Clinical Trials

• Development times for drug discovery not speeding up.

• Fewer trials included in the dossiers.

• Number of subjects showing little variation in recent years.

• Fewer bigger trials take the same time as smaller trials.

• Getting more drugs in the market in a shorter period remains the challenge

These have been some burdens for big pharma companies globally. These companies are increasingly considering outsourcing and off shoring their drug discovery processes, R&D and clinical research. And Clinical Research Organizations (CRO) want to tap that opportunity. But with costs and speed being the key concerns, India is emerging as an important destination for obvious reasons like talent pool, facilities, large and diverse patient pool, qualified doctors, and many more. Today, global companies are not asking a question as to if they should consider off-shoring to India, but which phase of the drug delivery process in order to derive the maximum value.

The number of companies participating in clinical research and trials is going up. Recently, the Genetic Engineering Approval Committee has given green signal for a couple of companies like Novo Nordisk and Reliance Clinical Research Services to begin clinical research in India. If global big pharma are doing it, would the India pharma stay behind? Some Indian big pharmaceutical companies like Wockhardt, Lupin, and Sun Pharmaceuticals are working on new chemical entities and have established their own clinical research units to conduct trials for their new molecules. Slowly but steadily, clinical research and trials in India is getting ready for a big take off. Read on …

Narayan Kulkarni with Ch. Srinivas Rao

Full of promise
Indian market is still unorganized.

Compared with the global CRO market, the Indian CRO market is very small mainly because the companies are offering low-end services. Companies are doing bio equivalence studies, bioanalytical studies, and Phase-II and Phase-III trials. Dr Satish Bhatia, president, Wellquest, division of Nicholas Piramal India Ltd, observed that India's share is less than one percent of the global CRO market size of $10 billion.

The industry is divided when it comes to estimating the market size. But most of them believe that the present Indian CRO market is in the range of Rs 200-250 crore. Few say, it is in the range of Rs135-150 crore, while Dr Ajit Nair, senior manager strategic planning and clinical operations, SIRO Clinpharm, the first Indian CRO to commence trials in 1996, puts the figure at a much higher side of Rs 550- 600 crore. There are about 25 CROs working in India with many pharma companies having their own clinical research units conducting trials in 80 odd government and private owned hospitals.

Going with the industry, Surinder Kher, senior vice-president, iGATE Clinical Research International Pvt Ltd, said that the present CRO market size should be approximately Rs 200-250 crore. This includes the clinical trials conducted by the independent clinical research organizations, the clinical research outfits of multinationals like Eli Lilly, Pfizer, Novartis, and Aventis and some in-house clinical research is being done by Indian pharma majors. Kiran Mazumdar-Shaw, CMD, Biocon and president ABLE said, "Currently according to the Organization of Pharmaceutical Producers of India (OPPI) statistics, Indian CRO business is worth $70 million growing at 30 percent annually. The Indian advantage in clinical development is clearly the speed of patient enrolment and thereby shorter time-lines for clinical trials." According to ABLE estimates, Indian clinical research and development business is expected to grow to $1.5 billion by 2010.

What is heartening is that companies now are getting more focused. For example, Wellquest is focused on clinical research to support introduction of generic and NDDS products. Dr Bhatia informed, "Soon it would be followed by Phase I-III trials for NCEs." Wellquest that has got three accreditations and done 40 studies was able to garner revenues of Rs10 crore for the year 2003-04.

Synchron Research Services, offering services in Phase-I, high throughput screening for rapid PK analysis, qualitative and

 quantitative medical imaging, in silico drug metabolism studies, was able to garner Rs 5 crore for 2003-04. It has conducted 200 bioavailability and bioequivalence studies and six studies in Phase II-IV. Commenting on the focus areas of SIRO Clinpharm, Dr Ajit Nair said, "Clinical project management and data management are of immediate focus and will continue to be the mainstay, with innovative solutions for convenience and cost-efficiencies in these areas being the key differentiators in the future. The vision is to move from being only an outsourcing agent to being a partner who can contribute in minimizing the drug development risks while maximizing competitive advantage." This has brought in more revenue to the company and was able to add Rs 31 crore in 2002-03.

Lotus Labs in 2003-04 has been very aggressive. Recently it announced to set up a 50-bed facility in Chennai to conduct clinical trials, bio studies and the center is expected to be operational in six months. "Lotus is spending Rs 1 crore on this. Over the past 36 months, we have conducted over 300 biostudies. We plan to build a separate facility in St John's Hospital to conduct Phase-I trials in-house at an investment of Rs 2.5 crore," informed VV Raghavan, managing director, Lotus Labs, on his company's current developments. The company is talking to Shantha Biotech to conduct Phase-III studies of the latter's erythropoetin. Lotus Labs is also in the process of setting up training centers in good clinical practice and good laboratory practice. Lotus Labs expects to touch Rs 14 crore during 2003-04.

ClinInvent Research Pvt Ltd has adequate staff for monitoring, project management, and quality assurance and has the backing of The Chatterjee Group. Dr Arun Bhatt, president of the organization, ClinInvent Research, said "Our focus is on all phases of clinical trials mainly in the areas of oncology, neuro-psychiatry, cardiology and diabetes drugs."

