Litigation Risks in FDA Remote Interactive Evaluations

Key Takeaways

• The COVID-19 pandemic led the U.S. Food and Drug Administration (FDA) to pause most foreign and domestic inspections and begin conducting remote interactive evaluations.  FDA has since issued a written policy for such evaluations. 
• A facility may decline FDA’s request to perform a remote interactive evaluation but doing so runs the risk of impeding FDA’s ability to make a timely regulatory decision on a pending application. 
• Stakeholders should consider potential litigation risks that may come with remote evaluations, including data and confidentiality concerns, the possibility that FDA’s observations and opinions will be made public, and the likelihood of claims alleging that remote evaluations involve lowered standards.
• This alert discusses practical considerations in deciding whether to agree to a remote interactive evaluation and ways to mitigate the potential risks of doing so.

Introduction

In March 2020, as the COVID-19 pandemic unfolded across the United States and around the world, FDA paused most foreign and domestic inspections in accordance with federal guidelines to mitigate the spread of the COVID-19 virus. Although FDA resumed certain “prioritized domestic inspections” in July 2020 using a risk-based Advisory Rating System to determine the regulatory activities that could safely take place within a geographic region,¹ many inspections—which may include routine surveillance and for-cause inspections that are not deemed “mission-critical”—remain postponed. FDA determines whether a given inspection is mission critical on a case-by-case basis, weighing “its resources and capabilities for the inspection during the public health emergency against the public health risk or benefit posed by the potential inspection site.” 

In April 2021, FDA established a new policy for the use of remote interactive evaluations—which are distinct from but may supplement or complement inspections—under certain circumstances. This alert discusses FDA’s planned use of remote interactive evaluations, potential litigation risks to facilities and sponsors who participate in such evaluations, and practical considerations for mitigating those risks.   

Overview of FDA Remote Interactive Evaluations

FDA has provided several resources that may help those in the drug and biologics manufacturing and bioresearch industries understand, prepare for, and participate in remote interactive evaluations. On April 14, 2021, FDA published “Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency: Guidance for Industry,”² which established the policy for remote interactive evaluations. In May 2021, FDA published its “Resiliency Roadmap for FDA Inspectional Oversight,”³ a report on FDA inspections during the pandemic that included a plan for moving forward. And in August 2021, leaders from FDA’s Center for Drug Evaluation and Research (CEDR) held a webinar entitled “Manufacturing, Supply Chain, and Inspections During the COVID-19 Public Health Emergency,”⁴ which was targeted at quality assurance, manufacturing, and regulatory affairs professionals in the drug and biologics industries and included a discussion of remote interactive evaluations. Highlights from these resources are set out below.   

What is a remote interactive evaluation?

FDA has made clear that a remote interactive evaluation is “not the same as an inspection…or a request for records or other information in advance of or in lieu of an inspection.”⁵ Rather, a remote interactive evaluation is a tool for FDA to meet approval and licensing deadlines set out in user fee commitments, continue monitoring facilities, and update FDA’s relevant internal databases. The information FDA gleans from a remote interactive evaluation may be used to support a facility’s application action (including whether to approve an application), supplement or replace a post-approval inspection, preclude the need for an inspection in follow-up to a reported concern or defect, or determine the scope and timing of future surveillance inspections.  

A remote interactive evaluation may be comprised of a number of different interactions between FDA and the facility undergoing evaluation. As part of the evaluation, FDA may:

• Request and review documents, records, and other electronic information; 
• Use livestream or prerecorded video to examine facilities, operations, and data;
• Schedule and hold interviews and meetings to address any questions or concerns;
• Provide verbal feedback to the facility on observations and outstanding issues, whenever feasible and/or necessary;
• Evaluate a facility’s corrective actions. However, FDA may require an inspection instead of a remote interactive evaluation to verify some corrective actions, or if evaluating the corrective actions remotely would unreasonably extend the duration of the evaluation.

Which facilities may be eligible for remote interactive evaluations?

FDA may ask to conduct a remote interactive evaluation in any and all drug and biologic inspection programs, including but not limited to pre-approval and pre-license inspections to assess marketing applications, post-approval inspections to assess changes to a drug’s manufacturing operations, surveillance inspections that evaluate overall operations and quality controls, follow-up and compliance inspections arising from specific drug quality or facility issues, and Bioresearch Monitoring (BIMO) inspections. FDA’s guidance for remote interactive evaluations remains in effect only during the COVID-19 emergency and does not affect food, tobacco, or medical device inspections.

