Introduction to cGMP

compliance

Course Title: Introduction to cGMP compliance

Course Code: BTC 623
Program: Master of Biotechnology
Department: Biology
College: Sciences and Arts at Khulais
Institution: University of Jeddah
1
 Contact
No List of Topics
Hours
1 Introduction to Current Good Manufacturing Practices 2
Regulations of Current Good Manufacturing Practices in the pharmaceutical 2
2
and Biotech industries
3 Regulations related to General Provisions, Organization and Personnel 2
4 Regulations related to Buildings, Facilities and Equipment 2
Regulations related to the Control of Components, Drug Product Containers 2
5
and Closures, and Production Process
Regulations related to Packaging, Labeling, Holding, Distribution and 2
6
Laboratory Controls
2
7 Regulations related to Records, Reports, Returned and Salvaged Drug Products
8 FDA’s guidance documents and training manuals 2
Industry trade publications, international compendia, and standards-setting 2
9
organizations
10 History of the regulations 2
2
12 Industry standard implementation strategies and -best-practices- approaches
13 FDA’s current expectations 2
Practical solutions to the regulatory issues faced in the pharmaceutical and 2
14
biotech. Industries
Total 30

2
Introduction

3
 What is GMP ?
• GMP is that part of Quality assurance which ensures
that the products are consistently manufactured and
controlled to the Quality standards appropriate to
their intended use

• A set of principles and procedures which, when

followed by manufacturers for therapeutic goods,
helps ensure that the products manufacture will
have the required quality.

4
 Good Manufacturing Practices
• A basic tenet of GMP is that quality cannot be
tested into a batch of product but must be
built into each batch of product during all
stages of the manufacturing process.

• It is designed to minimize the risks involved in

any pharmaceutical production that cannot be
eliminated through testing the final product.

5
 Some of the main risks are
– unexpected contamination of products, causing
damage to health or even death.

– incorrect labels on containers, which could mean

that patients receive the wrong medicine.

– insufficient or too much active ingredient,

resulting in ineffective treatment or adverse
effects.

6
 Why GMP is important

• A poor quality medicine may contain toxic

substances that have been unintentionally added.

• A medicine that contains little or none of the claimed

ingredient will not have the intended therapeutic
effect.

7
GMP

QA

GMP

QC

8
QA, GMP & QC inter-relationship

It is the sum total of the

organized arrangements with
the objective of ensuring that
products will be of the quality
required for their intended use

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 GMP

Is that part of Quality

Assurance aimed at
ensuring that products are
consistently manufactured
to a quality appropriate to
their intended use

10
QA, GMP & QC inter-relationship

Is that part of GMP concerned with

sampling, specification & testing,
documentation & release
procedures which ensure that the
necessary & relevant tests are
performed & the product is
released for use only after
ascertaining it’s quality

11
 QC and QA
• QC is that part of GMP which • QA is the sum total of
is concerned with sampling, organized
specifications, testing and arrangements made
with in the organization,
with the object of
documentation,and release
procedures which ensure ensuring that product
that the necessary and will be of the Quality
relevant tests are carried out required by their
intended use.

12
 QC and QA
• Operational laboratory • All those planned or
techniques and systematic actions
activities used to fulfill necessary to provide
the requirement of adequate confidence
Quality that a product will
satisfy the requirements
for quality

13
 QC and QA

• QC is lab based • QA is company based

14
 GMP
• The Quality of a formulation or a bulk drug
depends on the Quality of those producing it
• GMP is the magic key that opens the door of
the Quality
• In matter of GMP, swim with the current and
in matter of Quality stand like a rock!

15
 GMP helps boost pharmaceutical
export opportunities
• Most countries will only accept import and
sale of medicines that have been
manufactured to internationally recognized
GMP.

• Governments seeking to promote their

countries export of pharmaceuticals can do so
by making GMP mandatory for all
pharmaceutical production and by training
their inspectors in GMP requirements.

