Overview%20of%20the%20Canadian%20Federal%20Drug%20Review%20Process%20University%20of%20Toronto%20 - PowerPoint PPT Presentation

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Overview%20of%20the%20Canadian%20Federal%20Drug%20Review%20Process%20University%20of%20Toronto%20

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Title: Overview%20of%20the%20Canadian%20Federal%20Drug%20Review%20Process%20University%20of%20Toronto%20


1
Overview of the Canadian Federal Drug Review
ProcessUniversity of Toronto Faculty of
Pharmacy
  • Marilyn Schwartz
  • A/Director, Bureau of Operational Services
  • Therapeutic Products Directorate
  • September 27, 2004

2
Responsibilities for Drugs
  • Federal
  • Regulates the safety, efficacy and quality of
    drugs
  • Ensures patent linkage
  • (Health Products Foods Branch)
  • Controls the price of patented medicines
  • (Patented Medicines Prices Review Board)
  • Coordination and leadership on FPT pharmaceutical
    issues
  • Provincial
  • Delivery of healthcare
  • Practice of Medicine/Pharmacy
  • Reimbursement issues
  • Drug Formularies

3
Federal Legislation and Guidance for Drugs
  • Food and Drugs Act and Regulations
  • Governs the safety, effectiveness and quality of
    drugs and medical devices available to Canadians.
  • Patented Medicines (NOC) linkage Regulation
  • Financial Administration Act

    (fees for review-cost recovery)
  • Access to Information and Privacy Act
  • Controlled Drugs and Substances Act
  • (governs narcotic controlled drugs)
  • Policies and Guidelines (including International
    Guidelines - ICH) in support of the Acts and
    Regulations

4
Health Canada
5
Health Products and Food Branch
6
Therapeutic Products Directorate
Therapeutic Products Directorate
Effective April 1, 2002
7
Health Products and Food Branch (HPFB)
Responsibilities for Drugs
  • Therapeutic Products Directorate (TPD)
  • Responsible for evaluating the safety,
    effectiveness and quality of pharmaceutical drugs
    and medical devices available to Canadians.
  • Similar to CDER in U.S. F.D.A.
  • Biologics and Genetic Therapies Directorate
    (BGTD)
  • Responsible for evaluating the safety,
    effectiveness and quality of biological and
    radiopharmaceutical drugs, as well as blood and
    blood products, viral and bacterial vaccines,
    genetic therapeutic products, tissues, organs and
    xenografts.
  • Similar to CBER in U.S. F.D.A.

8
Health Products and Food Branch (HPFB)
Responsibilities for Drugs - contd
  • HPFB Inspectorate Compliance Enforcement
  • Responsible for delivery of inspections and
    investigations, and for most establishment
    licensing and related laboratory analysis
    functions.
  • Marketed Health Products Directorate (MHPD)
  • Responsible for post-market assessment and
    surveillance of pharmaceutical and biological
    drugs, medical devices, natural health products,
    radio-pharmaceuticals.

9
Health Products and Food Branch
  • Natural Health Products Directorate (NHPD)
  • Ensures that Canadians have ready access to
    health products that are safe, effective, and
    high quality by maintaining proper labelling and
    implementing regulatory framework which supports
    freedom of choice and cultural diversity
  • New regulations came in Jan 2004
  • Veterinary Drugs Directorate (VDD)
  • Ensures the safety of foods such as milk, meat,
    eggs, fish and honey from animals treated with
    veterinary drugs, and that veterinary drugs sold
    in Canada are safe and effective for animals

10
Product Types Regulated as Drugs
  • Pharmaceuticals (prescription, non-prescription,
    brand name, generic)
  • Biological drugs (vaccines, recombinant drugs,
    blood products)
  • Radiopharmaceuticals
  • Natural Health Products (Transition to NHPD,
    January 1st, 2004)
  • Homeopathic products
  • Traditional herbal medicines
  • Other Herbals
  • Disinfectants for use on medical instruments,
    hospital and food preparation surfaces
  • Veterinary Drugs

