Clinical Research: A new frontier in the Pharmaceutical Field

Clinical Research: A new frontier in the Pharmaceutical Field

Dr. Subhash C. Mandal

1. Introduction:

Clinical research is now considered as one of the promising areas in the pharmaceutical field. This is one of the fastest growing disciplines in the Pharmaceutical industry. According to the Lead Discovery reports, the global clinical trials industry is currently about $10 billion and has the potential for fast growth in the future. The Indian clinical trial market has grown from $35 million in 2002 to $120 million in 2006. It was estimated that this market will grow to a large extent by 2010. Centre Watch expects it to be around US$ 250-300 million1, whereas McKinsey estimates a much higher figure of US$ 1.0-1.5 billion2. In 2002 40-50 clinical trials were conducted by 200-250 investigators and presently we have 700-1000 investigators in India. In USA 40000 investigators are conducting about 60000 trials.

In the recent past, there were several controversies noted that the existing legislature needed extensive changes for the safety of the patient, as well as to meet up the surrounding clinical trials and their procedures and it was needs of the clinical research industry in India. As a result, a number of regulations emerged and the existing Acts & Rules were amended. In the past Latin America and Eastern European countries like- Romania, Russia, Poland, Czech Republic, Hungary, Slovenia, Croatia etc. were preferred over India, but recently India is being considered as a global hub for clinical trials3. A report by Rabo says that India has the largest pool of patients with many diseases, including cancer and diabetes. This serves as a good volunteer base for clinical trials.

Pharma giants are also attracted to India due to the fact that the country has about 700,000 speciality hospital beds, 221 medical colleges and skilled English-speaking health care personnel. It was also pointed out that the low cost of study is the biggest advantage of conducting clinical research in India. For instance, trials for a new drug in the United States can cost about $150 million, where as a similar drug could be tested in India at 60 per cent of the cost involved in US.

Multinationals like Pfizer, Novartis, Eli Lilly have started clinical trials in India. A few Global CROs like- Quintiles are operating in India since 1997, where as a number of new CROs started by big companies of India like- Advinus Therapeutics Pvt. Ltd. promoted by TATA, Reliance Clinical Research Services promoted by Reliance Group etc.

2. Problems and peculiarities in India:

  • Patients / Subjects are not aware of their rights.

  • Patients have full faith in a doctor, equating them with almost living Gods.

  • Doctors / Scientists not are aware of obligations.

  • Status of Institutional Ethics Committee is not transparent.

  • Monitoring Mechanism is lax.

  • Diversity of Population.

  • Poor Awareness about –

  • transfer of biological material,

  • data transfer,

  • Intellectual Property Rights,

  • Social and political sensitivities in collaborative research.

  • Practice of different systems of medicines like- Ayurveda, Unani, Siddha and Homoeopathy.

3. Regulatory Changes:

3.1. Schedule Y: It was introduced in Drugs Act in 1998, prescribing the regulatory requirements for conducting clinical trials in India. This initiative encouraged the industry to conduct Phase III trials for registering new drugs for marketing in the Indian market. It also provides requirement for registering new molecules as drugs. However it was not considered comprehensive enough in comparison to the standards set by other countries/ organizations. However as a result of this initiative, 441 new drugs were approved for marketing in India during 1988-20024. 750 more new drugs have been approved by the DCGI following schedule Y during 1st January 2003 to 31st July 2008, most of them being FDCs. Very few new molecules were introduced, may be due to the effect of Patent Act effective from 1st January 2005

3.2. Ethical Guidelines for Biomedical Research in Human Subjects: This document was framed by the Indian Council of Medical Research (ICMR) in the year of 2000. All biomedical researchers in India for drug development should follow this guideline, whether prior or subsequent to product registration in India5.

3.3. Good Clinical Practices GCP6: Good Clinical Practices (GCP) prescribes the Guidelines for Clinical Trials on Pharmaceutical Products in India. It was adopted in 2001 in India, (along the lines of Helsinki declaration) by Central Drugs Standard Control Organization (CDSCO), Director General of Health Services, Govt. of India. In order to establish the rights of the human subject and to maintain authenticity of the data generated. GCP prescribed a set of rules for biomedical studies to design, conduct, terminate, audit, analyze, report as well as ensure documentation of the studies involving human subjects. This document not only set rules for clinical research of new molecules, it also has prescribed rules for clinical trials for Vaccines, Contraceptives, Diagnostic agents, Surgical procedures/ Medical devices and herbal remedies and medicinal plants.

3.4. Revised Schedule Y7: This schedule was revised in January 2005 to remove its limitations and encourage clinical trials, protecting the rights of the trial subjects. The scope and definition of clinical trials are more clear and pragmatic in the amended version.

Rights of the human subjects are also protected by stipulations like- adhering to GCP, formation of ethics committee, prescribing formats for documents like – informed consent, report, EC approval reporting, ADR reporting, undertaking by the investigator etc.

