The United Natural Products Alliance (UNPA) submits these comments in. response to the Food and Drug Administration s Draft Guidance on New Dietary

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1 December 2, 2011 VIA ELECTRONIC SUBMISSION Division of Dockets Management (HFA-305) Food and Drug Administration 5630 Fishers Lane, Room 1061 Rockville, MD Re: Draft Guidance for Industry Dietary Supplements: New Dietary Ingredient Notifications & Related Issues Docket No. FDA-2011-D Fed. Reg (July 5, 2011) The United Natural Products Alliance (UNPA) submits these comments in response to the Food and Drug Administration s Draft Guidance on New Dietary Ingredient Notifications (NDIG) published on July 5, UNPA is a dietary supplement trade association founded in 1992 to promote sound legislation and regulation of dietary supplements. We represent over 40 companies worldwide with combined dietary supplement and natural product sales of over $6 billion. Our purpose is to support the safe and beneficial use of dietary supplements and 1075 Hollywood Avenue. Salt Lake City, Utah (p) (f) i

2 to support consumer confidence in supplements by assuring Good Manufacturing Practices and quality standards for dietary supplements. UNPA has been actively engaged with other interested parties in the full and proper implementation of the Dietary Supplement Health and Education Act of 1994 (DSHEA). To that end, we have read with great interest FDA s NDIG. While UNPA recognizes the need for an efficient and fair NDI notification process, the current draft guidance creates procedures and safety review standards inconsistent with DSHEA. This would result in higher costs and loss of access to dietary supplements among consumers, create significant loss of productivity for manufacturers, and impose food additive safety evaluation procedures on the NDI notification process that are unintended by DSHEA. We conclude that the NDIG as currently drafted should not be implemented by the agency. Until the FDA and the dietary supplement industry have an opportunity to work together through a guidance or rulemaking process that achieves a balance between FDA s consumer protection mandate, industry s ability to innovate new products and consumers need for unhindered access to safe dietary supplements and ingredients, UNPA respectfully urges the agency to withdraw the current NDIG and to refrain from adopting or enforcing its current thinking contained in the draft guidance. ii

3 TABLE OF CONTENTS I. What is an NDI? - An Ingredient or a Finished Dietary Supplement Product? 1 II. Who Must File a New Dietary Ingredient Notification?. 2 III. Need for Old Dietary Ingredient Authoritative Lists IV. Synthetic Botanicals Are Not Dietary Ingredients.. 7 V. Microbial Dietary Ingredients Are They Biologics in FDA s View?.. 8 VI. Food Additive Safety Requirements for Dietary Supplements are Inconsistent with DSHEA. 9 VII. Chemical Alteration 11 VIII. Protection of NDI Submitter s Intellectual Property. 12 IX. Conclusion.. 14 iii

4 I: What is an NDI? - An Ingredient or a Finished Dietary Supplement Product? A central element of DSHEA is Section 413 (New Dietary Ingredients) which defines the term new dietary ingredient as a dietary ingredient that was not marketed in the United States before October 15, This provision thus created two classes of dietary ingredients old and new, based on a grandfathering date of October 15, Those members of Congress who crafted Section 413 recognized the need to establish a safety review mechanism for ingredients unknown to the U.S. market in To this end, Section 413 was titled, New Dietary Ingredients, and the definition in Section 413(c) refers only to new dietary ingredients. Section 413(b) refers only to new dietary ingredients, and, importantly, Section 413(a)(1) and (2) defines an adulterated dietary supplement as one which contains a new dietary ingredient for which a notification has not been filed. In each case, the intent of Section 413 was to grandfather ingredients, not individual products, based on both the history of individual food ingredient usage and evidence of safety. Thus, the simplest and most direct reading of Section 413 must lead to the conclusion that Congress intended a process whereby dietary ingredients (not products) that meet the definition of new dietary ingredient would be subject to a 75-day notification requirement. Indeed, archived working drafts of Section 413 show that the word supplement was struck out and replaced with the word ingredient as a further indication that the negotiators of DSHEA made a conscious decision to create an NDI process based on individual ingredients rather than finished products. (See Attachment I.) Therefore, UNPA disagrees with the FDA s interpretation in the draft guidance that Congress intended notification of safety on dietary supplement products and urges the agency to focus safety on (new) dietary ingredients rather than on dietary supplements. 1

