09.11.2021

FDA´s Q&As regarding Clinical Trials during the COVID-19 Pandemic

The U.S. Food and Drug Administration, FDA, updated the Q&As concerning the conduct of clinical trials during the COVID-19 pandemic. The document provides general considerations to assist sponsors in assuring participants´ safety, maintaining GCP compliance (Good Clinical Practice), and minimizing risks to trial integrity.

Electronig Signatures, Remote Monitoring and Re-Monitoring

Amongst others the guidance deals with electronic signatures, remote site monitoring visits and re-monitoring after pandemic-related restrictions are lifted.

Electronic Signatures: According to the agency, electronic systems used to generate electronic signatures on trial records must comply with the requirements outlined in 21 CFR Part 11. When an electronic system that is Part 11 compliant is not available, regulated entities must have alternative methods for obtaining required signatures (e.g., handwritten wet ink signatures executed on documents, handwritten stylus or finger-drawn signatures executed on electronic documents that are then printed or appropriately witnessed). In addition, alternative methods for obtaining signatures on informed consent documents are described (e.g. from patients in isolation or when electronic and paper forms cannot be provided). When handwritten methods are used, the sponsor or other regulated entities should ensure that all records containing original handwritten signatures are collected and archived, as either original paper copies or certified electronic copies (e.g., using a validated process for scanning paper copies).
Remote Site Monitoring: Traditional on-site monitoring might be difficult for several reasons such as monitors may not be able to travel to trial sites. When planned on-site monitoring is not possible, the reason should be documented and available for review by the sponsor and during inspections. The decision regarding which sites to prioritize for remote monitoring should be guided by information available about site performance (e.g., frequency and severity of protocol deviations, site staff experience, prior major audit or inspection findings).
Remote monitoring should focus on review of critical documentation and source data. When remote monitoring processes and procedures have not previously been described by the sponsor (like, for example, handling of source document copies that were placed in temporary storage locations for remote review and that are no longer needed after remote monitoring), these processes and procedures should be established (e.g., in a revised study monitoring plan). According to the FDA, "remote monitoring activities, including remote review of source documents, should be documented in the same level of detail as on-site monitoring activities, and any resulting actions to address issues identified from the remote source document review should be consistent with procedures and processes described in the study monitoring plan".
Re-Monitoring after Pandemic-Related Restrictions are lifted: The FDA regulations are not specific about how sponsors must conduct monitoring and are therefore compatible with a range of approaches. FDA’s guidance for industry Oversight of Clinical Investigations – A Risk-Based Approach to Monitoring clarifies that sponsors can use a variety of approaches to fulfill their responsibilities for monitoring. The guidance also describes monitoring activities that reflect modern approaches, including remote monitoring when appropriate. "The decision as to whether remote monitoring conducted for a given site or clinical investigation was adequate or should be followed up with additional on-site monitoring visits should be based on the sponsor’s ongoing risk assessment". Thus, the sponsor may determine that on-site follow-up of remote monitoring is necessary (e.g., for sites with certain data anomalies or a higher frequency of errors, important protocol violations, or dropouts relative to other sites).