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REGULATORY ASPECT

FOR HERBAL
MEDICINES
By:

Md Abul Barkat

M.Pharm, (Ph.D)

Lecturer
IIT Dwarka, New Delhi

INDIA
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HERBAL MEDICINES

It Include herbs, herbal materials, herbal


preparations and finished herbal products
that contain as active ingredients part of
plant, or other plant materials or
combinations.

Traditional/ Complementary
Medicine -WHO perspective

Traditional Medicine Indigenous Medicine


existent in the region either recognised or
ethnic as in Chinese medicine, Indian
Ayurveda, Arabic Unani medicine, African
& Latin American practices.

Complementary / Alternative Medicine


Added or used alternatively to dominant
health care system of allopathic medicine
as in US, Canada and Europe
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Herbal drug products constitute a major share of all


the officially recognized systems of health in
India,like Ayurveda, Yoga, Unani, Siddha,
Homeopathy and Naturopathy.

Research Councils (ICMR and CSIR), Department


of AYUSH (Ayurveda, Yoga & Naturopathy, Unani,
Siddha and Homoeopathy) & Drugs and
Cosmetics Act 1940 (Amendment) regulates
herbal medicines in India.

Department of AYUSH, ICMR and CSIR work together


to achieve safe, effective AYUSH products for the
identified diseases and to develop new drugs.

Regulatory Intervention

Regulation of Herbalists:
Ensures

purchase of medicines and ingredients


from reputable suppliers

Ensures

practitioners take responsible, informed


approach regarding safety issues

Appropriate

training and skills necessary

Products -Integrity

QUALITY: Certificate of Analysis

Conformity assessment for proper identity

Content verification

Impurities/contaminants

Heavy metals, aflatoxins, moisture. Synthetic material added?

Raw materials - source etc.

GMP, GAP

Product stability

Integrity contd.
EFFICACY

Ability to effect label claim - indication/action

Pharmacological activity

Potency -justification for effective dose.

Rationale for combination therapy multi-herb combination a matter of


concern

Nature of claims - justification

Integrity contd.

SAFETY

Toxicity

Acute

Long-term

Mild, severe

Reporting responsibility

Interactions, contraindications

Use in children

Documentation Requirements for


Registration- Herbal Remedies
Statement

of content

Posology
Rationale

for combinations
Toxic/side effects
Tests to confirm quality, potency
Approval in country of origin
Samples
Fees
Other pertinent information

Regional Challenges:

Availability of resources to effectively address issues.

Geographical barriers- distance, absence of physical


borders

Commitment to follow-up

Matter of Whose priority

Regulatory Challenges

Attempts to circumvent existing


legislation
Need for constant market vigilance Cosmetics with herbs?
Teas & other beverages
Persistence of local Alt Med.
Practitioners in use of prohibited herbs
eg. Chaparral, Comfrey, Ma Huang
Customs. Trinidad has dedicated
inspectorate

Regulatory Challenges
Public

suspicion-inadequate public
education.
Insufficient scientific information
on many herbs presents barrier to
proper scientific review
Inability of many applicants to
provide requisite documentation
Lack of resources to develop
adequate laboratory support.

Indian Council of Medical


Research

Founded in 1911 as Indian Research Fund


Association

Renamed as ICMR in 1949

Apex organization to formulate, conduct,


coordinate and promote biomedical
research

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ICMRs Research on herbal


drugs

1911 onwards - ICMR

1964 70 : Composite Drug Research Scheme

1983 Disease oriented approach

2000 onwards - Collaboration between ICMR &


Dept. of AYUSH (earlier ISM & H) Golden Triangle
Partnership Program

2005 ICMR NIF (National Innovation


Foundation) Initiative
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Quality Standards of Indian


Medicinal Plants

Standards set as per


WHO guidelines.

Use conventional and


modern scientific
approach.

Developed at 4 national
laboratories.

3 Volumes.

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MAJOR ACTIVITIES

Status Report on propagation techniques


of Pterocarpus marsupium, Saraca
indica and Streblus asper IHBT,
Palampur.

Agrotechnology of P. kurroa, IHBT


(Institute of Himalayan Bioresource
Technology), Palampur

Clinical trial with Vijayasar (Pterocarpus


marsupium) in Chronic Diabetics

Survey of Medicinal plants of Western


Ghats
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Spends on Traditional Medicine


Development

NCCAM, USA USD


123.1 m in 2005
increase by 0.5 %
in 2006

WHO - <.1 % of
budget

India & China


spend more
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1980 ICMR Guidelines Policy Statement on


Ethical Considerations involved in research
on Human Subjects

Ethics Committee

Informed consent

Clinical trials

Research on children, mentally


disadvantaged,

those with diminished autonomy

Traditional Medicine

Publications
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Revised ICMR Ethics Guidelines

Released in 2000

All institutions involved


in biomedical research
involving human beings
should follow these
guidelines to protect
safety and well being of
all individuals.

