Development Of Traditional Drugs For Global Positioning With Major Emphasis On Efficacy And Safety

Development Of Traditional Drugs For Global Positioning With Major Emphasis On Efficacy And Safety

اسلاید 1: www.tabaye.ir

اسلاید 2: International Conclave on Traditional Medicine, Delhi(16-17th November 2006)Development Of Traditional Drugs For Global Positioning With Major Emphasis On Efficacy And SafetyC K KatiyarDirector – Herbal Drug ResearchRanbaxy Research LaboratoriesPlot 20, Sector 18, Gurgaon, Haryana (INDIA)

اسلاید 3: Introduction Why Global Strategy Results of Global Survey of Regulatory Status Global Vs Regional Strategy ProposalsFLOW OF PRESENTATION

اسلاید 4: CAM1999 (%)Use of any CAM in past 12 months20Of which: *  Herbal medicine34Aromatherapy21Homeopathy17Acupuncture / acupressure14Massage6Reflexology6Osteopathy4Chiropractic3*: Percentages of those who had used CAM. It must be noted that some individuals use more than oneTherapy and thus the numbers above do not add up to 100.USE OF CAM IN THE UNITED KINGDOMErnst, E. & White, A. The BBC Survey of Complementary Medicine Use in the UK in Complementary Therapies in Medicine, 8 (2000), 32-36.

اسلاید 5: USE OF CAM IN THE USAEisenberg, D.M., Davis, R.B., Ettner, S.L. et al. Trends in Alternative Medicine Use in the United States, 1990-1997: Results of a Follow-up National Survey in The Journal of the American Medical Association, 280 (1998) 1569-1575. CAM1990 (%)1997 (%)Use of any CAM in past 12 months33.8†42.1†of which‡    Relaxation techniques13.116.3Herbal medicine2.512.1Massage6.911.1Chiropractic10.111.0Spiritual healing4.27.0Homeopathy0.73.4Acupuncture0.41.0†: Percentages of the total sample population (1539 for the 1990 data; 2055 in 1997)‡: Table shows selected figures relating to the top five therapies based on the 1997 survey

اسلاید 6: Own Fundamental Principles Own Unique Ingredients Own Composition Own Process of ManufacturingEACH TM/CAM HAS

اسلاید 7: GLOBAL HERBAL MARKET INCL NUTRACEUTICALS $ 70.4 BILLIONEXCLUSIVE GLOBAL HERBAL MARKET $ 24.2 BILLIONGLOBAL SCENARIO49%31%70%10%33%49%42%12.414.024.1819.58

اسلاید 8: The World Bank estimate world trade in medicinal plants and related products  $ 5 trillion by 2050 A.D. Global Herbal market including Nutraceuticals  $ 70.4 Billion with an average growth rate of about 12% a year. However, exclusive herbal drug market is estimated to be around $ 25 Billion.Worldwide phytopharmaceuticals market is growing @ 12%.GLOBAL SCENARIO

اسلاید 9: WHITHER GLOBAL STRATEGY?

اسلاید 10: INCREASING POPULARITYALSO INVITESCRITICISMARE WE PREPARED TO FACE IT ?

اسلاید 11: TRADITIONAL SYSTEMS OF MEDICINEREMEDY OR FALACYPANACEA OR POISONTHE DEBATE STILL GOES ON……….

اسلاید 12: 2 0 0 0Obach RS. J Pharmacol Exp Ther. Jul;294(1):88-95CONCLUSIONS: In vitro data indicate that St. Johns Wort preparations contain constituents that can potently inhibit the activities of major human drug-metabolizing enzymes.Impact on Business:Not MuchConsumer Comments:Don’t give credence to researches conducted by Scientists who don’t know the subject

اسلاید 13: CONCLUSIONS: Echinacea purpurea, as dosed in this study, was not effective in treating URI symptoms in patients 2 to 11 years old, and its use was associated with an increased risk of rash.2 0 0 3Taylor et al. JAMA. Dec 3;290(21):2824-30

اسلاید 14: CONCLUSIONS: Guggulipid did not improve levels of serum cholesterol over the short term, and might in fact raise levels of LDL-C. 2 0 0 3Szapary et al. JAMA. Aug 13;290(6):765-72Rejoinders from India regarding Clinical Trial material remains unanswered

اسلاید 15: 2 0 0 4Saper et al. JAMA. Dec 15;292(23):2868-73CONCLUSIONS: 17 out of 70 Ayurvedic/Unani medicines contained heavy metals, therefore, not safe to be consumed.Does mere presence of a heavy metal in trace amounts in a plant source of soil/other origin make it toxic?