11
Life of a New Drug
  • Research
  • Create/Isolate Chemicals
    Tissue/Culture More
    Specific animal
  • (14,000 tested to get one as marketable)
    small animals testing and
    in vitro tests
    (e.g. carcinogenicity, reproductive
    studies)
  • Human Testing
  • Special Access Program (SAP)
    (Clinical Trial)
  • (emergency release)
  • HC approval required
  • (Food Drug Act Regulations
    30 day default) Post Market Surveillance
  • Provincial Formulary
    Decisions All testing is done, drug
    company completes analysis of data,
    prepares New Drug
  • PMPRB Submission (NDS)
  • (price controls) HC Review Decision

12
Life of a New Drug contd
  • Industry Government
  • Create/Isolate Chemicals
  • Tissue/Culture
  • More Specific Animal Tests
  • Human Testing (Clinical Trials) ?HC Approval
    required
  • ?Special Access
  • Complete Analysis of data ?HC Review / Decision
  • Prepare New Drug Submission ?PMPRB Federal Price
    Control
  • Negotiate with Provinces ?P/T Formulary
    Decisions
  • Marketing and Promotion to Physicians
    ?Post-Market Surveillance
  • Updates to Product Monographs
  • Dear Health Care Provider Letters ?Post-Market
    Regulatory Actions
  • Product on Market or Removal

13
Drugs Sold in Canada
  • All drugs sold in Canada must be approved by
    Health Canada. These include but are not limited
    to the following
  • drugs imported from other countries
  • drugs manufactured in Canada
  • drugs for export where the exporting company
    needs a Canadian approval in order to enter into
    another country.

14
New Drug Approval Process
15
New Drug Approval Process More Details
16
Submission Processing more details
17
Submission Type (examples)
  • Submission Type Examples
  • NDS New Drug Submission
  • SNDS Supplement to New Drug Submission
  • ANDS Abbreviated New Drug Submission
    (generics)

18
Classifying Submissions
  • The submission package determines the class of
    the submission. Listed below are examples of
    submission classes.
  • NAS New Active Substance (pharmaceuticals
    biologicals)
  • Clin Only clinical data only (e.g. new
    indication)
  • Clin/CM clinical and chemistry manufacturing
    data but is not a NAS (e.g. new dosage form, new
    use)

19
Classifying Submissions contd
  • Comp/CM comparative (clinical, bioavailability,
    etc.) data and CM (e.g. generics new dosage
    forms for innovator products)
  • CM/Labelling no clinical data (e.g. ANDS where
    no clinical data is required - injectable,
    ophthalmic, nasal soln)
  • The submission class determines the performance
    target.

20
Data Requirements Summary
  • New Drugs typically require preclinical,
    clinical,
  • chemistry manufacturing data
  • Generics typically require bioequivalence and/or
    pharmaceutical equivalence data
  • Other Drugs (not new) - information ranging from
    chemistry manufacturing data and/or only
  • formulation and labelling

21
Priority Review
  • ... for a drug submission for a serious, life
    threatening or severely debilitating disease or
    condition for which there is substantial clinical
    evidence that the drug provides
  • effective treatment/prevention/diagnosis of a
    disease or condition for which no drug is
    presently marketed in Canada
  • http//www.hc-sc.gc.ca/hpb-dgps/therapeut/zfiles/e
    nglish/policy/issued/prirevw_e. pdf

22
Performance Targets
  • The type of data package (safety, efficacy,
    quality) submitted and whether or not it is
    accepted for priority review determines the
    performance target
  • Examples
  • Processing - 10 days
  • Screening priority - 25 days
  • Screening - 45 days
  • NDS Review priority - 180 days

  • non-priority - 300 days
  • ANDS - Review - 180 days
  • Calendar days

23
Performance Reporting
  • Drug submission performance is reported
    quarterly and annually
  • Reports are posted on our website
  • http//www.hc-sc.gc.ca/hpb-dgps/therapeut/htmleng/
    drug_submission_reports

24
Cost Recovery
  • Involves the processing of fees for
  • Annual authority to market a drug in Canada
    (8-10 million)
  • 1300 companies
  • 22,000 marketed products
  • Submission evaluation fees (determined by data
    package submitted i.e. number of indications,
    number of dosage forms, etc.) 20 million
  • Fees for Establishment Licences for drugs (1000
    licences) and medical devices (900 licences) 6
    million
  • As outlined in the Financial Administration Act

25
Submission Evaluation Fees
  • The type of data package submitted determines the
    submission evaluation fee
  • Examples New Drugs
  • Preclinical Clinical - 117,000
  • Clinical (no preclinical) - 52,900
  • Comparative data - 17,200
  • C M for active ingred. - 11,500
  • CM for 1 dosage form - 15,300

26
Drug Identification Numbers (DINs)and Notices of
Compliance (NOC)
  • DINS are issued to all drugs approved for
    marketing in Canada.
  • (8 digit number generated by DPD)
  • Must appear on the label
  • Notification of first sale
  • NOC are issued to all new drugs that are
    approved.

