Readers with long memories will remember that the agency released its first version of the draft guidance in 2011, and then announced it would revise that document in the summer of 2012 after a strong industry and political reaction, including a meeting between Senators Orrin Hatch (R-Utah) and Tom Harkin (D-Iowa) and senior FDA officials in June 2012.
While the Agency has consistently stated that reissuing the draft guidance was a priority, it has taken four years to produce the new document.
“This revised draft guidance is an important step forward in the agency’s work to protect public health from potentially dangerous new dietary ingredients,” said Steven Tave, acting director of the FDA’s Office of Dietary Supplement Programs.
“Notification of new dietary ingredients is the only pre-market opportunity the agency has to identify unsafe supplements before they are available to consumers. The revised draft guidance is intended to improve the quality of industry’s new dietary ingredient reporting so the FDA can more effectively monitor the safety of dietary supplements.”
The FDA is encouraging public comments on the revised draft guidance during the 60-day comment period.
According to the FDA, there are over 55,600 dietary supplements on the market, and about 5,500 new dietary supplement products come on the market each year.
However, the agency states it has received fewer than 1,000 NDI notifications since DSHEA was passed in 1994.
The industry is still digesting the new document, which can be read HERE, but preliminary reactions are a mixture of excitement and cautious welcome.
George Paraskevakos, executive director of the International Probiotics Association, told us: “I would say this is good for the industry that FDA released this second draft, that all of us have been waiting for. However, we do need to go through it thoroughly and understand how it will touch the probiotic sector as we are a unique category.”
The American Herbal Products Association (AHPA) said its staff is reviewing the revised draft guidance to determine the extent of changes and whether FDA has brought the revised draft into alignment with the law. The association will provide members with additional analysis in the near future, it said.
"The dietary supplement industry and FDA should have a shared goal to ensure that NDI notifications, when they are required, are clearly presented and thorough in providing to FDA the safety information that is required under the law," said Michael McGuffin, AHPA's president. "This system is in need of improvement, so it AHPA's sincere hope that FDA has not missed another opportunity in this draft guidance to assist industry in meeting this goal."
Master Files, grandfathering, electronic submissions and more
Dr Dan Fabricant, who was director of the FDA’s dietary supplement division when the first draft guidance was published in 2011 and who is now CEO and executive director of the Natural Products Association, shared his preliminary reactions based on the notice with us:
“The Master File is very good news for the industry as it does help firms protect their IP/trade dress which makes sense when you look at the NDI portion of the statute tying the notification to the finished supplement as well as the ingredient,” said Dr Fabricant. “I would imagine the agency will use imports heavily to enforce such a policy but we’ll seek clarity on that.”
“The other highlights are somewhat to be expected,” he added. “It still has some restrictions on “synthetic” botanical ingredients but I gather more discussion will be needed as there are some areas of confusion. For example vinpocetine has been successfully notified to the agency 5 times, yet to my understanding it is completely synthetic, so what is the agency’s rational there? More clarity will be needed on that.”
Dr Fabricant also noted that an accepted grandfathered list, “is a good start. We can start with those ingredients there’s a CFR notice for (GRAS and food additive substances) and from there we can pull from some of our old catalogues to see what else is there. Some safe harbor for some ingredients is step one and we’ll engage the agency on how we expand that to those that have been in the marketplace pre-DSHEA,” he said.
Electronic submissions were also “nice to see”, he said, although the industry will need some dialogue on part 11 compliance there.
“We will submit more to the agency to better understand their view of chemical alterations as technology has advanced significantly since 1994 on extraction of molecules from natural sources,” he said.
An economic analysis of compliance
NPA also wants to see more of an economic analysis of compliance with the provision, he said, including an understanding of what acute/sub-acute tox in an animal model(s) costs.
NPA’s own research of its member companies that have submitted NDI notifications reveal that a typical submission can cost $368,000 and upwards: Toxicology Studies range from $178,000 to $328,000; FTE & Consultants for preparing the NDI submission can cost $162,500; and analysis of analytical and physical properties can cost $27,500, said NPA.
“The numbers speak for themselves. It is critical for FDA to conduct a fair and accurate economic impact analysis for the cost of an NDI submission” said Dr Fabricant.
Both the Natural Products Association and the Council for Responsible Nutrition have announced they will host webinars to explore the guidance in more detail within the coming days.
“We’re taking the time to review the substance of the draft guidance in order to bring [together] the most qualified regulatory experts, and we expect the experts to include representatives from FDA,” said Duffy MacKay, ND, senior vice president, scientific & regulatory affairs, CRN. Dr MacKay added that the webinar will take place in September.
NutraIngredients-USA will bring more reaction, analysis and insights in the coming days about the new NDI draft guidance.