Guidelines on website http://www.icmr.nic.in

To be legislated - The
Biomedical Research on
Human Subjects
(Promotion and
Regulation) Bill, 2006
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Research on herbal drugs


Reverse Pharmacology

No toxicity study to be done for Phase II


trials. if there are no toxicity reports when
use is for less than 3 months.

It should be necessary to undertake 4-6 weeks


toxicity study in 2 species of animal to be
used for > 3 months if there are reports
suggesting toxicity when a larger multicentric
Phase III trials are subsequently planned
based on the results of Phase II study.

Adverse Drug Reaction & drug-herb


interaction should be reported
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Protocol

Group of experts should include experts from


traditional systems of medicine.

GCP compliant trial design

Biostatistician to be involved while designing


clinical trial protocol.

Pilot studies can be observational

Ideal to conduct a randomized, controlled trial to


validate

Monitoring must to detect toxicity as well as


efficacy

Statistical analysis should be presented in a


manner that is likely to facilitate the
interpretation of their clinical importance.
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Monitoring

To be based on considerations such as objective,


purpose, design, complexity, blinding, size and
end points of the trial.

To be conducted and documented properly in


accordance with GCP.

Efficacy to be based on such defined endpoints as,


specific clinical symptoms or signs, or defined
prognostic laboratory markers.

Safety to be monitored on the basis of either


symptoms or signs,particularly to end points that
may signal anticipated toxicity.

Laboratory indicators of liver, kidney, cardiac or


haematological toxicity.
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Special Concerns for Herbal


Remedies
1)For all researchers

GCP Guidelines also pertain to traditional drugs

Herbal remedies and medicinal plants to be


incorporated in modern system must follow DCGIs
guidelines

Multidisciplinary Expert group for designing and


evaluating the study from concerned systems : ideal for
multicentric studies.

Association with physicians from the concerned system


shall be necessary as co-investigators / collaborators if
trial is in Modern Medicine Hospitals

2)Researchers from Indian Systems of Medicine

Guidelines not binding for evaluation of traditional


drugs for use in their own hospitals / clinics

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QUALITY CONTROL AYURVEDIC


DRUGS (Drugs & Cosmetics Act,
1940 & Rules, 1945)

Separate Chapter for Ayurveda, Siddha & Unani


medicines introduced in Chapter IV A.

33 C - Separate Drug Technical Advisory Board


under Drugs & Cosmetics Act, 1940 for Indian
Systems of Medicines to advise Government on all
aspects related to quality control and drug
standardization.

33 D - Separate Drugs Consultative Committee


comprising State Drugs Licensing Authorities set up
under the Act for securing uniformity in the
administration of the Act throughout India

33 E misbranded drugs, 33 EE adulterated


drugs, 33EEA spurious drugs.
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IMPORTANT PROVISIONS OF INDIAN DRUGS &


COSMETICS ACT, 1940 RELATING TO
AYURVEDA, SIDDHA AND UNANI DRUGS

33EEB - Regulation of manufacture for


sale of Ayurvedic drugs through drug
license system.

33EEC-Prohibitionof manufacture and sale


of certain drugs.

33EED Power of Central Government to


prohibit manufacture etc., of drugs in
public interest.

33 F - Provision for Government Analysts.

33 G - Provision for Inspectors to visit


factory.

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33 H - Penalty for manufacture, sale etc.,


of drugs in contravention of the Act.

33 J - Penalty for subsequent offences.

Prescribe qualifications and duties of the


Government analysts.

Prescribe methods of testing and analysis.

Establish Good Laboratories for Testing


and Analysis of drugs.

33 EEB heavy metals within permissible


limits - Mandatory testing for heavy
metals (Arsenic, Lead, Mercury &
Cadmium) in export formulations.
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Permissible Limit of Heavy Metals in


ASU Formulations with only Herbal
Ingredients
As per W.H.O & US F.D.A

Lead (Pb) 10 ppm

Cadmium (Cd) 0.30 ppm

Arsenic (As) 10 ppm

Mercury (Hg.) 1 ppm

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List of Approved ASU Drug Testing


Laboratories
1)Under Rule -160 A to J of the Drugs and Cosmetics
Rule 1945 12 Labs

5 Madhya Pradesh, 4 - Bangalore, 2 - Hyderabad,


Chennai, 1 Haryana, New Delhi, Jammu

2)GLP Compliant NABL Accredited Laboratories

a. International Institute of Bio-technology (IIBT),


Padappai, Tamil Nadu

b. Rallis Research Centre, Peenaya, Bangalore,


Karnataka

c. Jai Research Foundation, VAPI, Gujarat

d. Reddys Lab, Hyderabad, Andhra Pradesh


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EUROPE
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European Community
Directives

CD 2001/83(basic regulation)

CD 2003/63 of 25 June 2003 (Annex I, criteria)

CD 2004/24 (Traditional herbal medicinal


products)

CD 2004/27 of 31 March 2004 (HMPC)

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European Medicines Agency EMA

Central European Authority with specified


tasks.

