Supplement Firms Making Drug Claims Land On Fast Track To Notoriety At FDA

FDA is compiling an ongoing list of “online advisory letters” to identify supplement firms that fail to respond within 30 days to notices about noncompliant claims. The agency anticipates spurring an uptick in NDI notifications by publishing a draft guidance by the end of the year.

A recently launched FDA program more rapidly points a finger of noncompliance at dietary supplement firms making drug claims, making them known to consumers and the rest of the industry.

The Division of Dietary Supplement Programs is working with the agency’s Office of Regulatory Affairs to compile an ongoing list of “online advisory letters” to identify supplement firms that fail to respond within 30 days to FDA notices about noncompliant claims, such as labeling or online statements that indicate a supplement will treat a disease condition or that are otherwise outside the health, qualified health and structure/function claims allowed for supplements.

“We’re trying to get the word out there. We’ll give them notice to fix their problem but if they don’t fix their problem and they continue to thumb their nose, then we’re going to post their name on there,” said Cara Welch, DDSP acting deputy director, at the Regulatory Affairs Professionals Society annual conference in Baltimore on Oct. 27.

The online advisory letters page on FDA’s website went live earlier in October. Through Oct. 30, the page listed four firms that failed to correct problems FDA officials identified in Aug. 4 letters.

Manufacturers and other firms that fail to respond to FDA notifications about violative claims, good manufacturing practices problems or other supplement regulation violations generally are identified in warning letters often published months or even more than a year after agency officials find the problems.

Warning letters are not submitted until after firms are allowed sometimes multiple opportunities to correct problems ORA officials find in facility inspections or website reviews. The list of online advisory letters accelerates making noncompliant firms known.

“It’s been some time in the making. It’s important for us to identify those who are making violative claims,” Welch said.

“If someone were to search on the firm [using an online search engine] it would come up that they are in violation because they have disease claims, most likely on their website,” she added.

Without Guidance, NDI Notifications Still Required

Welch also discussed DDSP’s revision of the draft guidance on new dietary ingredient notifications that FDA published in 2011 and began revising a year later following wide criticism and questions from the industry and from members of Congress (Also see "A Tale Of Two Expectations: NDI Notification Estimate And Guidance" - Pink Sheet, 27 Feb, 2015.).

She said the revised draft should be out “soon,” with publication before the end of 2015 the division’s goal.

Meanwhile, though, supplement marketers still are required to submit notifications to FDA about NDIs at least 75 days before launching a product containing one.

“What we really feel like we need to see is more submissions. We think that there is under-reporting, under-notifying out there,” Welch said.

FDA cannot evaluate whether an ingredient a firm plans to use, or already is using, is an NDI that is safe for its intended use without NDI notifications.

“A higher number of acknowledgment letters would be great. We know that there are firms out there that have submitted successful NDI notifications,” Welch said.

She added, though, that DDSP realizes NDI notifications guidance would help the industry.

“You need to make sure you’re putting together a coherent and strong package. We’ve generally seen those firms that are in communication with FDA before notifying have a higher rate of acknowledgment versus objections or other responses.”

“Ideally, the draft guidance will also provide that clarification that is needed to put together a clear, coherent and strong package for NDI notification,” Welch said.

The Dietary Supplement Health and Education Act allows firms, without pre-market approval, to sell supplements that contain dietary ingredients available in the US food supply before Oct. 15, 1994, but requires NDI notifications for ingredients not available before that date.

The notifications “are the only pre-market opportunity we have to see what’s coming to market,” Welch said.

However, whether certain ingredients were available pre-DSHEA, as well as whether some are dietary ingredients, is only one of numerous issues that have divided the industry and the agency since the act’s passage (Also see "Supplement NDI Draft Guidance Discussions Snagged On Basic Criteria" - Pink Sheet, 12 Jul, 2013.).

Acknowledged But Not Known?

FDA does not approve NDI notifications, but informs firms either that agency officials do not question the information and their submissions have been filed, or that their information was insufficient to support a substance as an NDI.

The agency is hardly proficient, though, in making known NDI notifications that are filed, says Ray Matulka, director of toxicology for the Burdock Group consultancy.

In his presentation during a separate session at the RAPS conference, Matulka advised supplement manufacturers and other firms to consider FDA's filing of notifications "with a caveat."

He said FDA officials have posted the notifications in as many as four different places on its website. "Even at that, I have had the FDA tell me that the ability to post those documents for public view is pretty low on their priority scheme and they'll get to it when they have time."

"If you want to see a whole list of NDIs out there that are available, good luck, because I don’t think even FDA has put up all of the NDIs that have been notified to them, Matulka added.

He also suggested submitters will need a measure of good fortune to succeed with NDI notifications.

Although FDA's standard for a dietary supplement ingredient is a reasonable expectation of safety, the agency essentially is applying its standard for food to NDIs, Matulka said.

"It is now going to the point where the dietary supplement industry needs to almost go up to the point of showing that it is reasonably certain to be safe. FDA is holding that bar higher and higher, reaching toward the same standard of safety as food.”

The difference in standards is due to supplements being considered optional additions that can benefit a person's diet, while foods are defined as necessary for health and sustenance.

Because supplements are "voluntary, you don't have to take them, it is an expectation of safety. That is different from food, even though dietary supplements are under the umbrella of food," Matulka said.

Imposing the food standard on supplement NDIs is another complaint industry stakeholders made about FDA's draft guidance, which contained several references to the Redbook, the agency's manual for evaluating food additives (Also see "New Dietary Ingredient Notification Draft Guidance Must Be Withdrawn – CRN and CHPA" - Pink Sheet, 5 Dec, 2011.).

Industry stakeholders have a more favorable view toward a separate potential change in FDA's oversight. Agency officials agreed with industry trade groups' suggestion to upgrade DDSP to an office within the Center for Food Safety and Applied Nutrition and the Health and Human Services Department has endorsed a request to Congress to approve the change (Also see "Upgrading Dietary Supplement Programs On Org Chart Catches On At FDA" - Pink Sheet, 14 Sep, 2015.).

Matulka said making DDSP an office "will help in increasing the availability of personnel in that part to put [NDI notifications] on the docket and have more transparency."

After HHS or other federal departments approve restructuring by their agencies, they notify Congress of the proposals; members’ approval is not required, but they have 30 days to object.

The same problems that currently trouble the agency and the industry will remain if DDSP becomes an office. However, as an office, CFSAN's supplement programs could better compete for resources within FDA; and even without additional resources, the programs' staff could make enforcement a higher priority.