1. Supaporn Phumiamorn Division of Biological Products
Materials/Standards
GMP course, Jan, 2006
Supaporn Phumiamorn
Division of Biological Products
เอกสารประกอบการอบรมเรื่อง หลักเกณฑ์และวิธีการที่ดีสำหรับโรงงานผลิตชีววัตถุ

2. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Type of materials
Starting materials
Packaging materials
Intermediate and bulk materials
Finished products
Rejected and recovered materials
Returned goods
Recalled products
Supaporn Phumiamorn,GMP course Jan,2006

3. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Reagent and culture media
Reference standards
Waste materials
Miscellaneous materials
Supaporn Phumiamorn,GMP course Jan,2006

4. General requirements for materials
All incoming materials and finished products
- quarantined after receipt
- until release for use
- distribution
Supaporn Phumiamorn,GMP course Jan,2006

5. General requirements for materials
Stored
- under appropriate condition
-orderly fashion (batch segregation)
- materials management
-stock rotation (FIFO, FEFO)
Supaporn Phumiamorn,GMP course Jan,2006

6. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
General requirements for materials
Documentation
- SOPs
- Records
- Labels
- Specifications
Supaporn Phumiamorn,GMP course Jan,2006

7. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Starting materials
Purchasing
Suppliers
Consignment
- integrity - delivery note
- seal - supplier’s label
- order
Cleaned and labeled
Supaporn Phumiamorn,GMP course Jan,2006

8. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Starting materials
Damaged containers
Starting materials label:
- name and internal code
- batch number
- status
- expiry date or re-test date
Sample container identified
Supaporn Phumiamorn,GMP course Jan,2006

9. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Starting materials
Use only released material
Dispensing
- designated persons
- written procedure
- accurately weighed
- clean, labeled containers
Supaporn Phumiamorn,GMP course Jan,2006
เอกสารประกอบการอบรมเรื่อง หลักเกณฑ์และวิธีการที่ดีสำหรับโรงงานผลิตชีววัตถุ

10. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Starting materials
Independent checks
- material and weight
Dispensed material
- kept together and labeled
Supaporn Phumiamorn,GMP course Jan,2006

11. Why starting materials are so important?
Because their quality can directly
affect the quality of finished
products
Supaporn Phumiamorn,GMP course Jan,2006

12. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Packaging materials
Primary and printed materials:
- as for starting materials
purchasing, handing and control
No unauthorized access
Storage and transport
- avoid mix-ups
- issue and return: SOP
Supaporn Phumiamorn,GMP course Jan,2006

13. Intermediate and bulk products
Appropriate conditions
Purchased:
-as starting materials
Supaporn Phumiamorn,GMP course Jan,2006

14. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Finished products
Quarantine until released
Storage conditions
Evaluation and documentation
- product release
Supaporn Phumiamorn,GMP course Jan,2006

15. Rejected and recovered materials
Rejected materials
- clearly marked
- stored separately in restricted areas
- take action rapidly
Supaporn Phumiamorn,GMP course Jan,2006

16. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Reprocessing
- exceptional
- procedure and records
- batch number
- additional testing
Supaporn Phumiamorn,GMP course Jan,2006

17. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Recovery
- prior authorization
- additional testing
Supaporn Phumiamorn,GMP course Jan,2006

18. Recalled products and returned goods
- identified
-stored separately
- access controlled
Supaporn Phumiamorn,GMP course Jan,2006

19. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Returned goods
- SOP: decision regarding the fate
- nature of product, storage conditions
- history, time lapse
- records
Supaporn Phumiamorn,GMP course Jan,2006

20. Reagents and culture media
Record upon receipt or preparation
Reagents:
- preparation in accordance with SOP
- label:
- concentration, shelf-life, storage conditions
- signed and dated
Supaporn Phumiamorn,GMP course Jan,2006

21. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Culture media:
- positive and negative controls
Supaporn Phumiamorn,GMP course Jan,2006

22. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Reference Standard
Standard must be stable
Sufficient standard must be available for several years
Supaporn Phumiamorn,GMP course Jan,2006

23. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Secondary or working standards:
- appropriate checks and tests
- regular intervals
- based on official reference standards
Supaporn Phumiamorn,GMP course Jan,2006

24. WHO Expert Committee on Biological Standardization (ECBS)
One of the oldest WHO committees
Began as a mechanism for developing primary biological standards
Meet each year in Geneva
Members chosen from the Expert Advisory Panel
Reports published in WHO Technical Report Series
Supaporn Phumiamorn,GMP course Jan,2006

25. WHO Expert Committee on Biological Standardization (ECBS)
Purpose
- To establish primary biological standards
- To prepare written guidance on production and quality control of biological medicinal products
- To develop international consensus on issues of quality, safety and efficacy related to biological products
Supaporn Phumiamorn,GMP course Jan,2006

