Health Products and Food Branch Direction générale des produits de santé et des aliments Overview...
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Health Santé C anada C anada Health Products and Food Branch Direction générale des produits de santé et des aliments Overview of the Canadian Federal Drug Review Process University of Toronto – Faculty of Pharmacy Marilyn Schwartz A/Director, Bureau of Operational Services Therapeutic Products Directorate September 27, 2004
Health Products and Food Branch Direction générale des produits de santé et des aliments Overview of the Canadian Federal Drug Review Process University
Health Products and Food Branch Direction gnrale des produits
de sant et des aliments Overview of the Canadian Federal Drug
Review Process University of Toronto Faculty of Pharmacy Marilyn
Schwartz A/Director, Bureau of Operational Services Therapeutic
Products Directorate September 27, 2004
Page 2
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 3
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 4 Health Canada
Page 5
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 5 Health Products and
Food Branch
Page 6
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 6 Therapeutic Products
Directorate Effective April 1, 2002 Therapeutic Products
Directorate
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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. o 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. o Similar to CBER in U.S.
F.D.A.
Page 8
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 8 Health Products and
Food Branch (HPFB) Responsibilities for Drugs - contd % HPFB
Inspectorate Compliance & Enforcement n Responsible for
delivery of inspections and investigations, and for most
establishment licensing and related laboratory analysis functions.
% Marketed Health Products Directorate (MHPD) n Responsible for
post-market assessment and surveillance of pharmaceutical and
biological drugs, medical devices, natural health products, radio-
pharmaceuticals.
Page 9
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 10
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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 1 st, 2004) Homeopathic products
Traditional herbal medicines Other Herbals Disinfectants for use on
medical instruments, hospital and food preparation surfaces
Veterinary Drugs
Page 11
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 12
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 12 Life of a New Drug
contd IndustryGovernment 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
Page 13
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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.
Page 14
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 14 New Drug Approval
Process
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 15 New Drug Approval
Process More Details
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 16 Submission
Processing more details
Page 17
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 17 Submission Type
(examples) % Submission Type Examples: NDS New Drug Submission SNDS
Supplement to New Drug Submission ANDS Abbreviated New Drug
Submission (generics)
Page 18
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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/C&M:
clinical and chemistry & manufacturing data but is not a NAS
(e.g. new dosage form, new use)
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 19 Classifying
Submissions contd % Comp/C&M: comparative (clinical,
bioavailability, etc.) data and C&M (e.g. generics; new dosage
forms for innovator products) % C&M/Labelling: no clinical data
(e.g. ANDS where no clinical data is required - injectable,
ophthalmic, nasal soln) % The submission class determines the
performance target.
Page 20
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 21
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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/english/policy/issued/prirevw_e.
pdf
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 23
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 24
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 24 Cost Recovery %
Involves the processing of fees for: n Annual authority to market a
drug in Canada ($8-10 million) o 1300 companies o 22,000 marketed
products n Submission evaluation fees (determined by data package
submitted i.e. number of indications, number of dosage forms, etc.)
$20 million n Fees for Establishment Licences for drugs (1000
licences) and medical devices (900 licences) $6 million L As
outlined in the Financial Administration Act
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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 % C&M for 1 dosage form - $ 15,300
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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.
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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.
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 28 Tracking Drugs in
Canada contd % Continued monitoring, enhancement, synchronization
for: n Drug Submission Tracking System (DSTS) n Drug Establishment
Licensing System (DEL) n Drug Product Database System (DPD) n 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
Page 29
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 30
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 30 Biologics and
Genetic Therapies Directorate
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 31 Key Differences with
Biologicals % Biological drug review also includes: n On-site
evaluations o Assessment of the production process and facility for
a specific product which ensures that the manufacturing process
conforms to information described in the submission. n Additional
GMP (Good Manufacturing Practices) o Special considerations and
issues pertinent to manufacturing and control of biological drugs,
blood and blood components. n Lot-release o Laboratory work on
samples received from drug companies to confirm potency, purity and
safety. o Only high risk products are tested (new products and
vaccines).
Page 32
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 32 Review of Generic
New Drugs Federal Level n Food & Drugs Act and Regulations
amended 1995 o Allows for a generic manufacturer to file an ANDS o
Establishment of bioequivalence by requiring a Canadian Reference
Product (CRP) o Same route of administration as CRP o Same
conditions of use as the CRP o Ensured safety, efficacy and high
quality
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 33 Review of Generic
New Drugs contd ANDS Patent check Pharmaceutically equivalent
and/or Bioequivalence data ( Canadian Reference Product required )
Review Approval recommended Patent Check NOC on HOLD (until patent
issued get resolved NOC issued (approval & declaration of
Bioequivalence) Provincial Assessment Bioequivalence info PM/ label
Chemistry & Manufacturing Pharmaceutical equivalent
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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.
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 35 Regulatory
Scheme
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 36 Patented Medicines
(NOC) Regulations
Page 37
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 37 Post Market Roles
and Activities % Role n Legislated responsibilities, Duty of Care
regarding safety of new drugs % Activities n 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) n Review and analyze safety data n Conduct
risk/benefit assessments of marketed products n Overview of
regulatory advertising activities
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 38 Strengthening
Post-Market Safety of New Drugs Measures will include: n Moving
from reactive to proactive and preventative measures n Expanding
network of Regional Adverse Reaction Centers n Launching
investigations and requiring manufacturers to conduct post-approval
clinical trials n More timely and accurate advice to health care
professionals and the public Outcomes: n Will reduce risks to
Canadians from preventable adverse drug events
Page 39
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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).
Page 40
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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)
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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)
Page 42
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 42 Drugs Marketed in
Canada % 22,000 (approx.) Human Drug Products n 6,000 Prescription
n 9,000 Non-Prescription (includes natural health products with
DINs) n 6,000 Homeopathics n 1,000 Controlled Drugs, Narcotics
& Biologics % 1,450 (approx.) Veterinary Drug Products
Page 43
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 43 The expectations of
stakeholders are clear.. A review process that is more: % Timely %
Predictable % Consistent % Sustainable % Transparent
Page 44
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 44 The TPD Journey from
where we are.to where we need to be Some of the timeMeet
Performance Target Not alwaysPredictable Not necessarilyConsistent
Resource poorSustainable Not veryTransparent Current State Desired
State
Page 45
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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
Page 46
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 46 Strategic
investments in key areas will drive our Business Transformation
Strategy InvestmentsObjectivesAttributesResults Project
ManagementQuality SubmissionPredictable Good Review Practices Good
GuidancesQuality ReviewConsistent A timely Enhanced Capacity drug
International Cooper-Quality DecisionSustainable approval ation
process TransparencyPerformance Transparent
E-ReviewMeasurement
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 47 Backlog Reduction
Milestones and interim commitments
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 48 Workload
Management
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 49 Continuous Balancing
Act % Drug submission review performance is impacted by the many
other issues and challenges which we strive to keep in balance: o
advancements in science and technology o timeliness vs. ensuring
safety / efficacy o adhering to strict regulations/policies and
being flexible and reasonable o participating in an international
community while respecting our domestic environment
Page 50
Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 50 Lexicon ADR Adverse
Drug Reaction ANDS Abbreviated New Drug Submission API Active
Pharmaceutical Ingredient C&M 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
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 51 Lexicon- contd GCP
Good Clinical Practices GMP Good Manufacturing Practices ICH
International Conference on Harmonization ICDRA International
Conference of Drug Regulatory Authorities NHPDNatural 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
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Health Sant Canada Health Products and Food Branch Direction
gnrale des produits de sant et des aliments 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