5 II. Who Must File a New Dietary Ingredient Notification? The agency takes the extraordinarily expansive view that any manufacturer or distributor of a dietary supplement must file a new dietary ingredient notification (NDIN) for each dietary supplement containing an acknowledged new dietary ingredient (ANDI) if: 1) The daily intake of the ANDI in the dietary supplement changes upward. 2) The dietary supplement contains any other dietary ingredients not noted in the original ANDI. 3) The target population of the dietary supplement changes from the original ANDI. 4) The conditions of use noted on the dietary supplement label change. 5) There are manufacturing process changes to the DS containing the ANDI. In short, FDA proposes to create a new dietary supplement (NDS) notification system whereby virtually all dietary supplements would be subject to a mandatory re-notification to FDA as a result of changes in formulation, labeling, or manufacturing process of any dietary supplement containing an ANDI. FDA bases this requirement on a reading of DSHEA that treats individual dietary supplements as if they are individual dietary ingredients. This, in turn, allows FDA to argue that any change to a finished dietary supplement is, in fact, a change to the new dietary ingredient, thus creating a new NDI (NNDI) subject to the notification requirements of Section 413. As noted elsewhere in our comments, we believe that FDA has fundamentally erred in its interpretation of what is a new dietary ingredient and who is responsible for filing NDI notifications. 2

6 Under FDA s current view, each of the changes noted above would require the manufacturer or distributor of such dietary supplements to prepare an updated NDIN, submit the notification to FDA, be prepared to wait the 75-day response period and to cease manufacturing, distribution, sale, and marketing of such dietary supplements or risk being in violation of Section 413, i.e., selling an adulterated dietary supplement (a dietary supplement containing a new dietary ingredient that is not the subject of a Section 413 notification). UNPA believes FDA s proposed policy is tantamount to requiring new drug approval requirements for dietary supplements in the same manner that changes to the labeling, manufacture, or formulation of a new approved drug are subject to similar requirements. UNPA has commissioned a dietary supplement industry survey to assess the number of new dietary ingredient trigger events to determine the effect on productivity and estimated economic loss such a requirement would have. The findings of the survey will be submitted to FDA as additional comments to this docket. However, our initial estimates indicate economic impact in the form of revenue losses to the industry caused by such interruptions in production feared to be in billions of dollars not to mention such revenue losses in turn causing shrinking employment opportunities on companies production lines. 3

7 III: Need for Old Dietary Ingredient Authoritative Lists The agency states there are no authoritative lists of Old Dietary Ingredients (ODIs) but notes that some trade associations have published lists of ODIs that have not been verified by FDA and are not backed up by evidence the ingredients listed were actually marketed before October 15, FDA also notes these lists contain inappropriate ingredients, such as acetaminophen or pharma glaze, or vaguely described mixtures (sterol complete premix). UNPA agrees that the current ODI lists require further review, editing, and revision. To this end, UNPA s NDI Working Group has undertaken a review (included as Attachment II) of UNPA s current ODI list (included as Attachment III) which is a compilation of the ODI lists of the American Herbal Products Association, the Council for Responsible Nutrition, the Natural Products Association, and the United Natural Products Alliance. The purpose of this review has been to: 1. Remove non-qualifying ingredients and substances. 2. Add botanical nomenclature throughout. 3. Create annexes to recognize: a. Additional qualified Old Dietary Ingredients. b. Probiotic and microbial substances recognized as Old Dietary Ingredients. c. Addition of Herbs of Commerce I & II as an authoritative reference source. d. Relegation of ingredients removed from the original ODI lists to a separate annex for ease of reference; there were 273 listings removed from the current ODI list. (See pp of Attachment II.) This and other enhanced or updated ODI lists should provide industry and FDA a much needed reference tool to guide decisions with respect to determining NDI/ODI status of various 4

8 ingredients. This, in turn, would substantially reduce costs to industry by avoiding the unnecessary preparation and filing of NDI notifications and would serve to reduce costs to consumers who will ultimately bear the economic burden of NDI notification costs. UNPA urges FDA to recognize the value and importance of authoritative ODI lists and to provide industry with confirmation of its willingness to accept authoritative lists that are based on credible/adequate research. Old Dietary Ingredients are defined as vitamins, minerals, herbs or other botanicals, amino acids or dietary substances for use by man to supplement the diet by increasing the total dietary intake, or concentrates, metabolites, constituents, extracts or combinations of any ingredient described above, and that were marketed prior to October 15, 1994, in the United States. In the NDIG the agency takes the position that an ingredient used in a conventional food before October 15, 1994 is not an ODI because it was not marketed as a dietary ingredient in a dietary supplement. Until October 25, 1994, there was no legal definition for dietary supplement or dietary ingredient. However, hundreds, if not thousands, of ingredients that are described by this definition were marketed in the United States before October 25, 1994 and were consumed by the public to increase their total dietary intake of such substances. It is entirely inconsistent with the principles of DSHEA to strictly limit Old Dietary Ingredients to those ingredients that used a nonexistent legal definition before October 25, In fact, the last sentence of Section III of DSHEA states, Except for purposes of Section 201(g), a dietary supplement shall be 5

