By Amelie Rodrigue-Way, Ph.D., RAC (CAN), Clinical Scientist, Cato Research Canada.
If you have an open Investigational New Drug application (IND) then you are all too familiar with the periodic reporting requirements. Many US-based sponsors have opted for the Annual Report format when it comes to their IND (sections 1.13.1 to 1.13.14 of the IND; see http://www.ask-cato.com/2010/09/annual-reports-a-time-for-reflection). If you are one of them and you are conducting or planning to conduct a study in Canada, then this might be a good time to consider changing your annual reporting format.
To conduct a clinical trial in Canada, a Clinical Trial Application (CTA) must be submitted and a No Objection Letter (NOL) must be granted by Health Canada before the trial can begin. During the course of the study, the CTA “annual report” is submitted in the form of the annually updated Investigator’s Brochure. No other annual reporting documentation is required under your active CTA.
Nevertheless, Health Canada adopted the International Conference on Harmonization (ICH) guidance E2F: Development Safety Update Report in June 2012 (http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/ich/efficac/e2f-step4-etap4-eng.php). A safety pilot was launched for pharmaceuticals and biologics, and selected sponsors were requested to submit annual DSURs. The safety pilot was successfully completed in 2015, and as of 04 December 2015, DSUR and the DSUR Checklist must be provided upon request, directly to Health Canada’s Office of Submission and Intellectual Property (OSIP). Alternatively, DSURs may be submitted voluntarily by sponsors when important new safety information on a drug needs to be communicated. Health Canada also mentions that a strong rationale/justification for the voluntary filing of the DSUR should be included in the cover letter. The objectives of DSUR review at Health Canada are as follows:
- Enhance the safety surveillance of drugs in development and protect clinical trial subjects;
- Analyze important identified and potential risks;
- Identify potential safety issues at the pre-approval stage;
- Support, when required, the safety assessment of drugs submitted for market authorization; and
- Support the life cycle approach to product vigilance.
What does this mean for your CTA? Unlike the IND, which houses several studies and progresses as the drug development process evolves, the CTA is related to a single clinical study. Once the study ends, Health Canada is notified of study completion and the CTA is no longer updated. The DSUR is not submitted as part of your CTA since by definition the DSUR is prepared per active substance and will contain data pertinent to all dosage forms and strengths, all indications, and all patient populations under study with the investigational product during the reporting period. While the new requirement for providing a DSUR upon request has no immediate impact on your CTA, Health Canada may still monitor the updated safety information outside the realm of your active CTA. If requested, you should be able to quickly provide the most current DSUR.
Therefore, when the time will come to prepare your IND annual report, think of your friendly neighbors to the north suggesting to replace your Annual Report with a DSUR, as it also meets the FDA’s requirements for an IND application annual report and has its own section in your Module 1 (Section 1.13.15).