16
 GMP Covers…
• ALL aspects of production; from the starting materials,
premises and equipment to the training and personal
hygiene of staff.

• Detailed, written procedures are essential for each

process that could affect the quality of the finished
product.

• There must be systems to provide documented proof

that correct procedures are consistently followed at
each step in the manufacturing process - every time a
product is made.
17
 GMP guidance documents
• 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 Good Manufacturing Practices for
pharmaceutical products, Annex 4 to WHO
Technical Report Series, No. 908, 2003
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 Ten Principles of GMP
1. Design and construct the facilities and equipments
properly
2. Follow written procedures and Instructions
3. Document work
4. Validate work
5. Monitor facilities and equipment
6. Write step by step operating procedures and work on
instructions
7. Design ,develop and demonstrate job competence
8. Protect against contamination
9. Control components and product related processes
10. Conduct planned and periodic audits
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‫عشرة مبادئ من ‪GMP‬‬
‫تصميم وبناء المرافق والمعدات بشكل صحيح‬ ‫•‬
‫اتبع اإلجراءات والتعليمات المكتوبة‬ ‫•‬
‫وثيقة العمل‬ ‫•‬
‫التحقق من صحة العمل‬ ‫•‬
‫مراقبة المرافق والمعدات‬ ‫•‬
‫اكتب إجراءات التشغيل خطوة بخطوة واعمل على التعليمات‬ ‫•‬
‫تصميم وتطوير وإثبات الكفاءة الوظيفية‬ ‫•‬
‫حماية من التلوث‬ ‫•‬
‫مكونات التحكم والعمليات المتعلقة بالمنتج‬ ‫•‬
‫إجراء عمليات تدقيق مخططة ودورية‬ ‫•‬

‫‪20‬‬
 10 attributes of a good document

1. Accurate
2. Clear
3. Complete
4. Consistent
5. Indelible
6. Legible
7. Timely
8. Direct
9. Authentic
10. Authorized
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 Beyond GMP
• Reduce pollution - Zero discharge

• Adaptation of environment friendly methods

• Consideration for better and healthier life tomorrow

• Consideration of ethics in life

• One should begin with end in mind otherwise it will be

the beginning of the end
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23
 APIs
• Manufacture of active pharmaceutical
ingredients (APIs) and intermediates as
finished product, must follow well-defined
operating principles

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 What are Active Pharmaceutical
Ingredients (APIs)
• Any drug formulation is composed of two components or
aspects. The first is the actual API or Active Pharmaceutical
Ingredients, which is the central ingredient. The second is
known as an excipient which is the inactive ingredient.
• Excipient serves as a medium for conveying the active
ingredient.
• Active Pharmaceutical Ingredient: Any substance or mixture
of substances intended to be used in the manufacture of a
drug (medicinal) product and that, when used in the
production of a drug, becomes an active ingredient of the
drug product. Such substances are intended to furnish
pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment, or prevention of
disease or to affect the structure or function of the body. 25
 FDA Definitions of API:
• Any substance that is represented for use in a drug and that,
when used in the manufacturing, processing, or packaging of
a drug, becomes an active ingredient or a finished dosage
form of the drug. Such substances are intended to furnish
pharmacological activity or other direct effect in the
diagnosis, cure, mitigation, treatment or prevention of
disease, or to affect the structure and function of the body of
humans or other animals. APIs include substances
manufactured by processes such as (1) chemical synthesis; (2)
fermentation; (3) recombinant DNA or other biotechnology
methods; (4) isolation/recovery from natural sources; or (5)
any combination of these processes.

