FDA REGULATION OF DIETARY SUPPLEMENTS AND FOODS Presented by W. Patrick Noonan And Chris Noonan For NUTRITION INDUSTRY ASSOCIATION W. Patrick Noonan, P.C. 21800 Oxnard Street, Suite 840 Woodland Hills, California 91367 1
What is the legal definition of Dietary Supplement? (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 above. 21 U.S.C. 321(ff)(1) 2
MARKETING OF HOMOTAURINE AS AN AMINO ACID FDA denied a citizen petition filed on behalf of OVOS Natural Health, Inc. ( OVOS ) that asked the agency to issue a regulation under FDC Act 201(ff)(3)(B) or 301(ll) acknowledging that marketing of homotaurine as a dietary ingredient in dietary supplements is permissible. OVOS filed the citizen petition because OVOS had not marketed homotaurine as a dietary supplement or food before OVOS obtained authorization for an IND pursuant to which at least two substantial clinical investigations have been instituted and made public; thus, FDC Act 201(ff)(3)(B) appeared to prohibit the marketing of homotaurine as a dietary supplement, and FDC Act 301(ll) appeared to prohibit its addition to food. However, both sections contain provisions that authorize FDA to issue a regulation that essentially waives their applicability to a particular substance. In its response, FDA concluded that the request to exercise its rulemaking authority under FDC Act 201(ff)(3)(B) or 301(ll) was moot because homotaurine is not a dietary ingredient within the meaning of FDC Act 201(ff)(1)(A)-(F). FDA determined that homotaurine is not an amino acid under FDC Act 201(ff)(1)(D) because it is a gammaamino sulfonic acid, and not an alpha-amino carboxylic acid or a constituent of proteins. FDA also determined that OVOS s homotaurine does not qualify as a botanical (or extract thereof) because it is made synthetically. Further, FDA determined that there was no evidence that homotaurine has ever been a dietary substance for use by man to increase the total dietary intake. 3
DEFINITION OF DIETARY SUBSTANCE FDA Informal Guidance The term dietary substance is not defined in the Act. FDA interprets it with its common or usual meaning. Therefore, a dietary substance means a substance that is commonly used as human food or drink. The statutory language for use by man to supplement the diet by increasing the total dietary intake supports this interpretation; and one cannot increase the total dietary intake of something that is not commonly part of the diet in the first place. Humans do not commonly use chemically manufactured or synthetic CLA as food or drink.* *(CFSAN s Felicia Satchell NDI CLA letter to Jason Crush August 29, 2002.) 4
Race To The Market Provision An ingredient does not qualify as a dietary supplement If the ingredient is subject to a new drug application under Section 505 of FDC Act that was approved prior to initial marketing of the dietary supplement ingredient. If the ingredient is subject to an approved investigational new drug IND application by FDA, for which one clinical study has been published that occurred prior to the initial marketing of the dietary supplement ingredient. See Section 201(ff)(3)(B) of the FDC Act 5
FDCA SECTION 301(ll) FDCA Section 301(ll) makes it a prohibited act to introduce or deliver for introduction into interstate commerce any food to which has been added a drug approved under section 505, a biological product licensed under section 351 of the Public Health Service Act, or "drug or biological product for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public." Of the four limited exceptions outlined in Section 301(ll) the most useful is the "first to market" exception that allows the addition of a drug or biological product to food if that drug or biological product was first "marketed in food. " 6
Regulatory Issues Concerning New Dietary Ingredients 7
Safety Standard for Dietary Ingredients in Dietary Supplements The Dietary Supplement Health and Education Act of 1994 (DSHEA) explicitly exempts dietary ingredients in dietary supplement products from regulation as food additives (and therefore, from any need to be GRAS). 21 U.S.C. 321(s)(6). Instead, a dietary ingredient in a dietary supplement is subject to other, somewhat-more-tolerant safety requirements. Such an ingredient must not present a significant or unreasonable risk of illness or injury under... conditions of use recommended or suggested in labeling, or.... if no conditions of use are suggested or recommended in the labeling, under ordinary conditions of use. 21 U.S.C. 342(f)(1)(A). 8
Old or New? Is it an old dietary ingredient, or a new dietary ingredient? The Dietary Supplement Health and Education Act (DSHEA) of 1994 makes a distinction between the two. 9
Old Dietary Ingredient A dietary ingredient that was lawfully marketed in the U.S. before Oct. 15, 1994. Lawfully marketed means written evidence that the ingredient in question is chemically identical to a dietary ingredient that was marketed in the U.S. before Oct 15, 1994. 10
FDA Informal Guidance FDA informal guidance to prove an ingredient is not a new dietary ingredient: (1) Marketed as a DS before October 15, 1994. You need to demonstrate that the listing of an old ingredient in a given publication is founded on accurate and reliable evidence sufficient to support a finding that the ingredient was marketed dietary ingredient prior to October 15, 1994 in the United States. (2) Alternatively, you could submit independent documentation that the ingredient is not a new dietary ingredient, such as an invoice, a bill of lading, or a product label.* *(See CFSAN NDI letter dated July 15, 2001 concerning Glucose Metabolism Modulator) 11
