White Paper on

Global Clinical Trials in India Prospects and Challenges

Federation of Indian Chambers of Commerce & Industry

White Paper onGlobal Clinical Trials in India Prospects and Challenges

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Cygnus Business Consulting & Research

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PREFACE
This White Paper on Global Clinical Trials in India Prospects and Challenges is presented in six parts. To begin with, the introduction to clinical trials and its background have been mentioned in the basis of a consensus among the stakeholders has been elaborated. The regulatory framework for conducting Stem Cell, tissue engineering, vaccines, molecular diagnostic products Research in India is discussed in part 3. The ways of strengthening Institutional ethics is briefed in part 4. The regulatory issues for import and export of biological materials are reviewed in part 5. Finally, Part 6 & 7 deals with the Capacity building in medical institutions and career options in Clinical research respectively. The future outlook for clinical trials is given in part 8.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

part 1. In Part 2, a review and analysis of the opportunities and operational deficiencies evolved on

Table of Contents

2. Opportunities and Operational Deficiencies for Clinical Trial in India ................................................................... 2 3. Regulatory framework for conducting Stem Cell, tissue engineering, vaccines, molecular diagnostic products Research in India .............................................................. 6 3. Strengthening Institutional Ethics at par with Global Benchmark ........................................................................... 11 5. Regulatory issues for import and export of biological materials........................................................................... 17 6. Capacity building in clinical research at medical institutions .......................................................................... 22 7. Career options in Clinical trials ...................................................... 25 8. Future Outlook ................................................................................ 29

White Paper onGlobal Clinical Trials in India Prospects and Challenges

1. Introduction ........................................................................................ 1

Introduction
White Paper onGlobal Clinical Trials in India Prospects and Challenges

India is fast emerging as a favoured destination for clinical trials by global pharmaceutical and biotech companies that are looking for partnerships or setting up new operations. Two major reasons for its popularity are: easy access and availability of a large, diverse and therapy-nave population with vast gene pool and lower cost of technical services resulting into lower per patient trial cost. It is well documented that the average costs of doing Phase I/II/III drug trials in US are $20/50/100 million respectively whereas in India they are 50-60% of the same and could be up to 75% faster. India also has the advantage of having a large pool of highly trained physicians, nurses, and technical personnel; numerous world-class medical facilities; broadly developed information technology infrastructure; a favourable IPR environment (post signing the WTO agreement) and use of English as the primary business and medical language. The total value of clinical research performed in India in 2004-05 was about US$100 million. The nature of players involved in these clinical trials in India is given in chart 1. The size of the global clinical trials market is nearly US$10 billion today, and could rise to US$26 billion by 2007, according to an US estimate. It has been reported that approximately 3,500 drugs are under development at a given time and the number of new dr ug applications are nearly 4,000. Approximately 90,000 clinical trials were performed globally in 2003 and nearly nine million patients participated in them. To speed up the clinical trails and their analysis, pharmaceutical industry is using the latest technology tools such as Recombinant DNA technology, biotechnology and bioinformatics in the research and trials activities. Analysis of clinical trials data is the major step in the drug development and release. The major objectives of the summit are discussed in the paper under the following heads: 1. Opportunities and operational deficiencies in conducting clinical trials in India 2. Regulatory framework for conducting stem cell, tissue engineering, vaccines, molecular diagnostic products Research in India. 3. Strengthening Institutional ethics at par with global benchmark 4. Regulatory issues for import and export of biological materials 5. Capacity building in clinical research at medical institutions 6. Career option in Clinical Research

Opportunities and Operational Deficiencies for Clinical Trial in India

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Clinical research industry in India is set for a major growth in terms of revenue, thanks to the countrys inherent advantages like lower cost, fast patient recruitment, large pool of patients, large base of qualified personnel, etc. The growth of clinical trial industry is directly linked to the growth of health care industry in India as well as world over. In particular, increase in research and development activities would lead to a higher demand for clinical trial services which meet global standards.

Opportunities
India has a vast population with wide range of races, living in different climatic conditions, suffering from various diseases on the basis of socio economic, environmental and seasonal changes. A huge patient population, genetically distinct groups, specialty hospitals with state-of the-art facilities, nearly 7 lakh hospital beds and 221 medical colleges, and skilled, English-speaking investigators, are Indias Key strengths. India is recognised as one of the leaders in the IT industry. This strength is already being leveraged in the bioinformatics area to support a variety of drug discovery efforts. In addition, a number of large pharma companies are leveraging Indias IT strength to support clinical trials and data management. This can be easily extended to safety monitoring and postmarketing surveillance.

Favorable environment
Increasing the expenditure on drug development, lengthening time lines for clinical trials, patent regime, changing regulations have become serious problems/bottlenecks in pharmaceutical research for development of new drugs in developed countries for the past decade. The emerging positive trends in India offer a potential solution to some of these problems. There are key broad areas to leverage the advantages that India offers to the established pharma and biotech industries. These include contract research, R&D alliances, clinical trials, R&D for neglected diseases, in-licensing of preclinical as well as early clinical drug candidates, IT applications and data management and herbal heritage.

