Health Products and Food Branch Direction générale des produits de santé et des aliments Overview of the Canadian Federal Drug Review Process Pharmaceutical

Health SantéCanada Canada

Health Products and Food BranchDirection générale des produits de santé et des aliments

Overview of the Canadian Federal Drug Review Process

Pharmaceutical Marketing Club of QuebecEducation Day Seminar

Micheline Ho

Therapeutic Products Directorate

October 19, 2004



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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



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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 Canada

Health CanadaMinister

Deputy Minister

AssociateDeputy Minister

Pest ManagementRegulatory Agency

Office of theChief Scientist

Audit and Accountability

Bureau

Health Policyand

Communications

Population and

Public Health

Health Productsand Food

HealthyEnvironmentsand Consumer

Safety

First Nationsand

Inuit Health

Information,Analysis

andConnectivity

CorporateServices

British Columbiaand

Yukon

Alberta and

NorthwestTerritories

Manitoba and

Saskatchewan

Ontario and

Nunavut

Quebec Atlantic

Regions

Branches



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Health Products and Food Branch



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Roland RotterActing DirectorMedical Devices

Bureau

Paul RoufailInterim Leader

Bureau of Metabolism,Oncology and

Reproductive Sciences

Jacques BouchardInterim Leader

Bureau ofGastroenterology,Infection and Viral

Diseases

Brigitte ZirgerInterim Leader

Bureau of Cardiology,Allergy and

Neurological Sciences

Sultan GhaniInterim Leader

Bureau ofPharmaceutical

Sciences

Hélène BélangerInterim Leader

Bureau of OperationalServices

Kevin DoyleInterim LeaderPolicy Bureau

Brian GillespieInterim Leader

Senior Medical AdvisorBureau

David K. LeeDirector

Office of PatentedMedicines and Liaison

Robert PetersonDirector General

Lynn BernardAssociate Director General

Marilyn SchwartzManager

SubmissionInformation Policy Div.

Effective April 1, 2002




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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.



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Health Products and Food Branch (HPFB) Responsibilities for Human Drugs - cont’d

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.



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Product Types Regulated as “Drugs”

Pharmaceuticals (prescription, non-prescription, brand name, generic)

Biological drugs (vaccines, recombinant drugs, blood products)

Radiopharmaceuticals Natural Health Products

Homeopathic products Traditional herbal medicines Other Herbals

Disinfectants for use on medical instruments, hospital and food preparation surfaces

Veterinary Drugs



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Life of a New Drug

ResearchResearch

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



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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; Division 8 / C.01.014 (DIN) New drug



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New Drug Approval Process

Drug Submission Filed

Initial Processing

Screening Validation

Scientific Review

Safety andEfficacy

Quality(Chemistry and Manufacturing)

Labelling

Approval - recommendation / rejection ( NOC,NON, DIN)

Final Processing

Central Submission ProcessingCost RecoveryApplicability of Patented Medicines (Notice of Compliance) Regulations

DIN IssuanceFinal Patent CheckFinal InvoicingNOC for sign-off

Type/depth of review is dependent on data

requirements



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Submission Processing – more details

Administration DSTS,

acknowledgement, packing, storage

TPD/BGTD

Verificationsubmission

content, forms

Patent CheckPatent Register,

forms

verification of company info

Cost Recoveryinvoicing

Classificationsubmission type, class,



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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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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 - 45 days* NDS – Review : priority - 180 days* non-priority - 300 days* ANDS - Review : - 180 days*

* Calendar days



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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



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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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DIN / NOC / NOC-C

NOC NOC Letter Product Monograph Labels

NOC-C NOC Letter Product Monograph Labels Letter of Undertaking

DINA Authorized labels Prescribing Information



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NOC-C

For: Serious, life-threatening Severely debilitating conditions, or Significant improvement in efficacy Significant decrease in side-effects

when no marketed treatment to adequately manage the condition



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NOC-C (continued)

May provide earlier access Physicians and patients to be aware Letter of Undertaking

Clinical studies ADR monitoring Distribution / Advertising conditions Pre-clearance by PAAB



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Therapeutic Access Strategy (TAS)

Key Business Transformation Strategy

Speech from the Throne - 2002As part of its focus on Smart Regulation, the government …. (will) speed up the regulatory process for drug approvals to ensure Canadians have faster access to the safe drugs they need.”

Budget - 2003Provide $190 million over 5 years “to improve the timeliness of Health Canada’s regulatory processes with respect to human drugs – while preserving the principle that safety is of paramount concern.”



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Health Canada’s Response:The Therapeutics Access Strategy

In the near term, improve regulatory

performance around timeliness and

transparency, benchmarked against

leading international practices



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The Initiatives

Project Management Good Review Practices International Cooperation Transparency E-Review Regulatory Policy Expert Advisory Capacity



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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



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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



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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).



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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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Drug Submissions Received Annually (approx.) (TPD & BGTD) – cont’d

1700 – DINA (Drug Identification Number Application)

360 – Administrative Change SubmissionsChange in manufacturer’s name and/or product

name; cross-reference submissions

1200 – Clinical Trial Applications (previously INDs – Investigational New Drug Submissions)



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Drugs Marketed in Canada

22,000 (approx.) Human Drug Products 6,000 Prescription 9,000 Non-Prescription 6,000 Homeopathics 1,000 Controlled Drugs, Narcotics & Biologics

1,450 (approx.) Veterinary Drug Products



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TPD Websites / Contact Points

TPD Main Website:www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_e.html

SIPD – Marketing Status (Drug Product Database [DPD]): www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_dpd_e.html

NOC Database:www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_noc_e.html

Food and Drugs Act and Regulationswww.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_regulations_e.html

Guidance Documents, Policies, Templates, Forms:www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/index_drugs_information_e.html

Specific Product Information – RPM’s



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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 technologyo 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



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Lexicon

ADR Adverse Drug ReactionANDS Abbreviated New Drug SubmissionBGTD Biologic and Genetic Therapies

DirectorateCDER Center for Drug Evaluation & ResearchDIN Drug Identification Number

(an 8-digit number that all drugs in Canada must have)

DINA Drug Identification Number ApplicationDPD Drug Product DatabaseFDA United States Food and Drug

Administration



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Lexicon- cont’d

FPT Federal / Provincial / TerritorialICH International Conference on

HarmonizationIND Investigational New Drug SubmissionMHPD Marketed Health Products DirectorateNC Notifiable ChangeNDS New Drug SubmissionNOC Notice of Compliance

(an approval letter to market a product in Canada)

NOC-C Notice of Compliance with Conditions



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Lexicon - cont’d

RPM Regulatory Project ManagerSRPM Senior Regulatory Project ManagerPM Product MonographSANDSSupplemental Abbreviated New Drug

SubmissionSIPD Submission Information Policy

DivisionSNDS Supplemental New Drug SubmissionTAS Therapeutic Access Strategy