GMP

GOOD MANUFACTURING PRACTICES

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 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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 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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 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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 cGMP: The Basics

• Quality Control
– Product meets specifications
• Quality Assurance
– Systems ensure control and consistency
– Validation, validation, validation
• Documentation
– If it is not documented, it did not happen

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 cGMP: Raw Materials

• Active ingredients
• Excipients
• Audit suppliers on regular basis
– Before entering into contract, review regulatory history
– Monitor regulatory compliance

• Test incoming raw material

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cGMP: Buildings and Facilities
• Separate or defined areas as are necessary to prevent
contamination or mixups
• Air filtration systems (HVAC) in production areas
• Sanitation

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 cGMP: Production and Process Controls
(“SOPs”)

Written production and process control procedures shall

be followed in manufacturing and shall be documented at
the time of performance. Any deviation from these
procedures shall be recorded and explained or justified.
Standard Operating Practices (SOP)

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 cGMP: In Process Testing

• Must have written procedures and testing of

product while being manufactured to assure
batch uniformity and integrity

• Control procedures shall be established to

monitor output and to validate manufacturing
processes that could cause variability

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 cGMP: Expiration Dating
• To assure that a drug • Expiration dates shall
product meets be related to any
applicable standards of storage conditions
identity, strength, stated on the labeling,
quality and purity at
the time of use, it shall
bear an expiration date

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 cGMP: Packaging and Labeling
Operations

• Company must have written procedures

designed to assure that correct labels,
labeling and packaging materials are used
for drug products; such written procedures
shall be followed.
• Label mix ups have been a major reason for
drug product recalls.

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 cGMP: Laboratory Controls

• Testing and release for distribution

– For each batch of drug product, there shall be laboratory
determination of satisfactory conformance to final specifications
for the drug product, including the identity and strength of each
active ingredient prior to release.

– There shall be appropriate laboratory testing, as necessary, of

each batch required to be free of objectionable microorganisms.

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 cGMP: Stability Testing

A written testing program designed to assess

stability characteristics is required. Stability
testing results must be used in determining
storage conditions and expiration dates.

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cGMP: Production Record Review
• Production and control records shall be reviewed and
approved by the quality control unit to determine compliance
with all established, approved written procedures before a batch
is released or distributed.

– Product Impact Assessment

– Trend Analysis

– Distributed Product

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 cGMP: Responsibility and Authority of
Quality Control
• Quality control unit “shall have the responsibility and
authority to approve or reject all components, drug product
containers, closures, in-process materials, packaging
material, labeling, and drug products, and the authority to
review production records to assure that no errors have
occurred or, if errors have occurred, that they have been fully
investigated.
• The quality control unit shall be responsible for approving or
rejecting drug products manufactured, processed, packed, or
held under contract by another company.”

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 cGMP: Complaints

• Written procedures describing the handling of all

written and oral complaints
• Review by Quality Control unit
– Possible failure to meet any specification
– Determine need for deviation investigation
– Adverse Drug Experience report assessment

• Documentation of complaint and investigation or

reason for not investigating
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 cGMP: Records and Reports
Contemporaneous documentation critical
– Laboratory and production records
– Trending analysis
Data Integrity
Internal review: OOS results, complaints, R&D
External review: FDA inspections, business deals
(due diligence), and products liability cases

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GMP
QA

GMP

QC

QA: Quality Assurance

GMP: Good Manufacturing Practices
QC: Quality Control
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 Faculty of Pharmacy, Omar Al-Mukhtar
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University, Tobruk, Libya.
 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

Is that part of Quality Assurance

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 is that part of GMP • QA is the sum total of
which is concerned with organized arrangements
sampling, specifications,
made with the object of
testing and with in 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.

Faculty of Pharmacy, Omar Al-Mukhtar University,

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

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 QC and QA
• QC is lab based • QA is company based

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 GMP
• The Quality of a formulation or a bulk drug depends on the Quality
of those producing it
• In matter of GMP, swim with the current and
in matter of Quality stand like a rock!
• Provides a high level assurance that medicines are manufactured in
a way that ensures their safety, efficacy and quality
• GMP applies to both Active Pharmaceutical Ingredients (APIs) and
Finished Pharmaceutical Products (FPPs)

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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.

