For better regulation

Print edition : February 10, 2006

The country needs an effective regulatory framework to govern the production, sale and distribution of medicines prescribed by indigenous systems such as Ayurveda and Unani.


Samples of medicines produced by the Divya Yog Pharmacy.-T.K. RAJALAKSHMI

THE alleged violation of the provisions of the Indian Drugs and Cosmetics Act (DCA), 1940, which governs the production, sale and distribution of drugs including those of the traditional systems of Ayurveda, Siddha and Unani (ASU), by the Divya Yog Pharmacy in Uttaranchal in the production of Ayurvedic formulations has once again brought into focus the weak regulatory framework that exists in the country. The pharmacy is run by the popular yoga guru Ramdev.

The medicines in question were found to contain undeclared ingredients, including bones and other human and animal matter. The existence of such matter per se does not violate any of the regulations because the system of Ayurveda, as codified in the 56 ancient texts recognised under the DCA, allows the use of such substances in the preparation of certain formulations, scientists point out. That is, Ayurvedic medicines, though primarily herbal formulations, are not strictly speaking "vegetarian".

"Only about 15 per cent of Ayurvedic products use substances of animal origin," says M.S. Valiathan, a leading medical scientist and an authority on the well-known ancient Ayurvedic texts Charaka Samhita and Susruta Samhita. According to him, while milk and urine are more commonly used - and these would reveal animal/human DNA in DNA fingerprinting - the literature he is familiar with does not mention use of animal or human tissues and bones. However, according to a member of the Central Council for Research in Ayurveda and Siddha (CCRAS) under the Department of Ayurveda, Yoga & Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) of the Union Ministry of Health and Family Welfare (MoHFW), Ayurvedic drugs use about 2,500 ingredients of plant origin, 150 of mineral origin and 75 of animal origin.

Hence at issue seems to be the Divya Yog Pharmacy's failure to indicate, as required by Rule 161 of the Act, all the constituents of the medicines in their labels. The Ministry has confirmed the irregularities through tests carried out in various laboratories on samples provided by Brinda Karat, a Communist Party of India (Marxist) member of the Rajya Sabha. On December 29, 2005, Shiv Basant, Joint Secretary in AYUSH, informed Brinda Karat that there was prima facie evidence of "violation of licensing and labelling provisions of the DCA". Under Section 33EEC of the Act, such "misbranding" of the drug can attract the revocation of licence for its "production, sale and distribution". The Centre has instructed the Uttaranchal government to initiate appropriate action.

EXACTLY a year ago, scientists from the Harvard Medical School, led by Robert Saper, investigated 70 Ayurvedic herbal medicines manufactured by 27 companies (26 Indian and one Pakistani) purchased from 30 stores in and around Boston, United States. Of these, 14 (20 per cent) were found to contain heavy metals such as lead, mercury and/or arsenic, which could result in their daily intake being higher than the safety limits set by U.S. Pharmacopoeia or the U.S. Environment Protection Agency (EPA). Besides, some of the products contained metals such as gold, silver and tin. Most of these were manufactured by well-known Indian Ayurvedic brands. Canada issued an alert against the consumption of these drugs. Moreover, it set off an alarm in the West against Ayurvedic herbal medicines. Singapore too independently identified a few drugs from a reputed manufacturer as having high heavy metal content and withdrew them from the market.

In a knee-jerk reaction, the Indian government introduced regulations in October 2005 with regard to heavy metal content in Ayurvedic formulations, but, interestingly, only with the export market in view. The notification of October 14, 2005, made testing for arsenic, lead, mercury and cadmium "mandatory for export purposes in respect of every batch of purely herbal ASU drugs by every licencee".

Permissible limits for arsenic, lead and cadmium are as per the recommendations of the World Health Organisation (WHO) and, in the case of mercury, the permissible limit is one part per million (ppm). The regulations now require that from January 1 the container of ASU drugs to be exported must display conspicuously the words "Heavy Metals Within Permissible Limits". This self-certification is yet to be made mandatory for sale within the country. In October 2005 itself the Centre sent an advisory order to the State licensing authorities to ensure strict compliance to Good Manufacturing Practices (GMP) under the Act by ASU drug manufacturers and cancel the licences of those who do not comply.

However, the point to be stressed is that such irregularities should have come to light not through investigations of individuals or foreign agencies but by the state regulatory regime of inspection and monitoring of drugs as required under the Act. The inadequacy of the system for Ayurvedic drugs, as regards documentary evidence of safety, efficacy, standardisation and quality control methods, was pointed out by the Mashelkar Committee Report in November 2003.

"The entire issue of quality control of Ayurvedic drugs has unfortunately come up only with increasing export of these to the West. Although I have been saying for long the need for standardisation in the country, little has been done," said G. Satyavati, former Director-General of the Indian Council of Medical Research (ICMR) and a scientist credited with the identification of a plant-based molecular drug using knowledge from Susruta Samhita. She said: "Often because of commercial pressures, manufacturers resort to outsourcing raw material and products leading to poor quality of the drugs. And evolving standardisation for herbal drugs is difficult because Ayurveda is based on poly-formulations, and the dose is individual-dependent and often based on the principle of anupama (drug consumed along with a fluid vehicle)."