26. Biological reference materials
Standard and test must be similar in composition and behave in the same way in the test system
Standard does not have to be pure
Standard must have potency value assigned
Supaporn Phumiamorn,GMP course Jan,2006

27. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Calibration System
WHO: Calibration is generally achieved by parallel titration on at least six separate occasions.
NCL: Calibration is routinely performed at
least six times by at least two persons.
(2 NCL labs + Manufacturer lab)
Supaporn Phumiamorn,GMP course Jan,2006

28. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Calibration of WRP for Total OPV
(Measles, Mumps, Rubella)
Supaporn Phumiamorn,GMP course Jan,2006

29. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Parallel line assay
Parallelity
Linearity
Response
95% confidence limit
Probit analysis
Dose
(JE, Rabies ,Hepatitis B, Pertussis vaccines)
Supaporn Phumiamorn,GMP course Jan,2006

30. Reference Standard materials
assuring the uniformity of the testing results
assuring the reliability of the testing results
Supaporn Phumiamorn,GMP course Jan,2006

31. Waste materials and miscellaneous materials
- proper and safe storage
- toxic and flammable materials
- separate, enclosed, as per legislation
- not allowed to accumulate
- collected for safe disposal
- regular intervals
Supaporn Phumiamorn,GMP course Jan,2006

32. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Miscellaneous
- rodenticides, insecticides, sanitizing materials
- contamination risks
Supaporn Phumiamorn,GMP course Jan,2006

33. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Materials checklist
Quarantine
Storage condition
Purchasing
Labelling
Use of release material
Printed packaging material
Purchasing of intermediate or bulk
Supaporn Phumiamorn,GMP course Jan,2006

34. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Materials checklist
Records of the original and history of
seeds/ banks and etc.
Specifications for biological additives
Trypsin is mycoplasma free
Fetal calf serum if from BSC free animals
Certificate of analysis from the supplier
Records of audit of supplier
Supaporn Phumiamorn,GMP course Jan,2006

35. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Warehouse area
Entering
Sufficient capacity
Good storage conditions
Sanitation program
Receiving and dispatch bays
Quarantine areas
Sampling areas
Segregation
Supaporn Phumiamorn,GMP course Jan,2006

36. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Warehouse area
Highly active and hazardous materials
Handling and distribution
Contanmination and cross-contamination
The First Expired/First Out (FEEO)
Rejected materials
Narcotic
Damaged items
Supaporn Phumiamorn,GMP course Jan,2006

37. Warehousing and Distribution
Products
Quarantine
Quality control
Release FIFO
- FEFO
Supaporn Phumiamorn,GMP course Jan,2006

38. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Storage conditions
Stability
Monitoring
- Check and record
- Records
- Equipment calibration
Supaporn Phumiamorn,GMP course Jan,2006

39. Documentations and records
SOPs and Records
Written information
Container’s label
- Name
- Lot number
- Shelf life
- Storage conditions
Supaporn Phumiamorn,GMP course Jan,2006

40. Receipt of incoming materials
Check against the relevant purchase order
Uniformity
Container inspection
Record should be retained for each delivery
Sampling
Quarantine and batch segregation
Written release or rejection
Rejected materials cannot be used
Supaporn Phumiamorn,GMP course Jan,2006

41. Stock rotation and control
Comprehensive records
Periodic stock reconciliation
Significant stock discrepancies
Re-close and reseal
Damaged containers
Outdate materials
Supaporn Phumiamorn,GMP course Jan,2006

42. Dispatch and transport
Integrity
Special care for dry ice
Delivery order
Rules for dispatch
The outside container
Monitor conditions during transportation
Supaporn Phumiamorn,GMP course Jan,2006

43. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
Warehouse check list
Identification of all customers
Records of storage: time, temperatures
Records of date, quantity, mode of packaging
Distribution to customer
SOPs for storage of released products
Supaporn Phumiamorn,GMP course Jan,2006

44. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
SOPs for warehousing
SOPs for shipping, final transit conditions
and storage
Validation and monitoring of shipping methods
Recalled
Maintenance of records for 2 years beyond
Expiry date
Supaporn Phumiamorn,GMP course Jan,2006

45. Supaporn Phumiamorn,GMP course 17-18 Jan,2006
References
WHO,1997. Joint training on GMP for biological products in Thailand, 2-11 September, 1997
Chung Keel Lee, GMP and related topics, October, 2003.
Chung Keel Lee, Current GMP for biological products and its practical implementation, March, 2004.
FDA and WHO, GMP inspection workshop, June, 2004.
Supaporn Phumiamorn,GMP course Jan,2006