Higher growth in Asia Pacific

As pharmaceutical and biotechnology companies continue to explore new geographic opportunities to expand their pipelines of products and create business efficiencies, the importance of Asia-Pacific market is growing. The quality of science and capabilities in drug

New Patent Regime

The new patent regime will have a potential impact on domestic and foreign companies doing business in India. The protection of intellectual property rights in India which was one of the biggest concerns of global pharmaceutical companies seeking to enter India in the past has changed rapidly to post-TRIPS and WTO scenario. A well established statutory, administrative and judicial framework, to safeguard intellectual property rights in India is slowly gaining momentum. It is focused on issues like infringement drug discovery, patents, royalties, damage exemptions for clinical trials and statutes blocking importation of products.

Alliances
India has already established its strength in developing, manufacturing and marketing generic products for global market. This success is attributed primarily to its strength in the process chemistry, formulation development and manufacturing areas. Transition to innovative R&D is naturally the next step for India. There are a number of contract research organisations that offer quality and cost-effective services in medicinal chemistry, formulation development, and toxicology areas. In order to leverage these resources, pharma companies from developed countries are already forging R&D alliances with Indian companies. These alliances are giving preclinical candidates or clinical candidates with proof of concept in humans.

Cost Advantage
In developed countries, average cost of bringing new molecule to the market, is about US$800m including the cost of possible failures. Within the pharma R& D value chain, failures occur at various stages and cumulative success rate of a given drug discovery programme is about 1.5%. The probability of success increases to about 50-75% once a molecule enters Phase III clinical trials. By conducting R&D on new molecules up to Phase II of clinical trails in India, the cost of innovation and development can be drastically reduced. It is conceivable to reduce the cost of failure and eventually overall cost of bringing new medicines to patients. This is one of the unique opportunities in India. Low cost of innovation and development will allow bringing new molecules for the neglected diseases to market at a much reduced cost. Since the medicines for neglected diseases must be affordable to patients in the poor countries, it is essential to develop these drugs in the most cost-effective manner. Early estimates are that drugs could be tested in India at 60% of the price.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

discovery vary widely between India, China, Japan, Taiwan and Singapore. Pharmaceutical R&D expenditure in Asia is growing faster than in US and Europe. According to the various estimates, the global contract research market is estimated at US$10 billion in 2004 and about 40 to 50% of it will be outsourced to developing countries by 2010.

Established Pharma Companies

Indian companies are highly capable in research and development particularly in drug discovery. It has already proven its capabilities in discovering and developing drug candidate molecules. A number of development candidates are out-licensed by Indian companies to the medium size as well as large pharma companies in the developed countries. This trend is expected to continue. In India alternative medicine systems are well-established. However, the molecular mechanism of action and identity of active ingredient(s) may not be known for most of these traditional medicines. There are opportunities to apply modern science to elucidate molecular mechanism of action and to identify active ingredients of these medicines. The process of reverse pharmacology can be applied to discover new drug candidate molecules from these traditional medicines.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Operational Deficiencies
The increase in clinical trials is fueled by the recent push for global commerce. Regulatory uncertainties about time to approval, involvement of multiple agencies for approval of biotech products and for processing import/export licenses, and several other factors are hurdles in planning a clinical trial. A large majority of potential investigators lack knowledge of regulations, ethics and GCP, and skills for clinical trial management. The quality of global trials and academic clinical research is not uniform. There are also issues of inadequate permanent research staff and lack of adequate infrastructure for communication, drug / sample storage, archival. The situation is worse in non-metro cities which have tremendous potential for participation in global trials. In addition, the institutional policies are not yet geared up to support the investigator in managing clinical trials efficiently. Perhaps the most important challenge is that of designing elegant clinical trials that will test concepts rather than simply compare products. Some of the major operational deficiencies are as follows:

Training for Clinical Trials

Most medical schools lack a formal course in training for clinical research, and investigators have relied on mentors to learn how to conduct clinical trials. There is a shortage of trained manpower. India has about 500 1000 investigators in the country, as compared to United States that has 50,000 investigators. With the projections made for the industry in 2010, India would need about six times its present number of investigators.

Government Policies
Regulatory approvals in India can take three months or more, compared to 30 days in the US. Even more serious is the lack of confidentiality. Unlike China, India does not yet grant protection for data gleaned from clinical trials, which makes it easy for generic drug makers to copy the

drug under trial. Under Indias existing laws, only those drugs that have already passed Phase 1 safety trials in the country of their origin can be tested on Indians.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Weak Patent Law

In India, opportunities will become limited unless there is a very strong patent law and mechanism to enforce it. Drafting patent laws with the help of industry experts and its implementation is highly essential.

Good Clinical Practices (GCP)

The experience of conducting global GCP trials is limited. GCP is a shared responsibility amongst sponsors, investigators, regulators and ethics committees. In a country which boasts of a large medical fraternity, only 400-500 investigator sites have taken part in global GCP trials. As all stakeholders are still learning, the journey towards achieving global quality is unlikely to be smooth. The efforts of the government and industry to create awareness through GCP workshops and to provide training to the investigators and ECs will go a long way in creating a culture of global GCP quality trials.

