negative influences on the
compression rate.

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and therefore on the performance of the compressor. Therefore, superheating is controlled
through the expansion valve which, based on the superheating temperature, will vary the
flow of refrigerant fluid. In the event that the temperature increases, the expansion valve
will open the passage more, obtaining a greater flow of refrigerant and thus a decrease in the
superheat temperature.
The heat transfer fluid in the evaporator can be:

• Air (direct from the environment, direct expansion UMAS…)

• Water (fan&coils, UMAS…)
Complete cycle
Below is the complete operating diagram of a refrigeration unit.

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ENERGY EFFICIENCY
COP and EER
The COP is a unit of measurement that allows knowing the amount of electrical energy consumed by the system based on the heat produced
in the condenser.

The EER corresponding to the refrigeration energy efficiency indicates the same relationship, but with the cold produced in the evaporator.

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Note: Remember that these coefficients refer to energy consumption kw h., not electrical power in kw

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Effect of variations in conditions

To visualize the influence of the effect of varying conditions on the energy efficiency of the equipment, we take two common operating
situations.

In the event that the energy exchange in the evaporator decreases, the pressure difference between HP and BP is reduced, causing lower
electrical consumption and restoring more cooling energy, which obviously increases the efficiency of the equipment.

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Common EER values according to system typologies

As an indication, the average values of the most common refrigeration machine systems according to the ARI standard are reflected.
Team classification

Program Code heat rejection Code System Code Operation Code Duct Code CompressorCode

liquid coolers LCP TO Package Q c Duct d Centrifugal c

air cooled Cooling only

Cooled W Divided Yes Reversible cycle R Ductles N Other EITH

s ER
by water

Energy efficiency rating

The purpose of EEEC (Eurovent Energy Efficiency Classes) is to simplify the selection of the best unit for each type of chiller. The
classification is entirely voluntary.

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COP values according to EEEC Cooling mode

Ncooling odo
Cold air
water Remote
EER class air cooled Cold air in duct through the water cooled
cooled condenser
floor floor
TO >=3.1 >=2.7 >=3.8 >=5.05 >=5 1 >=3.55
b 2.9-3.1 25-2.7 3 65-3 8 4.65-5.05 4.9-5.1 3 4-3.55
c 27-2.9 2,3-25 3.5-3.65 4.25-4.65 47-4.9 3.25-3.4
d 2.5-27 2,1-23 3.35-3.5 3.85-4.25 4 5-4.7 3.1-3.25
AND 23-2.5 1.9-2.1 3.2-3.35 3.45-3.85 4.3-4.5 2.95-3.1
F 2 1-23 17-19 3.05-3.2 3.05-3.45 4.1-4.3 2.8-2.95
g <2.1 <17 <3.05 <3.05 <4 1 <2.8

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COP values according to EEEC Heat mode

moc or heat

COR class air cooled Cold air in Cold air through water cooled
duct the floor water cooled
floor
TO >=3.2 >=3.0 >=4.5 >=4.45 >=4.5
b 3.0-3.2 2.8-3.0 3.9-4.05 4.15-4.45 4.25-4.5
c 2.8-3.0 2.6-2.8 3.75-3.9 3.85-4.15 4.0-4.25
d 2.6-2.8 2,4-26 3.6-3.75 3.55-3.85 375-4.0
AND 2.4-2.6 2.2-2.4 3.45-3.6 3.25-3.55 3.5-375
F 2.2-2.4 2.0-22 3.3-3.45 2.95-3.25 3.25-3.5
g <2.2 <2.0 <3.3 <2.95 <3.25

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New regulations
The result obtained by both relationships fluctuates based on external conditions and thermal energy demand. Recently, manufacturers must
mention two new indicators, SCOP and SEER. The COP and EER are units of measurement that allow measuring the efficiency of
refrigeration machines for specific conditions of outdoor temperature and power load, which is why manufacturers favored technologies to
have high efficiencies for certain specific conditions. In light of this abuse, new SCOP and SEER ratios were developed that measure the
effectiveness of equipment for real-world conditions in a specific geographic area over a one-year period. This is because the equipment
operates partially since it is sized for maximum demand conditions. Therefore, the letter S that accompanies the new coefficients refers to
“seasonal”. There is no direct relationship between the previous coefficients and the new ones, these being parameters granted by the
manufacturers.
The COP reflects the energy performance of the cooling system (refer to section 1.3.1.3.1 to see how to evaluate it). If the installation has
measuring equipment such as pressure gauges, thermometers, etc., the COP of the system in operation can be measured and compared against
the theoretical COP. The theoretical COP is calculated from the nameplate data and the information available in the manufacturer's manual or
on the Internet.
Some standard COP values are listed in the following table.

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COP min.
Kind of team
(kWwheat/kWelec)

Window equipment 2,8

Split: 2,8
< 1TR 3,0
> at 1 TR

Packages (roof top)

air cooled
< to 30 TR 2,5
> 30 TR 2,9
water cooled 3,5

Chiller (piston compressor)

air cooled
< to 30 TR 3,0
> 30 TR 3,0
water cooled
< to 30 TR 3,7
> 30 TR 4,0

Chiller (screw compressor)

air cooled 4,5
water cooled
< to 220 TR 4,6
> at 220 TR 5,0
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These values apply to the following climate conditions:

1. Air-cooled systems: interior temperature of 27°C and 50% Relative Humidity (RH); outside temperature of 35°C in dry bulb and 24°C in
wet bulb.
2. Water-cooled systems: chilled water flow/return temperature of 6.7°C/12.2°C. Condenser inlet and outlet temperature 29.4°C/35°C.

These values only represent the COP of the compressor. To calculate the COP of the entire system, it will also be necessary to consider the
electrical consumption of the fans, pumps, and cooling towers. To illustrate this, consider an optimal COP of 4.8 in the 7°C/113°C regime.
This COP drops to 3.9 when the consumption of auxiliary equipment is considered. If we change the operating regime to 5°C/11°C, the COP
goes to 3.7 (lowers the evaporator by 2°C, therefore 6% performance).

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TYPES OF CAPACITORS
Air conditioning cabinets are distinguished by their technological characteristics at the
condenser level. There are various types of systems:
Air condenser integrated into the equipment
In this case, the unit has an outlet and inlet for the air required for condensation, directly
conducted through ducts to the outside of the premises.
Separate air condenser
The refrigerant fluid is directly cooled in the condenser that is located in equipment located
outside the premises. The separation distance is limited by the manufacturer, since the
greater the distance, the more charge losses, therefore, the less efficiency of the system.
Likewise, the difference in level between the condenser and compressor is subject to
manufacturer specifications, since the return of oil to the compressor must be encouraged.

Scheme of air conditioning cabinet with separate air condenser

1- Interior air intake

TREATED
2- Direct expansion cold coil (evaporator)
AIR 3- Heat battery (water,...)
4- Compressor
5- Capacitor
6- Expansion
7- Outdoor fan
8- Indoor fan

ABROAD

AIR INTAKE

REFRI

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Recycled water condenser
In this case, the condenser is cooled by glycol water, which in turn is cooled by the outside
air. This solution allows you to avoid distance and unevenness limitations, in addition to
being able to connect several cabinets or air conditioning equipment to the cooling water
network called condensation water.
This technology through condensation water has three possible equipment options to ensure
thermal exchange between water and outside air:
Aero:
The water is cooled in an air exchanger, where air circulation is ensured by one or more
fans. The most widespread regulation is to control the operation of the fans based on the
water temperature. This type of system has a clear disadvantage, since the air conditioning
cabinet will have low efficiency at certain times, since the water temperature is directly
affected by the temperature conditions of the outside air.

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Diagram of air conditioning cabinet with water condenser (aero)

1- Interior air intake

2- Direct expansion cold coil (evaporator)
3- Heat battery (water,.)
TREATED 4- Compressor
AIR 5- Capacitor
6- Expansion
7- Condensation circuit water pump
8- Outdoor fan
9- Indoor fan
10- Plate exchanger

ABROAD

■FRIGE RANTE
WATER TAKING
GLYCOLATED OF
AIR

Open cooling tower:

In this case, the water from the condensation circuit is sprayed countercurrent to the air flow
driven by the fans. This heat exchange is very effective since part of the water is
evaporated, implying a strong cooling of the fluid that is below the temperature of the
outside air. This phenomenon

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It implies a considerable improvement compared to the aero since the temperature
conditions of the condensation water are low and therefore improves the refrigeration cycle
of the system. However, it also has disadvantages such as the loss of glycol water due to
evaporation, corrosion problems and fouling of the system.

HVAC cabinet diagram with open cooling tower

1- interior air intake

AIR 2- Direct expansion cooling coil (evaporator)
TREATY 3- Heat battery (water,...)
4- Compressor
5- plate exchanger
6- Expansion
JJJ 7- Condensation circuit water pump
8-Outdoor fan
9-Indoor fan

FRIGE ÍANTE
TAKING OF
AIR

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Closed cooling tower:

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It is a system similar to the previous one, providing the advantages of evaporation, but
avoiding the disadvantages of corrosion and fouling. Its operation is based on the circulation
of condensation water through the interior of the tower, where water is sprayed from an
independent circuit, producing evaporation and achieving significant cooling. The water
outlet temperature is slightly higher than that of an open tower.

Lost water condenser:

In this case, the water destined for condensation comes from:
Water from the municipal network: once it passes through the condenser, it is evacuated
to the drain. This solution is not advisable and must be eliminated from the facilities, since it
generates a significant financial expense.
Water from natural wells, rivers, among others: It is an interesting solution in terms of
operating costs since the amount corresponding to m³ disappears. However, environmental
permits must be requested in certain areas to visualize the viability of said solution.
Components of a refrigeration installation
As indicated in the Refrigeration Cycle section, refrigeration machines are made up of four
main elements:

• The compressor

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• The capacitor
• expansion valve
• The evaporator
In this section, each component will be detailed.
The compressor
It is the heart of a cold machine system since it pumps the refrigerant to the other elements
of the system.
It is the most expensive component and the one that consumes more than 80% of the
electrical energy of the cold system (this element is generally driven by an electric motor).
The five most common types of compressors used in cold production machines are the
following:
• Piston compressor (alternative),
• scroll compressor
• rotary compressor
• screw compressor,
• centrifugal compressor,

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Piston compressor scroll compressor

Inlet: low
pressure steam
Inlet: low Exit:
pressure steam compressed
steam

compressed

screw compressor centrifugal compressor

Outlet: compressed steam - Outlet:

w
compressed
steam

Entrance;
* steam □
low pressure

Inlet: low pressure steam

Piston compressors
The piston compressor needs to be permanently lubricated. The lower part of the crankcase
forms an oil reserve. The pressure prevailing in the crankcase is the suction pressure. The
oil pump delivers a higher pressure (between 0.5 and 4 bar) than the pressure prevailing in
the crankcase.
The piston compressor is relatively sensitive to the arrival of liquid fluid, since the slightest
drop of liquid on the valves generates continuous and slow wear of the assembly. In the
event of a significant fluid entry, the destruction of the valves is immediate. For this reason,
these devices have anti-liquid shock protection (spring on the cylinder cover, capable of
lifting in case of liquid arrival).

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The dead space corresponds to the volume that remains between the piston and the bottom
of the cylinder, when the piston is in the maximum high position. This space is necessary to
avoid possible collisions when the piston is at the end of its travel. Its value is around 4% of
the cylinder volume. It must be taken into account that the smaller the space, the greater the
volumetric performance of the compressor.
Open construction piston compressor
Open compressors differ from semi-hermetic compressors because they have a shaft
(crankshaft) that extends to the outside. It can be coupled with an electric, diesel or gas
motor.
Unlike the other two types of compressors, these devices allow access to all the elements.
The power is regulated by the start or stop of certain cylinders or by the change in speed of
the coupled engine.
Its use is generally for installations with cooling capacities less than 500 kW.

The piston compressor is classified according to its construction into three types: sealed,
semi-sealed and open.
Semi-hermetic construction compressor
This type of equipment is enclosed in a casing equipped with an access cover to carry out
inspections. They are widely used in both commercial refrigeration and air conditioning and
are intended for

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installations less than 500 kW of cooling. Unlike hermetic equipment, they can be repaired
but their cost is higher.

Hermetic construction compressor

Also known as sealed compressors, they are built inside a metal casing. They work at
speeds from 1,750 to 3,500 rpm with 2 and 4 pole motors. These motors are manufactured
from 1/20 HP to 7 ½ HP, meaning they are equipment found in SMEs.
They are silent and cheap equipment. However, they cannot be repaired because they are
sealed.
However, they have disadvantages such as:
• The cooling fluid and lubrication oil must be compatible with the materials that
make up the engine.
• The cooling of the engine is enhanced by the refrigerant fluid, heating it and
obviously damaging the refrigeration cycle. Furthermore, when the engine is
damaged, it is the entire refrigeration circuit that will be affected and must be
subject to general cleaning. In the event of a breakdown, this type of compressor
does not allow repairs. To limit possible breakdowns due to overheating, these
devices have safety devices such as Klixon mounted on the motor winding,
disconnecting the power supply in case of overheating.
The cooling power cannot be regulated unless a frequency converter is incorporated.

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scroll compressor
The scroll compressor is made up of two spirals: the first is fixed, attached to the casing,
and the second is rotating. The spirals are 180° out of phase. The moving spiral is driven by
the motor and rotates inside the fixed spiral, forming a gas pocket. This orbital movement
produces a progressive reduction of the gas pocket until its total disappearance, thus
carrying out the compression cycle of the refrigerant.

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By having much fewer moving parts than in piston compressors (60% less), there is less
friction, so this compressor is more efficient, low in noise, with little vibration.
This translates into a COP of around 4 on an annual average, while piston compressors have
a COP of approximately 2.5.
Its maximum power is 50 KW but several devices can be installed in parallel up to 300 kW.
To regulate your speed, there are three options:

• “All or nothing” regulation

• Regulation by a two-speed motor
• Regulation by a frequency converter
rotary compressor
It is a compressor from the family of volumetric equipment, and two technologies are
distinguished:

• Rolling piston rotary compressor

• rotary vane compressor

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In both of these cases, a cylindrical stator contains a rotor offset from the stator axis. A
volume of refrigerant is isolated and compressed until the desired pressure is obtained.
The cooling powers for this type of technology do not exceed 10 kW. They are usually used
in individual air conditioners.
screw compressor
They are devices with a variable operating range: from 10% to 100%, with a fairly constant
performance. There are open or closed machines.
Its mode of operation consists of compressing the refrigerant by means of a helical screw
that rotates at high speed. This compressor is powered by an electric motor.

screw compressor

Source: Bitzer

The volumetric efficiency of a screw compressor is high due to the absence of dead spaces,
as in piston compressors. This property ensures a high compression ratio. It must be well
lubricated to ensure tightness between the different moving parts, reduce noise and also to
cool the coolant. The compression ratio then reaches values of 20 without altering the
refrigerant.