27
Tracking Drugs in Canada
  • Health Canada keeps records of drugs marketed in
    Canada it does not keep records of drugs
    approved in the US or any other country.
  • DPD web query a database on our website
    http//www.hc-sc.gc.ca/hpb/drugs-dpd/
  • listing all products marketed in Canada.

28
Tracking Drugs in Canada contd
  • Continued monitoring, enhancement,
    synchronization for
  • Drug Submission Tracking System (DSTS)
  • Drug Establishment Licensing System (DEL)
  • Drug Product Database System (DPD)
  • SAP Financial System
  • 6000 Licence / DIN holders / importers / agents /
    sites
  • Mergers, buyouts, bankruptcies, licence
    agreements
  • Account access, training, management of pick
    lists and linkages between systems

29
Why are Some Drugs not Approved?
  • All drugs must be reviewed to ensure that they
    meet the requirements of the Food and Drugs Act
    and Regulations
  • Drug must have sufficient evidence to support the
    safety, efficacy or quality claims, to be
    approved
  • Drug companies may submit further info. to ensure
    that the safety, efficacy, and quality standards
    are met
  • (e.g. may require further research in animals
    and/or humans)
  • HPFB decision not to approve a drug may be
    appealed by applicant

30
Biologics and Genetic Therapies Directorate
31
Key Differences with Biologicals
  • Biological drug review also includes
  • On-site evaluations
  • Assessment of the production process and facility
    for a specific product which ensures that the
    manufacturing process conforms to information
    described in the submission.
  • Additional GMP (Good Manufacturing Practices)
  • Special considerations and issues pertinent to
    manufacturing and control of biological drugs,
    blood and blood components.
  • Lot-release
  • Laboratory work on samples received from drug
    companies to confirm potency, purity and safety.
  • Only high risk products are tested (new products
    and vaccines).

32
Review of Generic New Drugs
  • Federal Level
  • Food Drugs Act and Regulations amended 1995
  • Allows for a generic manufacturer to file an ANDS
  • 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

33
Review of Generic New Drugs contd
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)
Patent Check
NOC on HOLD (until patent issued get resolved
Provincial Assessment
34
Patented Medicines (NOC) Regulations
  • Protect intellectual property while allowing
    generics to come on the market immediately after
    patent expiry.
  • Brand name companies can file a patent to protect
    a drug which is added to the Patent Register.
  • Generic companies have to clear all patent issues
    before being allowed to market.

35
Regulatory Scheme
36
Patented Medicines (NOC) Regulations
37
Post Market Roles and Activities
  • Role
  • Legislated responsibilities, Duty of Care
    regarding safety of new drugs
  • Activities
  • Monitor and collect adverse drug reaction and
    medication incident data and communicate these to
    health professionals and public
  • (e.g. Advisories for therapeutic products,
    Canadian Adverse Drug Reaction Newsletter,
    Health_Prod_Info)
  • Review and analyze safety data
  • Conduct risk/benefit assessments of marketed
    products
  • Overview of regulatory advertising activities

38
Strengthening Post-Market Safety of New Drugs
  • Measures will include
  • Moving from reactive to proactive and
    preventative measures
  • Expanding network of Regional Adverse Reaction
    Centers
  • Launching investigations and requiring
    manufacturers to conduct post-approval clinical
    trials
  • More timely and accurate advice to health care
    professionals and the public
  • Outcomes
  • Will reduce risks to Canadians from preventable
    adverse drug events

39
International Harmonization
  • HPFB has been very active in helping develop and
    implement international standards for the
    registration of new drugs.
  • HPFB has contributed significantly to the
    development of over 45 harmonized technical
    guidelines.
  • Canada is the only observer country to the
    International Conference on Harmonization (ICH)
    and is committed to implementing finalized ICH
    guidelines and standards including the Common
    Technical Document (CTD).

