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International Conclave on Traditional Medicine, New Delhi16th-17th November 2006New Delhi, India.

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" Frame Work for Safety Assessment of  Traditional

Medicines"

by Dr. D B Anantha Narayana,

Head: Herbals Research, Hindustan Lever Research, Bangalore.

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Traditional Medicines Are:

Single herb, mineral or animal products. Mixture of multiple herbs without much processing. Mixture of multiple herbs with processing as per

traditional methods (water extract, self fermented wine like preparation, oil extracts etc.)

Complex multiple herb mixtures with complex processing.

Any one of the above converted into modern dosage form like tablets, capsules, gels, creams etc.

Herbs or multiple herbs processed using modern technology/ using today’s organic solvents.

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Traditional Medicines Used as:

As prophylactic or preventive medicine products. As a medicine ingestible for specific therapeutic

activity. As an external preparation as a medicine for

skin, scalp, hair, oral diseases. As an external preparation for application to skin,

hair, scalp for cosmetic benefits (leave on preparations).

As an external preparation for application to skin, hair, scalp for cosmetic benefits (wash off

preparations). As preparations for eye nose ear or as enemas.

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Requirements for registration across boundaries. TM’s are currently required to be registered as a “Drug”

or “Cosmetic” needing to meet the same requirements as of conventional products

Applicants need to submit dossiers with data on: 1. Composition 2. Process 3. Chemistry, manufacturing and QA/QC controls 4. Packaging and Shelf-life data 5. Indications and Dosages and directions for use. 6. Pharmacology 7. SAFETY information. 8. Efficacy and Claim Support data

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TM – Drugs Comparisons

Traditional Medicines Ayurveda & most TM takes a

holistic approach. Treats individual as a whole. Encompasses body, mind,

sense organs and spirit. Made of natural or processed

natural materials. Multi ingredient recipe. Each ingredient- multi

component (ginger-278 compounds).

Concurrently working at more than one target and by more than one mechanism.

Conventional Drugs Considered Reductionist in

approach. Focuses on acting on body’s organs,

cells and physiology. Focuses on specific targets or work

through single mechanism. Only recently, role of mind in

efficacy of drugs are getting recognised.

Normally single, well characterised chemical component based.

Last decade has seen drug cocktails (vitamin complex, anti-cancer, anti-AIDS, anti-TB combinations).

Advancing towards use of recombinant based therapies (complex, multi-component).

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TM-Has a History of use

Long history of use- greater than most of the current day drugs.1. Aspirin is known only for about 70 years.2. Cinchona alkaloids (quinine) known for about 100 years.3. Charaka Samhita the first ayurvedic treatise- 1500 BC.4. TCM pharmacopoeia more than 3000 years old.

Same herb present in more than one recipes. Herbs used both externally and internally. Herbs/ recipes are in commerce and usage even today. Possible to document quantum of production, quantum of usage,

potential exposure on population for each herb/ recipe. Possible to document usage experience on hundreds of patients as

observed by qualified traditional medicine doctors practicing today. Retrospective or prospective documentation possible.

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Traditional Medicines Consumers believe and say are “safe”. By safety consumers mean- they have not seen

or heard serious toxicities or side effects. Consumers also ignore minor side effects due to

TM. Believed to be used by over 70% population in

many countries. Scientists have problems in producing data to

substantiate the above.

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Safety

Require clarity- what are we looking for? “Proof that the TM is completely safe and

has no side effect whatsoever”. “Knowledge of the TM- what are the

known/ reported side effects, frequency, severity, how to prevent or manage them”.

Above knowledge- causality, linkability to the TM (same ingredient similarly processed?)

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Traditional Medicines

Are able to provide limited supporting documentation regarding safety.

Produce copies of treatises, books, Granthas and encyclopedias where the herb mineral or recipe are mentioned.( eg. 57 such authoritative books are recognised for Ayurveda by Govt of India)

Entries in above normally do not provide contra-indications or side-effects (except in some cases).

However they have strong and long history of usage.

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Regulators need data Regulators and scientists today demand

documented data regarding safety. Expertise in toxicological evaluation scientifically

exist today using drug development models. Toxicology primarily revolve around generation of

data using animal models and evaluation using animals.

Toxicological models specifically apply to characterised chemical compounds-Can they be just adopted to multi component herbs and recipes?

In absence of specific guidelines for safety assessment of TM, classical toxicology data are demanded.

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History of use Review all published scientific studies on the

herb/ TM- apply filter of applicability of data to TM processes.

Controlled human study can generate specific safety data as assessed by TM doctor concurrently with a conventional doctor and tools of both systems.

Mutagenicity data- Ame’s test and chromosomal aberration test (as per OECD guidelines).

Skin irritation, photo-sensitivity, allergenicity data.

Acute or chronic toxicity if TM is required for long periods of administration or history of use data found inadequate.

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Need for framework development TM doctors and scientists

need to move a few steps in creating comprehensive documentation of all available data.

TM doctors and scientists need to initiate new ways of generating current day usage and safety data.

TM doctors and scientists should be open to scientific scrutiny when required for limited/ specific safety testing viz. carcinogenicity, mutagenicity, allergenic activity, skin sensitivity etc.

Regulators should be open to, listen, read, discuss and appreciate TM w.r.t its philosophy, usage and treatment.

Regulators should also be open to appreciate the processing techniques and difficulties in generating data using current day scientific tools.

Regulators should also be open to review history of use and published data as available today with a view o decide missing links in data.

STEPS STEPS

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Collaboration required Traditional medicine doctors, pharmacologists,

toxicologists, measurement science experts and scientists.

Cross functional appreciation and approach required. Regulators involved should not be limited to

contemporary scientists alone. TM data- authentic translation to English for ease of

understanding. Involve scientists from companies practicing SHE as a

policy- draw from their rich experience in safety assessment.

Data generation should be need based. National Governments need to provide financial

support for generation of common safety data for TM and herbs.

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What India can offer Rich heritage of use of Ayurveda, Unani, Siddha for

healthcare. Strong expertise in both TM(A,U,S) food and

Pharma industry. Comprehensive database of both Ayurveda and

published data. Experience in regulating traditional healthcare

systems as well as traditional medicine based industry.

Leading companies converting traditional products to scientifically evaluated and tested formulations in all categories (food, medicine, cosmetic benefits).

Has a strong Herbal actives manufacturers. Will provide value addition to framework

development for safety assessment of TM.

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Thank you