PHARMACEUTICAL QUALITY

MANAGEMENT-I (614-T)

STANDARDIZATION OF
PHARMACEUTICALS
CHAPTER# 6, LECTURE-2
COURSE INCHARGE: Ms. Syeda Zainab
 OVERVIEW OF PREVIOUS LECTURE
Quality is the degree to which a set of inherent properties of a
product, system or process fulfills requirements specifically for
quality of drug substance and drug product.
Quality assurance” is a wide-ranging concept covering all
matters that individually or collectively influence the quality of a
product.
Good manufacturing practice is that part of quality assurance
which ensures that products are consistently produced and
controlled to the quality standards appropriate to their intended
use and as required by the marketing authorization.
Quality control is a part of quality management focused on
fulfilling quality requirements".
 OBJECTIVE OF TODAY’s LECTURE
Current Good Manufacturing Practices
General GMP guidelines for
pharmaceutical products
cGMP (Current Good Manufacturing
Practices)
 cGMP is current Good Manufacturing Practice.
 c in the cGMP stands for current and cGMP mean current good
manufacturing practices.
 c is always written in small letters and represents a continuous
improvement.
 cGMP is the current version of GMP or use of currently available
or recent techniques.
 The basic concept of GMP remains constant like Documentation
is the requirement of GMP and we have to prepare and maintain
a proper document record.
 cGMP is continuously changing with the development of new
techniques like documentation changes from papers to
electronic systems.
GENERAL GMP GUIDELINES
FOR PHARMACEUTICAL
PRODUCTS
 GENERAL GMP GUIDELINES FOR
PHARMACEUTICAL PRODUCTS
 Includes important aspects like:
 Personnel
 Premises
 Equipment
 Material
 Sanitation and hygiene
 Good practices in production
 Good practices in QC
 Validation
 Self-inspection and quality audit
 Documentation
PERSONNEL
 Qualified Personnel
 Experienced
 Sufficient Number
 Written job description
 Training should be regularly conducted by qualified individuals to
persons.
 Personnel should practice good sanitation and health habits.
 Personnel suffering from an infectious disease or having open
lesions on the exposed surface of the body should not engage in
activities that could result in compromising the quality of APIs or
products.
PERSONNEL
 For personnel suffering from infectious disease, their duties may
be delegated to designated deputies of a satisfactory
qualification level.
 The manufacturer should have an organization chart.
 All personnel should be aware of the principles of GMP that
affect them and receive initial and continuing training, including
hygiene instructions, relevant to their needs.
 All personnel should be motivated to support the establishment
and maintenance of high-quality standards.
 Steps should be taken to prevent unauthorized people from
entering production, storage and quality control areas. Personnel
who do not work in these areas should not use them as a
passageway.
PREMISES
 Premises must be located, designed, constructed, adapted, and
maintained to suit the operations to be carried out
 Design
 Minimize risks of errors
 Permit effective cleaning
 Permit effective maintenance
 Avoid cross-contamination, build-up of dirt and dust
 Maximum protection against entry of insects, birds and animals
 Separate facilities for other products such as some antibiotics,
hormones, cytotoxic substances.
 Finishing floors, walls, and Ceilings should be smooth,
impervious, hard-wearing, easy to clean
PREMISES
 Specific Areas
There should be defined areas or other control systems for the following
activities:
 Receipt, identification, sampling, and quarantine of incoming
materials, pending release or rejection;
 Quarantine before release or rejection of intermediates and APIs;
 Sampling of intermediates and APIs;
 Holding rejected materials before further disposition (e.g., return,
reprocessing or destruction)
 Storage of released materials;
 Production operations;
 Packaging and labelling operations; and
 Laboratory operations.
PREMISES
 Hygiene
 Eating, Drinking, Smoking should not be allowed in the
Production area.
 Other requirements
 Electrical supply, lighting, temperature, humidity and ventilation
should be appropriate
 Adequate, clean washing and toilet facilities should be provided for
personnel.
 Adequate ventilation, air filtration and exhaust systems should be
provided, where appropriate.
 Sewage, refuse, and other waste (e.g., solids, liquids, or gaseous by-
products from manufacturing) in and from buildings and the
immediate surrounding area should be disposed of in a safe, timely,
and sanitary manner.
EQUIPMENTS
EQUIPMENTS
Equipment must be located, designed, constructed,
adapted, and maintained to suit the operations to be
carried out.
Equipment should be installed in such a way as to
minimize any risk of error or of contamination.
Production equipment should be thoroughly cleaned on a
scheduled basis.
Should be made of non reactive material, such as High
grade of steel
EQUIPMENTS
 Equipment should be-
Calibrated.
Checked.
Labelled.
Sterilized (if required).
Accompanied with SOP.
MATERIALS
 RAW MATERIALS
 Should be purchased from approved sources.
 An Inventory should be maintained for Raw materials to be used
at any stage of manufacturing
 Records should be maintain.
 Must be checked by QC department on receipt .
 Should be labeled.
 Starting materials should be dispensed only by designated
persons, following a written procedure, to ensure that the
correct materials are accurately weighed or measured into clean
and properly labelled containers.
 Each dispensed material and its weight or volume should be