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API Manufacturing Process

‫طحن‬

27
Secondary Manufacturing
Dosage Forms

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Secondary Manufacturing
Process - Tablets

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Secondary Manufacturing Process –
Sterile parenteral for injection

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Biotechnology Manufacturing
Process

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 Definitions
• API Intermediate: A material produced during
steps in the synthesis of an API that must
undergo further molecular change or
processing before it becomes an API. Drug
Product: A finished dosage form, for example,
a tablet, capsule or solution that contains an
active pharmaceutical ingredient, generally,
but not necessarily, in association with
inactive ingredients (excipients).
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 Definitions
• Pharmaceutical Excipient: An excipient is
pharmacologically inactive substance formulated
along with the active pharmaceutical ingredient of a
medication or drug product. Examples of excipients
include fillers, extenders, diluents, wetting agents,
solvents, emulsifiers, preservatives, flavors,
absorption enhancers, sustained-release matrices,
and coloring agents.
• Fine chemicals: Fine chemicals are complex, single,
pure chemical substances, produced in limited
quantities. They are generally produced in
multipurpose plants by multistep batch chemical or
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biotechnological process
34
35
Current GMP in manufacturing
processes (cGMP)

36
 What are cGMPs?
• cGMP refers to the Current Good Manufacturing
Practice regulations enforced by the US Food and
Drug Administration (FDA).
• cGMP provide for systems that assure proper design,
monitoring and control of manufacturing processes
and facilities.
• Adherence to the cGMP regulations assures the
identity, strength, quality and purity of drug products
by requiring that manufacturers of medications
adequately control manufacturing operations
37
 What are cGMPs?
• This includes establishing strong quality management
systems, obtaining appropriate quality raw materials,
establishing robust operating procedures, detecting
and investigating product quality deviations, and
maintaining reliable testing laboratories.
• This formal system of controls at a pharmaceutical
company, if adequately put into practice, helps to
prevent instances of contamination, mix-ups,
deviations, failures, and errors.
• This assures that drug products meet their quality
standards.
38
 What are cGMPs?
• The cGMP requirements were established to be
flexible in order to allow each manufacturer to
decide individually how to best implement the
necessary controls by using scientifically sound
design, processing methods, and testing
procedures.
• The flexibility in these regulations allows
companies to use modern technologies and
innovative approaches to achieve higher quality
through continual improvement.
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 What are cGMPs?
• Accordingly the “c” in cGMP stands for
“current” requiring companies to use
technologies and systems that are up-to-date
in order to company with the regulations.
• Systems and equipment that may have been
“top-of-the-line” to prevent contamination,
mix-ups, and errors 10 or 20 years ago may be
less than adequate by today’s standards.

40
 What are cGMPs?
• It is important to note that cGMP are
minimum requirements.
• Many pharmaceutical manufacturers are
already implementing comprehensive,
modern quality systems and risk management
approaches that exceed these minimum
standards.

41
 Why are cGMP so important
• A consumer usually cannot detect (through smell,
touch, or sight) that a drug product is safe or if it will
work.
• While cGMPs require testing, testing alone is not
adequate to ensure quality.
• In most instances testing is done on a small sample
of a batch (for example, a drug manufacturer may
test 1000 tablets from a batch that contains 2 million
tablets), so that most of the batch can be used for
patients rather than destroyed by testing.
42
 Why are cGMP so important
• Therefore, it is important that drugs are
manufactured under conditions and practices
required by the cGMP regulations to assure that
quality is built into the design and manufacturing
process at every step.
• Facilities that are in good conditions, equipment that
is properly maintained and calibrated, employees
who are qualified and fully trained, and processes
that are reliable and reproducible, are a few
examples of how cGMP requirements help to assure
the safety and efficacy of drug products.
43
Packaging

44
Packaging

45
Packaging

46
 Packaging and holding of
drugs
• Care shall be taken when using automatic
tablet and capsule counting, strip and blister
packaging equipment to ensure that all
‘rogue’ tablets, capsules or foils from
packaging operation are removed before a
new packaging operation is commenced.
• There shall be an independent recorded check
of the equipment before a new batch of
tablets or capsules is handled.
47
 Packaging and holding of
drugs
• Uncoated tablets shall be packed on
equipment designed to minimize the risk of
cross-contamination. Such packaging shall be
carried out in an isolated area when potent
tablets or Beta-Iactum containing tablets are
being packed.
• The strips coming out of the machine shall be
inspected for defects such as misprint, cuts on
the foil, missing tablets and improper sealing.
48
 Packaging and holding of
drugs
• Integrity of individual packaging strips and
blisters shall be subjected to vacuum test
periodically to ensure leak proofness of each
pocket strip and blister and records
maintained.

