1. 1 FDLI:Safeguarding the Functional Food and Dietary Ingredient Supply Chain Comments by Daniel S. Fabricant, Ph.D. Director, Division of Dietary Supplements ONLDS, CFSAN daniel.fabricant@fda.hhs.gov September 10 th, 2013

2. Topics Background Where things stand 2

3. Dietary Supplements In 1 year - 3 rd Decade of DSHEA Approx. 400 recalls of spiked products since 2008 ~33% OAI on GMPs (slightly higher VAI) only ~50 NDINs annually Indication and Evidence of underreporting of AERs Increase in Claim WLs Evident of Systemic issues Use of our authorities (Seizures, Injunctions, Admin. Detention)

4. Harm Removal Business What are the major non-compliance problems in the Dietary Supplement Industry? How does the agency address them?

5. Defining the problem Invisible Harms - are those which are difficult to discern and analyze because they tend to be under-reported or unknown Conscious Opponents - agencies are confronted with individuals or groups of individuals who are engaged in creating a harm (i.e. tainted products) Catastrophic harms - relatively unlikely harmful events that produce enormous levels of victimization Character of Harms – M. Sparrow

6. General General Regulatory Paradigm –Very, very limited premarket review – No Premarket approval –No formulation standards –No product registration –No approval of claims –Manufacturer responsible for ensuring safety and compliance Where to find Information –Statutes (15, 21 & 42 U.S.C) –Code of Federal Regulations (Title 21) –Guidances

7. What is a Functional Food? 7

8. 8 “Energy” Products Many new products are being marketed Issue: Whether a product is a DS or a beverage (i.e., a conventional food) Developing guidance to address the issue (final guidance on distinguishing liquid dietary supplements from beverages)

9. 9 http://www.nytimes.com/2013/03/20/business/in-a-new-aisle-energy-drinks-sidestep- rules.html?pagewanted=all&_r=2&&pagewanted=print

10. “Represented for use as a conventional food” Not the same as prior definition of “simulate conventional food” (i.e., conventional food form) Generally, physical attributes of a food will not be primary determinant

11. “Represented for use as a conventional food” Think “how is it used” or “what is it a substitute for” – called a snack or uses another common or usual food name – uses a standardized food name – uses label representations/pictures that suggest conventional food uses –Packaging and serving sizes

12. Str/Fn Statements Statutory authority for dietary supplements to make Str/Fn statements Conventional foods aren’t authorized by statute (no guidance on substantiation) Deference to Nutrilab v. Schweiker –Taste –Aroma –Nutritive Value 12

13. Disease Definition 21 CFR 101.93(g)(1) “[D]amage to an organ, part, structure, of system of the body such that it does not function properly…or a state of health leading to such dysfunctioning…” http://www.fda.gov/Food/DietarySupplements/GuidanceComplianceRegulatoryI nformation/ucm107336.htm; January 6, 2000 Federal Register; 65 FR 999ttp://www.fda.gov/Food/DietarySupplements/GuidanceComplianceRegulatoryI nformation/ucm107336.htm

14. Substantiation of Section 403(r)(6) Dietary Supplement Claims Jan. 5, 2009 Federal Register; 74 FR 304 http://www.fda.gov/Food/GuidanceComplianc eRegulatoryInformation/GuidanceDocuments/ DietarySupplements/ucm073200.htm Describe the nature of the claim and the amount, type, and quality of evidence

15. Inflammation – Healthy Response

16. What is the substantiation standard? “Competent and reliable scientific evidence” –“tests, analyses, research, studies, or other evidence based on the expertise of professionals in the relevant area, that has been conducted and evaluated in an objective manner by persons qualified to do so, using procedures generally accepted in the profession to yield accurate and reliable results”

17. 4 principal issues guide whether a claim is substantiated Meaning of the claim being made Relationship of the evidence to the claim Quality of the evidence Totality of the evidence

18. Pitfalls Over-reliance on anecdotal/historical Fail to consider negative evidence Mistake number of publications as direct indicator of totality of evidence Over-reliance on disease treatment studies Not considering implied message/claims

20. 20 cGMPs FDA is finding that the basic tenets of cGMPs, and manufacturing in general, are not being adhered to, or in many instances are completely absent This is concerning as there isn’t much help that the agency can offer to assist with compliance in these instances Solutions

21. 21 CFR 111 Inspections* FY 2008 7 FY 2009 34 FY 2010 84 FY 2011 175 FY 2012 341

22. 21 CFR 111 Inspections* FY 2012 Inspection Classification by field: –No Action Indicated : 92 27% –Voluntary Action Indicated : 119 35% –Official Action Indicated : 116 34% –No decision 14 4% –Total:341 22 *-accounting isn’t final or QC-ed

23. FSMA PC regulations for ingredients previously left uncovered by 21 CFR Part 111 If in compliance with Part 111 and requirements of Sec. 761, exempt from PC regs. Are cGMP problems an indication of similar problems with DI’s? How do manufacturers “broaden” their quality systems? 23

24. Closing Some disparate playing ground? How do firms operate with “multiple personalities”? FSMA implementation, resources? 24