The special complexities of Ayurveda—and the very many mysteries wrapped in a classical drug formulation—pose unique conceptual questions for modern science. And we await the day when modern tools unravel those mysteries. Ayurveda’s historical encounter with modernity and science-based medicine, as well as its tryst with hi-tech diagnostic tools, form the backdrop that we covered in our last article. Here we delve a bit deeper into one of the fundamental realms affected by this conjuncture—Ayurvedic pharmacology. Which is to ask the following questions: What qualifies as an Ayurvedic medicine? How to test them? How to allow new ones? Questions that, as we shall see, open up Pandora’s box of complexities.
The West and the modern scientific community are sceptical about Ayurveda because not enough effort has been spent yet to gain a granular understanding of how a classical formulation works. What the drug does to the body—that is, pharmacodynamics—and how the drug is absorbed in the body and its timeline from the time of ingestion to excretion—the domain of pharmacokinetics—both these remain largely unknown.
The onus is on the Ayurvedic community to amend matters, but the initiative is largely lacking in evolving a methodology for testing formulations and studying the drug activity in detail. Technology investment in Ayurveda has been rather hesitant too. Perhaps a reason why little has been understood about polyherbal formulations, an Ayurvedic staple.
In a real sense, Ayurveda perhaps missed the bus when modern medicine took the leap as new technologies unfolded from the early 20th century onwards. For one, the colonial British promoted only modern medicine; at another, a large section of Ayurvedic physicians also perhaps believed that technology could hardly benefit the ancient healthcare system. That was, sadly, a fallacy: technology is a neutral tool and does not belong to anyone system. Even if allopathy’s concept world would have definitely inflected the development of technology itself, the two are not necessarily synonyms.
Dr P.Y. John, former senior drug inspector, Ayurveda, with the Kerala Drug Controller’s office, has an interesting thought to offer. “Perhaps this ancient science could be known better with nanotechnology,” he says. That’s because on most counts existing modern methods are inadequate to give us a finely-grained picture about how an Ayurvedic formulation works, he says. Many others also believe micro-level investigations conducted using nanotechnology tools could offer new revelations.
But even with little patronage from the powers that be, Ayurveda continued to serve the people in its own ways. And it not only survived for centuries—itself an informal marker of efficacy—but also thrived in certain places, like Kerala, where a number of subtexts also developed. But modern lifestyles and the movement away from holistic living, as propagated by Ayurveda, inevitably took its toll. It took people closer to modern medicine, which pervaded their lives and psyche as a life saviour even as its graph moved in lockstep with an alarming rise in lifestyle diseases—perhaps longevity increased rather than wellness.
Notwithstanding the all-pervasive presence of modern science, or perhaps because of the core tenets of neutral science, ancient Ayurvedic texts are now being seen as one of the earliest treatises on classification of medicines, their application and mode of administration, says Dr John. The texts are now recognised as rich repositories of high empirical and taxonomic standards: such are the specific details they contain on how, why, when and to whom a drug should be administered. Barring some social distortions peculiar to ancient India, this holds true.
But how do we translate ancient wisdom into a language comprehensible in our times? While the Ayurvedic Pharmacopoeia of India (API) now has about nine volumes, with monographs on single drugs and basic standards for about 600-odd classical formulations, a new drug formulation is a major challenge for the Drug Controllers.
What is a ‘new drug’ in Ayurveda?
Tough question. The fact is, the Drug Control laboratories have no universal standards for testing new drugs as the standards are fixed by the originator pharmaceutical company. One of the main drawbacks here is that unless specified by the company, the ingredients of the new drug cannot be known. So it’s often in the absence of details on a new combination—and a private, patented ‘standard’ as against a common one—that a drug gets marketing approval after studies support the drug’s validity.
What studies? The protocol is this: the results of a clinical trial or pilot study by the drug company are submitted to an expert committee under every State Ayush department for approval and grant of a drug licence. Unfortunately, this internal report, which lists the details of the new drug, is never made available in the public domain such that the Drug Controllers can refer to it in future when they may have to inspect them.
