Overview of the Clinical Trial Application Process
Introduction
Depending on the type of clinical trial, sponsors may be required to file a Clinical Trial Application (CTA) for human drug clinical trials. Instances where a CTA must be filed are summarized in the chart below.
| Types Of Clinical Trials | CTA Required? |
|---|---|
| Clinical trials in Phases I through III of developmen | Yes |
| Comparative bioavailability trials | Yes |
Clinical trials involving marketed drugs, where the proposed trial is outside of the parameters of the authorized NOC or DIN application, e.g., one or more of the following is different:
|
Yes |
| Clinical trials in Canada with products that have received a Notice of Compliance with Conditions (NOC/c) | Yes |
| Clinical trials involving marketed drugs where the investigation is to be conducted within the parameters of the authorized NOC or DIN application (Phase IV clinical trials) | No |
A CTA must be filed by the sponsor prior to the initiation of the trial. Approval from both Health Canada and the clinical site(s) Research Ethics Board(s) must be obtained prior to the initiation of the trial.
Sponsors must conduct all clinical trials, including Phase IV trials, in accordance with the principles of good clinical practices.
Pre-CTA Consultation Meeting
Sponsors may request a pre-CTA consultation meeting. Such consultations may be particularly useful for new active substances or applications that will include complex issues that may be new to Health Canada.
Clinical Trial Application (CTA)
The CTA is composed of three Modules:
- Module 1 - contains administrative and clinical information about the proposed trial
- Module 2 - contains Quality (Chemistry and Manufacturing) information about the drug product(s) to be used in the proposed trial
- Module 3 - contains additional supporting Quality information
Each Module should be submitted in a separate binder.
The CTA should be sent directly to the appropriate Directorate:
- CTAs involving pharmaceutical drugs should be sent to the Therapeutic Products Directorate (TPD).
- CTAs involving biologics and/or radiopharmaceuticals should be sent to the Biologics and Genetic Therapies Directorate (BGTD).
Changes to a previously authorized CTA must be submitted to Health Canada either as a Clinical Trial Application - Amendment (CTA-A) or a Notification.
Clinical Trial Application Review
All Clinical Trial Applications (CTAs) and Clinical Trial Application Amendments (CTA-As) are subject to a 30-day default review period from the date of receipt of a complete application in Health Canada.
The application first undergoes a screening phase to ensure that all submission components have been provided. Once screened for acceptability, the application is processed for review and an acknowledgement letter is issued to the sponsor to indicate the start of the review period.
Once review is completed, the application is either authorized (a No Objection Letter is issued) or rejected (a Not Satisfactory Notice is issued).
Post-Authorization Requirements
Once an application has received regulatory authorization, the sponsor is required to inform Health Canada of the following:
- Clinical Trial Site Information
- Changes to a Previously Authorized CTA
- Premature Discontinuation of a Trial
- Adverse Drug Reaction Reporting
- Research Ethics Board Refusals
- Lot Release Information (for Biologics and Radiopharmaceuticals)
- Updated Investigator's Brochure
Records Related to Clinical Trials
Records of clinical trials should be maintained by the sponsor for 25 years, as required in Part C, Division 5 of the Food and Drug Regulations ( C.05.012 - Sponsor's Obligations - Records).
Records must be made available to Health Canada within 2 days if there is a concern regarding the use of a clinical trial drug and/or a risk to the health of the clinical trial subject. In any other case, records must be provided within 7 days of request ( C.05.013 - Sponsors' Obligations - Submission of Information and Samples).