Good Practices in Production and Quality Control. Related Guidelines John Startup

1. Good Practices in Production and Quality Control. Related GuidelinesJohn Startup Good Practices in Production and Quality Control Related Guidelines • JOHN STARTUP Training workshop: Training workshop on regulatory requirements for registration of Artemisinin based combined medicines and assessment of data submitted to regulatory authorities, February 23-27, 2009, Kampala, Uganda.

2. Basic Principles of GMP Good Practices in Production and Quality Control. Related Guidelines

3. Basic Principles of GMP The Ten Commandments of GMP Section 16 and 17

4. Basic Principles of GMP • The Ten Commandments of GMP • 1 Build Adequate Premises • Equip Your Premises with plant and services fit for purpose. • Maintain your premises and equipment • Write procedures • Validate your work/procedures Section 16 and 17

5. Basic Principles of GMP • The Ten Commandments of GMP • Train your workforce • Record your work • 8 Be clean in all things • 9 Test for Quality • 10 Audit for compliance.

6. Basic Principles of GMP The WHO Guidelines EEC Guidelines(ORANGE GUIDE Eudralex Guidelines FDA Guidelines(CFR) MHRA Specific Topics

7. Basic Principles of GMP Well documented and respected guidelines. Most available on the internet (OG is the exception)

8. Basic Principles of GMP Do not forget EP, BP,USP Setting standards as opposed to guidelines

9. Basic Principles of GMP PREMISES EEC 1.3 Specifically Annexe 1 Sterile Manufacture WHO Chapter 1 .12 HVAC Chapter 3 Sterile Manufacture. Eudralex Monograph

10. Basic Principles of GMP EQUIPMENT EEC 3 and 5 (production) Specifically Annexe 1 Sterile Manufacture WHO Chapter 1 (includes HVAC) Chapter 3 Sterile Manufacture. Eudralex Guideline. Also Sterile Manufacture.

11. Basic Principles of GMP CARE and MAINTENANCE EEC 3.34 to 3.44 Cleaning and maintenance. WHO 1.13 Company SOP for service schedule and pre programmed Maintenance (PPM)

12. Basic Principles of GMP • WRITE PROCEDURES • Addressed in the Documentation chapters of the guidelines • EEC 4.19 to 4.29 • Include but not limited to • Inventory control • Sampling • Testing and status control • Manufacture and packaging • Hygiene /environmental monitoring & control

13. Basic Principles of GMP WRITE PROCEDURES Addressed in the Documentation chapters of the guidelines WHO 1.15 Eudralex PIC Annexe 13

14. Basic Principles of GMP VALIDATION Validation protocols usually have a generic format # See WHO 1 appendix 6 Validation Master Plan PIC guideline 10063

15. Basic Principles of GMP VALIDATION “A recorded protocol which demonstrates with a high degree of probability that any activity will repeatedly produce a result within a pre determined specification/requirement. ” All aspects of pharmaceutical manufacture require validation. Sufficiently important to be referred to throughout the guidelines. eg. WHO 1 appendix 6 Normally states the requirement (not negotiable) but rarely “how to”

16. Basic Principles of GMP • TRAINING • WHO 1.10 and EEC 2.8 to 2.12 • Detail training requirements • General company culture • On the job • Outside courses • Tests for proficiency • Authorisation • Training records

17. Basic Principles of GMP • RECORDS • Found in the documentation chapters of • the guidelines. • Examples • Analytical test records • Batch manufacturing documents (BMR) • Cleaning records

18. Basic Principles of GMP CLEANLINESS AND HYGIENE Fleeting reference in EEC and WHO Guidelines PIC gives better information #

19. Basic Principles of GMP QUALITY Quality Assurance Both OG and WHO describe in detail the elements of a robust quality system. Emphasises its all embracing function

20. Basic Principles of GMP QUALITY Quality Control Quality control of raw materials Components Intermediates and finished products. Microbiology

21. Basic Principles of GMP QUALITY Quality Control WHO 1.17 EEC 12.6 Quality control of raw materials Components Intermediates and finished products. Microbiology $ #

22. Basic Principles of GMP AUDITING FOR COMPLIANCE WHO 1.8 EEC2.9 Describes the procedures Aspects of pharmaceutical production to be assessed. Includes audits of suppliers.

23. Basic Principles of GMP So what else is there? ??? ISO9000 GAMP HTM 2010 Validation of Autoclaves BS 6001

24. Basic Principles of GMP OTHERS ISPE Publications on good Pharma Practice HTM 2010 Validation of Autoclaves

25. Basic Principles of GMP WHAT ELSE IS THERE Contract manufacture. Technical agreements. WHO 1.7 EEC 2.7 Both define contract giver and acceptor And their individual and shared responsibilities

26. Basic Principles of GMP WHAT ELSE IS THERE Complaints Recalls Returns Stability programmes.

27. Basic Principles of GMP All the guidelines presented are objectives which are not negotiable Nowhere does it say if it costs too much one can ignore the guideline Nowhere does it say if the resources are unavailable the guideline can be ignored. Whist not negotiable, the means /ways of achieving the objectives are a matter of company style” one man’s solution is another man’s disaster.