US FDA Is Developing Guidance For Interactive Video GMP Evaluations During COVID-19
Executive Summary
While agency prepares guidance, official advises manufacturers to prepare live streaming video systems if they want to host such inspection alternatives.
In the clearest sign yet of the US Food and Drug Administration’s growing acceptance of so-called virtual drug good manufacturing practice inspections during the coronavirus pandemic, an FDA official said 2 November that the agency is developing industry guidance on the topic.
The FDA has lagged behind other regulatory authorities including the European Medicines Agency and the UK Medicines and Healthcare products Regulatory Agency in adopting remote video virtual inspection approaches. (Also see "How The European Medicines Agency Inspected Thermo Fisher’s Florida Plant Without Leaving Europe" - Pink Sheet, 20 Jul, 2020.) (Also see "UK MHRA Relies On Remote Drug GMP Inspections As COVID-19 Pandemic Grounds Inspectors" - Pink Sheet, 16 Jul, 2020.)
But it appears to be catching up. The agency is preparing COVID-19 guidance “specifically on remote evaluations using interactive video or other types of interactive tools and techniques,” said Brian Hasselbalch, deputy director of the agency’s Office of Policy for Pharmaceutical Quality.
The guidance will describe basic expectations for industry and indicate what to expect from the FDA, Hasselbalch said during a virtual roundtable discussion on COVID-19-related issues hosted by the International Pharmaceutical Aerosol Consortium on Regulation & Science (IPAC-RS), an international association that works to advance regulatory science related to orally inhaled and nasal drug products.
He said the guidance will explain “how we’ll use that interactive engagement in our own decision making about pending applications but also surveillance activity and maybe for-cause types of evaluations and BIMO program work.”
BIMO inspections conducted for the FDA’s Bioresearch Monitoring Program focus on whether clinical investigators are protecting research subjects and the integrity of clinical data.
Legal Issues Must Be Resolved
The FDA has been producing COVID-19 guidance much more quickly than standard guidance. As part of the acceleration process, the agency has been issuing such guidance documents as final guidance instead of first considering comments on draft guidance.
However, it appears that a Food, Drug and Cosmetic Act provision may have slowed preparation of the remote evaluation guidance. Hasselbalch said the agency is “sorting through some legal issues” related to Section 704(A)(4) of the statute. That’s the provision introduced via the 2012 FDA Safety and Innovation Act that enables remote records review in advance of or in lieu of inspections.
Pandemic-related travel restrictions have severely limited the agency’s ability to conduct site inspections since March. Hasselbalch said that during this time, “we have multiplied by magnitudes our use” of the legal authority for remote records review. (Also see "US FDA Assesses Over 500 Biopharma Plants Remotely Via Records Review; Refines Process" - Pink Sheet, 17 Sep, 2020.)
Could Remote Video Become Mandatory?
Hasselbalch noted that many companies have volunteered to host live streaming videos and have done so for other FDA centers. Hasselbalch’s office is in the Center for Drug Evaluation and Research.
He noted as well that many other regulators are exploring this approach, “some very successfully, some with mixed results.”
As for the FDA’s center for drugs, Hasselbalch said, “we intend to continue to look at that and take advantage of that opportunity either voluntarily or perhaps as maybe we can make a requirement under the current statute.”
Certainly, there are drug manufacturing facilities around the world that would rather not let the FDA have a look around.
Live Streaming Advice
Hasselbalch advised manufacturers to have the technology ready if they have submitted or plan to submit applications involving facilities the agency is likely to want to inspect.
These would include, for example, new facilities and facilities where operations or the control strategy has changed or where there is something novel or different that is likely to require a pre-approval inspection.
“Be ready with live streaming video as an option,” he said. “I can’t tell you the platform, but obviously it should allow us to connect to it remotely and direct it to some extent with your help.”
It should for example, enable the FDA to virtually go to different rooms and areas, review records and observe operations “just as if we were on inspection."
Improving Remote Interactions
Hasselbalch also shared insights on what the agency is doing to improve remote interactions, along with some advice for industry.
Many interactions that occurred in person before COVID-19 now are taking place in teleconferences, where “we have to be clearer to each other than we might if we were face to face,” he said.
When unable to read body language even to the limited extent possible through videoconferencing, “we have to actually listen more carefully I think to each other than we maybe did before.”
Industry had adapted to the FDA’s increasing reliance on remote records review by finding ways to incorporate some type of discussion around the records to put them in context.
Hasselbalch agreed with an audience participant that a company could follow up with a conversation on a videoconference application after submitting records the agency asked to review.
He went on to discuss new opportunities and challenges that come with remote evaluations.
The agency usually only sends one or two people on inspections because of the cost. “If we can do it remotely, we can have a lot more of the CMC review experts.” Plus, he said, inspection experts could pop in and out of the live remote evaluation or engage in the background in real time with the inspection team.
The key challenge is organizational: “We don’t want just a big meeting with lots of FDA people badgering the company with questions all at once.” Instead there would be an inspection lead who asks the questions and coordinates the process.
The bottom line, he said, is that companies can “expect to see more expertise brought to a remote evaluation than you might see onsite during an inspection.”