www.cleanrooms-ireland.

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Update on ISO Cleanroom

Standards 14644 & 14698
Conor Murray
Chairman - Irish Cleanroom Society
Head of Delegation for Ireland at ISO TC 209

Conor Murray Bio

Conor Murray, an Engineer by profession is an independent
Technical Expert on GMP Cleanrooms and Biosafety Labs
Conor is a founder member and Chairman of the Irish
Cleanroom Society, (ICS). Conor is a past Chairman of the
ICCCS, (International Confederation of Contamination
Control Societies) and currently Chairman of the ICEB,
(International Cleanroom Education Board)
Conor is Head of Delegation for Ireland representing the
NSAI at ISO TC 209 and is on WG 01 & WG 02
Conor is Convener of Sub Group 13, (Cleanrooms) on the
Health Care Standards Consultative (HCSC) committee
Conor's particular areas of expertise include Green and
Energy Efficient Modular Design, Lifecycle Sustainability,
Process Integration, RABS and Fast Track Clean
Build Construction

Presentation Content
Irish Cleanroom Society
ISO 14644 & 14698 Overview
ISO DIS 14644 -1 & -2:2011 WG 01
14698 -1 & -2:2003 WG 02

Irish Cleanroom Society

www.cleanrooms-ireland.ie

Irish Cleanroom Society

The Irish Cleanroom Society (ICS) is a not for profit
membership subscription based organisation formed in
1998 to represent cleanroom professionals in Ireland
The ICS is affiliated to the International Confederation of
Contamination Control Societies (ICCCS)
The primary focus is to promote best practice knowledge
and skills, understanding and harmonisation of
cleanroom and contamination control technology and
standards among users and professionals in Life
Sciences, Healthcare, Food, Microelectronics and
Micromanufacturing

ICS Objectives
Promote the development of cleanroom and
contamination control technologies throughout Ireland
Heighten the awareness of cleanroom and contamination
control technology among all users inc industry, educational,
institutional establishments, government bodies & the public
Assist in the standardisation and harmonisation of
cleanroom and contamination control
Organise seminars, exhibitions and peer to peer forum
workshops for the dissemination of knowledge & experience
gained in cleanroom and contamination control technology
Represent Ireland on the international stage

ICS & Education

Education and Training are at the core of ICS activities
The ICS has been a major contributor to the CTCB-I
(Cleanroom Testing and Certification Board International) since its inauguration in 2002 and
has provided nearly 20 Cleanroom Technology and
Testing courses with over 200 candidates from Ireland
and around the world
Since 2005 the ICS has helped lead the ICEB initiative of
the ICCCS to accredit, harmonise & licence cleanroom
training courses across national cleanroom societies with
the emphasis on certification through examination

ICS on the International Stage

The ICS represents Ireland at international level on ISO
TC 209 for cleanroom standarisation where Ireland is a
voting member
Conor Murray is Head of Delegation for Ireland & a
subject matter expert on the TC & a number of WGs
The ICS is an active member of the ICCCS, International
Confederation of Contamination Control Societies
ICS an active member of the International Cleanroom
Education Board (ICEB)
Ireland hosted the 21st biennial symposium in 2008

ICS Linkages in Ireland

The National Standards Authority of Ireland are the
Irish representative body in CEN and ISO Standards
organisations
Their Health Care Standards Consultative (HCSC)
committee has established a subcommittee, SC 13
concerning cleanrooms
The Irish Cleanroom Society play a leading part in
this. Conor Murray is Convener of SC 13 and
represents Ireland at ISO TC 209 concerning
Cleanrooms and associated controlled environments
The ICS works closely with FAS on cleanroom training
and up skilling

10

ICS Initiatives - Education

International Cleanroom Education Board (ICEB)
Part of International Confederation of Contamination
Control Societies (ICCCS)
Set up in 2007
ICS playing a significant leadership role internationally
CTCB-I initiative set up with S2C2 in 2001
CTCB-I now includes Scandinavian Countries (R3) of
Norway, Sweden and Denmark & The Netherlands
(VCCN)
Capturing interest from the US, Baltic, Far East, South
Africa, Egypt

