25.kumud-uspstandards.pdf
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Set t ing St an dar ds for Diet ar ySupplem en t s & en abling st an dar ds
compliance
Kumud SampathVice President -International
United States Pharmacopeia - IndiaThese slides contain confidential information and trade secrets which maynot be copied or disseminated without the express permission of USP. 2007 U.S. P All rig hts reserved U.S.P.C. 2007
INDIA -LAC INTERNATIONAL PHARMA MEETJUNE 2007, HYDERABAD
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Agenda
USP A BRIEF OVERVIEW
DIETARY SUPPLEMENTS DEFINITION,LEGALITY & REGULATION
USP DIETARY SUPPLEMENT STANDARDS
USP STRENGTHENING BOTANICAL
STANDARDS
DIETARY SUPPLEMENTS THE NEED FOR USPVERIFICATION
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USP A BRIEF OVERVIEW
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What is USP
Established in 1820 by Lyman SpauldingMission is to protect public health byestablishing public standards
Independent; not for profit science basedStandard setting organizationUnique volunteer based organizationConvention meets every five years in
Washington, D.C. (2005)Headquartered in Rockville, MD
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What USP does
Through a unique & open Public process USP;
Establishes Public Standards for drugsubstances, drug products, excipients &Dietary supplements
Establishes General test Methods,definitions& Information
Supplies Reference Standards to enableanalytical tests for Standards compliance
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USP International Presence
Towards carrying forward its Mission of PublicHealth USP is reaching out Globally;
European Office started in 2005 at Basel, Switzerland
USP - India Estabished & Started operations in 2006
USP - China Established & Start operations in 2007
USP - Brazil Site approved by Board of Trustees & isslated to start operations 2008
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Objectives of USP InternationalOperations
Work closely with the Regional Industry & withRegulators & other stakeholdersInvolve the Regional Pharmaceutical Industry in theStandard Setting ProcessOffer USP Verification Services to the Industry & otherStakeholdersIncrease awareness of & availability of USP sPharmacopeial products and services like ReferenceStandards & Pharmacopeial Education Courses etc.Establish collaborative testing Lab for ReferenceStandard candidate materialEnlist regional pharmaceutical scientists in Council ofExpertsFacilitate structured information exchange throughScientific Meetings USP 7 th ASM I ndia w ill beheld in February 2008 at Hyderabad
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DIETARY SUPPLEMENTS DEFINITION,LEGALITY & REGULATION
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The Legality
Dietary Supplements Health and Education
Act (DSHEA) was Enacted by the U.S.Congress in October 1994
DSHEA Recognizes the USP Standards forDietary Supplements.
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What is a Dietary Supplement?
Dietary Supplement as per DSHEA
is a product that is intended to supplementthe diet and contains one or more of thefollowing dietary ingredients: a vitamin, amineral, an herb or other botanical, anamino acid, a dietary substance for use byman to supplement the diet by increasingthe total daily intake, or a concentrate,metabolite, constituent, extract, orcombinations of these ingredients.
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USP Standards Official Recognition
Federal Food, Drug, and Cosmetic ActSections 201 (g) and (j), 501(b), 502(g)USP and NF standards FDA enforceable for all drugs.
Conformance is generally not optional and is enforced by FDA
Dietary Supplement Health & EducationAct (DSHEA)Section 403(s)(2)(D) of the FD&C ActA dietary supplement represented as conforming to USP NF specifications shall be deemed misbranded if it fails to
do so.Conformance is optional, but enforceable by
FDA
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USP DIETARY SUPPLEMENT STANDARDS
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USP & Dietary Supplement Standards
USP s tryst withDietarySupplements
started way backin 1820 when itpublishedstandards for
natural medicinesin the firstPharmacopoeia
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Historical Perspective
USP adopted aresolution toexpandmonographdevelopmentfor vitaminsand minerals
1820 - 1900
1820 - 1940
1942 1990
USPmonographs forsingleingredientvitamins andminerals
USP s standardscompendium included onlynatural medicines. e.g.Chamomile, Valerian, andGinger
USP developed over600 botanicalmonographs
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Timeline of USP on Dietary SupplementsPublication
1995 2003
In response to DSHEA,USP explored thefeasibility of establishing
standards and informationfor botanical and non -botanical DietarySupplements with a GMP
General Chapter
USP 27 NF 22 includes aseparate dietary supplementssection with more than 200
monographs for botanicals,nonbotanicals, and vitamin -mineral combination productsused in nearly 900 dietarysupplement products.
