L’Inspectorat de la Direction générale des produits de santé et des aliments

1. L’Inspectoratde la Direction générale des produits de santé et des aliments Health Products and Food BranchInspectorate

2. Overview of Canadian GMP Inspection System Tho Huynh, Ph. D., Inspector Presented to SFDA, China, June 2006

3. Overview of Canadian GMP Inspection System Health Canada • Federal department • Committed to improving the lives of all of Canada's people and to making this country's population among the healthiest in the world as measured by longevity, lifestyle and effective use of the public health caresystem.

4. Overview of Canadian GMP Inspection System Health Protection Food Branch (HPFB) Mandate: Take an integrated approach to the management of the risks and benefits to health, related to health products and food by: • Minimizing health risk factors to Canadians while maximizing the safety of the regulatory system; and • Promoting conditions that enable Canadians to make healthy choices and providing information so that they can make informed decisions about their health.

5. Overview of Canadian GMP Inspection System HPFB Inspectorate mandate: • is delivered as a national program, using legislation, policy, science, communication, education and regional operations as the fundamental elements of compliance and enforcement activities; • Coordination in support of operational activities is done nationally to ensure fairness and consistency of approach, and to maintain functional links with other program areas in the Branch; • A quality system approach is followed to ensure uniformity and a high standard of quality for all operations delivered nationally and internationally.

6. Overview of Canadian GMP Inspection System Responsabilities of the Inspectorate: Compliance and enforcement activities Core functions: are compliance monitoring, and compliance verification and investigation, supported by establishment licensing of drugs and medical devices, and laboratory analysis.

7. Overview of Canadian GMP Inspection System • 1 Coordination Center – Ottawa • 5 Operational Centers: • Western Operational Centre • Manitoba and Saskatchewan Operational Centre • Ontario and Nunavut Operational Centre • Quebec Operational Centre • Atlantic Operational Centre

8. Overview of Canadian GMP Inspection System • Good Manufacturing Practices (GMP): • GMP for human and veterinary drugs. • GMP for biologics, blood, bloodproducts • Natural Health Products • Disinfectants classified as drugs. • API – regulatory frameworkunder development

9. Overview of Canadian GMP Inspection System Drug Establisments: • 241 fabricators • 157 packagers/labellers • 369 distributors/importers • 206 wholesalers • 74 testing laboratories • TOTAL = 1047 establishments • 800 foreign sites

10. Overview of Canadian GMP Inspection System Type of inspection: • regular: an inspection against all applicable GMP sections. • re-inspection: a follow-up inspection carried out in response to the assignment of an NC rating. • re-assessment: a follow-up inspection carried out in response to the assignment of an C rating, where corrective measures to previous inspection must be taken in a timely manner • investigative: the first inspection conducted prior to issuance of an establishment licence. Must be followed up with regular inspection in one year • other inspection: (i) a domestic inspection, done at the request of a foreign government or (ii) a domestic inspection conducted by a foreign inspector accompanied by an HPFBI Inspector.

11. Overview of Canadian GMP Inspection System Stages of an inspection: • Preparation • Opening meeting • Plant tour • Documentation review • Report writing • Exit Interview

12. Overview of Canadian GMP Inspection System Preparation: • scheduling • inspection team • notification • inspection plan • review files • samples required

13. Overview of Canadian GMP Inspection System Opening meeting: • discuss purpose and type of inspection • discuss inspection plan • update site profile • verify list of suppliers on Establisment Licence • discuss changes since last inspection • obtain organization chart • obtain floor plan • obtain Cvs from key people • assess the implementation of corrective actions to previous inspection

14. Overview of Canadian GMP Inspection System Plant tour: • follow safety precautions • be careful of what you touch • assess applicable GMP sections • check actual practices vs sops • question all levels of personnel • request pertinent documents • confirm accuracy of observations • keep management informed, esp. of critical observations • tell mgmt of any changes to inspection plan • be careful of entering aseptic areas • note products being manufactured .

15. Overview of Canadian GMP Inspection System Documentation review • assess applicable GMP sections • selecting docs for review: - include as many parameters as possible - inherent risk associated with use of the product - various dosage forms - storage conditions - manufacturing process - subcontractors - complaints and investigations - products that have recently received a Notice of Compliance - products with recent notified changes to their submission.

16. Overview of Canadian GMP Inspection System Documentation review… • Master Production Documents • batch production records • non-conformance or quality incident reports • standard operating procedures and records • validation master plan • qualification of equipment and utilities • process validation protocols and data • cleaning validation data • analytical method validation data • laboratory books • stability data. • review self inspection reports near the end of the inspection

17. Overview of Canadian GMP Inspection System Documentationreview… • Taking notes: Notes should be organized, legible and stored so that they are traceable • Requesting a HHE (Health Hazard Evaluation): If there is reason to believe that the use of the product could result in an unacceptable risk for the user, then request an HHE

18. Overview of Canadian GMP Inspection System Inspection Report: • base all observations of GMP deficiencies on evidence observed at the time of the inspection; • write in a manner that is clear, concise, accurate, is not subject to misinterpretation, and will facilitate corrective action; • cover only one issue per observation.

19. Overview of Canadian GMP Inspection System Inspection rating: • C : recommended for the continuation or issuance of the licence • NC : not recommended for the continuation or issuance of the licence

20. Overview of Canadian GMP Inspection System Exit interview • present draft exit notice • verify accuracy of observations and rating • ensure that the report is understood • allow mgmt to respond • modify exit notice if necessary

21. Overview of Canadian GMP Inspection System Inspection Rating Review Group (IRRG) • Review all NC rating reports • Review selected C rating reports • Rating could be changed

22. Overview of Canadian GMP Inspection System Follow up: • Review establishment's response; • Review the adequacy and completeness of the establishment's response to the Inspection Exit Notice; • Reply, indicating that the response was assessed and include any issues that require follow up.

23. Overview of Canadian GMP Inspection System Compliance and Enforcement: • Food and Drugs Act and Regulations • POL-0001 Compliance and Enforcement Policy • POL-0004 GMP and Establishment Licensing Enforcement Directive • POL-0006 Compliance Hearing, Prosecution and Injunction Policy Guideline • POL-0007 Seizure Policy Guideline.

24. Overview of Canadian GMP Inspection System Compliance and Enforcement Policy (POL-0001) Policy Statement: • Transparency • Fairness • Risk Management • Commitment to Quality • Qualified Staff

25. Overview of Canadian GMP Inspection System Compliance Activities: • Education, Consultation, and Information • Compliance Monitoring • Compliance Verifications and Investigations

26. Overview of Canadian GMP Inspection System Compliance Measures Initiated by the Regulated Party: • Consent to Forfeit • Voluntary Detention • Voluntary Disposal • Voluntary Stop Sale • Recall

27. Overview of Canadian GMP Inspection System Regulatory Measures: • Customs Activities /Target • Injunction • Forfeiture Following Seizure or Prosecution • Public Warning/ Public Advisory • Letters to Trade and Regulated Parties • Regulatory Stop Sale • Search, Seizure and Detention • Refusal, Suspension or Amendment of Establishment Licence • Suspension or Cancellation of Marketing Authorisation/Product Licence, Warning Letter • Appeals

28. Thank you - Merci • tho_huynh@hc-sc.gc.ca • http://www.hc-sc.gc.ca/ahc-asc/index_e.html • http://www.hc-sc.gc.ca/dhp-mps/compli-conform/index_e.html