Any drug discovery process that goes up to product approval involves 11 - 15 years of continuous effort covering five to six years of pre clinical trials, four to six years of clinical trials and another three years of regulatory follow-ups. Beginning with target discovery, validation, lead selection, lead optimization and pre-clinical trials, it covers manufacturing, phase-I, phase-II and phase-III trials and finally the marketing approval.
As we know, the traditional method of drug discovery focuses on development of natural (plant derived) medicines for treatment of a particular ailment or disease. Normally, it involves the isolation of active compound from natural sources. It is then synthesized, and the structure of the compound manipulated to get better drug having better efficacy and lesser side effects. By doing so we begin the conventional drug discovery process by identifying a disease (rather than a treatment). The disease model is used to pinpoint relevant genetic/biological components i.e., possible drug targets.
The modern drug discovery methods are totally different. Here, the development of appropriate screening assays is vital. The screening molecule libraries usually contain potential lead compounds, and include natural product libraries, existing compound libraries, combinatorial chemistry libraries and virtual libraries. Ideally, screening assays for lead compounds should provide information concerning the - mechanism, binding affinity, efficacy, specificity and toxicity of the compounds. It has to be rapid and automated and would not require large quantities of the test compounds so as not to deplete the library more than necessary. The modern drug discovery processes are also cost-effective in terms of labour and reagents and yield high-quality data so as to minimise re-testing.
As mentioned, the molecular libraries are of natural products like plant extracts, marine organisms, animal toxins, virtual chemistry (in silico virtual libraries of hypothetical pharmacophores), combinatorial chemistry (Nucleic acid (aptamer) libraries, small molecule (pharmacophores) libraries, `split-and-pool' combinatorial chemistry, and focused combinatorial libraries- by combining the pharmacophores in different ways like adding various substituents to the pharmacophores or chemically modifying the pharmacophores in defined ways.
However, drug discovery continues to be a high-risk process as over 90% of drugs entering clinical trials fail to make it to market and the estimated cost to bring a new drug to market is over $770 million.
The challenge before scientists is therefore to devise a discovery strategy, which simultaneously leverages both drug targets and chemical libraries. With technologies driving drug discovery chances are more for the development of better discovery tools like genomics and gene function, combinatorial chemistry, high throughput screening, in vitro pharmacology and toxicology, gene therapy, pharmacogenomics and animal-free disease models.
INDIAN POTENTIAL
Given our innovative skills and human resources, India should be able to climb up the value chain in drug discovery research. Let us try to understand the factors responsible for the rise of Indian pharmaceutical industry:
1. Generic Prospects:
Patented products in the US worth around US$ 70-80 bn set to expire over next 5 year
2. Remarkable increase in product filing from India (DMFs, ANDAs, CTD/COS) post-2000
3. Creating significant opportunities through patent challenges (Para IV ANDAs) and specialty filings (505 (b)(2) applications).
4. New opportunities are emerging in outsourcing
5. Scaling up of R & D efforts
6. Increase in global companies seeking alliances/ collaborations with Indian companies
What needs to be understood in this context is the fact that our national drug research laboratories are spending 55 - 60 crore per year on drug discovery research. In addition to this, the top 10 drug companies of the country spend about 7 - 10 per cent of their annual turnover on R&D.
PHARMACISTS INDRUG DISCOVERY
The major problem areas in drug discovery research are the absence or scarcity for specifically 'trained' work force. A lower overall budget in R&D and the incapability of majority of companies to develop specialised cells for each activity of a drug discovery centre are also issues of concern. These are the areas where future pharmacists can be of help. They can fill the gap for people having multiple expertise who can interact with specific areas/personnel from specific backgrounds. A pharmacist thus should become the interface who can co-ordinate and conduct multidisciplinary activity/ research projects. Keeping this in mind, Indian pharmacy institutions should start specialized courses that provide strong basics in science, humanities, management and engineering related subjects, provide clinical, industrial, research, regulatory affairs, management oriented syllabi, teach practical aspects - research methodologies, instrumental techniques and industrial operations, provide project work (study/ laboratory/ computer) and also provide elective option - towards a specific career path.
Establishment of univer-sity - industry linkage programmes, inclusion of courses to develop communication skills and personality, faculty development/ exchange/training, attract research grants, organizing regular symposia/ workshops/ invited lectures, providing good laboratory facilities are all important.
The introduction of a programme in drug discovery and development should look at the need for developing communication skills as well as the scientific knowledge needed to successfully participate in a drug discovery and development project team. The scientific skills necessary to choose, prioritize and compare drug targets, biological assays and lead compound, information technology skills required for effective communication with collaborators, senior scientists and internal management should all be developed through such courses.
The pharmacy students of future should be trained in skills like target identification and validation, assay development, high-throughput screening, combinatorial chemistry, lead optimization, statistics, scientific comprehension, presentation skills and communication.
- (The author is with Dabur Research Foundation)