FDA inspections of dietary supplement facilities in 2020 plunged amid COVID-19. But of the nearly 300 firms inspected, some of the raw data—including the most common violations of FDA manufacturing rules—resembled findings from previous years.
The agency in fiscal year 2020 conducted 289 inspections of dietary supplement facilities for compliance with cGMPs (current good manufacturing practices), according to FDA data Natural Products Insider obtained through the Freedom of Information Act (FOIA). The number of inspections was down 52% from 598 in the prior fiscal year.
On March 18, following the emergence of COVID-19 in the U.S., FDA announced it was postponing “all domestic routine surveillance facility inspections,” or what the agency described as inspections traditionally conducted “every few years based on a risk analysis.” FDA said it would continue to evaluate “domestic for-cause inspection assignments” and move forward with them “if mission-critical.” FDA previously revealed it was postponing most foreign facility inspections.
Dietary supplements were among the FDA-regulated commodities affected by the postponed inspections. From March to September 2020, the last seven months of FY20, FDA only inspected 55 dietary supplement facilities for cGMP compliance.
Of the 289 dietary supplement inspections conducted in FY20, 46 inspections were of foreign facilities, including 22 in Canada and nine in Poland. In the prior year, FDA conducted 60 foreign inspections of dietary supplement facilities, including six in China and five in Germany.
Asked about the impact of the reduction in inspections, former FDA investigator Larisa Pavlick of the United Natural Products Alliance (UNPA) said her group’s membership and most of the industry is “operating reasonably regardless if an FDA inspection is imminent or not.”
“The frustration really is those noncompliant companies that have no intention of complying are still … operating, and that’s what makes us look bad as an industry,” Pavlick, UNPA’s vice president of global regulatory and compliance, said in an interview.
Asked how the reduction in FDA inspections affects behavior in the industry, Dan Fabricant, Ph.D., president and CEO of the Natural Products Association (NPA), responded, “Best-case scenario—no impact. Worse-case scenario is you’ve got folks that go, ‘Hey, FDA’s not going to inspect. Let’s engage in practices that are less than ethical.’”
FDA estimates the market contains between 50,000 and 80,000 dietary supplement products or more. Fabricant, who previously led FDA’s Division of Dietary Supplement Programs, questioned whether FDA could help limit risks from the reduction in annual inspections by focusing on inspecting firms manufacturing many products.
“If you inspected 243 facilities and they [each] only make one product, it doesn’t really tell you much about the marketplace,” Fabricant said in an interview.
An FDA spokesperson, Lindsay Haake, said the agency’s “data set is even smaller than usual” so “we should exercise caution before drawing any conclusions from the data.
“That said, we believe that our prior observations surrounding dietary supplement cGMP compliance remain valid—that is, notwithstanding the commendable efforts of a number of firms who take compliance very seriously, the level of fundamental deficiencies industry-wide remains concerning,” she said in an email. “For example, establishing the finished product specifications and establishing the written procedures for quality control [QC] personnel, both of which are integral to an effective cGMP system, remain the top two most-cited violations again this year.”
The decline in FDA inspections of dietary supplement facilities is concerning, based on problems identified by FDA among the nearly 300 facilities inspected in FY20, suggested Peter Lurie, M.D., president of the Center for Science in the Public Interest (CSPI), in an interview.
Among the FDA FY20 data that a reporter shared with Lurie and other sources for this story:
- Of 288 inspections classified by FDA, 157—or 54.5%—received a document known as a Form 483 for alleged violations of cGMPs.
- Firms that received a 483 were cited for an average number of 5.7 observations, which included citations that don’t fall under 21 C.F.R. 111 (the cGMP regulations) since facilities may produce other commodities besides dietary supplements.
- Of the 147 firms that received a 483 as well as a final regulatory classification, the agency designated 30 of them—or 19%— “official action indicated” or OAI. The classification is associated with recommended regulatory and/or administrative actions.
- FDA designated 116 of the 147 inspections voluntary action indicated (VAI), while one inspection was classified no action indicated (NAI). According to an FDA webpage, VAI “means objectionable conditions or practices were found but the agency is not prepared to take or recommend any administrative or regulatory action.”
- FDA inspected 73 firms “for cause.” Of those firms, 53 received a 483 while 21 were not issued a 483.
- The most common observation reported by FDA inspectors was failure to establish product specifications for identity, purity, strength or composition of the finished dietary supplement.
- The second most common observation was failure to establish or follow written procedures for QC operations.
It appears firms cited for the most common cGMP violation “can’t establish with certainty what’s actually in the product,” said Lurie, who previously served as FDA’s associate commissioner for public health strategy and analysis. “That seems like job one if you’re a dietary supplement, so that particular violation is worrisome to me.”
Many of the cGMP violations identified by FDA reflect “paper violations,” noted Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN). Mister acknowledged these types of infractions “can lead to a potential health concern” and may reflect marketers’ lack of understanding of their cGMP obligations.
However, he and others have distinguished inadequate documentation practices from whether manufacturing facilities are actually producing safe and high-quality products.
For instance, Mister suggested the second most common observation in FY20 doesn’t mean manufacturing facilities actually neglected to follow QC operations.
“It just means you didn’t have it written down,” he said in an interview.
The FY20 cGMP data is “remarkably similar to prior years,” according to Pieter Cohen, M.D., an associate professor of medicine at Harvard University who researches dietary supplements and has been critical of the regulatory framework governing such products.
“This makes it exceedingly difficult for clinicians to reassure patients that the vitamin, mineral, botanical or probiotic that is listed on the supplement label will actually be found in the bottle,” Cohen said in an email. “Clearly, the FDA's prior inspections and warning letters have not been effective in improving compliance, and the agency needs to reconsider its approach to ensuring the quality of supplements.”
The industry’s improvement in cGMP compliance—not the number of FDA inspections conducted annually—should define success for the agency, Cohen added.
“Many supplement firms appear unwilling or incapable of producing high-quality health products, but the FDA has also failed to hold them accountable,” he concluded.
Pavlick, a former FDA investigator in the Denver District Office, acknowledged room for improvement exists, but she said the industry doesn’t “have massive challenges with the products” sold to consumers, such as a proliferation of product recalls.
She also pointed out it’s easy for an FDA investigator to cite a firm for paper violations, yet an inexperienced investigator may not understand how to interpret written materials kept by a facility, such as data on specification sheets, to determine whether a facility’s in compliance with certain cGMP requirements.
Both FDA and industry “can make improvements,” Pavlick said.