WHO GMP Certification Scheme M. Mitra Former Dy. Drugs Controller (I), CDSCO, HQ, New Delhi

1. WHO GMP Certification Scheme M. Mitra Former Dy. Drugs Controller (I), CDSCO, HQ, New Delhi

2. WHO GMP CERTIFICATION Originally promugulated in 1969 and revised in 1975. Main objectives were : • Guidelines be developed for official inspections of dug manufacturing facilities • To assess compliance of GMP This would facilitate implementation of the scheme Chennai_12

3. WHO GMP CERTIFICATION With 191 countries members in the scheme a solution was found for international commerce between these countries. The scheme offered a solution for those countries which did not have a developed regulatory agency yet wanted to import drugs. Chennai_12

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5. WHO GMP CERTIFICATION • Basic principles of WHO Good Manufacturing Practice is similar to any established GMP requirement. Allied documents like Schedule M, CFRs, ASEAN GMP, etc are all similar in nature. Anyone following any established GMP procedure will automatically understand the principles in the other GMP requirements. Chennai_12

6. WHO GMP CERTIFICATION WHO GMP requirements have been developed taking into account the principles in various GMP texts and also considering the requirements of developing countries. These requirements are not for domestic use but for international trade. Chennai_12

7. WHO GMP CERTIFICATION • There are around 1000 (?) WHO GMP certified manufacturing establishments in the country, with West Zone leading followed by the South, North and the East Zones. • New Applications are coming in everyday due to increase in exports of drugs, India being a major exporter of Drugs & Pharmaceuticals Globally. • Other purchasers like the State governments, ESI etc. have also started (erroneously) asking for the certificates as preconditions. Chennai_12

8. WHO GMP CERTIFICATION WHO GMP ensures the following: • Avoidance of Cross- Contamination • Prevention of Mix-ups • Provide Traceability • Accountability of actions • Responsibility • Product Performance Guarantee Chennai_12

9. WHO GMP CERTIFICATION Understanding WHO GMP Documents and Literature Chennai_12

10. WHO GMP CERTIFICATION A series of reports known as the WHO Technical Report Series (TRS) are available. • TRS 823 (1992) • TRS 834 (1993) • TRS 863 (1996) • TRS 885 (1999) • TRS 902 (2002) • TRS 908 (2003) • TRS 917 (2004) • TRS 929 (2005) • TRS 937 (2006) Chennai_12

11. WHO GMP CERTIFICATION Other documents A WHO Guide to Good Manufacturing Practice (GMP) Requirements (WHO/VSQ/97.02) (for validation) Chennai_12

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13. WHO GMP CERTIFICATION Various other documents are available with WHO which is freely available for users. WHO website is the best source for getting information. Similarly documents of other established Regulatory agencies can expand knowledge and understanding Chennai_12

14. WHO GMP CERTIFICATION Issue of Certificates What are the Certificates? Three types of Certificates are recommended by the WHO. These are: • Product Certificate(COPP) (TRS 823, 863) • Statement of Licensing Status (TRS 823, 863) • Batch Certificate (TRS 823, 863) There is another Certificate – Site Certificate. Described later Chennai_12

15. WHO GMP CERTIFICATION The member state shall attest the following conditions of a manufacturer if required to attest a product for the certification: • A specific product is authorized to be placed in the market of the exporting country, if not why not • The manufacturing plant is subject to regular inspections for WHO GMP compliance • All product information, including labeling is currently authorized in the certifying country. Chennai_12

16. WHO GMP CERTIFICATION Conditions to be satisfied before opting for the scheme by any member country • Effective national licensing system for products, manufacturers and distributor • Effective control of quality of products, including independent laboratory • A technically competent, experienced, resourceful National Pharmaceutical inspectorate, as part of NDRA having legal powers for investigations • Administrative capacity to issue Certificates and quickly notify WHO and other member countries Chennai_12

17. WHO GMP CERTIFICATION Understanding the Technical Report Series • TRS 823 – Salient features PART I Quality Management in the Drug Industry – Philosophy & Essential Elements • Quality Assurance • Good Manufacturing Practice • Quality Control • Sanitation & Hygiene • Validation • Complaints Chennai_12

18. WHO GMP CERTIFICATION PART I contd. • Product recalls • Contract Production & Analysis • Self-inspection and quality audits • Personnel (including key personnel) • Equipment • Premises • Material • Documentation Chennai_12

19. WHO GMP CERTIFICATION • PART II : Good Practices – Production & Quality Control • Good Practices in Production • Includes General requirements, prevention of cross contamination and bacterial contamination, processing operations, packaging operations • Good Practices in Quality Control • Control of starting material and intermediate, bulk, and finished products, test requirements, production record review, stability studies Chennai_12

20. WHO GMP CERTIFICATION • PART III: Supporting and Supplementary Guidelines • Sterile pharmaceutical Products • General requirements (air classifications), manufacture of sterile preps, personnel, premises, equipment, sanitation, processing, sterilization, filtration, finishing, quality control, • Good Manufacturing Practice for Active Pharmaceutical Ingredients • Explanation, general considerations, personnel, premises, equipment, sanitation, documentation, retention of records and ref samples, production, • Form and content of inspector’s report • Validation of analytical procedures A Model Certificate Format is also presented Chennai_12