11

ICS Initiatives - Education

5 ICEB accredited courses
Cleanroom Testing CTCB-I (03 250)
Advanced Cleanroom Technology - CTCBi
(05 100)
Airborne Particle Counting CTCB-I (08 20)
Introduction to Cleanrooms - SSE (09 50)
Cleanroom Cleaning - FLO (09 40)

12

ICS & International Associations

13

ICS Initiatives - ISO TC 209

Participation in Working Groups in TC 209 on
cleanroom standards
WG 01 - revision of ISO 14644 - 1 & 2 Classification by
total airborne particles
WG 02 - revision of ISO 14698 Biocontamination

(Irish Biocontamination Mirror Group)

WG 03 - revision on ISO 1464 - 3 Metrology

14

ICS & ISO TC 209

15

ISO 14644 & 14698

- Overview

16

ISO 14644 & 14698 Standards

ISO Document

Title

Status

ISO-14644-1

Classification of Air Cleanliness - 1999

WG01

ISO-14644-2

Testing for Continued Compliance to -1 - 1999

WG01

ISO-14644-3

Test Methods & Metrology - 2005

WG03

ISO-14644-4

Design, Construction & Start Up

2001

ISO-14644-5

Cleanroom Operations

2004

ISO-14644-6

Terminology - 2007

SG06

ISO-14644-7

Separative Enclosures

2004

ISO-14644-8

Classification of Airborne Molecular Contamination - 2007

WG08

ISO-14698-1

Biocontamination: General Principles - 2003

WG02

ISO-14698-2

Biocontamination: Evaln & Interpretation of Data - 2003

WG02

17

ISO 14644 & 14698 Standards

ISO Document

Title

Status

ISO-14644-1

Classification of Air Cleanliness - 1999

WG01

ISO-14644-2

Testing for Continued Compliance to -1 - 1999

WG01

ISO-14644-3

Test Methods & Metrology - 2005

WG03

ISO-14644-4

Design, Construction & Start Up

2001

ISO-14644-5

Cleanroom Operations

2004

ISO-14644-6

Terminology - 2007

SG06

ISO-14644-7

Separative Enclosures

2004

ISO-14644-8

Classification of Airborne Molecular Contamination - 2007

WG08

ISO-14698-1

Biocontamination: General Principles - 2003

WG02

ISO-14698-2

Biocontamination:
& Interpretation
of Data
- 2003
2
new standardsEvaln
under
development
to cover
SCP via WG9 & -9 and SCC via WG8 & -10

WG02

18

ISO 14644 TD Proposal

Deals with the role of an ISO 14644 Technical
Document as an Overview, Introduction,
Explanation and Context in dealing with
updates and changes to ISO 14644 & ISO
14698 re airborne and surface cleanliness
classification by total particles, viable, chemical
and nano particles
Approved in Milan 2011- to be presented to ISO
TC 209 in Zurich, September 2012

19

ISO 14644 Issues

Historical development and focus on Airborne
Particles
New standards deal with surfaces, chemicals
and nanoparticles
Need backward compatibility
Where to put the history, context, perspective,
objectives, usage & application notes

20

ISO 14644 Issues

Existing definition of cleanroom relates to
airborne particles ie total particle
concentration in air
New definition needs to address the
concept of a controlled environment where
the control could be total particles, viables or
chemicals in air and/or on a surface

21

ISO 14664/ 14698 Structure

Total
Particles

Viable
Biocontamination

Chemical

Nanoparticles

Airborne

ACP

ACV

ACC

ACN ?

Surface

SCP

SCV

SCC

SCN ?

Total
Particles

Viable
Biocontamination
14698-1
14698-2
14698-1
14698-2

Chemical

Nanoparticles

14644-8

14644-?