49
 Finished pharmaceuticals
Appropriate specifications for finished products
shall include: -

• The designated name of the product and the

code reference.
• The formula or a reference to the formula and
the pharmacopoeial reference.
• Directions for sampling and testing or a reference
to procedures.
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 Finished pharmaceuticals
• A description of the dosage form and package
details.
• The qualitative and quantitative requirements,
with the acceptance limits for release.
• The storage conditions and precautions,
where applicable, and the shelf-life.

51
 General provisions
• The processing of dry materials and products
creates problems of dust control and cross-
contamination. Special attention is therefore,
needed in the design, maintenance and use of
premises and equipment in order to overcome
these problems. Wherever required, enclosed
dust control manufacturing systems shall be
employed.

52
 General provisions
• Suitable environmental conditions for the
products handled shall be maintained by
installation of air-conditioning wherever
necessary. Effective air extraction systems,
with discharge points situated to avoid
contamination of other products and
professes shall be provided. Filters shall be
installed to retain dust and protect the factory
and local environment
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 General provisions
• Special care shall be taken to protect against
subsequent contamination of the product by
particles of metal or wood. The use of metal
detector is recommended. Wooden
equipment should be avoided. Screens, sieves,
punches and dies shall be examined for wear
and tear or for breakage before and after each
use. ‫يجب فحص المناخل والغرابيل واللكمات والقوالب للتأكد‬
‫من عدم وجود اهتراء أو تمزق أو كسر قبل وبعد كل‬
.‫استخدام‬
54
 General provisions
• All ingredients for a dry product shall be sifted‫منخل‬
before use unless the quality of the input material
can be assured. Such sifting shall normally be carried
out at dedicated areas.
• Where the facilities are designed to provide special
environmental conditions of pressure differentials
between rooms, these conditions shall be regularly
monitored and any specification results brought to
the immediate attention of the Production and
quality Assurance Department which shall be
immediately attended to.
(of material) having been passed through a sieve.
 General provisions
• Care shall be taken to guard against any material lodging and
remaining undetected in any processing or packaging
equipment. Particular care shall be taken to ensure that any
vacuum, compressed air or air-extraction nozzles are kept
clean and that there is no evidence lubricants leaking into the
product from any part of the equipment.

‫يجب توخي الحذر للحماية من أي مواد تخزين وبقايا غير مكتشفة في أي معدات‬
‫ يجب توخي الحذر بشكل خاص للتأكد من أن أي فوهات فراغ أو‬.‫معالجة أو تعبئة‬
‫هواء مضغوط أو فوهات شفط الهواء تظل نظيفة وأنه ال يوجد دليل على تسرب‬
.‫مواد التشحيم إلى المنتج من أي جزء من الجهاز‬

56
 Organization and personnel
1. Responsibilities of quality control unit.

2. Personnel qualifications.

3. Personnel responsibilities.

4. Consultants.

57
 Organization and personnel
• The manufacture shall be conducted under the direct
supervision of competent technical staff with
prescribed qualifications and practical experience in
the relevant dosage and/or active pharmaceutical
products.
• The head of the Quality Control Laboratory shall be
independent of the manufacturing unit. The testing
shall be conducted under the direct supervision of
competent technical staff who shall be whole time
employees of the licensee.
58
 Organization and personnel
• Personnel for Quality Assurance and Quality Control
operations shall be suitably qualified and experienced.
• Written duties of technical and Quality Control personnel shall
be laid and following strictly.
• Number of personnel employed shall be adequate and in
direct proportion to the workload.
• The licensee shall ensure in accordance with a written
instruction that all personnel in production area or into
Quality Control Laboratories shall receive training appropriate
to the duties and responsibility assigned to them. They shall
be provided with regular in-service training.

