On Wednesday, April 14, 2021, the FDA issued long-awaited guidance explaining its approach to remote interactive evaluations of drug and biomedical research facilities during the pandemic.
Read the full guidance on fda.gov: Remote Interactive Evaluations of Drug Manufacturing and Bioresearch Monitoring Facilities During the COVID-19 Public Health Emergency
Acting FDA Commissioner Janet Woodcock explained the thrust behind the new guidance:
"Inspections are an important tool to keep Americans safe, and are part of a set of tools used for regulatory oversight. As part of the wide variety of tools we have deployed during the COVID-19 pandemic, remote interactive evaluations have informed the FDA's regulatory decision-making, contributed to ensuring drug quality and helped determine the scope, depth and timing of future inspections. By necessity, we have adapted by conducting more remote interactive evaluations throughout the public health emergency and are continuing to expand their use as appropriate.”
Background: Pressure Mounts on FDA to Ramp Up Inspection and Oversight Activities
The FDA's remote interactive evaluation program comes as the agency faces pressure from the Government Accountability Office (GAO) and industry stakeholders to address a backlog of inspections that has grown significantly during the pandemic.
In a March report issued by the GAO, the office reveals that FDA was unable to complete more than 1,000 of its drug inspections, creating a significant lapse in quality oversight for new and currently marketed products.
We spoke with Mary Denigan-Macauley, Director of Health Care at the GAO to understand the key findings of the report, where the FDA currently stands with regard to its inspection program, and what the industry should expect in the near future. Watch the full conversation below.
Key Takeaways From the FDA's Remote Interactive Evaluations Guidance
Read on for a few of the important points of the FDA's new guidance manufacturers and other regulated organizations should be aware of and act on.
Tools the FDA Plans to Use for Remote Evaluations
The FDA plans to use tools including teleconferencing, live-streaming video, and screen-sharing technologies to conduct remote evaluations if remote evaluation is deemed appropriate for a facility.
Types of Inspections Subject to Remote Evaluation
Regulators say remote interactive evaluations will be considered for all of FDA’s drug inspection programs including:
- Pre-approval and pre-license inspections
- Post-approval inspections
- Surveillance inspections
- Follow-up and compliance inspections
Regulators also said that remote interactive evaluations are not a one-to-one replacement for inspections. Rather, remote evaluations may be used to:
- Support approval decisions for drugs
- Preclude the need for an inspection
- Support some enforcement actions
- Rank/prioritize facilities for future inspections
The Process of Remote Evaluations
If FDA determines a remote evaluation is appropriate, it says it will notify the facility or applicant and request confirmation of their willingness and ability to facilitate the technical aspects of the remote review.Prior to evaluation, FDA will schedule a virtual meeting to discuss logistics and expectations with facility staff.
FDA will conduct its remote evaluation, during which it says it may:
- “Request and review documents, records, and other information (electronic systems).
- Use livestream and/or pre-recorded video to examine facilities, operations, and 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.”
At the end of a remote evaluation, FDA will hold a closeout meeting with facility management and provide a written list of observations to them.
Unlike a typical inspection, though, FDA says the written list is not a final agency action or decision and that the agency will not issue a Form FDA 483 based on a remote interactive evaluation. Facilities are encouraged to respond to any observations during the discussion or to respond in writing to the agency within 15 business days.
Facilities may decline a remote interactive evaluation, but such a decision could lead to regulatory delays. According to regulators, “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)."
The agency says it will not accept requests from applicants or facilities for remote interactive evaluations.
Factors That May Preclude Remote Evaluations
The FDA says certain factors may preclude remote evaluations as an alternative to on-site inspection. These include, but may not be limited to data integrity and other compliance concerns.
How to Prepare Your Facility for Remote FDA Inspections/Evaluations
Quality and compliance teams can begin proactively taking steps to prepare accordingly. Here are just a few suggested tips based on our experience conducting remote audits.
