The FDA recognizes that the COVID-19 pandemic may impact the conduct of clinical trials of medical products, including drugs, devices and biological products. Challenges may arise, for example, from quarantines, site closures, travel limitations, interruptions to the supply chain for the investigational product, or other considerations if site personnel or trial subjects become infected with SARS-CoV-2, the virus that causes COVID-19. These challenges may lead to difficulties in conducting the clinical trials. The FDA is aware that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19. Although the impact of COVID-19 on trials will vary depending on many factors, including the nature of disease under study, the trial design and in what region(s) the study is being conducted, the FDA outlines considerations to assist sponsors in assuring the safety of trial participants, maintaining compliance with good clinical practice and minimizing risks to trial integrity. Considerations recommended include, among others, sponsors evaluating alternative methods for assessments, like phone contacts or virtual visits and offering additional safety monitoring for those trial participants who may no longer have access to investigational product or the investigational site.
Three of the regulations created to implement FSMA – the Preventive Controls for Human Food (PC Human Food) rule, Preventive Controls for Animal Food (PC Animal Food) rule, and Foreign Supplier Verification Programs (FSVP) rule – require receiving facilities and importers to conduct supplier verification activities based on the hazard analysis conducted as part of their written Food Safety Plan or FSVP. When receiving facilities and importers develop their Food Safety Plans or FSVP, they sometimes determine onsite audits to be the most appropriate supplier verification activity.
The new policy is for certain laboratories that develop and begin to use validated COVID-19 diagnostics before the FDA has completed review of their Emergency Use Authorization (EUA) requests. The FDA can issue an EUA to permit the use, based on scientific data, of certain medical products that may be effective in diagnosing, treating or preventing a disease or condition when there is a determination, by the Secretary of Health and Human Services (HHS), that there is a public health emergency or a significant potential for a public health emergency that has a significant potential to affect national security or the health and security of U.S. citizens, and a declaration that circumstances exist justifying the medical products’ emergency use.
“FDA recognizes that protocol modifications may be required, and that there may be unavoidable protocol deviations due to COVID-19 illness and/or … control measures,” the agency wrote. Among them: pausing recruitment or monitoring patients less frequently, or even virtually, rather than through hospital visits.
There are even more difficult decisions to consider, such as taking certain patients off of experimental medicines altogether if the risks outweigh the benefits. Patients who stop treatment might need extra monitoring, the FDA noted.
Trial sponsors should detail specifically how COVID-19 impacts their trials — from missed study visits or patients who drop out to contemplated protocol changes. That will keep the FDA up to date so it can understand reasons behind any “missing data” and more accurately review the drugs being tested, the agency said.
“Robust efforts by sponsors, investigators, and [review boards] to maintain the safety of trial participants and study data integrity are expected, and such efforts should be documented,” the FDA wrote. COVID-19-related trial issues are likely unavoidable, so “efforts to minimize impacts on trial integrity, and to document the reasons for protocol deviations, will be important.”