What are the latest developments at the FDA in risk-based quality management of GCP audits?
The U.S. Food and Drug Administration (FDA) has been continuously advancing its approach to Good Clinical Practice (GCP) audits by emphasizing risk-based quality management. This strategy focuses on identifying and managing potential risks to patient safety and data integrity throughout the clinical trial process.
August 2013 and March 2021
In August 2013, the FDA released the guidance document “Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring”, which assisted sponsors in developing monitoring strategies that allocated resources to the most critical aspects of study conduct and reporting. Building upon the groundwork of “Oversight of Clinical Investigations”, the FDA in March 2021 published “A Risk-Based Approach to Monitoring of Clinical Investigations: Questions and Answers”. This guidance provided additional information to facilitate sponsors’ implementation of risk-based monitoring. It included recommendations on planning a monitoring approach, developing the content of a monitoring plan, and addressing and communicating monitoring results.
ICH E6 (R3)
This focus on risk-based quality management (RBQM) has now significantly evolved under the most recent ICH E6 (R3) guidance, released in January 2025. Under E6 (R3), sponsors have a greater responsibility to maintain oversight of all trial-related duties, even if they delegate tasks to Contract Research Organizations (CROs) or other vendors. Ultimately, participant safety, data integrity and regulatory compliance remain the responsibility of the sponsor.
Also, under ICH E6 (R3), sponsors are encouraged to implement systems that allow real-time identification and management of potential risks, such as electronic monitoring systems. This real-time identification is designed to allow for timely interventions to address issues that could impact trial quality or participant safety.
Biopharma companies sponsoring clinical trials and CROs are both encouraged to conduct GAP analysis and update Standard Operating Procedures (SOPs) to meet ICH E6 (R3) guidelines. They are also encouraged to deliver comprehensive organization-wide training to educate all stakeholders on their new processes and the updated guidelines.
Conclusion
The impact of the more risk-based GCP audit approach has been more efficient trials, with an emphasis on high-risk elements rather than routine compliance checks. This leads to enhanced patient safety through faster detection and mitigation of safety concerns. It also aligns with the continually more risk-based regulatory environment of agencies such as the FDA and EMA which oversee clinical trials.