اسلاید 16: Saper et al. 2004. JAMA. Dec 15;292(23):2868-7317 out of 70 Ayurvedic/Unani medicines contained heavy metals, therefore, not safe to be consumed.July 20, 2 0 0 5Health Canada & MHRA of UK bans Indian Ayurvedic drugs based on controversial JAMA reportOctober 26, 2 0 0 5Central Government of India makes heavy metal testing mandatory for Ayurvedic drugs to be exported effective Jan I, 2006November 17, 2 0 0 5MHRA of UK recovered further Chinese/Ayurvedic productscontaining heavy metals

اسلاید 17: WHO - GLOBAL SURVEY(141 countries)Traditional Medicine/Complementary and Alternative Medicine products are used under the categories which include Prescription products OTC products Self medication Dietary supplements Health foods Functional foods & Others World Health Organization (2005), National Policy on Traditional Medicine and Regulation of Herbal Medicines. Report of a WHO global survey. WHO, Geneva.

اسلاید 18: WHO - GLOBAL SURVEYTraditional medicine/Complementary & Alternative medicineSurvey AttributesPresentAbsentNational policy in place45 (32%)90 (64%)National laws framed54 (38%)84 (60%)National program exists40 (28%)93 (66%)National office exists75 (53%)61 (43%)Expert committees constituted61 (43%)75 (51%)National research institutes exist38 (27%) Traditional medicines46 (33%) Herbal medicines9 (6%) CAMA. P O L I C I E S

اسلاید 19: WHO - GLOBAL SURVEYTraditional medicine/Complementary & Alternative medicineB. L A W S & R E G U L A T I O N SSurvey AttributesPresentAbsent1. Laws/regulations framed92 (65%)48 (34%) a. Partly same as conventional pharmaceuticals41 b. Separate laws for herbals22 c. Same as Pharma472. Registration system exists85 (61%)54 (38%)3. Post Marketing Surveillance conducted59 (42%)77 (54%)

اسلاید 20: WHO - GLOBAL SURVEYTraditional medicine/Complementary & Alternative medicineC. S T A T U S O F P H A R M A C O P O E I ASurvey AttributesYesNoNational Pharmacopoeia prepared34 (24%)104 (74%)Other Pharmacopoeia used58 (56%)No pharmacopoeia used31 (30%)

اسلاید 21: WHO - GLOBAL SURVEYTraditional medicine/Complementary & Alternative medicineD. L E G A L S T A T U SSurvey AttributesYesNoNational pharmacopoeia legally binding29 (85%)4 (12%)National monograph on herbal medicine prepared46 (33%)90 (63%)Other monographs in use34 (38%)No monographs used39 (43%)Monographs legally binding24 (52% of 46)17 (37%)

اسلاید 22: WHO - GLOBAL SURVEYTraditional medicine/Complementary & Alternative medicineE. N A T U R E O F C L A I M S A L L O W E DStatus of claimNo. of countriesMedical claims90Health claims62Nutrient content claims49Structure function claims39Other claims6

اسلاید 23: A REGIONAL STRATEGYRather than GLOBALLY HARMONIZED STRATEGYSo Much Diversity Justifies

اسلاید 24: Guiding Factors for REGIONAL STRATEGY History of Use of Traditional Medicines Regulatory Requirements Geographical Considerations Socio-Economic Conditions Level of commitment of respective Governments and their policies for Traditional Medicines Prevalence of sound system of Traditional Medicines

اسلاید 25: Development of Traditional MedicinesZoopharmacognosyTribal PracticesObservationAnimal useHuman useTribal & Ethnobotanical practicesHerbal practices Knowledge based Philosophical backgroundWell developed SystemsViz. TCM & AyurvedaDocumentationStrong fundamental principlesQUALITY, SAFETY, EFFICACY, AFFORDABILITY

اسلاید 26: Classification of Geographical Regions basis Traditional Medicine usage A. Countries with no official recognition to Traditional medicines & no regulatory mechanism viz. Africa Focus on Authentication and adulterationB. Countries with strong traditional systems of medicine viz. India, ChinaFocus on StandardizationC. Countries with no traditional systems but strong herbal practices viz. Europe & USAFocus on Efficacy evaluation

