Failing to establish specs is most common GMP citation in supplement industry

Eight years after FDA adopted manufacturing regulations governing the dietary supplement industry, a number of businesses are still failing to establish specifications, verify the identity of ingredients through tests and establish written procedures for quality control operations.

Last week during the Rocky Mountain Dietary Supplement Forum in Boulder, Colorado, a local FDA official presented data on the agency’s fiscal year 2015 (FY15) inspections of dietary supplement facilities for compliance with cGMPs (current good manufacturing practices). (The FDA regulations are contained in 21 C.F.R. Part 111).

In FY15, approximately 16% of the 303 total inspections conducted under Part 111 were cited for failing to establish specs (21 C.F.R. Part 111.70(e)), while nearly 14% of all inspections were cited for failing to verify the identity of ingredients through a test or examination (21 C.F.R. Part 111.75(a)(1)(i)), according to the Denver District’s presentation, and based on the total number of inspections provided by FDA’s headquarters in Silver Spring, Maryland.

But over a three-year period, FDA data show, the number of FDA citations for failure to test ingredients and failure to establish specifications has declined. FDA also has reported fewer violations of other regulations, including those related to master manufacturing records (MMRs), which are essentially the recipes used to make natural products.

For instance, in FY13, approximately 19% of FDA inspections, or around 76 citations, resulted in an observation for failure to test dietary ingredients or conduct an exam. The figure declined in FY15 to 41 citations, or 13.5% of all inspections.

“It’s good to see the year-over-year improvements in those sections of the rule where improvement is most needed," said Michael McGuffin, president of the American Herbal Products Association (AHPA), in an emailed statement.

Most companies can achieve full compliance with the FDA regulations, said McGuffin, who explained “companies are continuing to increase their understanding of FDA’s various interpretations of this regulation as they transition from the food-based cGMP rule of the past to the current rule, including those provisions that are similar to the cGMP rule for drugs."

Setting specifications

From October 2014 through September 2015, the most common cGMP infraction or “observation" reported by FDA inspectors was failure to establish specifications for the identity, purity, strength and composition of dietary supplement finished batches, according to the presentation by Nancy Schmidt, an FDA compliance officer in the Denver District.

“I often see no specifications, no specifications at all," said Kathleen Tormey, an FDA investigator in the Denver District, during a Q&A on Sept. 25 with conference attendees. Or a business will have an “unrealistic" specification, Schmidt noted. She cited as an example a claim that a substance is willow bark powder because it can be tasted, or an assertion that a product is blended properly because the different colors can be seen.

Commenting last year on FY14 data that showed similar problem areas, independent consultant Marian Boardley wondered how firms could “adequately test and release good quality products" if they have neglected to establish specifications that identify the expected results of testing and examinations. (For more data on FDA's GMP observations in FY15 based on the Denver District's presentation, see Boardley blog).

At least in part, the observations cited by FDA inspectors for failure to establish specifications may reflect a misunderstanding of own-label distributors’ obligations under Part 111. Steve Mister, president and CEO of the Council for Responsible Nutrition (CRN), pointed out a number of supplement marketers that have relied on contract manufacturers to set specifications have received warning letters from FDA.

“We may need to do more education in the industry among those own-label marketers so they understand what their requirements are under Part 111," Mister said in a phone interview. “I think there are some own-label marketers who still don’t understand 111 applies to them. The general rule is if your name is on the label as the distributor, you have the responsibility under 111 of knowing exactly what is in that product."

Although the number of FDA observations for failure to establish specifications has decreased in recent years from roughly 65 in FY13 to 49 in FY15, the percent of firms receiving the observation has remained the same: around 16 percent.

FDA inspections conducted under Part 111 declined from 396 in FY13 to 296 in FY14 to 303 in FY15, according to data Natural Products Insider obtained from the agency on Sept. 30, 2015. The agency cautioned that the numbers were not precise; FDA often updates the figures.

Tara Lin Couch, Ph.D., a senior advisor for dietary supplements with EAS Consulting Group LLC, said establishing specifications for identity, purity, strength, composition and lack of potential contaminants is challenging.

"That requires technical expertise," she said during an interview on Sept. 25 at the Rocky Mountain Dietary Supplement Forum. “It requires familiarity with the master formulation. It requires familiarity with the supply chain for the raw materials that are used themselves  ... so a lot of knowledge has to be available to create these specifications.

"And I think the industry as a whole does not have a lot of scientific expertise themselves and has to rely on contract laboratories," Couch added. “And that is not somebody who is familiar with the master formulation and not necessarily familiar with the product or the process at the manufacturing facility. So that makes it very challenging for them to come up with those specifications, and I think sometimes it's almost overwhelming to determine what those specifications should be and should look like."

Testing dietary ingredients

In FY15, FDA inspections, the second most common cGMP observation, or infraction, reported by FDA inspectors was failure to conduct an appropriate test or examination to verify the identity of a dietary ingredient (41 citations vs. around 76 citations in FY13).

Tormey, the FDA investigator, said supplement companies that are cited for failing to conduct an appropriate test may neglect to test at all or fail to use a scientifically valid testing method.

Failure to establish specifications and test ingredients have long been problem areas for the industry. Nearly one in five facilities that received a Form 483 in FY14 failed to verify the identity of a dietary ingredient prior to use through a test or examination, reflecting the most common infraction cited by FDA inspectors that year, according to data INSIDER obtained in March 2015 through a Freedom of Information Act request. In FY14, the second most common infraction was failure to establish specifications, according to the data.

"If you look back into the pharmaceutical regulations, it took the pharmaceutical industry 20-plus years to figure out how to comply with" the manufacturing regulations governing drugs, Couch said. “So eight years seems like a long time in some aspects but ... it's not necessarily that long for the supplement companies that had no familiarity with GMP regulations whatsoever."

Finally, Mister said there is a danger in reading too much into FDA data without analyzing individual cases.

“There is a real difference between a violation because you disagreed with FDA on whether your method is specific enough for that ingredient versus a company who also has that violation because they are not doing any ingredient testing at all," Mister said. “If they’ve got rodents running around their facility, that’s a big deal. If the 483 is because somebody forgot to take off their wedding ring or put on a beard guard, that’s a little different."