Present in the Food Supply DSHEA provides an important exception from the NDI notification requirement. According to Section 413 (a)(1) of the FDC Act a dietary supplement that contains an NDI is not adulterated 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 informal guidance suggests that the extract of the food source material is not the same as the actual article used for food or as an ingredient of food. (Malt barley extract is not the same as Malt Barley.) The mere presence of a substance as an inherent component of articles used for food does not establish that the substance itself is an article used for food. 12
New Dietary Ingredient Not marketed in the U.S. before October 15, 1994. Must notify FDA 75 days prior to the introduction of the ingredient into the market. Section 113 FSMA FDA must publish guidance by July 4, 2011 13
Section 402(f)(1) of FDC Act Safety of Dietary Supplements and Burden of Proof on FDA (f)(1) If it is a dietary supplement or contains a dietary ingredient that- (A) Presents a significant or unreasonable risk of illness or injury under (i) conditions of use recommended or suggested in labeling, or (ii) if no conditions of use are suggested or recommended in the labeling, under ordinary conditions of use; (B) 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; (C) the Secretary declares to pose an imminent hazard to public health or safety, except that the authority to make such declaration shall not be delegated and the Secretary shall promptly after such a declaration initiate a proceeding in accordance with sections 554 and 556 of title 5, United States Code, to affirm or withdraw the declaration; or (D) is or contains a dietary ingredient that renders it adulterated under paragraph (a)(1) under the conditions of use recommended or suggested in the labeling of such dietary supplement. In any proceeding under this subparagraph, the United States shall bear the burden of proof on each element to show that a dietary supplement is adulterated. The court shall decide any issue under this paragraph on a de novo basis. 14
The NDI Submission Process 21 CFR 190.6 1. Name and address. 2. Name of NDI; if botanical, full proper Latin name 3. Description including full characterization of the ingredient. 4. Level of NDI in dietary supplements in the amount included in dosage form products and expected daily consumption. 5. Conditions of use recommended in product labeling. 6. History of use or reasonably expected to be safe under conditions of use. 15
Background On September 27, 2007, the President signed into law the Food and Drug Administration Amendments Act of 2007 (FDAAA). This law amends the Federal Food, Drug, and Cosmetic Act (FT&C Act) by creating a new section 417, Reportable Food Registry. Section 417 requires the Secretary of Health and Human Services (the Secretary) to establish within the Food and Drug Administration (FDA) a Reportable Food Registry. The congressionally-identified purpose of the Reportable Food Registry is to Provide a reliable mechanism to track patterns of adulteration in food [which] would support efforts by the Food and Drug Administration to target limited inspection resources to protect the public health (Pub. L. 110-085, section 1005(a)(4)). 16
Responsible Party The responsible party is the person who submits the registration under section 415(a) of the FD&C act (21 U.S.C. 350(d)) for a food facility that is required to register under section 415(a), at which such article of food is manufactured, processed, packed, or held. Persons who are required to submit a facility registration under section 415 of the FD&C Act are the owner, operator, or agent in charge of a domestic or foreign facility engaged in manufacturing, processing, packing, or holding food for consumption in the United States. Person is defined in section 201(d) of the FD&C Act (21 U.S.C. 321(e)) as including individuals, partnerships, corporations, and associations. 17
Reportable Food A reportable food is an article of food (other than dietary supplement or infant formula) for which there is a reasonable probability that the use of, or exposure to, such article of food will cause serious adverse health consequences or death to humans or animals. [Added May 2010] Infant formula and dietary supplements are excluded from the requirements of the Reportable Food Registry. Are there other reporting requirements for these foods? 18
Submitting a Reportable Food Report A responsible party is required to submit a report to FDA through the Reportable Food electronic portal as soon as practicable, but in no case later than 24 hours after determining that an article of food is a reportable food. 19
When does a transfer to another person occur under section 417(d)(2)(B) of the FD&C Act? A transfer to another person occurs when the responsible person releases the food to another person. Person is defined in section 201(e) of the FD&C Act as including individuals, partnerships, corporations and associations. FDA does not consider an intra-company transfer in a vertically integrated company to be a transfer to another person, where the company maintains continuous possession of the article of food. For example, if Company A owns a processing plant, warehouse facility, and distribution facility, the intra-company transfer from the processing plant to the warehouse facility and/or the warehouse facility to the distribution facility would not be considered a transfer to another person. 20
If a reportable food is shipped to a third-party warehouse, but the responsible party maintains ownership and direct control over distribution, must the responsible party submit the reportable food report? Yes. Transfer to another person occurs when the responsible person releases the food to another person. Person is defined in section 201(e) of the FD&C Act (21 U.S.C. 321(e)) as including individuals, partnerships, corporations and associations. In this situation, the warehouse operator is a distinct legal person. 21
