Part C, Division 5 of the Food and Drug Regulations "Drugs for Clinical Trials Involving Human Subjects" (GUI-0100): Serious unexpected adverse drug reaction reporting

Serious unexpected adverse drug reaction reporting

Interpretation

The collection, assessment and reporting of adverse events (AEs, as defined in Appendix A) is a critical component of the conduct of any clinical trial. It is a sponsor's responsibility to keep records of all AEs in respect of the drug used in a clinical trial, whether those events occur inside or outside of Canada, including information that specifies the indication for use and the dosage form of the drug at the time of the AE [C.05.012(3)(c)]. The assessment of the site AEs should be done by the QI or the delegated sub-investigator(s) (physician or dentist who meets the criteria of a QI) for seriousness, expectedness and causality determination, when they become aware.

Section 2.7.2(b) of ICH E6 states all serious adverse events (SAEs) should be reported immediately (after the QI reasonably becomes aware of the event) to the sponsor. The QI should also include an assessment of causality. In accordance with applicable regulatory requirements, the protocol may identify SAEs not requiring immediate reporting; for example, deaths or other events that are endpoints. Subsequent information should be submitted as a follow-up report, as necessary.

In accordance with section C.05.014 of the Regulations, it is the responsibility of a sponsor to inform Health Canada, in an expedited manner, of all SUADRs in respect of a drug during the course of a Phase I-III clinical trial (refer to the boxes below for Phase IV trials), whether or not the event occurred inside or outside of Canada:

1. this information must be submitted within 15 calendar days after becoming aware of the event if it is neither fatal nor life threatening
2. if the event is fatal or life threatening, Health Canada must be advised of the event within 7 calendar days after the sponsor first became aware of it.

In cases where the event is fatal or life threatening, the sponsor must submit a complete report to Health Canada within 8 calendar days after the first notification (initial report) to Health Canada of the event. Follow-up reports of fatal or life-threatening reactions must include an assessment of the importance of the event and the implication of any findings, including relevant previous experience with the same or similar drugs.

The reporting of SUSARs to QI(s)/institutions(s) and to the REB(s) should be undertaken in a manner that reflects the urgency of action required and should take into consideration the evolving knowledge of the safety profile of the product and should be performed in accordance with applicable regulatory requirements. In some regions, periodic reporting of line listings with an overall safety assessment may be appropriate (ICH E6, 3.13.2(d)).

The sponsor should, in accordance with the applicable regulatory requirement(s) and with ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited Reporting, expedite the reporting to the regulatory authority(ies) of all suspected, unexpected and serious adverse reactions (for example, SUSARs) (ICH E6, 3.13.2(b)).

The sponsor should submit to the regulatory authority(ies) safety updates and periodic reports, including changes to the Investigator's Brochure, as required by applicable regulatory requirements (ICH E6, 3.13.2(a)).

Sections C.01.016 and C.01.017 of the Regulations (listed below), which also refer to prohibition and serious ADR reporting, do not apply to drugs used for the purpose of a clinical trial, except clinical trial drugs used in Phase IV trials.

Please refer to the following guidance documents for detailed guidance on how to report:

• Guidance document for clinical trial sponsors: Clinical trial applications (Phase I-III trials)
• Reporting adverse reactions to marketed health products – Guidance document for industry (Phase IV trials).

Examples of observations typically cited under this section of the Regulations include:

• The sponsor did not inform Health Canada within 15 days of becoming aware of serious unexpected adverse drug reactions in or outside Canada that were not fatal or life threatening.
• The sponsor did not inform Health Canada within 7 days of becoming aware of serious unexpected adverse drug reactions in or outside Canada that were fatal or life threatening.
• The sponsor did not submit a complete report with an assessment of its findings within 8 days of informing Health Canada of a fatal or life threatening serious unexpected adverse drug reaction.