What is the process involved in a remote interactive evaluation?

A facility may not request a remote interactive evaluation itself; FDA must request it. To determine whether and when to request an evaluation, FDA will apply risk management methods and tools. For example, FDA may request a remote interactive evaluation to assess a marketing application if it determines that remote interaction with the facility will help it assess risks identified during application review. Notably, FDA will not request a remote interactive evaluation if a facility has data integrity issues, a poor inspection history, necessary information that cannot be accessed remotely, or other concerns that FDA decides require an on-site inspection.  

Once FDA determines that a remote interactive evaluation is appropriate, they will contact the facility and applicant to confirm their willingness and ability to participate. A facility may decline FDA’s request to perform a remote interactive evaluation, but doing so runs the risk of impeding FDA’s ability to make a timely regulatory decision on a pending application. If the facility confirms its willingness and ability to participate, FDA will schedule a brief virtual meeting to discuss logistics, expectations, and responsibilities of both sides in the evaluation. They will also review the anticipated duration of the evaluation and schedule the virtual interactions that will make up the evaluation. Further, FDA may request and review documents in advance of the evaluation and could request additional documents and data during the evaluation. 

Upon the completion of a remote interactive evaluation, FDA will hold a closeout meeting with the facility’s management, in which they will present a written list of observations, if any, and discuss these observations in sufficient detail to enable understanding and foster an appropriate response by the facility or sponsor. This list of observations will not be a final FDA action or decision. Unlike an inspection, FDA will not issue a Form FDA 483. However, as with an inspection, FDA encourages facilities to respond during the discussion and/or provide responses in writing to FDA’s observations within 15 business days. Afterwards, FDA will provide a copy of the final remote interactive evaluation report to the facility. This evaluation report—along with any written list of observations given to the facility—may be subject to a disclosure request under the Freedom of Information Act.

Litigation Risks of Remote Interactive Evaluations

When faced with a remote interactive evaluation, facilities and sponsors in the drug and biologics industries would be wise to consider not only the potential regulatory implications, but also the potential litigation risks should they one day face litigation arising from or related to events that occurred while remote interactive evaluations were available. Such risks may include the following:

Litigants may contend that remote interactive evaluations involve lowered standards. 

As discussed above, in certain instances FDA may use remote interactive evaluations in place of traditional inspections, but FDA’s guidance makes clear that a remote interactive evaluation is not the same as an inspection. Litigants in future litigation may contend, albeit incorrectly, that the product or facility that underwent a remote interactive evaluation was not held to the same rigorous standard of review as those subjected to traditional inspections.  

In reality, the procedural differences between a traditional inspection and a remote interactive evaluation should have no bearing on the regulatory standards applied to inspected and evaluated facilities. Although for a remote interactive evaluation FDA will not issue a Form FDA 482 Notice of Inspection, FDA must still provide notice: FDA must request the evaluation, and the facility may affirmatively consent or decline. And although for evaluations FDA will not issue a Form FDA 483, FDA will still issue written observations and facilities will have the same opportunity to respond in writing. Indeed, the starkest difference is the fact that, by definition, FDA will not be physically present at a facility while evaluating it. That may lead some litigants to claim that simply by virtue of its remote nature, a remote interactive evaluation forces FDA to be less probing and allows facilities to be less forthcoming as compared with in-person inspections.   

Security issues may arise during remote interactive evaluations.

For security reasons, FDA uses its own IT platforms and equipment to conduct remote interactive evaluations. However, the FDA does not supply any equipment or software to the facility to enable the evaluation. It also does not use any third-party technologies. It is therefore up to the facility to arrange a high-quality remote connection, provide high-quality equipment like cameras and microphones, and allow access for remotely viewing operations at the facility. As such, ensuring the security of data transmitted remotely to and from FDA is paramount, to prevent any third party from gaining access to sensitive information. Lax security that leads to the disclosure of sensitive information could prompt litigation and undermine claims by counsel in pending litigation that communications with FDA are confidential. 

FDA’s observations may be made public, prompting litigation.

Facilities and sponsors should be mindful of the fact that a final remote interactive evaluation report and any written list of observations may be subject to a disclosure request under the Freedom of Information Act. At the Food and Drug Law Institute’s virtual annual meeting in May 2021, Elizabeth Miller, assistant commissioner for medical product and tobacco operations in FDA’s Office of Regulatory Affairs, said that “discussions are underway about potentially posting, for transparency, information about remote assessments that have been completed, including remote interactive evaluations.”⁶ If FDA posts information that otherwise would have remained non-public, such as a concern by FDA about a facility’s compliance with current good manufacturing practices or FDA regulations, that information may prompt product liability, securities, or other litigation, however unfounded and even if FDA’s questions or concerns are ultimately resolved. 

