FDA Supplement Enforcement Priorities Go Beyond NDI Notification

FDA’s plan to tighten enforcement of new dietary ingredient notifications with its controversial guidance still in draft form raises concerns for some stakeholders.

Daniel Fabricant, division director of FDA’s Dietary Supplement Programs, said enforcement is “on the radar screen for the agency and we are certainly taking a look at what we can do around NDIs as there hasn’t been much in terms of case law in the area.”

Fabricant spoke Oct. 20 at the Council for Responsible Nutrition’s conference in Rancho Palos Verdes, Calif., via a prerecorded webcast.

But FDA will not slow enforcement in other supplement regulation areas, such as good manufacturing practices and adverse event reporting, he cautioned.

“Out Of Bounds”

Fabricant hinted the agency would enforce some controversial provisions of the draft NDI guidance.

FDA will consider NDI enforcement a success “when the agency receives NDIs for the overwhelming majority of supplements containing new ingredients that are in the marketplace,” he said.

However, many in the industry argue NDI notification should apply only to a new ingredient once, not to all the products containing the new ingredient.

Fabricant’s announcement surprised some who expected the agency to refrain from enforcing controversial provisions of the recently released NDI guidance.

Marc Ullman, a partner with the New York law firm Ullman, Shapiro & Ullman, approves of increased NDI enforcement, but finds the guidance problematic.

NDI enforcement “has been woeful,” and it is about time FDA addressed “ingredients that are clearly NDIs for which no notification has been submitted, or for which flawed notifications have been submitted and the product is on the market nevertheless,” he said.

But if FDA plans to enforce “some of the controversial aspects of the draft guidance such as requiring notifications for all dietary supplements that contain a NDI, then I think it is way out of bounds,” Ullman said.

With formal comments on the draft still forthcoming and industry “openly communicating areas of concern with FDA … it would be reasonable for FDA to withhold action in areas of controversy until comments are received and these matters are resolved,” said Barry Ritz, VP of scientific and regulatory affairs at Atrium Innovations.

Fabricant acknowledged industry concerns. “This is all just a discussion right now, but we anticipate putting together a strategic plan around NDI notifications and releasing it” during this fiscal year (Also see "Industry Pushes FDA For Narrower Policy On NDI Notifications" - Pink Sheet, 8 Aug, 2011.).

Fabricant noted that FDA would like to open a dialogue with industry to address any concerns in the supplement area.

“More Than Just Hand Out Paper”

Industry stakeholders should not let NDIs “become a distraction” from several other FDA enforcement priorities, Fabricant said.

Good manufacturing practices, among other areas, are “critical right now,” he explained.

FDA is ramping up GMP inspections quickly and finding violations of “pretty basic tenets” of the 2007 final rule, Fabricant said.

The agency so far has reports from 145 facility inspections conducted during fiscal 2011 and expects the total will be around 240 when all reports are final.

In 2010, FDA conducted just 84 supplement GMP inspections. About 25% of them resulted in official actions, primarily warning letters, Fabricant said.

This trend continues. FDA sent a warning letter Oct. 17 to Health Advances USA, noting that the Chula Vista, Calif., firm’s products were adulterated because the manufacturing facility was not GMP compliant.

FDA said the firm failed to write manufacturing procedures, identify equipment and processing lines used in batch production, and establish in-process specifications for the master manufacturing record, among other violations.

When asked about firms that are “wholesale ignoring the GMPs,” Fabricant said violations could draw stronger enforcement than warning letters. FDA is “going to do more than just hand out paper,” he said.

He noted “a very strong provision” in the Food Safety Modernization Act allows FDA to deem a supplement adulterated simply if a firm fails to meet GMPs.

When an attendee asked how likely FDA would be to use this authority, CRN President and CEO Steve Mister noted FDA “has limited resources and prosecutorial and enforcement discretion, so I don’t see them turning … a disagreement about what assay you use for identity testing … into an enforcement action.”

But, “it is possible, technically, that the mere failure to comply is a violation so it opens a door for them to go after the most egregious offenders,” he added.

“They don’t have to show there is a danger to public health or someone died as a result of not doing identity testing, but the mere fact you are not doing it makes you vulnerable.”

Expanding Inspection Questions

Inspectors have focused on GMP basics such as master manufacturing records, batch records, certificates of analysis and lab tests and results.

But in the future, “we will ask more significant questions … that really get to the web that connects the product from where it is received as an ingredient to the facility that has a finished good,” Fabricant said.

He also warned inspectors likely will look more closely at “the lab side of things,” including how lab standards and results relate to ensuring product quality.

FDA also will enforce supplement manufacturer registration with FDA, which is “crucial” to facilitating GMP inspections, Fabricant said.

