With developed and newer technologies being the only way to success, medicinal chemistry services have of late displayed their potential in India as the next big avenue to be ventured.
With a large pool of qualified English speaking professionals, synthetic organic chemistry skills and its traditional strength in the pharma business - cost-effectiveness, quality of products etc., - India is in a position to attract multinational companies (MNCs). Also, foreign countries have always found cheap labour and volunteers in India, making them select India to outsource their drug research, development and manufacturing activities. There is an increase in the number of clinical trials being carried out in the country over the past few years.
Clinical trials done in India
The Indian Drugs & Pharmaceuticals Limited (IDPL), a government of India enterprise under the Ministry of Chemicals & Fertilisers, commenced the production of synthetic drugs in Hyderabad in early 1960s. Unfortunately, its objectives have not been fully materialised and the intended purpose has not been served. But one could say that IDPL played a critical role in generating outstanding process research and marketing, apart from inspiring consumerist skills related to the pharmaceutical industry in Hyderabad and in general throughout India. It takes at least the first six years of R&D to discover and develop high quality lead compounds. If carefully planned, this phase of R&D activity can reduce the risk of failure during clinical trials.
Medicinal chemistry is a discipline by itself but nonetheless, it is the bridge between organic chemistry and biological sciences. Research in medicinal chemistry can be multifaceted. It includes the design and synthesis of new biologically active moieties, development of new concepts for the design of selectively acting ligand, improvement of biological activity by molecular alteration, physicochemical and theoretical studies, molecular modelling on bioactive molecules, investigation of molecular structure on the distribution, pharmacokinetics, metabolism, toxicity of active chemical entities (ACEs) and several other activities.
The basic step towards any newer pharmaceutical product being introduced into the market involves drug discovery.
Steps involved in drug discovery
Weighing the various facts and figures of the past and the present scenario of the pharmaceutical and the biotechnological domain, experts predict what lies ahead for drug discovery and development.
Status of Indian drug discovery programme
The various medicinal chemistry services include:
" Synthesis of lead discovery libraries consisting of highly pure single compounds
" Hit to lead chemistry (small arrays)
" Lead optimisation
" Natural products chemistry
" Second generation drug projects
" Patent exemplification and circumvention services
" Scale-up chemistry
" Multi-step synthesis
" Asymmetric synthesis and optical resolution
" Development of synthetic routes
" Microwave chemistry
" Custom synthesis
" Synthesis of process impurities in active pharmaceutical ingredient (API) batches or drug metabolites
" Bioinformatics (collection, assimilation and application of proteomics and genomics data)
New technologies increase the number of targets and accelerate the identification of active compounds. There is increasing pressure to develop new lead compounds due to the near-term loss of patent protection for many drug products. And there is also pressure to reduce the time spent in drug discovery and to bring drugs to market sooner, as well as the ever-present cost considerations.
The role of the synthetic and medicinal chemists has changed considerably from a highly autonomous, independent inventor to a noteworthy player in a large interdisciplinary team progressively influenced by the business units. The discovery of a new drug not only requires its design and synthesis, but also the development of testing methods and procedures needed to establish how a substance behaves in the body and its suitability for use as a drug. Drug discovery may also require fundamental research into the biological and chemical nature of the disease state.
Various Indian companies involved in improving the scenario of medicinal chemistry services are Glenmark, Torrent, Lupin, Zydus Cadila, Wockhardt, Orchid, Sun Pharma, Piramal Healthcare, Suven, Shantha Biotechnics Pvt. Ltd., Landpower Biotech Ltd, Panacea Biotec, Novozymes, Biocon and Indian Immunologicals.
There have been quite a few collaborations of companies established out of India and the units existing in India. This has led to uplift the stand of our country in global market. Galapagos NV, a genomics-based drug discovery company, announced in June 2006 that its service division BioFocus DPI has signed collaborations with Indus Biosciences, a subsidiary of CiVentiChem LLC in Hyderabad and ProCitius, a division of Sanmar Speciality Chemicals Limited in Chennai. Both these companies will carry out chemistry services for BioFocus DPI discovery products division, with an option to provide support for client projects conducted by the BioFocus DPI medicinal chemistry division.