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In large capacity equipment, a regulation mechanism defines the use of a more or less long
part of the screw in the compression of the gases, this allows the compression ratio to be
varied.
In smaller units (which are still very large compared to piston compressors), the variation in
compressor power is obtained by changing the rotation speed of the screw or by using
auxiliary intake ports.

The advantages of the screw compressor are its low wear and easy regulation. However, it is
still an expensive technology. Recently, the screw compressor has been used for power of
20 kW and above.
Centrifugal compressor or turbocharger
They are equipment capable of moving large quantities of air. The centrifugal compressor is
a dynamic type device, not positive displacement like most equipment used in refrigeration
machines. It consists of one or more driving wheels, mounted on an axle and contained
within a casing. The increase in pressure is achieved by conversion from kinetic energy.
Its operating principle is similar to fans or centrifugal pumps.

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They do not have very high compression ratios. Its field of application is large air
conditioning installations.
In general, the piston (or reciprocating) compressor is used up to tens of kW. Up to
hundreds of kW, the screw compressor is used, also with positive displacement (or
volumetric), but from hundreds of kW onwards, the centrifugal compressor is used, and in
MW sizes the axial compressor is used.
When oil is not tolerated in the refrigerant gas, it is necessary to resort to the centrifugal
compressor, even in sizes that are the domain of the screw compressor (although oil-free
screw models exist). In cold production systems by compression of refrigerant gas, as in air
compressors, piston and screw compressors are used in smaller sizes. In large sizes,
centrifugal compressors are used, which are mainly used from 400 kW of shaft power.

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Condensers and cooling towers
It is an exchanger in which the refrigerant fluid in a gaseous state, after compression, is
condensed at a constant temperature, releasing the heat recovered in the evaporator and in
the compression into the medium (water or air).
The capacitor is divided into three parts that are delimited by the operating parameters:
• Zoneofoverheating
• Zoneofcondensation
• Zoneofsub cooling

water condensers
From a technological point of view, water condensers offer more diversity than air
condensers. The transmission coefficient K is higher and the cooling is guaranteed by water
whose specific heat is 4.18.

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kJ/kg°C (4 times greater than that of air), mean that for the same dissipation power, water-
based technology requires a smaller material.
However, water is not a free fluid like air, its flow in the condenser will therefore be limited.
Coaxial exchanger
This type of condenser is made up of two spirally wound tubes, the refrigerant fluid
circulates inside the central tube and the water circulates in the external area.
The two fluids circulate in countercurrent to promote the exchange of thermal energy. The
water heating range is between 8 and 12°C.

Bottle exchanger
This type of exchange has two purposes. The first is a liquid storage bottle and the second is
a condenser. It consists of a coil in which the cooling water circulates, the cooling fluid is
stored in the tank where it condenses upon contact with the water tube. The water heating
range is between 8 and 12°C.

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Multi-tubular exchange
A large number of horizontal pipes are housed inside a tank and connected at their ends to
two collectors. The water circulates inside the pipes and the cooling fluid through the tank
where it condenses in contact with the water tubes. The advantage of this type of system lies
in the possibility of disassembling the elements, allowing better maintenance of the
assembly.

plate exchanger

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This type of condenser is made up of an assembly of plates with slots where both fluids
circulate. The sealing between plates is done by means of polymer joints. This type of
exchanger has two fluid circulation configurations, countercurrent or parallel.
The advantage of this type of exchanger is that it has a large exchange surface in a very
small volume, although it is very sensitive to fouling.

air condensers
These exchangers allow superheated vapors from the compressor to change the state of the
refrigerant to liquid.
The superheated gases give up heat energy when they pass through the condenser in
exchange with the air, allowing the condensation of the refrigerant.
Air is an interesting condensation medium since it exists in large quantities. However, its
thermal transmission coefficient is very low, implying large exchange surfaces and air
flows.
The power of the condenser is equal to the sum of the cooling power (evaporator) and the
power of the compressor's electric motor.

Static capacitor

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In general, these are the condensers that equip small domestic refrigeration appliances. The
air circulates around a coil tied to a metal plate that serves as a heat sink.
Vented condenser
They are usually made of steel or copper equipped with aluminum fins. They generally
consist of a casing, a coil, and both axial and centrifugal fans. The condenser coil will have
tubes with staggered internal grooves (since it increases the exchange surface) and equipped
with corrugated aluminum fins that also promote thermal exchange. In corrosive
environments, the fins may be made of materials
stainless steel or steel coated with an anti-corrosive protective layer. The batteries can be
positioned horizontally or vertically as well as in a V.
Given that the air temperature can fluctuate significantly throughout the year, the air flow
must be able to be regulated either through a cascade of fans or through frequency
converters installed in their motors.
As a general rule, the temperature differential between the air inlet and outlet of the
condenser is 15°C. Condenser fouling can cause temperature increases in the condenser of
5°C, generating power losses in the refrigeration installation of approximately 7% and an
increase in consumption of 16%.

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COOLING TOWERS
Cooling Tower Components
Support structure
This is the framework that supports all the elements of the cooling tower. It is composed of
corrosion-resistant materials such as reinforced concrete, galvanized metal structures and
stainless steels.
Case
The casing corresponds to the tower component that covers the structure. It is a watertight
element that does not allow solar radiation to penetrate, therefore avoiding the heating of the
water and the formation of microorganisms. The materials of this element are reinforced
concrete, polyester, polyester reinforced with fiberglass or stainless steel.
Diffuser
It is a system that reduces the static pressure of the air and is located at the top of the tower.
This component eliminates existing turbulence in the fan area, avoiding possible
recirculation and as mechanical protection. The most common material is reinforced
concrete or fiberglass reinforced polyester.
Droplet separator
The function of the drop separator is to prevent water droplets from being expelled to the
outside of the tower, avoiding water replacement and limiting possible damage to adjacent
equipment. This is achieved by forcing the moisture-laden air to make sudden changes in
direction, involving the accumulation of water droplets on the body of the separator.
The material of the drop separator is similar to that of the fillers, although currently there is
a tendency towards materials of plastic origin. Below are the various types of droplet
separators.

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Sprayers or sprinklers
This is the water distribution system that distributes water homogeneously over the fill.
By pressure
This system is generally used in countercurrent towers, and uses nozzles that require a
certain water pressure (above 5 kg/cm²). Its regulation is complex compared to the gravity
system,

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By gravity
This system does not require high pressure, implying the corresponding savings in electrical
energy linked to the pumping system. The regulation of this type of system is carried out by
directly manipulating the control valve until the desired water level is obtained.

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Stuffed
The filling of the towers is one of the main elements of the tower, since it is responsible for
prolonging the contact time between air and water, favoring the exchange of heat energy
between both fluids.
These fillings are characterized by:

• Have a large contact surface

• Having great mechanical and chemical resistance (it does not alter and is immune to
microorganisms) as well as having little weight with respect to its volume.
• Have a low load loss
• low cost material
The different types of existing filling are reflected below:
Drip fillers
This type of filling encourages the creation of small water droplets that allow the
evaporation of water in contact with air. This filling is formed by superimposed floors or
successive grids involving the successive formation of smaller drops.
This technology requires much more height than laminar systems to obtain the same
operating conditions. Furthermore, drag flow is important, implying the placement of high-
efficiency water separators.
Film or sheet fillings
This filling creates a thin, large-surface water sheet, allowing part of the fluid to evaporate
and therefore considerably improving cooling performance. For this, highly adherent
materials are available, allowing the formation of this film with constant characteristics
throughout the filling.
This filling offers less drag than the previous one, implying the possibility of working with
higher air speeds, and therefore smaller dimensions than the drip filling. However, its
construction characteristics favor the accumulation of dirt, reducing the exchange surface.

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Mixed fillings
This type of filling is based on splash and film, allowing an improvement in exchange. To
do this, grids or tubes are available to encourage this type of phenomenon.
Fans
Cold or chilled water raft
This is the container where the water cooled by its passage through the filling is stored.
Cooling tower typologies
Induced draft open tower
In this type of towers, there are axial fans that, depending on the capacity, can be direct or
belt-driven.

Water is sprayed through a series of nozzles located in the upper part of the tower. In order
to size the pump, the manufacturer specifies the water pressure that must be maintained in
these sprinklers.

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Forced draft open tower
In this type of tower there are fans that can be axial or centrifugal, located on the sides of
the tower.

The water is sprayed through nozzles and, in the same way as for the previous type of
tower, the manufacturer indicates the water pressure required at that point.
Open crossflow and forced draft tower
This tower has large diameter, low speed axial fans. Its transmission is by mail.

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Water is sprayed by gravity through collection trays equipped with sprinklers located at the
top of the tower.
Open crossflow and induced draft tower
This type of system is usually used for large towers. There is axial type ventilation
equipment (by direct transmission or pulleys) in the upper central part of the tower. The air
is taken in from two of the sides of the equipment, forcing the passage of air through the
fillings and through the drop separators.
In this type of equipment, water spraying is usually carried out by gravity through collecting
trays and sprinklers located above the fill. The inclination of the filling and drop separator is
due to the compensation of the air pressure exerted on the water, thus favoring the passage
of water through the elements.

Crossflow and induced draft open tower scheme BAC cooling tower model S3000E

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Functions of a multipurpose machine

From now on we will use the term multipurpose in its "true" meaning to refer to a machine capable of carrying out a total
recovery in the summer season (not of provisional reversal of the cycle, to produce domestic hot water, with the consequent
inevitable losses of efficiency and comfort). It is therefore a so-called "4-tube" machine that must be hydraulically connected
to two different installations: the first will be the heating/air conditioning of the building; the second, the production of
domestic hot water. In general terms, versatility can characterize the air/water or water/water machine, both single-circuit
and double-circuit, monobloc or split version, with ON/OFF compressor or inverter (of the type with permanent magnet
motor, known as BrushLess-DC). .
Considering first, for simplicity, a single-circuit air/water machine, we can summarize the 5 different operating modes of a
"true" multipurpose machine, in the different seasons, as follows:

1. SUMMER SEASON: Production of cold water like a traditional chiller (evaporation by water "terminal use side" and
condensation by air "battery side").
2. SUMMER SEASON: Production of cold water with total recovery of condensation heat (total condensation by water, for
the production of DHW on specific plates).
3. WINTER SEASON: Production of hot water for heating, like a traditional heat pump (air evaporation "battery side" and
water condensation "terminal use side").
4. WINTER SEASON: DHW production momentarily interrupting the production of water for heating (DHW with priority). In
other words, air evaporation "battery side" and water condensation for the production of DHW on specific plates.
5. INTERMEDIATE SEASON: Production of DHW only (both in summer and winter) with battery evaporation.

Below is an image that shows the fundamental diagram of the refrigeration circuit of a multipurpose machine:

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The refrigerant path in the different operating modes is regulated by the solenoid valves shown in the figure,
open or closed depending on the required function.

Winter setup
r MA AC AIL NE WANM A

S20c5) !

. cAiztacOdN

Domestic hot water / in spring

MAMCMINENTE
MANLAHIA

S20c5 1

="

LMTMMMENTD i CMIITACON

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For water/water machines, the following points can be clarified (since the fin coil has been replaced by a plate exchanger
operating in the water on the “source side”):

• SUMMER SEASON: condensation will be done by water in the "source side" exchanger.
• WINTER SEASON: for the production of water for heating, evaporation is carried out in the plate exchanger "source side",
and condensation in the "application side"; The same occurs in the production of domestic hot water, with the natural
displacement of the condensation from the plate exchanger from the installation side to the DHW side.
• INTERMEDIATE SEASON: Production of only DHW with evaporation always in the "source side" plate exchanger.

In water/water versions, the source side can be represented by gravitational water, as well as fluid from a geothermal probe
field, among others.

Finally, in the case of two-circuit machines, it is specified that it is possible for one circuit to work on the production of DHW and
another to continue condensation on the hot water of the heating installation. This solution is the one that offers the greatest
flexibility.
The possible modalities for a two-circuit machine are listed below.

As you can deduce, these are machines that can be used all year round. This is
possible thanks to the adoption of a fairly "flexible" refrigeration circuit
managed by a regulation system that requires particularly advanced hardware
and software.

As mentioned above, DHW production has priority: this means that, regardless
of the working mode on the installation side (heating or cooling), the machine

will be put into DHW mode as soon as it receives the demand signal from the
DHW cylinder probe or a similar thermostat.

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Some points need to be clarified:

First of all, it is remembered that multipurpose units (both ON/OFF and modulating) are NOT suitable for use as "fast" heaters,
and therefore a thermal accumulator will always (necessarily) be required for the production of AC5.

When we talk about the production of domestic hot water, we refer to the storage of thermal energy in a "technical" water
accumulator ; the water for sanitary use must be heated by a stainless steel coil located inside the accumulator; in this way it
avoids the storage of domestic water and it is not necessary to predispose the management of an anti-legionella cycle {for more
detailed information , consult the recommended hydraulic diagrams). This solution, which in our opinion is the most
appropriate, is illustrated in more detail in the section relating to the DHW tank.

Water accumulator
AC5 Accumulator technique

As a clarification, we remember that, if the designer opts for DHW storage, the accumulator must be suitable for the storage of
drinking water and have a coil (on which the multipurpose machine works) with a surface that makes heat exchange possible.
The system is suitable for the power of the machine , considering its working temperatures and the storage temperature of the
DHW in the accumulator. Please remember that the ACS must not come into contact with the hydraulic circuit of the
multipurpose units for any reason (a separation must always be provided).

In this case, in addition, a legionella cycle will have to be managed (the software of the multipurpose units is prepared for this
purpose) generally using an additional heater (e.g. e.g. an electrical resistance). It should be emphasized that this generally
implies a certain waste of energy, which could be avoided with the storage of technical water.

Regarding the control of legionella, we attach an extract from the ''Trento and Be Izano Guidelines for the prevention and
control of legionellosis; Official Bulletin n® 103 of 05.0S.20O0"

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Main components of a multipurpose facility

In the detailed diagram below, we briefly describe the main components of a multipurpose installation:

Smartphone Web

Multipurpose machine

As said before, it is the core of the multipurpose system. It is a machine with 4 connections and as such, it manages two
completely independent hydraulic circuits: on the one hand there is the production of hot/chilled water, for heating/cooling the
environments; on the other, the production of DHW.

In the machine definition phase, the configuration of the machine can be decided according to what is considered most
appropriate for integration with the installation (for example, the circulation pumps on the installation side and/or DHW side ,
they may be introduced into the machine or installed outside, but they will be managed in any way by the control logic through
contacts in the unit's electrical panel).

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The part connected to the heating installation may or may not have an internal and/or external inertia accumulator (see the
observations below) while in the installation there will always be an accumulator for the storage of the energy required for
production. of the ACS.

Thermal solar panels may be part of the system (connected to the DHW accumulator through a specific coil and then
hydraulically separated from the multipurpose machine) and also another high temperature source, which may feed the
accumulator through a special coil located in the part of above it.

To manage the priority in DHW production, the machine has a temperature probe that must be inserted into a well in the
accumulation tank.
This probe activates DHW production every time the tank temperature drops below a programmable limit value.