اسلاید 27: Safety Aspects of Traditional MedicineWHO Survey in 130 countries on Regulatory RequirementsRegulatory requirementNo. of countriesSpecial requirement Traditional use without harmful effects Ref to documented scientific research on similar products Others (Bibliographic data etc.)82665321Same as Pharmaceuticals57No requirement 28Regulatory Requirements vary from country to countryWorld Health Organization (2005), National Policy on Traditional Medicine and Regulation of Herbal Medicines. Report of a WHO global survey. WHO, Geneva.

اسلاید 28: Indian Council of Medical Research guidelines for safety on products of Indian System of Medicine“Since the substance to be tested is already in use in Indian Systems of Medicine or has been described in their texts, the need for testing its toxicity in animals has been considerably reduced. If there are reports suggesting toxicity or when the herbal preparation is to be used for more than 3 months it would be necessary to undertake 4-6 weeks toxicity study in 2 species of animals”.Indian Council of Medical Research (2000). Ethical Guidelines for Biomedical Research on Human subjects, ICMR, New Delhi.

اسلاید 29: DRAFT Indian guidelines of Safety on Non-Ayurvedic Herbal MedicinesClassificationDefinitionClass 1Unprocessed powdered parts of plantClass 1AThose not containing poisonous plantsClass 1 BThose containing poisonous plantsClass IIProcessed parts of plantClass IIIProcessed or unprocessed parts together with metallic and/or mineral substances and/or productsGovt. of India, Circular No. 4-5/93 (1993). Issued by Drugs Controller India, Directorate of Health Services, Ministry of Health & Family Welfare, New Delhi.

اسلاید 30: Class Sub ClassFormulation in marketToxicity requirementsClass IA> 5 year< 5 yearAcute toxicityNo comment on toxicityClass IB> 5 year< 5 yearChronic toxicityChronic toxicityClass IANew drugSub-acuteClass IBNew Drug ChronicClass II-> 5 year< 5 yearNo comment on toxicitySub-chronic toxicityClass II-New drugSub-chronicClass III-In marketFull toxicological profile according to Schedule ‘Y’DRAFT Indian guidelines of Safety on Non-Ayurvedic Herbal MedicinesGovt. of India, Circular No. 4-5/93 (1993). Issued by Drugs Controller India, Directorate of Health Services, Ministry of Health & Family Welfare, New Delhi.

اسلاید 31: Efficacy Aspects of Traditional MedicineWHO recommends the following:A. Evaluate traditional medicine in its own theoretical frameworkB. Evaluate traditional medicine in the theoretical framework of conventional medicine C. Compare the efficacy of traditional medicine with conventional medicine D. Compare the efficacy of traditional medicine within the system of traditional medicineWorld Health Organization (2000). Annexure IV. General guidelines for methodologies on research and evaluation of traditional medicine, WHO, Geneva.

اسلاید 32: WHO-Levels of evidence for Efficacy studiesGrade/LevelRecommendationA:Ia. Evidence obtained from meta-analysis of randomized controlled trailsIb. Evidence obtained from at least one randomized controlled trialRequires at least one randomized controlled trial as part of the body of literature of overall good and consistency addressing the specific recommendation.B.IIa. Evidence obtained from at least one well designed controlled study without randomizationIIb. Evidence obtained from at least one other type of well-designed quasi-experimental studyIII. Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case control studiesRequires availability of well-conducted clinical studies but no randomized clinical trials on the topic of recommendation.C.IV. Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authoritiesRequires evidence from expert committee reports or opinions and/or clinical experience of respected authorities. Indicates absence of directly applicable studies of good quality.

