Contents USP Dietary Supplements Compendium. Volume 1. Volume 2. Contents iii

Transcription

1 DSC Contents iii Contents USP Dietary Supplements Compendium Volume 1 Volume 2 Members... v Mission and Preface General Notices and Requirements USP NF General Chapters USP NF Dietary Supplement Monographs USP NF Excipient Monographs FCC General Provisions FCC Monographs FCC Identity Standards FCC Appendices Reagents, Indicators, and Solutions Reference Tables Index I-1 USP Reference Standards Index I-35 Preface... v Dietary Supplements Admission Evaluations... 1 USP Dietary Supplement Verification Program Dietary Supplements Regulatory Framework Tables of Dietary Intake Levels Guidance Documents Illustrations Index I-1

2 DSC Dietary Supplements Admission Evaluations 1 Dietary Supplements Admission Evaluations This section includes summaries for some of the admission evaluations completed by the USP Dietary Supplements Information Expert Committee [ ] and by the USP Monographs Dietary Supplements and Herbal Medicines Expert Committee [ ] for commonly used dietary ingredients. USP s admission evaluation of a dietary ingredient under the Admission Criteria and Safety Classification for Dietary Supplements Guideline 1 is performed for the sole purpose of helping to inform the Dietary Supplement and Herbal Medicine Expert Committee s determination whether to proceed with consideration for admission into the compendia and should not be relied upon as any finding about the intrinsic safety or effectiveness of the dietary supplement ingredient under review. Summaries of Admission Evaluations are available for articles that were cleared for monograph development. The following articles did not clear the admission review stage and are not undergoing monograph development: Natto Extract, Phyllanthus amarus Extract, and Calcium Magnesium Phytate. Additional information on these articles may be available upon request under USP s document disclosure process. 2 Introduction to Dietary Supplements Summary Admission Evaluations Admission Criteria and Safety Classification for Dietary Supplements Guideline...8 N-Acetyl-D-Glucosamine Andrographis Ashwagandha Root Astaxanthin Esters Astragalus Root...25 Aztec Marigold Zeaxanthin Extract Bacopa Banaba Leaf...38 Beta Glucan...43 Black Cohosh Borage Seed Oil Boswellia serrata Calcium l-5-methyltetrahydrofolate Centella asiatica Chinese Salvia Diosmin Evening Primrose Oil...78 Fenugreek...82 Flaxseed Lignans Forskohlii...91 Ganoderma Lucidum Fruiting Body...95 Garcinia cambogia Garcinia indica Glutathione Green Tea Extract, Powdered Decaffeinated Guggul Gymnema Holy Basil Leaf Hydroxy-L-tryptophan (5-HTP) Available at 2 Available at

3 2 Dietary Supplements Admission Evaluations DSC Krill Oil Maca Malabar Nut Tree, Leaf Mangosteen Melatonin Menaquinone Methylcobalamin Noni Northern Schisandra Fruit Phyllanthus amarus Rhodiola rosea Rosemary Leaf Spirulina Tienchi Ginseng Root and Rhizome meso-zeaxanthin...201

4 DSC USP Dietary Supplement Verification Program 205 USP Dietary Supplement Verification Program USP conducts voluntary verification programs for manufacturers of dietary ingredients and dietary supplements. Through these programs, USP verifies the identity, strength, purity, and quality of ingredients and finished products. In this section, we include overviews, process flow charts, and checklists for these USP Dietary Supplement and Ingredient Verification Programs. This information is excerpted from the participant manuals for the verification programs. The complete and current version of the participant manual is available free of charge on the USP website at Notice Overview Criteria for Participation Required Process and Submissions Process Overview Chart USP-DSVP Product Category-Family Matrix Product Acceptance Evaluation of Initial Audit Documentation Sampling and Submission of Product Documentation Evaluation of Quality Control Documentation Evaluation of Manufacturing Documentation Testing of Product Samples Specifications for Dietary Supplement Raw Material and/or Finished Product USP-DSVP Notification of Findings Issuance and Use of the USP Verified Program Mark Need for Re-Evaluation Need for Re-Evaluation Participant s Internal Audit and Annual Product Reports Market Surveillance Appeals Product Recalls Glossary Forms and Checklists Checklist for Quality Control Documentation Checklist for Manufacturing Documentation Checklist for On-Site Audit Legal Notices

