The document provides an overview of Good Manufacturing Practices (GMP) guidelines from various regulatory bodies around the world such as the US FDA, WHO, EU, and India. It discusses the history and development of GMP guidelines and regulations. It also summarizes some key GMP guidelines including the US FDA's 21 CFR Parts 210 and 211, WHO's GMP guidelines, ICH Q7 guidelines for APIs, and India's Schedule M under the Drugs and Cosmetics Act. The document further highlights some historical incidents due to lack of GMP compliance and the importance of following GMP guidelines.

1. GOOD MANUFACTURING
PRACTICES
BY
Dr.A.S.CHARAN

2. GOOD MANUFACTURING PRACTICES (GMP)
• Good manufacturing practice is the phrase that is used to encompass all the requirements that need to be complied with in the manufacture
of pharmaceuticals that are both safe and effective.
• US FDA introduced GMP in 1963.
• Four years later WHO prepared GMP in 1967. Later revised in 1968;1971;1975;1992.
• The first GMP guide to be produced in the UK was published in 1971. It was subsequently updated in 1977; 1983;1997:Rules and Guidance
for Pharmaceutical Manufacturers and Distributors (Orange guide).
• In 1991, GMP was introduced by EU MHRA as The principles of GMP within the EU are laid down in Directive 91/356/EEC.
• In 1999, ICH introduced GMP.
• Good manufacturing practice is generally abbreviated to GMP in Europe and many other parts of the world.
• In the USA, the phrase used is ‘current good manufacturing practices’, abbreviated to cGMPs.
• In India, Good Manufacturing Practices guidelines come under Schedule M, The Drugs and Cosmetics Act and Rules.
• Pharmaceutical Inspection Convention (PIC)—guide to GMP for pharmaceutical products.
• Association of South-East Asia Nations (ASEAN)—GMP.

3. Worldwide incidents due to lack of GMP
• In 1937, the use of an oral Sulfanilamide elixir has caused the death of 107 people, many of them
children before the problem was discovered.
• During 1960’s Thalidomide was marketed in Europe as a sleeping pill and to treat morning sickness. An
estimated 10,000 cases of infant deformities in Europe were linked to Thalidomide use.
• At least 109 infants in Nigeria have died due to failure to follow GMP. This was caused due to the supply
of mislabeled ethylene glycol as propylene glycol. This mislabeled material was then supplied to a
pharmaceutical manufacturer.
• Diethylene glycol poisoning that occurred in Haiti from November 1995 to June 1996 due to
contamination of glycerol with diethylene glycol used in the preparation of paracetamol syrup. The
incident led to some 89 deaths of children.

4. Importance of GMP

7. IMPORTANT GMP GUIDELINES
• US FDA GMP:
• 21 CFR Part 210. Current Good Manufacturing Practice in Manufacturing Processing,
packing, or Holding of Drugs.
• 21 CFR Part 211. Current Good Manufacturing Practice for Finished Pharmaceuticals.
• WHO:
• WHO good manufacturing practices for pharmaceutical products: main principles
• WHO good manufacturing practices for biological products

8. INDIAN GMP-SCHEDULE M(D&C ACT & RULES)
• SCHEDULE M: GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES, PLANT AND EQUIPMENT FOR PHARMACEUTICAL
PRODUCTS
• PART 1: GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS
• PART IA : SPECIFIC REQUIREMENTS FOR MANUFACTURE OF STERILE PRODUCTS, PARENTERAL PREPARATIONS (SMALL VOLUME INJECTABLES AND LARGE VOLUME
PARENTERALS) AND STERILE OPHTHALMIC PREPARATIONS.
• PART IB: SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL SOLID DOSAGE FORMS (TABLETS AND CAPSULES)
• PART IC: SPECIFIC REQUIREMENTS FOR MANUFACTURE OF ORAL LIQUIDS (SYRUPS, ELIXIRS, EMULSIONS AND SUSPENSIONS)
• PART ID: SPECIFIC REQUIREMENTS FOR MANUFACTURE OF TOPICAL PRODUCTS , i.e. EXTERNAL PREPARATIONS (CREAMS, OINTMENTS, PASTES, EMULSIONS, LOTIONS,
SOLUTIONS, DUSTING POWDERS AND IDENTICAL PRODUCTS)
• PART 1E: SPECIFIC REQUIREMENTS FOR MANUFACTURE OF METERED-DOSE-INHALERS (MDI)
• PART 1F: SPECIFIC REQUIREMENTS OF PREMISES, PLANT AND MATERIALS FOR MANUFACTURE OF ACTIVE PHARMACEUTIAL INGREDIENTS (BULK DRUGS)
• PART 2 :REQUIREMENTS OF PLANT AND EQUIPMENT
• SCHEDUE M-I: GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES, PLANT AND EQUIPMENT FOR HOMOEOPATHIC
MEDICINES
• SCHEDULE M-II: REQUIREMENTS OF FACTORY PREMISES FOR MANUFACTURE OF COSMETICS
• SCHEDULE M-III: QUALITY MANAGEMENT SYSTEM –FOR NOTIFIED MEDICAL DEVICES AND IN-VITRO DIAGNOSTICS