2008
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USP Dietary Supplement Monographs
DS TypeTest Vitamin Minerals
NonBotanicals Botanicals
Identity IR, HPLC RT,UV, Chemical Chemical IR, HPLC RT,
UV, Chemical Microscopy, TLC,HPLC, GC
Purity
Chromatographicpurity, LimitTests, Microbial,Heavy Metals
Chemical Limittests, Limit offoreign metalsby AA, ICP
Chrom. purity,Limit Tests,Microbial, Heavy Metals,PCBs -Dioxins
Toxins, Aflatoxins,Heavy Metals,Pesticides, ForeignMatter, Residue OnIgnition, Microbial,Negative Markers
Quality
Packaging,Labeling,Uniformity.
Dissolution,Disintegration
Packaging,Labeling,Uniformity,
Dissolution,Disintegration
Packaging,Labeling,Uniformity,
Dissolution,Disintegration
Packaging, Labeling, Extractable Matter, Uniformity,
Dissolution,Disintegration
Content Spectroscopy,HPLC, Microbia l
AA, ICP,Titration
Spectroscopy,HPLC,Titration
HPLC, GC
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USP STRENGTHENING BOTANICALSTANDARDS
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GarlicEchinaceaSaw PalmettoGinkgoSoyCranberryGinsengBlack CohoshSt. John s wortMilk thistle
USP - Strengthening Botanical Standards
Evening primroseValerianGreen teaBilberryGrape seedHorny goat weedYohimbeHorse ChestnutEleutheroGinger
Top selling Botanicals (Journal of American Botanical Council, 2004)
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USP - Strengthening Botanical Standards
Recently Established USP Standards
Black CohoshSoy IsoflavonesTurmericGreen Tea ExtractBilberry ExtractSenna pods
USP Standards at different stages of development
Grape seeds extractBoswellia oleo - gum resinFenugreek seedsSpirulina blue green algaeGuggul oleo - gum resinAshwaganda roots
Articles for which USP seeks to Establish Standards on Priority
- Aloe vera gel - Cranberry fruit extract- Cinnamon bark - Linseed oil- Passionflower flowering and fruiting tops - Olive leaves- Elderberry flowers and berries - Borage oil- Mangosteen fruits - Artichoke leaves and flower heads- Reishi mushrooms - Pau d arco bark- Noni fruits - Black currant oil- Stevia leaves - Shiitake mushrooms
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USP - Strengthening Botanical Standards
Criteria for Consideration of Articles Proposed for Placementin the USP-NF
1. Human data : safety studies, clinical studies, post -marketing surveillance, adverse events, interactions,
publicly available data2. Pharmacological data : including reproductive toxicity,
experimental animal studies, pharmacokinetics,therapeutic index, presence of toxic constituents
3. Contemporaneous extent of use globally and in theU.S.; including misuse and abuse and taking intoaccount fluctuations of use; historical use,
5.Regulatory status in the U.S. and other countries:regulatory actions, OTC status, GRAS status, etc.
6. Existence of Official Pharmacopeial Monographs
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USP - Strengthening Botanical Standards
USP Dietary Supplement General Chapters relevant toBotanicals;
IDENTIFICATION OF ARTICLES OF BOTANICAL ORIGIN
BOTANICAL EXTRACTS MICROBIAL ENUMERATION TESTS - NUTRITIONAL AND
DIETARY SUPPLEMENTS MICROBIOLOGICAL PROCEDURES FOR ABSENCE OF
SPECIFIED MICROORGANISMS - NUTRITIONAL AND DIETARYSUPPLEMENTS MICROBIOLOGICAL ATTRIBUTES OF NONSTERILE
NUTRITIONAL AND DIETARY SUPPLEMENTS
SUPPLEMENTAL INFORMATION FOR ARTICLES OFBOTANICAL ORIGIN DISINTEGRATION AND DISSOLUTION OF DIETARY
SUPPLEMENTS WEIGHT VARIATION OF DIETARY SUPPLEMENTS MANUFACTURING PRACTICES FOR DIETARY
SUPPLEMENTS
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USP - Strengthening Botanical Standards
Revisions to General Chapters & New GeneralChapters under consideration;
The use of polymerase chain reactions (PCR) in
botanical identification.The use of electron microscopy in botanicalidentification.Bioassay of the antioxidant activity of dietarysupplements including botanicals.Revision to the pesticides testing in the USP GeneralChapter , Articles of Botanical Origin .Heavy metals in botanicals limits and testingprocedures for individual heavy metals.
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USP - Strengthening Botanical Standards
Collaboration with the Indian Stakeholders
MOU with Indian PharmacopoeiaCommission
MOU with PHARMEXCIL
R&D alliances with Industry & Institutions
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DIETARY SUPPLEMENTS THE NEED FORUSP VERIFICATION
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All Supplements Are Not Created Equal !