Ethical committees
The field is dogged by complaints that Indian trial investigators recruit patients unethically, exaggerate claims and downplay the risks of trial drugs. Institutional ethics committees cant help much either. In most of the cases, the committees are headed by the institutional heads, and follow their instructions rather than the ethical committees recommendations. At the federal level, the central ethics committee at the Indian Council of Medical Research issues guidelines but has no policing powers.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Regulatory framework for conducting Stem Cell, tissue engineering, vaccines, molecular diagnostic products Research in India
Stem Cells Stem Cell is a cell that has the ability to continuously divide and differentiate into various other kind(s) of cells/tissues is called stem cell. Stem cells are blank cells obtained from human embryos of a few weeks old, which can develop into a variety of cells in human body. It is believed that stem cells can transform eventually into any of human bodys approximately 260 different cell types. These cells can also develop into heart, muscle, brain, skin, bones or into any other body tissue. Scientists are of the view that these diverse cell types would lead to new forms of treatment for many serious diseases that cannot be cured presently. It is estimated that, roughly 128m people suffer from diseases that could be effectively treated or cured through stem cell research. Out of these, as many as 58m people suffer from some form of cardiovascular diseases treatable through the new form of medical research. Biotech companies based in the US namely Geron Corp and Curis Inc are already working on the commercial applications of this new medical technology. In coming 5-10 years, stem cell therapies will be able to treat a number of diseases.

Research
Since isolation of human embryonic stem cells, medical research has taken unprecedented turn to address many hard core diseases like kidney failure, blood transfusion and ophthalmic problems. Several medical research institutes around the globe have developed stem cell lines which are accepted for federal funding by the US Government. National Institute of Health which maintains stem cell registry has registered 64 stem cell lines so far. The distribution of the cell lines for research or for commercialisation purposes will be solely at the discretion of the individual laboratories which created them. In India, two prestigious institutes are recognised by federal governments for stem cell research: 1. National Centre for Biological Sciences, Bangalore 2. Reliance Life Sciences Laboratories, Mumbai

Issues in Stem Cell Research

Several important issues which impinge on the future of stem cell research are: scientific, technical, ethical and moral issues on use of human embryo or adult cells; Intellectual property rights, financial supports and funding. National and International Guidelines and Policies for stem cell research are

Regulatory environment
As these promising new therapies are going to be based on biological materials derived from human bodies, some of the social and ethical issues involved in procuring these materials need to be addressed. Currently there are no regulations governing the stem cell research in any of the countries which are identified to be having stem cell lines. But in USA, American Heart Association (AHA) is already developing a set of guidelines to be followed by the laboratories engaged in the stem cell research. These guidelines, under preparation, may prohibit payment or other inducement to donors, physicians, hospitals or research labs for stem cells derived for research purpose. AHA guidelines are also expected to ban creation of embryos for the purpose of harvesting stem cells, combining stem cells with animal embryos or even using stem cells to create a human being. These possible misuses are, no doubt, issues of extreme concern not only for the US but also for all countries including India. The Government of India too has set up a high level committee in a bid to frame an ethics policy for genomic research including stem cell technology. It is important, in this context, that these regulations are finalised without much delay and after adequate consultations with various non-government organisations and independent medical experts. Tissue Engineering Tissue engineering is the science of altering, modifying and controlling reproduction and degeneration of biological tissue along with complete tissues outside of the body ready for future transplant use. Using tissue engineering techniques, it is possible to regenerate dying tissues and organs in a human body; grow new blood vessels; heal wounds and new cartilage; or even stop cancerous cells from a multiplication spree. This technology is available with several types of replacement skin, cartilage, regeneration of bone and other connective structural substitutes.

Research
It is an emerging field with extraordinary advances in medical technology. Regenerative Medicine is one of the most rapidly advancing biotechnological areas of development and discovery in the medical field. Repairing/replacing the tissue/organs with the help of advanced technology like stem cell research/tissue engineering can treat many patients; particularly suffering from cardiovascular diseases which cannot be cured with medicines. Products currently in the market include simple tissues such as skin, cartilage and bone; the technology could lead to the in vitro construction of human organs. The estimated market for tissue engineering products is expected to be approximately US$5 billion worldwide by 2013.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

in the initial stages of drafting and implementation. In addition, it has been recently shown that the belief that adult cells are incapable of differentiation and hence are not useful is indeed a myth. In studies conducted on mice, adult cells from certain parts of the body could transform themselves to other cell types. The significance of these observations is that this technique of using adult cells could be more useful for repairing of tissues damaged by injury or disease.

