by Dr. M.D. Nair – Consultant to WHO and an Advisor to Government and Private Organisations on Science & Technology, Member of the Task Forces for Pharmaceuticals and Biotechnology Projects for the Governments of Andhra Pradesh, Gujarat, Kerala and Tamil Nadu and Director of the Boards of many Pharmaceutical Companies, Governing Councils of various Academic Bodies, Department of AYUSH, Ministry of Health, Kerala State Medicinal Plant Board, All-India Council of Technical Education, Export Promotion Council of India, etc.
During the last one hundred years, modern systems of medicine, including diagnostic methodologies, prophylactic measures for prevention of a number of communicable diseases and a host of therapeutic agents, have dominated the healthcare scene around the World. Prior to that, populations suffering from ill-health of various kinds and aetiology depended on several indigenous systems. While Modern Medical System, its products and practices have immensely contributed to improvement of the healthcare status of global populations, eradicated small pox, polio and guinea worm infestation , reduced disease- related morbidity and mortality and increased life expectancy, the time has come to evaluate the current limitations of the System. What are these limitations?
New Drug Discovery Research
One of the major costs for the management of healthcare is related to the costs of drugs and medical treatment in general. New Drugs are largely discovered and developed for distribution around the globe by the powerful group of healthcare companies mostly operating in the Developed World, dominated by countries of North America, Western Europe and Japan. The global market for pharmaceuticals alone, which is just one component of Health care, had crossed a trillion dollars in 2013, since growing at an annual rate of around 4%, while the growth in the developed world has been marginal, the economically emerging markets show a much higher growth rate. The industry continues to be the most R&D- intensive industrial segment with annual spending of > 85 billion dollars with the top 30 companies each spending $ 4 to 15 bio per year on this activity.
Investments of that order in R&D are considered necessary since the marketing of new drugs to meet unmet medical needs continues to be the lifeline of the industry and the primary conduit for its survival and growth. The costs of discovering a new molecular or chemical entity through the current and established approaches are estimated to be around $ 1.5 billion for every single drug reaching the market, which includes the costs of discovery research, pre-clinical and clinical investigations, regulatory approvals and marketing expenses in addition to the costs of failures.
The Negatives of Modern Medicines
1) Modern medicines hardly ever are successful in treating and curing chronic illnesses. They are primarily useful for alleviating morbidity resulting from disease conditions.
2) Being primarily of chemical origin, invariably, all of them pose problems of unacceptable adverse effects, particularly when used over long periods of time.
3) Being agents for treatment of symptoms of diseases , they need to be taken for life- time. Apart from the adverse effects they cause, chronic treatments imply heavy economic burden on patients. Examples are drugs for Cardiovascular Diseases, CNS disorders, Diabetes, Lipid disorders, Musculoskeletal diseases, Cancer, Endocrine and Gastrointestinal diseases etc.
4) Due to economic reasons and poor returns on investments, many diseases of the poor are not targets for R&D efforts by large Pharma Companies.
5) New drug research is moving into biologicals developed through modern sciences of genomics and proteomics.
6) Companies are shifting their focus to developing personalised medicines rather than blockbuster drugs.
7) The costs of treatment for these drugs are prohibitively high and unaffordable even to the patients in upper income countries. The costs of treatment with modern biotechnology drugs average > $ 50,000 per course of treatment in the U.S.
8) The high level of technology used for their production and the patent system prohibits the introduction of lower cost generic versions of these drugs.
9) Current approaches to new drug discoveries use in-vitro and animal (in-vivo) models which do not represent true human disease conditions. Hence failure rates in drug discovery are unacceptably high.
Compulsions to Look at alternate Approaches
The Pharma industry is, therefore, compelled to look at alternate and more productive and cost-effective approaches to make much- needed new treatments available. These include 1) a re-look at available drugs to make them better through development of new delivery systems 2) evaluation of existing drugs for new indications 3) Ensuring better distribution of drugs at lower costs and 4) Looking at Alternate Systems of Medicines used for several hundred years to complement modern medical systems.
Traditional Systems Of Medicine
These systems of Medicine, including practices and products, have been used by communities as long as they existed in developing countries, several thousands of years before modern medicines surfaced as a treatment modality. In a way, notwithstanding the so-called ‘evidence-based’ therapeutics, that modern medical system is presumed to have established, faith in and use of Traditional Medicines continues in most of the countries. While in the past, practice of these systems was largely localised with traditional healers offering healthcare to the communities in their vicinity, due to increased interest in the outside World, including the developed countries, there is a resurgence of interest in the globalization of these systems.
The Indian Scene
In India, between the main streams of indigenous systems (ISM recently renamed as AYUSH), namely Ayurveda, Siddha, Unani and Homeopathy, there are over 7000 manufacturing units, of which over 85% are in Ayurveda. Over 99% of these units are in the tiny sector, with annual turn-over ranging from 20 Lakhs to 2 Crores. The largest purely ISM company has a turn-over of around Rs 200 crores. Emphasising the interest for promoting and providing quality delivery of these systems, the Government of India has set up a separate Department of Indian Systems of Medicine and Homeopathy, (AYUSH), which also funds research carried out under the Central Council of Research in Ayurveda and Siddha. Several schemes to ensure rational and sustained availability of the needed medicinal plants are on the anvil. Documentation of Traditional Knowledge and practices under TKDL (Traditional Knowledge Digital Library) is a major project of the Council of Scientific & Industrial Research(CSIR) and the Department of Indian Systems of Medicine, with the objective of ensuring that these assets are not patented and exploited unauthorisedly by third parties. There are over 2500 TM Hospitals and 400,000 institutionally- trained practitioners of ISM &H in India.
