Regulatory Standards of GMP

1. The Language of Quality
for Pharmaceuticals
Dr. Md. Shah Amran
Professor
Molecular Pharmacol. & Herbal Drug Res. Lab
Department of Pharmaceutical Chemistry
Faculty of Pharmacy, University of Dhaka
-Quality, QC, QA
-GMP
-ISO
-TQM
-Validation
-ICH

2. GMP
GMP is a government regulation
Section 15 of Drugs (Control)
Ordinance of 1982
Mandatory for Pharma Industry
After the end of this Chapter we shall learn ….
What is GMP?
Why do we need GMP?
Parameters of GMP
GMP life cycle

3. 1. What Is Good Manufacturing Practice (GMP)?
1. GMP is a government regulation all over the world.
2. WHO defines the term ‘manufacturing’ as “all operations
involved in the production of a drug that include processing,
compounding, formulating, filling, packaging and labeling”.
3. According to WHO, “Manufacturing practices that result in
(i) good quality finished products, and at the same time has
adequate considerations for (ii) safety of the employees, is
called Good Manufacturing Practice”.
4. GMP refers to the Good Manufacturing Practice Regulations
promulgated by the US Food and Drug Administration under the
authority of the Federal Food, Drug and Cosmetic Act. These regulations
require that manufacturers, processors, and packagers of drugs, medical
devices, some food, and blood and service providers take proactive steps
to ensure that their products are safe, pure, and effective.
GMP regulations require a quality approach to manufacturing, enabling
companies to minimize or eliminate contamination, mix-ups, and errors.

4. Failure of industries to comply with GMP regulations can result in very
serious consequences including recall, seizure, fines, and jail terms.
5. GMP regulations address issues including recordkeeping, personnel
qualifications, sanitation, cleanliness, equipment verification, process
validation, and complaint handling. Most GMP requirements are very
general and open-ended, allowing each manufacturer to decide
individually how to implement the necessary controls. This provides
much flexibility, but also requires that the manufacturer interpret the
requirements in a manner which makes sense for each individual
business.
6. GMP is sometimes referred to as "cGMP". The "c" stands for
"current," reminding manufacturers that they must employ technologies
and systems which are up-to-date in order to comply with the regulation.
Systems and equipment used to prevent contamination, mix-ups, and
errors, which may have been "top-of-the-line" 20 years ago, may be less
than adequate by today's standards.
7. GMP is a good business tool which helps to refine both compliance
and performance at company level.

5. 2. Why do we need to study and obey the rules of
GMP?
GMP is a government regulation and the manufacturers of
medicines, food and cosmetics must abide by this
regulation.
Mainly three reasons:
1. To follow the drug Law
Section 15 of Drug control ordinance of 1982 and its
subsequent amendments which states that:
15. Good practices in the manufacturing and quality control
of drugs-
(i) Every manufacturer of drugs shall follow the good
practices in the manufacture and quality control of drugs
recommended by the World Health Organization.

6. (ii) If any manufacturer does not follow such good practices
his manufacturing license may be cancelled or suspended.
2. To follow the WHO guideline of Certification Scheme on
the Quality
The first 1969-First WHO Certification Scheme on the Quality
of Pharmaceutical Products Moving in International
Commerce.
3. To comply with foreign regulatory agencies for export of
drugs
Regulation of FDA, TGA, MHRA, regulatory affairs of the
related country are to be obeyed which is mandatory.

7. 3. Parameters of GMP
There are seventeen parameters or standards of GMP. A
product or service oriented company needs to obey maximum
number of standards and they have the opportunity to modify
these standards according to their needs as most GMP
requirements are very general and open-ended. There are 17
parameters of GMP. These are -
1. Quality Assurance
2. GMP for pharmaceutical products
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract Manufacturing and analysis
8. Self inspection and quality audits

8. 9. Personnel
10. Training
11. Personal hygiene
12. Premises
13. Equipment
14. Materials
15. Documentation
16. Good practices in production
17. Good practices in quality control

9. Ten Principles of GMP for Industrial Operations
1. Writing step by step operating procedures and work
instructions
2. Following written procedures and instructions
3. Documenting the works
4. Validating the works
5. Designing and constructing facilities and equipment
6. Maintaining Facilities and Equipment
7. Defining, developing and demonstrating job
competence
8. Protection against contamination
9. Controlling components and product related
processes
10. Conducting planned and periodic Audits