59
 Building and facilities
1. Design and construction features.
2. Lighting.
3. Ventilation, air filtration, air heating and
cooling.
4. Plumbing.
5. Sewage and refuse.
6. Washing and toilet facilities.
7. Sanitation.
8. Maintenance.

60
 Building and facilities
• The building(s) used for the factory shall be
designed, constructed, adapted and
maintained to suit the manufacturing
operations so as to permit production of drugs
under hygienic conditions. They shall conform
to the conditions laid down in the Factories
Act.

61
 Building and facilities
• The premises used for manufacturing,
processing, warehousing, packaging labeling
and testing purposes.
• Compatible with other drug manufacturing
operations that may be carried out in the
same or adjacent area / section.

62
 Building and facilities
• Adequately provided with working space to allow
orderly and logical placement of equipment,
materials and movement of personnel so as to:
 avoid the risk of mix-up between different
categories of drugs or with raw materials,
intermediates and in-process material.
 avoid the possibilities of contamination and
cross- contamination by providing suitable
mechanism.
63
 Building and facilities
• Designed/constructed/maintained to prevent
entry of insects, pests, birds, vermins, and
rodents. Interior surface (walls, floors and
ceilings) shall be smooth and free from cracks,
and permit easy cleaning, painting and
disinfection.

64
 Building and facilities
• Air-conditioned, where prescribed for the operations and
dosage froms under production. The production and
dispensing areas shall be well lighted, effectively ventilated,
with air control facilities and may have proper Air Handling
Units (wherever applicable) to maintain conditions including
temperature and, wherever necessary, humidity, as defined
for the relevant product. These conditions shall be
appropriate to the category of drugs and nature of the
operation. These shall also be suitable to the comforts of the
personnel working with protective clothing, products handled,
operations undertaken within them in relation to the external
environment. These areas shall be regularly monitored for
compliance with required specifications;
65
 Building and facilities
• Provided with drainage system, as specified
for the various categories of products, which
shall be of adequate size and so designed as to
prevent back flow and/or prevent insects and
rodents entering the premises. Open channels
shall be avoided in manufacturing areas and,
where provided, these shall be shallow to
facilitate cleaning and disinfection;

66
 Building and facilities
• The walls and floors of the areas where
manufacture of drugs is carried out shall be
free from cracks and open joints to avoid
accumulation of dust. These shall be smooth,
washable, covered and shall permit easy and
effective cleaning and dis-infection. The
interior surfaces shall not shed particles. A
periodical record of cleaning and painting of
the premises shall be maintained.
67
 Equipment
1. Equipment design, size, and location.
2. Equipment construction.
3. Equipment cleaning and maintenance.
4. Automatic, mechanical, and electronic
equipment.
5. Filters.

68
 Equipment
• Equipment shall be located, designed,
constructed, adapted and maintained to suit the
operations to be carried out. The layout and
design of the equipment shall aim to minimise
the risk of errors and permit effective cleaning
and maintenance in order to avoid cross-
contamination, build-up of dust or dirt and, in
general any adverse effect on the quality of
products. Each equipment shall be provided with
a logbook, wherever necessary.
69
 Equipment
• Balances and other measuring equipment of
an appropriate range, accuracy and precision
shall be available in the raw material stores,
production and in process control operations
and these shall be calibrated and checked on a
scheduled basis in accordance with Standard
Operating Procedures and records
maintained.

70
 Equipment
• The parts of the production equipment that come
into contact with the product shall not be
reactive, additive or adsorptive to an extent that
would affect the quality of the product.
• To avoid accidental contamination, wherever
possible, non-toxic/edible grade lubricants shall
be used and the equipment shall be maintained
in a way that lubricants do not contaminate the
products being produced.