5 DSC Dietary Supplements Regulatory Framework 283 Dietary Supplements Regulatory Framework This section of the compendium contains excerpted information on U.S. federal legal and regulatory requirements that are pertinent to dietary ingredients and dietary supplements. The publication of FDA guidances and other regulatory information in the USP Dietary Supplements Compendium is for informational purposes only and is not intended as legal advice or to impart any legal effect. Note that the information in this section may be revised from time to time, and it is the responsibility of the user to ascertain the most current version of these documents. Federal Food, Drug, and Cosmetic Act Requirements Relating to Dietary Supplements Good Manufacturing Practices for Dietary Supplements Good Manufacturing Practices for Foods FDA Guidance for Industry: A Dietary Supplement Labeling Guide FDA Guidance for Industry: A Food Labeling Guide 12. Appendix D: Qualified Health Claims FDA Guidance for Industry: Current Good Manufacturing Practice in Manufacturing, Packaging, Labeling, or Holding Operations for Dietary Supplements; Small Entity Compliance Guide FDA Compliance Program Guidance Manual: Dietary Supplements Import and Domestic FDA Guidance for Industry: Questions and Answers Regarding Adverse Event Reporting and Recordkeeping for Dietary Supplements as Required by the Dietary Supplement and Nonprescription Drug Consumer Protection Act FDA Guidance for Industry: Questions and Answers Regarding the Labeling of Dietary Supplements Federal Trade Commission Act Requirements Relating to Dietary Supplements Dietary Supplements: An Advertising Guide for Industry California Safe Drinking Water and Toxic Enforcement Act of FDA Guidance for Industry Gluten-Free Labeling of Foods; Small Entity Compliance Guide FDA Guidance for Industry: Distinguishing Liquid Dietary Supplements from Beverages...510

6 DSC Tables of Dietary Intake Levels 517 Tables of Dietary Intake Levels This section contains an international comparison of Dietary Reference Intakes (DRIs), Recommended Daily Intakes (RDIs), and Tolerable Upper Intake Levels (UL) of vitamins, minerals, and electrolytes for adults compiled by regulatory authorities and organizations. Comparison Chart of Dietary Reference Intakes (DRIs [USA & Canada]) and Recommended Daily Intakes (RDAs/PRIs) of Vitamins, Minerals, and Electrolytes for Adults; Vitamins Comparison Chart of Dietary Reference Intakes (DRIs [USA & Canada]) and Recommended Daily Intakes (RDAs/PRIs) of Vitamins, Minerals, and Electrolytes for Adults; Minerals and Electrolytes References for the Comparison Chart of Dietary Reference Intakes (DRIs [USA & Canada]) and Recommended Daily Intakes (RDAs/PRIs) of Vitamins, Minerals, and Electrolytes for Adults; Vitamins, Minerals, and Electrolytes Tolerable Upper Intake Levels (UL) of Vitamins, Minerals, and Electrolytes

7 DSC Guidance Documents 533 Guidance Documents These ancillary documents have been provided by stakeholder organizations. USP acknowledges the American Herbal Products Association, Natural Products Association, Consumer Health Products Association, and the Council for Responsible Nutrition for their contributions to this section. Guidance for Manufacture and Sale of Bulk Botanical Extracts Use of Marker Compounds in Manufacturing and Labeling Botanically Derived Dietary Supplements Guidance for the Retail Labeling of Dietary Supplements Containing Soft or Powdered Botanical Extracts Standardization of Botanical Products: White Paper AHPA-AHP Good Agricultural and Collection Practice for Herbal Raw Materials Standardized Information on Dietary Ingredients (SIDI ) Protocol Shelf Life Dating of Botanical Supplement Ingredients and Products

8 DSC Illustrations 623 Illustrations This section contains additional information for selected articles generally organized in two sections: botanical characteristics and chemical characteristics. The information provided in this section is not intended to impose any monograph requirements and is not official text. Botanical characteristics include macro/microscopic photographs and diagrams that are provided to aid in the interpretations of pharmacopeial descriptions of plant materials. These photographs and diagrams are intended to help users in the identification of plant specimens and determination of contamination with closely related plant species. Chemical characteristics include chemical structures of relevant constituents and marker compounds and chromatograms. The chromatograms are TLC color pictures and HPLC or GC of representative articles, provided to assist in the performance of compendial tests. N-Acetylglucosamine a. Chemical Structures b. High Performance Liquid Chromatography Ademetionine Disulfate Tosylate see S-Adenosyl-L-methionine Disulfate Tosylate American Ginseng see Ginseng, American, Asian, and Tienchi Andrographis a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Asian Ginseng see Ginseng, American, Asian, and Tienchi Ashwagandha Root a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Astaxanthin Esters a. Chemical Structures b. High Performance Liquid Chromatography Astragalus a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Aztec Marigold Zeaxanthin Extract a. Chemical Structures b. High Performance Liquid Chromatography Bacopa a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography Banaba Leaf a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Beta Carotene a. Chemical Structures b. High Performance Liquid Chromatography Bilberry Extract, Powdered a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Black Cohosh a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Black Pepper a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Borage Seed Oil a. High Performance Thin Layer Chromatography. 700

