The FDA released draft guidance Oct. 25 regarding remote inspections of drug manufacturing and bioresearch monitoring (BIMO) facilities.

The agency noted it successfully used voluntary remote interactive evaluations during the COVID-19 pandemic and issued the guidance “to inform industry about the agency’s continued use of such remote evaluations as an approach for evaluating drug facilities, as appropriate.”

The draft guidance describes the remote interactive tools the FDA may request to use to conduct a remote evaluation. The FDA “may request to conduct a remote interactive evaluation prior to or following other types of regulatory oversight activities (e.g., an inspection or a request for records or other information),” the guidance said. In addition, the FDA may request a remote interactive evaluation “whenever a program office determines it is appropriate based on mission needs and any travel limitations.”

The guidance said remote BIMO inspections will be risk-based. “While some facility selection factors such as inspection history and time since last inspection may be common across BIMO programs, other factors are unique to each BIMO program,” the guidance said, adding the “FDA intends to consider BIMO facilities for remote interactive evaluation according to existing risk-based facility selection methodologies when there are no data integrity or other concerns that FDA determines require an inspection, and information to be evaluated can be accessed remotely. Generally, FDA intends to use information obtained from a remote interactive evaluation to assess the facility’s conduct, including data reliability and human subject protections, to determine the acceptability of BIMO studies for FDA’s application decision-making,” the guidance said.

According to the guidance, the FDA intends to apply risk management methods and tools to determine when to request a facility’s participation in a remote interactive evaluation. “In some cases, FDA may request records or request that a facility participate in a remote interactive evaluation prior to an inspection,” the guidance said. “We do not intend to accept requests from applicants or facilities for FDA to perform a remote interactive evaluation. Such decisions depend on many factors and information not always known to applicants or facilities, and it would be unduly burdensome on all parties to establish a request-based program.”

Once the FDA determines that a remote interactive evaluation is appropriate for a particular facility or drug, the agency intends to notify the facility and applicant (when appropriate) by electronic correspondence or phone call. “We will use the facility’s registration or application information to identify the facility point of contact or U.S. agent,” the guidance said.

The correspondence or phone contact will include a request for confirmation of the facility’s willingness and ability to participate in a remote interactive evaluation, including the use of teleconference, livestream video, and screen sharing of data and documents. The request will indicate the name and address of the facility to be evaluated, the reason for the use of a remote interactive evaluation, and the names of the FDA participants, if known in advance. Where practicable, FDA generally intends to seek to obtain such facility consent in writing.

Following a facility’s agreement to be evaluated remotely, the FDA will contact the facility to confirm the point of contact for the remote interactive evaluation, facilitate planning, and determine a facility’s ability to transfer records and perform remote interactions with FDA staff. FDA will identify the FDA lead for the remote interactive evaluation. FDA also will work with facilities to procure information necessary to plan and coordinate the activities for a remote interactive evaluation. “The facility should meet these requests or inform FDA of any challenges in meeting these requests as soon as possible,” the guidance said. “Declining FDA’s request to perform a remote interactive evaluation could impede our ability to make a timely regulatory decision (e.g., regarding adequacy of a clinical trial used in support of a pending application or adequacy of a drug manufacturing operation described in the application).”

How To Prepare for a Remote Inspection

Once a facility confirms its willingness and ability to participate in a remote interactive evaluation, the FDA will schedule a brief virtual meeting to discuss logistics, responsibilities, and expectations. Discussion topics may include, but are not limited to:

• Objectives and scope of the remote interactive evaluation.
• Introduction of the FDA remote interactive evaluation team and the remote interactive evaluation lead.
• Identification of the facility point of contact and all other participants, such as sponsor or contract research organization, monitor, and remote ancillary operations.
• Schedule of virtual interactions and the anticipated duration of the remote interactive evaluation. FDA’s expectations during livestreaming walkthroughs of the facility.
• Time zone differences and translation services (i.e., spoken, and written translation), if applicable. Virtual interactions, including remote observation of manufacturing operations or livestream assessment of data, usually will occur during the facility’s normal business hours.
• Methods for sharing requested information, including sharing documents and the use of video-streaming technology.
• Technological limitations that could impair or prevent the FDA’s remote interactive evaluation of the facility.
• Check the internet connection throughout the facility to verify that the signal strength is adequate to support livestreaming video and audio during the actual remote interactive evaluation.