Committees and Working Parties

Herbal Medicinal Products Committee


HMPC

Monographs and List Working Party - MLWP

Coordination of National Competent


Authorities

Guidance Documents (www.ema.europa.eu)


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HMPC - Tasks

Monographs

List entries

Scientific opinions

Coordination

Scientific advice

Questions

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Herbal medicinal products fall within the


scope of the European Directive
2001/83/EC that foresees marketing of
each medicinal product and requires an ad
hoc authorisation to be granted on the basis
of results of tests and experimentations
concerning quality, safety and efficacy.

The main features of Directive 2001/EC


are traditional herbal medicine definition,
simplified registration procedure, provisions
for community herbal monographs and
community list of herbal substances and
preparations and establishment of the
Committee for Herbal Medicinal
Products(HMPC).
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Most individual herbal medicinal products


are licensed nationally by member states,
the process for licensing and information
of herbal substances and, preparations is
harmonised across the European Union. IN
United Kingdom, to get a product registered,
companies have to submit a dossier to
the Medicines and Healthcare products
Regulatory Agency (MHRA) demonstrating
that it meets the requirements of quality,
safety and patient information as per the
Traditional Herbal Registration Scheme.

The HMPC evaluates scientifically all


available information including non-clinical
and clinical data but also documented
long-standing use and experience in the
Community.
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Community monographs are divided into


two columns: well-established use
(marketing authorisation) and traditional
use (simplified registration).

Well-established use section describes the


safety and efficacy data while traditional use
section is accepted on the basis of
sufficient safety data and plausible efficacy.

The Committee on Herbal Medicinal Products


(HMPC) has developed procedure to invite
the public to submit scientific data on
herbal substances and preparations.

The provided information may then be


used by the Committee in the
development of Community monographs and
to Community list entries.
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The European Scientific Cooperative


on Phytotherapy (ESCOP)

The European Scientific Cooperative on


Phytotherapy (ESCOP) was founded in 1989, the
main objectives being to establish harmonized
criteria for the assessment of phytomedicines, to
support scientific research and to contribute to
the acceptance of phytotherapy at a European
level.

In October 1990, the first five monographs were


presented at a symposium in Brussels and were
officially handed over to representatives of the
European Community. After a thorough
assessment, the Committee on Proprietary
Medicinal Products (CPMP) published four
monographs on anthraquinone laxatives in May
1994

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United States of
America

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In United States, the term


complementary/alternative medicines (CAM)
are most commonly used for traditional
medicine systems.

"Complementary medicine" refers to use of


CAM together with conventional medicine,
such as using acupuncture, in addition to
usual care to help lessen pain.

FDA in its draft guidance Guidance for


industry on complementary and alternative
medicine products and regulation by the
food and drug administration clarified
different categories of Complimentary
Alternative Medicines (CAM) products into
cosmetic; device; dietary supplement; drug,
as well as "new drug" and "new animal drug;"
food; and food additive.

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FDAs Center for Drug Evaluation and


Research (CDER) Guidance for Botanical Drug
Products differentiates between those
botanical drugs that could be marketed as
Over-The-Counter (OTC) and those that
would require New Drug Application (NDA).

The current state of herbal research in the


United States also contrasts with that of
China and Germany. The limited availability
of funds (mainly in the Office of Dietary
Supplements and the National Center for
Complementary and Alternative Medicine)
greatly restricts the volume of research
conducted; thus, in comparison with China
and Germany, there is less published US
scientific and medical literature regarding
herbal use.
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Under DSHEA, the manufacturer or marketer of


dietary supplements containing new ingredients is
required to notify FDA 75 days before they are
marketed.

Under DSHEA, a 7-member Commission on


Dietary Supplements was formed to conduct
studies and make advisements on the
regulation of herbal label claims and
statements.

The Office of Dietary Supplements, an office


within the National Institutes of Health, was
established in 1995 to explore the potential role
of supplements for improving health care in the
United States.Along with herbs, supplements
also include vitamins, minerals, amino acids,
homeopathic remedies,concentrates,extracts,
and various combinations of these ingredients.
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REFERENCES

1)International journal of herbal medicine.


(www.florajournal.com)

2)WHO Regional Office for the Western


Pacific. Guidelines for the Appropriate Use of
Herbal Medicines.Manila, Philippines: World
Health Organization; 1998.

3)US Food and Drug Administration, Center for


Food Safety and Applied Nutrition. Dietary
Supplement Health and Education Act of 1994.
December 1, 1995. Available
at:http://vm.cfsan.fda.gov/~dms/dietsupp.html.
Accessed August 14, 2009.

5)Guidelines for the Regulation of Herbal


Medicines in the South-East Asia Region.
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