10. What is Quality Assurance ?
Quality assurance is a wide-ranging concept covering all
matters that individually or collectively influence the quality
of a product.
It is the totality of the arrangements made with the object of
ensuring that pharmaceutical products are of the quality
required for their intended use. QA therefore includes GMP
and other factors such as product design and development
QA=Product design + GMP + QC + quality goal activities
Criteria of Quality
Safety
Potency
Efficacy
Stability
Acceptability
Regulatory compliance

11. How was the concept of Quality Assurance
developed ?
A lot of factors are involved as the guiding force behind the
development of the concept of quality assurance. The story of
development of QA is that like the story of a kitchen, the
ultimate aim of which to deliver a good dish. The guiding
factors are -
(i) Drug tragedies
(ii) Regulatory / Legal requirements
(iii) Certification Scheme by WHO on Quality
of Pharmaceutical Products Moving in
International Commerce.
(iv) Economic considerations

12. (v) Ethical considerations
(vi) Manufacturing Conditions, such as
Firstly - products that fail to conform to quality when
manufactured.
Secondly - products that initially conform to quality,
but later deteriorate on the shelf before expiry date.

13. What are the General guidelines of GMP for
pharmaceutical products ?
General guidelines of GMP to be followed in a
pharmaceutical plant are -
i) All manufacturing processes are clearly defined,
systematically reviewed, and shown to be capable of
consistently manufacturing pharmaceutical products of
the required quality that comply with specifications.
ii) Validations of all works are performed

14. iii) All necessary resources are provided, e.g.
appropriately qualified and trained personnel,
adequate premises and space, suitable equipment and
services, proper materials, containers and labels,
approved procedures and instructions, suitable
storage and transport, proper personnel, lab and
equipment for in-process control.
iv) Instructions and procedures are written in clear and
unambiguous language
v) Operators are trained to carryout the procedures
correctly

15. vi) Records are made during manufacture to show that
all the steps required by defined procedures and
instructions have in fact been taken and that the
quantity and quality of the products are as expected.
vii) Records covering manufacture and distribution are
retained in a comprehensive and accessible form.
viii) Proper storage and distribution,
ix) A system is available for recall if necessary,
x) Complaints about marketed products are examined,
causes of defect investigated and measures taken to
prevent recurrence.

16. What is Contamination and what are the
major sources of Contamination ?
Anything undesirable and which does not belong to that
product is a contaminant. Though a complete freedom from
contamination is extremely difficult to achieve, some
contaminations can make a product hazardous and totally unfit
for use. Therefore, from the ethical as well as regulatory point
of view the control of contamination is an absolute necessity.

18. All types of contaminations can be classified into three groups
1. Particulate Contamination
2. Chemical Contamination (Primary and cross contamination)
3. Microbial Contamination
In this section attempts will be made to explain each type of
contamination with a few common examples to emphasize
GMP.
1. Particulate Contamination
Any foreign body or material in tiny pieces may result in
particulate contamination. For example it can be dust, pieces
of glass or metal, fabric, fibers, rubber materials, hairs, etc.
Garments themselves might shed particles and fibers if the
appropriate kind of fabric materials are not used.

19. In case of injectables, particularly intravenous fluids,
particulate matter can cause a great health risk. When a
product is sterilized through membrane filtration technique
there should not be any particulate matter in the filtrate, but
the problem can still arise from the container, closure,
environment, etc. The pharmacopoeial monographs provide a
guide-line for the acceptable limits of particulate
contamination in parenteral preparations. Although 100%
inspection of the parenteral preparations is mandatory, there is
very little scope for inspection of the particulate matters in the
dry fill injectables. Therefore, the right approach is to protect
the product in the first place.

20. Inspection of the liquid injectables are not easy either. A manual procedure may be
based on the inspection of liquid injectables in diffused light against black and white
back-ground. In this way particles down to 50 microns can be detected with the naked
eye during inspection, while for faster and more stringent inspection an instrument can
be employed. Contaminated units of injectables are a total loss to the company and a
tighter inspection does not eliminate the problem at source. A sound manufacturing
process will minimise this rejection loss.
Another area of potential risk in particulate contamination is in eye ointment. In this
case the manufacturer of the metal tubes can help a lot by ensuring that the metal
fragments which are generated during manufacture of the tubes are removed at source.
They can also protect the tubes from particulate contamination during transportation by
using non-particle shedding packaging materials such as polythene, shrink wrap, etc. It
is indeed more practical and economical to make the source reliable rather than
depending solely on air cleaning of the tubes before filling the product.
For oral preparation a similar approach should be taken. But in this case the
acceptable limit can be relaxed through a rational approach.

