Transcript " Frame work for safety Assessemnt of herbs / ingredients and

International Conclave on Traditional
Medicine,
New Delhi
16th-17th November 2006
New 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
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Are:
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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
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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.
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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
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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.
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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, antiAIDS, anti-TB combinations).
Advancing towards use of
recombinant based therapies
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(complex, multi-component).
TM-Has a History of use
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Long history of use- greater than most of the current day drugs.
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Aspirin is known only for about 70 years.
Cinchona alkaloids (quinine) known for about 100 years.
Charaka Samhita the first ayurvedic treatise- 1500 BC.
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
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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
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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
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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
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demanded.
History of use
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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
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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.
STEPS
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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
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Collaboration required
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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
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and herbs.
What India can offer
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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
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development for safety assessment of TM.
Thank you
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