By Len Monheit
Last week marked the deadline for the comment period for groups to respond to the US Food and Drug Administration's request for answers to several questions regarding the procedure for pre-market notification for New Dietary Ingredients (NDIs). The process has been poorly understood by many in the industry, one of the reasons for such high non-acceptance rates for NDI submissions by the FDA. It has also been poorly communicated to the media, depriving industry of key argument to challenge the belief that there is no requirement for presentation of safety information before a new ingredient can be introduced into the marketplace. And it has been inadequately or improperly used by industry, as evidenced by the scope of submissions, and the 'common' knowledge that several products are on the marketplace that really should be the subject of NDI filings - and hence are illegal.
So the desired outcome is obviously a clarification of the procedure and expectations, the augmenting or revising of this procedure (hopefully with some input and guidance from industry) followed by appropriate use of this process to not only ensure that all future products go through the system properly, but also to clarify the status of products currently on the market. It is this last which is probably the most contentious of the issues, with questions on the table such as "does a new extraction procedure constitute a new dietary ingredient?"
The next several months will be critical. It will be interesting to see the outcome of the submissions and the steps taken by the FDA. Will there be a further consultative process? Will a guidance document emerge that is realistic and fair? What will be communicated to the media? What will be the interim strategy if the process or understanding changes dramatically? If enforcement in the marketplace is not enhanced as rules are clarified and interpreted, will industry comply?
Many industry groups have weighed in on the argument and questions raised by the FDA. Several have referred to a proposal to create a positive list of 'Old Dietary Ingredients' with arguments noting that this list should be as broad in scope as possible, but that if not handled correctly, that it could become an exclusionary list - that is, similar to the EU supplements list, where if you do not specifically make the list, you're excluded and in this case, must go through the NDI process, both for current and future products. That said, if the list is created with broad interpretation, it might serve to manage the argument that many processing or use changes do not define or create new dietary ingredients, and that the only practical way of managing these processing or use changes is to focus on those that have shown evidence of introducing a safety or health risk.
The comments submitted by the Utah Natural Products Alliance (UNPA) note the potential benefits of a process which parallels the process for obtaining GRAS (Generally Recognized as Safe) affirmation. The Alliance argues that many ingredient companies know and understand this process, many follow it as they introduce products to the food markets in parallel with supplement applications, and it has proven effective in answering safety oriented questions relating to the use of these products in various formulation types.
The Alliance, along with the American Herbal Products Association (AHPA), pays specific and critical attention to a term raised by the Agency - 'chemical composition', responding specifically to the question, ""what changes in chemical composition to a dietary ingredient would cause it to become a substance that is not a dietary ingredient?" as well as "what changes in chemical composition of an 'old dietary ingredient' would cause it to become a 'new dietary ingredient'." UNPA suggests this question be reworded to focus on the issue of safety and risk, avoiding altogether the question of chemical composition, a real Pandora’s box for the industry. AHPA specifically "opposes FDA’s contention that the “chemical composition” or “active components” needs to be disclosed."
The concept of 'change of use' was also dealt with by UNPA in their comments, noting that "the agency would need to establish an underlying rationale that there is a problem that needs to be solved by requiring the filing of NDI notices for ordinary changes in conditions of use." The Council for Responsible Nutrition (CRN) notes its belief that "changes in dosage or intended use or processing do not make an old ingredient “new,” but such changes may well raise safety issues that need to be addressed by manufacturers and potentially by FDA", and suggests that companies might prepare and maintain a 'safety dossier', which might in effect be similar to that expected for a GRAS affirmation. CRN also notes exclusions from the requirements for filing an NDI, including "Any substance found naturally in the food supply -- at any level, and regardless of prior safety evaluation", with specific potential examples including 'a newly isolated polysaccharide from mushrooms.' AHPA, in its submission, also notes this provision of DSHEA.
The various submissions raise important issues for FDA to take into consideration in order to make the system better - in effectiveness and in compliance.
CRN suggests an industry-sponsored safety review panel and attention to issues such as confidentiality. CRN notes that a description of the intended use should be sufficient in a submission including serving size, dose and frequency, and does not believe that information regarding composition or formulation should be required. It recommends that FDA be willing to meet and discuss notifications with potential submitters.
AHPA comments on the concept of 'marketed in the United States before October 15, 1994' as not meaning "marketed in the United States as an ingredient in a dietary supplement before October 15, 1994," and therefore the term 'marketed' should be broadly interpreted. AHPA also points out instances where it believes that FDA officers have held ingredients which should not be considered NDI's as "accountable to a regulation from which these ingredients are specifically exempt," listing, in its submission, several traditional Asian animal ingredients offered for sale in the United States prior to October 15, 2004. AHPA also pointed out inconsistencies in actual wording and current expectations, which appear to be different, and suggests a requirement that plant part identification be a mandatory requirement for herbal submissions, and identifies a number of other pieces of information that would assist standardization of the submission process.
AHPA suggests that FDA should refuse to accept notifications for new dietary supplements, which in fact are illegitimate submissions. Their posting confuses, rather than clarifies or notifies. Both AHPA and UNPA suggest that submissions should be allowed to be withdrawn without prejudice. AHPA notes that the standard for an NDI to be 'reasonably expected to be safe' must be reasonable, it "does not require that an NDI be proven to be safe."
UNPA suggests that a moratorium period be established that would allow companies to assess whether some products, currently on the market, might require NDIs and submit these NDIs without jeopardizing current commercial viability during this period.
As this issue and dialogue evolves, it will impact many aspects of the industry, both from a product development standpoint, as well as a market analysis/compliance point of view. Many companies are already analyzing their ingredient lists and product portfolios, recognizing that this audit and status analysis is prudent risk management. Whatever the outcome of the current process, we can expect more focus on dietary ingredient status in the next few years.