Guidelines for Stem cell Research and Tissue engineering

Adult Stem Cells: Use of adult stem cells does not pose major ethical problems at present, as these are easy to obtain. All centres doing stem cell transplantation should register with this Committee. Bone marrow, peripheral blood, skin, limbal cells are some of the tissues in use. Proper informed consent procedures are to be followed as given in the ICMR ethical guidelines. Storage and preservation Standard Operating Procedures (SOPs) should be followed. In vivo studies: Experimental work on stimulation of adult stem cells also has tremendous future. Approval from NAC must be sought for carrying out these experiments, clinical or therapeutic trials.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Cord Blood Stem Cells: For using umbilical cord blood from a live foetus or a neonate, it must be ensured that no harm should occur to the foetus or the neonate. There is a risk that the neonate donor may need his or her own cord blood later. If the blood has been used for another, he or she may be left without much needed blood. Parents should be informed of the risks of donation and a written consent be obtained from them. Cord blood stem cell is generally used for haemopoietic stem cell transplantation. For any other form of therapy detailed protocol has to be submitted for approval. Foetal stem cells/tissue: These can be processed from spontaneously aborted foetus or from foetuses obtained from MTP clinics. DNA fingerprinting of the cell line should be preserved and it is advised to keep it in cell repository. Generally, EG cells will be permitted only for experimental purposes at present. Any therapeutic transplantation will not be permitted at present and this possibility will be examined at an appropriate time later. Embryonic stem cells (ES Cells): Embryo should not be generated for the sole purpose of obtaining stem cells. Only surplus or spare or supernumery embryos can be used with the permission of the couple from registered ART clinics. Cell lines generated should be registered. At present only research programme relating to in vitro induction of differentiation into various cell lines will be cleared by the Committee (NAC) on case-to-case basis. Reproductive cloning will not be permitted on ethical grounds. At present, human cloning is not permitted for the purpose of creating a new individual. However, in cases where cloning is for therapeutic purposes involving cells, tissues or organs; the committee will examine on a case-to-case basis. Monitoring Mechanism: A central monitoring committee a sub committee of the Apex Committee should be constituted to make site visits as and when required. Annual report should be submitted in appropriate format for further continuation of the project by 10th month of commencement of the project decision and review should be communicated in

4-6 weeks. Any violation of guidelines would be strictly dealt with. Commercialisation and Patent issues: Established stem cell lines can have considerable commercial value as wide ranging potential benefits for large number of patients is possible. Patent issues need wider discussion and public debates should be held on who should be the beneficiary and what type of patents can be taken. Regulation of stem cell lines: All cell lines should be registered with this committee. All proposals for therapeutic trial should be cleared by this committee before submitting to DCGI. Vaccines Preventing and controlling diseases with the help of vaccines has become common. Now most of the hardcore diseases have vaccines. With the help of latest technologies like tissue culture, recombinant DNA Technology and advanced equipments supported by computers and electronics, new vaccines are developed for many life threatening diseases.

Research
Presently, different types of vaccines are being developed with the help of advanced research tools. Researchers are able to identify certain biochemical components of a disease-causing microorganism that stimulate the immune response to that micro-organism in the body. They are able to identify the portion that reacts with the human immune system to build antibodies to defend against the disease or infection. This biochemical component of the pathogen is then produced in a laboratory and given to humans as a vaccine. Another approach being used is the Recombination of DNA technology. Vaccinia virus is produced by splicing and isolating the gene; producing immune components and combining it into DNA of an entirely different micro-organism. The altered virus is then injected into the human and stimulates antibody production both to itself and to the pathogen with the newly incorporated genes. This approach enables the vaccinia virus to function as a live vaccine against several diseases once it has received gene splices from the relevant disease-causing micro-organism.

Market
Vaccine producers in developing countries are strengthening their manufacturing capacities and are looking forward to development and launch of newer vaccines. The domestic vaccine market is currently US$100m and growing at the rate of more than 20% per year. The potential for these products is immense with the possible market for all types of diarrhea vaccines alone being about $200 million. Many developed countries are no longer interested in producing vaccines since production has become uneconomical due to drastic reduction in prices and less access to markets in the developing countries. India along with other developing countries such as Indonesia, Cuba and Brazil supplies 60% of UNICEFs global requirement for vaccines.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Regulatory environment
White Paper onGlobal Clinical Trials in India Prospects and Challenges

FDAs Centre for Biologics Evaluation and Research (CBER) is responsible for regulating vaccines. Vaccine clinical development follows the same general pathway as for drugs and other biologics. Successful completion of all three phases of clinical development can be followed by the submission of a Biologics License Application (BLA). The license application must provide the multidisciplinary FDA reviewer team (medical officers, microbiologists, chemists, biostatisticians, etc.) with the efficacy and safety information necessary to make a risk/benefit assessment and to recommend or oppose the approval of a vaccine. Until a vaccine is given to the general population, all potential adverse events cannot be anticipated. Thus, many vaccines undergo Phase 4 studies - formal studies on a vaccine once it is in the market. Also, the government relies on the Vaccine Adverse Event Reporting System (VAERS) to identify problems after marketing begins. At any stage of the clinical or animal studies, if data raises significant concerns about either safety or effectiveness, FDA may request additional information or studies, or may halt ongoing clinical studies.

Molecular Diagnostic Products

Molecular diagnostics is continuing to emerge as one of the dominant testing platforms and represents one of the fastest-growing segments of the In-vitro diagnostic tests (IVD) market. However, the contributions that molecular diagnostics can make to clinical decision making still face significant obstacles, including reimbursement issues, lack of standardisation and difficulties in interpreting test data.

Market
Use of molecular-based diagnostic solutions is expanding. The viral load monitoring and genotyping techniques that have increased the life expectancy of HIV-infected patients, have led to their emergence as valuable tools for the management of hepatitis C. The market for molecular diagnostics includes an extensive list of innovative products and testing solutions. New developments such as gene sequencing and nucleic acid amplification have revolutionised the in vitro diagnostics industry. Increasing insight into the ways in which genes influence a pathogens response to therapy is ensuring tremendous growth in pharmacogenomics. Collaborations between diagnostic and pharmaceutical companies are expected to drive sales of both products.

