Part C, Division 5 of the Food and Drug Regulations "Drugs for Clinical Trials Involving Human Subjects" (GUI-0100): Discontinuance, suspension and cancellation
On this page
- Discontinuance of a clinical trial
- Suspension and cancellation (Intent to suspend)
- Suspension and cancellation
Discontinuance of a clinical trial
C.05.015
- If a clinical trial is discontinued by the sponsor in its entirety or at a clinical trial site, the sponsor shall
- inform the Minister no later than 15 days after the date of the discontinuance;
- provide the Minister with the reason for the discontinuance and its impact on the proposed or ongoing clinical trials in respect of the drug conducted in Canada by the sponsor;
- as soon as possible, inform all qualified investigators of the discontinuance and of the reasons for the discontinuance, and advise them in writing of any potential risks to the health of clinical trial subjects or other persons; and
- in respect of each discontinued clinical trial site, stop the sale or importation of the drug as of the date of the discontinuance and take all reasonable measures to ensure the recovery of all unused quantities of the drug that have been sold.
- If the sponsor has discontinued the clinical trial in its entirety or at a clinical trial site, the sponsor may resume selling or importing the drug for the purposes of a clinical trial in its entirety or at a clinical trial site if, in respect of each clinical trial site where the sale or importation is to be resumed, the sponsor submits to the Minister the information referred to in subparagraphs C.05.005(c)(ix) and (x) and paragraphs C.05.005(d) and (h).
Interpretation
Please refer to section 2.8. "Post-Authorization Requirements" of the Guidance document for clinical trial sponsors: Clinical trial applications for further information.
In the event of the premature discontinuation of a trial (see ICH E6, 3.17.1), in its entirety or at a clinical trial site, for which a CTA or CTA-A has been filed in Canada, the sponsor is required to notify Health Canada with reason(s) for discontinuation (via CTA-Notification) as soon as possible, but no later than 15 calendar days after the date of discontinuance.
Notification of a premature discontinuation of a clinical trial or clinical trial site outside Canada, for which there are ongoing trials with the drug in Canada, should also be submitted to the appropriate Directorate (PDD or BRDD) if such discontinuation was carried out for safety reasons.
Essential records generated prior to discontinuation are expected to be maintained in accordance with GCP and applicable regulatory requirements (ICH E6, Principles 9.4 and 9.5).
Examples of inspection observations typically cited under this section of the Regulations include:
- The sponsor did not inform Health Canada within 15 days of a clinical trial being discontinued
- The sponsor did not take reasonable measures to ensure the recovery of all unused quantities of the drug (including returns from the subjects after discontinuing the clinical trial)
Suspension and cancellation (Intent to suspend)
C.05.016
- Subject to subsection (2), the Minister shall suspend the authorization to sell or import a drug for the purposes of a clinical trial, in its entirety or at a clinical trial site, if the Minister has reasonable grounds to believe that
- the sponsor has contravened these Regulations or any provisions of the Act relating to the drug;
- any information submitted in respect of the drug or clinical trial is false or misleading;
- the sponsor has failed to comply with good clinical practices; or
- the sponsor has failed to provide
- information or samples of the drug as required under section C.05.009 or C.05.013, or
- information or a report under section C.05.014.
- Subject to section C.05.017, the Minister shall not suspend an authorization referred to in subsection (1) unless
- the Minister has sent to the sponsor a written notice of the intention to suspend the authorization that indicates whether the authorization is to be suspended in its entirety or at a clinical trial site and the reason for the intended suspension;
- the sponsor has not, within 30 days after receipt of the notice referred to in paragraph (a), provided the Minister with information or documents that demonstrate that the authorization should not be suspended on the grounds that
- the situation giving rise to the intended suspension did not exist, or
- the situation giving rise to the intended suspension has been corrected; and
- the Minister has provided the sponsor with the opportunity to be heard in paragraph (b).
- The Minister shall suspend the authorization by sending to the sponsor a written notice of suspension of the authorization that indicates the effective date of the suspension, whether the authorization is suspended in its entirety or at a clinical trial site and the reason for the suspension.
- If the Minister has suspended an authorization under subsection (1), the Minister shall
- reinstate the authorization in its entirety or at a clinical trial site, as the case may be, if within 30 days after the effective date of the suspension the sponsor provides the Minister with information or documents that demonstrate that the situation giving rise to the suspension has been corrected; or
- cancel the authorization in its entirety or at a clinical trial site, as the case may be, if within 30 days after the effective date of the suspension the sponsor has not provided the Minister with the information or documents referred to in paragraph (a).
Interpretation
Health Canada shall suspend the authorization to sell or import a drug for the purposes of a clinical trial, in its entirety or at a clinical trial site, if Health Canada reasonably believes that any of the circumstances outlined in C.05.016 (1)(a) through (d) apply. Before suspending under C.05.016, Health Canada will send the sponsor a written notice of the intention to suspend the authorization that indicates whether the authorization is to be suspended in its entirety or at a clinical trial site, and the reason for the intended suspension.
