Filing a Clinical Trial Application in Canada

A Quick Primer for Filing a

Clinical Trial Application in Canada

Michelle DeLaCroix, RAC, Director, CTA Group, CanReg Inc.

Before a clinical trial can begin in Canada, it must receive approval from Health Canada. The submission of a Clinical Trial Application (CTA) is a pivotal step in this process and all clinical trials are subject to regulations defined in Division 5 of the Food and Drug Regulations, which apply equally to Sponsor/Manufacturer as to Investigators. Pre-CTA meetings are recommended if the trial is for a New Chemical Entity or if the sponsor has not filed a CTA in Canada before. There is a default 30 day review period for a CTA submission. Although clinical trials are permitted to begin after 30 days from the filing of the CTA, it is always recommended that the Sponsor wait for the No Objection Letter (NOL) to be issued before beginning the trial.

The Organization of a CTA

The Common Technical Document (CTD) format is utilized for the organization of a CTA in a modified form to include only modules 1, 2 and 3. CTAs are submitted as paper submission with the submission duplicated electonrically in a unique folder system. In addition to the GCP guidelines, there is a Clinical Trials guidance document and a online manual available, which provides general guidance about CTAs. Unlike the U.S. Investigational New Drug Applications (INDs), clinical trial applications in Canada require a CTA submission to be filed for each study to be conducted in Canada. Preclinical and clinical experiences are summarized and provided in an Investigator’s Brochure. Complete chemistry and manufacturing (CMC) data are required as part of the filing, but in the case of pharmaceuticals, the amount and level of information is determined by the phase of study. As sponsors advance in phases of development, it is required that new CMC information is submitted with the new CTAs for each phase. In the case of investigator-initiated studies (external to the pharmaceutical manufacturer), the CMC information is usually either cross-referenced to a previous Health Canada approved application for an investigational product, or cross-referenced to an active Canadian Drug Identification Number (DIN). The content of the Investigator’s Brochure and Protocol is expected to comply with International Conference on Harmonization guidelines. Since many Investigator CTAs involve marketed products that are being used outside their approved indication(s), a copy of the current Canadian product monograph may be supplied in lieu of an Investigator’s Brochure. Each CTA must include an attestation by a Senior Medical or Scientific Officer in Canada who has reviewed the protocol and certifies that the trial will be conducted according to GCP guidelines, Division 5 of the Food and Drug Regulations and all information contained with the CTA is accurate. In addition to Health Canada approval, a research ethics board must approve the protocol and consent form(s) before the study begins. The Qualified Investigator must be a medical doctor who is licensed and in good standing within the jurisdiction where the research will occur. If the product is being imported from a non-Canadian supplier, the lots of drug must be released for use in Canada by a Quality Representative in Canada.

During the Trial

Administrative changes to the protocol, consent form or issues related to GCP standards can be made by Notification to Health Canada within 15 days of the change. Significant protocol changes affecting the selection and monitoring or the patients or endpoints of the study or CMC changes warrant the submission of an amendment, which is subject to another 30 day review period. If the clinical trial or the use of the drug for the purposes of the clinical trial endangers the health of a clinical trial subject or other person, the sponsor may immediately make the amendment without prior review by Health Canada, but must submit a Notification within 15 days of making the change and following in 15 days by the filing of a CTA-Amendment for review by Health Canada. Safety concerns that arise during a clinical trial are often related to adverse drug reactions. Adverse drug reactions are defined as any noxious and unintended response to a drug that is caused by the administration of any dose of the drug. If the adverse drug reaction is unexpected, life-threatening or fatal, it must be reported to Health Canada within 7 days, with additional information provided within another 8 days or 15 days for reports considered unexpected and serious in nature. If at any time during a trial, Health Canada decides that the safety of subjects is at risk, the trial may be suspended or cancelled. The Investigator’s Brochures are to be reviewed and updated at a minimum of once each year and submitted to Health Canada as an update to the CTA. Canadian Regulations require sponsors to maintain all records for a minimum period of 25 years. The Inspectorate has the authority to inspect any site involved in a clinical trial, and inspects up to 2% of clinical trial sites each year. If any deviations from the regulations or GCP are noted, the site is expected to improve in these areas to assure proper conduct of the clinical trial. In conclusion, the success of any clinical development program relies upon the quality and accuracy of information provided in a clinical trial application and the compliance of all individuals involved in the studies. The authorization of clinical trials in Canada is straightforward, ensuring that Canada remains competitive with the U.S. and other countries.

About the Author: Michelle DeLaCroix leads the CTA Group at the CanReg Inc., one of the largest regulatory consulting firms in the world.

CanReg is a company dedicated exclusively to global regulatory affairs. Our clients trust more than 100 in-house regulatory specialists to keep their projects moving ahead.

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