FDA remote audits fall, as in-person cGMP inspections rise

Editor’s note: This is part two of a series of articles on FDA cGMP inspections of dietary supplement facilities in FY22.

During the height of the pandemic to mitigate the spread of Covid-19, U.S. regulators turned increasingly to another tool—remote regulatory assessments (RRAs)—to help check if domestic and foreign facilities were manufacturing products, including dietary supplements, in conformity to FDA regulations.

FDA in FY21 conducted 16 domestic and four foreign RRAs for compliance with cGMPs (current good manufacturing practices) in 21 C.F.R. Part 111, an FDA spokesperson in the Office of Regulatory Affairs (ORA) said, adding all the assessments were voluntary. The cGMPs are designed to ensure dietary supplement products are manufactured consistently to quality standards.

“In response to the coronavirus disease 2019 (Covid-19) pandemic, FDA adapted its operations for field activities to provide oversight of regulated industry while mitigating the spread of Covid-19,” the FDA spokesperson said. “Based on these experiences, FDA determined that RRAs are valuable and, under certain circumstances, will continue to assist FDA during and beyond the Covid-19 pandemic.”

In FY22, the most recent fiscal year that ended Sept. 30, FDA conducted no domestic RRAs for compliance with 21 C.F.R. Part 111. However, three foreign RRAs were conducted in FY22, the FDA spokesperson shared in an email.

Related:FDA audits climb in FY22 for dietary supplement facilities

The year-over-year decline in RRAs—remote assessments of an FDA-regulated establishment and/or its records—corresponded with an increase in physical cGMP inspections of dietary supplement facilities. FDA in FY22 conducted 471 domestic and 15 foreign dietary supplement inspections. Those figures are up from 277 domestic inspections and four foreign inspections in the previous fiscal year.

“While RRAs are useful, they will be used under certain circumstances and are not intended to limit or replace inspections,” the FDA spokesperson said. “In FY22, our focus was returning inspections to a steady state as a number of these facilities did not have on-site inspections since prior to the beginning of the Covid-19 pandemic.”

For the dietary supplement industry, RRAs are a voluntary program in which FDA requests cGMP paperwork from a firm, reviews it and then conveys its assessment to the business, according to Cara Welch, who oversees FDA’s Office of Dietary Supplement Programs (ODSP).

RRAs provide FDA an opportunity to keep informed of what’s happening at a facility, Welch said during a conference in September hosted by the Consumer Healthcare Products Association (CHPA).

“Used correctly, an RRA could provide insights into, for example, how urgent an actual FDA inspection might be, getting someone into the facility,” Welch said. “That sort of gets at the idea of prioritizing the right inspections, or if things are looking decent, maybe not prioritizing that inspection.”

Asked for comment on the use of RRAs, American Herbal Products Association (AHPA) President Michael McGuffin responded in an email that his organization “supports FDA’s continuing evaluation of the regulatory tools that it developed out of necessity during the pandemic.”

“We also encourage the continued inclusion of dietary supplement facilities in the voluntary RRA pilot program,” McGuffin said. “Continuing to gather data through the pilot program should allow FDA and stakeholders to learn whether and how RRAs may, for example, increase the efficiency of dietary supplement firm inspections and facilitate risk-based inspection prioritization decisions.”

FDA in July published a draft guidance on RRAs to increase industry’s understanding of them and to facilitate its process for conducting them.

RRAs “could be a good option” for the dietary supplement industry, said Larisa Pavlick, senior director of product quality and technical affairs with CHPA, in an interview. “However, what members are experiencing has been inconsistency in those inspections, which is true of any audit from any third party or a regulatory” body.

Pavlick mentioned CHPA members also have encountered other challenges with RRAs.

“CHPA members, who have participated in voluntary RRAs, have noted the time and resources needed for an RRA far exceeds an in-person FDA cGMP inspection,” CHPA stated in comments with FDA regarding the draft guidance. “In addition, a manufacturer who successfully undergoes an RRA does not realize a benefit to justify the increase in resource expenditure.”

The Washington, D.C.-based association expressed “concerns that industry may not participate in voluntary RRAs without a better understanding of the time and resources needed to complete the process and a clear incentive to agree to a voluntary request from FDA.”

CHPA cited an example in which one of its members received an RRA request that included an 11-page document request list.

A spokesperson for CHPA, Logan Tucker, raised concerns over the “willingness for responsible industry to voluntarily participate in RRAs without a better understanding of the excess time and resources needed to complete the process, which often means uploading hundreds of PDF files (depending on the list of requests), when time could be more efficiently used by handing them over directly to an onsite investigator.”

What’s more, she said, “FDA could still conduct an onsite inspection after the remote assessment, which potentially creates even less of an incentive for responsible industry to agree to a voluntary RRA.”

RRAs are voluntary for 21 C.F.R. Part 111, meaning companies can decline a request. FDA has no information that suggests supplement companies declined RRAs in FY22, according to an FDA spokesperson.

Duffy MacKay, senior vice president of dietary supplements with CHPA, said FDA expressed interest at one point in making RRAs mandatory for industry. Some RRAs, including records requests from drug establishments and relating to the Foreign Supplier Verification Program for U.S. food importers, are mandatory.

Mandatory RRAs, MacKay cautioned in an interview, could “turn into fishing expeditions” with ongoing requests for documents.

An inspection is “more targeted” if FDA is physically visiting a facility, he concluded. During an in-person inspection, MacKay said, a manufacturer can clarify with FDA investigators what documents they need, provide the records and get through the audit in a few days.

In comments on the draft guidance, a representative of the Council for Responsible Nutrition (CRN), Haiuyen Nguyen, described RRAs as “a useful tool in FDA’s risk-based approach to evaluating inspectional priorities and firms’ regulatory compliance.”

In a typical year, FDA conducts about 500 to 600 dietary supplement inspections, according to ODSP’s Welch. But she said the number of annual inspections only represents around 5% of facilities—considering there are as many as 10,000 FDA-registered facilities.

“While RRAs alone would not resolve FDA’s inspections backlog, the tool could help direct inspections of dietary supplement facilities with the highest risk, thereby protecting public health,” Nguyen, CRN’s vice president of regulatory and nutrition policy, wrote in the comments on the draft guidance.

However, Nguyen raised some concerns about the process for conducting remote assessments, including that FDA’s “use of livestream would pose a risk to confidentiality of processes and privacy of personnel in a facility.” She recommended FDA “limit RRA requests for video streaming to records review only.”

In addition to raising confidentiality and security concerns about the use of livestream and video recording, CRN further advised “FDA clearly identify the purpose of the RRA in its initial request and limit requested documents to only those directly related to the purpose of the RRA,” per Nguyen’s comments.