“The Indian pharma companies of late have been fairly successful in drug research and discovery.” -

Dr.Satish Bhatia,
CEO, Oscar Research Ltd.

What exactly is Clinical Research? When did this trend start in India?

The trend of drug discovery in India can be traced back to the signing of Paris Convention on Intellectual Property Rights by the country in 1994. Before that India never had any history of new drugs. We always copied the drugs discovered in the West. Discovery means invention of new chemical formula, working in the lab and coming up with new molecules. Development involves taking these into human volunteers, observing whether they are safe and efficient. So, clinical research leads to discovery of new molecules while clinical trials facilitate their development.

In fact drug development is a very long process. It takes about 10-12 years and involves a lot of initial studies on animals. The data is submitted to a regulatory body which grants permission to perform studies on human volunteers. While developing a molecule, we also have to test its safety and efficacy. In the process we have to counter numerous queries - Whether it is a totally new molecule with a new mode of action? Is it better than the existing one? Is it active with lower dose? Does it have less side effects?

So, when you do the testing of a new drug on human volunteers, or of old drugs whose patents have expired (clinically known as generic drugs), it is called clinical research.

Why has India lagged behind in the discovery of new drugs? How has it been able to meet the drug demands of millions of patients?

The estimated costs of drug discovery, right from discovering the drug in the lab to bringing it to the market is about $800 million to $1 billion. 99.9% of the molecules that are discovered and tested fail. Out of 10,000 chemicals that are discovered and developed, only one succeeds and goes to the market.

Since India is a poor country, it could not afford to pay for such massive losses. But, we wanted medicines for the millions of people of our country. So the Indian pharma industry resorted to copying drugs that are available in the Western countries. The Indian law did not recognize international product patents. It allowed Indian industries and companies to imitate and copy drugs and introduce them in the Indian markets. Western pharma companies could not protest till the Indian government provided regulations in this regard.

Indian companies copied western drugs using ‘process research’. It is the ability to synthesize molecules by different routes. Indian companies became very proficient and efficient in ‘process research’.

What is the current scenario on this front? Has any legislation been provided to ensure that Indian pharma companies respect product patents?

In the early 90’s when India sought loans from the World Bank, it was made to sign an undertaking saying that it would not infringe upon the patents and respect the intellectual property. This was a set back to India pharma industry which included about 10,000 companies, ranging from small garage operations to big companies like Ranbaxy and Dr. Reddy’s Labs.

As a signatory of Paris Convention, Indian pharma industry has only two options. First, they can develop and synthesize only those drugs whose patents have expired. These are called ‘generic drugs’. It doesn’t take much time, money and effort to produce generic products. The cost comes to 5-6 million dollars as opposed to $800 million-$1billion dollars in drug discovery.

It has brought down the cost of healthcare. The prices of the drugs have come down by ten folds. Even poor people and senior and retired people can afford them. Top pharma companies like Ranbaxy, Dr. Reddy’s Labs, Cipla, Wockhardt and many more are into developing generics for the western markets.

The other option, which is expensive, is that the Indian companies become party to a drug discovery. Developing a molecule right from the beginning takes 10-12 years and costs billions of dollars internationally. But it gives a high return. A single product of an international pharma company recorded annual sales of $10-12 billion, while the size of the Indian pharma industry is just $6.5 billion. Therefore, it makes enormous sense to invest in drug discovery. But there are only a handful of companies that have the financial capability and the desire to do that.

What is the success rate of Indian pharma companies in drug research and discovery? What are the main hurdles faced by them while conducting clinical trials?

The Indian pharma companies of late have been fairly successful in drug research and discovery. Some molecules have even reached the stage where they could be tried on human volunteers. You have to file all the relevant data with the Drugs Controller General of India (DCGI). They give permission to do human trials. In case of generics they give permission for Bio-Equivalence Test.

A lot of companies can do just discovery and animal experimentation. The main hurdle is to do clinical trials internationally. All communities need to be exposed to these trials before the drug’s safety, efficacy and tolerability are established. It’s an expensive exercise. No Indian company can do this entirely. It can be done in partnership.

Secondly, these clinical trials and studies have to be done under extremely controlled conditions. There have to be proper research center, either within a pharma company or, if the company does not want it in-house, then in a CRO (Contract/Clinical Research Organization). These research centers and CRO’s have good established facilities with wards, ICU’s, doctors, nurses, labs, instruments and so on. Oscar Research Ltd. is one such research center where we compare formulations apart from conducting a lot of Bio Equivalence studies.

The third hurdle is the screening of human volunteers. These studies are done on healthy volunteers. Their complete health check up is done to ensure that they do not suffer from any health problem. Volunteers have to stay at the center for 2-3 days under controlled conditions and the effects of both the new and original formulations are recorded. Since the original formulation has been in use for around 10 years, its efficacy and potential side effects, if any, are already well established. But in case of any side effects the center has to be well equipped to take corrective action. The volunteers are completely informed about the effects of the formulation, the motive and the procedure of the test.

What is your opinion regarding the debate on the ethical issues surrounding clinical research?

Ethics means that you cannot forcibly make a volunteer participate in the study. He should be well informed about the pros and cons of the procedure and his contribution. You should not exploit his social situation by giving him large sum of money and forcing him to agree to be a part of the trials. Even the compensation is given by international standards. The Indian Ethics Committee (IEC), a body of independent professionals evaluates whether you have the proper facilities, staff, training and equipment. Only after they are completely satisfied do they give permission to start the trials. If they turn down the protocol you cannot conduct the study. Even though the IEC does not have any constitutional power, if we have to do a study for international submission, the approval of IEC is a must.

Misconceptions about exploitation of people and using humans as guinea pigs partly stems from the fact that they are not well-informed about the drug discovery processes. They need to be educated that there are safeguards at every step. We cannot even test animals today, unless sufficient work has been done in the test tube. Animal activists in the west went into research centers and liberated all the thousands of animals that were there in the testing labs. This was in the 70’s and it changed the drug discovery. So it became imperative that a lot of study has to be done before testing on animals. In the west and in India the approval of Animals Ethics Committee is necessary before testing. This committee is registered nationally.

What are your guidelines to aspirants who want to make a mark in this field? What are the skills and qualities required to enter this field?

One should enter research only if one has the research temperament, commitment and dedication towards research and natural curiosity to find out. One should not come into it for money making. You need the commitment patience and dedication to spend long hours and long years in finding out and discovering.

If you are into clinical research, you are contributing to the development of new drugs, unmet medical needs, treatments for diseases like AIDS, diabetes and cancer. You can make so much of impact. Even in the case of generic drugs, by making generic versions of known molecules, you are making drugs cheaper for the poor.