9 deemed to be a food within the meaning of this Act. In view of this language, Congress could only intend that the operative definition of dietary supplement and dietary ingredient be both applicable and available to any substance or ingredient which otherwise meets the statutory definition, irrespective of its labeling as a food, nutritional supplement, dietary adjunct, or other term. UNPA does not disagree with FDA s list of documentation to support ODI status but believes other evidence such as personal correspondence, medical records, government documents, personal attestations, photographs, etc., are equally relevant to establish ODI status. UNPA believes that industry documents such as AHPA s Herbs of Commerce (1992, 2000 editions) represent a significant repository of evidence in support of botanical ODI status, and that Herbs of Commerce should be recognized by FDA as an authoritative reference source. 6

10 IV. Synthetic Botanicals are Not Dietary Ingredients In Section IV(D)(2) of the NDIG, the agency states that synthetic copies of botanical constituents are not dietary ingredients, pursuant to the rationale that the synthetic compound was never a part of the original botanical and thus cannot be a dietary ingredient. This new and unexpected policy, if enforced, would create a legal limitation on the definition of dietary ingredient neither intended by Congress nor found elsewhere in DSHEA. FDA provided no rationale for this policy other than noting its concern about synthetic derivatives of ephedrine alkaloids. Apparently this concern has migrated to this NDIG, which is both inconsistent with DSHEA and longstanding FDA policy. In fact, FDA has a longstanding policy prohibiting statements that natural vitamins are superior to synthetic vitamins. Without addressing the merits of that policy, it must be noted that FDA has heretofore not expressed a belief that synthetic analogs of natural substances are inherently unsafe. For example, FDA has affirmed as GRAS natural and synthetic riboflavin, vitamin A and vitamin D. The only basis on which FDA should deny NDI status of a synthetic botanical constituent or synthetic nutrient constituent would be failure to establish that such a constituent is reasonably expected to be safe under conditions of proposed use. We ask FDA to withdraw this provision of the NDIG and reaffirm that synthetic constituents of botanicals may be lawfully marketed as dietary ingredients if the ingredients otherwise satisfy the requirements of DSHEA. 7

11 V. Microbial Dietary Ingredients Are they Biologics in FDA s View? The NDIG states that: Not all bacterial microorganisms are dietary ingredients, and a microorganism that is not a dietary ingredient cannot be an NDI bacteria that have never been consumed as food are unlikely to be dietary ingredients FDA does not have a separate regulatory category or definition for dietary ingredients consisting of live or viable microorganisms. UNPA finds these statements to be confusing and troubling and requests that FDA confirm that probiotics, fungi, and other similar live or viable microorganisms and substances are recognized within the definition of dietary ingredient as found in Section 201(a)(ff)(1)(2)(3) of the Food, Drug & Cosmetic Act (FDCA). We recognize that the only exclusion would be failure to demonstrate that such substances could reasonably be expected to be safe under the conditions of labeled use. The agency has, at times, expressed the view that probiotics may in fact be biologics and thus subject to regulation as such. If such views are based on perceived drug claims made for probiotics and other microorganisms, we request the agency to clarify its views on this matter so industry may proceed with confidence in developing and marketing probiotics and other microorganisms without fear the agency will declare such products non-dietary ingredients. UNPA is also aware that new and updated inventories of lactobacteria with documented histories of safe use as foods are in publication, and we will update our comments with additional documentation to support the long and safe history of use of probiotics as articles of food and as additions to the daily diet. 8

12 VI. Food Additive Safety Requirements for Dietary Supplements In Section VI(B) and VI(C) of the NDIG, the agency articulates an expansive safety evaluation process for NDIs based on the general principles of food additive petitions. The agency is well aware that a central reason for the introduction and ultimate passage of DSHEA was the use of the food additive theory in the 1980s to remove dietary supplements from the U.S. marketplace. On a number of occasions, FDA used this tool to argue that dietary supplements were in fact food additives, thus requiring pre-market approval. The sale of a non-approved dietary supplement would therefore trigger unapproved food additive status resulting in FDA detention and seizure of dietary supplements. A series of court cases held that FDA s use of the food additive theory was unlawful. This was confirmed and codified in DSHEA by amending Section 201(s) of the FDCA by clarifying that dietary supplements are not food additives. The agency now proposes to reset the NDI safety standard from a reasonable expectation of safety to the different food additive safety standard of a reasonable certainty of no harm. FDA does not have the statutory or administrative authority to amend the NDI safety standard that was established in Section 413 of DSHEA. The agency refers to the Red Book, which is FDA s authoritative guide for safety and toxicology standards for food additives, as a general guideline for NDI safety dossier development. Based on recent conversations with NDI applicants, it appears that FDA is already requiring NDI submitters to develop and propose NDI safety packages based on Red Book principles. The direct economic impact of this new and unauthorized safety standard is already being felt by the supplement industry. 9

