Risk classification guide for observations related to inspections of clinical trials of human drugs (GUI-0043): Background
Disclaimer: This document does not constitute legislation. In the event of any inconsistency or conflict between the legislation and this document, the legislation takes precedence. This document is an administrative document that is intended to facilitate compliance by the regulated party with the legislation and the applicable administrative policies.
Version: 2
Date issued: September 29, 2022
Date implemented: September 29, 2022
Consulted: November 15, 2021 to December 14, 2021 (see the consultation)
Replaces: Classification of observations made in the conduct of inspections of clinical trials (GUI-0043), version 1
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Purpose
Regulated parties involved in conducting clinical trials of drugs in humans must comply with:
- the Food and Drugs Act (the Act) and
- Part C, Division 5 "Drugs for clinical trials involving human subjects" of the Food and Drug Regulations (the Regulations)
The Clinical Trial Compliance Program (CTCP) of Health Canada’s Regulatory Operations and Enforcement Branch (ROEB) inspects regulated parties for compliance with the Act and the Regulations. This guide:
- describes how inspectors classify clinical trial inspection observations based on risk
- describes how the overall rating is assigned to an inspection, when applicable, and includes situations that may result in a non-compliance (NC) rating
- promotes consistency in assigning risk ratings of inspection observations and in the overall inspection rating
- provides examples of inspection observations
A primary responsibility of a Health Canada regulated party is to understand its obligations under the Act and to comply with these requirements. Regulated parties that fail to comply will be subject to compliance and enforcement actions.
For more information, please refer to the:
Scope
This guide covers all clinical trials of drugs involving human subjects regulated by the Act and the Regulations.
Clinical trials of drugs involving human subjects include:
- phases I to IV
- commercial or academic
- ongoing or completed
They also include those trials involving pharmaceuticals, biologics, gene therapies, cell therapies, blood products, vaccines and radiopharmaceuticals for human use.
This guide does not apply to:
- clinical trials/investigational testing involving medical devices
- clinical trials involving natural health products (NHPs)
- observational studies, which do not include drug intervention
Inspections may include on-site or remote entry to the site. In both cases, it includes a review of records and procedures of:
- sponsors
- qualified investigators
- contract research organizations
- site management organizations
- any other party involved in the clinical trial
The authority under which site entry would take place falls under subsection 23(1) of the Act. The authority for remote entry falls under subsection 23(3) of the Act. This is described in the Policy on accessing the premises of a regulated party remotely to verify compliance (POL-0138).
For information on how to interpret various sections of the Regulations, please consult:
Introduction
Health Canada conducts inspections of clinical trials of drugs involving human subjects to verify compliance with the Act and Part C, Division 5 of the Regulations. For example, we verify:
- compliance with the principles of good clinical practices (GCP), referred to in section C.05.010 of the Regulations
- described by the ICH guidance document on good clinical practice: Integrated addendum to E6(R1), ICH topic E6(R2), which we adopted on April 3, 2019
- the level of protection of the rights and safety of the research subjects when conducting clinical trials of drugs for human use
- the validity and the integrity of the data
Inspectors will note all deficiencies and/or deviations from the Regulations as observations in the final inspection exit notice (IEN) provided to the regulated party.
An observation is a deficiency or deviation from the Regulations. For each observation made, the inspector assigns a risk classification, based on the severity of the deficiency or deviation (using this document as a guide). An observation can be classified as "critical" (risk 1), "major" (risk 2) or "minor" (risk 3).
All observations recorded in the final inspection exit notice require corrective and preventive actions (CAPAs).
Note: The inspector may assign a repeat observation at a higher risk level during a:
- re-inspection (follow-up inspection for a previous inspection that was rated non-compliant) or
- re-assessment (follow-up inspection for a previous inspection that was rated compliant)
A repeat observation describes a situation where a deviation or deficiency happens again in a follow-up inspection (for example, re-assessment or re-inspection). This includes:
- deviations or deficiencies reported during a previous inspection were not adequately addressed by the regulated party
- suitable corrective actions and/or preventive actions that would prevent the deviation or deficiency from recurring were not implemented
Refer to the page for sample observations listed under specific sections of the Regulations.
Health Canada may take further enforcement action if we find deficiencies or deviations that could result in products or procedures posing a significant health hazard. We will take action to mitigate potential risk and correct the observed non-compliance in accordance with sections C.05.016 and C.05.017 of the Regulations and our compliance and enforcement policy for health products (POL-0001).