FDA Revision Of NDI Draft Guidance Starts With Grandfathered List

Trade groups say FDA committed to revisiting issues in the NDI draft guidance including how firms prove ingredients’ grandfathered status, notifications required for ingredients or finished products and data necessary to demonstrate NDI safety. The agency’s decision followed a meeting between industry allies Sens. Hatch and Harkin and FDA Commissioner Hamburg.

FDA will revise its new dietary ingredient notification draft guidance to address industry concerns and further clarify the agency’s expectations, beginning with the issue of industry’s responsibility for proving the grandfathered status of ingredients.

“We are planning on promulgating a revised draft NDI guidance to address points that may need further clarity to avoid misinterpretation, and possibly being taken out of statutory context,” Daniel Fabricant, Center for Food Safety and Applied Nutrition Division of Dietary Supplement Programs director, said in a June 19 email to supplement industry trade groups.

The decision followed a same-day meeting between industry allies Sens. Orrin Hatch and Tom Harkin and FDA Commissioner Margaret Hamburg, Deputy Commissioner for Foods Michael Taylor and Assistant Commissioner for Legislation Jeanne Ireland, Fabricant added.

Five Points FDA Will Revisit In NDI Guidance

Although industry representatives did not attend the meeting, trade groups said they learned that FDA officials will revisit these provisions of the draft guidance published in July 2011:

• industry responsibility for proving grandfathered status of particular ingredients
• whether NDI submissions are required for an ingredient or finished products
• the extent and type of data necessary to demonstrate the safety of NDIs
• the use of synthetic versions of botanical components in supplements
• definition of “chemically altered.”

Few Simple Solutions Expected

In a June 19 statement, the Natural Products Association said FDA officials “singled out the issue of establishing an agreed upon list of grandfathered ingredients as an area where they would like to begin work in the next two weeks.”

In the draft guidance, FDA holds firms responsible for proving whether an ingredient was marketed in the U.S. before Oct. 15, 1994, when Congress passed the Dietary Supplement Health and Education Act. NDI notifications are not required for ingredients that were available pre-DSHEA.

While industry trade groups compiled lists of ingredients marketed before the cut-off date, FDA historically has refused to acknowledge the lists as substantiation and has required firms to provide sales receipts, marketing materials or other proof of an ingredient’s grandfathered status. But those documents can be difficult to find nearly 18 years after the law’s passage, stakeholders point out (Also see "FDA Should Accept Industry’s Grandfathered Ingredient Lists – NPA" - Pink Sheet, 5 Dec, 2011.).

NPA executive Cara Welch suggested FDA may be starting with addressing its position on industry responsibility for proving grandfathered status of ingredients because the solution to this question might be simpler than some of the others to revisit. One option is for FDA to accept trade groups’ lists of pre-DSHEA ingredients.

One of the potentially more complicated issues is the use of synthetic versions of botanical compounds in supplements, Welch, NPA’s scientific and regulatory affairs VP, said in an interview.

In the guidance, FDA says synthetic versions of botanicals are not dietary substances because they were “never part of the botanical and thus cannot be a ‘constituent’ of the botanical that qualifies as a dietary ingredient.” However, industry says synthetics should be allowed because they are identical to the natural components and often are more chemically stable and cost-effective (Also see "Synthetics Stance In NDI Guidance Raises Red Flag For Industry" - Pink Sheet, 11 Jul, 2011.).

“It’s interesting that in the vitamin area the FDA for many years had a regulation that prevented you from claiming natural source was better than synthetic source in a vitamin, so it’s odd for them to take a position in the NDI guidance that synthetic sources are not as good, or even not permitted,” said Annette Dickinson, past president of Council for Responsible Nutrition and an adjunct professor in the Department of Food Science and Nutrition at the University of Minnesota. She added the revision process is “a good chance to look at it again.”

The agency softened its take on synthetics slightly in recent warning letters to firms marketing bodybuilding products containing DMAA. The letters implied the agency could accept synthetic ingredients that are “commonly used as food or drink” to increase dietary intake (Also see "DMAA Warnings Shed Light On FDA NDI Enforcement" - Pink Sheet, 7 May, 2012.).

Some also want FDA to ease the definition of “chemically altered” as stated in the draft guidance. FDA said firms must submit an NDI notification for an old dietary ingredient if it is made with a manufacturing process or solvent other than water or aqueous ethanol (Also see "NDI Guidance Sparks Questions Even From Firms Ready To Comply" - Pink Sheet, 18 Jul, 2011.).