Alternatively, the voltage-free contact (connected to the electrical panel oven) can be used, coming from an external
thermostat.

LCP CCM

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DHW accumulator

As mentioned before, the DHW accumulator is only responsible for storing energy in a quantity (and at a temperature) that
guarantees DHW production that covers the daily demand, at the required temperature.
Since there is no DHW storage but only energy storage (which is why we speak of "technical water") the accumulator must
necessarily have a stainless steel coil for instantaneous production.
The exchange surface of said coil must be able to guarantee the production of hot water at at least a minimum comfort
temperature (e.g. e.g. 40°C).

On the contrary, the hydraulic connections for connection to the multipurpose machine will be free of coils: the machine must
work with the full water content of the accumulator.

In this way, the water content of the accumulator itself is sufficient to guarantee the correct operation of the machine (heat
contribution to the DHW without unnecessary AT), also avoiding continuous on/off of the compressor thanks to the reduced
water content of the coil. its limited exchange capacity.

As can be seen in the attached figure, the coil for DHW production will always be the one with the largest surface area.
The solar panel and high temperature coils (optional) have a smaller surface area (due to the higher water
temperatures produced by these sources).

In the lower part of the accumulator (if possible) it is

advisable to provide an "emergency" resistance, with
maximum absorption equivalent to the maximum
power consumed by the multipurpose machine.
In the event of a failure, the accumulator can be
"recharged" at night and the production of DHW is also
guaranteed at a temperature that, although not ideal, is
at least acceptable.

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It is worth making some specific reflections regarding the hydraulic connections for the multipurpose machine (which appear
marked with the acronym PdC on the plan) .
Note first of all that the water recovery is carried out in the lower part and the inlet of the hot water produced by the
multipurpose unit is in the upper part of the tank. At the point of the hydraulic connections (represented with a dotted line) are
the flow retarders , which are responsible for protecting the stratification of the tank, preventing the hot water produced, which
is in the upper part, from mixing with the water. recovery cold (present in the lower part).

Stratification is essential to ensure not only obtaining the necessary amount of energy, but also (no less important) the
production of DHW at a sufficiently high temperature .

For this, it is necessary that the upper part of the tank is always maintained at a temperature (e.g. e.g. 50 X) higher than that of
produced water (e.g. e.g. 40 °C). In the lower part, however, since the extraction temperature of the water distribution network
is much lower ( e.g. 15 °C), the heat exchange is also sufficient if the temperature of the technical water corresponds to the
recovery of the multipurpose machine .

It is worth making some additional reflections on maximizing efficiency in the use of a coiled accumulator to combine solar
panels.

Surely, in the season of highest radiation, the energy demand for the DHW is largely covered by the operation of the
multipurpose machine in full recovery (as long as, of course, it is used for air conditioning of the environments).
Considering this, the presence of the thermal solar panel would no longer be essential during the hottest season . This does not
apply to the season in which climate control is not required , and therefore the advantage of total recovery is not taken
advantage of. In this period, the solar thermal panel can supply part of the energy for the DHW without (or almost without)
consumption of electrical energy .
This is possible as long as the temperature of the water inside the accumulator, in the zone at. where the solar panel coil is
located, is low enough to guarantee thermal exchange with the water produced by the panel (which no longer has the high
temperatures that can be reached in the season of greatest radiation).
In other words, it is advisable that the lower part of the tank, thanks to the stratification, be at a lower temperature than the
recovery temperature of the multipurpose machine , but above the water inlet temperature of the distribution network. In
practice , one should think of two superimposed zones , with the serpentine lower part and the recovery of the I ACS above the
solar serpentine .

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The figure to the side is a schematic representation of the accumulator described previously:

The water from the network that enters the lower part is
heated anyway thanks to the energy provided by the solar
panel, before reaching the upper part of the coil, where the
exchange will be carried out with the technical water heated
by the multipurpose machine. .

The observations that we will present regarding the

estimation of the minimum water content for the production
of DHW (of the multipurpose unit) will be applied, in this
case, to the upper part of the accumulator itself (in other
words, the water content must be equal to that of the
recovery and drive of the machine, which in the figure are
indicated with
"PdC").

In many cases, what is known as a DHW “preparator” is used: it is basically a tank with an external plate exchanger, which heats
the water from the network quickly. The circulation pump in the figure is activated by a flow switch when water enters the
network (after opening the tap), or periodically to maintain the external exchanger plates at the required temperature.

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The reflections that must be made, in the sizing phase, have to do with the content of the technical water tank and the
characteristics of the plate heat exchanger.

Note: there are applications in which the DHW side accumulator is actually used as a hot water accumulator (from full
recovery), for example to cover an air treatment unit. In this case the rules to be applied are the same as those taken into
account for the buffer tank on the installation side.

Another fundamental aspect is the insulation of the DHW tank : this must limit leaks as much as possible, but also allow the
useful temperature to be maintained for a sufficiently long time: In fact there can be a fairly long time interval between the
"recharging" phase of the tank. and obtaining energy for the ACS. The most common materials are expanded polyurethane with
a thickness of approximately 100 mm and =0.038 W/mK.

Inertia accumulator on the installation side

In general terms, it is a simple inertia accumulator, with the sole function of having a sufficient water content in the installation
to guarantee correct operation (what this means will be explained later).

In general, there are several installation solutions, some better than others. Specific:

I. Tank in series, in the water return (at the machine inlet)

This was the solution that was most used in the past, to eliminate variations in the return temperature and therefore the
number of compressor starts/hour. Such a solution is no longer necessary for the compressor, since the number of starts/hour
is managed from the electronic control unit. The disadvantage is that the tank in the return exposes the use terminals to a
working temperature "in steps" (for example - in refrigeration - compressor on = cold water, compressor off = hot water).

II. Tank in series, in the impulsion (at the machine outlet, towards the use terminals) This solution is characterized by
guaranteeing the reduction of temperature variations towards the installation terminals. The disadvantage is that the working
flow rate of the machine is the same as that of the installation and, if, for example, the terminals have 2-way valves, the flow
imbalances that may arise must be taken into account. If diverter valves (known as 3-way valves) are adopted, the problem does
not arise.

III. Parallel tank (hydraulic decoupling with impulse pump towards the installation) It is the most refined solution, and allows
the working flow of the machine to be disassociated from that of the installation (which can even be set to zero, for example in
the case of start-ups). criticisms, zero thermal demands, etc.). The disadvantage is that installation and regulation are a little
more complex.

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Except for the solution with the tank in the return, for the reasons stated, we can recapitulate the functions of the accumulator
on the installation side by making references:

1. Reduction of temperature variations towards the terminals of the installation. Although the minimum water content of an
installation can be reduced through the use of sophisticated regulation algorithms, it must not be forgotten that terminals with
low inertia present lower performance with inlet water temperatures "in steps"
For more detailed information on the attenuation of variations, see the appendix "Installation-side accumulator inertia effects".

2. Maintenance of the supply temperature to the terminals in case of interruption of the heating/cooling phase for the priority
assigned to the DHW "call".

3. Reduction of the supply temperature to the terminals, in heating mode, during the defrost phase of the air/water machine,
during the winter season.
This effect can be mitigated by using "terminals" with high thermal inertia, but in other cases it represents a source of
inconvenience for the end user.

As mentioned before, it is possible that the accumulator represented in the diagram also performs the function of "hydraulic
separator" in such a way that the working flow rate of the machine and that of the distribution installation are completely
independent. In this case, it is necessary to pay close attention to the energy losses that are due to the mixing of the drive and
return fluids.

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The following figure describes the creation of a circuit in which 2 4-way valves allow water to be introduced and
taken into and from the tank, following the natural stratification and thus avoiding the losses that have been
mentioned before.

The colored arrows refer to operation in the heating phase (to the left of the tank is the machine that produces
hot water, and to the right is the distribution installation).

In the summer mode, the arrows are inverted: the introduction of the cold water produced is in the lower part of
the accumulator, and the extraction is towards the installation.

ProdypadndsseragdoheNTE WINTER MODALITY

PpdusebentamxuanfoA SUMMER MODALITY

NOTE: for all installations with partialization of the use terminals (for example two-way valves in the batteries or
similar) in the different operating conditions, the water content of the installation may vary appreciably. This must
be taken into account when calculating the dimensions of the accumulators.

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Environment use terminals

When we talk about the terminals of the facilities , we do so in the literal I sense, referring to the equipment in
charge of distributing heat in the environments (speaking specifically of the winter season).

It is necessary to make some reflections based on their characteristics ; If we simply consider two types of
terminals, fan coils and underfloor heating installations, we will notice some similarities and some distinctions,

1. The first reflection, common for terminals with high and low inertia, refers to the water temperatures. An
installation based on vapor compression machines will generally not be able to provide water at the same
temperature when external conditions vary. Specifically, operation in "heat pump" mode is affected by the
temperature of the outside air, both for the maximum thermal power and for the maximum temperature of the
water produced. It is therefore necessary, once the most critical conditions for the machine have been
established, evaluate what is the maximum thermal power actually available , the temperature of the discharge
water to the terminals, the integrated thermal power (excluding the defrost phases - as we will see later).

2. Naturally, the selected terminals must guarantee sufficient thermal input, depending on the demand of the
environment, with the temperature of the water actually produced by the machine. Practical problems often arise
because, in critical conditions, in addition to the reduction ( inevitable from the thermodynamic point of view) of
the thermal power of the machine , a decrease in the maximum temperature of the water produced can also be
obtained, with a consequent reduction in the exchange capacity of the terminals, and therefore with an
insufficient contribution to the environment. There are examples of implementations that work perfectly , which
include combinations of radiators and heat pumps, but without a doubt, the selection of the terminals itself must
be done paying close attention precisely to the water temperatures.

3. The speed of bringing the environment into operation must be considered depending on the required use. A
radiant system, in general terms, will not be suitable for applications that require rapid start-up; On the other
hand, a continuous use application can operate with temperatures that are a little more "convenient" from the
point of view of the energy efficiency of the heat engine. In the air conditioning phase, an "on demand" type of
use (as in the case of split and direct expansion systems) is not technically possible.

4. The defrosting phases of air/water machines (defrost) are considered from two points of view: it is necessary
that the integrated power (excluding what has been taken, for defrost, from the installation's water} allows it to
meet the demand and at the same time that the temperature of the water in the installation remains at a value
that allows the terminals to carry out a correct exchange. For high inertia terminals (such as underfloor heating)
their thermal capacity may be sufficient to guarantee the energy reserve necessary for defrost. For low inertia
terminals (for example fan coils) it is necessary to guarantee a sufficient water content (ta I and as described in
the corresponding chapter ).

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Humidity and ambient temperature control

A heat pump, combined with a fan coil or other ventilated terminals (typically built-in), can actively control the
humidity of the rooms and not just the temperature. The incorporation of a fan coil in the false ceiling, together
with a radiant system, guarantees both maximum thermodynamic efficiency, thanks to the radiant system, and
hygrometric control. In fact, by already having the production of chilled water for the air conditioning of the
environments covered, it will not be necessary to resort to other devices (which represent additional electrical
energy consumption and are most likely noisier due to the presence of a compressor, even if it is small).

The figure below illustrates a small installation diagram that represents a floor installation for "sensitive" cooling
(with dew point temperature control) and a fan coil that manages dehumidification, using water at 7' C that
produces the multipurpose machine.

We can make some additional observations:

1. Humidity behaves approximately like a perfect gas, and therefore the dehumidification (or humidification)
action can be "punctual" but the effects extend in a very short time to the entire volume of air in the
environment.

2. To optimize system efficiency, it is NOT necessary for the multipurpose machine to continuously produce
water at a temperature of 7°C; You can also work at slightly higher temperatures (closer to those required by the
radiant part) by modifying the set point only in case of dehumidification demand, for example by an advanced
control, as also managed by the fan coil.

As shown in the figure, the delivery temperature to the radiant part must certainly avoid condensation phenomena
(that is, be higher than the temperature of the return point, which will be determined for example by the control of
the fan coil, through the measurement of relative humidity in the environment and dry bulb temperature).

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Water temperatures and start-ups

- condensation control

The compressor of the refrigeration cycle of heat pumps guarantees high thermodynamic performance since it is of the scroll
type.
These compressors, in the versions with continuous variation of the rotation speed, are kept lubricated through a flow of oil,
guaranteed by a minimum pressure difference between the suction and discharge (and not by centrifugal force, as occurs
with fixed speed compressors).
If this pressure difference were to be lacking, the oil would stop passing, causing great risks of seizure in the mechanical
parts. A low pressure alarm in the delivery stops the machine at this moment, to avoid unpleasant consequences. A low
condensing pressure corresponds, for a fluid, to a low temperature and, in fact, if heat is removed too quickly from the
condensing fluid, a drop in its pressure occurs. Therefore, while the heat pump is in heating mode, if the water in the
accumulator is too cold (because the machine has been off for a long time or because it is the first time it is started in the
season or it is not have correctly calculated the dimensions of the accumulator), it will quickly extract the heat to the
condenser fluid. In machines with ON/OFF compressors (constant rotation speed), lubrication can be maintained, but in any
case, due to the drop in evaporation pressure, there is a significant reduction in evaporation pressure with the consequent
activation of useless defrost cycles and also, in any case, the activation of the low pressure switch.

Therefore it is necessary to artificially reduce the heat exchange in the condenser; There are two modalities:

- Use of a recirculation pump with an inverter: this will continuously reduce the flow rate that passes through the heat
pump condenser, reducing the heat exchange, and keeping the temperatures and pressures unchanged at the compressor
outlet. The pump inverter is driven directly by the unit's control processor, which is based on the pressure values recorded at
all times in the condenser.
We recommend this solution as it offers precise control and a reduction in the power consumed by the recirculation pump.

- Use of a three-way valve between the condenser and the accumulator, which allows, if it is open, to have a hot water
bypass (at the condenser outlet) that preheats the cold flow coming from the accumulator. In this case, the flow rate that
passes through the condenser remains constant (it is the temperature that changes) which allows obtaining an effect
analogous to that before in the refrigerant fluid. The three-way valve is managed by generating a signal from a temperature
probe at the condenser inlet, water side. This solution makes the pump operate at a constant speed.

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XIV.- ADVANCED CONFIGURATIONS OF HANDLING UNIT SYSTEMS
Airflow patterns
Airflow patterns or streamlines in clean rooms are strongly influenced by air supply and
return or exhaust configurations, their flow rates, personnel and material traffic routes, and
the design of process equipment. The first step to good clean room design is selecting air
pattern configurations. The selection of the final air pattern design is influenced by the
available space capable of installing air pattern control equipment (i.e., air handlers, clean
workstations, mini environments, exhaust processes, etc.), the arrangement of process
equipment, the level of cleanliness required by the user and the financial considerations of
the project.
Clean room airflow patterns can be classified as unidirectional or non-unidirectional, mixed
airflow is typically used when using a combination of air patterns. Airflow patterns for class
5 classrooms or travel plan typically.