Faculty of Pharmacy, Omar Al-Mukhtar University,

2014/02/18 30
Tobruk, Libya.
 GMP guidelines
• GMP as per Schedule “M”
• GMP as per WHO
• GMP as per MCA now known as MHRA
• 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-UK
TGA: Therapeutic Goods Affairs-AU
FDA: Food And Drug Administration-US
ICH: International Conference on Harmonization

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 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

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 List of important documents in GMP

• Policies
• SOP (Standard Operating Procedure)
• Specifications
• MFR (Master Formula Record)
• BMR (Batch Manufacturing Record)
• Manuals
• Master plans/ files
• Validation protocols
• Forms and Formats
• Records
Faculty of Pharmacy, Omar Al-Mukhtar University,
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Tobruk, Libya.
 10 attributes of a good document
1. Accurate
2. Clear
3. Complete
4. Consistent
5. Indelible (Marks cannot remove)
6. Legible (Handwriting or print)
7. Timely
8. Direct
9. Authentic(Genuine)
10. Authorized
Faculty of Pharmacy, Omar Al-Mukhtar University,
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Tobruk, Libya.
 What are the Benefits of cGMPs?
 They outline a Quality System that reduces or prevents
errors
 Ensures products are safe for use in humans
 Prevent/control contamination and cross-contamination
 Minimizes variations in potency of the drug
 Ensures reproducible physiological activity
 Prevent side effects and toxicity due to variations in drug
content and potency
 Prevents mislabeling and adulteration
 Good Manufacturing Practices

1. Quality assurance
2. Sanitation and hygiene
3. Qualification and validation
4. Product recalls
5. Contract production and analysis
– General
– The contract giver
– The contract accepter
– The contract
 Good Manufacturing Practices (cont'd)

6. Self inspection and quality audits

– Items for self-inspection
– Self-inspection team
– Frequency of self-inspection
– Self-inspection report
– Follow-up action
– Quality audit
– Suppliers’ audits and approval

7. Training
 Good Manufacturing Practices (cont'd)
8. Building and Facilities
– General

– Ancillary areas

– Storage areas

– Weighing areas

– Production areas

– Quality control area

9. Equipment
 Good Manufacturing Practices (cont'd)
10. Materials
– Starting materials
– Packaging materials
– Intermediate and bulk products
– Finished products
– Rejected, recovered, reprocessed and reworked materials
– Recalled products
– Returned goods
– Reagents and culture media
– Reference standards
– Waste materials
– Miscellaneous
Good Manufacturing Practices (cont'd)
11. Documentation or Records

 Documents required:
Labels

Testing procedures

Specifications for starting and packaging materials, for intermediate

and bulk products and for finished products

Master formulae and Batch Processing Records

Packaging instructions and Batch Packaging Records

Standard Operating procedures (SOP's) and records

Logbooks
 OUR EQUIPMENT OUR BUILDING

C THE PRODUCTION &

OUR RECORDS
G DISTRIBUTION OF OUR
M PRODUCTS

LABELLING &
HOW WE PURCHASE AND STORE PACKAGING
RAW MATERIALS
 Key Parts of cGMP’s
Subpart B: Organization and Personnel
Subpart C: Buildings and Facilities
Subpart D: Equipment

Supbart E: Control of Components and Drug Product Containers

and Closures

Subpart F: Production and Process Controls

 Key Parts of cGMP’s
Subpart G: Packaging & Labeling Control
Subpart H: Holding & Distribution
Subpart I: Laboratory Controls
Subpart J: Records & Reports
Subpart K: Returned & Salvaged Drug Product
 ACCURATE RECORD KEEPING IS VITAL …….

When did I
do…. that?

RECORDS MUST BE FILLED OUT AT THE TIME WE

COMPLETE THE JOB!!!
DON’T TRUST YOUR MEMORY!!

Maintenance
&
Cleaning
Record

RECORDS MUST BE FILLED OUT AT THE TIME WE

COMPLETE THE JOB!
 Quality Records
• Records are legal documents and can be subpoenaed in a court
of law as evidence

• Signatures on documentation have the same meaning as on any

kind of contract

• Information must be recorded and signed for at the time of

performance on the original record
 API Manufacturing Process

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Secondary Manufacturing Dosage Forms

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Secondary Manufacturing Process - Tablets

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Secondary Manufacturing Process – Sterile parenteral for injection

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Biotechnology
Manufacturing Process

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Packaging

Faculty of Pharmacy, Omar Al-Mukhtar University,

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Tobruk, Libya.
 Packaging

Faculty of Pharmacy, Omar Al-Mukhtar University,

2014/02/18 54
Tobruk, Libya.
 Packaging

Faculty of Pharmacy, Omar Al-Mukhtar University,

2014/02/18 55
Tobruk, Libya.