Vimta Labs, which operates in the areas of testing and validation, clinical research, clinical pathology, pre-clinical safety evaluations, environment assessment, and inspection and certification services, has seen 81 percent growth in its revenues over that in the previous fiscal. It ended March 2004 at Rs 35.11 crore in income.

Clinigene International, a Biocon subsidiary, offers clinical, bio analytical, bio statistical and data management services to its clients. Said AS Arvind, chief operating officer, Clinigene, "We concentrate on Phase-I–IV clinical trials, bioavailability/bioequivalence studies, and data management." The company has recently inaugurated a state-of-the-art human pharmacology unit at Sagar Apollo Hospital. This unit is spread over 3,000 sq. ft and can accommodate 26 volunteers at a time.

The Indian arm of the American pharma giant Eli Lilly & Company is putting its concerted efforts in conducting clinical research by partnering with key thought leaders and experts in the therapeutic areas. Working with over 40 hospitals in India, including government and private hospitals, Eli Lilly (India) has 17 large and small clinical research projects running involving both phase II and III trials.

Quintiles Spectral (India), a subsidiary of Quintiles Transnational, leads the segment in India with turnover of more than Rs 38 crore for 2002-03. It is conducting clinical research involving more than 70 research sites and involved in over 40 research projects for 20 different pharmaceutical companies.

India is taking this opportunity seriously. And it has to as it has immense potential. "India due to lack of penetration of drugs has a huge patient population that has never been subjected to any drug and this gives a critical pool of naïve, uncontaminated patients which is important in conducting certain development work and clinical trials. Significant population biodiversity in India with its wide and varied gene pools can provide wealth of information for target identification, a key for the CROs," noted Alok Gupta, director, life sciences, Rabo India. "India will gain by researching diseases. The cost of clinical trials is 50 percent lower in Phase-I, 60 percent lower in Phase-II. Cost saving is not the only advantage. Ability to find and qualify the right patient pool is an appealing factor for Indian trials, and India also offers genetically and culturally diverse population where treatment-naive patients are willing to participate in trials. For all this to happen, we have to be an ethical community," added Mazumdar-Shaw.

Nascent sector's woes
Issues confront this sector too.

The awareness about mega CROs opportunity is familiar topic these days. But this does not mean that the industry is not confronted with hurdles. Indian companies have their own share of woes while conducting the trials on human beings. This, the industry says, is mainly because there is no clear regulatory framework, which would support and encourage the companies to take up human trials in proper manner.

Dr Ajit Nair observed that the regulatory (DCGI) approval timelines in India are high as against the US. While it takes about 30 days in the US, here it is about 90-120 days. This puts a crimp in the project timelines. However, more often than not, this is made up by the enrollment timelines, as the enrollment rates in India are mostly higher than most developed nations. Expressing the same views, Dr Arun Bhatt of ClinInvent Research noted that lack of trained manpower, GCP culture, working of the independent ethics committees, regulatory uncertainties are coming in the way for the growth of the segment. According to Dr Shiv Prakash, managing director, Synchron, "The Indian CRO industry is still in an unorganized sector and regulatory approvals take long time. Maintaining confidentiality of data (data protection) is key issue before of the segment."

Dr Bhatia noted that the Indian companies are not able to conduct the phase I trials for foreign sponsors as these are not allowed at present. And the delays in getting approvals from the DCGI for starting clinical trials (phase I-III) have to be sorted out immediately. Further, " The challenges that are confronting the segment are the unstructured environment in hospitals and government institutions, lack of GCP awareness amongst the large institutions, and regulatory environment which is not well defined for all aspects of research," pointed Rajiv Gulati, managing director, Eli Lilly (India).

Dr Swati Piramal, director, strategic planning, Nicholas Piramal India Ltd said that the most worrying factor is outsourcing by Indian pharma companies for Phase-I clinical trials when Indian companies are capable of doing the same at a lesser cost are looking at MNCs to outsource their R&D work. She informed that this might be due to data protection, regulatory fear and delay in getting the approvals. Companies are working on how to protect the data. Dr Piramal said that Nicholas Piramal is discussing the issues like data protection, data security with Infosys Technologies.

Considering that CROs in India have a good potential and scope for attracting outsourced R&D, Ranjit Shahani, managing director, Novartis India Ltd, pointed, "The main hurdle will be the absence of data protection. Hopefully, there may be clarity and some positive policy framework that should be established by the end of 2004. Some of the other barriers include: absence of a clearly laid down time frame for permission of clinical trials and difficulties in custom clearance of clinical trial samples."

What do the outsiders think? Dr William A Haseltine, founder and former chief executive officer, Human Genome Sciences, who was there recently in India, told the biotech forums, "India can partner early with companies, take the products through clinical trials and develop them. But there are issues of ban on Phase-I clinical trials of outside drugs and pharma companies face problems in getting animals for testing. Both of these issues should be solved politically. Also for clinical trials, hospitals records need to be automated and the general infrastructure needs to be improved. India is an attractive destination for outsourcing because of the trust that the western countries have in it."