Horizontal and vertical unidirectional flow

Unidirectional airflow can be in a horizontal or vertical flow pattern (see Figure 14.1). The
goal is to keep the airstream as straight and parallel as possible and to minimize air
turbulence within a clean room. Unidirectional flow typically uses higher air velocities, air
change rates, and high-efficiency particulate air/ultrafine particulate air (HEPA/ULPA)
filter densities (coverage) in ceilings or in walls other than directional or mixed flows;
therefore, unidirectional flow typically produces better air cleaning. Whether in a horizontal
or vertical design, the important element is to ensure that the airflow pattern is disrupted as
little as possible within the clean room, particularly around the crisis.

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In a horizontal design, air flows horizontally from a wall filled with filters through the side
of wall returns located on the opposite wall. In a vertical design, clean air is pushed
downward from HEPA/ULPA filters located on the ceiling; Air then typically carries
contaminants generated by people and processes into the clean room, and this contaminated
air is drawn into the perforated raised floor panels. The rule for selecting a horizontal or
vertical pattern is that vertically distributed processes require horizontal airflow and
horizontally distributed processes require vertical airflow.
For example, horizontal air is a flow that can be used in operations with strict cleaning
requirements; they occur near the filter wall and operations with lower cleaning
requirements occur further downstream from the filters. In some industries, such as the
pharmaceutical industry, perforated flooring is generally not feasible; Instead, solid
floors and low-level wall returns are most commonly used.
The main places of particle generation are generally not in the HEPA/ULPA filters (unless
there is a leak) but at the working and processing height where people, processes,
equipment, furniture, and particles are emitted. Therefore, the areas immediately below the
HEPA/ULPA filters offer the best air cleaning and the air becomes less clean at lower
elevations.
While personnel, workstations and equipment are inevitable obstacles to airline distortion,
flow lines for empty clean rooms must be designed and arranged with minimal flow
interruptions. Turbulent zones may have stagnation zones with no flow at all (stagnation),
reverse flow, or high velocity. When counter and currents produce stagnant areas, small
particles can clump there and

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settle on surfaces or product. Countercurrents can also lift particles from contaminated
surfaces and deposit these particles on other surfaces or products.
NON-UNIDIDECTIONAL FLOW
Non-unidirectional airflow has characteristics of non-parallel flow or multi-pass circulation,
with variations based on the location of air filters and supply air inlets and outlets (see
Figure 14.2).
Although airflow parallelism deteriorates much more than in unidirectional flow, if
designed correctly, non-unidirectional airflow can provide contamination control
satisfaction of ISO cleanliness classes 6 to 8 (ISO 2015 ).

In this flow pattern, air can be supplied from HEPA filters located at various positions in the
ceiling and returned through low sidewall returns. Ceiling-mounted HEPA filters can be
distributed at equal or near-equal intervals throughout the cleanroom and grouped in critical
process areas. Using HEPA filters in the ceiling without diffusers provides a more direct
flow and therefore cleaner air below; however, cleaning the air away from the area under
the HEPA filters will be worse.

HEPA filters can also be placed in a remote location, such as on the discharge side of an air
handling unit (AHU) or recirculating fan unit (RFU), which provides the HEPA filter.
Air can be drawn directly into the clean room, or they can be placed within an extended
HEPA filter bank downstream and separate from the AHU or RFU with a lower face
velocity through the filters. In both cases, ceiling air diffusers can be used.

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Changing and replacing HEPA filters can be accomplished in a mechanical room rather than
on the clean room ceiling. Supply air ducts generally carry a positive pressure, and it is less
likely that dirty particles can be introduced into a supply duct. However, special precautions
must be taken to avoid introducing contamination between the HEPA filters and the clean
room.
A ceiling HEPA module with an integral diffuser can also be used to provide well-mixed
conditions throughout the clean room. Because the cleanliness (or classification) of room air
is determined by the average concentration of particles measured throughout the room,
usually equally spaced, it is difficult to say that the average concentration of the room is
lower or higher. high for HEPA filters with or without a diffuser. Care should be taken to
distribute return air grilles to minimize dead zones within the clean room.

MIXED FLOW
As shown in Figure 14.3, mixed flow combines unidirectional and non-unidirectional
airflow in the same room; Separation enclosures such as one-way cabinets (clean benches),
isolators or minienvironments can be used to improve air cleanliness in more critical areas.

POLLUTION CONTROL OF DESIGN ROOMS WITH AIR FLOWS

Clean room airflow pattern design is often associated with airflow path design, greater
scope when contamination control and contaminant removal are also requirements. The
table below lists some common concerns and typical treatments.

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Common concern Typical treatment Air flow

Protection of product from particle contamination Maintain personnel process Air cleaning by HEPA filtration:
by personnel or process downstream of the product. 1 .- Product
2 .- Process Area
3 .- Staff

Personal process protection associated with harmful Air cleaning by HEPA filtration:
contaminants 4.- Staff
5.- Process Area
Positioning of upstream 6.- Extraction process
personnel and providing
segregation to allow personnel to
have indirect contact with process
when necessary
Remove harmful contaminants from clean room to Thoroughly provide capture and Air cleaning by HEPA filtration:
protect room occupants eliminate air contaminated by 4.- Staff
particles, gases, chemicals. 5.- Process
Fumes, or microbes, and use of 6.- Extraction of the Enclosure
cleaning filters supplied to the
room.

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CONFIGURATION OF CLEANING HVAC SYSTEMS
The HVAC system configuration for general purpose commercial or industrial buildings is
designed primarily to meet the heating and cooling loads of the interior space, or more
specifically to achieve the temperature and humidity requirements of the space. However,
for clean room installations, the HVAC configuration must be prepared in a way that not
only meets the heating and cooling loads, but also meets the space air cleanliness
requirements with the same HVAC system. Air cleaning has traditionally been performed
by using high airflow rates to dilute the concentration of particles in the air of a clean room,
which represents the cleanliness of the room air. The challenge is how to configure an
HVAC system when the airflow rate required by dilution is significantly higher than that
required by the heating and cooling loads.
Depending on the intensity of dilution, a clean class cleanroom typically requires a higher
airflow rate (cfm [L/s]), which can also be calculated in air changes per hour (ACH, ach) or
in average room speed (fpm om/s). For example, commercial buildings may have a “cooling
and flow rate” at 250–600 cfm (120–280 L/s) per ton, an ISO Class 7 clean room may have
a ratio of 2500 cfm (1200 L/s). ) per ton, and an ISO Class 3 clean room may require 25,000
cfm (12000 L/s) per ton. A typical AHU is commonly designed and manufactured at around
400 cfm (200 L/s) per ton, which can be stretched to a possible range of 300–600 cfm (140–
280 L/s) per ton. Therefore, it is clear that a single AHU system in the later cases (ISO 7
and 3 clean rooms) is not capable of achieving the dilution and cooling objectives.
Cleanroom design engineers often use multiple units of measure and units of measure to
handle this challenge based on cleaning classes. Figures 14.4 to 14.7 illustrate typical
HVAC configurations of primary primary AHU, primary RFU with secondary AHU,
primary fan filter units (FFU) with secondary AHU, and primary RFU with secondary AHU
and tertiary configuration AHU.

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Table 14.2 provides a general selection guide for choosing the cleanroom HVAC system
configurations shown in Figures 14.4 through 14.7. Engineers can first calculate the airflow
required to meet the heating/cooling load and then calculate the airflow required to achieve
air cleaning, then simply use the flow ratio to determine which configuration is most
suitable for the design objectives.
Figure 14.4
Single AHU
(Type 1)

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Figure 14.5
Primary RFU with Secondary

AHU (Type2A)

Figure 14.6 Primary FFUs with

Secondary AHU (Type 2B)

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Figure 14.7 Primary RFU
with Secondary AHU and
AHU (Type3)

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TABLE 14.2 TYPICAL APPLICATIONS
Guy of ISO Flow relationship between units Scheme
HVAC class Amount of type
configuration air flow for
Cleaning the air
of the
room and total
of
burden of
cooling

n/a
9,8,7 AHU for
1 Simple meet the
requirements of Figure 14.4
AHU
ACH and of
refrigeration
7,6,5,4
2A Primary • AHU
RFU mainly for Figure 14.5
achieve
and with the flow rate of RFU greater equals
AHU secondary requirements of Flow rate of AHU
school cooling
• RFU for
comply with the
ACH requirement
(or speed
average) of the
room

2B Primary 7,6,5,4 •AHU mainly for

FFUs achieve Figure 14.6
with the
and requirements of
AHU Secondary cooling
• FFU for
comply with the
ACH requirement
(or speed
average) of the
room

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3 Primary 4,3,2,1 • The
RFU, supporting AHU
secondary complies with
AHU, the
Figure
outside air
14.7
and requirements,
tertiary unit pressurization
suppor of and exhaust air
t compensation.
• AHU to meet
cooling
requirements
• The RFU
must comply
with the
requirement of
ACH

(either
average speed)
of the room

Definitions
RFU: Recirculation fan unit: Recirculation fan unit
AHU: Air handling unit : air handling unit
: MU : Makeup Unit Tertiary handler
FFUs: Fan-Filter-Units :Fan Filter Unit

The design engineer can select a configuration with necessary modifications (such as dual return
paths) that can achieve indoor conditions. Air flows can be combined, diverted or sequentially
combined from both.

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Instead of using guesswork for selecting an HVAC configuration, airstream properties (dry and wet
bulb temperatures, moisture content, flow rate, enthalpy, etc.) must be calculated and psychometric
characteristics can be analyzed. to obtain more predictable indoor conditions through computer
simulations.
CLEAN DESIGN
Interior clean room surfaces and filtered air supply systems have some impact on the final
cleanliness of the room air. The following considerations can help improve HVAC system and
clean room cleanliness:
• Corrosion resistant interior surfaces within clean rooms.
• Direct drive instead of belt driven fan motors
• Sealed bearings for motors.
• Ultraviolet (UV) lights for cooling coils and wet surfaces
• Antimicrobial coating on cooling drain pans
REDUNDANCY AND RELIABILITY DESIGN
Redundancy must be provided at a level that matches the process requirements. Redundancy can be
addressed at the component level, such as multiple fans operating in parallel (fan wall), or at the
system level with multiple air handlers operating in parallel.
Careful design considerations should be provided throughout the design process to minimize or
eliminate single points of failure. For example, multiple fans serving one may appear to provide
redundancy in the system, but if the electrical distribution is not properly designed, a single circuit
breaker failure can cause an unplanned shutdown.

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DESIGN OF COMMISSIONABLE SYSTEMS

The following elements can be considered for the design of the system taking into account the
future commissioning:
• Critical parameters and operational values monitored and tracked.
• Total system power monitored
• Power monitoring of large equipment.
• Shut-off and isolation valves.
• Test ports and sensor locations
• Selected sensor locations for stable operation

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CLEANING AIR FLOW RATE DETERMINATION
SUMMARY
The air supply rate to a clean room can be expressed in an absolute volumetric flow rate
(cfm [L/s or m3/min]); However, it is difficult to use the absolute rate to compare airflow
intensity between clean rooms when clean room size is not included. Therefore, the size-
neutral relative airflow magnitude is more commonly used.

Where :

v = Velocity m/s
Q = Flow m3/h
A = Area m2
For non-unidirectional airflows, it is more common to use the air change rate (ACR), often
expressed in air changes per hour (ach):

Where
N = Renewals hour (dimensionless)
Q = flow m3/h
V = Volume of the enclosure m3

Please note that not all unidirectional flow cleanrooms are arranged with 100% ceiling
coverage of HEPA filters, ULPA filters or FFU; some may only have 30% to 90% coverage
of the roof filter. In these cases, the actual air velocity at a process/operating height could be
much lower than the face velocity on HEPA/ULPA filters. From

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It has long been mistakenly believed that airspeed can only be used for unidirectional flows
and ACR can only be used for non-unidirectional flows. In fact, when the dimensions of the
room are known and air is supplied from the ceiling, the average room velocity and ACR
can be mutually converted as follows, with a similar term for air supplied from the wall
where the Height of the room is replaced with air traveling the length of the room:

N _ 60 Q _ 60 y^A _ 60- v I VJ HH

Where :
Q = flow rate, fpm(m3/h)
V = Clean room volume in ft3 (m3)
A = Clean room area ft2 (m2)
v = speed in fpm (m/min)
H = Height of the room ft (m)
N = ACR in the room, time changes
60 = One hour is 60 minutes

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IMPACT OF CLEANING HEIGHT ON AIR CHANGES RATE AND AIR
VELOCITY DETERMINATIONS

Cleanroom designers should be aware that using ACH values to compare two cleanrooms
with different heights is sometimes meaningless. For example, the aerospace industry
uses high-rise clean rooms for aircraft assembly, which could have room heights of 40
to 160 ft (12 to 50 m).
PRESSURE CONTROL IN CLEAN ROOMS
SUMMARY
Clean spaces use room pressurization or depressurization to create desired flow patterns
from less clean rooms to cleaner rooms and to minimize particulate, biological, gaseous,
and/or chemical contamination in the air. It is achieved by mechanically creating air
pressure differences between rooms to cause intentional air movement through the room
leak.
Traditionally, cleanroom pressurization control technologies have been based on intuitive
suggestions rather than well-established guidelines. A pressure differential of 0.05in. toilet
(12.5 Pa) has been used since it was adopted in US Federal Standard (FS) 209A, Cleaning
of Airborne Particles, Cleanrooms and Zone Cleaning (GSA 1966), and the "Clean Spaces"
chapter of the ASHRAE Handbook — HVACApplications (US). USA).
It was assumed that maintaining a closed-door cleanroom enclosure at 0.05 in. toilet (12.5
Pa) differential pressure meant that during door operation the desired flow patterns between
the two rooms would be maintained and that contamination caused by air flowing from the
less clean areas into the clean room would be minimized (even if the pressure differential
decreased significantly) (Sun et al. 3013a). However, using 0.05 in. toilet (12.5 Pa) for each
differential pressure step is believed to be oversimplified and may not be accurate enough
(Sun 2003), especially when a clean room is surrounded by an adjacent less clean area that
could be one, two, three or more, dirtier classes. Therefore, the recommendation is that
clean rooms be surrounded by areas of no more than one class less.

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The information section ISO 14644-4, Clean rooms and associated controlled environments,
Part 4: Design, construction and commissioning (ISO 2001), currently allows a differential
pressure between 0.02 in 0.08en.wc
Furthermore, pollution barriers, such as minienvironments, clean benches (foil covers), and
airlocks, which virtually impose an additional level of resistance to the migration of
airborne contaminants, have not been proven. quantitatively (Sun et al. 2013a).
Additionally, the airtightness level of the room enclosure, which is a critical element in the
design consideration, has for decades been ignored during pressurization designs.
The purpose of clean room pressurization is to define a flow pattern and act as a particle
migration barrier. A specific pressure differential in a closed door between rooms with two
different air cleanliness can generally prevent cross-contamination in the air from the less
clean room to the clean room, because even if the door frame has some air gaps minor
(cracks), these openings are small and the air leak rates through these cracks are high
enough to prevent backflows. However, when the door is opened, the pressure differential
changes rapidly and the functionality of the barrier becomes questionable (Sun et al. 3013a).
In addition to the minimum required pressure differential, treatment in the gate-operating
condition should be considered to prevent backflow.
HOW TO ACHIEVE ROOM PRESSURE DIFFERENTIALS
There is an important relationship between the room pressure and the flow difference inside
the room, which is the difference between the room difference and the outgoing air flow,
generally called make-up flow. The room pressure variables and their relationships can be
expressed as shown in Figure 14.8.
To obtain a pressure differential across a wall separating two rooms, air must be filtered
between the rooms by a compensating flow to allow a surplus of air in one room and a
deficit in the other (see Figure 14.9).

