1. WHO - PSM Materials Pharmaceutical Quality, Good manufacturing Practice & Bioequivalence Kiev, Ukraine 3 - 7 October 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 Basic Principles of GMP Part One, 14

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

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

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

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

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

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

8. WHO - PSM Materials Starting Materials – III l Identification ä every container ä Identification of sampled container l Release ä Only released materials within their shelf-life should be used Part One 14.14–14.15

9. WHO - PSM Materials Examples of Labelling of Starting Materials

10. WHO - PSM Part One 14.16–14.18 Materials Starting Materials – III l Dispensing: ä designated persons ä written procedure ä accurately weighed ä clean, labelled containers l Independent checks ä material and weight l Dispensed material: ä kept together and labelled

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

12. WHO - PSM Part One 14.21–14.23 Materials Packaging materials II l Specific reference number for batch or consignment l Packaging department checks ä quantity, identity and conformity l Outdated or obsolete material l Printed packaging material ä reconciliation

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

14. WHO - PSM Part One 14.26–14.27 Materials Finished products l Quarantine until released l Storage conditions l Evaluation  product release ä of manufacturing documentation ä QC certificate of analysis ä other documentation (environmental control) ä authorised person

15. WHO - PSM Part One 14.28–14.29 and 14.31 Materials Rejected and recovered materials l Rejected materials ä Clearly marked ä Stored separately in restricted areas ä Action l Reprocessing: ä exceptional ä procedure and records ä batch number ä additional testing

16. WHO - PSM Part One 14.30–14.31 Materials Rejected and recovered materials l Recovery only exceptional!! ä prior authorization!!!! ä additional testing ä accurate documentation

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

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

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

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

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