1. REGULATORY ASPECT
FOR HERBAL
MEDICINES
Presented by:
Vishal ganda
M.Pharm (2ndSem.)
Parul Institute of
Pharmacy
Guided by:
Mr. Rikin Patel
Asst. Professor
Parul Institute of
Pharmacy
1

2. I N D I A
2

3. 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.
3

4. 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
4

5.  Herbal drug products constitute a major
share of all the officially recognized
systems of health in India,like
Ayurveda, Yoga, Unani, Siddha, Homeopa
thy 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. 5

6. 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
6

7. ICMR’s 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 Initiative
7

8. 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.
8

9. MAJOR ACTIVITIES
 Status Report on propagation techniques
of Pterocarpus marsupium, Saraca
indica and Streblus asper – IHBT,
Palampur.
 Agrotechnology of P. kurroa, IHBT,
Palampur
 Clinical trial with Vijayasar (Pterocarpus
marsupium) in Chronic Diabetics
 Survey of Medicinal plants of Western
Ghats
9

10. 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
10

11. 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
11

12. 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
12

13. 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
13

14. 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.
14

15. 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.
15

16. 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 DCGI’s
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
16

17. 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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18. 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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19.  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.
19

20. 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
20

21. 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. Reddy’s Lab, Hyderabad, Andhra Pradesh 21

22. E U R O P E
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23. 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)
23

24. 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)
24

25. HMPC - Tasks
 Monographs
 List entries
 Scientific opinions
 Coordination
 Scientific advice
 Questions
25

26.  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).
26

27.  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. 27

28.  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.
28

29. 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 29

30. United States of
America
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31.  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.
31

32.  FDA’s 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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33.  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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34. 34

35. 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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