India: setting the stage for a CT boom

With new legislation to improve its clinical trials r&d to global standards, India is emerging as a strategic location for drug companies to pursue their drug development activities. Manufacturing Chemist's Indian correspondent reports

Clinical research, a crucial part of drug development, is gaining importance in an era of evidence-based medicine, and research-orientated pharmaceutical companies want to adopt effective and economic methods to develop this process; hence the selection of strategic locations for global trials is very important for them as far as the marketing potential of the drug is concerned. With a varied patient population, skilled human resource, a pool of GCP trained investigators, good cost leadership and promising market growth, India is currently considered to be a classic example of this ideal concept.

The country's outstanding IT skills offer companies online data generation and management using the standard operating procedures (SOPs) in accordance with international protocols. Furthermore, the multinational clinical research organisations (CROs) believe that their global SOPs are supplemented by local working practice documents to incorporate regional differences.

As an English speaking country, India has no language problems for global companies, and promises yet more economies for clinical research because, for international trials, documents do not need to be translated into local languages. This is currently one of the most difficult hurdles in China, Japan and even some European countries.

cost value

More importantly, India's multifarious ethnicity offers a pool of generic material for clinical drug research. Experts believe that even China, which is more populous than India, is not as abundant in ethnic varieties. The country is unique in this respect, with remote unstudied populations. In Assam, for example, one tribe has been found to be devoid of exposure to hypertension, the incidence of which is clearly on the rise, especially in the urban population.

Cost values and the rapid patient recruitment are two other important strengths, so India can not only reduce the cost of research, but contribute enormously to the increasingly multicentric, multicountry clinical trials.

improving CT

Ethnicity typing can account for two thirds of the total development cost (US$500-800m) of a new chemical entity (NCE) with validated therapeutic value, and according to leading CROs, in India they can enrol 30% more patients in a global trial at significantly less cost and time compared with concurrent trials in the West.

The CROs can help reduce enrolment challenges by accessing large, diverse patient groups that are often unstudied. A leading CRO official estimates that a delay of a single day can cost the innovator companies $5-6m (€4-5m).

'Until a few years ago, Indian drug companies were almost completely alien to the prerequisites of making an Investigational New Drug application. Now we receive as many as 107 applications in single year,' comments Dr N K Ganguly, director general, Indian Council of Medical Research (ICMR) who heads the IND application clearance committee attached to the office of the Drugs Controller General of India (DCGI).

Apart from the natural advantages mentioned above, recent developments in infrastructure, information technology, and an improved healthcare segment have also boosted India's emerging pre-eminence in the area of drug research.

Nevertheless, the country needs further improvement to keep the CT practices on a par with international standards, including an epidemiological database, basic infrastructure and regulatory supports.

The country currently lacks the availability of readymade epidemiological databases on patient populations, and CR-specific infrastructure in certain institutions. Similarly, the GCP training and culture could be further improved to make India globally competitive.

obstacles to process

Another key area that needs the urgent attention of the government is the functioning of ethical committees. Many ethics committees do not have a composition or functions in line with GCP. This uncertainty in obtaining clinical trial permission within a reasonable time and the lack of regulatory inspection of clinical trials also need to be changed for better.

Though the overlapping role of the regulatory authority and other government agencies creates confusion at present, current moves are expected to bring more clarity. Other obstacles to progress include:

• the lack of a clinical trial registry from the regulatory office and accredited central labs,

• the lack of availability of special service providers like special couriers and contract clinical trials management suppliers;

• low public awareness about the need for clinical trials and current provisions for patient protection; and inadequate media support for creating a favourable opinion about drug development and clinical trials.

However, the recent changes in the regulatory framework for clinical trials, such as the acceptance of concurrent phase II-III trials; the adoption of Good Clinical Practice (GCP) guidelines; the Ethics Committee functioning, and provisions for patient protection are significant milestones in policy initiatives towards the growth of this emerging sector in India.

The IND committee, and the biotech products committee attached to the DCGI's office, give suggestions to the companies, and they have the freedom to seek clarifications and get reviews by the committees. While making sure that the investigators follow the GCP standards, the government doesn't want the regulation to be so restrictive.

Along with the amendments proposed in Schedule Y of the Drugs & Cosmetics Act, which deals with the norms for conducting clinical trials, the ICMR's ethical norms for biomedical research will be made mandatory by a new law to be enacted shortly.

This means that all biomedical research involving human subjects will be conducted only as per mandatory ethical principles of informed consent of the subject. In addition, the GCP standards published by the government are claimed to be superior even to the International Conference on Harmonisation (ICH) norms in certain aspects. Although the GCP norms have not been made a law at present, compliance with them would, practically, be necessary for obtaining the DCGI's approvals and clearances. And as a signatory to the WTO, the country is set to comply with the TRIPS requirements in terms of IPR protection by the year 2005.

Current clinical research spending in India is estimated at $100m (€79m), which is tiny compared with the worldwide spend of $25bn. Industry experts predict that the spend in the country will double by 2008, even if there is no significant support coming from the regulatory front.

This natural increase in the CR spend is estimated on the basis of the pharmaceutical market growth in the country expected by the local as well as global drug companies. However, with policy measures suggested by the industry and improvements in the regulatory framework, the size of the business in India is likely to touch $1bn within the same period.

multinational presence

According to Dr S Mukherjee, medical director, Pfizer India, if the regulatory framework in the country is further tightened to ensure adequate protection of the data and also to patenting, the multinational companies would surely look forward to shifting a sizable amount of research to India. 'The government seems very supportive to local as well as foreign companies aspiring to the big league in drug research. But the authorities are yet to become familiar with the technical aspects of it to come out with clear policy initiatives and so open the floodgates,' Mukherjee said.

Dr Arun Bhatt, president, ClinInvent Research, an emerging CRO in India, points out that current trials are essentially a mixture of local Phase III and IV and also bio-equivalence. At present in India some 50 GCP trials are in progress and the country now has about 200-250 GCP trained investigators. Though the total spending on these trials is put at $30m, this is likely to grow to $300m by 2010. Pfizer has 20 projects presently under way in India, of which 10 are international trials and another 10 are targeting the Indian market alone.

Multinational CROs with a presence in India include Simbec Research - UK, RCC, Quintiles and Covance-Siro, while the Indian majors like Speciality Ranbaxy, Reliance, Well quest, Clinigene, Lotus and Strand Genomics are handling both local and global trials for Indian and multinational innovator drug companies.

future gains

Future projections of the country's clinical research potential seem realistic. Normally, pharma companies are interested in conducting the trials in a country where they have a sizeable market; however, given India's large population, significant growth in its pharma market is expected, so they include the country in their long-term strategy.

According to senior professionals in the Indian drug industry, the country could emerge as one of the top 10 destinations worldwide for innovation in pharma in the next 10 to 15 years.

Conversely, the country could benefit in a variety of ways by participating in global trials: accessing the latest therapies for the population, training for medical professionals and inputs to academia are a few of the prospective gains. For example, India's participation in global clinical trials would mean that a new drug introduced in the US market would be available in India, and also that it is tested and validated in the specific context of the genetic conditions of Indian population.

The country would also ultimately gain if it could attract more global companies by providing tax and duty incentives. As the market expands, companies will assign more projects here, which will result in more foreign currency flow towards CR spending.

With the government incentives and other regulatory supports, some 10% of the worldwide patient enrolment in CR could be achieved in India by 2008, providing an employment opportunity for another 16,000 people.