21. 2. Chemical Contamination
Chemical contamination can be divide into two groups, viz- (i) primary contamination and (ii)
cross-contamination.
(i) Primary Contamination: Contamination can occur in the finished product through starting
materials. Therefore, the raw material specifications should clearly state the limits, if any, of the
potential Impurities. The packaging materials such as glass or plastic container can also
contribute significantly with release of chemicals as contaminants which could be harmful in
themselves or affect the product stability. The BP and DSP provide a detailed monograph on glass
quality, Also in case of plastic components proper control procedures need to be followed to
check the extractability of toxic heavy metals, stabilizers, antioxidants, etc. that could be present
In the packaging materials. Rubber closures also require a proper control Step, The suitability of
particular types of rubber materials should be considered. Problems may also occur due to
constituents of adhesives migrating through plastic containers into the product.
Anti-microbial treatment without proper safety steps could lead to a major source of
contamination. For instance improper application of ethylene oxide treatment for sterilization can
result a degradation product such as ethylene chlorohydrin which is also known to be harmful. A
routine testing procedure should be employed to confirm that any residual trace of ethylene oxide
or its degradation product are within safety margin. When formalin is used, the residual formalin
and any paraformaldehyde formed can be difficult to remove completely. Sensitive GC and
HPLC methods are now-a-days available for the detection of trace impurities.

22. Cross-Contamination
The term cross-contamination refers to product-to-product contamination. It can be through
careless sharing of the manufacturing equipment and utensils, sharing of space without proper
cleaning, poor production planning and particularly inadequate dust control. It is known that
contamination by some potent drugs, even at a very minute level, can cause hyper-sensitivity
reaction like anaphylaxis which may even risk the life of the patient under certain clinical
circumstances. In the current GMP approach the possibility of cross-contamination with
penicillin, steroids and some highly sensitive drugs has become a great concern to all. For
instance a very small fraction of population may get severe allergic reaction to penicillin called
anaphylactic shock with nominal amounts of penicillin i.e. as low as 0.01 IU with parenteral
dosage. In case of oral administration the tolerance limit is higher .
While dealing with a highly sensitive product like penicillin the recommended approach is having
a dedicated manufacturing facilities where the objective is totally isolating such facilities.
3. Microbial contamination
Microbes such as virus, bacteria molds etc can freely exist in the uncontrolled environment.
-Parenteral preparations
-Pyrogenic substance released from microbes
-Ophthalmic preparations
-Careful control program for control of contamination

23. 8. Self inspection and quality audits
-The purpose of self-inspection
is to evaluate the manufacturers compliance with GMP in all aspects of
production and quality control.
-Items of self-inspection include
personnel, premises, maintenance of buildings and equipments, storage
of starting materials and finished products, equipments, production and
in-process controls, quality control, documentation, sanitation and
hygiene, validation and revalidations, calibration of instruments, recall
procedures, complaints management, label control, results of previous
self-inspection and corrective steps taken.
-Self-inspection team
-Frequency of self-inspection
-Self-inspection report
-Suppliers’ audit and approval
-Follow-up action and
-Quality audit

24. Self-inspection report
8.5 A report should be made at the completion of a self-inspection. The report should include:
(a) self-inspection results; (b) evaluation and conclusions; (c) recommended corrective actions.
Follow-up action
8.6 There should be an effective follow-up program. The company management should evaluate
both the self-inspection report and the corrective actions as necessary.
Quality audit
8.7 It may be useful to supplement self-inspections with a quality audit. A quality audit consists
of an examination and assessment of all or part of a quality system with the specific purpose of
improving it. A quality audit is usually conducted by outside or independent specialists or a team
designated by the management for this purpose. Such audits may also be extended to suppliers
and contractors (see section 7, “Contract production and analysis”).
Suppliers’ audits and approval
8.8 The person responsible for quality control should have responsibility together with other
relevant departments for approving suppliers who can reliably supply starting and packaging
materials that meet established specifications.
8.9 Before suppliers are approved and included in the approved supplier’s list or specifications,
they should be evaluated. The evaluation should take into account a supplier’s history and the
nature of the materials to be supplied. If an audit is required, it should determine the supplier’s
ability to conform to GMP standards.

