Basic Principles of GMP

1. Good Manufacturing Practice
(GMP)

2. What is GMP?
“GMP is the documented way
of using your common sense.”
 Good manufacturing practice (GMP) is the
minimum standard that a medicines
manufacturer must meet in their production
processes. Products must:
be of consistent high quality
be appropriate to their intended use
meet the requirements of the marketing
authorisation (MA) or product specification

3. What is GMP?
Good Manufacturing
Practices are a set of
regulations, codes, and
guidelines for the
manufacture of:
- Drug substances and
drug products
- Medical devices
- In vivo and in vitro
diagnostic products
- Foods

4. A Time line of GMP
1902 - Development of the Biologic Control Act
1906 - Development of the Pure Food and Drug Act
1938 - Federal Food, Drug and Cosmetic Act
1941 - Initiation of GMP
1944 - Development of Public Health Services Act
1962 - Kefauver-Harris Drug Amendments released
1963 - Establishment of GMPs for Drugs
1975 - CGMPs for Blood and Components Final Rule
1976 - Medical Device Amendments
1978 - CGMPs for Drugs and Devices
1979 - GLPs Final Rule
1980 - Infant Formula Act is passed

5. Provisions
21 CFR Parts 210 and 211
(Drug Industry)
21 CFR Part 820
(Medical Device Industry)
21 CFR Part 110
(Food Industry)
21 CFR Part 606
(Blood Industry

6. Why GMP?
 Provides a high level assurance that
medicines are manufactured in a way
that ensures their safety, efficacy and
quality
 Medicines are manufactured to
comply with their marketing
authorization
 Quality is built in
◦ Testing is part of GMP, but alone does not
provide a good level of quality assurance

7. OBJECTIVE
Guarantee high quality products to the
consumer.
Delivering products free of all
possible contamination

8. cGMP Violations -- severe
Consequences
Product is “adulterated”
Shutdown of manufacturing facility
Seizure of product
Recall product
Front page press coverage
Competitive disadvantage

9. cGMP Violations -- severe
Consequences
 GMP Hold on product applications
◦ International sites
 Injunction / Consent decree
◦ Schering Plough ($500 Million)
◦ Abbott Laboratories ($100 Million)
◦ Wyeth–Ayerst Laboratories ($30 Million)
◦ Individual Defendants
 Criminal Investigations and Indictments
 Lawsuits
◦ United States ex rel. King

10. The ten commandments for GMP
• Write the procedure
• Follow the written procedure
• Document the work
• Validate the work
• Design the building, facilities & equipment's properly
• Personnel shall be Competent
• Maintenance of the building, facilities & Equipmets
• Shall be Clean
• Control for Quality
• Audit for compliance

11. Write the procedure
 All work/process must be written.
 Write the SOPs, Spec., MOA,
Protocol, Report etc.
 Documents should not be hand
written.
 All documents should be kept up-to-
date.

12. Follow the written procedure
 Written procedure has to follow 100%.
 If it is difficult to follow written
procedure discuss with your
supervisor and make deviation note, if
needed.
 Violation of written procedure is a
crime.

13. Document the work
Document the work means records &
reports. It should be
 Accurate
 Prompt
 Legible
 Clear
 Consistent
 Complete
 Direct
 Truthful

14. Document the work
 No written evidence No work.
 All records should include date and
identity of people (Signature).
 All records should include second
check Signature.

15. Validate the work
Validation:
Establishing a documented evidence
which provides a high degree of
assurance that any procedure, process,
equipment, material, activity will
consistently produce a product meeting its
pre-determined specification and quality
attributes.

16. Validate the work
Types of Validation:
Process Validation
Cleaning Validation
Computer system validation
Analytical method Validation
System, facilities, equipment Validation
 In accordance with GMP, each
pharmaceutical company should identify
what qualification and validation work is
required to prove that the critical aspects
of their particular operation are controlled.