14644-10

14644-?

Airborne

14644-1

Surface

14644-9

22

ISO Support Standards

Standard

Existing
Testing for Ongoing Compliance to
14644-1

New
Testing for Ongoing
Compliance to 14644-1

14644-3

Test Methods

Supporting Test Methods

14644-4

Design, Construction & Startup

Design, Construction &

Startup

14644-5

Operations

Operations

14644-6

Terminology

Terminology

14644-7

Separative Devices

Separative Devices

14644-2

14698-?

Supporting ?

23

ISO DIS 14644 -1 & - 2

24

ISO DIS 14644 -1 & -2

Apply good science and statistics
Remove confusion and inconsistencies
Simplify terms
Use more precision
Use a Table for Classification instead of the
universal formula

25

ISO DIS 14644 -1

Copenhagen
DIS Vote May 11 unanimous but > 200
comments
Differences over no of samples for confidence level
and maximum area to determine classification
Differences over method of selection of sample
locations, application of statistics random selection
Differences over treatment of 5 micron particles
Differences over normative use of ISO 21501-4

26

ISO DIS 14644 -2

Copenhagen
DIS Vote May 11 unanimous
Decided to remove classification and keep to
Periodic Testing & Monitoring
Agreed that Classification and Periodic Testing are
NOT the same amount of testing
Differences over inclusion of Differential Pressure

27

ISO 14698 -1 & -2:2003

- Biocontamination WG 02

28

ISO 14698 -1 & -2: 2003

29

ISO 14698 Issues

ISO 14698 not in line with ISO 14644
No Tables of Classification
Not up to date with Risk Assessment & Risk
Management techniques (eg ICH Q9 QRM)
No Check Lists of Things to Consider
Not up to date with technology advances in
Rapid Microbiological Methods (RMM) &
Instantaneous Microbiological Detection (IMD)
(eg ATP, Bioluminescence)

30

ISO 14698 Issues

Cannot Monitor a process into Control
Not enough clarity on differences, issues and
guidance on Aseptic vs Non Sterile applications
Not enough guidance on Airborne vs Surface
biocontamination risks and control
Overall seen as not easy to read & use

31

ISO TC 209
Preliminary Work Items WG02
IS O/T C 2 09 N 187

Re so lution s from ISO/ TC 20 9 M ee ting 9-10 No v em be r 2007

R sol utio ns de l' IS O / T C 20 9 (1 9 m e ru nion, 9 et 1 0 Nov e mbr e 2 00 7)

Re so lution 1
IS O/T C 209 reso lv es th at W G 2 co m m ence s w ork on thes e tw o doc um ents :
a. C lassi fication of airb orne bi oc onta m inatio n in c leanroo m s, inc luding m etho ds of
m eas ure m ent a nd their v alida tion.
b. C lassi fication of s urf ace bioc ontam inatio n in c le anroo m s, including m ethod s of
m eas ure m ent a nd their v alida tion.
At t he appropriat e time during the de velopm ent of these docu m ents, t he position of IS O 14 698
Parts 1 a nd 2 sh ould b e cons idered, as w ell as a Risk M anage m ent St andard.
(All in fa vor)

32

ISO Standard Principles

ISO Standards are NOT industry specific Birds Eye view from 25,000 feet
Normative (Must do) & Informative (Should do)
Based on good science with clear and
independent guidance
Short & concise, easy to read & use
Check Lists, flow charts, suggested methods,
options on best practice methods, choices,
examples.

