United States Pharmacopeia (USP) Quality Standards for Dietary Supplements. Nandu Sarma, PhD, RPh. Director, Dietary Supplements

Transcription

1 United States Pharmacopeia (USP) Quality Standards for Dietary Supplements Nandu Sarma, PhD, RPh. Director, Dietary Supplements ACPM webinar, July 17, 2014

2 Objectives Describe the dietary supplement regulations with regard to quality and safety expectations, Discuss the pharmacopeial perspectives on the quality and safety of dietary supplements, Describe the challenge and tools to address adulteration of dietary supplements. 2

3 Outline U S Pharmacopeia Dietary supplement regulations quality and safety Pharmacopeial perspectives on the quality and safety of dietary supplements, Adulteration of dietary supplements Disclosures I am an employee of US Pharmacopeia I do not have any other financial or professional conflict of interest I do use dietary supplements 3

4 Mission

5 USP Organization What We Do: Establish and disseminate public written standards for the quality, purity, identity, strength, and labeling of medicines, dietary supplements and foods Provide physical Reference Standards to support tests and assays in the USP NF, DSC, HMC and FCC Educate producers, practitioners, and others seeking information on quality and USP standards 5

6 USP: The Organization Who We Are Over 440 volunteer convention members Over 850 volunteer scientists Over 850 paid staff Locations in Rockville, MD, USA Hyderabad, India Basel, Switzerland Shanghai, China São Paulo, Brazil

7 Call for Candidates Web Page

8 USP Resources Official Documentary Standards New Publications with Authorized Information Compendial Reference Materials Verification Services 8

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11 USP's Relationship to FDA USP: Private Not-For-Profit Organization Development and Revision of Compendial Standards Establish Public Standards strength, purity, quality, identity, packaging, labeling FDA: Government Agency Enforcement Safety (GRAS, Food Additive reviews, etc.) 11

12 Outline U S Pharmacopeia Dietary supplement regulations quality and safety Pharmacopeial perspectives on the quality and safety of dietary supplements, Adulteration of dietary supplements 12

13 Dietary Supplement Health & Education Act 1994 Dietary supplements defined Labelling expectations New Dietary Ingredients Good Manufacturing Practices Compliance with USP: optional. A dietary supplement is deemed misbranded if it (i) is covered by the specifications of an official compendium; (ii) is represented as conforming to the specifications of an official compendium; and (iii) fails to so conform. [FDCA 403(s); 21 U.S.C. 343(s)] Dietary Supplement Health and Education Act of 1994, Public Law (Oct. 25, 1994).

14 Dietary Supplement cgmps and USP Manufacturers decide their own specifications for identity, quality, strength, composition and absence of contaminants. Manufacturers decide how to qualify their suppliers in order to avoid 100% testing of components (condition to accept certificate of analysis) Manufacturers decide on the quality of Reference Materials to calibrate analytical equipment USP mentioned many times in the Preamble as a guidance (scientifically valid methods, reference materials, specifications for dietary ingredients, water purity, etc.) Not included as requirement (consistency with DSHEA) FDA's dietary supplement CGMPs: standards without standardization, FDLI, 63 (4), 2008

15 Safety standards for DS under DSHEA SEC 402 [21 USC 342] A food shall be deemed to be adulterated (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.

16 Outline U S Pharmacopeia Dietary supplement regulations quality and safety Pharmacopeial perspectives on the quality and safety of dietary supplements, Adulteration of dietary supplements 16

17 White paper 17

18 USP Dietary Supplement Safety Review

19 USP DS Expert Committee: Active Monitoring Program PubMed alert for all the dietary supplements (with monograph in USP) and their marker compounds FDA MedWatch and National Toxicology Program reports British MHRA, Germany, and European Medicines Agency safety alerts TGA (Australia / New Zealand) bulletin Canadian MedEffect bulletin Mailing lists from DS trade associations USP Admission Criteria and Safety Classification for Dietary Supplements Guideline.

20 Evidence-based review Ko et al., Nutrition Reviews, 72(3), , 2014

21 Dietary Supplements Monograph Development 21

22 What is in a USP Monograph? A list of official and validated tests Their analytical procedures Their acceptance criteria In conjunction they define specifications for Identity Quality (Purity, limit for contaminants, Performance and other requirements) Strength Consistent with cgmps for DS

23 Echinacea angustifolia USP 37

24 Echinacea angustifolia USP 37

25 Echinacea angustifolia

26 Echinacea angustifolia

27 Are Disintegration and Dissolution Needed?

28 Goals of Performance Tests Diagnostic Quality Control tool to identify variations in the manufacturing process Confirm the robustness of manufacturing process Predict availability for absorption 28

29 The Value of Public Standards Conservation of FDA and manufacturer resources Uniform standards allow comparisons between products in clinical trials and market place Under DSHEA, consumers don t know to what standards two seemingly equivalent products are held USP promotes Standards with Standardization Private standards not subject to public review - Miller, Celestino, Giancaspro, Williams, Food and Drug Law Journal, 63 (4), 2008

30 Outline U S Pharmacopeia Dietary supplement regulations quality and safety Pharmacopeial perspectives on the quality and safety of dietary supplements, Adulteration of dietary supplements 30

31 Tainted products marketed as Dietary Supplements Phosphodiesterase type 5 inhibitors (e.g., sildenafil) Weightloss drugs (e.g., sibutramine) Controlled substances (e.g., benzodiazepines and anabolic steroids) Anticoagulants (e.g., warfarin) Anticonvulsants (e.g., phenytoin) HMG-CoA reductase inhibitors (e.g., lovastatin) NSAIDs(e.g., indomethacin) Beta blockers (e.g., propranolol) 31

32 General Chapter <2251> Adulteration of Dietary Supplements with Drugs and Drug Analogs Focus on categories of products marketed for sexual enhancement, weight loss, and sport bodybuilding. To develop screening methods for drugs as adulterants for dietary supplements based on the claimed benefits and similar drug effects of such adulterants. 32

33 USP-PDE5i-001-H USP-PDE5i-001-H Bali Mojo CD3CN Extract 1H NMR JCE-PNA-MVX300 2 USP-027-H USP-027-H USP Standard - Tadalafil 1H NMR in CD3CN JCE-PNA-MVX f1 (ppm)

34 Summary USP is a self-supporting, private, non-profit organization. Regulations require use of scientifically valid methods to assure quality of dietary supplements, but may lead to standards without standardization Public standards help conserve resources for the regulators and manufacturers, and help provide confidence for the consumers Uniform standards allow comparisons between products in clinical trials and market place

35 Abbreviations cgmps: current Good Manufacturing Practices ( DS EC: USP Dietary Supplements Expert Committee ( DSC: Dietary Supplements Compendium ( DSHEA: Dietary Supplements Health Education Act ( FCC: Food Chemical Codex ( GRAS: Generally Recognized as Safe ( HMC: Herbal Medicine Compendium ( MHRA: British Medicines and Healthcare Regulation Agency TGA: Australia Therapeutic Goods Administration USP NF: United States Pharmacopeia National Formulary ( 35

36 Nandu Sarma, PhD, RPh. Director, Dietary Supplements Gabriel Giancaspro, PhD. Vice President, Foods Dietary Supplements and Herbal Medicines