FDA remains concerned over cGMP 'deficiencies' in dietary supplement audits

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

FDA investigators continue to find nonconformity with rules intended to ensure dietary supplement products are consistently manufactured and contain what’s being represented to U.S. consumers.

Of firms in fiscal year 2022 (FY22) that were visited by FDA for compliance with cGMPs (current good manufacturing practices), the most common violation cited by FDA investigators related to the requirement to establish product specifications for the identity, purity, strength and composition of the finished batch of the dietary supplement.

The specific regulation, known as 21 CFR 111.70(e), also requires establishing limits on contamination that may adulterate the finished batch.

Forty one percent of firms that received a Form 483 (103) were cited for the “observation,” FDA data showed. The third and fourth most common violations related to requirements to either establish an identity specification for each component used in the manufacturing of a dietary supplement (21.1% of Form 483s) or to establish component specs related to purity, strength and composition (17.9%).

FDA disclosed the above findings in response to a Freedom of Information Act (FOIA) request. Based on the FDA data, Natural Products Insider calculated that a little over half of all facilities inspected in FY22 did not receive a Form 483 for purported cGMP infractions.

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

The cGMP requirements “are integral to a safe and high-quality dietary supplement marketplace,” Lindsay Haake, an FDA spokeswoman, declared in an emailed statement. “That said, notwithstanding the commendable efforts of a number of firms who take compliance very seriously, the level of fundamental deficiencies observed during dietary supplement facility inspections remains concerning.”

For instance, she referenced the most common cGMP observations noted above, including requirements to establish specifications.

“It is important for a dietary supplement manufacturer to have controls in place to help ensure that the product contains what it purports to contain and is consistent across batches,” Haake explained. “Quality must be built into the product throughout the manufacturing process. It begins with quality starting materials and continues with the product being manufactured in a reproducible manner according to established specifications. Therefore, having established specifications for the components and finished products is fundamental to building a quality product.”

Related:FDA audits climb in FY22 for dietary supplement facilities

Many firms inspected by FDA also are not sufficiently establishing and following written procedures for the responsibilities of the quality control (QC) operations, which is incorporated in 21 CFR 111.103. This was the second most common cGMP infraction in FY22, FDA data showed. Twenty-two percent of firms issued a Form 483 were cited for this observation.

“Quality control oversees the entire manufacturing process from the starting materials to the finished products being distributed to the marketplace,” Haake said. “The regulations lay out specific responsibilities of quality control personnel—from approving or rejecting all processes and product specifications, to reviewing and approving documentation, ingredients and finished products. Because of this, it is important that firms establish written procedures for the breadth of quality control operations.”

CHPA, CSPI reactions to cGMP violations

In an interview, former FDA investigator Larisa Pavlick said there remains a significant opportunity for trade associations and consultants to educate the industry on FDA’s expectations concerning the requirements to establish proper specifications. She underscored the importance of incorporating the “big five—identity, purity, strength, composition and limits of potential contaminants.”

“There’s huge opportunity for education and to support the FDA in these regulatory inspections and helping ensure that there’s a good communication between industry and the regulators,” said Pavlick, senior director of product quality and technical affairs with the Consumer Healthcare Products Association (CHPA).

She said many large brands aren’t being cited for the observations above, adding “smaller and mid-sized companies always struggle with resources or an understanding to implement the regulations.”

In the fiscal year that ended on Sept. 30, FDA conducted 517 inspections—and the vast majority were domestic (500), FDA data showed. Those figures are up from less than 300 inspections in the prior year during the height of the Covid-19 pandemic.

The number of FY22 inspections reported for this story (500 domestic and 17 foreign inspections) is slightly higher than what Natural Products Insider previously reported (471 domestic and 15 foreign inspections). An FDA official who helped respond to the FOIA request explained all inspections occurring near the end of the fiscal year hadn’t been reported when an FDA spokesperson commented on the total figures in late September.

Pavlick described the increasing number of cGMP inspections as “refreshing.”

However, she noted the number of inspections still hadn’t reached pre-pandemic numbers, and CHPA officials observed FDA only inspects a small fraction of registered facilities annually. CHPA has proposed filling the gap in inspections by authorizing third parties to conduct audits to FDA’s standards that can take the place of an FDA inspection.

Jensen Jose, regulatory counsel to the Center for Science in the Public Interest (CSPI), welcomed the increasing number of cGMP inspections. However, he observed an average annual number of 500 to 600 FDA audits (based on statements from an FDA official) is a “small drop in the bucket,” compared to the number of firms producing dietary supplement products.

Commenting on cGMP violations cited frequently by FDA investigators, he suggested consumers deserve to receive what brands are representing to them on their product labels.

“Consumers purchase dietary supplements with the expectation that they’re getting a safe product and that specific amounts of dietary ingredients will address their specific health needs,” Jose said in an interview. “As much as these [FDA cGMP] numbers can be indicative of the dietary supplement marketplace, that’s a real problem.”

As to whether FDA should be inspecting a significantly larger number of facilities annually, Jose said such a solution is “not cost effective,” so the agency “definitely needs other tools in the market.” CSPI favors reforms to the Dietary Supplement Health and Education Act of 1994 (DSHEA), including FDA’s proposal for mandatory product listing (MPL), which would require that all dietary supplement products marketed in the U.S. are listed with the agency.

An MPL, Jose said, could give FDA a better sense of the products on the market and prioritize its inspections to focus on supplements that pose a high risk to consumers, for example.

“We believe listing and other comprehensive reforms of DSHEA would help the FDA address these problems, get a better snapshot of what’s on the market and be able to focus on categories … of dietary supplements that might have more issues with tainting and quality control,” he concluded.