The Pandemics Effect on FDA Inspections

The COVID-19 pandemic affected many aspects of medical device firms operations, from supply chain challenges, including shortages of raw materials, to production changes needed to accommodate social distancing and to account for employee illness.

Likewise, the FDA's operations were and continue to be greatly affected by the pandemic, as the Agency shifted focus and employee resources to areas of greatest need (eg, COVID-19 vaccines and therapies, SARS-CoV-2 diagnostic tests, personal protective equipment, and ventilators) to help meet the public health need, first in the early days of the COVID-19 pandemic and, later, as the nation learned to live with the virus. Inspections conducted by the Office of Regulatory Affairs (ORA) are an aspect of FDA operations that may be permanently affected by the pandemic.

The FDA's normal inspection routines were upended by the pandemic as health and safety needs prevented ORA from sending investigators to conduct routine inspections on-site at manufacturing facilities.

The limitations of the FDA's authority to conduct medical device inspections via alternative methods came starkly to light. The FDA and Congress have already shown sensitivity to this issue, and we expect that the nature of FDA inspections may shift going forward.

In March 2020, shortly after the global COVID-19 pandemic was officially declared a public health emergency in the United States of America, the FDA announced a halt to nearly all foreign and domestic inspections across all industries, conducting only limited mission-critical inspections. Since then, the pandemic has forced the FDA to take a start and stop approach to resuming inspection activity as the waves of the pandemic have ebbed and flowed.

In July 2020, the FDA announced its intent to resume routine inspection activity based on the level of infection in a community, based on its red-yellow-green COVID-19 Advisory Rating system. Due to the continued spread of COVID-19 infection, the FDA was able to conduct relatively few inspections under this system and, at times, put inspection activity on hold, as with an Omicron-related halt in inspections from late December 2021 to early February 2022.

During this time, the FDA's backlog of inspections grew, as both routine and mission critical inspections were continuing at a record low pace. In January 2021, the Government Accountability Office took the FDA to task for its inspection backlog, primarily in relation to drug facilities.

In response, in May 2021, the FDA issued its Resiliency Roadmap, setting forth its plan and priorities for more consistent inspection activity. The FDA also described its alternative tools for oversight of FDA-regulated products, but these tools relied on existing statutory authorities and international partnerships.

Since the enactment of the Food and Drug Safety and Innovation Act in 2012, the FDA has had the authority, under Section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FDCA), to request records in advance or in lieu of an inspection, a so-called 704(a)(4) records request. This statutory authority currently applies only to drug manufacturers. Although a 704(a)(4) records request does not constitute an inspection, refusal to comply nevertheless results in the adulteration of drugs made at the facility. Therefore, these requests are actually mandatory requirements.

In 2021, the FDA issued three Warning Letters to drug firms that refused to provide the requested records or information. In 2021 and 2022 to date, the FDA has issued 13 Warning Letters to drug firms citing records submitted in response to a 704(a)(4) records request as the basis for the Warning Letters citations.

The FDA does not currently have the statutory authority to issue a 704(a)(4) records request to medical device firms. The House Energy & Commerce Committee included a provision in its draft user fee reauthorisation legislation that would extend the statutory provision to device firms.

However, with the current uncertainty about the final form of the user fee reauthorisation, due to the wide variance between the House and Senate bills is it not clear at this time whether expansion of this statutory authority is imminent.

In the absence of 704(a)(4) records requests for device firms, the FDA instituted a voluntary Remote Regulatory Assessment (RRA) process in early 2021. To begin, the FDA sends a letter to a device firm asking whether it agrees to participate in a voluntary RRA, under which ORA investigators electronically collect records and files that the FDA would typically review during an inspection. At the close of the RRA, the investigator meets, virtually, with the firm to discuss the investigators findings.

The FDA warns that, if the investigator identifies significant deficiencies, the FDA can subsequently conduct an on-site inspection or take other action as warranted. Unlike 704(a)(4) records requests, RRAs are truly voluntary and declining to participate will not result in negative regulatory action. However, it is likely that declining to participate in an RRA would put a firm higher on the list for an inspection relative to firms that choose to co-operate.

In a third type of remote assessment, in April 2021, FDA announced a process for voluntary Remote Interactive Evaluations (RIEs) during the COVID-19 pandemic using live-streaming video, screensharing, and teleconferencing and videoconferencing tools. Device firms are not subject to the RIE process for good manufacturing practice (GMP) inspections; the RIE process is limited to drug GMP inspections and bioresearch monitoring (BIMO) inspections.

The FDA recently brought all of these remote strategies together in a draft guidance on Remote Regulatory Assessments released on 22 July 2022. Whereas the remote inspection approaches the FDA implemented earlier in the pandemic were justified by the pandemic-related necessity of using alternatives to in-person inspections, the current guidance looks forward and aims to apply these new approaches in the post-pandemic world.

The FDA states in the draft guidance that FDA has noted the value of RRAs and concluded that they should be used for certain scenarios outside the current pandemic and for all types of FDA-regulated products. Some key points of this new draft guidance are as follows.

Even though the guidance is still in draft form, it represents a strong signal that the FDA will continue to use alternative and remote inspection approaches even after the pandemic subsides and there are no health or safety restrictions on investigators conducting on-site inspections.

Further, it is expected that the FDA and Congress will seek to strengthen the FDA's statutory authority to use remote assessment and inspection techniques by amending the FDCA to extend mandatory 704(a)(4) record requests to medical device firms and, potentially, to grant the FDA the authority to conduct fully-remote, mandatory inspections.