Role of medical institutions in the development of new drugs

UK Sheth 
 Department of Pharmacology, Seth G.S. Medical College, Bombay-12., India

Correspondence Address:
U K Sheth
Department of Pharmacology, Seth G.S. Medical College, Bombay-12.
India

Full Text

Majority of new drugs introduced dur­ing the last two decades represent mainly an effort on the part of the phar­maceutical industry. In U.S.A., U.K. and Europe, drug research is carried out mostly in the research laboratories of pharmaceutical industry, which later on takes help of various institutions for cli­nical evaluation of the new drugs. Medi­cal institutions like National Research Bodies, national laboratories and univer­sity departments mainly carry out funda­mental basic research and are only peri­pherally concerned with search for new drugs. Situation in our country is a little different. Pharmaceutical industry as yet has not developed laboratories of their own for drug research with a few exceptions in our country. On the other hand national laboratories, principally drug research laboratories under Council of Scientific & Industrial Research (CS­IR), are committed to a great extent in search for new drugs. This has become necessary, since majority of drug research in pharmaceutical industry is carried out in the West which does not face some of the peculiar problems of communicable diseases, which pose a great problem to us. Drug research in these areas is not very attractive and often not possible for the pharmaceutical industry in U.S.A. or U.K. This makes it necessary for our national laboratories and our medical institutions to collaborate in search for new drugs for the problems that we face.

In our country till now drug research and development is, to a great extent, handled at the national level by CSIR through its national laboratories, princi­pally the Central Drug Research Institute at Lucknow. Indian Council of Medical Research by supporting research on vari­ous medical problems at different medi­cal colleges and through some of its own laboratories, also plays an important role in this area. Some of the regional research laboratories and research insti­tutes like Haffkine Institute are also en­gaged to a certain extent in research on development of new drugs. I would like to mainly concentrate on the role that more than hundred medical colleges in our country can play in various aspects of research and development of drugs. As yet this vast area of available talents has not been geared to this end, since we traditionally consider medical colleges and hospitals to be mainly concerned with the training of doctors and patient care.

Drug research does not necessarily mean finding of new drugs, but also is concerned with many other aspects which I would like to point out and indicate how medical colleges could contribute both in the field of new drug develop­ment and also in many related areas, connected with development and use of drugs.

New drugs derived either from plants or developed by the efforts of synthetic chemists have to be screened for biologi­cal activity. Such screening is usually carried out by pharmaceutical industries for their own new molecules. National laboratories like C.D.R.I. have their own plant and synthetic drug development programme for which they have developed excellent facilities for screening. Many university departments all over the country also carry out plant work and synthesize a number of new com­pounds which till now remain mainly as chemical entities. These new chemical molecules should be subjected to bio­logical evaluation. This has been taken care of to a certain extent by pharma­ceutical and drug research committee, by creating facilities at a few medical col­leges to establish a screening programme. In a medical college, drug screening for all biological activities becomes a difficult problem, due to the extent of involve­ment needed both in terms of equipment, personnel and animal house facilities. However, pharmacology departments of a number of medical colleges are interested in different areas of drug activities for instance, central nervous system, work on allergy and anaphylaxis, cardiovascu­lar activity, etc. If a liaison is created between various departments of pharma­cology in the medical schools and the national medical research bodies like ICMR and CSIR, areas of specific acti­vities and investigators could be identi­fied, and a liaison established for screen­ing new drugs for specific activities with a moderate financial support. The aca­demic departments would be happy to do this work since it would help them to develop their specific areas of activity and the funds available for such work could also support fundamental work in these areas. At least in highly specialised areas such centres in medical colleges would play an important role in drug development. Such activities could also include departments of bacteriology, microbiology, parasitology and bio­chemistry.

In the medical colleges in a number of good departments, fundamental research work is carried out in different fields. Very often the findings of such funda­mental work are not exploited for prac­tical application, as most of the academic departments are not geared in their think­ing towards the possibility of development of new drugs. The close collabora­tion as envisaged above, will bring the academic scientists in close contact with the scientist specially involved in the field of drug research. This will lead to exchange of information and may con­tribute important leads in drug develop­ment.

