Materials

1. Materials Rutendo Kuwana Technical Officer, WHO, Geneva 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 Materials 14

3. 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

4. Materials Principle • Objective of the pharmaceutical manufacturer • produce finished products for patient's use from a combination of materials • Materials combined • Active pharmaceutical ingredients and • Excipients (auxiliary materials) • Packaging materials • Materials include also • Gases, solvents, reagents, process aids, etc. • Special attention 14.1, 14.2

5. Materials General requirements for materials • Materials for cleaning, lubrication, and pest control • Not in direct contact with product • Suitable grade, e.g. food grade if possible • All incoming materials and finished products • quarantined after receipt or processing • until released for use or distribution • stored • under appropriate conditions • orderly fashion (batch segregation) • materials management • stock rotation (FEFO) • Water – suitable for use 14.3–14.6

6. Materials Starting Materials – I • Purchasing – important operation • From approved suppliers – if possible, direct from the manufacturer • Specifications for materials • Consignment checks • Integrity of package • Seal intact • Corresponds with the purchase order • Delivery note • Supplier’s labels • Cleaned and labelled with information 14.7 – 14.10

7. Supplier Evaluation • Historical experience • Questionnaire – including reputation within industry, availability of certificates e.g. ISO 9000 certificates, GMP • Check/compare own analytical results e.g. three batches/shipments with suppliers CoA • Site audit of supplier (case by case basis) • Name and address of manufacturer of critical material must always be known Changes in source (manufacturer or supplier) of critical material should be handled according to Change Control procedure

8. Materials Starting Materials – II • Different batches in one delivery/consignment • Starting materials labelled • name and internal code • Supplier's batch number(s) and manufacturer's on receipt • Status (e.g. quarantine, on test, etc.) • expiry date or retest date Role of validated computer systems • "Sampled" containers identified 14.11 – 14.14

9. Basic Principles of GMP

10. Sampling and Testing • Sampling plans should be scientifically sound (not just statistically based) and appropriate for material being sampled. • They must also be practical/easy to use - obtain a representative sample • Should be based on Risk Assessment • Criticality of the material • Manufacturers/suppliers quality system and manufacturing process • Historical data • Homogeneity

11. Basic Principles of GMP • Damage to and problems with containers • Recorded and reported to QC • Investigated

12. Materials Examples of Labelling of Starting Materials

13. Materials Starting Materials – III • Use only QC released material if within shelf-life • Dispensing • designated persons • written procedure • Correct materials accurately weighed • clean, properly labelled containers • Independent checks and record • material and weight or volume • Dispensed material • kept together and labelled 14.15 – 14.18

14. Basic Principles of GMP

15. Materials Packaging materials - I • Primary and printed packaging materials • purchasing, handling and control • as for starting materials • Printed packaging materials: particular attention • Stored in secure conditions with authorized access • Roll labels where possible in place of cut labels • Loose materials stored and transported in separate, closed containers - to avoid mix-ups • Issued by designated personnel • SOP for issue and returns 14.25–14.20

16. Basic Principles of GMP

17. Materials Printed and primary packaging materials - II • Each delivery or batch: specific reference number or identification mark • Delivery to packaging department • Check quantity, identity and conformity to packaging instructions • Outdated or obsolete material • Destroyed • Disposal record 14.21 – 14.23

18. Basic Principles of GMP Intermediate and bulk products • Kept under appropriate conditions • If purchased as such • Handled on receipt as though these are starting materials 14.24 – 14.25

19. Basic Principles of GMP Finished products • Held in quarantine until their final release • Then stored as usable stock under suitable storage conditions • Evaluation and documentation necessary for release • Product release procedure • Batch record review and related procedure 14.26 – 14.27

20. Materials Rejected, reworked and recovered materials • Rejected materials and products • Clearly marked • Stored separately in restricted areas • Action – returned to supplier/destroyed, etc. in timely manner • Action approved by authorized personnel – records maintained 14.28

21. Materials Rejected, reworked and recovered materials • Rework and recovery • Should be exceptional cases • Only if: • Risks involved have been evaluated and the quality of final product will not be affected • Specifications are met • Defined procedure • Records maintained • New batch number • additional testing to be considered by QC 14.29 – 14.30

22. Materials Recalled products and returned goods • Recalled products • Identified • Stored separately • Secure area - access controlled • Decision taken on their fate • Returned goods • Destroyed unless suitable quality • SOP: decision regarding their fate (relabelling, resale, etc.) • Consider: nature of product, special storage conditions, condition, history, time elapsed since issue • Action taken to be recorded 14.32 – 14.33

23. Materials Reagents and culture media • Records for receipt or preparation • Reagents • Preparation in accordance with SOP • Appropriately labelled: • concentration, standardization factor, shelf-life, date that restandardization is due, storage conditions • signed and dated • Culture media • positive and negative controls each time prepared and used • Inoculum size appropriate 14.34 – 14.36

24. Materials Reference standards - I • Official reference standards • Use preferable whenever these exist • Only for the purpose as per monograph • Storage conditions • Reference standards prepared by the producer • Tested, released and stored in the same way as official standards • In a secure area • A responsible person • Secondary or working standards • Appropriate checks and tests at regular intervals • Standardized against official reference standards – initially and at regular intervals 14.37 – 14.40, 14.42

25. Materials Reference standards - II • Reference standards labelled with information including • Name • Batch, lot or control number • Date of preparation • Shelf-life • Potency • Storage conditions • Stored and used in an appropriate manner 14.41, 14.43

26. Materials Waste materials • Waste materials • proper and safe storage when awaiting disposal • toxic substances and flammable materials: • in suitably designed, separate, enclosed areas as per national legislation • not to be allowed to accumulate • collected in suitable containers for removal to collection points • safe and sanitary disposal • regular and frequent intervals 14.44

27. Materials Miscellaneous materials • Miscellaneous • Rodenticides, insecticides, fumigating agents • Sanitizing material • No contamination risk to equipment, starting materials, packaging materials, in-process materials, finished products 14.45

28. Materials Group session • List specific aspects of GMP requirements, in relation to the groups of materials listed below, that you would assess when inspecting a manufacturer • Printed packaging materials • Thermolabile materials • Water • Sterile materials • Identify three materials that present problems in your experience • What are some of the problems that you have experienced before and during inspection of materials?