21. WHO GMP CERTIFICATION • TRS 863 – Salient features Useful guidelines: • Guidelines for Stability Testing • Guidelines for Validation • Import Procedure for Drugs • Guidelines for implementation of the Scheme (including model certificate) • Guidelines on import procedures for pharmaceutical products Chennai_12

22. WHO GMP CERTIFICATION • TRS 885 – Salient features GMP – Authorised Persons - Role, Functions & Training Role and position of authorized person, implementation of the quality system, education and training., routine duties of an authorized person, • GMP – Supplementary Guidelines for the Manufacture of Pharmaceutical Excepient General considerations, self inspection and quality audits, use of equipment, cleaning programme, starting material, rejected and recovered materials, returned excepients, storage practices, specifications, BPRs, change control and process validation, prevention of cross contamination, blending, microbial contamination, water systems, packaging, quality control etc. Chennai_12

23. WHO GMP CERTIFICATION • TRS 902 – Salient features • Good Practices for National Control Laboratories • Basic elements of GMP (definition) • GMP for Sterile Products – revision • Inspections • National GMP Inspectorate • Guidelines on Packaging of Pharmaceutical Products • Storage areas • Labels Chennai_12

24. WHO GMP CERTIFICATION • TRS 908 – Salient features • GMP for radio pharmaceuticals • GMP for Pharmaceutical Products • Main principles • HACCP • Guidance on GMP: Inspection report • Guide to good storage practices for pharmaceuticals • Model Certificate of a Pharmaceutical Product • Site Certificate – does not replace the Product certificate Chennai_12

25. WHO GMP CERTIFICATION • TRS 917 – Salient features • Active Pharmaceutical Ingredients API • Herbal Chennai_12

26. TRS 929 – Salient features • Concept of sampling of starting materials • Heating ventilation and air conditioning • Validation • Water for pharmaceutical use ..\GMP matters\WHO_TRS_929.pdf Chennai_12

27. TRS 937 – Salient features One of the most important TRS • Supplementary guidelines on GMP for HVAC • (Supplementary guidelines on GMP for Herbals) • Supplementary guidelines on GMP : Validation • HVAC Water Systems • Cleaning • Analytical Method • Computerized Systems • Qualification of systems and equipment • Non-sterile process validation • Good Distribution Practices for pharmaceutical products Chennai_12

28. WHO GMP CERTIFICATION • How to Certify a Product Certification of products are done after thorough examination of the product and the facilities where these are manufactured Chennai_12

29. WHO GMP CERTIFICATION • How to Certify a Product • The facilities are Inspected NRA Inspectors with good knowledge of GMP • The inspection may take two or more days • Certificates are issued by the Issuing Authority on the recommendation of the joint report Chennai_12

30. WHO GMP CERTIFICATION • Requirements • Procedures Main Requirements • Product • Procedures • Facilities Chennai_12

31. WHO GMP CERTIFICATION • Requirements • Product The basic requirements of the product are: • Product design • Stability Studies • Process validation Chennai_12

32. WHO GMP CERTIFICATION • Requirements • Procedures All actions taken in the facility which leads to the production of the final product as per specification. Chennai_12

33. WHO GMP CERTIFICATION • Requirements • Facilities This encompasses the building, machinery, services and utilities, manpower etc. These are guided towards making a properly designed product. Chennai_12

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37. WHO GMP CERTIFICATION • Inspection Points 1. Quality Management 2. Sanitation and hygiene 3. Validation 4. Complaints and recalls 5. Contract production and analysis 6. Self Inspection 7. Personnel Chennai_12

38. WHO GMP CERTIFICATION Discussions: 8. Premises 9. Equipment 10. Materials 11. Documentation 12. Sterile production 13. Active pharmaceutical ingredients Chennai_12

39. WHO GMP CERTIFICATION • GMP consists of various activities which an be grouped together as follows: • Training - induction, ongoing, refresher etc.alonwith such documents like SOP, training calendar, assessment etc. • Cleaning sanitation and hygiene - may also include workers entry procedure, cleaning of the premises etc • Validation and calibration - qualification of machinery, equipment etc. • Storage - apart from normal ware-housing facilities, this should also address quarantine, procedure Etc. Chennai_12

40. WHO GMP CERTIFICATION • movement of manpower, material - uni-flow movement, movements control etc. • Quality assurance – • Quality control • Documentation- must include MFR, BPR, SOP Documents control & distribution, cleaning, training, and document regulating and recording other activities • Change control – • Self inspections and audits Chennai_12

41. WHO GMP CERTIFICATION • Usual Problems faced by Regulatory Agencies: • Fund problems • Lack of knowledge on the part of applicants • Lethargic mindset • Back to original condition after Certification • Usual Problems faced by applicants: • Sometimes lack of Knowledge on the part of auditors • Teacher as well as Examiner status • Lack of time for thorough auditing Chennai_12

42. WHO GMP CERTIFICATION • Useful Web Sites: • http://www.who.int/en/ • http://www.who.int/bookorders/anglais/ • subscription1.jsp?sesslan=1 • http://www.who.int/medicines/organization/ • qsm/activities/qualityassurance/gmp/gmpcover.html • http://www.fda.gov/ • http://www.health.gov.au/tga/docs/html/gmphome.htm • http://www.mca.gov.uk/ Chennai_12

43. WHO GMP CERTIFICATION M. Mitra Former Dy. Drugs Controller (India), CDSCO (M) 9716755102 Email : gmpro@rediffmail.com Chennai_12

44. Thank you Chennai_12