New Standards And Prioritization For Development . - USP

New Standards and Prioritization forDevelopment, Non-Botanical andBotanical StandardsGabriel Giancaspro, Ph.D.Vice President, Foods Dietary Supplements and HerbalMedicinesMaría Monagas, Ph.D.Scientific Liaison, Dietary Supplements and HerbalMedicines

Content1. FISCAL YEARS 2016 AND 2017 PRODUCTION New Monographs Revisions /Modernizations General Chapters2. EC PORTFOLIO New Consolidated List of Monographs Top 50-Botanicals Non-Botanicals Ingredient and Dosage Forms3. PRIORITY TOOL Updates: EC feedback on Scientific Feasibility and Public Health Impact Changes proposed in variables, scores and weights Analysis of the Consolidated List2

1. FISCAL YEARS 2016 AND 2017 PRODUCTION Non-Botanicals New MonographsVitamins COBAMAMIDE CHOLECALCIFEROLTABLETS MENAQUINONE-4 ASCORBIC ACIDCHEWABLE GELS CHOLECALCIFEROLCHEWABLE GELSMinerals CALCIUM CITRATEMALATEAminoAcids CITRULLINESpecialtiesProbiotics CREATINE CHIA SEED OIL PLANT STANOLESTERS ANNATTO SEEDTOCOTRIENOLSEXTRACT CONJUGATEDLINOLEIC ACIDSFREE FATTY ACIDS CONJUGATEDLINOLEIC ACIDSTRIGLYCERIDES CITICOLINE SODIUM CAROTENES LACTOBACILLUSACIDOPHILUS LA-14 LACTOBACILLUSACIDOPHILUS NCFM LACTOBACILLUSRHAMNOSUS HN001 LACTOBACILLUSPARACASEI LPC-37 BIFIDOBACTERIUMANIMALIS SSP.LACTIS BACILLUSCOAGULANS GBI-30,6086 BACILLUSCOAGULANS GBI-30,6086 CAPSULES Stimuli ArticlesFACTORS TO CONSIDER FOR ESTABLISHING OVERAGES OF DIETARY INGREDIENTS INDIETARY SUPPLEMENTS

Fiscal Years 2016 and 2017 Production Non-Botanicals Revision/ModernizationVitamins CYANOCOBALAMIN METHYLCOBALAMIN METHYLCOBALAMINTABLETS NIACIN EXTENDEDRELEASE TABLETS THIAMINEHYDROCHLORIDETABLETS RIBOFLAVIN TABLETS ASCORBIC ACIDINJECTION CALCIUM L-5METHYLTETRAHYDROFOLATE TABLETS CALCIUM L-5METHYLTETRAHYDROFOLATE CAPSULESMinerals TRIBASIC CALCIUMPHOSPHATE POTASSIUM GLUCONATE POTASSIUM CITRATEEXTENDED-RELEASETABLETS 91 CALCIUM PANTOTHENATE ASSAY 115 DEXPANTHENOL ASSAYAmino Acids CYSTEINEHYDROCHLORIDE ASPARTIC ACID LEUCINE ISOLEUCINE VALINE METHIONINE GLYCINE TAURINESpecialties OMEGA-3 ACIDS ETHYLESTERS OMEGA-3-ACID ETHYLESTERS CAPSULES RUTIN CRYPTHECODINIUMCOHNII OIL BETA CAROTENEPREPARATION FLAX SEED OIL CHONDROITIN SULFATESODIUM, SHARK

