Scientific validation and standardization of traditional ... Session 1/pdf/Dr... · preservation to illness cure ... diseases having multiple causes like cancer, diabetes, arthritis,

AMITYWe nurture talent

Raw material: Sustainable availability and concern regarding medicinal plants on negative list

Palpu Pushpangadan([email protected])

Director GeneralAmity Institute for herbal and Biotech Products

Development Trivandrum, Kerala

International Conclave on 16th & 17th Nov, 2006Traditional Medicine New Delhi

AMITYWe nurture talent Traditional Medicine (TM)

All healthcare practices and treatment of diseases practiced by traditional communities or local people in most of the third world nations are termed as Traditional Medicine.

In fact all medicare practices of whole humankind before the on set of modern medicine in 19th Century were all Traditional Medicine.


TM:World Health Organization (WHO) defined TM as the sum total of the knowledge, skills and practices based on the theories, beliefs and experiences of indigenous cultures whether explicable or not used in the maintenance of health and in the prevention, diagnosis, improvement or treatment of physical and mental illness. The term ‘complementary medicine’, ‘alternate medicine’, and ‘non-conventional medicine’ etc. are used interchangeably with ‘traditional medicine’ in some countries. The raw materials for TM is mainly medicinal plants.

Fact file on Medicinal Plants

• Medicinal plants are important components of Biodiveristy-a product of 3500 million years of evolution life on Earth. 30-100 Million species of life on Earth today– 300,000 higher plants – out of which 216,000

are in TROPICS– Over 75,000 higher plants are used by

different cultures for medicinal & aromatic purpose

– Over 15,000 higher plants species are used in Asia

• About 7,000 in China & About 8,000 India



Flowering plants used in Traditional Systems of Medicine in India

54

321

Modern Medicine 30 spp.

Amchi 300 spp.

Unani 700 spp.

Siddha 800 spp.

Ayurveda 900 spp.

Some features of modern health care


Modern health care policies largely market driven by the pharmaceutical industry diverting attention from health preservation to illness curePrevention and eradication of diseases undermines the economic basis of this industryNo satisfactory drugs available for most of the degenerative disorders characteristic of graying population and for re-emerging resistant infections


Modern Drugs / Herbal Drugs• Modern drugs normally single molecules,

rigorously tested, structures optimized, toxicologically cleared, Mechanism generally known and clinical trials done.Herbals have many molecules, safety and efficacy based on experiences of practitioners.

• Many modern drugs known to have severe side reactions (4th – 6th largest cause of death in US)Herbals generally considered benign. Mechanism of action not known

• More than 40 % modern drugs are plant based.

AMITYWe nurture talent Advantages of Herbal Drugs

Modern drugs can produce serious side effects • Iatrogenic diseases fourth leading cause of death

in USA and other developed nations (JAMA, April 1998).

• Side effects of drugs kill more Americans annually than the world war II and Vietnam war combined (N. Y. Times 28.02.2003)

• Around 2600 persons died in the Twin Tower tragedy on 11th September 2001 causing global repercussions. It is, however, not recognized that about the same number die in USA from side effects of prescription drugs every 10 days (JAMA, April 1998).

AMITYWe nurture talent Strength of Ayurveda:

Challenging diseases for which herbal drugs can be an answer

For stand alone therapies:- Degenerative, metabolic and immune based diseases having multiple causes like cancer, diabetes, arthritis, peptic ulcer, cardiovascular disorders, osteoporosis, Alzheimer and other CNS disorders.-parasite based diseases like malaria, filaria.Adjuvants: primarily to reduce side effectsMop-up therapy: immuno-stimulants for cancer TB etc.Prophylactics for diabetes, cancerDetoxifiers based on Ayurveda/Sidda/Unani

AMITYWe nurture talent Weakness: Lack of Quality

assurance of raw materials/medicinal plants

The therapeutic quality/effect of medicinal plants are due to the presence of the biologically active chemicals which are mostly secondary metabolities such as alkaloids, glycosides, saponins, coumarins, flavonoids and terpenes, etc.75% to 80% of the medicinal plants required in Traditional Medicines (TM) is collected from wild. Sustained supply of quality raw materials is therefore difficult.

Weakness: Lack of Quality assurance


35 to 40% of the Medicinal plants used in TM are cross-pollinated species and hence there exists vast intraspecific genetic variability with respect to the morphological and chemical constituents.Heritability of these compounds are controlled by a variety of factors-genetic and macro and micro environment, season and stage, growth and development of the plant.


Weakness:• Lack of written documentary evidence on clinical

efficacy.• TM- more particularly Ayurveda was/is

essentially a highly customized/ individualized medicine. Transformation into a generalized and commercial system has adversely affected the system

• Lack of consistency in quality in batch to batch production of products.

• Lack of a well defined and well orchestrated SOP.

Quality assurance of raw materials


Genetic variants (at ploidy level or gene level) leading to the variability in the chemical composition in the population.Geographical and edaphic factors-altitude, soil composition, microbial load/association, climate, temperature, season etc can cause variation.Association with plants, animals and insects.

Quality assurance of medicinal plants


Eg. Seasonal variations in the alkaloid composition in the leaves of Adhatoda vasicahas been recorded. It is lowest in February and March and highest in the months of August, September and October. Similarly variation of alkaloid contents based on the age of the plant is reported in Holarrhenaantidysenterica


Herbal Medicine Regulation in European Union

TM like Ayurveda gained popularity in Europe as a willness system. Ayurveda and other TM drugs were marketed as food supplements, cosmetics and health promoters. After the formation of European Union, the member countries decided to have their herbal industries and products under identical medicine controls by the end of 1992.