13 Congress intentionally established a different safety standard for NDIs, fully understanding the existing safety standard for food additives. Congress did so, recognizing that dietary ingredients are largely derivatives of foods and other dietary components found in the human diet and for which there is often an existing history of consumption and use. It was also recognized that the history of safe use of dietary ingredients and dietary supplements did not merit adoption of the new food additive safety standard. FDA s proposal to merge the NDI safety standard into the food additive safety standard is without statutory basis and represents a major departure from FDA s NDI evaluation over the past 16 years. UNPA requests that FDA withdraw all reference to food additive safety standards and evaluation procedures and re-propose a standard of safety within an appropriate level of evidence based on the reasonable expectation of safety standards laid down by DSHEA. 10

14 VII. Chemical Alteration DSHEA created a category of dietary ingredients that do not require NDI notification: 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. The legislative history of DSHEA provides examples of processes that do not result in chemical alteration. They include minor loss of volatile components, dehydration, lyophilization, milling and formation of a tincture or a solution in water, a slurry, a powder or a solid in suspension. The agency interprets these examples as an exclusive list of processes that do not trigger chemical alteration. We disagree. The examples provided in this legislative history are illustrative of but not exclusive of other processes that may not result in chemical alteration of food. Food manufacturing and extraction techniques have evolved substantially since 1994, resulting in ingredients, food extracts and dietary ingredients that provide greater purity or consistency while not resulting in a chemical alteration of the original ingredient. We request that the agency evaluate the dietary ingredient itself rather than applying a restricted list of illustrative processes to determine whether chemical alteration has occurred resulting in a new dietary ingredient. 11

15 VIII. Protection of Intellectual Property The development of successful new dietary ingredients requires substantial investments in research and development, clinical studies, safety assessments, and regulatory review. In addition, companies often spend millions of dollars to develop more efficient manufacturing and sourcing means and methods. Collectively, this development process represents the greatest intellectual property investment many dietary ingredient/dietary supplement companies will make, with the expectation of realizing an appropriate return on investment. Section 413 recognizes the importance of protecting information assets by stating: The Secretary shall keep confidential any information provided under paragraph two (2) for 90 days following its receipt. After the expiration of such 90 days, the Secretary shall place such information on public display, except matters in the information which are trade secrets or otherwise confidential, commercial information. This protection of confidential commercial information is fundamental to the decision to file an NDIN. Additional steps helpful to this end would be: 1. Recognition that the NDI (and its intellectual property) is the ingredient not the finished product. The NDI functions as a passport which, once issued, may be used in any dietary supplement within the specifications permitted in the ANDI. This grants the ANDI holder the freedom and incentive to fully develop market potential for the new dietary ingredient. 12

16 FDA s current proposal does the opposite by establishing a finished dietary supplement-based system of endless NDI re-filings for the same ANDI as sold in various finished dietary supplements. Under FDA s approach, the ANDI actually serves as the trigger to cause the continuous re-filing of notifications to describe minor changes to finished products which contain the ANDI. For this reason alone, such a system would widely discourage companies from filing NDIs. 2. Appropriate use of enforcement discretion. An ANDI is unique. Other similar dietary ingredients may not piggyback on an ANDI as the basis on which to affirm Section 413 compliance. While ANDI holders have a private right of action to protect their intellectual property investments in their new dietary ingredient, the costs are often prohibitive. UNPA believes that FDA, as part of a fair and efficient NDI policy, should recognize the role of appropriate enforcement discretion to affirm that an ANDI is unique to the ANDI holder, and that other similar dietary ingredients may not rely on such ANDI as a basis to assert Section 413 compliance. 13

17 IX. CONCLUSION This draft guidance misinterprets the plain language of DSHEA and imposes needlessly burdensome and expensive requirements on dietary supplement producers and marketers without advancing the overall safety of dietary supplements. This would lead to higher consumer prices, reduced variety of product choices, contraction of jobs and innovation and would foster an inequitable competitive environment between manufacturers. While we share, with FDA, the goal of full and efficient implementation and enforcement of DSHEA, this draft guidance will not help achieve that objective. Consequently, we request that FDA withdraw this draft guidance and re-propose further guidance, taking into account Congressional intent and comments by industry, consumers, and other interested parties. UNPA reaffirms its commitment to work with FDA to achieve a robust and efficient NDI policy that encourages continued safety evaluation of dietary ingredients and the protection of industry s investments in science and research toward this end. Respectfully submitted, Loren Israelsen Executive Director United Natural Products Alliance 1075 Hollywood Avenue. Salt Lake City, Utah (p) (f)