Materials Workshop on GMP and Quality Assurance of TB products Kuala Lumpur Malaysia, 21 – 25 February 2005 Maija Hietav

1. Basic Principles of GMP Materials Workshop on GMP and Quality Assurance of TB products Kuala Lumpur Malaysia, 21 – 25 February 2005 Maija Hietava M.Sci.Pharm Quality Assurance and Safety: Medicines, Medicines Policy and Standards, Health Technology and Pharmaceuticals Cluster Tel: +41.22.791.3598 Fax: +41.22.791.4730 World Health Organization E-mail: hietavam@who.int Part One, 14

2. Materials Objectives • To review specific requirements for each type of material: • Starting materials • Packaging materials • Intermediate and bulk products • Finished products • Rejected and recovered materials • Recalled products • Returned goods • Reagents and culture media • Reference standards • Waste materials • Miscellaneous materials. • To examine (in groups) the problems associated with materials, and how to overcome them.

3. Materials Principle • Objective of the pharmaceutical manufacturer: • produce finished products from a combination of materials • Materials combined: • active pharmaceutical ingredients • auxiliary materials (excipients) • packaging materials • Special attention: specified materials, specified quality of materialsIF NOT  rejected or recalled  lost money, lost time Part One 14.1–14.2

4. Materials General requirements for materials • All incoming materials and finished products • quarantined after receipt, • until released for use • distribution • stored • under appropriate conditions • orderly fashion (batch segregation) • materials management • stock rotation (FIFO or EEFO) • Materials for cleaning, lubrication of equipment, pest control • No direct contact with the product • Should be of suitable grade  minimise health risks Part One 14.3–14.5

5. Materials General requirements for materials • Materials for cleaning, lubrication of equipment, pest control • No direct contact with the product • Should be of suitable grade  minimise health risks • Water • Suitable for the intended use • Sterile • Non-sterile • laboratory Part One 14.3–14.5

6. Materials Starting Materials – I • Purchasing • Competent personnel; regulatory affairs • Suppliers • Approved suppliers • Quality agreement: critical aspects, specifications, rejection,complaint and recall procedures • Consignment • integrity • seal • order • delivery note • supplier’s labels • Cleaned and labelled Part One 14.7–14.10

7. Materials Starting Materials – II • Damaged containers • Different batches in one consignment • Starting material label: • name and internal code • batch number(s), (supplier and manufacturer on receipt) • status • expiry date or re-test date • Sampled containers identified Part One 14.11–14.14

8. Materials Starting Materials – III • Identification • every container • Identification of sampled container • Release • Only released materials within their shelf-life should be used

9. Materials Examples of Labelling of Starting Materials

10. Materials Question no 11 • What is the procedure or test that has to be carried out for every starting material?

11. Materials Starting Materials – III • Dispensing: • designated persons • written procedure • accurately weighed • clean, labelled containers • Independent checks • material and weight • Dispensed material: • kept together and labelled Part One 14.15–14.18

12. Materials Packaging materials I • Primary and printed materials: • as for starting materials • purchasing, handling and control • No unauthorized access • Storage and transport • avoid mix-ups: sealed containers!! • issue and return: SOP • Note: storage and responsible persons of printed packaging material in production! Part One 14.19–14.20

13. Materials Packaging materials II • Specific reference number for batch or consignment • Packaging department checks • quantity, identity and conformity • Outdated or obsolete material • Printed packaging material • reconciliation Part One 14.21–14.23

14. Materials Intermediate and bulk products • Appropriate conditions • Controlled and tested (or validated) • Appropriate time (tested or validated) • Sampling should not have negative affect (cross-contamination, contamination) • Purchased: • as starting materials Part One 14.24–14.25

15. Materials Finished products • Quarantine until released • Storage conditions • Evaluation  product release • of manufacturing documentation • QC certificate of analysis • other documentation (environmental control) • authorised person Part One 14.26–14.27

16. Materials Rejected and recovered materials • Rejected materials • Clearly marked • Stored separately in restricted areas • Action • Reprocessing: • exceptional • procedure and records • batch number • additional testing Part One 14.28–14.29 and 14.31

17. Materials Question no 12 • What is needed from the QC laboratory before a product can be released?

18. Materials Rejected and recovered materials • Recovery only exceptional!! • prior authorization!!!! • additional testing • accurate documentation Part One 14.30–14.31

19. Materials Recalled products and returned goods • Recalled products: • identified • stored separately • access controlled • fate • Returned goods: • SOP: decision regarding the fate • nature of product, storage conditions • history, time lapse • records Part One 14.32–14.33

20. Materials Reagents and culture media • Recorded upon receipt or preparation • Reagents: • preparation in accordance with SOP • label: • concentration, standardisation factor, shelf-life, date that re-standardisation is due, storage conditions • signed and dated • Culture media: • positive and negative controls Part One 14.34–14.36

21. Materials Reference standards-I • Official reference standards • use only as per monograph • storage • Reference standards prepared by the producer: • tested, released • stored in same way as official reference standards • Secondary or working standards: • appropriate checks and tests • regular intervals • based on official reference standards Part One 14.37–14.40

22. Materials Reference standards-II • Labelling of reference standards • minimum information • In-house standards • standardised against an official reference standard • when available • Initially and at regular intervals thereafter • Storage • quality maintained Part One 14.41–14.43

23. Materials Waste materials and miscellaneous materials • Waste materials • proper and safe storage • toxic and flammable materials • separate, enclosed, as per legislation • not allowed to accumulate • collected for safe disposal • regular intervals • Miscellaneous • rodenticides, insecticides, sanitizing material • contamination risks Part One 14.44–14.46

24. Materials Question no 13 • This standard has to be standardised against an official reference standard.

25. Materials Workshop on design of the pharmaceutical facilities 5 groups • Material • Personel flow • Air considitionning • Finishing • QC/QA activities

26. Materials Workshop on design of the pharmaceutical facilities Introduction – 10 min Working – 30 min – leader and secretary Presentations 10 min/group Results also in writing At the end the concesus of the group