Good Manufacturing Practices

Learning Outcomes

• Understand GMP concept, the principles as

well as the practice.

• Understand the importance of GMP

Ten (10) Principles of GMP
1. “Writing detailed step-by-step procedures that
provide a roadmap for controlled and consistent
performance”
Ten (10) Principles of GMP
2. “Carefully following written procedures to
prevent contamination, mixups and errors”
 Operations performed within specifically defined areas
Separate or defined areas to prevent contamination or
mixups as follows:

• Areas for receipt, identification, storage

• Areas for folding rejected components;
• Storage of released components;
In order to prevent contamination or mixups the areas
must also include as follows:

• “Storage of in-process materials”

• “Manufacturing and processing operations”
• “Packaging and labeling operations”
• “Quarantine storage before release of drug products”
• “Storage of drug products after release”
• “Control and laboratory operations”
• “Aseptic processing, which includes anything as appropriate”
Ten (10) Principles of GMP
3. “Promptly and accurately documenting work
for compliance and traceability”

Note: Refer to GMP Chapter on Documentation

Ten (10) Principles of GMP

4. “Proving that systems do what they are

designed to do by validation work”

Note: Refer to GMP Chapter on Validation

Ten (10) Principles of GMP
5. “Integrating productivity, product quality, and
employee safety into the design and
construction of facilities and equipment”
• Paragraph 42 of CFR 211 Design and
Construction of features:
• § 211.42 Design and construction features.
– (a) “Any building or buildings used in the
manufacture, processing, packing, or holding of a
drug product shall be of suitable size, construction,
and location to facilitate cleaning, maintenance,
and proper operations”.
– (b) “Any such building shall have adequate space
for the orderly placement of equipment and
materials to prevent mixups between different
components of drug product, containers, closures
(lids), labeling, in-process materials, or drug
products, and to prevent contamination”.

– (c) ”The flow of components, drug product

containers, closures, labeling, in-process materials,
and drug products through the building or
buildings shall be designed to prevent
contamination”.
Ten (10) Principles of GMP
6. Properly maintain facilities and equipment
 (d) “Operations relating to the manufacture, processing, and
packing of penicillin shall be performed in facilities separate
from those used for other drug products for human use”.

Paragraph 44 of CFR 211 addresses lighting issues and states:

§ 211.44 Lighting: Adequate lighting shall be provided in all areas
(d) “Operations relating to the manufacture, processing, and
packing of penicillin shall be performed in facilities separate
from those used for other drug products for human use”.

Paragraph 46 of CFR 211 addresses ventilation systems and states:

§ 211.46 Ventilation, air filtration, air heating and cooling.
• (a) “Adequate ventilation shall be provided”.
• (b) “Equipment for adequate control over air pressure,
microorganisms, dust, humidity, and temperature shall be
provided when appropriate for the manufacture, processing,
packing, or holding of a drug product”.
§ 211.46 Ventilation, air filtration, air heating and cooling.

• (c) “Air filtration systems, including prefilters

and particulate matter air filters, shall be used
when appropriate on air supplies to production
areas. If air is recirculated to production areas,
measures shall be taken to control recirculation
of dust from production”.
§ 211.46 Ventilation, air filtration, air heating and cooling.

• “In areas where air contamination occurs

during production, there shall be adequate
exhaust systems or other systems adequate to
control contaminants”.
§ 211.46 Ventilation, air filtration, air heating and cooling.

• (d) “Air-handling systems for the manufacture,

processing, and packing of penicillin shall be
completely separate from those for other drug
products for human use”.
• The regulations dealing with equipment
requirements:
• § 211.63 Equipment design, size, and location.
– “Equipment used in the manufacture,
processing, packing, or holding of a drug
product shall be of appropriate design,
adequate size, and suitably located to
facilitate operations for its intended use and
for its cleaning and maintenance”.
• § 211.65 Equipment construction.
– (a) “Equipment shall be constructed so that
surfaces that contact components, inprocess
materials, or drug products shall not be reactive,
additive, or absorptive so as to alter the safety,
identity, strength, quality, or purity of the drug
product beyond the official or other established
requirements”.
• § 211.65 Equipment construction.
– (b) “Any substances required for equipment
operation, such as lubricants or coolants, shall NOT
come into contact with components, containers,
closures, in-process materials, or drug products so
as to alter the safety, identity, strength, quality, or
purity of the drug product beyond the official or
other established requirements”.
Ten (10) Principles of GMP
7. Clearly defining, developing and demonstrating
job competence
Ten (10) Principles of GMP
8. Protecting products against contamination by
making cleanliness a daily habit

(d) “Operations relating to the manufacture, processing, and

packing of penicillin shall be performed in facilities separate
from those used for other drug products for human use”.
Paragraph 46 of CFR 211 addresses ventilation systems and states:
§ 211.46 Ventilation, air filtration, air heating and cooling.

