L’Inspectorat de la Direction générale des produits de santé et des aliments
Health Products and Food Branch Inspectorate
Overview of Canadian GMP Inspection
System
Presented to SFDA, China, June 2006
Tho Huynh, Ph. D., Inspector
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.
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.
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.
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.
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
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
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
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.
Overview of Canadian GMP
Inspection System
Stages of an inspection:
•
•
•
•
•
•
Preparation
Opening meeting
Plant tour
Documentation review
Report writing
Exit Interview
Overview of Canadian GMP
Inspection System
Preparation:
•
•
•
•
•
•
scheduling
inspection team
notification
inspection plan
review files
samples required
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
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
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.
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
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
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.
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
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
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
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.
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.
Overview of Canadian GMP
Inspection System
Compliance and Enforcement Policy (POL-0001)
Policy Statement:
• Transparency
• Fairness
• Risk Management
• Commitment to Quality
• Qualified Staff
Overview of Canadian GMP
Inspection System
Compliance Activities:
• Education, Consultation, and Information
• Compliance Monitoring
• Compliance Verifications and Investigations
Overview of Canadian GMP
Inspection System
Compliance Measures Initiated by the Regulated
Party:
•
•
•
•
•
Consent to Forfeit
Voluntary Detention
Voluntary Disposal
Voluntary Stop Sale
Recall
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
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/compliconform/index_e.html