The regulatory system in India is maturing quickly. Just a few years ago, it was said to be in its infancy—with drug makers and contract research organizations (CROs) largely having to regulate themselves. Now it is an adolescent, and growing up fast. To explain where India's been and where it's going with respect to regulating clinical trials, we have a created a time line:

1940 to 1945: India's parliament, under British rule, passed the Drug & Cosmetic Act of 1940, which led to the Drugs & Cosmetics Rules of 1945, the central legislation that regulates India’s drug and cosmetic import, manufacture, distribution and sale. This established the Central Drugs Standard Control Organization (CDSCO), and the office of its leader, the Drugs Controller General (India) (DCG(I)).

1950s to the 1980s: India follows socialist-inspired policies. It was a time of extensive regulation, protectionism, and public ownership, leading to slow growth and corruption. Most industry did not flourish.

The exception was the generics industry. The Indian Patents Act of 1970 originally recognized only process patents and not product patents. So Indian companies were able to copy still-patented Western drugs by slightly altering a production process. India's generics boomed as a result, as did the perception that the pharmaceutical trade in India was lawless. Western firms rarely considered the country as a potential destination for new trials or drugs.


1988: The Indian government added Schedule Y to the Drug and Cosmetics Rules of 1945. Schedule Y established a set of guidelines and requirements for clinical trials. However, Schedule Y was written with the generics industry in mind, and little applied to trials. But it was a start. d9A2t49mkex

1991: The more liberal Congress Party won election in India. Under the New Industrial Policy, the nation began moving toward a market-based system, using foreign trade and investment as integral parts of the economy. “India basically threw itself open, opened its doors to the world then,” remembers Simon Britton, vice president of Asia Pacific for PPD who has worked in India on and off for 24 years. The technology and pharmaceutical sectors took note, but still hung back due to a lack of intellectual property protection.

1999: India began to tighten its IP rules, with a somewhat dramatic result. “The whole attitude of pharmaceutical companies changed toward India,” recalls Bob Scott-Edwards, president of Icon Clinical's central laboratories. Icon just opened a central lab in Bangalore last fall. The innovative side of the research industry began entering the market, but with trepidation.

2000 to 2001: The trade group Indian Council of Medical Research (ICMR) issued the Ethical Guidelines for Biomedical Research on Human Subjects. CDSCO released Indian Good Clinical Practice (GCP) guidelines. Without a regulatory requirement for GCP compliance, however, most companies did not invest in GCP trials. Low quality data resulted, worsening India's reputation.

Also, India's bureaucracy there made it hard to manage simple tasks like getting equipment out of customs. Worse, regulations mandated a phase lag, allowing companies to conduct a Phase II trial in India only if a Phase III study was going on somewhere else. The drug development industry, beginning to spread to other emerging markets at this point, became interested in India, but many were too troubled by these impediments to enter.

2005: A handful of watershed events took place: CDSCO made sweeping revisions to Schedule Y to try to bring it up to par with internationally accepted definitions and procedures. The changes: 1) Establishing definitions for Phase I–IV trials, which, to the industry's excitement, eliminated the phase lag. 2) Establishing clear responsibilities for investigators and sponsors, which had previously been vague and open to interpretation.

Also in 2005: The Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement, which India had signed in 1995, became effective, at long last changing the country's patent laws to recognize 20-year product patents. Indian companies began to respect IP rights, consistent with international standards.

The result of all this? Life sciences companies flooded the market. “That had a great impact on business,” says Pramod Kabra, director of clinical operations for PRA International and formerly head of the Indian CRO Reliance Clinical Research Services. “People had more faith in the system then; people involved in trials were going to need to be more accountable. And more global trials came.” PRA itself came into the market in 2006.

2006: The DCGI sped things up for global clinical trials by dividing them into two categories: A) Those also being conducted in other markets with competent, mature regulatory systems, and B) everything else. Trials that fell into category A (having received approval in the U.S., Britain, Switzerland, Australia, Canada, Germany, South Africa, Japan and countries in the European Medicines Agency [EMEA]) would be eligible for fast tracking in India, with approval taking no more than eight weeks. Trials in category B would fall under more scrutiny, with approval taking 16 to 18 weeks. Nearly all global trials are on the A track.

2007: The Indian Government gave another boost to the drug-development industry by cancelling the 12 percent service tax on clinical trials. It had just instituted the tax the year before.

2009: In February, the industry applauded new regulations on exporting samples. Previously, an export license was needed to get samples out of India. This took several weeks to obtain. But now that rule is gone. If a sample is associated with an approved trial, it is good to go. “From this, we will save six to seven weeks time,” said Larisa Nagra Singh, Icon's senior director of clinical operations in India.

What changes are expected soon? Rumors abound that India will permit the currently prohibited Phase I/first-in-man trials on compounds not developed in India. Many CROs are ready, having established and staffed Phase I units in anticipation. Indian regulators are also said to be preparing to begin registration of CROs and inspections of sites. It's all part of India's regulatory-reforms road map released last year titled “CDSCO: Vision 2020.” In some respects that could vault India ahead of some western countries.

The country's regulatory body is doing its best to become more FDA-like, and is getting help. “For the last year or so, the Indian regulatory authority has been undergoing aggressive training from the U.S. FDA and Health Canada in order to gear up with the challenge of becoming a part of a global clinical research scenario,” says Gaurav Mathur, Inc. Research's manager of regulatory operations in India.

That could make for a win-win, he adds: Enabling India to adopt more sophisticated regulations to better protect their citizens and invite more industry, while at the same time helping the FDA by ensuring that the data emanating from India is more acceptable for the marketing of drugs in the U.S.

Meantime, India's regulatory body is on a hiring binge. So is the industry itself. A recent report from the Indian Government’s Planning Commission found that the country needs between 30,000 and 50,000 additional research personnel. That includes investigators, auditors and staff qualified to serve on ethics committees and data safety management boards.

by Suz Redfearn