• (a) “Adequate ventilation shall be provided”.

• (b) “Equipment for adequate control over air pressure,
microorganisms, dust, humidity, and temperature shall be
provided when appropriate for the manufacture, processing,
packing, or holding of a drug product”.
Ten (10) Principles of GMP
9. “Building quality into products by
systematically controlling our components and
product related processes such as manufacturing,
packaging and Labelling, testing, distribution and
marketing”
Ten (10) Principles of GMP
10. Conducting planned and periodic audits for
compliance and performance
 Definition of GMP

WHO defines Good Manufacturing Practices

(GMP) as “that part of quality assurance which
ensures that products are consistently produced
and controlled to the quality standards
appropriate to their intended use and as required
by the marketing authorization”
• In GMP quality is built into a product.
• Quality Assurance the product meets the final
specifications.
GMP covers all aspects of the manufacturing
process:

– “defined manufacturing process”

– “validated critical manufacturing steps”
– “suitable premises, storage, transport”
– “qualified and trained production and quality
control personnel”
GMP covers all aspects of the manufacturing
process:

– “Adequate laboratory facilities”

– “approved written procedures and instructions”
– “records to show all steps of defined procedures
taken”
– “full traceability of a product through batch
processing records and distribution records”
– “systems for recall and investigation of
complaints”.
• The pharmaceutical industry needs to produce
safe products.
• Challenges to plan, design, construct, validate
manufacturing facilities.
• Due to increased demand for pharmaceuticals.
• Combined with growing productivity in research
and development.
• Guidelines were developed by the pharma-
focused regulatory bodies.
• The modern pharmaceutical industry took
shape in the mid-20th century.
• International pharmaceutical organizations
were forming to manufacture drug products,.
• Today, several firms have over 5% share and
Pfizer acquired Warner-Lambert and
Pharmacia, has over 11% worldwide market
share.
• Manufacturing requirements increasingly
complex.
• The pharmaceutical industry is strongly
regulated.
• The primary health care regulators (FDA,
Medicines and Healthcare products Regulatory
Agency (MHRA) and WHO) are cooperating to
rationalize rules and improve risks assessment
and safety profiles
• There are many ways this is controlled:
A) controlling facility and its systems
B) controlling raw materials,
C) controlling production at all stages,
D) controlling the testing of the product,
E) controlling the identity of materials
F) controlling the storage, etc.
• All of these controls must follow prescribed,
formal, approved procedures, written as
protocols, SOPs or Master Formulae.
 GMP Family

Other good-practice systems, along the same lines as GMP,

exist:
• “Good laboratory practice” (GLP).
• “Good clinical practice” (GCP).
• Good regulatory practice (GRP).
 GMP Family

• Good Distribution Practice (GDP)

• Good Transportation Practice (GTP)
• Referred to as "GxP" requirements.
• Other examples include Good Agriculture Practices, good
guidance practices, and good tissue practices.
 Enforcement / Regulatory Agency

• In the United Kingdom by the ”Medicines and

Healthcare products Regulatory
Agency” (MHRA));
• in the Republic of Korea (South Korea) by
the ”Korea Food & Drug
Administration” (KFDA)
• in Australia by the “Therapeutical Goods
Administration” (TGA)
 Enforcement / Regulatory Agency
• in South Africa by the “Medicines Control Council
(MCC)”
• in Brazil by the ”Agência Nacional de Vigilância
Sanitária” (National Health Surveillance Agency
Brazil) (ANVISA)
• Each of the inspectorates carry out routine GMP
inspections to ensure that drug products are
produced safely and correctly;
 cGMP

• The “current” in current Good Manufacturing

Practices allows solutions to technical issues
to vary.
cGMP
• Manufacturer can decide individually.
• Allows companies to use modern technologies
and innovative approaches to achieve higher
quality through continual improvement.
 cGMP
• Accordingly, the "c" in cGMP stands for
"current," requiring companies to use
technologies and systems that are up-to-date.
• Systems and equipment that may have been
"top-of-the-line" to prevent contamination.
U.S. Food and Drug Administration (FDA)

• FDA’s cGMPs regulations provide minimal

guidance.
• The cGMPs outline facility requirements and
the requirements for the documentation of
manufacturing procedures.