FSMA requires supplement and other food product manufacturers to renew their registrations every two years with FDA. Previously, firms registered once.

FSMA Could Deem Supplements High Risk

Inspections under FSMA will be risk-based, and how risky FDA deems supplements and dietary ingredients is up to the industry to decide, which highlights the importance of GMP compliance, Fabricant said.

CRN VP of Scientific & Regulatory Affairs Douglas “Duffy” MacKay said “the writing is on the wall that we will be identified as a high-risk category.”

He noted FDA Commissioner Margaret Hamburg’s December 2010 open letter identified tainted supplements as a public health problem (“FDA, Trade Groups Team Up To Bolster Enforcement On Tainted Supplements,” “The Tan Sheet” Dec. 16, 2010).

The Department of Health and Human Services Office of Inspector General’s 2012 Work Plan also identifies supplements as a priority, as does FDA’s draft 2012-2016 strategic plan for food programs (Also see "FDA Tightens Supplement Oversight In Food Program Strategic Plan" - Pink Sheet, 10 Oct, 2011.).

Based on this, industry can expect FDA to implement strategies to keep tainted supplements off the market and compel compliance from more firms.

FDA Suspects Serious AEs Underreported

GMP inspectors also could check whether a firm is reporting serious adverse events, another top enforcement priority. The agency is worried firms are underreporting, Fabricant said.

“We receive approximately 1,200 adverse event reports per year and there are about 55,000 products on the market, so … the numbers paint an interesting picture,” he explained, suggesting that the large number of products available should translate to more AERs.

Ullman said several clients “are extremely conservative about this and, if anything, over report.”

So far, FDA has not sent warning letters about failing to file serious AERs, but Fabricant stressed AE reporting is “certainly” a high priority.

Spiked Supplements Remain A Concern

Spiked supplements continue to be a major enforcement concern.

Fabricant noted that since 2008, more than 400 supplements were recalled because they were spiked with Rx or illegal drugs or steroids, including 20 weight-loss products FDA warned the public about Oct. 18 (“ (Also see "Tainted Supplement Warnings Stress FDA’s Enforcement Limitations" - Pink Sheet, 24 Oct, 2011.)).

Fabricant said rooting out tainted supplements is a shared responsibility and industry must “draw a line in the sand” if it identifies illegal products.

One way is through FDA’s anonymous tip line, which Fabricant said is yielding actionable tips.

An opportunity for reputable firms to find ways to “call out and distance themselves” from disreputable firms came earlier in October at SupplySide West, where Fabricant said he noticed a firm on the show floor selling steroid-containing products as supplements. He said FDA is looking at its enforcement options and he hopes the industry is too.

For example, the industry should prescreen products to ensure they are legitimate before they appear on a tradeshow floor, or alert authorities about illegal products at the shows.

Ullman suggested another option is “for big retail chains to insist on testing for adulteration and for manufacturers in [high-risk] categories to do the same with ingredient suppliers.”

Liquid Supplements Versus Foods

Distinguishing between liquid and conventional foods is another hot topic FDA is “looking to get at in the near future,” Fabricant said.

FDA issued draft guidance on liquid dietary supplements in 2009 that says liquid products are not supplements if they suggest “through their serving size, packaging or recommended daily intake” that they are meant to compose “all or a significant part” of a consumer’s fluid intake.

Previously, FDA defined supplements apart from foods based on a product’s claims (Also see "FDA Supplement Beverage Guidance May Open Can Of Regulatory Worms" - Pink Sheet, 14 Dec, 2009.).

FDA’s emphasis on “clarifying the line between liquid supplements and conventional beverages is in line with Sen. [Dick] Durbin’s Dietary Supplement Labeling Act and seems to be directed at conventional beverages, labeled as beverages, that contain dietary supplement ingredients or make claims that may be appropriate for dietary supplements, not foods,” Atrium’s Ritz said (Also see "Durbin Bill Would Narrow Definition Of Dietary Supplement" - Pink Sheet, 4 Jul, 2011.).

“The most important thing for the industry to emphasize is that dietary supplements can lawfully exist as liquids,” he said.

Health Fraud, Disease Claims Pose Concerns

Finally, FDA hopes to work with industry to reduce health fraud and disease claims for supplements.

FDA earlier this year “did a blitz” on products with sexually transmitted disease claims, Fabricant said. “Obviously, supplements are not there to treat STDs, so this is something we continue to take very seriously.”

“I think working together, especially with competing priorities and resources right now, really sharing responsibility is critical” to increase compliance and elevate the industry’s overall reputation, he added.

By Elizabeth Crawford