independently checked and the check recorded
RAW MATERIALS
 Labels should bear at least the following information:
 the designated name of the product and the internal code
reference where applicable;
 the batch number given by the supplier and, on receipt, the
control or batch number given by the manufacturer, if any,
documented so as to ensure traceability;
 the status of the contents (e.g. on quarantine, on test, released,
rejected, returned, recalled);
 where appropriate, an expiry date or a date beyond which
retesting is necessary.
RAW MATERIALS
PACKAGING MATERIALS
 The purchase, handling and control of primary and printed packaging
materials should be as for starting materials.
 They should be stored in secure conditions so as to exclude the
possibility of unauthorized access.
 Packaging materials should be issued for use only by designated
personnel following an approved and documented procedure.
 Each delivery or batch of printed or primary packaging material should
be given a specific reference number or identification mark.
 Outdated or obsolete primary packaging material or printed packaging
material should be destroyed and its disposal recorded.
 All products and packaging materials to be used should be checked on
delivery to the packaging department for quantity, identity and
conformity with the packaging instructions
SANITATION & HYGIENE
 A high level of sanitation and hygiene should be practiced in
every aspect of the manufacture of drug products.
 The scope of sanitation and hygiene covers
o personnel,
o premises,
o equipment and apparatus,
o production materials and containers,
o products for cleaning and disinfection,
o and anything that could become a source of contamination to
the product.
 Potential sources of contamination should be eliminated through
an integrated comprehensive programme of sanitation and
hygiene.
SANITATION & HYGIENE
 Practice good Hygiene
 Health examinations
 Written procedures and instructions –
o to wash hands before entering production areas
o gowning and de-gowning S.O.P.
o hygiene, health
o waste disposal
 Implementation and training of the employees in basic
sanitation
 Direct contact between product, raw materials and
operator should be avoided
SANITATION & HYGIENE
 Protection of product from contamination:
o Clean clothes appropriate to personnel activities
o Including hair covering (e.g. caps)
 Check change rooms/changing facilities
 Smoking, eating and drinking not allowed in production
areas, laboratories and storage areas
 No chewing (e.g. gum), or keeping food or drinks
allowed
 No plants kept inside these areas
 Rest and refreshment areas should be separate from
manufacturing and control areas
 GOOD PRACTICES IN PRODUCTION
PRODUCTION AND PROCESS OPERATIONS
 Must have and must follow clearly defined written procedures .
o Examples: – (Manufacturing) Work Instructions, SOPs, Testing
Procedures ,Quality Manual.
 Deviations must be recorded and justified
 Calculation of yield and reconciliation of quantities
 Operations on different products should not be carried out
simultaneously or consecutively in the same room or area unless
there is no risk of mix-up or cross- contamination.
 Equipment should be labelled
PRODUCTION AND PROCESS OPERATIONS
 Cleanliness of tanks, paddles, piping, probes etc
 Access to production premises should be restricted to authorized
personnel
 Sampling and testing of in-process materials and drug products.
 Appropriate Control of cross-contamination and bacterial
contamination during production
 Monitoring of process to make sure they are in control
 Line clearance
 Double checks
 Document activities
 Batch Record
 Log Books
PACKAGING AND LABELLING OPERATIONS
 Examination of packaging and labeling materials for suitability and
correctness before packaging operations, and documentation of
such examination in the batch production record.
 The name and batch number of the product being handled should
be displayed at each packaging station or line.
 Regular on-line control of the product during packaging should
include at least checks on:
o the general appearance of the packages;
o whether the packages are complete;
o whether the correct products and packaging materials are
used;
o whether any overprinting is correct; (e)the correct functioning
of line monitors.
PACKAGING AND LABELLING OPERATIONS
A representative sample of units
shall be collected at the completion
of finishing operations and shall be
visually examined for correct labeling.
Results of these examinations shall
be recorded in the batch production
records
GOOD PRACTICES IN QUALITY CONTROL
 GOOD PRACTICES IN QUALITY CONTROL

QUALITY CONTROL OPERATIONS

Quality control is the part of GMP concerned with
sampling, specifications and testing, and with the
organization, documentation and release procedures
Quality control is not confined to laboratory operations but
must be involved in all decisions concerning the quality of
the product.
The independence of quality control from production is
considered fundamental.
• Area of QC may be divided into chemical, instrumentation,
microbiological, biological.
 SUMMARY
 Current Good Manufacturing Practices
 General GMP guidelines for pharmaceutical products
 Personnel
 Premises
 Equipment
 Material
 Sanitation and hygiene
 Good practices in production
 Good practices in QC
 REFERENCES
EU Good Manufacturing Practice (GMP)
Guidelines, Volume 4 of “The rules governing
medicinal products in the European Union”
US FDA current Good Manufacturing Practice
(cGMP) for finished pharmaceuticals, 21 CFR,
210 and 211
WHO_Quality Assurance Pharm Vol 2