Fiscal Years 2016 and 2017 Production Botanicals New Monographs TIENCHI GINSENG ROOT AND RHIZOME POWDER TABLETSSALIX SPECIES BARKSALIX SPECIES BARK POWDERSALIX SPECIES BARK DRY EXTRACTCINNAMOMUM CASSIA TWIGCINNAMOMUM CASSIA TWIG POWDERST. JOHN'S WORT FLOWERING TOP DRY EXTRACT CAPSULESST. JOHN'S WORT FLOWERING TOP DRY EXTRACT TABLETSCOFFEE FRUIT DRY EXTRACTELEUTHERO ROOT AND RHIZOME POWDER CAPSULESECHINACEA SPECIES DRY EXTRACT CAPSULESECHINACEA SPECIES DRY EXTRACT TABLETSRHODIOLA CRENULATA ROOT AND RHIZOMERHODIOLA CRENULATA ROOT AND RHIZOME POWDERRHODIOLA CRENULATA ROOT AND RHIZOME DRY EXTRACTTANGERINE PEELTANGERINE PEEL POWDERTANGERINE PEEL DRY EXTRACT COIX SEEDCOIX SEED POWDERECHINACEA SPECIES POWDER CAPSULESEUROPEAN ELDER BERRY DRY EXTRACTVALERIAN ROOT DRY EXTRACT CAPSULESVALERIAN ROOT POWDER CAPSULESVITEX NEGUNDO LEAFVITEX NEGUNDO LEAF POWDERVITEX NEGUNDO LEAF DRY EXTRACTSICHUAN LOVAGE RHIZOMESICHUAN LOVAGE RHIZOME POWDER Stimuli ArticlesTHE ADVISABILITY AND FEASIBILITY OF DEVELOPING USP STANDARDS FOR MEDICAL CANNABIS

Fiscal Years 2016 and 2017 Production Botanicals Revision/Modernization POWDERED ELEUTHERO (Future: ELEUTHERO ROOT AND RHIZOME POWDER) POWDERED ELEUTHERO EXTRACT (Future: ELEUTHERO ROOT AND RHIZOMEDRY EXTRACT) ELEUTHERO (Future: ELEUTHERO ROOT AND RHIZOME) ST. JOHN'S WORT POWDERED ST. JOHN'S WORT POWDERED ST. JOHN'S WORT EXTRACT POWDERED ASHWAGANDHA ROOT EXTRACT ASHWAGANDHA ROOT POWDERED ASHWAGANDHA ROOT MENTHOL COLCHICINE POWDERED DECAFFEINATED GREEN TEA EXTRACT Revision of General Chapters 2251 SCREENING FOR UNDECLARED DRUGS AND DRUG ANALOGUES DIGOXINCARAWAYCARDAMOM SEEDCASCARA SAGRADAALOECHOCOLATEDIGITALISIPECACMYRRHPLANTAGO SEEDPODOPHYLLUMRAUWOLFIA SERPENTINABELLADONNA LEAFSENNA LEAFSENNA PODSSTORAXVANILLAWITCH HAZELPOWDERED DIGITALIS

2. EC PORTFOLIO USP Missing Universe of DS Identification ofCandidate Monographs-Nutritional Business Journal-100 top List-Herbal Gram Report-Trade Journals/Newsletters-DS Products Catalogs-Mintel-USP Marketing Department and DSVerification ProgramIngredientsDosage formsTOTAL14687233

New Consolidated List of Monograph topics1East Asia-EP2South Asia-EP3Priority BotanicalsNon-Botanical Ingredients and Dosage Forms4 Dietary Supplements Verification ProgramTop 50-Botanicals

New Consolidated List of Monograph topicsSouth Asia-EPEast Asia-EPOther Priority BotanicalsNon Botanical Ingredients and Dosage FormsTOTAL27332644130Monograph list per category is located in Annex I

3. PRIORITY TOOL Original versionShould we do it ?Can we do GRAS-Self-GRAS-Grandfathered List-EU Novel Food Overlapping with foods/excipients-Overlapping with chemical medicines (drugs)Scientificfeasibility-Existence of specific ID tests-Existence of Assay tests-Lab Resources NeededPublic HealthRegulatoryReliefDemand/SalesNumber ofproducts inmarket-Adulteration/ Safety-Existence of EP, BP or JP Monograph-Existence/position on the NBJ Top 100 DS list-Existence/position on the HerbalGram list-USP Marketing and DS Verification awareness-DS Label Database (NIH)-USA data-Mintel Database-Global data

PRIORITIZATION TOOL: UPDATES -Grandfathered List-Other (EU Novel Food Approval/DMF)-Overlapping with foods/excipients/drugs-Overlapping with HM-SA and EA Panels-Existence of specific ID tests-Existence of Assay tests-Lab Resources Needed-Reference Standard Availability-Sponsor Availability

PRIORITIZATION TOOL: UPDATES ryInformation-NDI-FDA-GRAS-Grandfathered List-Other (EU Novel ents/drugs-HM SA and ES Panel7420%Scientificfeasibility-Lab Resources Needed-Existence of specific ID tests-Existence of Assay tests-RS Availability-7710425%Sponsor/Donor-Sponsor Availability1025%Total Probability Score (ScoreWeight)

PRIORITIZATION TOOL: UPDATES ImpactImpactPublic HealthRegulatoryReliefDemand/SalesNumber ofproducts inmarket-Known intrinsic Safety Issues-Known or likely Adulteration Issues-Absence of EP or JP Monograph-Existence/position on the NBJ Top 100 DS list-Existence/position on the HerbalGram list-Nielsen data ?-DS Label Database (NIH)-USA data-OWL database ?-Innova ?