25. Definition and educational qualification of Key personnel?
Key personnel include the head of production, the head of quality control and the
authorized person. Normally, key posts should be occupied by full-time personnel. The
heads of production and quality control should be independent of each other. In large
organizations, it may be necessary to delegate some of the functions; however, the
responsibility cannot be delegated.
Key personnel responsible for supervising the manufacture and quality control of
pharmaceutical products should possess the qualifications of a scientific education and
practical experience required by national legislation. Their education should include the
study of an appropriate combination of:
(a) chemistry (analytical or organic) or biochemistry; (b) chemical engineering; (c)
microbiology; (d) pharmaceutical sciences and technology; (e) pharmacology and
toxicology; (f) physiology; (g) other related sciences.
They should also have adequate practical experience in the manufacture and quality
assurance of pharmaceutical products. In order to gain such experience, a preparatory
period may be required, during which they should exercise their duties under
professional guidance. The scientific education and practical experience of experts
should be such as to enable them to exercise independent professional judgment, based
on the application of scientific principles and understanding to the practical problems
encountered in the manufacture and quality control of pharmaceutical products.

26. Job description of Production manager
The head of the production generally has the following responsibilities:
(a) to ensure that products are produced and stored according to the
appropriate documentation in order to obtain the required quality;
(b) to approve the instructions relating to production operations, including
the in-process controls, and to ensure their strict implementation;
(c) to ensure that the production records are evaluated and signed by a
designated person;
(d) to check the maintenance of the department, premises, and equipment;
(e) to ensure that the appropriate process validations and calibrations of
control equipment are performed and recorded and the reports made
available;
(f) to ensure that the required initial and continuing training of production
personnel is carried out and adapted according to need.

27. Job description of QC manager
The head of the quality control generally has the following
responsibilities:
(a) to approve or reject starting materials, packaging materials, and
intermediate, bulk and finished products in relation with their
specifications;
(b) to evaluate batch records;
(c) to ensure that all necessary testing is carried out;
(d) to approve sampling instructions, specifications, test methods and
other quality control procedures;
(e) to approve and monitor analyses carried out under contract;
(f) to check the maintenance of the department, premises and equipment;
(g) to ensure that the appropriate validations, including those of
analytical procedures, and calibrations of control equipment are
carried out;
(h) to ensure that the required initial and continuing training of quality
control personnel is carried out and adapted according to need.

28. Jointly shared Job description of Production and QC manager
The heads of the production and quality control generally have some shared, or jointly
exercised, responsibilities relating to quality. These may include, depending on
national regulations:
(a) authorization of written procedures and other documents, including amendments;
(b) monitoring and control of the manufacturing environment;
(c) plant hygiene;
(d) process validation and calibration of analytical apparatus;
(e) training, including the application and principles of quality assurance;
(f) approval and monitoring of suppliers of materials;
(g) approval and monitoring of contract manufacturers;
(h) designation and monitoring of storage conditions for materials and products;
(i) performance and evaluation of in-process controls;
(j) retention of records;
(k) monitoring of compliance with GMP requirements;
(l) inspection, investigation and taking of samples in order to monitor factors that may
affect product quality.

29. Training
Training is defined as the “special education program to
make a person expert on a particular discipline to
make him able to perform selected tasks”.
It may include formal class lecture to practical demonstration.
Training and personnel development are inseparable.
Remember: The purpose of generalized education is “Jack of
all trades, Master of none”.
The purpose of training is to make someone Master on
ONE particular subject or field.
Master of none VS Master on ONE

30. Training
Contents of Training for Pharma plant
The training program designed for pharmaceutical industries must cover all important
aspects of its functions in a logical sequence appealing to workers. For example-
-How medicines directly affect the health of the people?
-Company's key manufacturing activities
-Importance of personnel health and hygiene
-importance of safety precautions, -Importance of cleanliness
-Need for effective work system, -Need for conscientiously carrying out the laid down
system,
-Importance of manufacturing and testing procedures
-Problem of Faulty/ Rejected batches
-Role of Production, QA/QC and Engineering
-Importance and the principles of GMP
-Importance of validation, -Importance of productivity and profitability
Through training it is also important to make it clear to the staff how the non
compliance with standards and procedures will effect – (i) Patients / Consumers, (ii)
Company, (iii) Employee.