While reliable information on industrial activity in this sector is not readily available, it is estimated that the annual total market for the products of Indian systems of medicine is of the order of Rs. 5000 Crores in the domestic market and around Rs. 500 Crores in exports. Both in turn-over and in the number of units , Ayurveda constitutes over 85 % of the total, which is followed by Homeopathy, Unani and Siddha. In the case of the number of Hospitals, Educational Institutes and Practitioners, the same order prevails. Of the 7000 Units, only around 35 have sales of over Rs 5 Crores per annum, the majority of the balance are in the range of Rs. 50 lakhs to Rs. 1 Crore. Of the larger Units, most of them market proprietary products, developed from the knowledge base of the traditional systems converted to various modern solid and liquid dosage forms. Due to concessions in excise and sales tax and exemption from price controls, several products are marketed under the traditional systems label, with little resemblance to their heritage. A few products of the larger companies have also established a certain degree of Brand Equity, particularly for products in the therapeutic areas where modern medicines offer only palliative therapy, such as Rheumatic disorders, Chronic Respiratory diseases , and Skin diseases. Practically none of them have been validated clinically to satisfy modern standards of assessment of their safety and efficacy.
Research On Indian Systems Of Medicine
Ayurvedic drugs largely rely on the use of medicinal plants which have been traditionally used for hundreds of years for their therapeutic properties. A few preparations do contain minerals, metals and metalloids which, according to the classical texts, do not possess any toxicity issues when processed according to established methods. However,
this aspect needs to be looked into to establish unequivocally that they do not possess hepatic or other toxic effects as has been alleged in certain publications a few years back. Other issues of concern are related to the quality of the drug with respect to sourcing of raw- materials, processing under GMP standards and ensuring appropriate quality assurance systems. A systematic approach to standardise these preparations and to ensure that there is no batch- to- batch variation in quality is essential. Each raw- material that is used should be subjected to qualitative and quantitative analysis , if necessary by using specific markers identified for that purpose. Extraction and processing technologies should, to the extent possible, rely on mild conditions to avoid degradation of active principles contained in them. Once the standardised preparations are available, they should be subjected to minimal animal toxicity studies preferably in two species, the rodents and mammals. Since no final parenteral formulations are involved, oral dosing would suffice for both acute, sub-acute and chronic toxicity studies. It would also be necessary to carry out confirmatory tests to prove efficacy in animals and in humans through abbreviated clinical trials.
A product which passes through these steps of development would qualify for acceptance even in Western Countries, since these efforts would ensure evidence-based therapy rather than reliance on empirical and sometimes even anecdotal data.
Regulatory Requirements For Ayurvedic Drugs
In India, the standards required for manufacturing and marketing of Ayurvedic drugs are considerably less stringent than for modern drugs. According to the definitions under the Drugs & Cosmetics Act 1940, Ayurvedic drugs are classified under Clause 3-a and Clause 3-h , the first falling under classical preparations and the second under Patent & Proprietary Medicines. Classical preparations are defined as those
manufactured exclusively in accordance with the formulae described in the classical texts on Ayurveda, Siddha and Unani Tibb Systems of Medicine, specified under the First Schedule. The list has 54 Books in Ayurveda including the recent Ayurvedic formularies. The classical texts include Ashtanga Hridaya, Ayurveda Samgraha, Charaka Samhita, Sahasrayoga, Sushruta Samhita, Ayur Chintamani, Dravya guru Nikanta and others. Patent & Proprietary medicines are defined as those formulations which are produced and packaged based on the classical texts, but not included under classical formulations. For example, a large number of Arishtas, Ghritas, Churnas, Rasayanas and Ras are produced, packaged and marketed in modern galenic forms ), of tablets, capsules, powders, syrups, ointments or even gels. Today, in the open Indian market, over three fourths of the drugs sold under the Ayurvedic label are branded versions of the drugs classified under Patents & Proprietary medicines, which have no resemblance whatsoever with the classical Ayurvedic products. Under the new Schedule T all medicines falling under ISM should satisfy GMP standards stipulated under that Schedule.
In view of the shortcomings of modern medical system and its practices, there is a need to look at well- established and clinically- accepted systems of traditional medicines. Both due to the long heritage of its use as well as the documentation available, Ayurveda , among the major Indian Systems of Medicine, deserves to be evaluated to supplement and complement available modern therapeutic modalities. To ensure that this can be done, it is essential that adequate evidence- based trials are carried out as per modern trial protocols and limited safety data generated to gain regulatory approvals from even the most regulated markets. For many diseases for which modern medicines have little to offer even for control of the disease processes, let alone their cure, resort to Ayurvedic products and practices may add considerable value and provide much- needed benefits for ailing humanity. To achieve this , there is an urgent need to set up a fully- integrated program for the development of Ayurveda, which will meet the standards of efficacy and safety stipulated by even the most stringent regulatory agencies.