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EQUATIONS TO CALCULATE AIR FLOW LEAKAGE THROUGH LOCK
DOORS

To study the performance of air lock quantitatively, one has to analyze the air flow leakage
through doors in closed and open conditions. The “power equation” is commonly used:

This equation is used to describe air leakage through irregular cracks, such as an air gap between
a door and its frame or through joints between floor and walls, walls and ceiling, ceiling tiles and
celling grids, and wall penetrations for ductwork, conduits and piping , etc.
Another single parameter to quantify the leakage opening is the effective leakage area (ELA). The
definition of ELA and its data tables for building components can be found in ASHRAE Handbook—
Fundamentals (ASHRAE 2017). Once a Q-APdata set is obtained. C and n can be calculated as
follows (Sun 2005):

m mhm

> In > InAP, - m- > (InQ, • InAP,)

n = k-1_________k-1_____________k=1_____________
fm 2m
> InAP, -m-> (InAPp2
i=1 k=1

The characteristics of air flows through large designated openings, such as doors, are
somewhat different from those through small crevice openings. The sharp-edged orifice
flow equation is more suitable for describing larger openings (ASHRAE 2017):

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Q = 2610 -4 TAP (iP)

Q = 840 A/AP (YE

AH)
where
A = large designated opening area(s), ft 2 (m 2 )
2610 = unit conversion factor, dimensionless 840 = unit conversion factor, dimensionless

AIR LEAK RATE VS. PRESSURE DIFFERENCE UNDER VARIOUS LEAK

ZONES

Both the power equation and the orifice equation can be presented in a set of curves that
design engineers can easily use. Figure 14.10 illustrates the hole equation in a group of
curves. Among the three variables of leak air rate, differential pressure across the leak path,
and leak area, once two of them are known, the third variable can be identified.

BALANCE EQUIPMENT AND PRESSURIZATION RATIO

Key relationships in air flow rates between the central AHU and room pressurization
variables can be found in Figure 8.20, where SA is supply air, RA is return air, EA is
exhaust air, FA is relief air and Q is leakage air.

Two mass balance equations can be simplified as volumetric balance equations when air
density is ignored:

SA = RA+EA+Q (Volume balance for a space)

SA = DA + (RA - FA) (Volume balance for a typical AHU)

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The space pressurization index is an indicator of the relative pressurization level. It can be
used to adjust air gains or losses between zones, to organize the desired air flows within a
building.
If a room has multiple leak openings with adjacent rooms, the room pressurization ratio is:

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Clean rooms in pharmaceutical facilities
CURRENT GOOD MANUFACTURING PRACTICES (CGMPs)
Adherence to cGMP regulations ensures the identity, strength, quality and purity of
pharmaceutical products by requiring drug manufacturers to adequately control
manufacturing operations. This includes establishing robust quality management systems,
sourcing adequate quality raw materials, establishing robust operating procedures, detecting
and investigating product quality deviations, and maintaining reliable testing laboratories.
This formal system of controls in a pharmaceutical company, if properly put into practice,
helps prevent cases of contamination, confusion, deviations, failures and errors. This
ensures that pharmaceutical products meet their quality standards.
Failure to comply with regulations will result in the adulterated drug being prosecuted.
Although numerous, cGMP guidelines follow some basic principles, with processing
and accounting capabilities currently available for the GMPs that are of most
importance (GPO2016a):
• The processes used in manufacturing products are clearly defined and controlled, with
critical processes undergoing validation to ensure consistency and compliance with
specifications.
• Good documentation practices are used for instructions and procedures and are written
clearly and unambiguously.
• Operators are responsible for manufacturing products and are trained to operate in
document procedures.
• Records were prepared for the product during the process that was ordered, pre-procedure
steps and instructions cleared, and the quality and quantity of the expected rule.
• Manufacturing records, including distribution records, are tracked and maintained in an
understandable and accessible form, allowing the complete history of necessary information
to be retrieved.
• The distribution of the manufactured product minimizes the risk to the quality of the
products.

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• There is a system available to retain copy of supplied or dispensed medications if
required.
• Product complaints are reviewed and investigated accordingly. If necessary, measures
must be taken regarding suitable products and taken into account to prevent the occurrence
of defects.

BRIEF COMPARISON OF THE FDA AND EMA

Country-specific GMPs are presented globally, but most, if not all, are based on the US one
below.
• US Guidelines USA, enforced by the US Food and Drug Administration. USA (FDA):
• United States Codeof Federal Regulations, Chapter 1, Title 21, Parts 11,210,211,600–680
and 820 (GPO2016c)
• ISO 14644, Clean rooms and associated controlled environments (ISO2016)
• European guidelines, imposed by the European Medicines Agency (EMA):
• EU Guidelines on Good Manufacturing Practice: Medicinal Products for Human and
Veterinary Use, Volume 4 f EudraLex
The Rules Governing Medicinal Products in the European Union(EudraLex)(EC2010)
• Annex 1: Manufacture of style medicinal products products
• Annex 2: Manufacture of biological active substances and medicinal products for human
use
The type of enjoyment of the person who is at the level of the vein is a type of enjoyment.
Strong collaboration and harmonious coordination has been observed across the world.
GMP standard rules among other regulatory agencies of various countries, but it has been
shown that there is a lot of discussion.
The ISO 14644 series, however, points out the essential requirements of the company, that
is, different from the ISO14644-1 and 14644-2 standards. It is important for the community

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pharmaceutical for consistency of health, appearances of animals in critical areas.
European Medicines Agency (EMA)
The European Medicines Agency (EMA), formerly known as the European Agency for the
Evaluation of Medical Products (EMEA), is a decentralized body from the headquarters of
the European Union (EU) in the United Kingdom. The main responsibility of this type is the
body of the organization.
The safety of medicines is constantly monitored through the weaponry network access
method. In the most varied versions it is suggested that a risk adjustment should be made in
the market for animal products and animal parts in animal parts or in animal parts.
In addition, the ESA system stimulates pharmaceutical research and innovation and
scientific projections and communication aids to improve the development of new
medicinal products. The system has published safety, quality and requirements guides
(EC2017).
FACILITY DESIGN CONSIDERATIONS
All pharmaceutical products are composed of active ingredients: inactive and active
ingredients. Active pharmaceutical ingredients (APIs) are considered as a real
pharmacological effect.

Non-sterile products include pellets, capsules, liquids, topi-cals, and non-invasive medical
devices and supplies. Stated above, the objectives of pharmaceutical products and room
design and corrosion resistance are proposed.

In a typical non-sterile facility there are six basic areas:

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•Administrative
•Laboratory
• Storage
•Manufacturing
•Main packaging
• Secondary packaging

Administrative
Administrative areas, conference rooms, locker rooms, cafeterias and other support
functions. The air conditioning system for these purposes has been designed to meet the
basic comfort requirements of employees.
Laboratory
The laboratory may require close monitoring to identify classified spaces, including
adjacent corridors and administrative spaces, depending on the function (for additional
discussion see Section 19.3.5).
Storage
The HVAC is designed so that minimum requirements for the materials being stored are
met.

The requirements for the state of service are therefore simulated manufacturing, for
example, the materials being processed are generally class 8 (grade C) equivalent
(ISO2015).
An inadequately designed installation, the transition point between the two, software and
manufacturing, and the cost of the installation, was performed and evaluated at a location
where the device was inspected.
Typically, a high value area will be used in a flow cabinet (DFB) designed to create a
mining environment atmosphere in the living room. Emergency actions have been used in
the lower part, within which a flow of light is shown in the background of the city.

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Manufacturing
Once a manufacturing zone was set up, materials were transferred through a corridor to
which the ID card procedure was identified.

In the design of new functions, processing equipment can be designed to protect first-level
protection for the product, by using material transfer systems of a pair of counters and other
types of control security elements.
Primary packaging
Once materials are processed into bulk products, they must be packaged. Once again, the
focus should be on protecting the product and the product contact surfaces (in this case, the
inside of the packaging materials), as the package now becomes an additional contact
surface. case of solid dosage forms, current designs for packaging lines, including the
limitation on a filling suite found with the same ISO Class 8.
Below we show a typical example of different types of UMAS.

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An example has been taken for different UMAS configurations, the only difference lies
in the type of installation configuration:
100% outside air:
INDICATE THE SENSITIVE THERMAL LOAD 20KW
INDICATE THE VOLUME OF THE 150m3
ENCLOSURE
INDICATE THE OUTDOOR TEMPERATURE 35°C
INDICATE THE INTERIOR TEMPERATURE 22°C
LEAK AREA 0,045m2
PRESSURE DIFERENCIAL 12pa
QTS INJECTION FLOW 4.977m3/h
TIME RENEWALS 132
FLOW FOR RENEWALS 19.800m3/h
DESIGN FLOW 19.800m3/h
VR/VQT RATIO 4,0
COOLING POWER 152,5KW
LEAK FLOW 471m3/h
INDICATE EXTRACTION FLOW 19.329m3/h
RETURN FLOW 0m3/h
COMPRESSOR POWER 38KW
UMA FLOW 19.800m3/h
TOTAL COOLING POWER 399KW
ELECTRICAL POWER 99,75KW
These results are based on 100% outside air, the diagram and flow diagram are shown in the
following diagrams:

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Altitu
DAIKIN Specific volume (m'/kg) Absolute humidity
de •When Relative humidity (%) 100 90 80 70 (kg/kg)
Altitu passing 60
—0,05!
Point definition
de through
Point name [P3 Add Edit Delete
Dry bulb Data point (P1) Dry
0,051
temperature bulb temperature 35.0°
RH %[30,0< > Wet bulb C
Flow nffli 19800 ,< temperature Dew 28,2°

Point name Dry P2 point 26.1°

Point name P1 RH ■0
bulb temperature 12.0°C C 04!
Dry bulb 35,0°Relative humidity Absolute 0.0214kg/
80.0% 60.0
temperature
RH 60.0%Flow rate humidity kg
19800m %
Flow 19800m* Enthalpy
»/h 21.5kcal/ ■0
h Density
Point name PP1 Specific kg 041
Dry bulb 35.0° 1.131kg/
volume
temperature
RH C 19.9%
Pressure
Flow m,
Flow 19800m*/
0.903m*/ ■0
Definition of action h 03!
kg
0 Show intermediate lines | Add ] Edit Delete Cooling v 101325.0
Pa -0 031
P1v P2v PP2 19800m»
| Connect P1. P2 /h 1,000)
• P1 cooling. P2. PP1
Total Capacities = 399.82kW. Sensitive = 154.65kW (39%). -0.02!
Latent = 245,

001!

-0 01

-0 00

Density (kg/m 1 )
Wet bulb temperature (°C)
Enthalpy (kcal/kg)
0,8 0w 0,9 0,9 O

80 20 40
OOI

Dry bulb temperature

(°C)

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If a type 1 configuration is used

INDICATE THE SENSITIVE THERMAL LOAD 20KW
INDICATE THE VOLUME OF THE 150m3
ENCLOSURE
INDICATE THE OUTDOOR TEMPERATURE 35°C
INDICATE THE INTERIOR TEMPERATURE 22°C
LEAK AREA 0,045m2
PRESSURE DIFERENCIAL 12pa
QTS INJECTION FLOW 4.977m3/h
TIME RENEWALS 132
FLOW FOR RENEWALS 19.800m3/h
DESIGN FLOW 19.800m3/h
VR/VQT RATIO 4,0
INDICATE EXTRACTION FLOW 1.000m3/h
LEAK FLOW 471m3/h
RETURN FLOW 18.329m3/h
EXTERNAL FLOW 1.471m3/h
TMMIX 23,0°C
COOLING POWER 73KW
COMPRESSOR POWER 18,2KW
SENSITIVE SAVINGS 52,32%
UMA FLOW 19.800m3/h
TOTAL COOLING POWER 84,2 KW
TOTAL ELECTRICAL POWER 21,1 KW

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Type 2A configuration, if the second AHU cools to a

temperature of 12 °C, consumption is similar to type 1
configuration.
INDICATE THE SENSITIVE THERMAL LOAD 20KW
INDICATE THE VOLUME OF THE 150 m3
ENCLOSURE
INDICATE THE OUTDOOR TEMPERATURE 35°C
INDICATE THE INTERIOR TEMPERATURE 22°C
LEAK AREA 0,045 m2
PRESSURE DIFERENCIAL 12pa
QTS INJECTION FLOW 4.977 m3/h
TIME RENEWALS 132
FLOW FOR RENEWALS 19.800 m3/h
DESIGN FLOW 19.800 m3/h
VR/VQT RATIO 4,0
INDICATE EXTRACTION FLOW 1.000 m3/h
VERTICAL RECIRCULATION PERCENTAGE 75%
HORIZONTAL RECIRCULATION 25%
PERCENTAGE
LEAK FLOW 471 m3/h
GENERAL RETURN FLOW 18.329 m3/h
VERTICAL RETURN FLOW 13.746,45m3/h
HORIZONTAL RETURN FLOW 4.582,15 m3/h
EXPULSION FLOW 0 m3/h
UMA FLOW 6.054 m3/h
EXTERNAL FLOW 1.471 m3/h
EXTERNAL MIX TEMPERATURE 25,2 °C
UMA OUTLET TEMPERATURE 7 °C
UMA POWER 36,8 KW
VIN INLET MIXTURE TEMPERATURE 17,41 °C
POWER SERPENTIN VIN 36 KW
TOTAL COOLING POWER 73 KW
TOTAL ELECTRICAL CONSUMPTION 18 KW
SAVING 52 %
TOTAL COOLING POWER 62 KW
TOTAL ELECTRICAL CONSUMPTION 15,5 KW

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If the second AHU cools to a temperature of 17°C, we have:

AIR TEMPERATURE DIFFERENTIAL 5 °C
SECONDARY UMA OUTLET TEMPERATURE 17 °C
38
INDICATE THE SENSITIVE THERMAL LOAD 20 KW
INDICATE THE VOLUME OF THE ENCLOSURE 150 m3
INDICATE THE OUTDOOR TEMPERATURE 35 °C
INDICATE THE INTERIOR TEMPERATURE 22 °C
LEAK AREA 0,045 m2
PRESSURE DIFERENCIAL 12 pa
QTS INJECTION FLOW 4.977 m3/h
TIME RENEWALS 132
FLOW FOR RENEWALS 19.800 m3/h
DESIGN FLOW 19.800 m3/h
VR/VQT RATIO 4,0
INDICATE EXTRACTION FLOW 1.000 m3/h
VERTICAL RECIRCULATION PERCENTAGE 75 %
HORIZONTAL RECIRCULATION PERCENTAGE 25 %
LEAK FLOW 471 m3/h
GENERAL RETURN FLOW 18.329 m3/h
VERTICAL RETURN FLOW 13.746,45 m3/h
HORIZONTAL RETURN FLOW 4.582,15 m3/h
EXPULSION FLOW 0 m3/h
UMA FLOW 6.054 m3/h
EXTERNAL FLOW 1.471 m3/h
EXTERNAL MIX TEMPERATURE 25,2 °C
UMA OUTLET TEMPERATURE 7 °C
UMA POWER 36,8 KW
VIN INLET MIXTURE TEMPERATURE 17,41 °C
POWER SERPENTIN VIN 3 KW
TOTAL COOLING POWER 40 KW
TOTAL ELECTRICAL CONSUMPTION 10 KW
SAVING 74 %
TOTAL COOLING POWER 62 KW
TOTAL ELECTRICAL CONSUMPTION 15,5 KW

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The savings are achieved because the UMA is only used to cool the air or to overcome the sensible Thermal Load and the Fan only produces a
small 17.41°C to 17°C. Obtaining a saving of 74% compared to the initial configuration.