33

ISO Working Group Principles

Working Group is a team of international experts
nominated by each member country
Terms of reference set by TC 209
Duration varies but typically 2 - 5 years
Act as Subject Matter Experts (SMEs) in their
field

34

ISO Working Group Principles

Capture best science and international expertise

Get all the toys on the table and play with them
Everything on the table
Open dialogue encouraged until the end
Let good science prevail

35

ISO 14698 Challenges

- Limitations of Quantitation
Current measurement technologies limited to
orders of magnitude resolution, especially in low
density populations
Species recovered using these technologies
limited due to incubation methodology (inc
media, temperature, pH, aerobic/anerobic, etc.)
Environmental microbiologists recent research
indicate that some species are inter-dependant
& one species will not culture successfully
without the presence of the other

36

ISO 14698 Challenges

- Diversity of People
People are the greatest source of
biocontamination
Unpredictability and uncertainty of Human
behaviour
80% of the species found in the human upper
respiratory tract cannot be recovered

37

ISO 14698 Challenges

- Issues in clean spaces
Below limit of resolution for current
technologies
i.e. 1 cfu recovered may be indicative of 1cfu
or perhaps >10cfu, impossible to accurately
and repeatably determine
Risk of false positives high due to likelihood of
accidental contamination during collection and
incubation

38

ISO 14698 Challenges

- Process/ Application Specific
In some cases, all species are considered
harmful
In some cases there is background counts of
cfu of species considered normal and nonharmful
In some cases, some species are considered
objectionable and are not tolerated at all

39

Aseptic Processing
- 5m Particles & EU GMPs
In Grade A and B zones, the monitoring of the
5.0 m particle concentration count takes on
a particular significance as it is an important
diagnostic tool for early detection of failure.
... consecutive or regular counting of low
levels (of 5.0 m) is an indicator of a possible
contamination event and should be
investigated.
Particles 5.0 m could be skin particles
carrying biocontamination

40

ISO 14698
- Proposed New Structure

41

New ISO 14698 Flowchart

42

New ISO 14698 Flowchart

43

New ISO 14698 Flowchart

44

Proposed New ISO 14698 -1

- Establishing Control
Risk Analysis/ Assessment
Risk Management
Establishing (Risk) Control

45

ISO 14698
- Establishing Control Step 1
Identify typical, non-harmful species
- typical in cleanroom
- not harmful to product or
application/customer
Identify objectionable species
- atypical in cleanroom
- harmful to product and/or harmful to
customer

46

ISO 14698
-Establishing Control Step 2
For normal, non-harmful:
- establish typical background counts, e.g.
<10cfu
- establish acceptable incidence of higher
than normal counts, where maximum limit is
defined
- anything above incidence rate or maximum
triggers investigation

47

ISO 14698
- Establishing Control Step 3
For Objectionable:
- establish acceptable incidence, including
maximum number process will tolerate
- anything above incidence rate or maximum
triggers investigation

48

ISO 14698
- Establishing Control Step 4

Classify your process/cleanroom:

Normal, non-harmful
- species
- by background counts
- by acceptable incidence of higher than
normal (maximum limit is defined)
Objectionable
- establish acceptable incidence, including
maximum number process will tolerate per
incidence

49

ISO 14698
- Airborne Classification
Class

*Airborne limit In
Operation
cfu/m3

ACVx 1
ACVx 2
ACVx 3
ACVx 4

<10#
< 100
< 1000
< 10000

1. *Combined with an appropriate incidence rate

2. x is the species of interest
3. # still under discussion (added error by air collection
method)
4. Intermediate classes are permitted, eg SVCx 3,5

50

ISO 14698
- Surface Classification
Surface
Contamination
Class (SCV)

*Surface Count
Limit (CFU)

Sampled Area

SVCx 1

<4

1 m2

SVCx 2

<40

1 m2

SVC x3

<40

1 cm2

SVCx 4

<300

1 cm2

SVC x5

>300

1 cm2

1. Numbersareopenforfurtherdiscussion
2. *Combinedwithanappropriateincidencerate
3. x isthespeciesofinterest
4. Intermediateclassesarepermitted,egSVCx3,5

51

ISO 14698
- WG 02
Next meeting Zurich Sept 2012
New Work Item Proposal (NWIP)
Formal Vote required for approval
ISO timetable of CD, DIS FDIS, & IS
over 3 years

52

Thank You for Your Attention