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Research
Molecular based diagnostics are used in genotyping, viral load monitoring and single nucleotide polymorphism detection. Molecular diagnostic products become vital components of disease prevention, management and treatment. Innovative molecular-based diagnostic solutions have provided healthcare professionals with valuable data unobtainable by other means. Current trends

merge the benefits of assays and drugs, and work synergistically in the treatment of disease. The implementation of nucleic acid testing reduces the time lag between infection and detection to half of that taken by traditional immunoassays. Development of polymerase chain reaction (PCR) technology, with an emphasis on practical applications, has direct benefits to healthcare. This was possible with the commitment in the form of grants to academic institutions, government laboratories and non-profit organisations for PCRrelated research. HIV and Hepatitis C Virus (HCV) immunodiagnostic tests became popular through molecular diagnostics and critical care blood gas analyzers. Molecular diagnostics test for tuberculosis, strep throad, pneumonia, and fungal infections have become routine. Instruments like Turgene HIV-1 genotyping assay, homogenous amplification and real time detection technology, real time DNA amplification assay, energy transfer detection method, isothermal amplification technology for rapid generation of single DNA or RNA templates are becoming easy with the help of molecular diagnostics.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Regulatory environment
At present, more than half of the diagnostic kits are imported at higher cost and are often ineffective as they are not designed for variant Indian strains of microbes. There are no standard guidelines to grant license for manufacturing diagnostic products and for the approval of all ranges of products (for either imported or products manufactured in India). These vary from state to state. There is also no special package and exemption in taxes from the government for establishing diagnostic manufacturing units. The number of cheaper and efficient technology transfers in the area of diagnostics is limited. High import duty and custom clearance procedures, competition, logistics, lack of knowledge, licensing, slow pace of approvals from statutory authorities, lack of national laboratory network for evaluation and approval of new products are some of the factors slowing down the pace of indigenization.

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White Paper onGlobal Clinical Trials in India Prospects and Challenges

Strengthening Institutional Ethics at par with Global Benchmark

Since the research activities in biomedical sciences have increased and many live biological organisms are used for the purpose of research, ethical concerns have been raised throughout the globe. New drug development for the treatment of many diseases and its clinical trials on human population by many countries are drawing the attention of many ethical groups. All the developed countries who are actively involved in biomedical research are following institutional guidelines of the ethical committee for conducting research, be it laboratory animals, patients in hospitals or volunteers for clinical trials.

Global Ethical Principles and Guidelines for Biomedical Research using Human Subjects:
Three fundamental ethical principles that are relevant to all research involving human subjects are globally accepted: 1. Respect for Persons, 2. Beneficence, and 3. Justice. These three provide a comprehensive framework for ethical decision-making in research involving human subjects. 1. Principle of Respect: Persons acknowledges the dignity and autonomy of individuals, and requires that people with diminished autonomy be provided special protection. The human potential vulnerability, certain subject populations are provided with additional protections. These include live human fetuses, children, prisoners, the mentally disabled, and people with severe illnesses. 2. The principle of Beneficence: It requires protecting individuals by maximizing benefits and minimizing possible harms. It is necessary to examine carefully the design of the study and its risks and benefits. Identifying alternative ways of obtaining the benefits sought from the research. 3. The principle of Justice: It requires treating subjects fairly. Subjects should be carefully and equitably chosen to insure that certain individuals such as prisoners, elderly people, or financially impoverished people are not systematically selected or excluded, unless there are scientifically or ethically valid reasons for doing so. Each of these principles carries strong moral force, and difficult ethical dilemmas arise when they conflict. A careful and thoughtful application of the principles will not always achieve clear resolution of ethical problems. However, it is important to understand and apply the principles, to assure that people who agree to be experimental subjects will be treated in a respectful and ethical manner. In hospitals throughout US, Institutional Ethics Committees (IECs) have become a standard vehicle for the education of health professionals about biomedical ethics, for the drafting and review of hospital policy, and for clinical ethics case consultation. In addition, there is an increasing

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interest in the role for the IEC in organizational ethics. Recommendations are made for the membership and structure of an IEC, and guidelines are provided for those serving on an ethics committee.

IEC Members The quality of an ethical consultation rests on the IECs ability to provide a forum for open discussion of the 1. Chairperson medical, moral, and legal issues surrounding a difficult 2. One or two basic medical scientists. situation. The authority, whether institutional, moral, or 3. One or two clinicians from various Institutes legal, of an ethics consultant and an IEC, is limited. The 4. One legal expert or retired judge Academy supports the view that the recommendations from an ethics consultation are advisory only, with all 5. One social scientist / rep. of NGO parties to a disagreement taking full responsibility for 6. One philosopher / ethicist / theologian their own actions. Improved communication, clarification 7. One lay person from the community of differences and available options, and careful 8. Member Secretary documentation of the decisional process may well reduce the potential for future legal action. Ethics consultations should be documented in the committee records, and, in most cases, a summary of the consultation should be briefly, yet completely, included in the patients medical record. The form and extent of chart documentation of ethical consultations may vary depending on local hospital regulations and requirements.
Composition: Institutional Ethical Committees should be multidisciplinary and multi-sectoral in composition. Independence and competence are the two hallmarks of an IEC. The number of persons in an ethical committee is fairly small. It is generally accepted that a minimum of five persons is required to compose a quorum. There is no specific recommendation for a widely acceptable maximum number of persons but it should be kept in mind that too large a Committee will make it difficult in reaching consensus of opinion. Around 12-15 is the maximum number recommended. The Chairperson of the Committee should preferably be from outside the Institution and not head of the same Institution to maintain the autonomy of the Committee. The Member Secretary who generally belongs to the same Institution should conduct the business of the Committee. Other members should be a mix of medical /non-medical, scientific and non-scientific persons including lay public to reflect varied viewpoints.

