Background

Food and Drugs Act and Regulations

The Food and Drugs Act and Regulations provide authority to Health Canada to regulate the sale of drugs for the purposes of use in human clinical trials. Part C, Division 5 of the Regulations defines specific Clinical Trial Application (CTA) and Clinical Trial Application Amendment (CTA-A) requirements for the sale and importation of drugs for use in human clinical trials in Canada. Links to sections of the Regulations that are relevant to the conduct of clinical trials are listed in the Relevant Links page.

Division 5 of the Regulations came into force in September 2001 and was developed to recognize the generally accepted principles of good clinical practice and internationally competitive submission review time lines.

The Regulations are consistent with the principles, definitions and standards found in the Health Canada / ICH Guidance Documents E6: Good Clinical Practice: Consolidated Guideline, E8: General Considerations for Clinical Trials and E2A: Clinical Safety Data Management: Definitions and Standards for Expedited Reporting. These guidance documents, developed through the International Conference on Harmonisation (ICH) process have been adopted by Health Canada. Together, they define parameters for the design, conduct, performance, monitoring, auditing, recording, analysis and reporting of clinical trials.

Clinical Trial Application (CTA)

Sponsors must file a Clinical Trial Application (CTA) to conduct clinical trials in Phases I through III of drug development and comparative bioavailability trials. This includes applications to conduct clinical trials involving marketed products where the proposed use of the product is outside the parameters of the authorized Notice of Compliance (NOC) or Drug Identification Number (DIN) application (e.g. using a marketed product for a 'new' indication or using an unauthorized dose etc).

Sponsors conducting clinical trials in Canada with products that have received a Notice of Compliance with Conditions (NOC/c) are also required to file a CTA.

Applications to conduct Phase IV trials (i.e. using the drug product within the parameters of the authorized NOC or DIN application) are not subject to filing with Health Canada.

Health Canada reviews the applications and notifies the sponsor within 30 calendar days if the application is found to be deficient. If the application is deemed acceptable, a No Objection Letter (NOL) will be issued within the 30-day review period.

A CTA contains information and documentation to support the objectives and goals of the proposed clinical trial. It also includes data to support the drug product quality. The clinical and quality components of the application are reviewed in parallel and both must be satisfactory before a No Objection Letter can be issued. The approval of local/institutional Research Ethics Boards at each institution must also be obtained before a clinical trial is initiated.

Changes to a previously authorized CTA must be submitted to Health Canada either as a CTA-Amendment or a Notification.

Roles of Stakeholders

Health Canada

Reviews clinical trial protocols to assess the protection and safety of the participants; assesses the quality of the drugs; assures review by Research Ethics Boards; verifies the qualifications of Principal Investigators and monitors and reviews Adverse Drug Reactions (ADRs).

Sponsor

In compliance with the Canadian Food and Drug Regulations, Division 5: adheres to good clinical practices for the proper use of the drugs, record keeping and reporting of Adverse Drug Reactions (ADRs).

Research Ethics Board

Considers ethical issues, such as the protocol, the informed consent documents, conflicts of interest, and financial agreements.

Qualified Investigators

Investigators conducting clinical trials must provide care according to principles of good clinical practice, monitor Adverse Drug Reactions (ADRs), obtain informed consent, and comply with the approved study protocols (issues such as patient selection, dosing, frequency, monitoring etc.). Adverse Drug Reactions (ADRs) must be reported to sponsors and the Research Ethics Board.

Compliance to Regulatory Framework

Compliance to the Regulatory Framework is assured via assessment of submitted applications for clinical trials and oversight of trials during their course. The Health Products and Food Branch Inspectorate has the mandate to conduct inspections of clinical trials. Approximately 2% of trials are inspected each year, with the primary focus on protection of subjects participating in the trial. Inspections are also conducted in the case of complaints or concerns relayed to Health Canada.

Classification of Clinical Trials

Phase I trials

Initial safety studies on a new drug, including first administration of the drugs into humans, usually conducted in healthy volunteers.

Phase II trials

Clinical trials to evaluate the efficacy of the drug in patients with medical conditions to be treated, diagnosed or prevented and to determine the side effects and risks associated with the drug.

Phase III trials

Controlled or uncontrolled trials conducted after preliminary evidence suggesting efficacy of the drug has been demonstrated.

Phase IV trials

All studies performed after the drug has been authorized by the regulator for the market, and related to the authorized indication.

Refer to the GUIDANCE FOR INDUSTRY: General Considerations for Clinical Trials - ICH Topic E8 for more information regarding the phases of clinical development.