NDI: LOOKING BACK & AHEAD

Transcription

1 NDI: LOOKING BACK & AHEAD Chi Hee Kim D i r e c t o r, W o r l d w i d e R e g u l a t o r y, G o v e r n m e n t a n d I n d u s t r y A f f a i r s H e r b a l i f e I n t e r n a t i o n a l o f A m e r i c a, I n c. O c t o b e r

2 Dietary Supplement Health and Education Act (DSHEA) of 1994 Defined dietary supplement and dietary ingredient The term "dietary supplement" a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E) Section 201(ff)(1) of the FD&C Act, 21 U.S.C. 321(ff)(1).

3 New Dietary Ingredient ( 8 of DSHEA) Definition: a dietary ingredient that was not marketed in the United States before October 15, 1994 A dietary supplement which contains a new dietary ingredient shall be deemed adulterated under section 402(f) unless it meets one of the following requirements: (1) 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. (2) There is a history of use or other evidence of safety establishing that the dietary ingredient when used under the conditions recommended or suggested in the labeling of the dietary supplement will reasonably be expected to be safe and tstothefdcact/ucm htm#sec8

4 New Dietary Ingredient ( 8 of DSHEA) NDI Notification submission at least 75 days before being introduced or delivered for introduction into interstate commerce, the manufacturer or distributor of the dietary ingredient or dietary supplement provides the Secretary with information, including any citation to published articles, which is the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe. FDA reviews notification Issues letter of nonobjection Issues letter of objection Requests more information

5 NDI Notification Represents FDA s only means of pre-market review A dietary supplement shall be deemed to be adulterated if It is a new dietary ingredient for which there is inadequate information to provide reasonable assurance that such ingredient does not present a significant or unreasonable risk of illness or injury (Sec [21 USC 342] Adulterated Food) Critical step in assuring the safety of dietary supplements in the US

6 NDI Notification: Current Status Since 1994, majority of NDI notifications have been met with objection (>~60-70%) In 2011, FDA has received approximately 700 NDI notifications; acknowledged 158 notifications (no objection); and objected 442 notifications. Reasons for objections: Lack of proper characterization (unable to establish identity) Failed basic requirements (e.g., providing Latin binomial and authority, including references, or submitting English translation for documents in another language) Unresolved safety issues Non dietary ingredients (drugs)

7 Industry Guidance Needed Lack of clarity on FDA s expectations and differences in interpretation of the law Contributed to low success rate Varied compliance by industry Many companies ignoring NDI notification requirement Under the FSMA (Food Safety Modernization Act), FDA is required to publish NDI notification guidance no later than 180 days after the date of enactment. FDA published the NDI notification draft guidance on July 2011

8 FDA Draft Guidance on NDI notification (July 2011) m

9 Draft NDI Guidance: Main Areas of Focus When Is a Dietary Ingredient New? When are NDIs exempt from the Notification Requirement? What should be included in a NDI Notification and how should it be presented? History of Use and Other Evidence of Safety

10 Draft NDI Guidance: Areas of Controversy Substantiation for what constitutes an Old Dietary Ingredient (pre-oct 1994) Burden to prove an ingredient is grandfathered is on the marketer Definition of chemically altered FDA s definition of chemically altered is broad Notifications for ingredients vs. finished products DSHEA says the dietary ingredient must reasonably be expected to be safe, but FDA wants each finished product containing NDI to have its on notification on file Exclusion of synthetic constituents of botanicals from the definition of dietary ingredient Even if bio-identical, synthetic version was never part of the botanical so it cannot be characterized as a botanical constituent Me too ingredients NDI is not about marketability or the protection of intellectual property Can competitors use your NDI filing? Guidance Regulation

11 How to substantiate if a Dietary Ingredient is Old? these lists have not been verified by FDA and are not backed by evidence that the ingredients listed were actually marketed prior to October 15, 1994 FDA does not accept the inclusion of an ingredient on an industry list of pre-dshea dietary ingredients as proof that the ingredient is not a NDI Documentation include sales records, manufacturing records, commercial invoices, magazine advertisements, mail order catalogues, or sales brochures.