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1. Psychrometric points
P1 P2 PP1 P3
Dry bulb temperature 35.0°C Dry bulb temperature 22.0°C Dry bulb temperature 25.1°C Dry bulb temperature 7.0°C
Wet bulb temperature 28.2°C Wet bulb temperature 13.9°C Wet bulb temperature 18.0°C Wet bulb temperature 5.5°C
Dew point 26.1°C Dew point 7.8°C Dew point 14.1°C Dew point 3.8°C
RH 60,0% RH 40,0% RH 50,4% RH 80,0%
Absolute humidity 0.0214kg/kg Absolute humidity 0.0066kg/kg Absolute humidity 0.0100kg/kg Absolute humidity 0.0050kg/kg
Enthalpy 21.5kcal/kg Enthalpy 9.3kcal/kg Enthalpy 12.1kcal/kg Enthalpy 4.7kcal/kg
Density 1,131kg/m s Density 1,191kg/m s Density 1,177kg/m 3 Density 1,256kg/m 3
specific volume 0.903m'/kg specific volume 0.845m'/kg Specific volume 0.858m 3 /kg Specific volume 0,800m 3 /kg
Pressure 101325,OPa Pressure 101325,OPa Pressure 101325,OPa Pressure 101325,OPa
Flow 1472m'/h Flow 4582m3/h Flow 6054m 3 /h Flow 6054m3/h
PP2 P4 PP3 P5
Dry bulb temperature 25.1°C Dry bulb temperature 23.0°C Dry bulb temperature 17.9°C Dry bulb temperature 12.0°C
Wet bulb temperature 13.6°C Wet bulb temperature 14.7°C Wet bulb temperature 12.0°C Wet bulb temperature 8.2°C
Dew point 3.8°C Dew point 8.7°C Dew point 7.3°C Dew point 4.5°C
RH 25,2% RH 40,0% RH 49,7% RH 60,0%
Absolute humidity 0.0050kg/kg Absolute humidity 0.0070kg/kg Absolute humidity 0.0063kg/kg Absolute humidity 0.0052kg/kg
Enthalpy 9.0kcal/kg Enthalpy 9.8kcal/kg Enthalpy 8.1kcal/kg Enthalpy 6.0kcal/kg
Density 1,180kg/m 3 Density 1,187kg/m 3 Density 1,208kg/m 3 Density 1,234kg/m 3
Specific volume 0.852m'/kg Specific volume 0.848m 3 /kg Specific volume 0.833m 3 /kg Specific volume 0.815m'/kg
Pressure 101325,OPa Pressure 101325,OPa Pressure 101325,OPa Pressure 101325,OPa
Flow 6054m'/h Flow 13746m 3 /h Flow 19800m 3 /h Flow 19800m 3 /h
PP4
Dry bulb temperature 17.9°C
Wet bulb temperature 10.9°C
Dew point 4.5°C
RH 41,0%
Absolute humidity 0.0052kg/kg
Enthalpy 7.5kcal/kg
Density 1,209kg/m'

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XV.- ANALYSIS OF CONTROL SYSTEMS FOR HANDLING UNITS IN
HIGH HUMIDITY ENVIRONMENTS
ANALYSIS OF CLEAN ROOM HVAC CONTROL SYSTEMS, HIGH
HUMIDITY AREAS

• Three typical air conditioning system options are comparatively analyzed.

• The "partially decoupled option" is proposed for modernization projects.
• Simulation and results of in situ tests.

Compared to spaces air conditioned for thermal comfort, clean rooms control other
variables in dry bulb temperature, relative humidity, and particle concentrations. It is
a difficult task to achieve those requirements with minimum energy consumption,
especially when different parameters interfere with each other. A significant amount
of energy would be wasted if the system is not properly designed and controlled.
Firstly, this document provides an overview and discussion of the essential elements
for the design and control of cleanroom air conditioning systems. Existing systems
and controls are classified into three typical options and their performances are based
on different conditions and loading conditions.
For a new design, the fully decoupled option is the preferred option for wetter areas.
The results of the analysis are applied in a modernization project for a
pharmaceutical factory located in Hong Kong, a humid subtropical city, which used
the "interactive option". This system is proposed to operate as a "partially decoupled
option" in this retrofit project requiring no modification to existing hardware. The
upgraded system option has been tested, providing reductions of 69.6% and 87.8%
in cooling and heating respectively.
Extensive comparison tests are performed on a dynamic Matlab/Simulink-based
platform.

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1. Introduction
Clean rooms can consume 30 to 50 times more energy than the average US
commercial building. USA due to the high ventilation rates required to maintain low
particle concentrations. Clean room environmental control systems or air
conditioning systems consume about 30 to 65% of the total energy use in high-tech
manufacturing.
A Class 10 environment generally costs around US. In the US, $2,000 per square
foot to build and $1 million a year to operate. It is essential to reduce energy use in
clean rooms for two main reasons. First, cleanrooms have been growing rapidly,
increasing from 4.2 million m2 in 1993 to an estimated 25.5 million m2 in 2020 in
the US. USA [5], and increases even faster in southern China, hence energy
consumption and installed energy capacity.
The savings potentials are very high compared to many other air conditioning
systems.
The proper design of clean room or air conditioning environment control systems are
essential for energy efficiency, which are closely related to each other both
environmentally and controlling energy performance. Only when an air conditioning
system is properly designed can it be implemented to achieve the desired
environmental control, with high energy efficiency. Additionally, controls engineers
should be involved in the design process so that all elements are considered.
Many researchers have addressed the design of air conditioning for clean rooms.
Yang and Eng Gan analyzed the essential elements of clean room design that
significantly affect construction, with their costs and provided strategies for
designing control of air change rates in clean rooms, that is, demand controlled
filtration ( DCF), based on real-time monitoring of particle concentrations. Lin et al.
developed a dry cooling unit return fan. That

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is a system to improve the energy efficiency of clean rooms. Hu and Tsao compared
the energy efficiency of five different clean rooms with air conditioning systems
composed of different combinations, recirculation air unit (RCU), make-up air unit
(MAU), fan coil unit (FCU), air coil dry cooling (DCC), fan filter unit (FFU), etc.
The MAU and FFU provided the highest energy efficiency. They also proposed a
makeup air system for energy conservation.
Kircher et al. compared energy efficiency methods through simulation modeling of
the Solar system, including a system of
heat recovery, preheating for the dehumidification system, control of
lighting and filtration controlled by
demand. Some other studies addressed exhaust air recovery energy using a
regenerative-desiccant wheel.
Although many studies for clean room design appear in the literature, few
studies have investigated the control of the clean room with the air conditioning
system. Good HVAC design, but not properly controlled, can consume a large
amount of energy. Some studies discussed clean room pressure control. Wang et al.
provided an operation strategy to control the gradient in a multi-zone clean room.
Their experimental research showed that the strategy achieved energy savings of
around 24.5%. Van den Brink et al. also proposed improved pressure control in clean
rooms with a focus on clean room pressure.
Due to special requirements, those approaches for thermal comfort air conditioning
systems, such as outside airflow reduction and some complex control methods, may
not be applicable for clean room applications. Only a few publications addressed
local controls that aim to control the process variables, to follow their set points in
clean rooms. For example, it provided an automatic tuning approach for temperature
control structure variables in clean rooms.

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Since most air conditioning systems use cooling process for dehumidification,
counter heating and cooling for humidity and temperature control which takes large
amount of energy. Alternative approaches should be considered to improve the
energy efficiency of air conditioning. First, the system design must consider the
climatic conditions. Secondly, the control of the system under year-round operating
conditions should be properly considered.
The control design must consider the system's energy use seriously.
This document provides an overview and discussion of key design and control issues
for cleanroom air conditioning systems.
Three typical systems are then described and compared under different climatic and
loading conditions. The analysis of the results is applied in a modernization project
for a pharmaceutical factory located in Hong Kong, a humid subtropical city, which
originally used an interactive option air conditioning system.
The system is adapted to function as a partially decoupled system, it is the option in
this project since such modification is the most cost-effective and does not change
the existing hardware.
Although different clean rooms have the same problem for different reasons. The
results of the comparative analysis of the three systems presented in this document,
whose guidance is very useful for the design, internal control of the environment, its
control system or reconditioning of air conditioning systems of new projects.
Section 2 presents an overview and discussion of key design and control issues for
cleanroom air conditioning systems. Section 3 describes cleanroom configurations
and control methods. Section 4 shows the comparative analysis of these three
systems.

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2. Key issues in the design and control of air conditioning in clean rooms.
Compared to the common purpose of air-conditioned spaces for thermal comfort,
clean rooms control dry bulb temperature (DBT), relative humidity (RH), and
particle concentrations. High flow rate air supply is often required in clean rooms to
remove airborne particulate contaminants. In addition to the large power
consumption of the fan, the high air supply also causes large energy consumption for
dehumidification and temperature control of clean rooms. The classic design and
control methods directly from the point of supply for dehumidification and then
reheating, to achieve the desired clean room temperature. Due to the high supply air
flow rate, the cooling and reheating energy for dehumidification would be extremely
high, when the humidity load is low.
To solve the problem of high power consumption, high supply air flow, some key
problems must be properly addressed at the design stage. First, it is essential to
design the supply air duct with low resistance to air flow, so that the supply air fan
can be reduced in static pressure and size.
Secondly, air treatment processes, have alternative methods to control dry bulb
temperature, relative humidity and particle concentration.
Two common approaches to address the problem of high energy consumption can be
summarized and the relative concepts are described as follows.

Approach 1: Dehumidify outdoor air in primary air handling units (PAU) to

decouple humidity and temperature controls, while dry outdoor air is used to
dehumidify air in indoor spaces.
This system is particularly suitable for clean rooms with relatively low
dehumidification load.

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Approach 2: Decouple temperature and humidity controls by using two parallel
cooling coils in addition to heating. The supply air flow is separated into two
streams. One stream passes through the wet cooling coil, for humidity control. Its
flow rate is optimized so that the wet coil has minimal cooling energy consumption
for dehumidification. The other stream passes through the dry cooling coil for
temperature control only. Furthermore, the total flow rate of the two streams is equal
to the total supply air flow required for particle concentration control.
3. Three typical air conditioning system options.
Based on a survey of existing systems and controls appearing in the literature and in
actual practice, for the control of a clean room environment, air conditioning systems
or systems are classified into three typical options according to the degree of
decoupling, control of dry bulb temperature, particulate matter concentrations and
relative humidity.
3.1. Option A - Interactive option
Fig. 1(a) shows the configuration of the interactive option, and Fig. 1(b)
demonstrates the control of the air treatment process plotted on the psychrometric.
The system consists of PAUs and several AHUs.
Each AHU serves several clean rooms. The PAU cools the outside air to a certain
temperature, for example, 15 C, at its mechanical dew point (O------------L1). Fresh
outside air is mixed with recirculation air, in an AHU with a certain outside
air/recirculation flow ratio, for example, 15/85, (L1--- M, I--- M). The mixed air is
handled further by the AHU cooling coil, for dehumidification and possible cooling
as well (M--- L2) and heating by the AHU heat coil, if necessary to reach the
temperature set point of the dehumidification supply air (L2--- S). The supply air is
further heated if necessary to the reheat terminals of each clean room, to maintain
individual space temperatures at their set points.
Fig. 1(a) also demonstrates the control mechanism of cleanroom AHUs. PAU fan
speed and valve opening of the hot and cold coils that are modulated by PID and the
temperatures of

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injection at their corresponding setpoints. The maximum relative humidity between
all associated clean rooms is controlled by a PID controller below a preset threshold
upper limit, modulating the AHU cooling coil valve. The AHU heating from the heat
coil valve is modulated to the AHU supply air temperature, at its set point.
When the supply air becomes supercooled, so dehumidification or heating is needed
in cold season clean rooms. The valves on the individual cleanroom terminal reheat
coils are modulated by their PID controllers to control the cleanroom dry bulb
temperature at their set points. The AHU Fan speed is modulated to maintain the
static air pressure set point in the supply duct to provide sufficient airflow to all
associated clean rooms. Clean room supply air dampers are used to achieve the
required supply air flow rates in individual rooms. Which are maintained by the air
supply corresponding to the rate measured in the start-up stage or in the online
control process, therefore there is a VAC control with a proportional actuator motor.
PID controllers control individual clean room pressures at their set points by
modulating the corresponding return air dampers.

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(b) Air handling process control in PAU and AHU of Option

A

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3.2. Option B: partially decoupled option
The system configuration of Option B is quite similar to Option A.
As shown in FIG. 2(a). The only difference is that Option B does not require a
heating coil in the AHUs. However, the air control management process of Option B
is quite different from Option A, this is demonstrated in the psychrometric chart in
Fig. 2(b). Only outside air is used for dehumidification of humid air in clean rooms.
In case the humidity ratio of the outdoor air is higher than that of the indoor air, the
outdoor air is cooled and dried in PAU, i.e. the O curve --L in Fig. 2(b). The PAU
outlet air temperature set point should be set quite low, so that the air in the clean
rooms can be dehumidified by the outside air of the PAU only. In case the humidity
ratio of outdoor air is low enough, the air in clean rooms can be dehumidified by
directly supplying the dry outdoor air to the AHUs without cooling in the PAU. The
airflow rate is determined according to the need for contaminant control or relative
humidity control in clean rooms, depending on which is critical.
The control of Option B is also demonstrated in FIG. 2(a). The PAU is controlled
using the same logic as Option A, but the PAU outlet air temperature is reset to
ratios of outside air and inside air. The AHU air supply fan, its speed is modulated to
keep the air in the duct at its set point. Its cooling coil is modulated to control the
AHU supply air temperature at its set point, which is reset to maintain clean room
dry bulb in the terminal units. Air is heated by the heat coil, in each of the individual
clean rooms where these are controlled, to ensure the clean room dry bulb
temperature above pre-set lower limits and the clean room relative humidity below
of its upper limits. The airflow demand and static pressure control mechanism in
clean rooms are the same as Option A.