Despite the increasing popularity of herbal medicines and herbal cosmetics abroad, it would seem that Ayurveda is yet to gain wider acceptance among medical scientists internationally. Consider the following: In 2002, there were three reviews of traditional medical systems in the New England Journal of Medicine, but none of them even mentioned Ayurveda. The journal refused to publish a letter to the editor from Bhushan Patwardhan, director of the Inter-Disciplinary School of Health Sciences, University of Pune, and his associates on the omission of what perhaps is the world's oldest system of traditional medicine. Other journals too, according to Patwardhan, have not included Ayurveda in their studies and analyses. A Time cover story on traditional medicine omitted it. Apparently, all this happened because of the authorities' failure to evolve an effective regulatory framework and the scientific community's failure to put the system on a sound scientific footing.

In a recent editorial titled "Ayurveda: Putting the House in Order" in the journal Current Science, Valiathan wrote: "What should really concern us is not the analysis of herbal products done by Western workers, their bias against Ayurveda or the opinion of a committee in the U.K., but what we have done to safeguard the health of our people and promote the science and healthy practice of Ayurveda in India... . The herbal products industry in India is on a cusp, eyeing the global market with eager anticipation. These are signs of vitality for Ayurveda, but growth in an unequal and competitive world calls for more than vitality."

Thus, while in the case of allopathic drugs the chief problem is of spurious drugs, the issues regarding Ayurvedic drugs are more complex. Under the DCA, licence is issued solely on the basis of the description of a certain formulation in any of the 86 (56 of Ayurveda and 30 of Siddha) officially recognised ancient texts, whose interpretation and methods of preparation could vary from one vaidya to another and from region to region. The raw materials, such as the herb extracts, too would vary from place to place. Therefore, standardisation and quality control can be only in terms of safety of a drug and not with regard to its efficacy, points out Valiathan.

Although the Act brought within its ambit ASU drugs in the 1960s, it is incomplete and inadequate and has failed to evolve with growing knowledge, says Valiathan. He notes: "For instance, extensive use of herbicides and pesticides in today's agricultural practices and the resultant contamination of herbs, or heavy metal residues from groundwater which go into plants, are not factored in. There is also no regular updating of the Ayurvedic formularies [list of drugs from the classical texts and other sources] prepared by the government and included among the 56 texts under the Act."

The Mashelkar Report observed: "[S]everal national laboratories and organisations have brought out research-based compilations involving experts of indigenous systems of medicine and modern scientists, which have clarified anomalies and have provided interpretation of the well-known [ancient] books and recipes. There is a need to review and update the list of books included." Interestingly, while currently the formulary includes 635 formulations (of which 431 have some kind of pharmacopoeial standards specified), there are over 1,000 formulations in the market. How were these licensed in the first place?

Given the traditional nature of the system going back to thousands of years, licensing in the present regulatory framework allows manufacture of drugs by a vaidya or hakim who just has to be "registered in a State Register of Practitioners of indigenous systems of medicine, having experience of at least four years in the manufacture of ASU drugs". According to Patwardhan, there are about 400,000 registered practitioners of indigenous medicine. Given the numbers involved, there can be no effective mechanism, particularly at the State level where the State Drug Controllers are not usually equipped to deal with indigenous systems of medicine, to ensure that the registered vaidya or hakim has the requisite skill and expertise. Besides, the Act allows ASU drugs to be produced unlicensed if the drugs are not marketed, but prescribed by the practitioners to their own patients. "This is a very contentious issue because how does one verify the claims of a practitioner? And the issue concerns thousands of very small-scale industries run by such people. There is no ready solution for this problem," admits Valiathan.

The most important lacuna in the regulatory framework for the indigenous systems of medicine, particularly Ayurveda, is the lack of a national pharmacopoeia, Valiathan points out. In the absence of such a reference document, many Ayurvedic drugs enter the export market as nutriceuticals or dietary supplements, thereby evading the drug regulatory authorities of other countries. "The pharmacopoeia should include the botanical identity of plants, other constituents, processing, pH [measure of acidity/alkalinity], content of solids, fats, metals, shelf life, and so on. It should prescribe the labelling procedure too. Without such a reference there is no way to ensure quality or set norms for good manufacturing practices. The present pharmacopoeia and other documents of the Ministry do not contain many of these," says Valiathan.