The sponsor then has 30 calendar days after receipt of this notice to provide Health Canada with information or documents that demonstrate that the authorization should not be suspended on the grounds that:
- the situation giving rise to the intended suspension did not exist, or
- the situation giving rise to the intended suspension has been corrected, and will be given an opportunity to be heard as required under the Regulations
If a suspension is deemed necessary, Health Canada shall suspend the authorization by sending to the sponsor a written notice of suspension of the authorization that indicates the effective date of the suspension, whether the authorization is suspended in its entirety or at a clinical trial site, and the reason for the suspension.
Health Canada shall reinstate the authorization if, within 30 calendar days after the effective date of the suspension, the sponsor provides Health Canada with information or documents that demonstrate that the situation giving rise to the suspension did not exist or it has been corrected. Failure to provide any or adequate information within 30 calendar days after the effective date of suspension will result in cancellation of the authorization, either in its entirety or at a clinical trial site, as the case may be.
Health Canada shall also suspend an open trial as a result of an inspection with a "non-compliant" (NC) rating if Health Canada reasonably believes that any of the circumstances outlined in C.05.016 (1)(a) through (d) apply. In such circumstances, Health Canada would issue a "Notice of Intent to Suspend", along with the Final Inspection Exit Notice (inspection report).
The sponsor would have 30 calendar days to respond to the observations in the Exit Notice. Depending on the deficiencies noted in the conduct of the study, the sponsor may also be requested to provide an impact analysis on the safety of the subjects in the study and the integrity of the collected data at that site. After reviewing the information or documents the sponsor provides, Health Canada would determine whether the situation giving rise to the intended suspension did not exist or has been corrected.
Suspension and cancellation
C.05.017
- The Minister shall suspend an authorization to sell or import a drug for the purposes of a clinical trial, in its entirety or at a clinical trial site, before giving the sponsor an opportunity to be heard if the Minister has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a clinical trial subject or other person.
- The Minister shall suspend the authorization by sending to the sponsor a written notice of suspension of the authorization that indicates the effective date of the suspension, whether the authorization is suspended in its entirety or at a clinical trial site and the reason for the suspension.
- If the Minister has suspended an authorization, the Minister shall
- reinstate the authorization in its entirety or at a clinical trial site, as the case may be, if within 60 days after the effective date of the suspension the sponsor provides the Minister with information or documents that demonstrate that the situation giving rise to the suspension did not exist or that it has been corrected; or
- cancel the authorization in its entirety or at a clinical trial site, as the case may be, if within 60 days after the effective date of the suspension the sponsor has not provided the Minister with the information or documents referred to in paragraph (a).
Interpretation
Health Canada shall suspend an authorization to sell or import a drug for the purposes of a clinical trial under section C.05.017, in its entirety or at a clinical trial site, before giving the sponsor an opportunity to be heard if Health Canada has reasonable grounds to believe that it is necessary to do so to prevent injury to the health of a clinical trial subject or other person.
Health Canada shall suspend the authorization by sending to the sponsor a written notice of suspension of the authorization that indicates the effective date of the suspension, whether the authorization is suspended in its entirety or at an individual clinical trial site, and the reason for the suspension.
If Health Canada has suspended an authorization, Health Canada shall:
- reinstate the authorization in its entirety or at a clinical trial site, if within 60 calendar days after the effective date of the suspension the sponsor provides Health Canada with information or documents that demonstrate the situation giving rise to the suspension did not exist or that it has been corrected, or
- cancel the authorization in its entirety or at a clinical trial site, if within 60 calendar days after the effective date of the suspension the sponsor has not provided Health Canada with the required information
Investigator / Institution's responsibilities
Section 2.6 of ICH E6 sets out the responsibilities of a QI/institution in the event of premature termination or suspension of a clinical trial.
If a trial is prematurely terminated or suspended for any reason, the QI/institution should:
- promptly inform all trial participants
- ensure appropriate care and follow up of participants
- where required by regulatory requirement(s), inform the regulatory authority(ies)
If a QI terminates or suspends a trial without prior agreement of the sponsor:
- the QI should inform the institution where applicable
- the QI/institution should promptly inform the sponsor and the REB, and provide them with a detailed written explanation of the termination or suspension (ICH E6, 2.6.2)
If a sponsor terminates or suspends a trial (see ICH E6, 3.17.1):
- the sponsor should promptly inform the institution where applicable
- the QI/institution or sponsor should promptly inform the REB and regulatory authorities with a detailed written explanation of the termination or suspension (ICH E6, 2.6.3)
If the REB terminates or suspends its approval/favourable opinion of a trial (see ICH E6 1.2.3 and 1.4.9):
- the QI must inform the institution where applicable
- the QI/institution should promptly notify the sponsor and provide the sponsor with a detailed written explanation of the termination or suspension (ICH E6, 2.6.4)
Sponsor's responsibilities
In addition to those requirements set out in the Regulations with respect to the discontinuance, suspension or cancellation of authorisation to sell or import a drug for the purpose of a clinical trial, section 3.17.1 of ICH E6 states that in the event of such an occurrence, the sponsor should:
- promptly inform the QIs/institutions and the regulatory authority(ies) of the termination or suspension, and provide the reason(s) for the termination or suspension
- promptly inform the REB and provide the reason(s) for the termination or suspension
This can be done by either the sponsor or the QI/institution, as specified by the applicable regulatory requirement(s).