4 Compliance Takeaways from the Joint US-FDA, MHRA-UK, and Health Canada GCP Symposium

The Florence Compliance Team joined the Joint US-FDA, MHRA-UK, Health Canada Good Clinical Practice & Pharmacovigilance Compliance Symposium in February 2024 and below are our takeaways of some sessions that relate to the use of Electronic Systems such as Florence’s Site Enablement Platform.

The symposium had a session dedicated to updates to ICH E6(R3), however this was a topic seen throughout the sessions. R2 was revised to address the principles that support the conduct of clinical trials as they become more complex globally. Technological advances were taken into account to add flexibility to the management of trials and their records in a compliant manner. The session provided an overview of the draft R3 principles, including Annex 1, and discussed plans for Annex 2 to provide additional GCP considerations.

As acknowledged with the ICH E6(R3) revisions, Decentralized Clinical Trials (DCTs) allow trial-related activities to occur at locations other than traditional clinical trial sites, accelerating safe drug development and increasing efficiency. The COVID-19 pandemic accelerated the use and acceptance of DCT’s, proving that this framework is going to be an option moving forward. During the symposium, representatives from all three regulatory agencies voiced support for the use of DCTs, however there are some key considerations to keep in mind:

• Local differences that may arise due to the remote nature of DCT’s.
• How essential and source documents will be stored, and how electronic systems can be used.
• How staff and participants will be trained on the use of Digital Health Technology (DHT).
• Regardless of where the trial takes place, DCT’s must follow the same overarching regulations and expectations laid out by Regulatory Authorities; and the responsibilities of the Sponsor/Investigator do not change.
• How centralized monitoring will play into DCTs, and how to document this accordingly in the monitoring plan.
• Remote Informed Consent may be needed to support DCT’s, and the use of electronic consent can help ensure appropriate documentation is maintained. With the use of eConsent, it is important to maintain regulatory compliance with key considerations such as inclusion in the protocol, document version control, and the option to use a legal representative on behalf of the participant.

Data governance is a new addition into ICH E6 with the R3 addendum, and with that also warranted its own session at the joint symposium. Overall, there should be a risk proportionate approach that extends to data governance activities. This should include a process to identify which computerized system data has an impact on data integrity and clinical trial quality, including which data is critical; and reviewing, evaluating and documenting those risks and the corresponding risk mitigation measures that were implemented.

The processes included in the full data lifecycle should include processes to:

• Ensure data protection of trial participants;
• Manage computerized systems to ensure that they are fit for purpose and used appropriately;
• Safeguard essential elements of the clinical trial, such as randomization, dose escalation and blinding;
• Support key decision making, such as data finalization prior to analysis, unblinding, allocation to analysis data sets, changes in clinical trial design and, where applicable, the activities of, for example, an Independent Data Monitoring Committee (IDMC).

Computerized systems should have appropriate controls in place to ensure data capture, relevant metadata (including audit trails), data corrections, data transfer and data finalization meet regulatory requirements. When using computerized systems such as Florence Site Enablement Platform, the sponsor and investigator both have their own responsibilities to ensure the integrity of data within those systems. Validation is a key piece of this to document that the system is fit for purpose and appropriate controls are in place.

During the symposium, representatives from Health Canada, FDA and MHRA discussed lessons learned from COVID-19, including those that had an impact on the state of GCP inspections. During the pandemic, on-site inspections were generally paused, switching to remote and hybrid inspections in their place.

Processes such as Compliance Readiness Inspection (CRI) in Health Canada arose from the pandemic to help reduce non-compliance during the trial, and the use of CRIs is expanding from its original scope post pandemic. Similarly in the US, the FDA set up Remote Regulatory Assessments (RRA) while on-site inspections were not feasible during the pandemic to provide a review of critical information. The FDA since has noted the value of RRAs and concluded that they should be used for certain scenarios outside the COVID-19 pandemic, as seen in the current draft guidance.

Overall, it can be seen that the lessons learned from the pandemic are now shaping the future state of inspections. While on-site inspections are back, regulatory authorities are still completing remote and hybrid inspections when appropriate, and compliant use of computerized systems helps enable these remote workflows.