31. For whom and how to conduct a training program?
The training program must cover employees of all departments, sections/and
designed, for various levels, with definite objectives.
Depending on the levels of staff - formal lecture, symposium, discussion groups,
workshop, etc, should be organized.
Various training aids should be adopted for effective communication. When
information is received through eyes the retention is better than ears.
Discussions and exchange of views generate thinking and its application at the
work place makes even a better impact on retaining the information by fixing it
more firmly in the minds (Fig. 8.1).
So a more penetrating and successful training program can be undertaken
through audiovisual systems like slides/tape presentation, video recorded
program and practical demonstration, rather than a simple class-room type
lectures. Programmed question and answer training aids are also very valuable.
Thus by combining active learning methods one will retain much more
information. (Fig. 8.1).

33. Why is it necessary to continue the training program?
No person can retain every piece of information in the memory forever. Forgetting
things once learned is a natural process. So training should be a continuous effort to
achieve a better perfection in the employees skill. A systematic approach to Training,
learning, application, assessment and monitoring (PT-LAMA) should be followed with
refresher training courses (Fig 8.2)
It is important to keep the training records of each staff to plan for further training
necessary. In modern management multi-skill training is a proven means of making the
best use of human resources with flexibility.

34. xiv. Materials
-Finished products for patients from starting and packaging materials
-Intermediate and bulk products, Finished products,
-Also gases, solvents, process aids, labeling materials
-Rejected, recovered, reprocessed and reworked products
-Reagents and culture media
-Recall goods
- Returned goods
-Reference standards,
-Waste materials and
-Miscellaneous
14.1 Principle. The main objective of a pharmaceutical plant is to produce finished products for patients’ use
from a combination of materials (starting and packaging).
14.2 Materials include starting materials, packaging materials, gases, solvents, process aids, reagents and
labeling materials.
General
14.3 No materials used for operations such as cleaning, lubrication of equipment and pest control, should
come into direct contact with the product. Where possible, such materials should be of a suitable grade
(e.g. food grade) to minimize health risks.
14.4 All incoming materials and finished products should be quarantined immediately after receipt or
processing, until they are released for use or distribution.
14.5 All materials and products should be stored under the appropriate conditions established by the
manufacturer and in an orderly fashion to permit batch segregation and stock rotation by a first-in, first-
out (FIFO) or First expirer-First out (FEFO) rule.
14.6. Water used in the manufacture of pharmaceutical products should be suitable for its intended use.

35. 15. Documentation
Master formulae
15.22 A formally authorized master formula should exist for each product and batch size to be
manufactured.
15.23 The master formula should include:
(a) the name of the product, with a product reference code relating to its specification;
(b) a description of the dosage form, strength of the product and batch size;
(c) a list of all starting materials to be used (if applicable, with the INNs), with the amount of
each, described using the designated name and a reference that is unique to that material
(mention should be made of any substance that may disappear in the course of processing);
(d) a statement of the expected final yield with the acceptable limits, and of relevant intermediate
yields, where applicable;
(e) a statement of the processing location and the principal equipment to be used;
(f) the methods, or reference to the methods, to be used for preparing and operating the critical
equipment, e.g. cleaning (especially after a change in product), assembling, calibrating,
sterilizing, use;
(g) detailed step-wise processing instructions (e.g. checks on materials, pretreatments, sequence
for adding materials, mixing times, temperatures);
(h) the instructions for any in-process controls with their limits;
(i) the requirements for storage of the products, including the container, the labeling, and any
special storage conditions;
(j) any special precautions to be observed.

