If you are a Sponsor/CRO conducting clinical research in both Canada and the U.S., there are important differences between the Canadian Clinical Trial Application (CTA) and the U.S. Investigational New Drug (IND) submission process.

IND Submission Process in the U.S.

In the U.S., once the IND has been submitted for review, the FDA has 30 calendar days in which to determine whether a clinical hold is necessary. If the Sponsor does not hear back from the FDA, on day 31 after submission of the IND, the Study may proceed as submitted once it has been approved by an IRB. A written acknowledgement from the FDA is not always provided. Once an IND application is in effect, the Sponsor is expected to submit Protocol Amendments to the FDA for review prior to implementation. However, a written acknowledgement from the FDA is not required for implementation of the Amendment; the Amendment may be implemented once it has been submitted to the FDA and approved by an IRB (21 CFR § 312.30). If the Sponsor wishes to receive comments regarding a submission from the FDA, a request for such comment – along with the specific questions to be addressed – must be provided at the time of submission.

CTA Submission Process in Canada

The approval process is different in Canada. Once a CTA has been submitted and reviewed, Health Canada notifies the Sponsor within 30 calendar days if the application is found to be acceptable or deficient. If the application is deemed acceptable, a No Objection Letter (NOL) (Guidance Document For Clinical Trial Sponsors: Clinical Trial Applications, section 2.5) is issued by Health Canada. Clinical study activities cannot begin until the NOL has been issued by Health Canada and the Study has been approved by an IRB/REB. The same process applies when there is an Amendment to the Clinical Study Protocol. As per Canadian regulations, the Amendment may not be implemented at any Sites in Canada until Health Canada has issued a new NOL (or an Acknowledgement of Notification for non-substantive modifications to the Protocol). It is the Sponsor/CRO’s responsibility to ensure that no Sites implement the Amendment until Health Canada has issued the new NOL.

Management of Submissions by Veritas IRB

Submissions may be made to Veritas IRB prior to, or concurrently with, submission to the FDA and/or Health Canada. The IRB/REB can approve a clinical trial prior to the end of the 30-day FDA IND review period or the issuance of the NOL by Health Canada. In the latter, however, a note should be included in the IRB/REB’s Approval Form stating that research activities may not begin until the NOL has been issued. The NOL must be submitted to the IRB/REB once it has been issued by Health Canada.
Martin Letendre
Martin Letendre

Martin Letendre is responsible for managing Veritas IRB's business operations and administering the activities of the Veritas IRB Boards. Martin is a member of the Quebec Bar and brings more than a decade of experience in health law and research ethics. His expert knowledge of, and ongoing activity and interest in research ethics have led to the publication of several reports and articles in peer-reviewed journals, and invitations as guest speaker at numerous conferences and scientific meetings. Martin was actively involved in the creation of an on-line tutorial for institutional research ethics boards in Quebec and is currently a member of Canada's three federal research agencies' Panel on Responsible Conduct of Research.