Thursday, April 26, 2007
Ashok B Vaidya
Ashok B Vaidya
India is one of the largest manufacturers of drugs in the world; it is number fourth in the total volume of drugs produced and the thirteenth in terms of the market value. With very low prices of drugs in India, the basic research in new drugs is not only considered difficult but almost impossible to support. Only few Indian companies have engaged in a quest for new molecules, which can be patented globally and probably become blockbuster drugs. Ranbaxy, Dr. Reddy's NPIL, Cadilla and some other companies are now on the learning curve of the drug discovery path.
The current estimates of a new drug, being discovered and launched, are around $1.3 billion. The multinational companies, with huge global sales, are also finding it difficult to be productive in their R&D process. Besides the cost in terms of money, the other constraints are also daunting. It takes one in 50,000 molecules to emerge as a drug. The time taken is anywhere between six to twelve years for the drug to reach market. Hundreds of scientists of multidisciplinary expertise have to dedicate to chemistry, pharmacology, toxicology and clinical research on new molecules. Despite such massive inputs the pipeline of new drugs is almost dry for even the big multinational drug companies. No wonder there is a global rethinking on the conventional way of drug discovery - combinatorial chemistry, genomic-proteomic targets and most expensive toxicity studies and extensive clinical trials. Indeed there appears to be a leadership crisis in pharmaceutical research.
Over the years, without the process patent regime the pharmaceutical industry would not have grown to its current size and quality. But imitation of drug molecules, for too long, by some minor but patent-savvy process variations does not equip research scientists for innovation. And the way sizeable revenue has been generated by imitation, it has led to a mindset of the Indian pharma industrial czars that is of complacency and inertial. There was a one-man crusade against this bleak scenario of "We cannot discover". That person is Dr. R.A. Mashelkar. As the Director General of the Council of Scientific and Industrial Research (CSIR), he received all the accolades and honours by the industry, Government and academia, while he held the office. As soon as he left that position, there was unfortunately an avalanche of aspersions on his integrity and motives. Dr. Mashelkar has expressed his deep pain for the unfounded allegations.
The CSIR under Dr. Mashelkar has emphasised (1) the public-private partnerships in drug research, (2) enhancement of networked projects of CSIR Laboratories in products for defined diseases, (3) the golden triangle approach of integrated research in modern medicine, traditional medicine and basic sciences, (4) new millennium Indian technology leadership initiative (NMITLI) for drugs inspired by Ayurveda, through reverse pharmacology, systems biology and ethnobotany paths, (5) facilitation of intellectual property rights for Indian drugs, (6) enchancing the national property rights and traditional products through traditional knowledge digital library in several foreign languages, (7) personal encouragements to a large number of young drug researchers, within and outside CSIR. The list is quite a long one. The CSIR succeeded in opening up of Indian sciences to global challenges.
What could be the research strategy for pharmaceutical industry in India? The captains of Indian Pharmaceutical industry should prepare for a paradigm shift in new drug research. Then possibly the crisis of leadership will reduce and aping the western model of new drug research will cease. There is a need to include as a mentor on the Board of the Company Directors, leaders of Life and drug sciences, with a proven track record. The mentor would monitor the new drug R&D path of the company and also scan for rapid opportunities.
The industry should also establish excellent post-marketing drug surveillance units in the company for a continued survey of safety, efficacy and novel unforeseen effects. The latter can serve as opportunities in therapeutics. The industry should also consider: To sponsor hospital facilities of excellence for phase 0, 1 and 2 clinical trials and human pharmacology. Only judiciously the contract research organizations, have to be used for defined projects on phase 3 and special studies; to promote the novel Reverse Pharmacology path, by sponsoring units of Pharmacoepidemiology and Observational Therapeutics at outstanding medical institutes and hospitals; to scan and activity do talent-scouting in academic, chemical, pharmaceutical, medical and biological institutions for innovative paths; to support the institutions of excellence in pharmaceutical and biological research.
It may be also take up those molecules, discovered in India, but not taken beyond.
Phase 1 or 2, for political or not-invented-here (NIH) approach of some of the MNCs. Several such candidates do exist and are still relevant e.g. CGI 13744, as an antidiabetic agent. There is also need to encourage basic research, in orphan or tropical diseases relevant to India, through time-bound networked programmes among the national laboratories and universities and to invest and engage in a serious effort to explore the wealth of Ayurveda for natural drugs: as activity - standardised extracts, fractions, active molecules or their more active or safer derivatives, with the state-of-the art scientific evidence.
The aforesaid suggestions are to be given a suitable company-specific business plan with investment needs and also time-frame for the deliverables. That demands a type of top management leadership that does not shy of a paradigm shift and also a major shake-up of their existing R&D set up. Essentially, the paradigm shift is to be back to the patient as central stage. The bedside is the best side to discover not only the pathogenesis of diseases but also their reversal. Too long, the chemists have dominated the field of drug discovery. Biologists have now entered and are close to the centre-stage. But clinical Pharmacologists and clinical scientists are not still enjoying the status of drug discoverers. It is time that these investigator "clinicians" cease to be mere handmade on the Clinical trialists of the CROs and pharma as academic clinical drug - discovery scientists. They have to use the paths of observations, pharmacoepidemiology and reserve pharmacology to identify clinical hits, develop experimental therapeutic leads and select new drug candidates, through a networked R&D programme.
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