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3.3. Option C: fully decoupled option
Fig. 3 shows the system configuration and air handling of Option C. This
configuration differs from Option A and Option B, primarily at the AHU, because
the AHU employs two parallel cooling coil systems. The air handling process is
therefore more complicated than the other two options, as shown in Fig. 3(b). The
PAU lowers the outside air to a very low temperature, to share the cooling and
dehumidification loads of the outside air in the clean rooms (O--- L1). The outside
air is mixed with the recirculation air (L1--- M1, I1--- M1) and then divided into two
streams, each going through a cooling coil and mixed back to the supply air for the
terminal units.
One of the AHU cooling coils is used as a wet coil for dehumidification, (M1
-------------------------------------------------------L2), the other is used for control
temperature (M1-----------D). The two air streams mix as (L2--
M2, D---M2).
The control of Option C is shown in FIG. 3(a). Compare with option A and option B,
the main difference of this option is the clean room humidity control. The maximum
relative humidity of the associated clean rooms is used to control the airflow ratio of
the two airstreams in AHU. The exit air temperature of the wet cooling coil is
controlled at a low set point for dehumidification and the other coil is controlled to
maintain a reasonable supply of air cooling based on the unit's air reheat need.
terminal, if not necessary. The controls for superheat terminals, air supply dampers,
and return air are the same as Option B.

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DM

M2(S)

(b) Air handling process control in PAU and AHU of Option

C
Fig. 3. System configuration and air handling process control of Option C - Fully Decoupled Option.

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4. Comparative analysis of the performance of typical air conditioning systems

The three typical system options are analyzed based on the same working conditions: a clean room with an area of 64.2 m2, and a volume of
162.5 m3. The required air change per hour (ACH) is 20, and the minimum outside air flow is 150 L/s.
The internal sensible heat ratio is 0.95 and fixed. The performance of the three system options is compared under different weather and load
conditions.
Fig. 4 shows the cooling and heating energy required in the three system options when the cooling load is 30 W/m2 and the outdoor dry bulb
temperature (Tdb) varies from 15 C to 35°C. Option A requires more cooling and heating.
The other two options, options B and C show the same performance since they require the same amount of cooling and heating energy under
these working conditions. When comparing the three systems, it is clear that there is a trade-off between heating and cooling in Option A.
Fig. 5 shows the cooling and heating energy when the cooling load changes and the outside temperature of the dry air bulb is set to 35° C.
As the internal cooling load required by option A increases, it remains at a high level with a slight increase, while the other two options
require lower cooling energy.
The heating energy required by Option A decreases with increasing cooling load. Options B and C require very limited or very low heating
energy and do not require heating when the cooling load is slightly higher. It can be seen that the difference between the energy consumptions
of Option A and the other two options the load increases. In other words, Options B and C apparently have an advantage over Option A under
partial load conditions.

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Theoretically, Option C reaches the limit of energy efficiency, because it completely decouples temperature and humidity control in the
system. It is recommended for new systems.
Although option B has the same performance with option C in the analyzed condition, its dehumidification capacity is limited to the amount
of fresh air flow.
Since the system configuration of Option B is almost the same as that of Option A, it is considered for modernization projects where the
system configuration of Option A is originally designed, according to the modernization project case reported in this document. Hereinafter,
the control method of option A is called the “reference method” and the control method of option B is called the “proposed method”.

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XXVI.- UMAS SYSTEMS CONFIGURATIONS FOR DIFFERENT PHARMACEUTICAL ROOM APPLICATIONS

GRADES A,BC AND D

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1.0.- ANALYSIS SCHEME

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The following diagram shows a methods
Laboratory pharmacist with carefully specified and validated.
approximately eight rooms, the steps to
Sterility or other quality aspects should
follow are shown below:
not be limited to the last manufacturing
Step 1 step or the control of the final product.
Determine the leakage flow rates of • Class A (high risk)
each room based on each of the doors:
The local area for high-risk work
Qf1 = Af1 * root ( P1 – P2 ) * 840 *3.6 processes, such as filling area, covered
Qf1 = Af1 * (P1 – P2) * Cte containers, open jars and bottles, aseptic
compounding manufacturing.
Then you have:
Qf2 = Bf2 * *(P2 – P3) * Cte Such conditions are usually guaranteed by
a laminar air flow system. Laminar
Qf3 = Bf3 * *(P3 – P4) * Cte
airflow systems must ensure a uniform
Qfn =Afn * *( Pn- P n+1 ) *Cte flow rate of 0.36 0.54 m/s (recommended
value) in the workplace. Maintenance of
Step 2 laminarity must be checked and validated.
Flow balances must be carried out by Directional airflow and lower velocities
zones, the following nomenclature will be can be used in closed isolations.
used:
V = Volume m3
P = Room pressure (Pascals)
Class = Because it is a pharmaceutical
laboratory, it is classified by GMps as
grade A, B, C and D.
Clean room classes A (high risk) to D are
valid for the production of sterile
pharmaceutical products in clean rooms.
There are special requirements for the
manufacture of sterile products, in order to
maintain the risk of contamination.
With microorganisms, particles and
pyrogens at a minimum, much depends on
skill, training and behavior of the
staff
involved. Quality assurance is of
particular importance here and production
must take place in agreement with

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Step 3
• Class B
The injection and extraction flow rates of
For aseptic preparation and filling; This is the Umas must be identified, by the room
the background of the environment for a classifications in:
class A zone.

• Classes C and D
Clean areas for less critical cases in the
production of sterile products.
I = equivalent to injection or supply of air,
generally obtained by hourly renewals or
by Thermal Load (m3/h)
E = Expulsion, encompasses general air
extraction, bathroom extraction, dust
extraction or air return (m3/h)
a.- Room 1
I1 = QF1 + E 1

E1 = I1 – QF1

Assuming that the greatest flow is due

to hourly renewals:
I1 = r/h (1) * V1

E1 = r/h(1) *V1 - Af 1 * (P1-P2)*Cte

b.- Lock 1
qf1 + I2 = qf2 + E2

E2 = I2 – ( qf1 – qf2)

c.- Room 2
qf2 + I3 = qf3 + E3

E3 = I3 – (qf2 – qf3)

Finally, it can be estimated

mathematically
In = In – ( (qf n-1) – (qf n) )

In this way, it can be taken to an Excel

spreadsheet.

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ROOM ENGINEERING DESIGN 1
WHITE 1
FOREWORD 4
INTRODUCTION 23
II.- INTERNATIONAL STANDARDS FOR CLEAN ROOMS 54
INTRODUCTION 54
Environmental factors of other types 56
III.- THE DESIGN OF CLEAN ROOMS FOR THE 70
MICROELECTRONICS INDUSTRY 70
IV THE DESIGN OF CLEAN ROOMS FOR INDUSTRY 87
PHARMACEUTICAL 87
V.-INDUSTRY VALIDATION AND QUALIFICATION119
PHARMACEUTICAL 119
ALL ROOM WITHOUT BEFORE ROOM 272
Supply/Exhaust Tracking Pairs 279
Supply/Exhaust Tracking Pairs 283
Supply/Exhaust Tracking Pairs 284
Examples of flows inside a pavilion 293
Resolution 298
Resolution 299
• AHU 03 injection (grade C and D)
• Rooms withoutClassification I uma 03 = r/h(5) * V5+ r/h(6)*V6 + r/h(7)*V7
+r/h(8)*V8
For our case
E uma 03 = ( I5 – ( qf4 – qf5) ) + ( I6 – ( qf5 –
AHU 01 injection (grade A) qf6) ) + (I7 – ( qf6-qf7) ) +(I8 – ( qf7-qf8) )+
+(I9 – ( qf8-qf9 )
I I uma 01 = r/h (1) V1 o

I uma 01 = QTS1 / ( 1-f)* dA * cpa * Dt air

E uma 01 = I1 – QF1

AHU 02 injection (grade B)

I uma 02 = r/h(2) * V2+ r/h(3)*V3 + r/h(4)*V4 I
or by thermal load

E uma 02 = ( I2 – ( qf1 – qf2) ) + ( I3 – ( qf2 –

qf3) ) + (I4 – (qf3-qf4))

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Having reviewed the above, a general represents the cleanliness of the room air.
formula for this would be: The challenge is how to configure an
HVAC system when the airflow rate
For UMAS environment type A, B and C
required by dilution is significantly
Injection flow rate UMA = I n = max ( Vi thermal load ; VI r/h)
higher than that required by the loads.
Expulsion flow rate UMA = E n = ( I n - ( qf n - qf n-1) of heating and
refrigeration.
Depending on the intensity of dilution, a
Step 4, Choose the UMA system clean class cleanroom typically requires a
configuration. higher airflow rate (cfm [L/s]), which can
also be calculated in air changes per hour
Savings in energy efficiency in AHU
(ACH, ach) or in average room speed
configurations
(fpm om / s). For example, buildings
Within the recommendations established commercial may have a “flow and cooling
by ASHRAE, there are four configurations rate” at 250–600 cfm (120–280 L/s) per
of units ton, an ISO Class 7 clean room may have
handlers used in clean rooms, which are a ratio of 2500 cfm (1200 L/s) per ton, and
Type 1, Type 2A, Type 2B and Type 3, an ISO Class 3 clean room may require
each one is applied with the objective of 25,000 cfm (12000 L/s) per ton. A typical
minimizing the size of the equipment. AHU is

The 100% outside air flow configuration

is only used in special Local Government
applications, for example in Chile, but in
Europe and the United States, it is normal
to use recirculation in surgical wards.
HVAC system configurations for general
purpose commercial or industrial
buildings are designed primarily to meet
the heating and cooling loads of the
interior space, or more specifically to
achieve the temperature and humidity
requirements of the space. However, for
clean room installations, the HVAC
configuration must be prepared in a way
that not only meets the heating and
cooling loads, but also meets the space air
cleanliness requirements with the same
HVAC system. Air cleaning has
traditionally been performed by using high
airflow rates to dilute the concentration of
particles in the air of a clean room, which

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It is commonly designed and MU : Makeup Unit: Tertiary Manager
manufactured at around 400 cfm (200 L/s)
per ton, which can be stretched to a FFUs : Fan-Filter- Units: Fan Filter Unit
possible range of 300–600 cfm (140–280
L/s) per ton. Therefore, it is clear that a
single AHU system in the later cases (ISO
7 and 3 clean rooms) is not capable of
achieving the dilution and cooling
objectives.
Cleanroom design engineers often use
multiple units of measure and units of
measure to handle this challenge based on
cleaning classes. Figures A through D
illustrate typical HVAC configurations of
primary AHU, primary RFU with
secondary AHU, primary fan filter units
(FFU) with secondary AHU, and primary
RFU with secondary AHU and tertiary
configuration AHU.
Table 1 provides a general selection guide
for choosing the cleanroom HVAC system
configurations shown in Figures A
through D. Engineers can first calculate
the air flow rate required to meet the
heating/cooling load and then calculate the
air flow rate required to achieve air
cleaning, then simply use the flow ratio to
determine which configuration is the most
suitable for the design objectives.
Ratio = Flow R/h / Flow QTs

In simple terms, according to the value of

the previous relationship, it is the
recommended type of configuration.
Some definitions :
RFU : Recirculation fan unit:
Recirculation fan unit
AHU : Air handling unit: Air handling
unit

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TABLE 1

TYPICAL APPLICATIONS
Guy of ISO class Flow relationship between units Scheme type
HVAC configuration

Airflow amount
for
Room air
cleanliness
and total
cooling load
n/a
1 Simple AHU 9,8,7 AHU to meet
ACH and TO
refrigeration
requirements

2A Primary RFU and

7,6,54 - AHU
mainly to
secondary AHU
comply with
the flow rate of RFU greater than 4 Flow rate
cooling
of AHU
requirements
b
* RFU to meet
the ACH (or
average
speed )
requirement of
the room
•AHU mainly
2B Primary FFUs and
7,6,5,4 to comply with
Secondary AHU
the
cooling c
requirements
• FFU to meet
the ACH (or
average speed)
requirement of
the room

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TYPICAL APPLICATIONS

3 Primary RFU,
4,3,2 • The support
secondary AHU, and
tertiary unit ,1 AHU complies
support
requirements of Flow rate of RFU > 10
outside air, Flow rate of AHU “
pressurization or and

• AHU to meet
cooling
requirements

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Figure A

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Figure B

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Figure C

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Figure D

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How equipment is selected based on the It is important to highlight that the AHU
different types of configuration . Air Treatment Unit must only be able to
overcome the flow rate per sensitive
Type 1
thermal load and the RFU fan is designed
The Type 1 configuration is used where to overcome the flow rate per hourly
the flow ratio is 0.1 to 3.99. This means renewal.
that the only savings achieved come from
In order to reduce the static pressure
the mixing temperature that occurs
differences of the fan, it is recommended
between the return and
to only generate recirculation without
using metal ducts. It is advisable to only
the
use a plenum fan, the range of use for this
outside temperature.
configuration is between the ratio 4.0 to
But the size of the hot and cold battery is 9.99.
much smaller, because it requires cooling
and heating at more convenient Type 2B
temperatures. This configuration uses an AHU handling
This type of configuration is widely used unit, to absorb the sensitive Thermal Load
in ISO Type Classifications class 9, 8 of the room and the Fan Filter Units
7. That is, in AHU grade C (FFU), to move the flow required by the
and room for renovation purposes. Compared
d. to the previous configuration, it is much
more useful to reduce the electrical
In any case, it is much more profitable consumption of the sum of all the fans.
than using a handler with 100% outside They have a lower static loss.
air.
Type 2A
This configuration is widely used to avoid
sizing the cooling flow, with the
high
hour renewals. Therefore, the system is
divided into two parts, an AHU handler
unit, which must have a cooling power,
based on thermal load calculations. The
support fan, the flow rate required by the
room classification, for contaminant
dilution issues.
With this configuration, greater savings
are achieved than the Type 1
configuration.
This is intended for ISO class 7,6,5 and 4
room classifications.