The earlier restriction on the number of subjects and number of sites has been omitted allowing flexibility to the investigator in this regard and has encouraged researchers. The new amendment allows concurrent phase II, III & IV trials and also encourage clinical trial in India.

Amendment of Schedule Y is under serious consideration with respect to integrating the IPR status of the drug and framing more stringent norms regarding the Pharmacovigilance in post marketing surveillance.

3.5. Setting up of a Pharmacovigilance system in India 8:
A well-established Pharmacovigilance system is required to protect patients from the potential harm that may be caused by some of the newly introduced drugs. Though several key components of Pharmacovigilance were incorporated in to the Drugs & Cosmetics Act since 1940, there was no established set- up for Pharmacovigilance in India. During the last decade, several amendments were made and implemented to incorporate the idea. During last few years CDSCO is setting up a mechanism of Pharmacovigilance in India with the assistance of WHO. Presently an effective system has been established. Two Zonal centers have been established at Mumbai and Delhi. 5 regional centers were established at Kolkata, Mumbai, Nagpur, New Delhi and Pondicherry. 24 peripheral centers are now operating from different medical colleges or Pharmacy colleges throughout the country. The national Pharmacovigilance programme encourages the reporting of all suspected adverse reaction to drugs and other medical substances including herbal, traditional or alternative remedies. Recently Schedule Y has been amended including mandatory requirement of post marketing surveillance of any new drug. A National Pharmacovigilance Advisory Committee (NPAC) has been formed to oversee the performance of various zonal, regional and peripheral centers and to recommend possible regulatory measures based on data received from different centers. This is an important step for developing confidence of the sponsors to outsource their clinical trials from India.

4. West Bengal is in tune with time: Due to globalization, West Bengal is also into the process of changes and is gearing up to take up this challenge. We have 8 medical colleges, twelve Pharmacy colleges who are producing clinical manpower. A new medical college started its operation from this session at Kolkata in private sector. Three more such proposals are also in the process. A number of Pharmacy colleges are offering M. Pharm. courses since the last couple of years, besides Jadavpur University.

Department of Pharmaceutical Technology, Jadavpur University has started M. Pharm Course on Clinical Pharmacy & Pharmacy Practice in collaboration with AMRI and will also play an important role in producing trained manpower. A good number of volunteers are available in this state easily. A few CROs are already operating from this state like, Chembiotec, Chemgen, Pharmaintel, TCG Life Sciences and the Bioequivalance Centre of Jadavpur University. More organizations both in private & Government sector are in the process of setting up of Clinical Research Centers in West Bengal. The recently formed West Bengal University of Health Sciences may coordinate in developing trained clinical manpower. There is a plan to upgrade Calcutta Medical College to the standard of All India Institute of Medical Sciences (AIIMS). National Institute of Pharmaceutical Education & Research (NIPER) has started its operation since 2007 from the campus of Indian Institute of Chemical Biology (IICB). Presently the institute is offering M.S.(Pharm.) courses in three specializations – Medicinal Chemistry, Natural Products and Pharmacoinformatics, which will certainly boost the Clinical research scene in West Bengal.

West Bengal Govt. has taken a pragmatic step in creating a new Ministry of Biotechnology, which brightens up the prospects in this area.

5. Conclusion: India has inherent advantages for conducting clinical trials because of availability of a large pool of patients, a sizeable English speaking & IT savvy manpower. India has also framed suitable regulations to protect the rights of the trial subjects and made some provisions to encourage clinical investors. Presently the condition is conducive to clinical research which has put India in the global map and has also made it a lucrative place for conducting clinical trials. West Bengal is not an exception and is ready to match with the situation.

References: 1. Borfitz D, “Lifting India’s Barriers to Clinical Trials”, Centre Watch, 10 (8): 1-9, 2003. 2. Bhatt A. D, Sahoo U.K, “2010: Indian Clinical Research Odyssey”, Chronicle Pharma Biz, Feb. 26, 2004. 3. Kulkurni N& Suresh N, “Clinical Trials in the eye of a storm”, Biospectrum, 2(11), 40-51, 2004. 4. Ghosh A., Hazra A., Mandal S.C, “New Drugs in India over the past 15 years: Analysis of trends” The National Medical Journal of India, 17(1), 10-16, Jan-Feb 2004. 5. Ethical Guidelines for Biomedical Research on Human subjects, Indian Council of Medical Research, New Delhi 2000. 6. Good Clinical Practices, Central Drugs Standard Control Organization, Directorate General of Health Services, Ministry of Health & Family Welfare, Govt. of India, 2001. 7. The Drugs & Cosmetics Rules 1945, Ministry of Health and Family Welfare, Govt. of India, 425-459, 2005.

8. Mandal S.C, Mandal M., “The role of hospital pharmacists in the new global scenario: A paradigm shift” Pharmatimes, 39 (60), 21-24, 2007.

(The Author is Hony. Vice-President, Indian Pharmaceutical Association, Bengal Branch)