اسلاید 33: European Union AspectHerbal Medicinal Products in the European Union. Study carried out on behalf of the European Union by The Association of the European Self-Medication Industry. Brussels – Belgium. Country Simplified ProofBibliographic ProofFull Clinical ProofAustriaYesOnly supportiveYesBelgiumYes(Yes)YesDenmarkNoYesNoFinlandNoYesNoFranceYes(Yes)YesGermanyYesYesYesGreeceNoYesYesIrelandNo(Yes)YesItalyNoYesYesLuxembourgNo(Yes)(Yes)NetherlandNo(Yes)YesPortugalNo(Yes)YesSpainYesYesYesSwedenNoYesYesUnited KingdomNoYesYesComparison of the requirements for proof of efficacy

اسلاید 34: Proposals for Regional Positioning of Traditional Medicines - SAFETYSince the traditional medicines may contain ingredients of mineral/metal/and or animal origin in addition to herbal ingredients, the requirement of toxicity should depend on the composition besides the usage of the product.Class of drugAcute Tox28 day Tox90 day ToxAMES test1A. Traditional Herbal Medicine (same composition, formulation & use as in text or traditionally used)*----1B. Traditional Herbal Medicine (modified composition, formulation & use) -2. Herbo-mineral medicine-3. Herbo metallic medicine-4. Herbal Medicine containing known toxic herbs-* However, if reports are available suggesting toxicity or if the product is to be used for more than 3 months then 4-6 weeks toxicity studies should be conducted in 2 species.

اسلاید 35: Proposals for Regional Positioning of Traditional Medicines - EFFICACYAdopt a flexible approach to review the data with respect to efficacy. Randomized double blind placebo controlled studies may not be always suitable to evaluate the efficacy of Traditional Medicine products.

اسلاید 36: Proposed Parameters for assessing Efficacyof Traditional Medicine 1.Traditional/Historical Usage2.Published/Bibliographical references (incl textbook refs)3.Uses mentioned in Pharmacopoeia & Monographs e.g. Ayurvedic Pharmacopoeia of India, WHO Monographs, German Commission E Monographs, British Herbal Pharmacopoeia, PDR for Herbals etc.4.Pharmacological Evidences using appropriate model a). In vitro b). In vivo5.Clinical Experience/Usage/Trial a). Single case design b). Ethnographic studies c). Consumer Usage Test d). Pragmatic trial design e). Observation Research f). Randomized double-blind placebo controlled design g). Post Marketing Surveillance

اسلاید 37: CategoryIngredientsIndicationIndicationCategoryIngredientsIndicationIndicationClinical TrialPMSI. Classical medicinesAs per textAs per textAs per textNAII. Proprietary medicinesII. Proprietary medicinesII. Proprietary medicinesII. Proprietary medicinesII. Proprietary medicines A. With ingredients mentioned in the ASU books & products for same indication already in the market for more than 5 yearsAs per textAs per Mktd productsAs per Mktd productsNAB. With ingredients mentioned in the ASU books & products for same indication in the market for less than 5 yearsAs per textAs per Mktd productsAs per Mktd productsClaim Support Data to be providedC. With ingredients mentioned in the ASU books but to be used for new indication As per textAnyAny (CT using suitable design)III. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksIII. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksIII. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksIII. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksIII. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksIII. Plant based medicines prepared from ingredients not mentioned in traditional medicine booksA. Presence in the International Market for more than 5 years-AnyBibliography dataBibliography dataB. Presence in the International market for les than 5 years-Any (Bibliography data & CT on Indian population) (Bibliography data & CT on Indian population)C. New Products (products not yet marketed)-Any (CT on Indian population) (CT on Indian population)Reproduced below is a model which was proposed to Govt. of India to regulate Ayurveda, Siddha and Unani (ASU) drug licensing.

اسلاید 38: This may be modified for assessing the Efficacy of Traditional Medicines to evolve a Regional Strategy TM ProductDocumentationIngredientsMfg processClaimsEfficacy requirementTraditional+TraditionalTraditionalTraditionalNILTraditional+TraditionalModifiedTraditionalExperimental studiesNew-TraditionalNewAnyExperimental studies orHuman Efficacy studiesNew-NewNewAnyExperimental studies and Human efficacy studies

اسلاید 39: S U M M A R Y The popularity of Traditional Medicines is on a Northward movement Due to non-uniformity in their status in various countries, Regional harmonization strategies are more appropriate than developing Global strategies Stepwise flexible approach should be adopted for considering quality, regulatory, safety and efficacy requirements considering multiple factors Traditional/Historical use and Bibliographical referencing should be given due importance but should not be allowed to be used as a shield

اسلاید 40: ACKNOWLEDGEMENTDr Navin SharmaSr Res ScientistHerbal Drug ResearchRanbaxy Research LabsGurgaon

اسلاید 41: THANKS