71
 Equipment
• Defective equipment shall be removed from
production and Quality Control areas or
appropriately labeled.

72
 Control of components
1. General requirements.
2. Receipt & storage of untested components, drug
product containers, and closures.
3. Testing and approval or rejection of components,
drug product containers, and closures.
4. Use of approved components, drug product
containers, and closures.
5. Retesting of approved components, drug product
containers, and closures.
6. Rejected components, drug product containers,
and closures.
7. Drug product containers and closures.
73
 Control of components
• Each tablets compressing machine shall be
provided with effective dust control facilities
to avoid cross-contamination. Unless the same
product is being made on each machine, or
unless the compression machine itself
provides its own enclosed air controlled
environment, the machine shall be installed in
separate cubicles.

74
 Control of components
• Suitable physical procedural and labeling
arrangements shall be made to prevent mix
up of materials, granules and tables on
compression machinery.
• Accurate and calibrated weighting equipment
shall be readily available and used for in-
process monitoring of tablet weight variation.
Procedures used shall be capable of detecting
out-of-limits tablets.
75
 Control of components
• At the commencement of each compression run and
in case of multiple compression points in a
compression machine, sufficient individual tablets
shall be examined at fixed intervals to ensure that a
tablet from each compression station or from each
compression point has been inspected for suitable
pharmacopoeial parameters like ‘appearance’,
‘weight variation’, ‘disintegration’, ‘hardness’,
‘friability’ and ‘thickness’. The results shall be
recorded as part of the batch documentation.

76
 Control of components
• Tablets shall be de-dusted, preferably by
automatic device and shall be monitored for
the presence of foreign materials besides any
other defects.
• Tablets shall be collected into clean, labeled
containers.
• Rejected or discarded tablets shall be isolated
in identified containers and their quality
recorded in the Batch Manufacturing Record.
77
 Control of components
• In-process control shall be employed to ensure that
the products remain within specification. During
compression, samples of tablets shall be taken at
regular intervals of not greater than 30 minutes to
ensure that they are being produced in compliance
with specified in-process specification. The tablets
shall also be periodically checked for additional
parameters such as ‘appearance’, ‘weight variation’,
‘disintegration’, ‘hardness’, ‘friability’ and ‘thickness’
and contamination by lubricating oil.

78
 Containers and closures
• All containers and closures intended for use shall
comply with the pharmacopoeial requirements.
Suitable validated test methods, sample sizes,
specifications, cleaning procedure and
sterilization procedure, wherever indicated, shall
be strictly followed to ensure that these are not
reactive, additive, absorptive, or leach to an
extent that significantly affects the quality or
purity of the drug. No second hand or used
containers and closures shall be used.
79
 Containers and closures
• Whenever bottles are being used, the written
schedule of cleaning shall be laid down and
followed. Where bottles are not dried after
washing, they should be rinsed with de-ionised
water or distilled water, as the case may be.
• For in-process and bulk products. - Specifications
for in-process material, intermediate and bulk
products shall be available. The specifications
should be authenticated.

80
 Containers and closures
• All containers and closures intended for use shall
comply with the pharmacopoeial and other specified
requirements. Suitable samples sizes, specifications,
test methods, cleaning procedures and sterilization
procedures, shall be used to assure that containers,
closures and other component parts of drug
packages are suitable and are not reactive, additive,
adsorptive or leachable or presents the risk of
toxicity to an extent that significantly affects the
quality or purity of the drug. No second hand or used
containers and closures shall be used.
81
 Containers and closures
• Plastic granules shall also comply with the
pharmacopoeial requirements including physio-
chemical and biological tests.
• All containers and closures shall be rinsed prior
to sterilization with Water for Injection
according to written procedure.
• The design of closures, containers and stoppers
shall be such as to make cleaning, easy and also
to make airtight seal when fitted to the bottles.
82
 Containers and closures
• It shall be ensured that containers and
closures chosen for a particular product are
such that when coming into contact they are
not absorbed into the product and they do
not affect the product adversely. The closures
and stoppers should be of such quality
substances as not to affect the quality of the
product and avoid the risk of toxicity.

