A proportionate approach to the identification and management of risk is described below:
3.10.1.1 Risk identification
The sponsor should identify risks that may have a meaningful impact on critical to quality factors prior to trial initiation and throughout trial conduct. Risks should be considered across the processes and systems, including computerised systems, used in the clinical trial (e.g., trial design, participant selection, informed consent process, randomisation, blinding, investigational product administration, data handling and service provider activities).
3.10.1.2 Risk evaluation
The sponsor should evaluate identified risks and existing controls in place to mitigate the risk by considering:
(a) The likelihood of harm/hazard occurring;
(b) The extent to which such harm/hazard would be detectable;
(c) The impact of such harm/hazard on trial participant protection and the reliability of trial results.
3.10.1.3 Risk control
Risk control should be proportionate to the importance of the risk to participants’ rights, safety and well-being and the reliability of trial results. Risk mitigation activities may be incorporated, for example, in protocol design and implementation, monitoring plans, agreements between parties defining roles and responsibilities, and training.
Where relevant, the sponsor should set pre-specified acceptable ranges (e.g., quality tolerance limits at the trial level) to support the control of risks to critical to quality factors. These pre-specified ranges reflect limits that when exceeded have the potential to impact participant safety or the reliability of trial results. Where deviation beyond these ranges is detected, an evaluation should be performed to determine if there is a possible systemic issue and if action is needed.
3.10.1.4 Risk communication
The sponsor should document and communicate the identified risks and mitigating activities, if applicable, to those who are involved in taking action or are affected by such activities. Communication also facilitates risk review and continual improvement during clinical trial conduct.
3.10.1.5 Risk review
The sponsor should periodically review risk control measures to ascertain whether the implemented quality management activities remain effective and relevant, taking into account emerging knowledge and experience. Additional risk control measures may be implemented as needed.
3.10.1.6 Risk reporting
The sponsor should summarise and report important quality issues (including instances in which acceptable ranges are exceeded, as detailed in section 3.10.1.3) and the remedial actions taken and document them in the clinical trial report (see ICH E3).