27 multivitamin / multi - mineral products tested 9 failed
1 prenatal vitamin had only 75% and 1multi had only 50% of its claimed amountof folic acid
2 products had less than 40% of their
labeled amount of beta - carotene, 1 had excessive amounts1 product failed to disintegrate
The remaining failures either had excessor were deficient in labeled content
A study of Coenzyme Q10 showedthat consumers could go from175% to 0% of the labeled amountby simply changing brands
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All Supplements Are Not Created Equal !
Recent survey of 10 herbs in 20 retailstores showed;
A total of 880 products37% were deficient in labeling information
92 products for Echinacea (27 brands)Strengths on product labels varied by a factorof five
42 products for Goldenseal (15 brands)Strengths on product labels varied by a factorof twenty
J. Garrard et al, Arch Inter Med, 163 p.2290.
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All Supplements Are Not Created Equal !
Routine problems associated with DietarySupplement Ingredients;
Failure to meet an assay consistently
Failure to meet a minimum impurity profile consistently
Failure to meet GMP requirements
Heavy metals and pesticide contamination
Microbial contamination
Adulterated materials
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USP I ngre dient Verif icat ion Program s
A Public Health opportunity
Increased Regulatory pressure in most countries forimports & for dosage form manufacturers
Increasing risk in global supply chainHyper - competitive market drives need to visiblydemonstrate qualityLiability remains high for high - margin markets, drivingneed for quality assurance can help reduce risk
Trending towards uniformity in quality standards willallow for independent certification to serve multiplepurposes
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USP s Verification Products
For Dietary SupplementFinished Products
For Dietary SupplementIngredients
For PharmaceuticalIngredients, including DrugSubstances and Excipients
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USP Verified Dietary Supplements
The USP Verified Mark means:What s on the label is in the bottle.The supplement does not contain harmfullevels of contaminants.
The supplement will break downproperly to allow ingredientsto dissolve in your body.The supplement has beenmade under safe, sanitary,manufacturingprocesses.
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Customers use USP to show quality
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USP Dietary Supplement IngredientVerification
Ingredients covered by this program
Vitamins
Minerals
Amino acids
Powdered botanicals and botanical extracts
Non - botanical dietary supplements coveredby DSHEA and legally marketed in the U.S. (e.g.fish oil, chondroitin sulfate sodium, glucosamine ,etc.)
Excipients
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USP Dietary Supplement IngredientVerified Mark
The USP Verified Mark means:
Pre - audit documentation approved
On - site GMP audit approved
Quality control documentation approved
Manufacturing documentation approved
Drug substance samples tested approved
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Sigma - tau HealthScience advertisementfor the USP Verified Ingredients
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USP Pharmaceutical IngredientVerification
Ingredients covered by this program
Drug substances used in the manufacture ofpharmaceutical products
Excipients
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USP Pharmaceutical IngredientVerified Mark
The USP Verified Mark means:Pre - audit documentation approved
On - site GMP audit approved
Quality control documentation approved
Manufacturing documentation approved
Drug substance samples tested approved
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The Verification Process
1. Guidelinesfrom USP
ExpertCommittees
2. Audit ofmanufacturingsites for GMP
compliance
3. Review ofdocumentationmanufacturing,
QA, QC
4. Laboratory
testing ofproductsamples
5. Review of
conformancewith markusage
guidelines
6. Surveillancetest of productusing the mark
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The Verification Benefit
Succesful conclusion of theVe r ifica t ion process w ill en t it lethe Client to;
Certificate of Standards Compliancevalid for 3 - years
Right to use the USP Verified mark onthe Ingredient/ Product packaging &on the certificate of Analysis
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The Value of USP Verification
For ingredient producers
Demonstrate the quality of your productDifferentiate your product from othersShow that you meet world class quality requirements
Earn preferred supplier status with brokers, distributors,and manufacturers
For distributors, brokers, and finished productmanufacturers
Reduce the risk of inconsistent and sub - standard qualityfrom suppliersReduce the time and effort needed to qualify incomingproductReduce the likelihood that ingredients will be rejected andmust be returned
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The Value of USP Verification
Benefits for Regulatory authorities
Promote the public health
Build on Extended regulatory capacities
Reduce the regulatory burden by creating acommon review and audit function in participatingcountries
Get the assurance of USP, a name associated withQuality & recognized world - wide and working asan independent, science based organization drivenby its mission for ensuring Good Pharmaceuticalcare for all
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USP India Contact Information
Address:
ICICI Knowledge ParkGenome ValleyTurkapallyShameerpetHyderabad 500 078Tel: 40 - 2348 - 0088Fax: 40 - 2348 - 0089
Contacts:
Kumud SampathVice President - International, IndiaEmail: KXS@usp.org
A.V. Murali KrishnaCustomer Relationship ManagerE- mail: AVM@usp.org
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