Good Practices in Production and Quality Control

1. Basic Principles of GMP Good Practices in Production and Quality Control Section 16 and 17

2. Good Practices Objectives • Discuss aspects of good practices in production • Discuss aspects of good practices in quality control • Group session

3. Good Practices Manufacture • WHO Definition: All operations of purchase of materials and products, production, quality control, release, storage and distribution of pharmaceutical products, and the related controls • Production and QC are parts of GMP • Separate training module on QC Glossary

4. Good Practices Design of Premises • Design • Walls, floors, ceilings, ledges, drains, air supply, dust extraction • Prevention of build-up of dirt and dust to avoid unnecessary risks of contamination • Cleaning programme, appropriate cleaning, cleaning records • Effective cleaning and disinfection • choice of materials and chemicals, validation • Drains – prevent backflow • Protection from insects, birds, vermin and weather • from receipt of raw materials to dispatch of released product 12.2, 12.3, 12.7, 12.9, 12.29

5. Basic Principles of GMP • Walls, floors, ceilings – smooth and easy to clean • No ledges or areas where dust can accumulate • Prevention of build-up of dirt and dust to avoid unnecessary risks of contamination

6. Good Practices Avoidance of Cross-Contamination I • Special precautions should be taken to prevent generation and dissemination of dust • Proper air control – supply and extraction, suitable quality • Due to uncontrolled release of: • dust, gas, particles, vapours, sprays, organisms, residue, insects 16.10 - 11

7. Good Practices Avoidance of Cross-Contamination II • Dedicated and self-contained areas for: • Live vaccines • Live bacterial preparations • Certain other biological materials • Penicillin products 16.12(a)

8. Good Practices Avoidance of Cross-Contamination III • Campaign production: • Separation in time • Followed by appropriate cleaning • Validated cleaning procedure 16.12(b)

9. Good Practices Avoidance of Cross-Contamination IV • Ventilation systems and airlocks • Appropriately designed ventilation system with air supply and extraction systems • Supply or incoming air should be filtered • Recirculation of air versus 100% fresh air supply • Proper airflow patterns • Pressure differentials • Appropriately designed airlocks 16.12 (c and d)

10. Good Practices Avoidance of Cross-Contamination V • Clothing • Protection of operator and product • Highly potent products or those of particular risk - need for special protective clothing • Personnel should not move between areas producing different products • Garments need to be cleaned 16.12(e)

11. Good Practices Avoidance of Cross-Contamination VI • Cleaning and decontamination • Procedure for removing soil and dirt • Remove all cleaning chemical residues or disinfectant residues • Remove and/or reduce micro-organisms • Validated (known effectiveness of the procedure) • Use cleanliness status labels • Test for residues 16.12(f, h and i)

12. Good Practices Avoidance of Cross-Contamination -VII • Closed processing systems • For example: totally enclosed water purification systems • Tanks fitted with appropriate filtration - without removable lids • Present special cleaning difficulties, sometimes use clean-in-place (CIP) 16.12(g)

13. Good Practices Production Operations – Sanitation – I • Work-flow • designed to avoid potential contamination • Access • to production areas restricted to authorized personnel • direct operators, QC staff, warehouse staff, maintenance personnel, cleaners • the more critical the area - fewer number of persons there

14. Good Practices Production Operations – Sanitation – II Simultaneous operations • not permissible to process different products in different areas with a common ventilation system • permissible to carry out secondary packaging activities for different products within a packing hall with adequate physical separation

15. Good Practices Production Operations – Sanitation – III Area clearance checks • Process of checking • all materials and documentation from the previous batch removed • all plant and equipment thoroughly cleaned and appropriate status labelling • checklist useful

16. Good Practices Production Operations – Sanitation – IV Area clearance checks • The area clearance check should be carried out by two people • between batches of same product, acceptable for both checks to be carried out by production personnel • for product changeover, second check carried out by QC staff • all checks carried out in accordance with written SOP and results recorded on the batch documentation.

17. Basic Principles of GMP Line opening: • Includes checks on materials and components • Batch number • Expiry date • Printed packaging material including cartons, leaflets, foil . . .

18. Good Practices Production Operations – Sanitation – V • Cleaning and cleaning validation • degree of cleaning depends on whether consecutive batches are of same or different product • Check cleaning agent is fully removed • If possible hot water alone used for cleaning • all cleaning and disinfecting solutions carefully prepared and expiry dated • Final rinse with purified water, or water for injection (for sterile products) • Full records kept

19. Good Practices Production Operations – Sanitation – VI • Water systems • Water - major constituent of most products • SOP for cleaning and sanitization of the water purification system should include distribution pipework • Validation and removal of disinfectant before reuse

20. Good Practices Production Operations – Sanitation – VII • Maintenance and repair • activities inevitable in manufacturing area • Should present no risk to product • Whenever possible, all planned maintenance outside normal operating hours • Emergency work in working area followed by thorough clean down and disinfection before manufacturing recommences • Area clearance by QC

21. Good Practices Good Practices in Quality Control (QC) • Complete module on Quality Control Laboratories. This section only reflects some aspects of good practices in QC labs • Each manufacturer should have a QC Department • Independence from production and other departments is fundamental • Under the authority of an appropriately qualified and experienced person with one or several control laboratories at his or her disposal 17.3

22. Good Practices Basic Requirements for Quality Control Resources • Adequate facilities • Trained personnel • Approved procedures 17.3(a)

23. Good Practices Basic Requirements for Quality Control Tasks • Sampling • Inspecting • Testing • Monitoring • Releasing/rejecting 17.3(a)

24. Good Practices Basic Requirements for Quality Control - I Objects • Starting materials • Packaging materials • Intermediates • Bulk products • Finished products • Environmental conditions 17.3(a)

25. Good Practices Basic Requirements for Quality Control– II 1. Sampling: Methods and personnel approved by QC department 2. Qualification and validation done 3. Making records 4. Ensure ingredients and finished products are of the required quality and comply with marketing authorization, are in correct containers and have correct labels 17.3 b- e

26. Good Practices Basic Requirements for Quality Control – III 5. Records of tests made 6. Review production documentation 7. Assess deviations 8. Retain samples of starting materials and products 9. Release of batches together with the authorized person 17.3 f- h

27. Good Practices Other Duties of the Quality Control Department 1. Establish, validate and implement QC procedures 2. Evaluate, store and maintain reference standards 3. Correct labelling of containers and materials and products 4. Monitor stability of APIs and products 5. Participate in complaint investigations 6. Participate in environmental monitoring 17.4

28. Good Practices Assessment of Finished Products Should embrace all relevant factors, including: • production conditions • in-process test results • manufacturing documentation • compliance with finished product specification • examination of the finished pack 17.5

29. Good Practices QC Access • QC Personnel must have access to production areas: • for sampling • and investigation • As appropriate 17.6

30. Good Practices Quality Control - summary • QC is part of GMP - refer to the handout • sampling • specifications • testing • release procedures • recalls and complaints • decision-making in all quality matters • authorization • definition of product quality • laboratory operations • release decisions • investigation and reporting Part One 3.1, 3.2