According to a recent performance audit of AYUSH by the Comptroller and Auditor General (CAG), even after four decades of constituting pharmacopoeia committees for evolving uniform pharmacopoeial standards for the preparation of ASU drugs, the task has not been accomplished. Development of these standards was the responsibility of the Pharmacopoeial Laboratory for Indian Medicine (PLIM), Ghaziabad. But, according to the Union Health Ministry, this could not be achieved because of lack of accepted Standard Operating Procedures (SOPs). "Committees achieve little. It has to be a science-based project, as a joint R&D effort between AYUSH and national laboratories, say, the CSIR [Council of Scientific and Industrial Research]," says Valiathan.

An important component of a regulatory system is testing centres for ASU drugs, particularly for post-market surveillance in the case of traditional medicines. Unfortunately, there are very few laboratories that are accredited under the National Accreditation Board for Testing and Calibration Laboratories (NABL), points out Patwardhan. The issue again stresses the need for a national pharmacopoeia for ASU drugs that sets out the protocols and methodologies of their preparation. According to the CAG, the Health Ministry launched a Centrally sponsored scheme towards ensuring quality control of ASU drugs in 2000-01. This scheme included strengthening and upgrading the 21 State-level drug testing laboratories (DTLs) with a funding of Rs.1 crore a unit. Nothing happened even after five years because the Statesa either did not release or delayed the release of funds.

The Parliamentary Standing Committee on Health noted in its April 2005 report that even the PLIM was functioning without a director. It noted that the Health Ministry had failed to provide adequate staff to the laboratory.

Although budgetary allocations had been substantially increased during the Tenth Plan to improve its infrastructure, the amounts were drastically and inexplicably cut at the Revised Estimates (RE) stage, the report said. The committee observed that, despite the increase in the number of spurious herbal and Ayurvedic products, the feedback from the States was scant with regard to testing drug samples in the market and AYUSH had failed to ensure that the State Drug Controllers enforced the regulations.

The committee expressed surprise that though a Drug Control Cell for indigenous systems of medicine was set up under AYUSH, it had so far not handled any case of misbranded/adulterated and spurious drugs. In response to this observation, the Health Ministry stated in December 2005 that it would appoint an Additional Drug Controller and four drug inspectors to assist the Drug Controller General of India (DGCI) in the task of quality control of AYUSH drugs. Clearly, this points to gross laxity towards quality control of ASU drugs by the Ministry, resulting in Ramdev-like cases. For every case discovered, there would be several hundreds of firms thriving in their business with questionable formulations.

On the recommendation of the Parliamentary Standing Committee, AYUSH has undertaken a study of the toxicity/safety profile of metal-based bhasmas, an important component in the preparation of Ayurvedic drugs. Bhasmas are essentially processed metallic compounds including those of heavy metals. Eight most widely used bhasmas have been chosen for analysis under a joint project of AYUSH, the CSIR and the ICMR. The use of heavy metals in the practice of Ayurveda, with no apparent harmful side effects for centuries, requires a thorough science-based investigation into the forms in which they occur after the very complex and detailed method of detoxification and purification (shodhana) over seven or eight days that is supposed to be followed, says Valiathan. It is quite possible that the methods are not strictly followed, given the present-day commercial exigencies, leading to their occurrence in nascent elemental form, in which they are toxic.

According to Patwardhan, there is a very complex chemistry involved in making a bhasma which, as per Ayurvedic definition, should be devoid of free metallic content. Moreover, he says, it is just not metal oxide resulting from combustion but a very complex bio-organo-metallic compound. Apparently, some investigations have revealed the presence of nanoparticles in genuine bhasmas. Given the larger surface area of nanoparticles as compared to atoms and molecules, it is possible that in these forms they do not attach themselves to tissues or accumulate producing a toxic long-term effect. But the microstructure of heavy metals in Ayurvedic drugs has never been studied as a pure scientific question. That is required for standardisation and quality control of the bhasmas. "I strongly believe that many new scientific leads and therapeutic applications might emerge from such systematic research on bhasmas," he says.

Study of heavy metal microstructure in bhasmas is only one of the several important scientific issues that need to be investigated, points out Valiathan. "Unfortunately," he says in the Current Science editorial, "research in Ayurveda has become identified with herbal products to the detriment of much else that is valuable in this ancient system of knowledge." According to him, these issues are different from drug development and clinical research, and include such questions as do dosha prakritis, which are specific to the individual and determine the manifestation of the disease in the individual, have any genomic counterparts? Does the highly popular panchakarma, which apparently detoxifies the body, alter the biochemical and immunological profile of a person? Do rasayanas speed up the healing of DNA chain breaks? Would they inhibit the accumulation of beta-amyloid in the brain of mouse-model of Alzheimer's? The answers to these and a host of similar questions could become the building blocks of Ayurvedic biology, Valiathan feels.

Valiathan has recommended a multi-institutional, coordinated study of the issues. It should go hand in hand with the publication of a complete Ayurvedic pharmacopoeia of, say, 1,000 widely used products and introduction of an effective post-market surveillance and testing mechanism to develop an effective science-based continually evolving regulatory framework that will help generate faith in an indigenous medical system that has stood the test of time for millenia.

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