Ayurvedic Herbal Industry: QUEST for Global Acceptance
Dr Arun Bhatt MD (Med) FICP (Ind) MFPM (UK)
President
ClinInvent Research Pvt Ltd
Mumbai
arunbhatt@clininvent.com
Introduction
Worldwide, alternative medicine is becoming popular and herbal medicine has become one of the
most common forms of alternative therapy. The international herbal market is approximately $61
billion. Annual sales of herbal medicinal products (HMPs) are approximately $3 billion in Germany
and $1.5 billion in the US. 1
Annual turnover of Indian Ayurvedic industry is $ 0.8 billion (Rs 35,000 million). 2 The Indian
market is growing at 15-20% per annum (Rs 7,000 million or $150 million). With world demand
growing at 1% annually ($ 610 million), the size of export market for medicinal plants appears
bigger than the Indian domestic market. As compared to China, which boasts of herbal exports of
$ 3 billion, Indian exports are dismal - $ 100 million. For Indian herbal industry, there is a huge
export opportunity. However, this QUEST is full of challenges of meeting global requirements of
Quality, Efficacy, Safety and Standardization.
Challenges
As the global market is big and expanding, the Indian herbal industry is focusing on exports. From
a global perspective, critical challenges for herbal industry are:
 Regulatory concerns
 Consumer perceptions
 Competition
Regulatory concerns
The regulatory agencies, world over, are focusing on:
 Quality
 Efficacy
 Safety
 Standardization
of herbal medicines. The new guidelines from US FDA and EMEA cover the need for
documentation in the above areas.3
Quality – A Major Concern
Quality of herbs has become a major concern following reports of heavy metals in Indian herbs.4-6
Adulteration of plants is a serious problem. Some of the common adulterants are: botanicals,
toxic metals, microorganisms, microbial toxins, pesticides, and fumigation agents. One study
showed that 64% of HMP samples collected in India contained significant amounts of lead (64%
mercury, 41% arsenic and 9% cadmium). 5 A recent Harvard Medical School study reported that
14 (20%) of 70 HMPs contained heavy metals.6 However, this problem is not unique to
Ayurvedic medicine. Other traditional medicines – Chinese, Middle East and South Americanhave also been implicated. 6 Such contamination can lead to serious harm to patients taking such
remedies and could also interfere with the assessment of safety in a clinical trial. Quality has to
be assured at all stages – herbal raw materials, processing of herbals and finished herbal
medicines.
1
Substantiation of Clinical Efficacy
One of the major issues with HMPs is lack of good quality clinical trials. Even if the animal studies
or anecdotal clinical experiences are promising and use of an herb is widespread, such
observations cannot predict the results of well-designed randomized, controlled trials.
Some of the Indian medicinal plants - Phyllanthus amarus, Picrorhiza kurroa, Tinospora cordifolia,
Commiphora mukul, Mucuna pruriens, Boswellia serrata, - have been tested in clinical trials.
However, a recent review concluded that evidence-based studies on the efficacy and safety of
traditional Indian medicines are limited. 7 As there are few good quality clinical trials on Indian
HMPs, international researchers have made efforts to confirm Indian data. In a recent double
blind randomized placebo controlled trial, 8-week treatment with guggulipid 1 gm or 2 gm did not
improve levels of serum cholesterol in population of adults with hypercholesterolemia, and raised
levels of LDL-C. 8 Besides, 6 participants taking gugulipid developed a hypersensitivity rash. Such
studies cast doubt on the quality of clinical trials of HMPs conducted in India.
Most regulatory authorities ask documentation on clinical efficacy of HMPs. Department of
AYUSH recommends that manufacturers would be expected to conduct efficacy and safety
studies before licenses are granted for Ayurvedic Patent and Proprietary medicines.2
Safety Issues - Adverse Reactions and Drug Interactions
Herbal medicines are generally considered comparably safer than synthetic drugs. However,
recent reports challenge such assumptions. 9 Ephedra marketed as a dietary aid in USA, led to at
least a dozen deaths, heart attacks and strokes. Other well-known safety issues have been
hepatotoxicity of kava and renal effects of aristolochic acid. Besides, drug interactions of herbal
drugs are of a serious concern. Serious adverse effects have been reported when the addition of
St. John's wort caused serum levels of cyclosporine and antiretroviral agents to fall to sub
therapeutic levels. Garlic is reported to increase clotting time in patients taking warfarin.
WHO has urged the governments to establish regulatory mechanisms to control the safety and
quality of products. 10
Standardization of herbal drugs
For safe and effective use of herbal drugs, consistency in composition and biologic activity are
essential. However, herbal drugs frequently fail to meet this standard, because there are
problems of 1) difficulties in identification of plants, 2) genetic variability, 3) variations in growing
conditions, 4) diversity in harvesting procedures and processing of extracts, and 5) the lack of
information about active pharmacologic principles. 11
In a study of ginseng preparations, the amount of ginsenosides varied from 11.9-327.7% of the
amount on the label 12 Medical letter cautions, “Their (herbal medicines) potency may vary and
their purity is suspect,” 13Australian medicines regulatory body the Therapeutic Goods
Administration, recalled over 1500 HMPs and suspended production license of Pan
Pharmaceuticals after an audit, which revealed problems with company's quality control
standards. 14
The Indian companies must focus attention on quality during the whole process chain from accessing raw materials to finished products – to meet global expectations.
Consumer Perceptions
HMPs have become popular because of perceived safety and economy and inability of allopathy
to cure everything. However, recent reports of contamination and potential for adverse reactions,
2
have tempered the enthusiasm of consumers for these "natural" cures, resulting in decline of
sales of herbal products in the United States.12 The consumers now want more authentic