Often a new drug is developed on the basis of biological activity and introduced in the clinic if it is found to be non­toxic and effective. The exact mechanism of action of the drug, may or may not have been worked out during this period. In practice, mechanism of action of a drug especially at a molecular level is very often found out much later after its introduction in the clinics, e.g. peni­cillin. Academic department in a medi­cal college and other medical research institutes can play a vital role in estab­lishing site and mechanism of action of a drug which by itself may lead to better understanding about its use or lead to development of safer and more effective drugs. Work in such fundamental areas would interest as a challenging problem to a number of research scientists in medical colleges who may not be directly interested in development of new drugs. Their contribution would be of immense use in drug research and development.

Development of a new drug cannot be a reality unless adequate arrangements are available for its clinical evaluation regarding its safety, efficacy and compa­rative assessment with available drugs. Any new drug developed either by phar­maceutical industry or national laboratories, has to be screened in man for establishment of safety, dosage, etc.; a scientific discipline unique by itself is designated as Clinical Pharmacology and has developed as an inevitable necessity over last one decade. It is evident that such work could be best carried out in a teaching medical institution associated with a hospital. Assessment in a teach­ing institution would be highly academic devoid of emotional bias and acceptable. Clinical Pharmacology as a discipline if developed at all major medical colleges will play an immense role not only in development of new drugs but also in clarifying a number of dilemmas asso­ciated with the use of even known drugs. Carrying out studies on drug levels on biological fluids and relating these to effi­cacy and side effects, helps in under­standing undue toxicity to drugs, thera­peutic failures at accepted dosage and also helps in re-evaluating frequency of administration of drugs, etc.- Such stu­dies also help the industry in establish­ing better drug delivery system to the body by changing formulations. Compa­rative studies of available formulations would help in understanding biological and therapeutic equivalence of drugs available for treatment. This would lead to a better quality control which is so essential for pharmaceutical industry. Careful clinical observations learnt as a result of training in clinical evaluation of drugs and fundamental academic work in establishing mechanisms of actions of drugs often leads to newer uses of known drugs, widening its therapeutic range. Use of diphenylhydantoin sodium in treat­ment of digitalis toxicity and cardiac arrhythmias, use of allopurinol for treat­ment of gout, recently suggested use of the new anthelmintic levimisol in treat­ment of herpes labialis, Crohn's disease and rheumatoid arthritis, use of metra­nidazole in treatment of amebiasis, are but a few examples illustrating new uses of known drugs.

Introduction of new drug, of proved efficacy and immediate safety is but only a step towards its more permanent acceptance. Wider use of a drug at times brings out unexpected toxicities or pro­blems of drug interactions which are important, but could not be foreseen from early limited clinical trials. A continu­ous follow up of use of a drug and a feedback on adverse drug reactions if any, is extremely important. Before one can attempt adverse drug recording sys­tem at a national level, in a large country like ours, it is necessary to establish ad­verse drug reactions recording centres at medical colleges. Establishment of such centres in a number of medical colleges and collecting data from such centres by a central agency could at least make a beginning of getting data on a large num­ber of patients for such studies. Results of these studies would be of extreme importance in the drug research and development. Patterns of drug usage, effects of drug combinations and studying their mechanisms could also serve as important feedback information to drug industry as a whole and to the national laboratories and medical research agencies for planning their future work.

Importance and role of Clinical Pharmacology in drug research and develop­ment for the reasons mentioned above has been well accepted both by ICMR and CSIR, but needs urgent implementa­tion. At present there are only a few medical colleges where such work is car­ried out and only one centre which imparts training in Clinical Pharmacology. It is necessary to establish a few more centres of Clinical Pharmacology where training can be imparted in the principles and methodology of this disci­pline. The training could be both, either a: a full-fledged course of one or two years duration, or short-term course of 4 tc 8 weeks duration, depending, upon the needs of the trainees. These centre; could also carry out early clinical evaluat1ions of new drugs and pharmacokinetic studies. In addition, there should be number of centres available for carrying out work in Clinical Pharmacology o drugs useful in different disorders. These would serve as specialised areas for drug evaluation and development.

I.C.M.R. plays a major role in supporting medical research in our country. The support is available both for fundamental and applied research, though understandably majority of attention is usually directed towards support of more funda­menal work and community medicine. By laying down guidelines for the need of research in drug development oriented towards the national need, ICMR can provide a lead to medical institutions for research in particular areas which could be suppotred by national agencies like 1CMR, CSIR, etc., and also by pharma­ceutical industry. Thus, medical institu­tions can and should play a vital role in the field of drug research and develop­ment.