According to Dr John, this leaves the Drug Controller with a rather narrow mandate. They inspect only the physical/material attributes of the drug—texture, hardness, consistency, things at that level. And then a chemical analysis to judge for the presence of toxic elements. Nothing in this can count as a real pharmacological analysis. He feels a real beginning could be made if the drug companies at least share their own standards for their new drug, with all the ingredients clearly specified, so that these can be checked in future against some known parameter. The real rubicon is crossed when each ‘reformulation’—each new combination of elements—is tested for safety as well as efficacy. By universal protocol, the ball is in the court of the companies who do clinical trials.
Here, besides paucity of trust, there’s another dilemma now: the much-debated scrapping of three-phase clinical trials for any new drug which contains ingredients that have been part of classical formulations. This is merely the victory of the pharmaceutical lobby, says an Ayurvedic drug formulary expert, who feels the logic behind the move is rather absurd. Just because the ingredients used in a new drug are time-tested, it cannot be the benchmark for automatic approval when used in a new drug formulation.
Its votaries say the benefit of this relaxation can be considered as part of allowing ‘reformulations’ to be developed through clinical wisdom—allowing them to be marketed as new products. Clinical wisdom is a valid factor to be considered if we take Ayurveda to be a science capable of renewing itself. However, there’s a counter-question. If a classical formulation is to be repurposed for any indication other than those mentioned in the texts, surely some sort of validation is required before it can be used on people? Is there a more foolproof way than a three-phase clinical trial?
Given the loosely regulated nature of the market in Ayurveda pharmaceuticals, many believe an Ayurvedic rationale could be missing altogether in various new drug combinations. With over 9,000 small, medium and large Ayurvedic pharmaceuticals across the country, even if the parameters of Good Manufacturing Practices are met, there could be many who could be producing drugs that may not have any Ayurvedic value. Besides, some herbal extracts that may not be harmful per se may only be placebos, giving only an aura of Ayurveda.
Modern medicine doctors argue that herbal extractions could also be harmful for the liver and kidneys as many cases have come up in various hospitals because of Ayurvedic drug complications. However, their Ayurveda counterparts say that herbals may turn toxic only if large quantities are consumed over an extended period—usually seen in patients taking to self-medication. The common notion that Ayurvedic drugs are ‘safe’ under all circumstances is misleading and a distortion of how Ayurveda itself would describe it: herbal medicines are meant for specific reasons, in specified doses.
At any rate, safety is a key component of why clinical trials are important. This is especially so when drugs containing mineral and metal elements are used in new combinations or even if there is a different dosage of the classical formulation, says Dr S. Anand, associate professor, Department of Rasasastra and Bhaishajyakalpana, Government Ayurveda Medical College, Thiruvananthapuram.
When formulations comprising heavy metals like mercury or semi-poisonous herbs like datura (Datura metel) or strychnine (Strychnos nux-vomica) are merely converted into a different drug delivery system—for example, a change of form from kashayam to capsule—a pilot study would suffice if there is no change in dosage. But the same drug with a different dosage would require safety studies and clinical trials before being approved, he adds.
Even the WHO’s guidelines for the Methodologies for Research and Evaluation of Traditional Medicine says that new herbal medicines, a new indication for an existing herbal medicine, or even a significantly different dosage or route of administration call for a very similar application of the general principles and requirements for a clinical trial as those that apply to conventional drugs.
In some cases, however, the design of such studies must be adapted to deal with the particularities of herbal medicines. While randomised controlled clinical trials provide the highest level of evidence for efficacy, that method may not always be feasible as they may involve ethical issues as well as technical problems. For example, it may not be possible to have placebo control if the herbal medicine has a strong or prominent smell or taste. That’s partly why while most researchers in the industry believe clinical trials are the benchmark for any new drug development, pharmaceutical companies may have a different approach.
Dr P.R. Ramesh, the chief clinical researcher at Arya Vaidya Sala, Kottakkal, is a votary of well-founded experimental freedom with a pragmatic approach. For instance, could the source of known ingredients, where chemical profiling is available, be widened? Instead of a whole herb, probably just the bark could be more effective, or the leaves. Also, since the texts are millennia old, one has to consider possible environmental effects on a plant’s development, besides changes in the nature of diseases too over time, he says. For him, live clinical wisdom is what must guide such experiments in drug development; this could also help conserve rare plants. Ayurvedic science does give physicians the flexibility to use known ingredients in a variety of proportions without losing out on Ayurvedic rationale, he adds. If such small variations have to go through a three-phase clinical trial all over again, it does not prove any point, he feels. Toxicity studies, wherever applicable, and pilot studies to test efficacy would suffice, he says.