40
Drug Submissions Received Annually (approx.)
(TPD BGTD)
  • Total 4,400 per year
  • 80 NDS (New Drug Submission)
  • 35 for new active substances
  • 170 SNDS (Supplement to NDS)
  • 80 ANDS (Abbreviated New Drug Submission)
  • 10 SANDS (Supplement to ANDS)
  • 800 NC (Notifiable Change)

41
Drug Submissions Received Annually (approx.)
(TPD BGTD) contd
  • 1700 DINA (Drug Identification Number
    Application)
  • 360 Administrative Change Submissions
  • Change in manufacturers name and/or product
    name cross-reference submissions
  • 1400 Clinical Trial Applications (previously
    INDs Investigational New Drug Submissions)

42
Drugs Marketed in Canada
  • 22,000 (approx.) Human Drug Products
  • 6,000 Prescription
  • 9,000 Non-Prescription (includes natural health
    products with DINs)
  • 6,000 Homeopathics
  • 1,000 Controlled Drugs, Narcotics Biologics
  • 1,450 (approx.) Veterinary Drug Products

43
The expectations of stakeholders are clear..
  • A review process that is more
  • Timely
  • Predictable
  • Consistent
  • Sustainable
  • Transparent

44
The TPD Journey from where we are.to where we
need to be
Desired State
Current State
  • Some of the time Meet Performance Target
  • Not always Predictable
  • Not necessarily Consistent
  • Resource poor Sustainable
  • Not very Transparent

45
Business Transformation Strategy Plan for Change
  • Project Management Tools
  • Enhance Capacity internal external
  • eg Expert Advise, Academic Instructions
  • Good Guidance Practices
  • Communication/Consultation
  • eg Public Advisory Committee (PAC), ACM, PPF
  • International Regulatory Cooperation
  • E-Review eCTD
  • Transparency eg PM project, Summary Basis of
    Decision

46
Strategic investments in key areas will drive our
Business Transformation Strategy
  • Investments Objectives Attributes Results
  • Project Management Quality Submission Predictable
  • Good Review Practices
  • Good Guidances Quality Review Consistent A
    timely
  • Enhanced Capacity drug
  • International Cooper- Quality Decision Sustainable
    approval
  • ation process
  • Transparency Performance Transparent
  • E-Review Measurement

47
Backlog Reduction Milestones and interim
commitments
48
Workload Management
49
Continuous Balancing Act
  • Drug submission review performance is impacted by
    the many other issues and challenges which we
    strive to keep in balance
  • advancements in science and technology
  • timeliness vs. ensuring safety / efficacy
  • adhering to strict regulations/policies and being
    flexible and reasonable
  • participating in an international community while
    respecting our domestic environment

50
Lexicon
  • ADR Adverse Drug Reaction
  • ANDS Abbreviated New Drug Submission
  • API Active Pharmaceutical Ingredient
  • CM Chemistry and Manufacturing
  • CBER Center for Biologics Evaluation Research
  • CDER Center for Drug Evaluation Research
  • CRP Canadian Reference Product
  • DIN Drug Identification Number
    (an 8-digit number
    that all drugs in Canada must have)
  • DMF Drug Master File
  • DPD Drug Product Database
  • FPT Federal / Provincial / Territorial

51
Lexicon- contd
  • GCP Good Clinical Practices
  • GMP Good Manufacturing Practices
  • ICH International Conference on Harmonization
  • ICDRA International Conference of Drug
    Regulatory Authorities
  • NHPD Natural Health Producs Directorate
  • NDS New Drug Submission
  • NOC Notice of Compliance
    (an approval letter to
    market a product in Canada)
  • NON Notice of Non-Compliance
  • (letter outling deficiencies after completion
    of review)
  • PAAB Pharmaceutical Advertising Advisory Board
  • PM Product Monograph

52
Lexicon - contd
  • PMPRB Patented Medicines Prices Review Board
  • POA Plan of Action
  • QC Quality Control
  • SDA State Drug Administration
  • SIPD Submission Information Policy Division
  • TCM Traditional Chinese Medicine
  • TOR Terms of Reference
  • US FDA United States Federal Drug Administration
  • WHO World Health Organization
  • WTO World Trade Organization
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