1. Prepare your IT service environment.
The technical components of a remote audit can be fraught with IT issues that may not be apparent, such as available bandwidth throughout a facility (for virtual walkthroughs), firewalls, software limitations, and security risks.
- As such, IT resources should be included in the planning process to identify potential problems in the project plan and make any necessary policy or technical adjustments to accommodate potential virtual visitors.
2. Invest in high-quality A/V equipment and systems.
With regard to ensuring a quality remote connection and the quality of cameras used, FDA states, “To the extent practicable, technologies employed also should allow access for remotely viewing and evaluating operations at the facility, as necessary (e.g., aseptic practices, equipment cleaning and set up, material weighing and dispensing, instrument set up, sampling, testing).”
Noisy environments and the limitations of older or low-quality AV equipment can make real-time communication and peripheral observations difficult, if not impossible.
- Given the strong likelihood that regulators will conduct their remote inspections in real-time, it’s important to be prepared with high-quality camera and audio equipment to make real-time virtual facility tours both possible and efficient.
- Be sure to dry run your technology throughout your facility to ensure connectivity doesn’t pose problems. Strive to make the virtual experience as close to an in-person one as possible.
- Citing security reasons, FDA says it will only use its own IT platforms and equipment to host virtual interactions, including Microsoft Teams, Zoom for Government, and Adobe Connect. Consider connectivity capabilities with these tools in particular.
3. Make documents easy to access and share remotely upon request.
In its April 2021 guidance, FDA notes that documents requested during the remote interactive evaluation should be provided in an electronic format or made accessible by screen sharing. Facilities should ensure that FDA is able to access encrypted and password-protected files and should be ready to provide PDF files of paper-based documents.
Many facilities are organized to make documents easy to find and reference on site. It may take more time to prepare and upload documents to a platform suitable for sharing materials with investigators versus paper record storage organizers or digital database storage.
- Carefully determine how and how long it will take to convert your documentation into a reviewable file format and make them available for viewing. They should be quickly retrievable without a need to scan or otherwise process into viewable formats.
- Make sure you can share documentation in standard file formats and types.
- Have file conversion capabilities on-hand in case documents need to be printed, scanned, copied, and shared.
4. Update your inspection “war room” materials.
Whether it’s an inspection binder or other type of document organizer, make sure you’re prepared to field all submission requests virtually.
- Every document must be cross-referenced to any electronic file to ensure records are complete. Make it very clear which assets relate to which requests.
The Heightened Importance of a Mock Audit
Mock FDA audits are an essential assurance activity for “dry-running” an inspection and identifying and remediating issues before they’re detected by the FDA. These audits can be performed by an internal team using FDA procedures, or, ideally, by an external team of former FDA employees serving as outside consultants.
Given the unique challenges and requirements of remote assessment, an experienced third-party auditing consultant can be invaluable in preparing for remote audits and inspections. As we cover in another article exploring mock audits more in-depth, information provided by mock FDA audits gives quality and compliance teams the ability to:
- Obtain evidence that management is overseeing operations effectively;
- Review the compliance of contract service providers;
- Verify that quality assurance and regulatory affairs departments are operating appropriately;
- Evaluate process controls, records, and document controls; and
- Determine whether the mechanisms are compliant.
We routinely help manufacturers in the FDA-regulated life science industries conduct mock GMP, GCP, and GLP audits in a number of specific applications, both on-site and remotely. Learn more about our auditing services and connect with us to schedule a mock audit.
Want to dive deeper into planning and hosting remote audits? Grab our free guide below, packed with expert advice and a series of steps quality and compliance teams can take to fully prepare for remote or virtual audits.
GMP Auditing and COVID-19: A Guide to Remote Auditing and Workforce Recovery
Learn the challenges of remote auditing get strategies and best practices for overcoming them throughout each phase of the assessment process. This guide offers a playbook you can use to plan and host a successful remote audit.