Health Canada Review and International Liaison

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• Health Canada Review and International Liaison
• Brigitte Zirger, Director
• Bureau of Policy, Science and International
  ProgramsTherapeutic Products Directorate Health
  Canada
• Access to Medicines and Intellectual Property
  Workshop
• April 21, 2007

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New Drug Review Process (Innovator)
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Review of Generic New Drugs

• Food Drugs Act and Regulations amended 1995
• Allow for a generic manufacturer to file an ANDS
• Allows for establishment of bioequivalence by
  requiring a Canadian Reference Product (CRP)
• Same route of administration as CRP
• Same conditions of use as the CRP
• Ensured safety, efficacy and high quality

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Review of Generic New Drugs
ANDS
Patent check
Pharmaceutically equivalent and/or Bioequivalence
data
(Canadian Reference Product required)
Review
Bioequivalence info PM/ label
Chemistry Manufacturing Pharmaceutical
equivalent
Approval recommended
NOC issued (approval declaration of
Bioequivalence)
NOC on HOLD (until patent issued get resolved)
Patent Check
Provincial Assessment (related to formularies)
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TPDs International Program

• International Regulatory Cooperation (bilateral)
• Bilateral initiatives with other Regulatory
  Authorities on specific initiatives, e.g., MOUs
  to share information, joint initiatives on drugs
  or medical devices
• International Harmonization (multilateral)
• International Conference on Harmonization (ICH)
• Chair, Global Cooperation Group of non-ICH
  Regions
• Global Harmonization Task Force (GHTF) medical
  devices
• Pan-American Network of Drug Regulatory
  Harmonization (PANDRH)
• World Health Organization (Expert Committees)
• Pan-American Health Organization (PAHO)
• Capacity Building and Technical Assistance
• WHO PQP and WHO Alternative Procedure (CAMR)
• Bilateral initiatives
• Foreign Delegations and study session

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Dimensions of Medicines Regulation

• Oversight
• Government
• Public, Professionals
• NGOs, Media

• Levels
• Central
• Region
• District
• Community

• Legal and Administrative Structures
• Policy and Legislation
• Organization
• Human resources
• Financing
• Facilities

Regulatory functions
Inspection GMP, GCP, GLP
Information control of promotion
Marketing Authorization

• Technical
• Elements
• Standards norms
• Guidelines
• SOPs
• Forms
• Certification

Licensing of Persons, premises, and firms
Monitoring drug quality safety
Authorization of clinical trials
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Regulatory Gaps A Global Picture
192 Member States
Developed
20 developed 50 Varying 30 limited or no
capacity
Developing a
Developing b
Developing c1
LDC/CPA - a
Developing c2
LDC/CPA - b
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WHOs Pre-qualification of Essential Medicines

• UN Action Plan for expanding access to medicines
• HIV/AIDS
• Malaria
• Tuberbulosis
• Reproductive Health (Oct 2006 1st Expression of
  Interest)
• Ensuring the safety, efficacy and quality of
  medications procured by international funds

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Why is pre-qualification needed?

• Problems
• Millions of people living with HIV/AIDS, TB and
  malaria have no or limited access to treatment
• Substandard and counterfeit products in different
  countries
• Weak or absent QA systems in the medicines supply
  chain
• Significant investment in procurement, but
• There was no harmonized quality assurance system
  for procurement
• Wide range of quality in drugs procured
• Risks
• Poor quality or counterfeit products
• Risk to patients, toxic reactions, treatment
  failure, resistance
• Risks undermining public confidence

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PQP Basic Principles

• Voluntary for participating manufacturers
• Legitimate General procedures and standards
  approved through WHO Expert Committee involving
  all WHO Member States and WHO Governing bodies
• Widely discussed
• e.g., International Conference of Drug Regulatory
  Authorities (ICDRA), involves more than 100 DRAs
• Transparent
• all information posted to the website
  http//mednet3.who.int/prequal/
• Open to both innovators and multi-source/generic
  manufacturers
• Currently no cost for applicants

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Expected outcome of pre-qualification

• Public lists of products and manufacturing units
• Meeting international norms and standards on
  quality, safety and efficacy
• Capacity building and harmonization
• DRAs, manufacturers, WHO treatment programs,
  NGOs, procurement organizations
• Ongoing quality monitoring
• Pre-qualified products
• Pre-qualification of QC labs (pilot project,
  current focus on AFRO)
• Facilitate access to treatment
• Through fair procurement mechanisms (e.g.,
  tender, competition based on the same quality
  standards)
• WHO commitment to developing better access to
  quality medicines

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How pre-qualification is organized?

• WHO manages and organizes the project on behalf
  of the United Nations
• Provides technical and scientific support, and
  assures that international norms and standards
  are applied to the assessment, inspection (GMP,
  GCP, GLP) and quality control
• Partners
• Aid and funding organization
• Assessors and Inspectors
• Mainly qualified assessors from National Drug
  Regulatory Authorities (also from Nationals
  Quality Control Laboratories) of ICH and
  associated countries, and inspectorates belonging
  to PIC/S

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Assessment of Product Dossiers

• 8-16 professional assessors from DRAs meet in
  Copenhagen for 1 week, every 2 months
• Use a first review / second review system
• Requests for clarification and assessment report
  signed by both reviewers
• Provides opportunity for capacity building by
  pairing experienced assessors with those less
  experienced complements formal training
  activities

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Alternate Procedures

• Innovator products
• Abridged procedure if the product approved by
  stringent authorities like the EMEA and US FDA
• Assessment report from the DRAs, WHO Certificate
  of Pharmaceutical Product (CPP), batch
  certificate, update on changes
• Trusting the scientific expertise of
  well-established DRAs
• Multisource products
• Quality information
• Efficacy and safety bioequivalence study or
  clinical study report via alternate procedure for
  US FDA, EU Article 58 and CAMR)
• Commercial Sample requested but not always tested
  before prequalificaiton

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Steps of Pre-qualification

• Expression of Interest published by WHO for
  required medicines
• Guidance on application process and dossier
  preparation provided on the WHO website
• Dossier received at UNICEF in Copenhagen and Site
  Master File in WHO, Geneva
• Screening of the dossier and samples
• Assessment of the dossier and preparation of a
  written report and assessment letter
• Outcome of the assessment communicated to the
  supplier

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Steps of Pre-qualification - continued

• Inspection of the site(s) of manufacturing and
  follow-up inspection when necessary ? GMP
  compliant list of manufacturers
• Inspection of the Research Laboratory or Contract
  Research Laboratory (CRO) where the
  bioequivalence study has been performed ? GCP
  compliant list of CROs
• Conclusion and listing of the product in the
  prequalification list
• Publication of the WHO Public Assessment and
  Inspection Reports (WHOPARs and WHOPIRs)
• Assessment of the variations when submitted,
  market survey, de-listing if necessary
• Re-qualification after 3-5 years