36. Packaging instructions
15.24 Formally authorized packaging instructions should normally include:
(a) the name of the product;
(b) a description of its pharmaceutical form, strength and, where applicable, method of
application;
(c) the pack size expressed in terms of the number, weight or volume of the product in the final
container;
(d) a complete list of all the packaging materials required for a standard batch size, including
quantities, sizes and types, with the code or reference number relating to the specifications
for each packaging material;
(e) where appropriate, an example or reproduction of the relevant printed packaging materials
and specimens, indicating where the batch number and expiry date of the product have been
marked;
(f) special precautions to be observed, including a careful examination of the packaging area and
equipment in order to ascertain the line clearance before and after packaging operations;
(g) a description of the packaging operation, including any significant subsidiary operations, and
equipment to be used;
(h) details of in-process controls with instructions for sampling and acceptance limits.
15.25 A batch processing record should be kept for each batch processed. It should be based on
the relevant parts of the currently approved specifications on the record. The method of
preparation of such records should be designed to avoid errors. (Copying or validated
computer programs are recommended. Transcribing from approved documents should be
avoided.)

37. Batch processing records
Batch packaging records
15.28 A batch packaging record should be kept for each batch or part batch processed. It should
be based on the relevant parts of the approved packaging instructions, and the method of
preparing such records should be designed to avoid errors. (Copying or validated computer
programs are recommended. Transcribing from approved documents should be avoided.)
15.29 Before any packaging operation begins, checks should be made that the equipment and
work station are clear of previous products, documents or materials not required for the
planned packaging operations, and that equipment is clean and suitable for use. These
checks should be recorded.
15.30 The following information should be recorded at the time each action is taken, and the date
and the person responsible should be clearly identified by signature or electronic password:
(a) the name of the product, the batch number and the quantity of bulk product to be packed, as
well as the batch number and the planned quantity of finished product that will be obtained,
the quantity actually obtained and the reconciliation;
(b) the date(s) and time(s) of the packaging operations;
(c) the name of the responsible person carrying out the packaging operation;
(d) the initials of the operators of the different significant steps;
(e) the checks made for identity and conformity with the packaging instructions, including the
results of in-process controls;
(f) details of the packaging operations carried out, including references to equipment and the
packaging lines used, and, when necessary, the instructions for keeping the product
unpacked or a record of returning product that has not been packaged to the storage area;

38. (g) whenever possible, samples of the printed packaging materials
used, including specimens bearing the approval for the printing of and
regular check (where appropriate) of the batch number, expiry date,
and any additional overprinting;
(h) notes on any special problems, including details of any deviation
from the packaging instructions, with written authorization by an
appropriate person;
(i) the quantities and reference number or identification of all printed
packaging materials and bulk product issued, used, destroyed or
returned to stock and the quantities of product obtained to permit an
adequate reconciliation.

39. Standard operating procedures (SOPs) and records
15.31 Standard operating procedures and associated records of actions
taken or, where appropriate, conclusions reached should be available
for:
(a) equipment assembly and validation;
(b) analytical apparatus and calibration;
(c) maintenance, cleaning and sanitization;
(d) personnel matters including qualification, training, clothing and
hygiene;
(e) environmental monitoring;
(f) pest control;
(g) complaints;
(h) recalls;
(i) returns.

40. Standard operating procedures (SOPs) and records
15.32 There should be standard operating procedures and records for the receipt of each
delivery of starting material and primary and printed packaging material.
15.33 The records of the receipts should include:
(a) the name of the material on the delivery note and the containers; (b) the “in-house”
name and/or code of material if different from (a); (c) the date of receipt; (d) the
supplier’s name and, if possible, manufacturer’s name; (e) the manufacturer’s batch or
reference number; (f) the total quantity, and number of containers received; (g) the
batch number assigned after receipt; (h) any relevant comment (e.g. state of the
containers).
15.34 There should be standard operating procedures for the internal labeling,
quarantine and storage of starting materials, packaging materials and other materials, as
appropriate.
15.35 Standard operating procedures should be available for each instrument and piece
of equipment (e.g. use, calibration, cleaning, maintenance) and placed in close
proximity to the equipment.
15.36 There should be standard operating procedures for sampling, which specify the
person(s) authorized to take samples.

41. How to Prevent cross-contamination and bacterial contamination during
production?
16.12 Cross-contamination should be avoided by taking appropriate technical
or organizational measures. For example-
(a) carrying out production in dedicated and self-contained areas for penicillin,
live vaccines, live bacterial preparations and certain other biologicals,
(b) conducting campaign production followed by proper cleaning in accordance
with a validated cleaning procedure;
(c) providing appropriately designed airlocks, pressure differentials, and air
supply and extraction systems;
(d) minimizing the risk of contamination caused by recirculation or re-entry of
untreated or insufficiently treated air;
(e) wearing protective clothing where products or materials are handled;
(f) using cleaning and decontamination procedures of known effectiveness;
(g) using a “closed system” in production;
(h) testing for residues;
(i) using cleanliness status labels on equipment.