PRIORITIZATION TOOL: UPDATES IMPACTCriteriaScoreWeightPublic Health-Known Intrinsic PublicHealth-Known or LikelyAdulteration10720%RegulatoryRelief-Absence of EP or JPMonograph105%Demand/Sales-Existence/position on theNBJ Top 100 DS list-Existence/position on theHerbalGram listNumber ofproducts inmarketTotalSub-CriteriaImpact Score-DS Label Database (NIH)USA data (Score20%1-4-7-10(Brackets setin quartersfrom 1-100position)1-4-7-10(Brackets setfrom 101000products)Weight)25%

Calibrators: Vitamins, Minerals and SpecialtiesPriority Score

Top 50-BotanicalsPriority Score

Non-Botanical Ingredients and Dosage Forms (DSVP)Priority Score

FY17 Q4 New Monographs, Modernizations andRevisions Bitter Orange Flavonoids ExtractGuarana SeedGuarana Seed PowderGuarana Seed ExtractCalcium Magnesium CitrateMenaquinone 7 RevisionMenaquinone Preparation RevisionHistidine RevisionD-Chiro-InositolOmega-3 Free Fatty AcidsTocotrienolsLeucine modernizationIsoleucine modernizationKrill Oil revisionCod Liver Oil RevisionVitamins and Mineral Powders (Unicef)Krill Oil Capsules RevisionKrill Oil Delayed Release Capsule RevisionRhodioloa rosea Capsules/Tablets RevisionEleuthero Finished Products RevisionCyanocobalamin Chewable GelsB. coagulansL. fermentum GC 2040 Revision GC 64 Probiotics18

FY18 New Monographs (Estimated timing for PF submission)Q1 Magnesium GlycinatePlant SterolsPlant Sterols and Stanols EstersOmega-3 Acids EE60/ConcentrateCobamamideCollagen Type IIHydrolyzed CollagenHVP ChelateWhey ProteinVitamin premixes (DSM)Ginkgo Capsules/Tablets RevisionRed Clover Tablets RevisionSAMe 1,4-butanedisulfonateSodium SelenateSodium MolybdateSodium SelenitePQQ SodiumCholine CitratePomegranate ExtractColaQ2 Inositol HexanicotinateInositol Hexanicotinate CapsulesThiamine Mononitrate TabletsCyanocobalamin CapsulesZinc Oxide TabletsPantethineLevocarnitine TartrateAgmatine Sulfate (?)Salmon OilLutein and ZeaxanthinAstaxanthin ester capsulesMaca19

FY18 New MonographsQ4Q3 Magnesium Citrate Capsules Omega-3 Acid Triglyceride Preparation Omega-3 Acid Triglyceride Preparation ChewableGels Omega-3 Acid Triglycerides with Vitamin D Capsules Plant Sterols Tablets Plant Sterols and Stanols Esters Capsules Fe Glycinate Zn Glycinate Phytosterols Omega-3 Acids Ethyl Ester- DS Specification GABA Cranberry extract Squid oil with omega 3 Molybdenum citrate20

FY18 Modernizations, New GCs and Major GCRevisionsModernizations Oil and Water Soluble Vitamins CapsulesOil and Water Soluble Vitamins TabletsOil Soluble Vitamins CapsulesWater Soluble Vitamins CapsulesOil Soluble Vitamins TabletsWater Soluble Vitamins GC 171 Vitamin B12 582 Multivitamin Determinations 561 Articles of Botanical Origin 2750 Update to meet CFR 117Water Activity21

Points for Discussion Approach to identify the “top-50” based on our knowledge Parameters for impact and probability and their relative weightsfor the decision making Sources of information for the parameters Information gaps for several parameters, such as analyticalmethods data, regulatory status, etc. Challenges when we do not have sponsor data on high priorityingredients How to reduce the complexity of the analysis without losing theinformation from important variables Next steps ?

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