Clinical trials are cost-intensive and have extensive timelines—which makes the process of getting a new drug into the market a long one. At least a year is required for even fast-track clinical trials, and it could cost over Rs 10 lakh. It may take another two years to get the report published. Toxicity studies that precede clinical trials could take about a month and costs vary between Rs 50,000 and a lakh.
Modern Processing: Is There an Issue?
Manufacturers have largely adopted modern methods of drug extraction—that is, isolating the active ingredients from the source. Many of them use methods that incorporate the old Ayurvedic method, so do not see modern methods as a deterrent, only an enhancer. But there remain unanswered questions. The Ayush Ministry has recommended drug extractions in 50% hydro-alcoholic solutions—different from water extractions—because that increases the yield. But while the mass production rationale is clear, perhaps it leaves certain grey areas, says Dr Ramesh. Researchers like him wonder if there could be changes at the molecular level in such extractions. No studies have come out into the public domain that would clarify matters, he says.
Dr A. Rajendra Prasad, chief executive officer, SG Ayurveda, Coimbatore, points to another major flaw in modernising manufacturing processes. Products are being manufactured in bulk essentially with the support of biochemists, biotechnologists and other experts who have no background in Ayurveda and its basic principles. Ayurvedic doctors are merely asked to endorse these products for licensing. And thousands of such products target physicians and retail outlets, with companies claiming them to be genuine and effective. At a parallel level, even Drug Controllers appointed to oversee new products are often clueless about Ayurvedic pharmacology—though Dr John says there has been a positive move from the Ayush Ministry recently on this front. So far, the expert committee’s recommendations are being taken at face value. But now, Drug Controllers related to Ayurveda must be qualified enough to understand Ayurvedic pharmacology. If implemented, there will be better checks on which products get a marketing licence.
Certainly, not all new products can be looked upon as suspect. Many new products developed using modern methods have given positive results, says Dr A.N.N. Nambi of SNA Oushadashala, Thrissur. New drug development based on clinical wisdom is fine—these entail only a slight modification of existing formulas or a combination of two or three formulations, or a readjusted proportion of the same classical yoga. These can give good results because they are based on the same expression as prescribed by the classical texts, says Dr Nambi.
But when new drugs are made by picking up and combining various herbs based on a common characteristic vis-à-vis controlling a specific condition, it is not based on any Ayurvedic rationale. For example, if various herbs good for haemorrhoids or ano-rectal disease are collected and put together to form a powder or tablet, it does not make sense because there may be many herbs that do not combine well—and may have an antagonistic action. This is plainly against the principles of Ayurveda, says Dr Nambi.
Dr Sheela Karalam, researcher at Vaidyaratnam Ayurvedic Research Centre, Ollur, says a number of herbal preparations are described as ‘Ayurvedic’ even though they do not in any way conform to the principles of Ayurveda. There are several such examples in the market, for example the sheer variety of cosmetic products or ‘Ayurvedic’ food supplements. Herbal extracts mixed together and sold as ‘Ayurvedic’ hair care oil is mislabelling too, she adds.
Some of this indeed looks like a lawless frontier. Given this backdrop, Dr P. Rammanohar, director, Amrita Advanced Ayurveda Research Centre, agrees that regulations are necessary to prevent malpractices. But regulations must help the system to progress and be relevant to Ayurveda, he adds. Loopholes can be found in every set of regulations, but the existing regulations can perhaps themselves be seen as a large, functional loophole. When products that catch the public eye have flooded the market, it is even more imperative that the basic questions of pharmacology are addressed.
(The writer is an independent journalist based in Kochi, and covered health for The Hindu for 20 years. This report was supported by a grant from the Thakur Family Foundation. The foundation did not exercise any editorial control over the contents of this report. The next article in this series will look at the buzzing field of research within Ayurveda.)
