Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
DSHEA and Bioavailability Elizabeth A. Yetley, Ph.D. Ctr. Food Safety & Applied Nutrition Food and Drug Administration Approach: • Regulatory Applications – How has concept been applied? – General characteristics • Specific questions for dietary supplements • Science and research needs Regulatory Applications Regulatory Experience • Drugs -- separate regulations • Foods -- case-by-case – Safety – Labeling Food Safety -- Bioavailability • Safety – – – – Food additive authorizations GRAS status GMPs Infant formula quality factors Safety Example: Food Additive • Olestra • Must add fat soluble vitamins • Label information required Safety Example -- GRAS • GRAS -- Nutrients: • Amounts not in excess of that required to produce intended effect • Levels not to exceed GMPs Safety Example -- Finished Products • Calcium and iron supplements – Less effective than expected • High doses of selenium -- low toxicity • Contaminants – Mercury – Lead in calcium supplements Safety Example-- Infant Formula • • • • Infant formula “Quality Factors” Statutory requirement Failure to meet --> adulteration Proposed definition: Food Labeling -- Bioavailability • Label information – Nutrition or Supplement Facts declarations – Claims – “Enriched” products Label declarations -- History • Based on analytical amounts • Nutrients: – Derived from 1968 RDAs – 1968 RDA’s -- some “correction” for bioavailability – FDA’s compliance method for some nutrients -microbiological assay Label declarations -- History • Calorie content – – – – May use specific Atwater factors May use specific food factors Correct for insoluble dietary fiber Correct for protein indigestibility Label Declarations -- History • Non-nutrients: – No correction for bioavailability Claims -- History • Truthful and not misleading • Meets regulations • “More” claims: >= 10% RDI Health claims -- History • Calcium and osteoporosis • Folic acid and neural tube defects • Meet USP standards: dissolution & disintegration • Calcium: “assimilable” “Enriched” products -- History • Nutrient -- physiologically available • Level --> not result in excessive intake • Nutrient -- suitable for intended purpose “Enriched” products -- History • • • • Iron and Calcium “Safe and suitable”, or “Harmless and assimilable” Research – Predictive validity of animal bioassays – Identification relative bioavailability of ingredient sources General principles -- History • • • • • • Affects both safety and effectiveness Case-by-case Physiological effects, not just absorption Linked to intended use Amounts not to exceed intended effects Not to deceive consumer Current Marketed D.S. Products Ingredients • • • • • Vitamins and minerals Macronutrients Botanicals Amino Acids Substances intended to supplement the diet Potential Bioavailability Issues • • • • • Source ingredient Extraction and processing procedures Interactions -- “active” constituents Effects of “inert” ingredients/coatings… Interactions – with diet – with drugs Next Steps -- Science & Research Issues to be addressed • Definition: What is it? • Compliance (analytical) methods? • Specific regulatory impacts – Safety requirements? – Label information? – GMPs? Definition: Why Discuss? • When to consider bioavailability? • How to monitor compliance? • Substantiation or documentation? Definition: • • • • • Absorption? Digestion? Metabolism? Excretion? Summary: Utilization? Definitional Challenges? • Case by case vs. general? • Ingredient vs. finished product? Definitional Challenges? • New RDI’s based on “equivalents” – Example: Folic acid • Applicability to other ingredients? Definitional Challenges? • New Upper Limits based on “synthetics” – Example: Folic acid • Applicability to other ingredients? Safety and Effectiveness Challenges • • • • How to deal with exposure levels Effectiveness Safety Safety factors for uncertainty Host and Use Challenges • • • • Label information Appropriate use conditions Vulnerable populations Consumer right to know issues Other Challenges • Effect of processing? • Effect of storage? Science and Research Needs • Bioavailability: High priority research need for CFSAN • Definition • Analytical methods • Meaningfulness of measures Key issue • On food - drug continuum • Where do dietary supplements fall relative to bioavailability?