Herbal Medicine Regulation

UK was the first to introduce a Medicine Law in 1968 which made it mandatory to license all Herbal (Medicine) manufactured. Pure herbal medicine prepared by herbalist for treating his patients are exempted under sec. 12 of the Act licensing herbal medicine demanded documentary proof of efficacy and safety data.


Herbal Medicine RegulationThe European court (EC) directed that any product legally sold in one country of the Union must be freely sold in all other countries-with a provision “as long as the product was safe and did not harm consumers. EC Directive on Traditional Herbal medicine products (2001/83/EC and amendment 2004/27/EC). The Directive came into force from 1st Nov 2005 with a transitional period upto 2011. It introduced a fast track Traditional Use Registration (TUR) which need not supply any costly safety studies that need to provide documentary evidence of its traditional use.


Traditional Use Registration (TUR)

Under TUR, TM can be sold without the intervention of practitioner. For registering such products has to produce data on quality, traditional use history for a total of 30 yrs of which 15 years should be within EU countries. Registration of such product, however, could cost as much as E 7500 to 100,000 per product.


Positive list of herbal substance

A committee for Herbal Medicinal products is established by the Directive, to prepare a positive list of herbal substances with therapeutic indicators, specified strength, route of administration and relevant safety information. The applicant can get the exemption from licensing without any traditional use data or safety data of the concerned herbal substance is in the list but just providing the quality data in the form of monographs.


Positive & Negative List

The German commission E came out with monographs for Therapeutic Guide to Herbal medicine which covered extensive published literature as chemistry, pharmacology, clinical and toxicology of herbal drugs and preparing a positive as well as negative list of herbal drugs and medicinal plants. The German Commission so far made a list of 254 positive monographs and 126 unapproved (negative) monograph. 45 herbs were negatively evaluated based on document risk.


Negative List:

This include Indian plants like:Basil, Celery, Chamomile, Cocoa, Colycynth, Ergot, Lemon grass, Liver wort, Marjoram, Nutmeg, Periwinkle, Oleander, Nuxuomica, Passely seeds, Papain seeds, Rhododendron, saffron, Sarasaparilla roots, walnut null. The commission also developed a neetral list which are suspected danger list.Basil is Ocimum basilicum having estragolewith mutagenic effect


Neutral list57 unapproved monographs due lack of scientific documentation of the use claimed by industry is kept under neutral list with the condition that if safety and efficacy data is provided it can be included in the positive list.This include:Calendula, Chestnut leaf, Pimpenella, Papaya leaf, Corsuflower, Red sandalwood, Spinach leaf, Figs, Echinacea angustifolia, Ginkgo biloba etc.

AMITYWe nurture talent Sweden’s negative list of

medicinal plants for health food

June 2005 Sweden came out with another negative list of medicinal plants based on toxicological evaluation of medicinal plants and recommended not to use them in health food, or nutraceuticals or in food supplements. This include plants of Indian origin such as

Acorus colamus, Aristolochia spp, Cinnamon flowers, Balladonna, Berberis, Cannabis sativa, Taxus baccata, coleus forskohlii, Ephedra sppGingo biloba, Ruta graveolens, Strychnos seeds, Veronica Solanum nigrum etc.


Reason for decline of quality in TM like Ayurvedic medicine

TM like Ayurveda was/is essentially a personalized/customized system of diagnosis and treatment. Collection of raw materials, preprocessing were done as per strict guideline which was based on experiential wisdom. Transformation into generalized and commercial system Ayurveda suffered greatly in quality assurance.


Traditional Medicine: Threats

Poor positioning on a global levelIgnored by global scientific communityVery little work on scientific validationsLack of well defined and well orchestrated

SOPVery little publication in peer reviewed

journalsDeliberative negative propaganda


• Demonstrated Safety• Mapped Efficacy (Pharmacologically

credible formulation)• Sustained availability of quality raw

materials• Consistency in batch to batch quality• For polyherbals, contribution of each herb to

be proved along with synergism. It should be synergistic rather than additive

• Avoidance of endangered species• Easy availability and accessibility of

medicinal plant.

Minimum requirements for TM for global acceptance


Need for:• Domestication, genetic enhancement &

cultivation of important wild medicinal plants with stable heritable characters of therapeutic importance.

• Development of package of practices & post harvest handling of medicinal plants/ raw material.

• Scientific validation of the therapeutic claims• Safety• Customer satisfaction and confidence

Need for: Standardization of raw materials


• Correct taxonomic identification of medicinal plant.• Study on the medicinal part: root, stem, bark, leaves,

flowers, fruits, nuts, gum, resins, etc.• Collection details: location, stage & development/growth

of the plants, time, pre-processing if any, storage etc.• Organoleptic examination of raw drug-Evaluation by

means of sensory organs: touch, odour taste• Microscopic & molecular examination• Chemical composition (TLC, GLC, HPLC and DNA

fingerprinting of the plant.• Identification of biologically active marker compound(s)• Shelf life of raw drugs

Need for: Good practices/Techniques in Herbal

products


• Good survey of literature (Ancient & Modern)• Develop and Observe Norms of:

Good Agricultural Practices (GAP)Good Collection/Harvesting and Post Harvest Handling Practices (GCP/GHP & GPHP)Good Laboratory Practices (GLP)Good Clinical Practices & Pharmacovigilence (GCP & PV)Good Manufacturing Practices (GMP)Good Marketing Techniques (GMT)


Documents

Scientific validation and standardization of traditional ... Session 1/pdf/Dr... · preservation to illness cure ... diseases having multiple causes like cancer, diabetes, arthritis,