Another hot button issue is the agency’s interpretation that DSHEA requires firms to submit a notification for all products that include the same NDI, rather than one notification for the ingredient. Stakeholders complained preparing and submitting a notification for every product with a new ingredient is unnecessarily repetitive and would overburden the agency, delay innovation and increase development costs (Also see "AHPA Rewrites NDI Guidance, Argues FDA Proposes Premarket Approval For Supplements" - Pink Sheet, 12 Dec, 2011.).

Similarly, supplement firms claimed their development costs would increase if they were required to provide the volume of data FDA asked for in the guidance to demonstrate the safety of an NDI, another issue the agency committed to revisit and clarify.

Timeline For Revision Is Unknown

While FDA is “working diligently on the matter, the timeline is unknown at the present,” Fabricant said in the message to trade groups. He noted the agency still is reviewing comments submitted on the current draft guidance.

Trade groups do not expect the revised guidance before the November elections, but hope it will not take as long as the original draft guidance, which was published nearly 17 years after DSHEA was enacted.

The elections could influence how long revising the guidance takes, said Anthony Pavel, a partner at K&L Gates in Washington. “If Obama gets back in and we have the same administrators and senior officials at FDA, I don’t think this will be dropped, but I don’t think it’ll be a quick process. … If it’s a Republican administration, I could see this potentially going away for some time. But it really depends.”

“Industry would like to see a guidance sooner rather than later, but it has to be workable, bearing a resemblance to the intent of DSHEA and the current regulations,” he added.

Fabricant assured the trade groups the agency “will keep all parties posted on progress to the extent we can,” and said that FDA representatives likely will be in contact with the groups “in the near future on the issue, maybe for a possible meeting.”

CRN says it looks forward to working with FDA to ensure the revised draft guidance is manageable for industry, enforceable for the agency and beneficial to consumers.

“We are grateful to FDA for its willingness to have an open and ongoing dialogue with our industry. We understand the complexities involved for FDA in developing practical and workable regulation, and we remain willing to work cooperatively,” said CRN President and CEO Steve Mister.

Mister added CRN will “continue to help educate the industry about the statutory requirements for NDI notifications, even as we engage in dialogue with the agency about specifics of FDA’s interpretation of the law.”

Many are welcoming FDA’s decision to revise the draft guidance, which has faced opposition on several fronts.

The agency did not act on a December request by Sens. Harkin, D-Iowa, and Hatch, R-Utah, to “immediately withdraw this guidance and start the process of crafting a new document.” The senators’ letter outlined several of the concerns FDA agreed to reconsider at the recent meeting (Also see "Hatch, Harkin Call For Withdrawal of NDI Draft Guidance" - Pink Sheet, 9 Jan, 2012.). They also spoke frequently to industry and regulators at conferences leading up to and following the release of the draft guidance.

House members, including industry stalwarts in the Dietary Supplement Caucus, also contacted FDA with questions on the draft guidance, threatening legislation to pressure the agency to withdraw or substantially revise it (Also see "Reps Threaten Legislation To Align NDI Guidance With DSHEA" - Pink Sheet, 12 Mar, 2012.).

House Appropriations Committee also included language in the report accompanying the spending bill issued June19 that urged FDA to withdraw the July 2011 NDI draft guidance and re-engage the dietary supplement community to develop a new guidance.

The committee adds that while it “wants to ensure dietary supplements are safe, it is concerned that the draft guidance is being utilized by FDA for enforcement activities against manufacturers despite the guidance only being in draft form, containing nonbinding recommendations and for comment purposes only.”

Welch said FDA’s decision to revisit the guidance “shows FDA’s desire to get it right,” and its willingness to listen to industry and Congress.

“We are really pleased to hear this from FDA and we think it is indicative of the communication industry has had with FDA as well as the work our congressional champions have put into this issue,” she added.

Industry stakeholders should take this opportunity to reach out to FDA directly and through trade groups to ensure the next version of the guidance is more palatable, Welch advised.

United Natural Products Alliance Executive Director Loren Israelsen agreed. He noted in an email that the draft revision will provide “the opportunity to revisit key elements of DSHEA via an FDA guidance. What it means is we must be clear (as possible) to lay out a framework of how we believe the NDI process should operate. This is not as easy as it may seem. Clarity is what is required on our side, and following that, compliance!”