Conduct of Remote Inspection Detailed

When sites agree to participate in a remote interactive evaluation, the “FDA expects them to cooperate with the same level of transparency as they would during an FDA inspection. We expect appropriate staff to be available at scheduled times for interviews and other virtual interactions, and we expect the facility to be operational to the extent possible for FDA to evaluate areas and operations of interest,” the guidance said.

“If a site is unable to support video or other virtual interactions, or if FDA determines that the video or any other virtual interaction during the remote interactive evaluation does not permit a sufficient examination of the facility or of a corrective action, FDA may terminate the remote interactive evaluation and instead perform an inspection or use other available tools,” the guidance said.

As part of a remote inspection, the FDA may:

• Request and review documents, records and other information (electronic systems).
• Use livestream and/or prerecorded video to examine facilities, operations, data and other information.
• Through the facility’s point of contact, schedule interviews and meetings to address any questions or concerns.
• Evaluate a facility’s corrective actions (e.g., in response to a previous inspection or evaluation, or to the current remote interactive evaluation). An inspection instead of a remote interactive evaluation may be necessary to verify the adequacy of some corrective actions, or if evaluating the corrective actions remotely would unreasonably extend the duration of the remote interactive evaluation.
• Provide verbal updates to the facility on observations and outstanding issues, whenever feasible.

The guidance noted that the FDA will not issue a Form FDA 482, Notice of Inspection, to announce or open a remote interactive evaluation.

The guidance said the quality of the remote connection (e.g., connectivity, image quality, cameras used) “should be adequate for the FDA to remotely review, observe, examine, and evaluate the information requested. To the extent practicable, technologies employed also should allow access for clear and stable remote viewing and evaluation of operations at the facility, as necessary (e.g., aseptic practices, equipment cleaning and set up, material weighing and dispensing, instrument set up, sampling, testing),” the guidance said.

The “FDA understands that there may be temporary connection issues during the virtual interaction, and we expect either party to resolve the issue in a timely manner. For security reasons, FDA will use its own IT platforms and equipment to host virtual interactions during remote interactive evaluations (e.g., videoconferences, livestreaming video of the facility and operations in the facility).” FDA currently uses:

• FDA Microsoft Teams;
• FDA Zoom for Government; and
• FDA Adobe Connect.

According to the guidance, the FDA will usually request and review documents and other information in advance of a remote inspection to ensure the livestream interactions are as efficient as possible. However, the agency may request additional documents and other information, including video recordings, at any time during the remote inspection to address questions and to explain observations. Documents and other information requested during a remote interactive evaluation should be provided within a reasonable timeframe.

The FDA expects all documents provided during the remote inspection in response to agency requests to be provided in electronic format or accessible by screen sharing during a live interaction. The FDA will provide a secure means to send the requested information.

For electronic documents and other information, sites should identify any limitations and ensure that encrypted and password-protected files can be accessed by the agency.

Documents submitted should be in English. However, if translation is needed during a livestream interaction, the site may need to provide a translator. “When such a facility agrees to participate in a remote interactive evaluation, they should consider taking steps to enable FDA’s remote viewing and verification of the facility’s documents, procedures, and electronic systems. Requested documents maintained in paper format should be scanned as searchable PDF files, when possible,” the guidance said.

After the remote inspection, the FDA will have a closeout meeting with the facility’s management in which the agency 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. “This written list of observations will not be a final agency action or decision,” the guidance said. “FDA will not issue a Form FDA 483, Inspectional Observations. 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.”

Depending on the purpose and outcome of the remote inspection, the information and documentation collected may be used to:

• support the 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 site for an inspection; or
• justify a follow-up or compliance inspection or any other surveillance activity.

After the remote inspection, the agency generally will provide a copy of the final remote inspection report to the site. Both the report and written list of observations may be subject to a disclosure request under the Freedom of Information Act.

In addition, if the agency determines an inspection is necessary based on the outcome of the remote inspection, the FDA intends to use the information obtained in the remote inspection to prepare for and conduct the on-site inspection.

The FDA also encourages establishments to provide responses in writing to the observations made during the remote inspection within fifteen (15) U.S. business days. “Any responses or corrective actions submitted to FDA during that timeframe in response to the issues identified during the [remote inspection] generally will be considered before further agency action or decision,” the guidance said.