17. Validate the work
Validation of System, facilities, equipment
also called Qualification.
Design Qualification (DQ)
Installation Qualification (IQ)
Operation Qualification (OQ)
Performance Qualification (PQ)

18. Design the building, facilities & equipments
properly
 The layout and design of premises must aim to minimize 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.
Main consideration to good pharmaceutical factory design
are-
 Segregation of different types of operation
 Grouping together of related types of activity or product
 Internal layout- Logical flow of material and personnel
 Appropriate plant services, systems & utilities
 Protection from weather, pests, dust, dirt etc.
 Easy to clean and sanitize
 Rest and refreshment rooms should be separate from
manufacturing and control areas.
 Proper Security

19. Design the building, facilities & equipment
properly
Plant services, systems & utilities include-
HVAC
Lighting (300 Lux - 500 Lux) FDA
Electricity
Water
Air
Dust control and collection system
Drains and waste disposal system
Steam
Cooling system etc.

20. Design the building, facilities &
equipment properly
 Equipment must be located, designed, constructed, adapted,
and maintained to suit the operations to be carried out. The
layout and design of equipment must aim to minimize 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.
 Production equipment should not present any hazard to the
products.
 Laboratory equipment and instruments should be suited to the
testing procedures undertaken.
 Washing, cleaning and drying equipment should be chosen and
used so as not to be a source of contamination.
 Fixed pipework should be clearly labelled

21. Personnel shall be Competent
 The manufacturer should have an adequate number of
personnel with the necessary qualifications and practical
experience.
 All responsible staff should have their specific duties recorded in
written descriptions and adequate authority to carry out their
responsibilities.
 All personnel should be competent
Competent as a result of-
Education
Training
Experience

22. Personnel shall be Competent
 Key personnel 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.

23. Maintenance of the building, facilities &
equipment
 Premises should be carefully maintained,
and it should be ensured that repair and
maintenance operations do not present
any hazard to the quality of products.
Maintenance of the system to ensure that it
continues to operate to designed
standard.
a) Preventive Maintenance
b) Maintenance after shutdown
For Preventive Maintenance there shall be
i) Maintenance schedule
ii) Written Maintenance procedure

24. Shall be Clean
 Cleaning is required to prevent contamination
 There shall be a written program and procedure for cleaning
 Disinfectant shall be used on an alternating or rotating basis
 Disinfectant should always be used as per instruction and at the
right dilution.
 A high level of sanitation and hygiene should be practised in every
aspect of the manufacture of drug products. The scope of sanitation
and hygiene covers personnel, premises, equipment and
apparatus, production materials and containers, products for
cleaning and disinfection, and anything that could become a source
of contamination to the product.

25. Control for Quality
 There shall be well established Quality
control department
 Quality control department should be
independent from production department
 Materials are not released for use, nor
products released for sale or supply, until
their quality has been judge satisfactory
 Control of quality is a combined effort of
all departments
 Quality can not be controlled it should be
built into product.

26. Audit for compliance
Quality Audit:
A systematic and independent
examination to determine whether
quality activities and related results
comply with planned arrangements
and whether these arrangements are
implemented effectively and are
suitable to achieve objectives.
Two types-
a) Internal

27. Audit for compliance
Self-Inspection-
- Follow a prearranged plan
- Inspection should be independent
(unbiased)
- Conducted by competent person
- Results and findings should be recorded
- Report should contain all observations
- Recommend for corrective action
- Follow up
- Monitor for improvement

28. Audit for compliance
Inspection Musts
Ensure that the
RIGHT PEOPLE
discuss the
RIGHT INFORMATION
at the
RIGHT TIME
in the RIGHT WAY!

29. Conclusion
Result of cGMP compliant
Compliant with regulatory authorities
Manufacture & Release quality
products in respect of Quality, Safety
& Efficacy
Increase productivity
Increase company image
Customer satisfaction