Practical Considerations for Mitigating Litigation Risks

A remote interactive evaluation is a critical tool in FDA’s toolbox to ensure continued oversight and movement of pending applications during the COVID-19 pandemic. However, a facility is not required to accept FDA’s request to conduct a remote evaluation. After receiving such a request from FDA, a facility should first consider whether agreeing to a remote interactive evaluation is in its best interest. 

Factors to consider in deciding whether to accept FDA’s request for a remote interactive evaluation will largely be facility-specific but may include: the likely delay of a timely regulatory decision on a pending application if the facility declines, whether the facility has the necessary information technology capabilities and equipment, whether the facility is able to securely provide all documentation FDA may request before and during the remote evaluation including by “screen sharing during a live interaction,”⁷ and whether the facility is able to have appropriate personnel participate virtually. If a facility believes that an in-person inspection would be more likely to yield a favorable outcome, it should weigh the potential risk of a delayed decision with the potential risk of an unfavorable or less desirable result due to the remote nature of the evaluation. 

If a facility decides to proceed with a remote interactive evaluation, it should prepare for the evaluation as thoroughly and thoughtfully as it would prepare for a traditional inspection. By taking into account the considerations below, facilities may be able to reduce the litigation risks of remote interactive evaluations. 

Keep clear, comprehensive records throughout the remote interactive evaluation process.

A clear, comprehensive record of all communications and productions to FDA before, during, and after a remote interactive evaluation may be critical to rebutting litigation claims that the evaluation process is less demanding than that of a traditional inspection. Facilities invited to participate in remote interactive evaluations may want to err on the side of documenting everything they provide to FDA—perhaps even everything they had available to provide to FDA, even if it was not requested—so that, if litigation ever arises, they will have a valuable log of evidence showing their compliance with even the strictest of regulations.  

Understand and plan for the technological aspect of remote interactive evaluations.

Facilities should assess their procedures for FDA inspections and adapt them to remote interactive evaluations. They should secure the technology and equipment needed to participate in a remote interactive evaluation while ensuring data privacy; familiarize themselves with and ensure compliance with state and federal (and if applicable, foreign) laws concerning recording and transmitting communications; and implement protocols to prevent any portions of evaluations from being recorded and/or disseminated without their consent. They should become familiar with any new equipment or programs obtained for purposes of the evaluation and ensure that all employees who may be involved in meetings or interactions with FDA during the evaluation are well-versed in using the necessary technology, including taking all necessary precautions to ensure data privacy.  

Prepare rigorously and continually.

Because a remote interactive evaluation may replace a traditional inspection, it is crucial to prepare for such an evaluation as if it were a traditional inspection—and then some. The best way to safeguard against litigation arising from FDA findings is to avoid such findings in the first place. Facilities and sponsors should routinely conduct audits and other self-evaluative activities to minimize the risk that FDA will observe any non-compliance.

Footnotes

1) Press Release, Stephen M. Hahn, Comm’r of Food and Drugs, FDA, Coronavirus (COVID-19) Update: FDA Prepares for Resumption of Domestic Inspections with New Risk Assessment System (July 10, 2020), https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-prepares-resumption-domestic-inspections-new-risk-assessment-system 

2) U.S. Food & Drug Admin., Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency: Guidance for Industry (Apr. 14, 2021), https://www.fda.gov/media/147582/download (“FDA Remote Interactive Evaluations Guidance”). 

3) U.S. Food & Drug Admin., Resiliency Roadmap for FDA Inspectional Oversight (May 5, 2021), https://www.fda.gov/media/148197/download. 

4) U.S. Food & Drug Admin. Ctr. for Drug Evaluation Rsch., Manufacturing, Supply Chain, and Inspections During the COVID-19 Public Health Emergency (Aug. 25, 2021), https://www.fda.gov/drugs/news-events-human-drugs/manufacturing-supply-chain-and-inspections-during-covid19-public-health-emergency-08252021-08252021. 

5) FDA Remote Interactive Evaluations Guidance at 6 n.7. 

6) https://pink.pharmaintelligence.informa.com/PS144354/US-FDAs-Remote-Evaluations-Of-Drug-Manufacturing-Facilities-May-Become-Public

7) FDA Remote Interactive Evaluations Guidance at 11.