India's leading generics major Dr Reddy's Laboratories (DRL) kick-started its transition from reverse engineering to discovery and development of new molecules. It did this by hiving off its drug discovery related R&D activities into a separate company called Perlecan Pharma.
The Indian biotech industry today encompasses 325 companies. According to the fifth Bio Spectrum-ABLE (Association of Biotechnology Led Enterprises) Biotech Industry Survey, the industry has grown by 30.9 per cent in 2006-2007 alone. The contract research industry in India could reach as high as US $270 million by 2009.
Outsourcing seems to be the key word towards development, especially for a developing country like India. MNCs looking to outsource products and services regard Aurobindo Pharma as a valuable partner. Tie-ups with Aurobindo Pharma give customers the competitive edge through faster product development and optimised costs. The company can help reduce the transition time between drug discovery, development and entry into the market. The customer gains reproducible, innovative solutions to synthetic chemistry problems.
Research companies around the world experience the need for massive computing and data management competencies to sequence and categorise data generated by drug discovery labs. To aid the storage, management, retrieval and analysis of this large-scale data, the application of information technology to the life sciences sector like bioinformatics assumes increasingly higher significance. Bioinformatics is an optimised blend of interdisciplinary talents analysing immense biological information computationally. Its productive output is aiding different industries starting from agriculture to medicinal drugs in India and abroad. India's bioinformatics services outsourcing revenues are about US $32 million, and are expected to grow at a compound annual growth rate of 25 per cent to reach US $62 million by 2010.
While considering all the innovations put into drug discovery - be it outsourced or insourced - one of the factors that choose to cross our minds is about the legalities involved. To be precise, how good does the patent law look in India?
India's patent act of 1970 granted patents on chemical processes but did not sanction patents on drugs. This allowed Indian drug companies to reverse engineer molecules to produce generic versions of patented drugs. The law permitted process patents. Millions of people in the developing world would lose their lifeline of generic drugs from India if the amendments were passed as debated in 2005 when the amendments were being contemplated on. A two tier system was envisaged prompting the fact that there would be patented drugs for the rich and generic drugs for the poor.
But in December 2004 the government issued a presidential ordinance to bring the country into obligatory compliance with Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS) by January 1, 2005. The government had six months to codify this ordinance by obtaining the approval of the parliament. This was done on March 23, when, after virtually no public debate, India's parliament passed the third amendment to its 35-year-old patent act. The latest amendment has been dubbed TRIPS-plus by a number of commentators because it actually went beyond World Trade Organisation (WTO) requirements. For instance, the new legislation allows a pharmaceutical company to obtain additional patents when one of its already patented drugs was discovered to be of use in combating other illnesses and conditions, thus extending the number of years over which the company will exert proprietary control over the said drug's production and marketing.
With the amendment to patent law already in effect, drug discovery seems inevitable as far as profit is concerned for the Indian companies. Generic market wouldn't fetch much of the revenue as it could prior to 2005. Ranbaxy has been able to take one of its new chemical entities (NCE) as anti-malarial into phase II trials and claims to launch it in 2011.
The drug discovery stage consists of biology as well as chemistry research. While India is strong in talent pool for chemistry services like NCE research or novel drug delivery systems development, there exists a dearth of professionals for biological services such as protein structural analysis or expression profiling. This is one of the main challenges Indian companies are facing at this time. Government has already set up an Rs150 crore R&D corpus fund for the industry. In addition to this, the union government has decided to set up six National Institutes of Pharmaceutical Education and Research at Ahmedabad (Gujarat), Hyderabad (AP), Hajipur (Bihar), Kolkata (WB), Rae Bareli (UP) and Guwahati (Assam).
The Indian pharmaceutical industry, now a $17 billion (over Rs 68,000 crore) industry, has shown tremendous progress in terms of infrastructure development, technology base creation and a wide range of products. Innovating new chemical entities using medicinal chemistry services provided by various Indian companies and availing the facilities in India for outsourcing from various other industries all over the world gives an impetus to maximise the development of India on the economic scale as well as the humanitarian grounds. Keeping our fingers crossed and working in unity towards breaking the norms and generating new chemical moieties is the only way to improvise India's status and get hold of the global market.
(The authors are with Bharati Vidyapeeth's College of Pharmacy, Belapur, Navi Mumbai)