Title: Overview%20of%20the%20Canadian%20Federal%20Drug%20Review%20Process%20University%20of%20Toronto%20
1Overview 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
2Responsibilities 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
3Federal 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
4Health Canada
5Health Products and Food Branch
6Therapeutic Products Directorate
Therapeutic Products Directorate
Effective April 1, 2002
7Health 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.
-
8Health 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.
9Health 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
10Product 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
11Life 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
-
-
12Life 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
13Drugs 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.
14New Drug Approval Process
15New Drug Approval Process More Details
16Submission 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.
20Data 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
21Priority 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
22Performance 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
23Performance 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
24Cost 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
25Submission 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
-
26Drug 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.
27Tracking 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.
28Tracking 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
29Why 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
30Biologics and Genetic Therapies Directorate
31Key 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).
32Review 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
33Review 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
34Patented 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.
35Regulatory Scheme
36Patented Medicines (NOC) Regulations
37Post 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
38Strengthening 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
39International 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).
40Drug 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)
41Drug 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)
42Drugs 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
43The expectations of stakeholders are clear..
- A review process that is more
- Timely
- Predictable
- Consistent
- Sustainable
- Transparent
44The 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
45Business 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 -
46Strategic 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
47Backlog Reduction Milestones and interim
commitments
48Workload Management
49Continuous 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
50Lexicon
- 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
51Lexicon- 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
52Lexicon - 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