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Role of IEC in Organisational Ethics

Recent trends in the financing and provision of health care have raised concerns about the impact of institutional commitments such as managed-care contracts, integrated systems, and performance incentives on the care of patients. Organisational ethics in the purview of the IEC raises specific questions about its structure, function, and member qualifications.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Role of Research Body

Role of IEC in clinical ethics

The potential importance of the IECs consultative role has been recognised in numerous ways. Health care organisations have an established mechanism to address conflicts, a requirement most often met by establishing an IEC. Law suggests that IEC deliberations may serve as evidence in court; Proposals to establish an IEC as an alternative to judicial review; and Requirement of the Joint Commission on Accreditation of Healthcare Organisations

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Institutional ethical committees - Indian Scenario

In India, ethical guidelines were drafted by Indian Council of Medical Research (ICMR) for conducting biomedical research in laboratory animals and clinical trials for new drugs on human population. The institute was given authority to monitor the implementation of ethical guidelines in biomedical research. The ICMR and its allied research institutes in India are having the ethical guidelines and IECs for observing the guidelines in its biological research activities. Each institute has its own ethical committee for monitoring the guidelines. As per the guidelines, at any stage, any deviation in ethics, on the basis of religion, socioeconomic status, protecting the confidentiality of the volunteers will be awarded severe punishments. All the life science researchers, particularly biomedical researchers, working with laboratory animals, human patients, volunteers in clinical trials has to follow the guidelines strictly.

Strengthening Control
ICMR lacks the authority to take action against unethical IECs. There exists no mechanism for accreditation of IECs and quality control of ethics review is practically impossible. There is no comprehensive database on either IECs or research participants. India is also witnessing the birth of unaffiliated Ethics Committees to review protocols for institutions with no IECs, supported by fees from the pharmaceutical industry. In the West, there is an uneasy alliance between such bodies and the industry. Institutional mechanisms for ethical reviewing of research involving human participants in India are weak and vulnerable. A concerted effort is required to strengthen them to fulfil their stated missions. The problem is likely to be worse in India. These are major threats to the international companies to conduct clinical trials in India.

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ICMR Role
In addition to developing general research guidelines, it has started preparing guidelines for specific areas of research. It has constituted a Bioethics Cell under senior staff trained in bioethics. It is preparing standard operating procedures for IECs and standard formats for ethics review across IECs. It has supported the formation of a forum for ethics review committees in India, is working with similar bodies in the Asia-Pacific region, and is putting together a database on IECs in the country. To enhance ethics capacity, the ICMR identifies mid-career professionals to be trained in

Recommendations by ICMR 1. IEC should diverse and reflect different perspectives within hospital, general community. 2. IEC should owe responsibility within an institution for clinical ethical consultation, review of policies, education of professional, administrative, and support staff about ethical issues, regardless of whether these functions are delegated to other subcommittees. 3. IEC engaged in clinical ethical consultations should have policies and procedures that conform to ethical principles of fairness and confidentiality. 4. IEC should conduct education and training programs which ensure that members are qualified to perform specific duties. 5. Independent ethics committees, such as an infant care review committee, should be dissolved or restructured to report to the larger IEC. 6. IECs within a general hospital setting should ensure an adequate degree of multidisciplinary expertise for addressing ethical issues specific to pediatrics. bioethics through fellowships, training sessions for researchers, academicians, IEC members and students within India. With the help of National Institute of Health, USA, initiatives were taken to strengthen the capacity of bioethics in India to meet the global standards of World Health Organisation and UNESCO.

Guidelines for Institutional Ethics:

The IEC should establish standards of membership, process, and self-improvement specific to organisational ethics issues and to the organisational structure of its home institution. IEC should establish procedures for the evaluation and quality improvement of committee functions, process, and success in meeting institutional expectations. Establish an organizational ethics subcommittee of the IEC that includes additional representatives from administration and finance, along with persons committed to developing the requisite knowledge and skills in business ethics. Processes the organisational ethics teams commonly use to carry out their mission mirror Those of clinical ethics: education, policy development, and case consultation.

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Areas for strengthening

Effectiveness of IECs: According to a study by V Mohanan Nair and K Martin (*), Despite these guidelines, more than 50% of institutions conducting clinical research in India lack formal IECs. It is apparently difficult to get external members to volunteer, especially from among trained
** V Mohanan Nair: Civil Surgeon, General Hospital, Thiruvananthapuram, Kerala 695011, India. Douglas K Martin: Assistant Professor, Department of Health Policy, Management and Evaluation and the Joint Centre for Bioethics, University of Toronto, Canada.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

