1 International Conclave on Traditional Medicine, New Delhi 16 th -17 th November 2006 New Delhi, India.

2 " Frame Work for Safety Assessment of Traditional Medicines" by Dr. D B Anantha Narayana, Head: Herbals Research, Hindustan Lever Research, Bangalore.

3 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.

4 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.

5 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

6 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).

7 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 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.

8 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.

9 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?)

10 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.

11 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.

12 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.

13 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

14 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.

15 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.

16 Thank you