Basic Principles of GMP

1. Basic Principles of GMP Materials 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 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

4. 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

5. 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

6. 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

7. Basic Principles of GMP

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

9. Materials Examples of Labelling of Starting Materials

10. 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

11. Basic Principles of GMP

12. 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

13. Basic Principles of GMP

14. 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

15. 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

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. 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

23. 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

24. 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

25. 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?