83
 Containers and closures
• Whenever glass bottles are used, the written
schedule of cleaning shall be laid down and followed.
Where bottles are not dried after washing, these
shall be finally rinsed with distilled water or pyrogen
free water, as the case may be, according to written
procedure.
• Individual containers of parenteral preparations,
ophthalmic preparations shall be examined against
black/white background fitted with diffused light
after filling so as to ensure freedom from foreign
matters.
84
 Containers and closures
Glass Bottles:-
• Shape and design of the glass bottle shall be rational and
standardized. Glass bottles made of USP Type-I and USP
Type-II glass shall only be used. Glass bottles shall not be
reused. Before use, USP Type-II bottles shall be validated
for the absence of particulate matter generated over a
period of the shelf life of the product and shall be
regularly monitored after the production, following
statistical sampling methods. USP Type-III glass
containers may be used for non-parenteral sterile
products such as Otic Solutions.
85
 Containers and closures
Plastic Containers.-
• Pre-formed plastic containers intended to be used for packing
of Large Volume Parenteral shall be moulded in-house by one-
continuous operation through an automatic machine.
• Blowing, filling and sealing (plugging) operation shall be
conducted in room(s) conforming to requirements as
mentioned in Table III of Item 3.10. Entry to the area where
such operations are undertaken, shall be through a series of
airlocks. Blowers shall have an air supply which is filtered
through 0.22µ filters. Removal of runners and plugging
operations shall be conducted under a laminar airflow
workstation.
86
 Containers and closures
Rubber Stoppers:-
• The tuber stoppers used for Large Volume
Parenterals shall comply with specifications
prescribed in the current edition of the Indian
Pharmacopoeia.

87
 Production and process
control
1. Written procedures; deviations.
2. Charge-in of components.
3. Calculation of yield.
4. Equipment identification.
5. Sampling and testing of in-process materials
and drug products.
6. Time limitations on production.
7. Control of microbiological contamination.
8. Reprocessing.

88
 Production and process
control
• Production control is a process of making sure
that production is constantly maintained to
produce the products of given specifications.

• Control process have several aspects, such as

raw materials, tools, in-process materials and
finished products.

89
 Production and process
control
• Production control process can be made effective by:
 Setting standards
 Measuring the job performing
 Getting feedback of results
 Taking corrective action
• Production controls are to ensure that orders are not
misunderstood, standards are not violated and
objectives are not shifted unknowing. It is a means of
building quality.

90
 Packaging and labeling
control
1. Materials examination and usage criteria.
2. Labeling issuance.
3. Packaging and labeling operations.
4. Tamper-evident packaging requirements for
over-the-counter (OTC) human drug
products.
5. Drug product inspection.
6. Expiration dating.

91
 Packaging and labeling
control
• Care shall be taken when using automatic
tablet and capsule counting, strip and blister
packaging equipment to ensure that all
‘rogue’ tablets, capsules or foils from
packaging operation are removed before a
new packaging operation is commenced.
There shall be an independent recorded check
of the equipment before a new batch of
tablets or capsules is handled.
92
 Packaging and labeling
control
• Uncoated tablets shall be packed on
equipment designed to minimize the risk of
cross-contamination. Such packaging shall be
carried out in an isolated area when potent
tablets or Beta-Iactum containing tablets are
being packed.
• The strips coming out of the machine shall be
inspected for defects such as misprint, cuts on
the foil, missing tablets and improper sealing.
93
 Packaging and labeling
control
• Integrity of individual packaging strips and
blisters shall be subjected to vacuum test
periodically to ensure leak proofness of each
pocket strip and blister and records
maintained.

94
Packaging and labeling
control

95
 Holding and distribution
1. Warehousing procedures.

2. Distribution procedures.

96
 Holding and distribution
• Prior to distribution or dispatch of given batch of a drug, it
shall be ensure that the batch has been duly tested, approved
and released by the quality control personnel. Pre-dispatch
inspection shall be performed on each consignment on a
random basis to ensure that only the correct goods are
dispatched. Detailed instructions for warehousing and
stocking of Large Volume Parenterals, if stocked, shall be in
existence and shall be complied with after the batch is
released for distribution. Periodic audits of warehousing
practices followed at distribution centers shall be carried out
and records thereof shall be maintained. Standard Operating
Procedures shall be developed for warehousing of products.