9. WHO good manufacturing practices for pharmaceutical products:
main principles
1. Quality assurance
a. Product quality review
2. Good manufacturing
practices for pharmaceutical
products
3. Sanitation and hygiene
4. Qualification and validation
5. Complaints
6. Product recalls
7. Contract production and
analysis
a. General
b. The contract giver
c. The contract accepter
d. The contract
8. Self-inspection, quality
audits and supplier’s audits
and approval
a. Items for self-inspection
b. Self-inspection team
c. Frequency of self-
inspection
d. Self-inspection report
e. Follow-up action
f. Quality audit
g. Suppliers’ audits and
approval
9. Personnel
a. General
b. Key personnel
10. Training
11. Personal hygiene
12. Premises
a. General
b. Ancillary areas
c. Storage areas
d. Weighing areas
e. Production areas
f. Quality control areas
13. Equipment
14. Materials
a. General
b. Starting materials
c. Packaging materials
d. Intermediate and bulk
products
e. Finished products
f. Rejected, recovered,
reprocessed and reworked
materials
g. Recalled products
h. Returned goods
i. Reagents and culture
media
j. Reference standards
k. Waste materials
l. Miscellaneous
15. Documentation
a. General
b. Documents required
16. Good practices in production
a. General
b. Prevention of cross-
contamination and
bacterial contamination
during production
c. Processing operations
d. Packaging operations
17. Good practices in quality
control
a. Control of starting
materials and intermediate,
bulk and finished products
b. Test requirements
c. Batch record review
d. Stability studies

10. 21 CFR PART 211 - CURRENT GOOD MANUFACTURING PRACTICE
FOR FINISHED PHARMACEUTICALS
• Subpart A--General Provisions
§ 211.1 - Scope.
§ 211.3 - Definitions.
• Subpart B--Organization and Personnel
§ 211.22 - Responsibilities of quality control unit.
§ 211.25 - Personnel qualifications.
§ 211.28 - Personnel responsibilities.
§ 211.34 - Consultants.
• Subpart C--Buildings and Facilities
§ 211.42 - Design and construction features.
§ 211.44 - Lighting.
§ 211.46 - Ventilation, air filtration, air heating and cooling.
§ 211.48 - Plumbing.
§ 211.50 - Sewage and refuse.
§ 211.52 - Washing and toilet facilities.
§ 211.56 - Sanitation.
§ 211.58 - Maintenance.
• Subpart D--Equipment
§ 211.63 - Equipment design, size, and location.
§ 211.65 - Equipment construction.
§ 211.67 - Equipment cleaning and maintenance.
§ 211.68 - Automatic, mechanical, and electronic equipment.
§ 211.72 - Filters.
• Subpart E--Control of Components and Drug Product Containers and Closures
§ 211.80 - General requirements.
§ 211.82 - Receipt and storage of untested components, drug product containers, and closures.
§ 211.84 - Testing and approval or rejection of components, drug product containers, and closures.
§ 211.86 - Use of approved components, drug product containers, and closures.
§ 211.87 - Retesting of approved components, drug product containers, and closures.
§ 211.89 - Rejected components, drug product containers, and closures.
§ 211.94 - Drug product containers and closures.
• Subpart F--Production and Process Controls
§ 211.100 - Written procedures; deviations.
§ 211.101 - Charge-in of components.
§ 211.103 - Calculation of yield.
§ 211.105 - Equipment identification.
§ 211.110 - Sampling and testing of in-process
materials and drug products.
§ 211.111 - Time limitations on production.
§ 211.113 - Control of microbiological contamination.
§ 211.115 - Reprocessing.
• Subpart G--Packaging and Labeling Control
§ 211.122 - Materials examination and usage criteria.
§ 211.125 - Labeling issuance.
§ 211.130 - Packaging and labeling operations.
§ 211.132 - Tamper-evident packaging requirements for
over-the-counter (OTC) human drug products.
§ 211.134 - Drug product inspection.
§ 211.137 - Expiration dating.
• Subpart H--Holding and Distribution
§ 211.142 - Warehousing procedures.
§ 211.150 - Distribution procedures.
• Subpart I--Laboratory Controls
§ 211.160 - General requirements.
§ 211.165 - Testing and release for distribution.
§ 211.166 - Stability testing.
§ 211.167 - Special testing requirements.
§ 211.170 - Reserve samples.
§ 211.173 - Laboratory animals.
§ 211.176 - Penicillin contamination.
• Subpart J--Records and Reports
§ 211.180 - General requirements.
§ 211.182 - Equipment cleaning and use log.
§ 211.184 - Component, drug product container,
closure, and labeling records.
§ 211.186 - Master production and control records.
§ 211.188 - Batch production and control records.
§ 211.192 - Production record review.
§ 211.194 - Laboratory records.
§ 211.196 - Distribution records.
§ 211.198 - Complaint files.
• Subpart K--Returned and Salvaged Drug
Products
§ 211.204 - Returned drug products.
§ 211.208 - Drug product salvaging.