information on quality, safety and efficacy of HMPs.
The medical perceptions about complementary medicine (including HMPs) are diverse. 15, 16 Some
surveys show that, overall, physicians believe it is moderately effective, while many doctors
regard complementary therapies as scientifically unproved. The doctors' are concerned about 1)
use of such therapies as an adjunct or an alternative to conventional care, 2) comparative efficacy
of complimentary and allopathic therapies and 3) the possibility of adverse effects. In general,
globally, the trend amongst doctors is to support the patients' preferences for complementary
therapies. However, they want published information from reliable sources on quality, safety and
efficacy of HMPs.
Competition
Amongst the countries with herbal resources, China is a major competition. The discovery of
artemisinins as a new class of anti-malarial drugs from Chinese plant Artemisia, has brought
Traditional Chinese Medicine (TCM) practices and Chinese HMPs made attractive for research. A
random search of MedLine showed that number of publications on TCM was >3 times the
number of publications on Ayurveda.
The indications for clinical trials of TCM cover the current medical challenges of Allopathy. Some
of the therapeutic areas of TCM clinical trials are: neurology, oncology, cardiology, diabetic
complications, rheumatoid arthritis etc. These clinical trials are conducted according to scientific
and ethical principles of modern clinical research.
Chinese government highly values the development of TCM and has announced that by 2010 it
will establish a modern TCM innovation system along with a series of standards and norms for
modern TCM products, support development of a number of new TCM products and key
technologies, and encourage creation of a competitive modern TCM industry. The government
efforts are intended to boost the quality of Chinese medicine and enhance China's ability to
compete in world markets.
Conclusions
The future of Indian herbal industry depends on how it prepares it self to face the challenges of
the present – regulatory concerns, consumer perceptions, and competition.
The global regulatory agencies – US FDA, European Community – have made guidelines for
botanicals. 2 Recently, The Australian government has backed increased regulation of the
complementary health sector. These guidelines focus on documentation of the key issues Quality, Efficacy, Safety, and Standardization. Some of these issues will also be applicable to
dietary supplements. The international regulatory authorities would expect the data generated
(pre-clinical, CMC and clinical) should meet the standards of GxPs (Good Practices) – good
agricultural practices, good laboratory practices (GLP), good clinical practices (GCP) and good
manufacturing practices (GMP). These guidelines will make licensing difficult for HMPs. Besides,
the governments are likely to restrict availability of HMPs with toxic potential. WHO has also
recommended that it important for governments 10 to establish regulatory mechanisms to control
the safety and quality of products and of TM/CAM practice.
The consumers – doctors and patients- expect innovation and effective options for chronic
diseases. The industry has to 1) become creative in designing clinical trials, 2) developing
consumer friendly products and 3) effective marketing communication. Table 1 and 2 suggest
some innovative options for developing consumer friendly medicines.
3
The future belongs to an herbal company that is research-focused, quality-driven, regulatorycompliant, consumer-friendly and market-savvy!
References
1 De Smet PAGM Herbal Remedies N Engl J Med 2002 347: 2046-56
2 Department of Indian System of Medicine and Homeopathy Draft National Policy 2001
www.indianmedicine.nic.in
3 Bhatt A D Regulatory Issues for Herbal Medicines Ayurvedline 7th Edition 2004 p 95 -103
4 Ernst E. Heavy metals in traditional Indian remedies Eur J Clin Pharmacol 2002 57:891-6
5 Saper RB, Kales SN, Paquin J et al RS Heavy Metal Content of Ayurvedic Herbal Medicine
Products JAMA 2004; 292:2868-2873
6 Ernst E, Thompson Coon J Heavy metals in traditional Chinese medicines: A systematic review
Clin Pharm Therap 2001 70
7 Ladha R, Bagga A Traditional Indian system of medicine Ann Acad Med Singapore 2000 29:3741
8 Szapary PO, Wolfe ML, Blaydon L T et al Guggulipid for the Treatment of Hypercholesterolemia
A Randomized Controlled Trial JAMA 2003;290:765-772.
9 Stein MC Are herbal products dietary supplements or drugs? An important question for public
safety Clin Pharmacol Therap 2002; 71: 411-13
10 WHO Fact Sheet N°134, Revised May 2003
11 Marcus DM, Grollman AP Botanical Medicines — The Need for New Regulations N Engl J
Med 2002 347:2073-2076
12 Straus SE Herbal Medicines — What's in the Bottle? N Engl J Med 2002 347:1997-1998
13 Problems with dietary supplements Med Lett Drugs Ther 2002 44:84-6
14 Complementary medicines industry in crisis after recall of 1546 products BMJ 2003 326:1001
15 Zollman C, Vickers A . ABC of complementary medicine Complementary medicine and the
doctor BMJ 1999;319:1558-1561
16 Ernst E, Resch KL, White AR. Complementary medicine. What physicians think of it: a metaanalysis. Arch Intern Med 1995 155:2405-8
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Table 1 Clinically Relevant Evaluation of Advantages of Medicinal plants (CREAM)

Holistic therapy for disease and concomitant conditions –
o Poly-herbal for Diabetes mellitus to manage - Hyperglycemia, Hyperlipidemia

Adjuvant synergistic therapy to improve response to primary therapy
o Issues in Tuberculosis treatment - Hepato-toxicity, Immune-deficiency

Niche therapy when there are contraindications or cautions against allopathic agents –
o Arthritis with associated problems - Acid peptic disease, Edema,

Therapy to provide positive side effects
o Cough suppressants and constipation
Table 2 Development Rationale for Enhancing Advantages of Medicinal plants (D R E A M)






Conversion of powder to tablet / capsule / liquid form
Reduction in size of tablet or capsule
Reduced frequency of dosing
Improved solubility providing a liquid alternative for elderly and children
Improved palatability
Potential for parenteral formulation
5