97
Holding and distribution

98
 Records and reports
1. General requirements.
2. Equipment cleaning and use log.
3. Component, drug product container, closure, and
labeling records.
4. Master production and control records.
5. Batch production and control records.
6. Production record review.
7. Laboratory records.
8. Distribution records.
9. Complaint files.
99
 Records and reports
• The licensee shall maintain records of different
manufacturing activities with regard to each
stage of manufacture in-process control,
assembling, packing, batch records for the
quantity of devices manufactured from each lot
of blended granules, duration of work, hourly
quantum of production in respect of each item as
well as record of each sterilizing cycle of the
gaseous method employed.

100
 Records and reports
• Records shall be maintained for all disposal of
waste.
• The records shall be made or completed at the
time of each operation in such a way that all
significant activities concerning the manufacture
of pharmaceutical products are traceable.
• Records and associated Standard Operating
Procedures (SOP) shall be retained for at least
one year after the expiry date of the finished
product.
101
 Records and reports
• Records of receipt of all labeling and
packaging materials shall be maintained for
each shipment received indicating receipt,
control reference numbers and whether
accepted or rejected.

102
 Records and reports
The records of the receipts shall include;
a. The name of the material on the delivery note and the
number of containers;
b. The date of receipt;
c. The manufacturer’s and/ or supplier’s name;
d. The manufacturer’s batch or reference number;
e. The total quantity, and number of containers, quantity in each
container received;
f. The control reference number assigned after receipt;
g. Any other relevant comment or information.

103
 Records and reports
The manufacturing records
• Serial number of the Batch Manufacturing Record.
• Reference to Master Formula Record.
• Filter integrity testing records
• Leak test records.
• Inspection records.
• Container washing records.
• Environmental monitoring records.

104
 Records and reports
• Reports of serious adverse drug reactions
resulting from the use of a drug along with
comments and documents shall be forthwith
reported to the concerned licensing authority.
• Reference numbers of relevant analytical
reports.

105
 Returned savaged drug
products
1. Returned drug products.
2. Drug product salvaging.

106
 Returned savaged drug
products
• Adequate areas shall be designed to allow
sufficient and orderly warehousing of
returned or recalled products.
• Segregation shall be provided for the storage
of rejected, recalled or returned materials or
products.

107
 The inspection for compliance
with GMP regulations
• Short description of the self inspection system
indicating whether an outside, independent
and experienced external export was involved
in evaluating the manufacturer’s compliance
with Good manufacturing Practices in all
aspects of production.
• Periodic inspection of the garments shall be
done by responsible staff.

108
 The inspection for compliance
with GMP regulations
• When inspection is done visually, it shall be done
under suitably controlled conditions of illumination
and background.
• Operators doing the inspection shall pass regular
eye-sight checks with spectacles, if worn, and be
allowed frequent rest from inspection.
• Where other methods of inspection are used, the
process shall be validated and the performance of
the equipment checked at suitable intervals. Results
shall be recorded.
109
 The inspection for compliance
with GMP regulations
• Inspection of equipment for cleanliness
immediately before use;
• Clarity testing inspection units.
• Tablet Inspection unit/belt.
• Visual inspection area
• Medical inspection of workers at the time of
employment and periodically check-up thereafter
at least once a year.
• Needle Inspection Unit.
110
 Controlled substances
safeguards
• Hazardous, toxic substances and flammable materials
shall be stored in suitably designed and segregated,
enclosed areas in conformity with Central and State
Legislations.
• Highly hazardous, poisonous and explosive materials
such as narcotics, psychotropic drugs and substances
presenting potential risks of abuse, fire or explosion
shall be stored in safe and secure areas. Adequate fire
protection measures shall be provided in conformity
with the rules of the concerned civic authority.

111