Importantly, while the guidance is an important step forward and reflects the reality that FDA investigators aren’t going to be back out in full force any time soon, the guidance goes to great lengths to make clear that a “remote interactive evaluation” as described in the guidance is not the same as an “inspection” conducted under section 704 of the Federal Food, Drug, and Cosmetic Act (FDCA). Indeed, as discussed in greater detail below, some significant differences exist between remote interactive evaluations and traditional inspections. For example, the agency will not issue a Form FDA 482 or a Form FDA 483 during the course of remote interactive evaluation.
Background
With the vast majority of FDA’s inspectional activities on hold due to the pandemic, the agency has adapted and employed alternative oversight tools, including increased use of records requests under section 704(a)(4) of the FDCA , increased sampling and analytical testing of products at the border, and greater information sharing from trusted foreign regulatory partners through mutual recognition agreements (MRAs). We recently summarized those alternative tools online here, citing the summary report on FDA’s Pandemic Recovery and Preparedness Plan (PREPP) initiative.
While FDA’s foreign drug inspection program has advanced in response to the globalization of pharmaceutical manufacturing, the COVID-19 pandemic called greater attention to the United States’ reliance on foreign drug manufacturers and the adequacy of FDA’s oversight given that most inspection have been paused since last March. This guidance helps to respond to the Government Accountability Office’s and industry stakeholders’ repeated requests for a programmatic approach for the use of remote tools and greater transparency to allow drug sponsors and manufacturers to prepare.
Remote interactive evaluations for upcoming inspections
Against this backdrop, FDA released long-awaited guidance on the agency’s plans for performing “remote interactive evaluations” for the duration of the COVID-19 public health emergency. Teleconferencing, livestreaming video and screen-sharing technologies are among the various remote inspection tools described in the guidance. FDA is currently only conducting mission-critical foreign inspections and prioritized domestic inspections. Remote interactive evaluations will be used:
-
to supplement inspections;
-
to reduce the amount on on-site time during inspections;
-
where an inspection is not mission-critical or prioritized; or
-
when an inspection cannot be performed due to COVID-19 related travel inspections.
While FDA states that remote interactive tools may be considered for upcoming inspections, the guidance does not provide certainty around how the agency intends to address an increasing backlog of inspections. According to the January 2021 GAO report, FDA was unable to complete more than 1,000 of its planned fiscal year 2020 inspections.
Remote evaluations may be used for any drug inspectional program, including:
-
Pre-Approval Inspections (PAI) and Pre-License Inspections (PLI)
-
Product specific Post-Approval Inspections
-
Routine drug quality surveillance inspections
-
For-cause, follow-up, and compliance inspections
-
Bioresearch Monitoring (BIMO) inspections
The prioritization of facilities for remote interactive evaluations will follow the same risk-based approach currently used by FDA for surveillance inspections. BIMO facilities will also be considered based on risk. While facilities can choose to decline FDA’s request to perform a remote facility evaluation, that choice may impede the agency’s ability to evaluate the facility or product and make a timely regulatory decision. Notably, FDA states that it will not accept requests from sponsors or facilities for FDA to perform a remote evaluation.
As noted above, the guidance explains that a remote interactive evaluation is not the same as an inspection or records request described in section 704(a)(1) of the FD&C Act, and does not constitute an inspection for purpose of FDA’s risk-based inspection program. That being said, the guidance also states that the information and documentation collected may be used to, among other regulatory purposes:
-
Support FDA’s assessment of pending applications, including whether to approve an application;
-
Preclude the need for an inspection in follow-up to a reported concern or defect;
-
Support a regulatory meeting, warning letter, import alert, recall activities, or enforcement action;
-
Rank or prioritize a facility for an inspection, particularly a surveillance GMP inspection; and,
-
Justify a follow-up or compliance inspection or any other surveillance activity.
For PAI and PLI, FDA intends to use remote evaluations when: (1) remote interaction with the facility will help FDA assess risks identified during application review; and (2) there are no data integrity or other compliance concerns that FDA determines require an inspection. In addition, the guidance notes that for applications, generally, FDA intends to request records and other information under section 704(a)(4) of the FDCA, before initiating a remote interactive evaluation. When performed for a PAI or PLI, FDA expects that a remote interactive evaluation will allow the agency to meet a user fee goal date. However, FDA will notify applicants if the agency expects to miss a user fee goal date.
Remote evaluation process
In preparing for a remote interactive eva, FDA will schedule a brief virtual meeting to discuss logistics, responsibilities, and expectations. This discussion may encompass:
-
Objectives and scope of the remote interactive evaluation;
-
Identification of the facility point of contact and all other participants;
-
Schedule of virtual interactions and the anticipated duration of the remote interactive evaluation;
-
FDA’s expectations during the livestreaming walkthroughs of the facility, including technological limitations that could impair FDA’s remote interactive evaluation;
-
Time zone differences and translation services, if applicable; and,
-
Methods for sharing requested information, including sharing documents and the use of video-streaming technology.
Citing security reasons, FDA will use its own teleconferencing application to host virtual inspections. The agency currently uses Microsoft Teams, Zoom for Government, and Adobe Connect.
The guidance emphasizes that documents and other information requested during a remote interactive evaluation are expected to be provided within a reasonable timeframe, and made available in electronic format or accessible by screen sharing.
The guidance also explains that Form FDA 482, Notice of Inspection and Form FDA 483, Inspectional Observations will not be issued when conducting these “remote interactive evaluations.” However, the guidance explains that “[u]pon completion of a remote interactive evaluation, FDA will have a closeout meeting with the facility’s management. During this meeting, FDA will usually present a written list of observations, if any, and describe and discuss any observations in sufficient detail to enable understanding and foster an appropriate response and as with an inspection, FDA encourages facilities to respond during the discussion and/or provide responses in writing to the observations within 15 U.S. business days.”
The guidance continues by stating that after the remote interactive evaluation concludes, FDA will provide a copy of the final remote interactive evaluation report to the facility. Furthermore, if FDA determines that an inspection will be necessary based on the outcome of the remote interactive evaluation, the information obtained from the remote interactive evaluation will be used to prepare for – and to conduct – the on-site inspection.
More remote inspections to come
We expect FDA to continue to employ its records request authority and remote interactive evaluation tools to carry out its regulatory oversight responsibilities when the agency resumes normal operations. Expanding FDA’s use of new and innovative technologies for facility oversight will allow the agency to conduct more targeted on-site inspections.
Further, while FDA intends to use the information from a remote interactive evaluation to meet user fee commitments, an important open question for industry is whether the program helps to streamline the inspection process, or creates an additional regulatory step towards demonstrating compliance. For example, FDA’s focus on the pharmaceutical supply chain may lead to enhanced scrutiny for manufacturers of critical medicines and manufacturers that are the sole source of product. This would likely mean more inspections (both on-site and virtual), and more record requests for manufacturing sites critical to supply chain continuity — particularly those manufacturing sites critical to the supply chain that are located outside the United States.
The guidance is in effect for the duration of the public health emergency. As the coronavirus pandemic response evolves, we will continue to monitor FDA’s foreign and domestic drug inspection programs, related pharmaceutical supply chain issues, and the agency’s response to the COVID-19 outbreak more broadly. Please contact us if you have any questions.
Authored by Jim Johnson, Scott Kaplan, Robert Church, Lowell Zeta, Chris Fanelli, and Daniel Roberts
