25.Kumud-USPStandards.pdf

8/10/2019 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,


Packaging,Labeling,Uniformity,


Packaging, Labeling, Extractable Matter, Uniformity,


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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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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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 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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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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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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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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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: [email protected]

A.V. Murali KrishnaCustomer Relationship ManagerE- mail: [email protected]


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25.Kumud-USPStandards.pdf

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