By Ann Neuer 

January 22, 2013 | 1.2 billion people. Millions of treatment-naïve patients. Low cost of operations. Rising incidence of Western diseases. These compelling reasons for conducting clinical trials in India fueled an all out frenzy among pharmaceutical and biotech sponsors who flocked to India when the Indian government strengthened its regulations in 2005 to harmonize with those of the United States and the International Conference on Harmonization (ICH). Now, nearly a decade and thousands of trials later, a harsher reality has set in as sponsors have come face-to-face with widely reported ethics violations, a less than robust infrastructure and lack of experienced regulatory oversight needed to conduct high quality clinical research.

Nermeen Varawalla

This wake-up call has caused a flattening in the number of clinical trials taking place in India. Just a few years ago, there were projections that by 2011, 15% of global clinical trials would be taking place in India, but according to the clinicaltrials.gov website, as of January 2013, India now hosts a mere 1.6% of the registered clinical trials in the world. “This is a very small number given that India has 15% of the world’s population and 20% of the disease burden,” says Dr. Nermeen Varawalla, Founder and CEO of ECCRO, a contract research organization (CRO) specializing in India.

Dr. Varawalla points to the uncertainties in the trial approval process that make conducting global clinical trials in India a stiff challenge. First and foremost, she names uncertainties linked to the 2011 formation of New Drug Advisory Committees (NDACs) and their role in advising the Drugs Controller General of India (DCGI), the Indian regulatory agency, in the evaluation of new clinical trial applications. The committees, twelve in all, represent an array of therapeutic areas such as reproductive and urology, pulmonary, and vaccines, and contain experts in those fields. They review the protocol with an eye toward ensuring the ethical integrity of the study design, protecting the rights and safety of potential subjects.

“Oversight has been weak, and today, DCGI is taking the position that until strong oversight in place, it will control the volume of clinical trial activity in India. In other words, until there is reasonable assurance that Indian subjects will be protected, they will remain cautious about giving regulatory approval. This approach has resulted in a slow and uncertain regulatory environment, which has had a detrimental effect on the interests of international sponsors looking to place trials in India,” Varawalla explains. Furthermore, sponsors are now required to provide compensation to subjects who experience serious adverse events (SAEs) and/or death. In therapeutic areas, such as oncology, it is often impossible to ascertain whether a death is due to a study drug or to disease progression, causing further confusion.

Dr. Edward J. Brennan, President and CEO of IndiPharm, a Pennsylvania-based CRO with clinical operations in India, agrees that there is significant uncertainty and frustration surrounding the country’s regulatory environment, with approval times to start clinical trials highly unpredictable. Nevertheless, he takes a cautiously optimistic view. “India really does want to get this right. Regulators aren’t trying to keep clinical trials out of India intentionally. Instead, they are trying to find a middle ground whereby they can conduct trials in the country while ensuring the Indian public that patients will be safe. They are constantly fine tuning and adjusting their approval timelines, so it can appear to outsiders that there is no process at all,” Brennan says.

The media is very powerful in India, Dr. Brennan notes, so if stories are on the front page exposing problems with the country’s clinical trials industry, DCGI staff may be seen as accountable and may have to appear before the Indian Parliament. To avoid this scenario, regulators continue to delay and not make decisions about the merits of clinical trials that sponsors would like to pursue. “As a result, some companies have decided not to work in India,” says Brennan.

This is unfortunate as there are many excellent investigative sites in India with well-trained investigators able to produce clinical trial data indistinguishable from those coming from the best sites in the West. Building those sites takes years of diligence and strong oversight, with a goal of making the process more predictable.

Vijai Kumar

Dr. Vijai Kumar, President and Chief Medical Officer of Excel Life Sciences, a Chicago-based India-focused clinical trial management provider, also has a positive outlook. “The regulatory approval timeline in India, from start to finish, is averaging around four to five months. That timeframe is very competitive with the rest of the world. In 2012, studies we worked on had an average regulatory approval timeframe of about four months. Since in most cases we had already applied for and received approval from each of the Ethics Committees, we were able to initiate studies quickly after national regulatory approval,” Dr. Kumar says.

In the current evolving regulatory environment, Dr. Kumar stresses the critical importance of getting submissions right the first time. To achieve this goal, Excel pours resources into developing a solid regulatory strategy for its clients and holding pre-submission meetings with DCGI. That way, Excel knows what the concerns are from the agency early on and can address them or choose not to advance a study.   

Clinical trials is a nascent industry in India, yet with experienced companies and investigators operating there, and Food and Drug Administration (FDA) staff in Mumbai and New Delhi engaging with their Indian counterparts and offering expertise, the country holds promise. As the infrastructure slowly builds, the hope is that Indian regulators will eventually be comfortable moving forward with creating the kind of predictable environment needed to jump-start the clinical trials sector in that vast country.