Recordkeeping and Documentation What are the recordkeeping requirements for responsible parties? The responsible party shall maintain records related to each report received, notification made, and report submitted to the FDA under section 417 of the FD&C Act for 2 years. Is a report to FDA or notification of instances of reportable food an admission that the food involved is adulterated or caused or contributed to a death, serious injury, or serious illness? No. A report or notification of a reportable food shall not be considered an admission that the food involved is adulterated or caused or contributed to a death, serious injury, or serious illness. Any report or notification of an instance of reportable food is considered a safety report under section 756 of the FD&C Act (21 U.S.C. 379(v)), Safety Report Disclaimers, and may be accompanied by a statement, which shall be part of any report that is released for public disclosure, that denies that the report or notification constitutes an admission that the product involved caused or contributed to a death, serious injury, or serious illness. 22
THE FDA FOOD SAFETY MODERNIZATION ACT (FSMA) OF JANUARY 4, 2011 Pub. Law No. 111-353 A. Major provisions of FSMA that are effective immediately include: (1) Mandatory Recall Authority (FSMA Sect 206) (2) Stronger records access authority (FSMA Sect 101) (3) Whistleblower Protection (FSMA Sect. 402) (4) Foreign facilities and refusal of inspection (FSMA Sect. 306) An imported food will be refused admission if it is from a foreign establishment to which a US inspector is refused entry for an inspection. B. Additional significant provisions of FSMA that expected to take effect in the first year after enactment: (1)Targeting of inspection resources( FSMA Sect 201) increased inspection of domestic facilities with high risk foods and foreign facilities. (2) Suspension of food facility registration (FSMA Sect.102) Problems involving a food that may cause serious adverse health consequences, FDA can shut down facility that packed, received or held food by suspending registration (3) Administrative detention (FSMA Sect. 207) FDA will have stronger authority to administratively detain food. 23
MODERNIZATION ACT, cont. (4) Authority to require import certification (FSMA Sect. 303) FDA can require high risk food to be accompanied by a certification that the food complies with FDC Act. (5) Prior notice of imported food (FSMA Sect. 304) FDA will require prior notice of an imported food shipment to include information on any country where the food was refused entry. C. Additional Significant Provision of FSMA that are expected to take effect in the second year. (2012) (1) Hazard Analysis and Risk-Based Preventive Controls (HARBPC) FAMA Sect. 103 Domestic and foreign facilities (with some exceptions such as dietary supplements and infant formula, must develop a HARBPC plan (2) Foreign Supplier Verification Program (FSMA Sect. 301) Importers will have to verify that imported food complies with HARBPC requirements. (3) Protection against Intentional Adulteration (FSMA Sect. 106) (4) Laboratory Accreditation for Analysis of Foods (FSMA Sect.307) All testing of foods for regulatory compliance must be done at a FDA accredited laboratory. (5) Accreditation of Third-Party Auditors (FSMA Sect. 302) (6) Voluntary Qualified Importer Program (FSMA Sect. 302) (7) Improving the Reportable Food Registry (FSMA Sect. 211) 24
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D. No Observable Effect levels (NOEL) for heavy metals causing cancer or as reproductive toxins found in Dietary Supplement Products under Prop 65 (1) Arsenic 10 mcg/day (2) Cadmium 4.1 mcg/day (3) Lead 0.5 mcg/day (4) Mercury no established levels. E. Overview of Proposition 65 Settlements (1) Total Proposition 65 settlements Proposition 65 defendants have paid a total of $258,942,932 in various types of financial settlements. Of this roughly $259 million total, the California Attorney General has collected approximately 33% of all settlement dollars paid, while citizen enforcers and their attorneys have collected 66 % (1) Average Prop 65 settlement $65356 (2) Median Prop 65 settlement $17000 (3) Largest Prop 65 settlement $42,500,000 (4) Smallest Prop 65 settlement $160 F. Product Category and Settlement Averages (1) Dietary supplement and herbal remedies $89,669 (2) Food products $ 74614 G. 2010 Proposition 65Notices of potential Prop 65 violation (1) Dietary Supplement and Herbal products 629. (2) Food Products 1,018 (3) Personal Care products 449 28
Complaint for False Marking Violation of 35 USC Section 292 A. False marking includes whoever marks, or affixes to, or uses in advertising in connection with any unpatented article the word "patent" or any word or number importing the same is patented, for the purpose of deceiving the public: or whoever marks upon, or affixes to, or uses in advertising in connection with any article the words "patent applied for," "Patent pending," or any word importing that an application for patent has been made, when no application for patent has been made, or if made, is not pending, for the purpose of deceiving the public SHALL BE FINED NO MORE THAN $500 for every such offense. B. Any person may sue for the penalty, in which event one-half to the person suing and the other to the use of the United States. C. In other words, it is a violation of 35 USC Section 292 to intentionally mark an item in commerce with a patent number that has expired or that does not protect the item. D. Since December 2009, when the US Court of Appeals for the Federal Circuit, in Washington rules that defendants in such lawsuits could be liable for up to $500 per offense, nearly 700 lawsuits have been filed 29