9 624 Illustrations DSC b. Gas Chromatography Boswellia serrata a. Macroscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Calcium L-5-Methyltetrahydrofolate a. Chemical Structures b. High Performance Liquid Chromatography Capsicum a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. High Performance Liquid Chromatography Cascara Sagrada a. Macroscopic Description b. Microscopic Description a. Chemical Structures Cat s Claw a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Centella asiatica a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Chamomile a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography d. Gas Chromatography Chaste Tree a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Chinese Salvia a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Chondroitin Sulfate Sodium a. Chemical Structures b. High Performance Liquid Chromatography Cinnamomum cassia Bark a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography Cinnamomum verum Bark a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography Cod Liver Oil a. Gas Chromatography Coenzyme Q see Ubidecarone Cranberry Liquid Preparation a. Chemical Structures b. High Performance Liquid Chromatography Cyanocobalamin a. Chemical Structures b. High Performance Liquid Chromatography Diosmin a. Chemical Structures b. High Performance Liquid Chromatography Echinacea angustifolia Root, Echinacea pallida Root, Echinacea purpurea Root and Echinacea purpurea Aerial Parts a. Macroscopic Description b. Microscopic Description

10 DSC Illustrations 625 a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Eleuthero a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Elm a. Macroscopic Description b. Microscopic Description Evening Primrose Oil a. Thin Layer Chromatography b. Gas Chromatography Fenugreek Seed a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography Feverfew a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Fish Oil Containing Omega-3 Acids a. Gas Chromatography Flax Seed Oil a. Thin Layer Chromatography b. Gas Chromatography Forskohlii a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Ganoderma Lucidum Fruiting Body a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Garcinia cambogia and Garcinia indica a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Garlic a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Ginger a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Ginkgo a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Ginseng, American, Asian, and Tienchi a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Goldenseal a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Grape Seeds Oligomeric Proanthocyanidins a. Chemical Structures

11 626 Illustrations DSC b. Thin Layer Chromatography c. High Performance Liquid Chromatography Green Tea Extract, Powdered Decaffeinated a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Guggul a. Macroscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Gymnema a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Hawthorn Leaf with Flower a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Holy Basil Leaf a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Horse Chestnut a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography Hydroxocobalamin a. Chemical Structures b. High Performance Liquid Chromatography Krill Oil a. Chemical Structures b. Gas Chromatography Licorice a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Lutein a. Chemical Structures b. High Performance Liquid Chromatography Lycopene and Tomato Extract Containing Lycopene a. Chemical Structures b. High Performance Liquid Chromatography Malabar Nut Tree, Leaf a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Maritime Pine a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. High Performance Liquid Chromatography Melatonin a. Chemical Structures b. High Performance Liquid Chromatography Menaquinone a. Chemical Structures b. High Performance Liquid Chromatography Methylcobalamin a. Chemical Structures b. High Performance Liquid Chromatography Milk Thistle a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Myrrh a. Macroscopic Description

12 DSC Illustrations 627 a. Chemical Structures b. Thin Layer Chromatography Nettle see Stinging Nettle Northern Schisandra a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Phyllanthus amarus a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Plantago Seed a. Macroscopic Description b. Microscopic Description Pygeum a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Gas Chromatography c. High Performance Liquid Chromatography Quercetin a. Chemical Structures b. High Performance Liquid Chromatography Red Clover a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. High Performance Thin Layer Chromatography c. High Performance Liquid Chromatography Rhodiola rosea a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Rosemary a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Rutin a. Chemical Structures b. High Performance Liquid Chromatography S-Adenosyl-L-methionine Disulfate Tosylate a. Chemical Structures b. High Performance Liquid Chromatography St. John s Wort a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography SAMe see S-Adenosyl-L-methionine Disulfate Tosylate Saw Palmetto a. Macroscopic Description b. Microscopic Description a. Gas Chromatography Senna Leaf and Pods a. Macroscopic Description b. Microscopic Description a. Chemical Structures Siberian Ginseng see Eleuthero Slippery Elm see Elm Soy Isoflavones a. Chemical Structures b. High Performance Liquid Chromatography Spirulina a. Macroscopic Description b. Microscopic Description

13 628 Illustrations DSC a. Chemical Structures b. Gas Chromatography Stinging Nettle a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. Gas Chromatography d. High Performance Liquid Chromatography Turmeric a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Ubidecarenone a. Chemical Structures b. High Performance Liquid Chromatography Valerian a. Macroscopic Description b. Microscopic Description a. Chemical Structures b. Thin Layer Chromatography c. High Performance Liquid Chromatography Vinpocetine a. Chemical Structures b. High Performance Liquid Chromatography Wheat Bran a. Macroscopic Description b. Microscopic Description meso-zeaxanthin a. Chemical Structures b. High Performance Liquid Chromatography