legal scholars and ethicists. Most medical schools do not offer bioethics courses. Typically, wellknown people are nominated as IEC members. Finally, in the Indian context, lay persons can be intimidated in the presence of more powerful scientific members.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Infrastructure and processes : Many Institutional Ethical Committees do not have sufficient office space. There have been instances of protocols disappearing after the projects approval. The IEC secretary can be a middle or lower level staff or faculty member for whom this responsibility is in addition to a full workload. There are no post-approval monitoring systems in place, and IECs responsibilities tend to end with approval. Without standard operating procedures, the IECs may follow different methods for submission, approval and follow up of research. Monitoring: Monitoring of Institutional Ethical Committee is weak; researchers may be under pressure to cut corners. Drug companies hire practicing doctors as researchers for their prescribing potentials. The main aim of research professionals is publishing research articles in international reputed journals - a vehicle for career advancement. Most of researchers are middle- aged people who are physicians employed by educational institutions, carrying out research on a part-time basis. Many investigators who conduct clinical trials are beneficiaries of largesse from the pharmaceutical manufacturers. Institutional members in the IEC may be junior to these researchers. Since no overt conflict of interest is apparent to IECs, the indirect benefits and mutual1 arrangements between companies and doctors often go unnoticed. Institutions need for resources may also put subtle pressure on IECs to approve research.

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Regulatory issues for import and export of biological materials

Clinical research firms are, by far, the most research intensive among major industries. Government support, fiscal incentives and tax benefits are therefore critical to this sector. These measures will in turn help to capitalize on the inherent cost effectiveness of the Indian Clinical Research enterprises.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Overview of the Current Regulatory Framework

The Ministry of Environment & Forests has notified the Rules for the Manufacture, Use, Import, Export and Storage of Hazardous Microorganisms/Genetically Engineered Organisms or Cells 1989 (Rules 1989) under the Environment (Protection) Act, 1986. The biological materials are regulated under these Rules from the research and product development stage up to its release into the environment. Rules 1989 also define that the regulatory authorities are responsible for according various approvals. Presently there are three regulatory authorities for the rDNA research, product development and commercialization in the sector. Brief description and responsibilities of these regulatory authorities are as follows: (i) Institutional Biosafety Committee (IBSC) It is mandatory that the institutions intending to carry out research activities involving genetic manipulation of organisms constitute the IBSC. The Rules mandate the inclusion of nominee of DBT in the constitution of the IBSC. The IBSC is the nodal point for interaction within the institution for implementation of the rDNA Biosafety Guidelines. The activities of IBSC include training of personnel on bio safety and instituting health monitoring programme for laboratory personnel. (ii) Review Committee on Genetic Manipulation (RCGM) The RCGM is serviced by the Department of Biotechnology. Its mandate is to monitor the safety related aspects in respect of ongoing research projects and activities involving genetically engineered organisms/hazardous micro-organisms. The RCGM is also responsible to bring out manuals or guidelines specifying the procedure for regulatory process with respect to activities involving genetically modified organisms in research, utilization and their application including in industry with a view to ensure environmental safety. All on-going projects involving rDNA technology and controlled field experiments are reviewed by RCGM to ensure that adequate precautions and containment conditions are followed as per the guidelines. It is also empowered under Rules 1989 to lay down procedures restricting or prohibiting production, sale, import and use of genetically engineered organisms or cells as per the Schedule of Rules 1989.

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(iii) Genetic Engineering Approval Committee (GEAC) The Genetic Engineering Approval Committee (GEAC) serviced by the Ministry of Environment and Forests is responsible for approval of activities involving large-scale use of genetically modified/hazardous micro organisms and products thereof in research and industrial production from the environment angle. The GEAC is also responsible for approval of proposals relating to release of genetically modified/hazardous micro organisms and products into the environment including experimental field trials. The State Biotechnology Coordination Committee (SBCC) and District Level Committee (DLC) under Rules 1989 have the responsibility for post-release monitoring of genetically modified organisms/hazardous micro organisms and products thereof. The Drugs and Cosmetics Act 1940 and the Rules 1945 also regulate the biological materials, as amended from time to time. The Authority to regulate the biological products is the Drugs Controller General of India (DCGI) and the State Drugs Controller. The Recombinant Drugs Advisory Committee (RDAC) constituted by Ministry of Health and Family Welfare supports the DCGI.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Guidelines for Safety in Biotechnology aspects

Department of Biotechnology has evolved various guidelines, which have been adopted by RCGM and GEAC for the regulation of various biological products in the country. These guidelines include: a) Recombinant DNA Safety Guidelines, 1990: These guidelines include procedure for largescale production and deliberate release of GMOs and products thereof into the environment and shipment and import of GMOs for laboratory research. b) Guidelines for generating pre-clinical and clinical data for r-DNA based vaccines, diagnostics and other biologicals, 1999. The current practice of according approval for phase III clinical trials, both by the GEAC and the DCGI is based on the procedure outlined in the 1999 guidelines.

