1. Introduction to GMP

2. Objectives
Acquire basic knowledge of Good Manufacturing Practices (GMP)
What are GMPs ?
Why are they important ?

3. History of Food and Drugs Act
Government Authorities
Canada: Health Canada Health Products and Food Branch (HPFB)
USA: Food & Drug Administration (FDA)
Europe: EC Directives

4. History Food and Drugs Act Food and Drug Regulations
Division 2 : Good Manufacturing Practices
1900’s- Adulterated Food
First purity laws enacted
1930’s- Sulfanilimide
Drugs had to be proven safe
1960’s- Thalidomide
Drugs had to be proven safe and effective through clinical trials

5. Why are GMPs important? Government requirement Ensure quality product
Reduce rejects, recalls
Satisfied customers
Maintain manufacturing consistency
Company image and reputation

6. Drugs
HPFB Definition: Any substance or mixture of substances manufactured, sold or represented for use in
a) the diagnosis, treatment, mitigation or prevention of a disease, a disorder, an abnormal physical state or the symptoms thereof in humans or animals
b) restoring, correcting or modifying organic functions in humans or animals
c) “disinfection” in premises in which food is manufactured, prepared or kept
DIN
Label Claim

7. Food and Drugs Act Establishment license Site Reference File
HPFB Inspections

8. Production Goals Safety Identity Strength Purity Quality
Product is free of unwanted side effects when used appropriately by patient
Identity
Product exactly matches the labelling and related documents
Strength
Product has correct concentration, potency or therapeutic activity of active ingredient
Purity
Product is free from contamination
Quality
Product meets all standards, expectations; performs as claimed
Product made consistently

9. GMP Categories Sale Premises Equipment Personnel Sanitation
Raw Material Testing
Manufacturing Control
Quality Control Department
Packaging Material Testing
Finished Product Testing
Records
Samples
Stability
Sterile Products
Medical Gases

10. Sale C
No distributor … and no importer shall sell a drug unless it has been fabricated, packaged/labeled, tested, and stored in accordance with the requirements of this Division

11. Premises C.02.004 Equipment C.02.005 Permits effective cleaning
Prevents contamination
Orderly conditions
Good state of repair

12. Personnel C.02.006 Appropriate education, training and experience
Sufficient number of people
Receive GMP training
Initial and continuing training as relevant to job responsibilities

13. Sanitation C.02.007 - .008 Sanitation Program to prevent contamination
Limit the sources and types of contamination
Cleaning procedures for facilities & equipment
Pest control
Environmental monitoring
Documented evidence

14. Sanitation C.02.008 Hygiene Health and eye examinations
Report adverse health conditions
Clothing requirements
No direct skin contact with product
Wash hands
No jewelry or excessive makeup
No smoking, eating, drinking, chewing, or keeping of plants in operations areas

15. Raw Material Testing C.02.009 - .010
each lot or batch of raw material is tested
three objectives
confirm the identity of the raw materials
provide assurance that quality of the drug in dosage form will not be altered by raw material defects
assure that raw materials have the characteristics that will provide the desired quantity or yield in manufacturing process

16. Raw Material, Packaging Material and Finished Product Testing
Samples of incoming materials are collected and tested before use
Approved test methods and specifications are used
Results must conform to specifications for release for use or sale
Transportation and storage records

17. Manufacturing Control C.02.011
Written procedures are established and followed
Master formulae, manufacturing order and packaging order
Critical processes are validated
2nd person verification of activities
Quarantine system
Labelling requirements

18. Manufacturing Control C.02.012
Recall Programme
Self-Inspection Programme
Ensure compliance with vendors/contractors

19. Manufacturing Control (cont’d)
Validation: the documented act of demonstrating that any procedure, process, equipment, material, activity, or system will consistently lead to the expected results
TPP 1998 Edition
Design Qualification (DQ)
Installation Qualification (IQ)
Operational Qualification (OQ)
Performance Qualification (PQ)

20. Quality Control Department C.02.013 - C.02.015
Quality Control Responsibilities
Testing of bulk components prior to use by production
Testing of finished product prior to release for sale
Stability program (in association with QA)

21. Quality Control Department C.02.013 - C.02.015
Quality Assurance Responsibilities
Ensure GMP compliance
Review batch records, labels
Release product, based on QC test results
Authorize all master documents and SOPs
Training, auditing
Customer complaints
Recall

22. Key Quality Terms CHANGE CONTROL DEVIATION
written procedure that describes the action to be taken if a change is proposed to facilities, etc. used in fabrication, packaging, and testing of drugs or any change that may affect quality or support system operation
DEVIATION
Planned or unplanned temporary departure from an approved process, specification or procedure with the potential to impact product quality

23. Records C.02.020 - C.02.024 Document all GMP activities
Use Good Documentation Practices (GDP)
Records must be readily available
Needed to prove activities were done

24. Good Documentation Practices
Documentation must be:
permanent (black or blue ink)
legible, clear, concise
accurate
timely
consistent
complete

25. Samples and Stability Samples Stability
Retain samples of each lot of raw material and finished product for specified period of time
Stability
Establish the length of time in which the product meets all specifications
Monitor the drug for this period of time

26. Sterile Products C.02.029 Sterile Products
Packaged in separate enclosed area by trained personnel using method to ensure sterility

27. Summary Pharmaceutical Industry is regulated by GMPs
Good Manufacturing Practices must be followed
GMPs ensure drug products are safe, pure and effective.