Draft guidance published by FDA for the dietary supplement industry could burden manufacturers, chill investment, reduce choices for consumers, and fail to achieve its intended objective of facilitating increased compliance with federal regulations, industry trade organizations argued this week in comments filed with the agency.
Aspects of the 102-page document also are contrary to legislative history and the plain reading of the 1994 Dietary Supplement Health and Education Act (DSHEA), some commenters asserted, and would impose regulatory hurdles that Congress did not intend when seeking to make dietary supplements widely available to the American public.
It’s been 22 years since DSHEA was signed by President Bill Clinton, but FDA—the agency charged with overseeing dietary supplements—and the nearly US$40 billion industry continue to haggle over a provision in the law that falls short of premarket approval but requires manufacturers and distributors notify FDA before marketing new dietary ingredients (NDIs), and provide evidence of an ingredient’s safety.
Since the passage of DSHEA, FDA has received around 900 NDI notifications, or as FDA reported in a 2015 document, an average of 55 notifications annually. In August 2016, in efforts to increase compliance with the NDI notification (NDIN) requirement and improve the quality of submissions, FDA published draft NDI guidance, supplanting a 2011 document that had been heavily criticized by the industry—and lawmakers who crafted DSHEA.
Under DSHEA, the 75-day premarket notification must include information establishing the "dietary supplement containing such dietary ingredient will reasonably be expected to be safe." In 1997, FDA published a final rule, laying out the regulations that must be followed when making a premarket NDIN. The current rule is approximately two pages in length and describes, in large part, what information the notification must include.
The new document is about 50 times larger than the NDI regulation itself. The section of DSHEA under the heading "NEW DIETARY INGREDIENTS" is less than 135 words.
After the 2016 draft NDI guidance was released, the industry immediately praised FDA for responding, at least in part, to some of the criticisms of the 2011 document. However, in written comments submitted this week to the agency, industry trade associations argued FDA’s new document, if finalized, would impose undue burdens on manufacturers and distributors. The comment period closed on Dec. 12.
"Instead of facilitating compliance with the NDI provision of the law, the 2016 revised draft guidance increases the burden on the supplement industry far beyond the intent of DSHEA with no concomitant benefit for consumers," the American Herbal Products Association (AHPA) declared in comments filed with FDA.
AHPA further predicted implementation of the current NDI draft guidance would stifle innovation and drive supplements out of the market, curtailing consumer choice. According to an annual survey conducted by Ipsos Public Affairs on behalf of the Council for Responsible Nutrition (CRN), more than 170 million adults take dietary supplements.
The guidance represents FDA’s thinking on the issues and is not legally binding. However, it remains to be seen whether regulators will take enforcement actions based on the principles contained in the massive document, such as its assertion in the draft guidance that synthetic botanicals don’t qualify as dietary ingredients.
FDA’s view on synthetic botanicals stems from the definition of a botanical or herb as only including "plants, algae, fungi, their exudates (secretions, such as sap or resin), and their physical parts."
"A substance that has been synthesized in a laboratory or factory has never been part of an herb or other botanical," FDA explained in the guidance, "and, therefore, is not a dietary ingredient" under the law.
The industry’s position on synthetic botanicals is rooted in arguments that neither DSHEA nor the legislative history prohibits the substances from being sold in supplements, and that FDA—the agency charged with implementing the statute and enforcing the law—has acted outside its authority.
"In defining dietary ingredient, Congress did not distinguish between natural and synthetic versions," the United Natural Products Alliance (UNPA) observed in comments filed with FDA. "Indeed, in 1994 synthetic versions of numerous vitamins, minerals and other dietary ingredients were being sold in the U.S."
CRN indicated FDA’s position cannot be reconciled with the 1976 Vitamin-Mineral Amendment to the Federal Food, Drug, and Cosmetic Act (FDCA), also known as the Proxmire amendment.
As FDA explained on its website, the Proxmire amendment prohibited the agency from establishing standards to limit the potency of vitamins and minerals in food supplements or regulating them as drugs based entirely on their potency. The legislation applied to both natural and synthetic vitamins and minerals, CRN pointed out.
"This language makes clear that Congress did not view the terms ‘vitamin’ and ‘mineral,’ standing alone, as inherently meaning the natural form of these dietary ingredients," the trade group asserted in comments filed with FDA. "[O]therwise, there would have been no need in the Proxmire Amendments to specify natural as well as synthetic vitamins and minerals."
The industry also is concerned FDA’s guidance would subject most products containing an NDI to a notification, even if FDA reviewed the safety of the same ingredient in a previous NDI submission. AHPA recommended FDA encourage the industry "to provide in their notifications broad descriptions of all of the dietary supplements that will include or may include the NDI, so long as the information submitted provides the basis for the submitter’s conclusion that the dietary supplements containing the NDI will be reasonably expected to be safe."
Some trade associations have raised concerns that FDA’s interpretations in the 2016 guidance could require tens of thousands of NDINs, overburdening the industry and an agency with a modest supplement staff of less than 30 full-time employees.
For example, UNPA has referenced the various manufacturing changes that would transform an old dietary ingredient into a new one, triggering an obligation to submit an NDIN to FDA. Manufacturing changes that trigger an NDIN should be based on ingredient identity and safety, UNPA recommended in its comments filed with FDA.
DSHEA developed a notification system focused on the ingredient to examine the safety of supplements, according to UNPA. "To read the statute otherwise, as FDA has done, subjects over 75,000 dietary supplements and nearly 10,000 dietary ingredients to persistent re-review for safety at an economic cost that is unjustifiable to the industry, that cannot be funded or staffed by FDA, and places the costs of many dietary supplements out of the consumer’s reach," the Salt Lake City-based organization declared.
The Natural Products Association (NPA), whose executives are former FDA officials, said in comments filed with FDA that demonstrating the safety of NDIs should not be tied to a standard that applies to food additives. The trade association requested FDA rewrite the toxicology sections in the document that relate to testing protocols and study designs.
"The way it stands now, the guidance could actually result in more bad actors skirting the law entirely, which is the opposite of what a sensible regulatory regime should be," said Daniel Fabricant, Ph.D., CEO and executive director of NPA, in a written statement.
FDA’s attempt to apply food additive-level toxicology tests to NDIs could wound small businesses, chill innovation and result in fewer NDI submissions, added Fabricant, a former director of FDA’s Division of Dietary Supplement Programs, who left the agency in 2014.
Yet another point of contention surrounds FDA’s interpretation of a provision in DSHEA that grants manufacturers and distributors an exemption from an NDI submission. The exemption applies if the "dietary supplement contains only dietary ingredients which have been present in the food supply as an article used for food in a form in which the food has not been chemically altered."
FDA has interpreted "present in the food supply" as only correlating with the conventional food supply. Some trade associations argued FDA’s interpretation of the law is too narrow and contradicts the ordinary meaning of "food" in DSHEA and the broader FDCA.
"This inaccurate interpretation would render ‘food’ and ‘food supply’ so narrow that it would leave out many ingredients long understood to be food—dietary ingredients with a history of safe use in dietary supplements in the food supply," CRN stated in its comments.
However, FDA explained why it did not broaden its interpretation of "present in the food supply" to supplements. Such a reading of the law, FDA explained in the 2016 draft guidance, "would risk swallowing the [NDIN] rule, as prior use in even one dietary supplement manufactured in small quantities and distributed over a small area would exempt all dietary supplements containing the NDI from the notification requirement, even if the intake level and conditions of use were much different."