By Mark Durivage, Quality Systems Compliance LLC
On July 22, 2022, the FDA released for public comment Conducting Remote Regulatory Assessments Questions and Answers. The FDA believes the use of both voluntary and mandatory remote regulatory assessments (RRAs) for all types of FDA-regulated products is in the interest of the public health. The purpose of this guidance is to provide transparency to stakeholders about the circumstances in which RRAs may be used both during and beyond the COVID-19 pandemic and to promote greater consistency in the way RRAs are conducted by the FDA.
The FDA defines an RRA as “an examination of an FDA-regulated establishment and/or its records, conducted entirely remotely, to evaluate compliance with applicable FDA requirements. RRAs assist in protecting human and animal health, informing regulatory decisions, and verifying certain information submitted to the Agency.” The FDA may also refer to RRAs as remote interactive evaluations and remote record reviews. RRAs are facilitated using remote livestreaming video technology, teleconferences, and screen sharing.
The FDA’s experiences using RRAs have so far been beneficial and have been used to:
- support regulatory decisions
- provide oversight activities
- conduct follow-up activities
- assist in verifying corrective actions
- add foreign firms to import alerts
- assess foreign manufacturing process records
- aid in the issuance of warning letters
- plan future inspections
RRAs may be requested (voluntarily or required as appropriate) using a risk-based approach by the FDA to fulfill regulatory responsibilities when inspections are not possible due to pandemics, natural disasters, unstable conditions, or when the FDA determines they will assist in supporting regulatory decisions or conducting establishment oversight. The FDA does not intend to use RRAs during or as part of an FDA inspection. However, RRAs could precede, prompt, or be used to seek additional follow-up information after an inspection and to verify corrective actions.
The FDA does not intend to substitute RRAs with other means of acquiring information independent of inspections, including applicant information request letters, registration confirmations, meetings, product submissions, application assessments, or follow-up communications during outbreaks or other emergencies. The FDA does not consider RRAs equivalent to physically entering establishments to determine compliance with applicable regulations. However, remote requests for records function as inspections for compliance with the Foreign Supplier Verification Program (FSVP).
There are two types of RRAs: voluntary and mandatory. The FDA may request that establishments such as drug manufacturers, biologics manufacturers, tissue establishments, medical device manufacturers, clinical investigators, food producers, and tobacco product manufacturers to voluntarily participate in an RRA. The FDA may require drug manufacturers and manufacturers subject to the FSVP to participate in an RRA.
Voluntary requests for RRAs may be declined and will not result in any enforcement action. However, the FDA may not be able to provide an applicant with a timely decision on an application or product’s approval, clearance, or authorization. Declining a voluntary RRA could, based on the risks involved, result in the FDA deciding to perform an inspection.
Mandatory RRAs may not be declined. Refusing to participate is a violation of various sections of the FD&C Act and may have potential regulatory consequences.
The FDA may request an RRA by contacting the establishment’s point of contact by official correspondence, email, or phone to schedule virtual interviews, meetings, confirm technological capabilities, and request records and other information. The requests are required to “include a sufficient description of the records;” however, there is not a requirement for the FDA to disclose the intent of the request. The FDA will not issue a Form FDA 482, Notice of Inspection, when using an RRA.
The FDA may request records or other information appropriate to determine whether an establishment, regulated product, or clinical study complies with applicable requirements for voluntary RRAs. The FDA will “take appropriate efforts to minimize the quantity of records or other information requested.” It is important for establishments to fully communicate with the FDA to ensure the request is understood and the FDA receives the information requested. Additionally, if the requested records are stored off-site, let the FDA know about the time required to retrieve them.
For voluntary RRAs, the FDA may suggest time frames to ensure the RRA is completed in a reasonable amount of time. The FDA expects establishments to work diligently to provide the requested records.
For mandatory RRAs, the FDA will request that records be submitted within a specified time frame that provides an establishment with a reasonable time to respond, based on the individual circumstances of the request. Circumstances for reasonable request time frames may include the size, available resources, and capabilities of the establishment; the type, complexity, and volume of the records being requested; the reason for the request, such as an application action goal date, deadline, or other time- sensitive reasons; and the need for document translation.
The RRA Report
The FDA will generally prepare a report consisting of a narrative and supporting documents that communicates the summary of information reviewed, conditions and practices found, and the observations identified. The FDA will provide a written copy of the narrative portion of the RRA report to the establishment, following the determination that the RRA is closed as described in 21 CFR 20.64(d)(3). The report and supporting documents, with any applicable redactions, are available for public disclosure upon request under the Freedom of Information Act. The FDA may have a meeting with the establishment’s management to present a written list of observations and describe and discuss any observations in sufficient detail to enable understanding and foster an appropriate response at the completion of an RRA. RRA observations will not be considered a final agency action or decision. However, evidence collected during an RRA may be used in support of any such action or decision.
A Form FDA 483, Inspectional Observations, will not be issued by the FDA for RRA observations. However, RRA observations may be confirmed during an inspection and included on a Form 483. Following an RRA, the FDA may conduct an inspection or take any other appropriate actions, including an enforcement action, when significant issues are discovered.
The FDA encourages establishments to respond during the meeting and/or provide responses in writing to the observations within 15 U.S. business days. Responses or corrective actions submitted to FDA during that time frame in response to the issues identified during the RRA generally will be considered before further agency action or decision. Establishment responses are available for public disclosure as described in 21 CFR 20.103 with redaction of non-public information, as appropriate.
Please submit written comments to the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852 or electronic comments to https://www.regulations.gov. Please reference docket number FDA-2022-D-0810 with all comments by Sept. 30, 2022. For questions regarding this draft guidance document, contact the Office of Regulatory Affairs (ORA), Office of Strategic Planning and Operational Policy (OSPOP), Food and Drug Administration at ORAPolicyStaffs@fda.hhs.gov.
About The Author:
Mark Allen Durivage has worked as a practitioner, educator, consultant, and author. He is managing principal consultant at Quality Systems Compliance LLC, an ASQ Fellow and SRE Fellow. Durivage primarily works with companies in the FDA regulated industries (medical devices, human tissue, animal tissue, and pharmaceuticals) focusing on quality management system implementation, integration, updates, and training. Additionally, he assists companies by providing internal and external audit support as well as FDA 483 and warning letter response and remediation services. He earned a BAS in computer aided machining from Siena Heights University and an MS in quality management from Eastern Michigan University. He holds several certifications, including CRE, CQE, CQA, CSSBB, RAC (Global), and CTBS. He has written several books available through ASQ Quality Press, published articles in Quality Progress, and is a frequent contributor to Life Science Connect. You can reach him at firstname.lastname@example.org with any questions or comments.