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This is intended for ISO class 7,6,5 and 4 the cooling power required by the handler
room classifications. Especially in laminar unit. .
flow applications.
And finally, the RFU is used to move the
The only drawback is that this total flow required per hourly renewal.
configuration requires special mounting consequently, with the chillers and pumps
conditions and in relation to control of the variable flow system.
issues.
All the data is known and with that the
The space they occupy on the ceiling engine room can be designed.
makes their assembly very complicated, if
Step 6
the construction has not been carried out
for this type of assembly. Design the air duct network and the
hydraulic network if necessary.
It is not recommended to use direct
Type 3 expansion systems in the UMAS in
Configuration type 3 is the most complete particular and always use condensing
of all, but is designed for applications boilers
where hourly renewals exceed 150 R/h.
Step 7
Especially in ISO class 1, 2 and 3.
Elaborate a control system
The MU Tertiary Handler Unit is used
suitable for each of the configurations
only to lower the outside air temperature
shown, the following diagrams explain the
by a differential of 5°C. On the other
configuration 100% outside air, type 1,
hand, the AHU is used to manage the
type 2A
thermal load of the enclosure and obtain

Step 5
Obtain the selections of the cooling equipment, both AHU, MU and RFU,

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100% outside air configuration

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Configuration Type 1

eit
he
r-

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Type 2A Configuration

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XVII.- CONCLUSIONS
Introduction
Clean rooms are highly controlled environments where air quality is monitored to
ensure the extreme standards of cleanliness required for the manufacturing of
pharmaceutical, electronics and healthcare products. These strict standards typically
require high fresh air rates, extensive filtering, temperature and humidity control, all
of which result in increased energy use. Protection against uncontrolled entry of
external ambient air is achieved by creating a pressure differential between the clean
room and its surroundings. Contamination control is the primary consideration in
clean room design; However, the relationships between pollution control and airflow
are not well understood. Contaminants such as particles or microbes are mainly
introduced into clean rooms by people, although clean room processes can also
introduce contamination (Reinmüller, 2001).
During periods of inactivity or when no people are present, it is possible to reduce
airflow and maintain clean conditions. To design the clean room, the following
factors must be taken into account:
• Minimize clean space.
• Correct cleaning level.
• Optimize air exchange rate
• Optimize roof coverage
• Consider clean room protocol and cleaning class.
• Minimize pressure drop (airflow resistance)
• Consider the location of air handlers, close to the end use
• Provide adequate size and minimize duct length.
• Provide adequate space for low pressure drop air flow.

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• low speed preferably laminar
• Use of variable speed fans.
• Optimize pressurization
• Consider reducing airflow when unoccupied
• efficient components
• Fan design.
• Engine efficiency
• Differential pressure of HEPA filters ( ΔP )
• fan filter efficiency
• Electrical systems that feed air systems.
Cleanroom performance is defined by a set of complex interactions between airflow,
sources of contamination and heat, position of vents, exhausts and any objects that occupy
the space. Consequently, changes to any of these elements will potentially affect the
operation of the clean room and could invalidate aspects of the room design (Ljungqvist and
Reinmüller, 1997). In the pharmaceutical industry, airflow is the answer to many
contamination problems. There are four principles that apply to the control of airborne
microorganisms in clean rooms (Halls, 1994). These are:
• filtration
• Dilution
• unidirectional air flow
• air movement
These principles are examined below. This case study examines a clean room used for
aseptic filling. It is an EU GMP Grade B/ISO Class 7 room containing a microenvironment:
an EU GMP Grade A/ISO Class 5 clean area. The case study, the clean room considered in
this case study, is a room six meters wide

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and nine meters long. Inside the clean room is a unidirectional airflow cabinet, within which
aseptic operations take place. This is illustrated in Figure 1 below:

Figure 1: Clean room layout

The key design consideration for the clean room is the HVAC (Heating, Ventilation and Air
Conditioning) system (Whyte, 2001). For this, airflow and air changes must be controlled,
and air temperature and humidity must be maintained at appropriate levels. Additionally,
the air must be filtered, and for this, the clean room requires appropriate HEPA (high-
efficiency particulate air) systems. The HVAC system works on the basis of mechanical
ventilation. An example of the air supply is illustrated in Figure 2 below:

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Figure 2: Typical Vent Air Supply Temperature and Humidity

Temperature and humidity

A design consideration for air includes temperature and humidity control. High
temperatures and humid environments can encourage microbial growth, where
microorganisms are deposited from the airstream onto surfaces. These parameters are
controlled through HVAC systems. Air conditioning systems normally have two preheating
batteries. The first battery recovers waste heat from the chillers, while the second
supplements this as needed, followed by an aerosol humidifier and finally a cooling battery.
Heating and cooling batteries are used for temperature control only.

Filtration

Filtration eliminates microorganisms. In clean rooms, this is achieved through HEPA filters,
which are designed to remove up to 99.997% of particles from the air. HEPA filters are
protected from blocking by pre-filters, which remove up to approximately 90% of particles
from the air. Therefore, if the air contains approximately 3 x 10 8 particles per m3, and there
is a prefilter and a HEPA filter, the prefilter removes a sufficient number of particles to
leave approximately 3 x 10 7 per m3 as a challenge for the HEPA filter . The terminal
HEPA filter will leave approximately 10 3 per m3 to enter the clean room. In the US

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GMP, this relatively low number, is within the limits of Grade A/ISO Class 5 and Grade
B/ISO Class 7 "at rest" (Annex 1.4). In fact, most pharmaceutical air treatment systems
recirculate up to 80% of the air supplied to clean rooms. Therefore, the initial challenge for
HEPA filters is probably only 10 6 particles per m3. Therefore, in practice, no more than 3 x
10 2 particles per m3 are normally supplied to pharmaceutical clean rooms. This level is
further within the limits of Grade A/ISO Class 5 and Grade B/ISO Class 7 “at rest” in the
EU GMP (Annex 1.4).

A typical HEPA filter installation looks like this:

Figure 3: HEPA filter dilution

Particles accumulate in closed spaces where there is no ventilation. Ventilation is the

process by which particles generated in clean rooms (in addition to those passed
through filters) are carried away, and particles left in the room will be diluted with
new "clean" air. The minimum expected ventilation rate in pharmaceutical clean
rooms is 20 air changes per hour (up to double the modern requirement and up to 75
for a changing room). With 20 air changes per hour, the air in a clean room is
replaced at least every three minutes. In comparison, an air-conditioned office

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Standard might have only two or three air changes per hour. Although 20 air
changes are the minimum accepted standard, air change rate recommendations were
developed decades ago with little scientific research to support them. The
recommended design ranges for an ISO Class 5 clean area in terms of air change
rates are 250 to 700 air changes per hour. Recirculation air change rates are an
important factor in determining fan and motor sizing for a recirculation air handling
system. Air treatment size and air path design directly affect the capital costs and
configuration of a building. When evaluating airflow and air supply requirements,
airflow modeling is carried out during the design stage. The key information gleaned
from such modeling relates to establishing appropriate air change rates. Such
modeling allows the performance of the cleanroom environment to be assessed prior
to construction and therefore changes to the cleanroom design to be made. The
standard modeling approach is computational fluid dynamics (CFD).

Figura 4: Illustration of air movement: UDAF (laminar flow) unit within a turbulent
flow clean room

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The airflow is examined through airflow visualization mapping, by which smoke is
generated, and the behavior of the smoke is studied and then captured on a video camera.
With clean room, above the UDAF, air is extracted from the room through high level
returns. The air is then filtered and supplied back to the room through HEPA filters. Careful
consideration should be given to the equipment and other obstacles in the room. When air
hits an object, it can deposit any contamination in the air, or where air is trapped, then dead
air spots can develop.
An example of an airflow display is illustrated below:

Figura 5: An example of airflow visualization (turbulent flow)

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Microenvironments or minienvironments
Inside the clean room there is a UDAF unit. A UDAF is classified as an environment. This
is a localized environment created by an enclosure to isolate a product or process from the
surrounding environment. The advantages in using an environment include the following:
• Small environments can create better contamination control and process integration.
• Small environments can maintain better contamination control through better pressure
difference control or by using unidirectional air flows.
• Mini environments can potentially reduce energy costs.
Directional airflow
Directional airflow is essential for clean rooms. To illustrate this, imagine there is a room
full of "clean" air. Now imagine that staff have free access to this room from a surrounding
area containing normal ambient air. If this is the case, less clean air will enter the clean
room as staff access it. To prevent this in pharmaceutical manufacturing, systems are
designed to prevent "dirty" air from entering the clean room, ensuring there is always a flow
of air out. The way "dirty" air is prevented from entering the clean room is by ensuring a
very high rate of air delivery to the clean room, keeping it at a higher pressure than its
surroundings. If there is contact with "outside" air, any mixing of the two types of air takes
place outside the clean room, because the direction of air flow is from the clean area to the
dirty area. This directional airflow is measured and controlled through pressure differentials.
Therefore, air will always move from an area where it is at high pressure to one where there
is low pressure (this is due to the Law of Physics). Particles and microorganisms cannot
"swim upstream" against a directional air flow.
To prevent pressure from being lost too quickly, air locks are placed over the access and
exit doors of clean rooms. An example of the "pressure differential" cascade is as follows:

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Figure 6: Pressure Cascade

Environmental monitoring
With critical air control parameters established within the clean room and physical
monitoring established to ensure the HVAC system is operating as designed, the
clean room should be subject to environmental monitoring to demonstrate whether
the room remains under control (ISO 14.644 -1). Monitoring consists of:
• Particle monitoring
• Viable monitoring
With particle monitoring, this is carried out using mobile optical particle counters or
particle counters linked to a facility monitoring system (FMS). Locations for
monitoring are selected by covering representative areas in the room or by orienting
monitoring towards the main activities within the room.

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(Moldenhauer, 2008). With the clean room examined in this case study (Figure 1),
monitoring has been targeted towards the highest risk areas (Sandle, 2011b). The
rationale for the locations for monitoring is as follows:
With viable monitoring, monitoring is designed to ensure that critical activities and
areas are evaluated. Monitoring locations remain the same between monitoring
sessions. It is not practice to vary monitoring locations. By keeping locations
consistent, trends over time can be more easily assessed. The draft guidance for ISO
14698-1 (“Clean rooms and associated controlled environments – Biocontamination
control, Part 1: General principles”) recommends that locations used for
environmental monitoring be determined, reasoned and justified. To determine
monitoring locations, representative locations can be selected or a risk assessment
approach can be adopted. It is more typical to take the risk-based approach. Here,
each location receives a risk rating (high, medium or low). This is a qualitative
assessment based on proximity to critical area (such as exposed products or vials)
and taking into account the ease of transfer of any contamination to products, vials
or other critical areas.

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APPLICATION GUIDE INFORMATION
TUTORIAL VIDEOS
Below are a series of video tutorials
https://www.youtube.com/watch?v=ttzmmMAQT2o&t=156s
https://www.youtube.com/watch?v=jQGdRX645Qg
https://www.youtube.com/watch?v=oXUA2zBuvW0
https://www.youtube.com/watch?v=msuj_zXl9Jc&t=1890s
https://www.youtube.com/watch?v=GuiVoQINSXQ
https://www.youtube.com/watch?v=zD647uB7y-w&t=34s
https://www.youtube.com/watch?v=PmwE2Hy1Nuo&t=962s
SELECTION SOFTWARE
https://1drv.ms/x/s!AqH6JOjm_JybgYJ84p6NH0PFdVDFCw?e=6wIzsy

EXERCISE ON FLUID MECHANICS APPLICATIONS (CHAP.8)

https://1drv.ms/x/s!AqH6JOjm_Jyb_QdD94Wu_gBwf-GR?e=iPsa1W

EXERCISES ON APPLICATIONS OF CLEAN ROOMS AND SURGICAL

PAVILIONS
https://1drv.ms/u/s!AqH6JOjm_JybgYMnct-X14tNQ9QGJg?e=2rP1jY

ANALYSIS OF HOSPITAL STANDARDS

https://1drv.ms/b/s!AqH6JOjm_JybgYM5BmFH75VO8tXdyw?e=bMCvxe

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AUTHOR
INFORMATION
Celso Angelo Tapia Sanchez

Rut : 10,544,078-2

Address : Colon 7000. Dep. C-102, the Condes Santiago

Date of birth: September 15 , 1968

0: cell: 9 41353221
0: [email protected]
Profile and Competencies

Mechanical Civil Engineer from the Pontifical Catholic University of Valparaiso, Professional Energy
Manager (PEM) USA, Master in Energy Efficiency of Buildings (Spain). Master in Environment and
Sustainable Management ( Spain), more than 24 years of experience in commercial and industrial facilities
systems. Of which around 15 years in Works, projects, consultancies, technical inspection in National
Hospitals and Clinics , in addition to having a strong orientation to Energy Efficiency Projects in air
conditioning, Clean Rooms, data Center, solar energy, health, electricity, currents weak, centralized control
and some residential photovoltaic projects.

Professional with great management of interpersonal relationships , ability to work as a team and form high-
performance teams , leadership, customer orientation, achievement orientation, great communication and
negotiation skills, proactivity, self-motivation and positive attitude.

Experience in Administration of large-scale Contracts , such as Solar Panel Plants, Hydroelectric Power
Plants in the past and now recently Ezequiel Gonzales Cortes Hospitals ( 52,000 m2), Curlcó Hospital Project
Phase ( 102,000 m2) and Gustavo Frike Hospital ( 92,000 m2), I have knowledge of ISO 9001, 14,001 and
50,001 quality standards.

In addition to managing the regulations specific to the specialties, such as UNE Standard, ASHRAE, ASME,
GMPs ( Good Manufacturing Practices ) , etc.

Public and private hospitals, and knowledge finished in Certifications of indoor air quality of surgical
pavilions , among which we can highlight the Mutual de Seguridad, Clínica de los Andes, Clínica and
Hospital de la Católica, Hospital de la Universidad de Chile, German Clinic of Santiago and Temuco, Naval
Hospital of Viña del Mar. Which has meant that I have to get certified in all the International Regulations of
the USA and Spain, both in Ashrae St 62.1, ISO Standard 14.644-1-2-3-4-5, UNE 1713 30-1, UNE 171530-2,
UNE 171,340, UNE 100012.

Including certifications in the US in fungi, bacteria, molds, VOCs , etc., in the field of energy efficiency I am
certified in 120 specialties ( Centralized Control, Pumps, Air Conditioning, boilers, etc.).

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Academic training

1986-1992 Mechanical Civil Engineer

Pontifical Catholic University of Valparaíso

Bachelor of Engineering Sciences PUCV

Extra academic training

1999 Postgraduate degree in environmental management Universidad Católica del Norte

2010 Diploma in Energy Management. Polytechnic University of Madrid Spain

2013 International Certification in air quality in Buildings. Univ. Polytechnic of Catalonia

(CPU)

2013 International Certification in Chemical Air Pollution in Indoor Spaces , (UPC}

2014 Certification Verification of air quality and Hygiene in HVAC systems

Hospitals and Clean Rooms (Segla España).

2014 Certificate Membership Indoor Air Quality Association USA.

2014 PEM ( Project Manager Energy) United States Energy Institute , certification in HVAC Systems and
Schneiders data Center .

2014 Master in Energy Efficiency of Buildings Spain Euroinnova Spain

2015 Master in Environment and Sustainable Management Euroinnova Spain

2015 Diploma in Operations Management UNAB

2016 UNAB Senior Management Diploma

2016 Master in Industrial Engineering Andrés Bello University

2016 BASIC MEP REVIT COURSE.

Digital Book of Clean Rooms. Prepared by Ph Celso Tapia Sánchez