Draft guidance on human and veterinary drug submissions based on promising evidence and terms and conditions: Compliance and enforcement
On this page
- Annual progress reports of confirmatory trials for human drugs
- Progress reports for veterinary drugs
- Sample progress report
- Process for fulfillment of terms and conditions – Confirmatory trials
- Amending terms and conditions
- Failure to undertake, complete, and/or provide results of confirmatory trial(s) for a drug product
- Failure of confirmatory trial(s) to demonstrate clinical benefit of the drug product
- Unfavourable change to the benefit-risk profile of the drug product
Annual progress reports of confirmatory trials for human drugs
Although not required by the regulations, we ask that market authorization holders (MAHs) submit reports on the progress of ongoing confirmatory trials to Health Canada on an annual basis. The annual progress report should be submitted through the Common Electronic Submissions Gateway (CESG) for eCTD submissions.
The report should be submitted within 60 calendar days of the market authorization anniversary. Alternatively, it can be submitted by the agreed-upon date set by Health Canada and the MAH at the time of the market authorization issuance.
The annual progress report should be brief and include the following:
- a summary of the conditions outlined in the terms and conditions (T&Cs) letter and their outcomes
- the current status of the confirmatory trial(s), which may be pending, ongoing, delayed, terminated, submitted or fulfilled
- explanatory comments regarding the status of the confirmatory trials
- any actions taken by the MAH, for example, if the:
- status is "pending, delayed or terminated", the explanatory comments should indicate any other actions taken by the MAH
- trial was terminated, the explanatory comments should indicate the next steps by the MAH to confirm efficacy of the drug
- trial is delayed, the explanatory comments should indicate the actions that are being taken to mitigate the delay
If we have any questions regarding the content of the annual progress report, we will contact the MAH within 90 calendar days of receipt of the report by the relevant review bureau.
Progress reports for veterinary drugs
We may request a progress report on the status of ongoing trials on a case-by-case basis. If requested, the brief progress report should include:
- the summary of outstanding conditions
- the status of the trial (pending, ongoing, delayed, terminated, submitted or fulfilled)
- details explaining the status and subsequent action taken to address the T&Cs
The progress report should be submitted by an agreed-upon date at the time of the issuance of the market authorization. If there are any questions regarding the content, Health Canada will contact the MAH.
Sample progress report
Progress Report: Submitted on DATE (to be submitted annually for human drugs)
Manufacturer/Sponsor:
Product: BRAND NAME (active ingredients), route of administration, dosage form and strength, species (for veterinary drugs)
Submission and Control Number: NDS, SNDS, ANDS, SANDS (control number)
Terms and Conditions Letter Date: Year/month/day
Description of Confirmatory Trial:
Confirmatory Trial Schedule:
Protocol approval date; Confirmatory trial enrollment start date and conclusion date; Last patient evaluation date; Health Canada submission date.
Current Status:
Pending, Ongoing, Delayed, Terminated, Submitted or Fulfilled
Explanation of the Status:
Brief description and action taken.
The following are definitions that apply when providing the status of confirmatory trials:
- Pending: The confirmatory trial has not been initiated by the MAH.
- Ongoing: The confirmatory trial is proceeding according to the original schedule or is ahead of the schedule. The results of the confirmatory trial have not been submitted to Health Canada.
- Delayed: The progress of the confirmatory trial has fallen behind the original schedule. Examples of the delay status include difficulties in patient enrolment, delays in the analysis of the results, or delay in the filing of the submission to Health Canada.
- Terminated: The applicant ended the confirmatory trial before completion, and has not yet submitted a final trial report to Health Canada. Examples of termination include termination of trial arms that are no longer feasible. For specific safety, efficacy or quality concerns related to the drug, Health Canada should be notified within 15 days.
- Submitted: The MAH has submitted a final trial report to Health Canada, and the submission is currently in review.
- Fulfilled: Health Canada has conducted the review of the final trial report filed as a submission and has issued a notice of compliance (NOC) indicating that the MAH has met the T&C.
Process for fulfillment of terms and conditions – Confirmatory trials
Results from confirmatory trials must be submitted as a SNDS-Confirmatory (SNDS-C) according to the individual deadlines outlined in the terms and conditions letter. If multiple confirmatory trials are underway, the final results must be submitted by their respective target dates. It is acceptable to combine results from multiple trials into one SNDS-C, provided the submission is filed by the earliest requested deadline.
The SNDS-C must focus only on the original indication or condition of use for which the authorization was issued. Typically, additional information supporting a new or expanded indication cannot be included and must be submitted separately as a NDS or SNDS.
However, in some cases, the same submitted information may support both the confirmation of the clinical effectiveness and a proposed new indication. In these situations, MAHs may discuss with Health Canada the feasibility of a combined submission.
Once Health Canada has determined that the T&Cs for confirmatory trials have been satisfied, the SNDS-C must also be found to be acceptable. At that point, notations regarding T&Cs may be removed from the product monograph (PM) and product labelling. The T&Cs may also be removed from the drug identification number (DIN).
A NOC will be issued to confirm the acceptability of the SNDS-C and authorize updates to the labelling with the confirmatory trial results.
Amending terms and conditions
The T&C letter will be amended as T&Cs are fulfilled, indicating the date at which the T&Cs were met. It will also be amended if T&Cs need to be modified or additional T&Cs are to be imposed as a result of new information. For more information on amending T&Cs, refer to:
Failure to undertake, complete, and/or provide results of confirmatory trial(s) for a drug product
MAHs may be held criminally liable for not fulfilling T&Cs, including failing to submit confirmatory trials as per their deadlines outlined in the terms and conditions letter.
Failure of a MAH to undertake or complete a confirmatory trial listed in the T&Cs imposed on the DIN of a drug may give us a reason to reassess the drug's benefit-risk profile. This assessment will be based on all available information known about the drug. Relevant information may include post-market data, such as adverse drug reaction reports and information from foreign regulators.
Failure to provide results of a confirmatory trial by a specified date may provide us with a reason to assess the clinical effectiveness of the drug, which could result in consideration being given to invoking subsection C.01.013(1) of the regulations, that is, the manufacturer shall make no further sales of that drug unless the manufacturer has submitted the evidence requested.
For more information on failing to comply with T&Cs, refer to:
Failure of confirmatory trial(s) to demonstrate clinical benefit of the drug product
If one or more confirmatory trials for drug products that were market-authorized based on promising evidence of clinical efficacy fail to demonstrate clinical benefit, we may request withdrawal of the authorized indication(s). Depending on the context, this could also lead to a recommendation for complete market withdrawal of the drug product.
Unfavourable change to the benefit-risk profile of the drug product
We will contact the MAH to discuss next steps if there is an unfavourable change to the benefit-risk profile of the drug. An unfavourable change to the benefit-risk profile of a drug may occur if new information becomes available. For example, information from another regulatory jurisdiction may indicate that the anticipated benefits no longer outweigh the identified risks.