11. ICH-Q7:GOOD MANUFACTURING PRACTICE GUIDE FOR ACTIVE
PHARMACEUTICAL INGREDIENTS
1. QUALITY MANAGEMENT
1. Principles
2. Responsibilities of the Quality Unit(s)
3. Responsibility for Production Activities
4. Internal Audits (Self Inspection)
5. Product Quality Review
2. PERSONNEL
1. Personnel Qualifications
2. Personnel Hygiene
3. Consultants
3. BUILDINGS AND FACILITIES
1. Design and Construction
2. Utilities
3. Water
4. Containment
5. Lighting
6. Sewage and Refuse
7. Sanitation and Maintenance
4. PROCESS EQUIPMENT
1. Design and Construction
2. Equipment Maintenance and Cleaning
3. Calibration
4. Computerized Systems
5. DOCUMENTATION AND RECORDS
1. Documentation System and
Specifications
2. Equipment Cleaning and Use Record
3. Records of Raw Materials,
Intermediates, API Labelling and
Packaging Materials
4. Master Production Instructions (Master
Production and Control Records)
5. Batch Production Records (Batch
Production and Control Records)
6. Laboratory Control Records
7. Batch Production Record Review
6. MATERIALS MANAGEMENT
1. General Controls
2. Receipt and Quarantine
3. Sampling and Testing of Incoming
Production Materials
4. Storage
5. Re-evaluation
7. PRODUCTION AND IN-PROCESS CONTROLS
1. Production Operations
2. Time Limits
3. In-process Sampling and Controls
4. Blending Batches of Intermediates or
APIs
5. Contamination Control
8. PACKAGING AND IDENTIFICATION LABELLING
OF APIS AND INTERMEDIATES
1. General
2. Packaging Materials
3. Label Issuance and Control
4. Packaging and Labelling Operations
9. STORAGE AND DISTRIBUTION
1. Warehousing Procedures
2. Distribution Procedures
10. LABORATORY CONTROLS
1. General Controls
2. Testing of Intermediates and APIs
3. Validation of Analytical Procedures
4. Certificates of Analysis
5. Stability Monitoring of APIs
6. Expiry and Retest Dating
7. Reserve/Retention Samples
11. VALIDATION
1. Validation Policy
2. Validation Documentation
3. Qualification
4. Approaches to Process Validation
5. Process Validation Program
6. Periodic Review of Validated Systems
7. Cleaning Validation
8. Validation of Analytical Methods
12. CHANGE CONTROL
13. REJECTION AND RE-USE OF MATERIALS
1. Rejection
2. Reprocessing
3. Reworking
4. Recovery of Materials and Solvents
5. Returns
14. COMPLAINTS AND RECALLS
15. CONTRACT MANUFACTURERS (INCLUDING
LABORATORIES)
16. AGENTS, BROKERS, TRADERS, DISTRIBUTORS,
REPACKERS, AND RELABELLERS
1. Applicability
2. Traceability of Distributed APIs and
Intermediates
3. Quality Management
4. Repackaging, Relabelling and Holding
of APIs and Intermediates
5. Stability
6. Transfer of Information
7. Handling of Complaints and Recalls
8. Handling of Returns
17. SPECIFIC GUIDANCE FOR APIS
MANUFACTURED BY CELL
CULTURE/FERMENTATION
1. General
2. Cell Bank Maintenance and Record
Keeping
3. Cell Culture/Fermentation
4. Harvesting, Isolation and Purification
5. Viral Removal/Inactivation steps
18. APIS FOR USE IN CLINICAL TRIALS
1. General
2. Quality
3. Equipment and Facilities
4. Control of Raw Materials
5. Production
6. Validation
7. Changes
8. Laboratory Controls
9. Documentation

12. GOOD MANUFACTURING PRACTICES AND REQUIREMENTS OF PREMISES, PLANT AND
EQUIPMENT FOR PHARMACEUTICAL PRODUCTS
PART 1: GOOD MANUFACTURING PRACTICES FOR PREMISES AND MATERIALS
1. General Requirements
2. Warehousing Area
3. Production area
4. Ancillary Areas
5. Quality Control Area
6. Personnel
7. Health, clothing and
sanitation of workers
8. Manufacturing
Operations and Control
9. Sanitation in the
Manufacturing Premises
10. Raw Materials
11. Equipment
12. Documentation and
Records
13. Labels and other Printed
Materials
14. Quality Assurance
15. Self Inspection and
Quality audit
16. Quality Control
System
17. Specification
18. Master Formula
Records
19. Packing Records
20. Batch Packaging
Records
21. Batch Processing
Records
22. Standard Operating
Procedures (SOPs)
and Records,
regarding
23. Reference Samples
24. Reprocessing and
Recoveries
25. Distribution records
26. Validation and
process validation
27. Product Recalls
28. Complaints and
Adverse Reactions
29. Site Master File

18. THANK YOU