12 What is Chemically Altered? 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 do not chemically alter an ingredient All other processing equates to chemical alteration Nearly all novel extraction methods (solvents, super critical CO2) Affects many ingredients presumed to be Old but because of processing may now be considered NDIs (with no notification)

13 Ingredient or Product Notification? DSHEA refers to new dietary ingredient Industry assumed this for 16 years and submitted ingredient-based notifications But in draft guidance FDA interprets the language of the law as product the basis on which the manufacturer or distributor has concluded that a dietary supplement containing such dietary ingredient will reasonably be expected to be safe. Dietary supplement = finished product

14 Can synthetic bio-identical versions of botanical ingredients be dietary ingredients? (ff) The term ``dietary supplement''-- (1) means a product (other than tobacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: (A) a vitamin; (B) a mineral; (C) an herb or other botanical; (D) an amino acid; (E) a dietary substance for use by man to supplement the diet by increasing the total dietary intake; or (F) a concentrate, metabolite, constituent, extract, or combination of any ingredient described in clause (A), (B), (C), (D), or (E).

15 Can synthetic bio-identical versions of botanical ingredients be dietary ingredients? FDA: NO: A synthetic copy of a constituent of a botanical was never part of the botanical and thus cannot be a "constituent" of the botanical that qualifies as a dietary ingredient a synthetic version of a botanical extract is not an "extract" of a botanical because it was not actually extracted from the botanical. But manufacturers use bio-identical synthetics because they are more uniform, more environmentally sustainable or more commercially viable than harvesting the plant.

16 Me too ingredients NDI could potentially open door for me too ingredients. Until there is a final NDI guidance, it won t be clear. NDI process is about safety, not about marketability or the protection of intellectual property. Without protection, it discourages ingredient companies from abiding by regulations. Recent letter from Mitsubishi Gas Chemical Co., Inc. on pyrroloquinoline quinone (PQQ) regarding third parties purporting to rely on Mitsubishi s NDI when in fact two materials are not identical in terms of purity.

17 Guidance Regulation Represents FDA's current thinking on this topic does not create or confer any rights for or on any person and does not operate to bind FDA or the public use an alternative approach if the approach satisfies the requirements of the applicable statutes and regulations to discuss an alternative approach, contact the FDA staff responsible for implementing this guidance

18 Industry Reaction Majority of US industry strongly opposed to the Draft Guidance Increased burden on both industry and FDA without offering public more protection Concern that innovation would be limited and costs to bring new technologies to market would increase dramatically Concern that FDA s standard for safety is too high and inconsistent with Congress intent Trade associations in the industry had three meeting with FDA on the NDI issue in 2012 and provided at least five submissions to the docket.

19 Congress Reaction 2012 & members of Congress calls for withdrawal of draft guidance on NDI notification in a letter to Dr. Margaret Hamburg (02/29/2012) We strongly urge FDA to withdraw this guidance and instead design a fair and workable NDI notification system 27 key members of Congress voiced concern over the speed of progress of revising the draft guidance in a letter to Dr. Margaret Hamburg (07/09/2013) We hope that you will work toward completion in a timely manner.

20 FDA Response to Date FDA received 146,000 pages of comments following publication of the draft guidance in July 2011 FDA declined to withdraw draft guidance Agency in the process of reviewing comments Met with trade associations in the industry at least 5 times Warning letters in 2012 and 2013

21 Recent Enforcements by FDA Few regulatory action taken in 18 years since DSHEA until 2012 Eleven warning letters on dimethylamylamine (DMAA ) to 11 manufacturers and distributors of dietary supplements containing DMAA in April and August, 2012 ( htm#warning_letters) One warning letter on aegeline (N-[2-hydroxy-2(4-methoxyphenyl) ethyl]-3- phenyl-2-propenamide) in USP Labs LLC Oxy Elite Pro and VERSA-1 in October 2013

22 Warning Letter on Aegeline (10/11/13)

23 Final NDI Guidance? Timing of a final guidance: CFSAN s Plan for Program Priorities include guidance for NDIs. CFSAN s plans include publishing in 2013 revised draft guidance on NDI s to increase premarket oversight of dietary supplements. Under this plan, final NDI guidance will be issues in ( wedo/ucm htm)

24 Thank you!