42. 17. Good practices in quality control (GLP)
-QC is the part of GMP concerned with sampling, specifications and testing, and with the
organization, documentation and release procedures which ensure that the necessary and relevant
tests are actually carried out and that the materials are not released for use, nor products released
for sale or supply, until their quality has been judged to be satisfactory. QC is not confined to
laboratory operations but must be involved in all decisions concerning the quality of the product.
STEPS TO BE FOLLOWED FOR ASSURING QUALITY
-The independence of QC from production is fundamental
-Control of starting, intermediate, bulk and finished product
-Test requirements
-Control of packaging materials
-Batch record review
-Stability studies
Marketing authorization (product license, registration certificate)-A legal document issued by the drug
regulatory authority that establishes the detailed composition and formulation of the product and the
pharmacopoeial specifications of its ingredients and of the final product itself, and includes details of
packaging, labeling and shelf-life.

43. The basic requirements for quality control are as follows:
(a) adequate facilities, trained personnel and approved procedures must be available
for sampling, inspecting, and testing starting materials, packaging materials, and
intermediate, bulk, and finished products, and where appropriate for monitoring
environmental conditions for GMP purposes;
(b) samples of starting materials, packaging materials, intermediate products, bulk
products and finished products must be taken by methods and personnel approved
of by the quality control department;
(c) qualifications and validation must be performed;
(d) records must be made demonstrating that all the required sampling, inspecting and
testing procedures have been carried out and that any deviations have been fully
recorded and investigated;
(e) the finished products must contain ingredients complying with the qualitative and
quantitative composition of the product described in the marketing authorization;
the ingredients must be of the required purity, in their proper container and
correctly labeled;
(f) records must be made of the results of inspecting and testing the materials and
intermediate, bulk and finished products against specifications; product assessment
must include a review and evaluation of the relevant production documentation and
an assessment of deviations from specified procedures;

44. Batch record review
Retention samples from each batch of finished product should be kept for at least one
year after the expiry date.
Retention samples of materials and products should be of a size sufficient to permit at
least two full re-examinations.
(g) no batch of product is to be released for sale or supply prior to
certification by the authorized person(s) that it is in accordance with the
requirements of the marketing authorization. In certain countries, by
law, the batch release is a task of the authorized person from production
together with the authorized person from quality control;
(h) sufficient samples of starting materials and products must be
retained to permit future examination of the product if necessary; the
retained product must be kept in its final pack unless the pack is
exceptionally large.

45. The diagram illustrates the approach of creating and maintaining a GMP
lifestyle in a company. GMP lifestyle consists of four steps -
First Step: Set standards of performance
These include GMP regulations and other standards. Then, train the
peoples to those standards. All departments in the company should be
trained to varying degrees on GMP and other standards. The diagram
lists four types of employees to train: (i) top management, (ii) managers
and supervisors, (iii) operators and technicians, and (iv) support staff.
Second step : Training
The second step in the GMP Lifestyle is to reinforce what was learned in
training. This falls on the managers and supervisors in a
plant. Therefore, it is important that managers and supervisors be
involved in training, so that they can support it through
reinforcement. The same four job categories are listed as being the most
critical in promoting and receiving reinforcement.
GMP life cycle

46. Figure : GMP life cycle in a Pharma company

47. Third step : Reinforcement of knowledge into workplace
The third stage is reinforcement of knowledge in the workplace
gained in training.
Fourth Step: Audit
Audit ensures that the efforts have provided adequate
controls. Audits fall in three categories:
personal, whereby every individual does a self-check to make
sure that he is complying with all appropriate standards;
internal audit, which should be performed by the QA
department, and
external audits, which can consist of an FDA/DRA audit, a
consultant checking the compliance status.

48. Finally, the results of audits will help the industries
to know if they need to modify their standards of
performance.
The glue that sticks the whole process together is
commitment.
Commitment to GMP and quality is critical at all
levels of the organization, starting with top
management.