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India offers the global biopharmaceutical industry an array of opportunities in contract clinical research.1–3 The country has rapidly become one of the preferred destinations for clinical trials because of its large heterogeneous patient population and English-speaking western-educated physicians. It also has a track record of sincerity in meeting regulatory and recruitment timelines and, most importantly, well-accepted, good quality, auditable data. Although most media attention has been on the increasing clinical trial investment by major global pharmaceutical companies, there is growing interest in India from many other companies within the drug development sector.
From a sponsor's perspective, there has been a change in how India is viewed for clinical trials — from scepticism to acceptance — with it now being a core region in global plans. As a result, many pharmaceutical players (Pfizer, Novartis, Astra Zeneca, Eli Lilly, GSK, Aventis, Novo Nordisk, Bristol-Myers Squibb, Roche and Amgen — to name but a few) have expanded their existing clinical research investment and infrastructure in India.1–3
A decade ago, the contract research organization (CRO) sector was virtually nonexistent in India. As CROs were not operating in the country, there was a lack of commercial awareness concerning clinical trials and this created considerable apprehension in the minds of prospective clinical trial professionals. Pharmaceutical companies that performed clinical trials were mostly aiding their parent company in regulatory support and medical marketing functions. For professionally qualified pharmacists and medical doctors pursuing a career in the industry, clinical research was not seen as one of the best options, and most preferred a career in pharmaceutical sales and medical marketing. Only a handful of senior reputed doctors served as investigators for global multicentric studies under the direct monitoring of international sponsors.
Throughout the decade, attitudes changed as companies invested in India and were pleasantly surprised by the results. In many cases, severe competition elsewhere in the global market forced companies to expand their outlook, and most local and global CROs now consider an operational presence in India key to overall business plans. Most of these are global CROs, such as Quintiles, Covance, Chiltern, PPD, ICON and Pharmanet. To achieve greater economies of scale and increase profitability of the business, some have even reduced their existing operations in western countries and expanded similar operations in India. Hence, to a degree, there has been a steady process of business expansion from Europe and the US to India and other emerging markets. The key enablers for the Indian CRO business are:
Another factor that has attracted sponsors is the ability to conduct high-quality clinical research in India. The pace of change for improving quality was slow, with key stakeholders (i.e., sponsors, regulatory agency, ethics committee and investigators) being reactive and cautious to the challenges, which frustrated potential sponsors. As the number of trials conducted in India was small and global attention was limited, this unhurried style of facing key challenges was tolerable. However, in the modern era there has been a change in how clinical trial quality issues are viewed and the authorities have realized the benefits of making advances in these areas. An additional factor that makes India a favourite for clinical trials is the improvement in the intellectual property environment.
Early pharmaceutical pioneers in India faced the daunting task of operating in an unfriendly regulatory and ethical environment for quality clinical trials. There was little in the way of formal regulatory guidelines, and it was difficult to find out what documents were needed and then guarantee receiving approval to go ahead with the trial on the basis of those documents when submitted.
To make matters worse, there was also a dearth of experienced investigators and clinical research professionals. Despite this, with patience and persistence, these organizations and their supporters brought about a change in the quality of research professionals and made efforts to improve ethical aspects of clinical trial operations.
The country has also progressed slowly towards good clinical practise (GCP) clinical trial standards.2 The Indian regulatory agency — the Central Drugs Standard Control Organization (CDSCO) — is now very specific about what it needs and even informs you of the timelines you can expect before approval may be granted. Pressure from the industry (and proactive initiatives of the regulators) also encouraged the Central Ethics Committee on Human Research of the Indian Council of Medical Research (New Delhi) to issue Ethical Guidelines for Biomedical Research on Human Subjects in 2000. Subsequently in 2001, a central expert committee was formed by the Central Drugs Standard Control Organization to develop Indian GCP Guidelines in line with the latest World Health Organisation (WHO), International Conference on Harmonisation (ICH), FDA and Medicines and Healthcare Products Regulatory Agency (MHRA) guidelines. A continuation of this regulatory revolution has been the revision of Schedule Y, which deals with regulations relating to clinical trial requirements for import, manufacture and obtaining marketing approval for a new drug in India. The procedure for applying for marketing approval depends on the status of the new drug. When the revised Schedule Y fully comes into force, it will confirm India's image as a reliable clinical research destination.
In the early 1990s, sponsors often posed the question, "Are Indian clinical trials acceptable globally?" and, at the time, this was difficult to answer. Now, it has become easier to convince sponsors to consider India within their major clinical research plans. In a similar way to how other emerging markets developed, India has shown that quality data can be generated to satisfy major regulatory agencies. Most major pharmaceutical companies have overcome the psychological hurdle concerning data quality and now routinely include India in their plans.
According to CenterWatch, the approximate size of the Indian clinical trials market in 2002 (industry spend on CRO services and investigator grants) was US$30–35 million (€20.2–23.5 million). The estimated number of ICH-GCP clinical studies was 40–50, and the number of GCP-trained investigators was 200–250. Assuming there were 100 patients per study, or 20 patients per investigator, this translates to 4000–5000 patients. Most studies are conducted in 20–25 major public hospitals in major Indian cities, such as Mumbai, New Deli, Ahmedabad, Bangalore, Hyderabad and Chennai to name just a few.
Although promising, it is important to note that the present size of the Indian industry is still very small by global standards. In the US, for example, the number of GCP trials is 60000 and there are more than 40000 GCP-trained investigators. However, global pressure on the industry to recruit patients faster and make trials economically justifiable means that large numbers of clinical trials are likely to be conducted in countries such as India. Because of this, a dramatic expansion of the Indian clinical trials market is anticipated to take place during the next 5 years.
The most attractive business opportunity in clinical research appears to be setting up a CRO that can handle one or more functions for a sponsor. Today, there are at least 30 CROs that have established operations concentrating on the clinical monitoring work in Phases II–IV studies for the global pharmaceutical industry. Nevertheless, many global companies are managing the quality assurance, pharmacovigilance, medical affairs, regulatory affairs, medical writing work from their central offices outside India for reasons of control and absolute quality. As the Indian industry matures, it is likely that these functions will be handled from India with the support of the domestic qualified medico-scientific community. This approach could also prove to be cost effective. The success of this business opportunity in India depends entirely on quality resources (which are scarce at present), dedicated and experienced leadership, and established global contacts to attract first time and repeat business.
The contract research business is set to expand, and India's rapidly improving environment means that it is well-suited to accommodate this growth. The rise in pharmaceutical and biotech manufacturing, and contract research supported by IT skills, has also led to promising outsourcing business opportunities in various other segments including clinical trial data management and statistical analysis. The situation, at present, benefits all parties interested in clinical research, but long-term success depends on sustaining the improvements in the Indian environment to maintain quality and avoid complacency.
1. U. Sahoo and F. Kermani, "The Contract Research Industry in India," in E.S. Langer, Ed., Advances in Biopharmaceutical Technology in India (BioPlan Associates Inc., Rockville, MD, USA, 2007).
2. U. Sahoo, PharmaVoice, July, 38–39 (2005).www.pharmavoice.com
3. U. Sahoo, V. Sanghavi and F. Kermani, Applied Clinical Trials, 15(2), 54–62 (2006).