GOOD MANUFACTURING

PRACTICES FOR
PHARMACEUTICALS

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 CONTENTS
• Current GMP in manufacturing processes
• Packaging and holding of drugs
• Finished pharmaceuticals
• General provisions
• Organization and personnel
• Building and facilities
• Equipment
• Control of components
• Containers and closures
• Production and process control
• Packaging and labeling
• control Holding and
• distribution Records and
• reports
• Returned savaged drug
• products
• The inspection for compliance with GMP regulations
Controlled substances safeguards 2
 What is GMP ?
(Good Manufacturing Practices)

• 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.

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 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.

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 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.

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 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.

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GMP
QA

GMP

QC

QA: Quality Assurance

GMP: Good Manufacturing Practices
QC: Quality Control
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QA, GMP & QC inter-relationship

QA
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

GMP

Part of QA system aimed at

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

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QA, GMP & QC inter-relationship

QC
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

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

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 QC and QA

• Operational laboratory • those planned or

systematic actions
All techniques and activities
used to fulfill the necessary to provide
requirement of Quality adequate confidence
that a product will
satisfy the requirements
for quality

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 QC and QA

• QC is lab based • QA is company based

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 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
• Inmatter of GMP, swim with the current and
in matter of Quality stand like a rock!

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 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.

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 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.
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 GMP guidelines
• GMP as per Schedule “M”
• GMP as per WHO
• GMP as per DRAP
• GMP as per TGA
• GMP as per US FDA
• GMP as per ICH guidelines
WHO: World Health Organization
MHRA: Ministry of Health and Regulatory Affairs
TGA: Therapeutic Goods Affairs
FDA: Food And Drug Administration
ICH: International Conference on Harmonization

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 GMP guidelines
• GMP as per WHO www.who.int
GMP as per TGA www.tga.gov.au
• GMP as per US FDA www.fda.gov
GMP as per ICH guidelines www.ich.org
•

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 GMP
• GMP in solid dosage forms
• GMP in semisolid dosage forms
• GMP in Liquid orals
• GMP in Parenterals Production
• GMP in Ayurvedic medicines
• GMP in Bio technological products
• GMP in Nutraceuticals and cosmeceuticals

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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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 List of
important
• Policiesdocuments in GMP
• SOP (Standard Operating Procedure)
• Specifications
• MFR (Master Formula Record)
• BMR (Batch Manufacturing Record)
• Manuals
• Master plans/ files
• Validation protocols
• Forms and Formats
• Records
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API Manufacturing
Process

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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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 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
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 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.
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Packaging

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Packaging

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Packaging

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 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.
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 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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 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.

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 Organization and personnel
1. Responsibilities of quality control unit.

2. Personnel qualifications.

3. Personnel responsibilities.

4. Consultants.

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 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.

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 Equipment
1. Equipment design, size, and location.
2. Equipment construction.
3. Equipment cleaning and maintenance.
4. Automatic, mechanical, and electronic
equipment.
5. Filters.

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 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.
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 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.
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 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.

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 Packaging and
labeling
1. control
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.

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 Holding and distribution
1. Warehousing procedures.

2. Distribution procedures.

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 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.

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

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 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.

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 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.

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 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.

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 References
• EU Good Manufacturing Practice (GMP)
Guidelines, Volume 4 of “The rules governing
medicinal products in the European Union”
• US current GoodManufacturing
FDA
Practice (cGMP) for
pharmaceuticals, 21 CFR, 210finished
and 211
• WHO Good Manufacturing Practices for
pharmaceutical products, Annex 4 to WHO
Technical Report Series, No. 908, 2003
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