Diapositive 1

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LInspectorat de la Direction générale des
produits de santé et des aliments
Health Products and Food Branch Inspectorate
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Overview of Canadian GMP Inspection System
Presented to SFDA, China, June 2006

• Tho Huynh, Ph. D., Inspector

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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 care system.

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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.

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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.

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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.

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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

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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 framework under
  development

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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

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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.

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Overview of Canadian GMP Inspection System

• Stages of an inspection
• Preparation
• Opening meeting
• Plant tour
• Documentation review
• Report writing
• Exit Interview

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Overview of Canadian GMP Inspection System

• Preparation
• scheduling
• inspection team
• notification
• inspection plan
• review files
• samples required

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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

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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
• .

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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.

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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

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Overview of Canadian GMP Inspection System

• Documentation review
• 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

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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.

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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

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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

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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

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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.

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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.

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Overview of Canadian GMP Inspection System

• Compliance and Enforcement Policy (POL-0001)
• Policy Statement
• Transparency
• Fairness
• Risk Management
• Commitment to Quality
• Qualified Staff

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Overview of Canadian GMP Inspection
System

• Compliance Activities
• Education, Consultation, and Information
• Compliance Monitoring
• Compliance Verifications and Investigations

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Overview of Canadian GMP Inspection System

• Compliance Measures Initiated by the Regulated
• Party
• Consent to Forfeit
• Voluntary Detention
• Voluntary Disposal
• Voluntary Stop Sale
• Recall

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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

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Thank you - Merci

• tho_huynh_at_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/inde
  x_e.html