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Import and marketing of biological materials in finished formulation

In case of import of LMOs per se as products, in the absence of any product development within the country the probability of environmental risk would be less than that of indigenously manufactured products involving the use of LMOs. Since this scenario pertains to import of LMOs, the only activity envisaged within the country prior to issue of market authorization is the conduct of phase-III clinical trials. The product being a LMO, the procedure outlined therein from the clinical trial stage would be applicable in this case. Accordingly, GEAC to evaluate the environmental impact caused by handling and

Product Patents Regime

Biological material or traditional knowledge and any other subject matter of strategic importance that may be notified by the Government from time to time cannot be a subject for patent applications as per the new Amendment. They are related to lack of patentability of biological materials and various life forms including microorganisms, provision for parallel imports under the exhaustion of rights principle, liberal interpretation of the scope for issue of Compulsory Licenses, authority of the Controller and the Government to grant Compulsory Licenses for the domestic and export markets or even revocation or forced forfeiture of patent rights under a variety of conditions including high and unaffordable prices of drugs, definition of working of an invention not to include imports of the patented article, insistence on transfer of technology along with license to use the invention etc. Fiscal and trade policy initiatives Exemption of import duties on key R&D, contract manufacturing/clinical trial equipment and duty credit for R&D consumer goods to enable small and medium entrepreneurs to reduce the high capital cost of conducting research. Rationalization of import and export of biological material which is critical for clinical research and business process outsourcing. Remove customs duty on raw materials imported into India, where the finished product is imported duty free. Life Saving Drugs imported and sold in India are exempted from paying customs duty; whereas raw materials for diagnostics and other pharmaceutical biotech products manufactured in India have been levied customs duty. To promote the indigenous manufacturing industry and make it competitive globally, raw materials imported by Indian manufacturers should be eligible for Duty Drawback. Simplification and streamlining of procedures for import, clearance and storage of biologicals, land acquisition, obtaining environmental and pollution control approvals would be simplified and streamlined within shorter time frame lines through consultations with various central and state government departments. Analysis of the Current Regulatory Framework An analysis of the current regulatory framework was carried out in the context of regulatory objectives of various Authorities, other experts, industry associations as well as the developments

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White Paper onGlobal Clinical Trials in India Prospects and Challenges

large-scale use of LMOs, based on the data available from the country of origin and other countries where the product has been tested. Based on the assessment GEAC to accord in principle approval for import and recommend to DCGI the safety of the product from environmental angle for conduct of phase III clinical trials.

in the international scenario. The problems identified in import and exports of biologicals in the country are: Multiple approval system has led to cumbersome and lengthy approval process.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Regulatory objectives of the different agencies in the regulatory chain are sometimes overlapping leading to duplication in the approval process. Information sought tends to be sometimes duplicated and in piecemeal. Opportunity to an applicant to present proposal to the regulator is not a common practice. Frequencies of meetings of regulatory authorities are irregular and inadequate. Documents/information required by the regulatory authorities for review of the proposal is not clearly articulated. The sequential approval procedure under Rules 1989 off EPA and Drugs & Cosmetics Act and Rules are ambiguous. Environmental impacts of the GMOs / LMOs per se and the products thereof per se have not been clearly identified. Regulatory Committees lack expertise in some important aspects. The regulatory authorities also lack professional staffs to support the decision-making Committees. The risk assessment and management of micro organisms, bio-safety and risk categories as per WHO or other international standards/guidelines are not fully implemented. Imports off GMOs/LMOs as well as the non-GM micro organisms for R&D work has been made cumbersome with the new Plant Quarantine Order, issued by the Ministry of Agriculture, hampering the R&D, quality control and manufacturing activities. There is no mechanism for Post Marketing surveillance of biological products and feedback on product efficacy and environmental safety. The feasibility of establishing a single central regulatory body to address regulatory related issues in drugs, vaccines/ biologicals, diagnostics, industrial products, food and food products to overcome the constraints and bottlenecks in implementing the projects has not been seriously examined.

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Stakeholders views
Several views are expressed by stakeholders in favour of an independent National Biotechnology Regulatory Authority/Commission for providing a professionally managed single window mechanism for giving various clearances including biosafety issues. It was recognized that evolving such an institutional mechanism would involve a lengthy evolutionary process requiring extensive

To clearly define the roles of each regulatory authority and enumerate decision making criteria under Rules 1989 of EPA to remove ambiguity in the existing regulatory process To clearly enumerate the stepwise procedure involved in the bio safety regulations of LMOs and the products thereof for indigenous development as well as imported products. To specify the timelines for decision making by each regulatory authority To evolve the documentation system to be submitted by the applicant to the regulatory authorities for obtaining clearances.

Recommendations
Exemption of customs duty for materials and samples shall be a great boost to the CROs in bringing samples for trials. Pressure on the industry is also reduced by abolishing the minimum export turnover concept. Customs duty exemptions for specified pharma and biotech units approved by DSIR for importing equipment for R&D activities will include CROs as these are capital intensive and require sophisticated instruments for evaluation of drug substances. Income tax holiday for companies venturing into R&D extended by one-year up to 2004 shall encourage newer players in the R&D field. Speedier customs clearance of clinical trial materials and frozen biological samples shall provide a great opportunity for the clinical trial companies to grow and provide the much needed service to industry.

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White Paper onGlobal Clinical Trials in India Prospects and Challenges

consultations among various stakeholders. However, the feasibility of setting up such an institutional mechanism should be explored. Streamlining of the existing regulatory procedures for immediate redressal of the issues is required. The streamlining of the existing regulatory system under the Rules 1989 of EPA and the Drugs & Cosmetics Act and Rules are required as given below:

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Capacity building in clinical research at medical institutions

The total amount spent on new drug discovery in India is approximately 30%, while the remaining 70% is on development. In development, clinical research takes the huge chunk. Unfortunately, clinical research has not received the attention that it deserves in our country. In making research to work, to address the health needs of the poorest populations, a vital ingredient is to have local research capacity available. While it is not very expensive to develop cutting-edge innovative research programs, it is necessary to have the research capacity to identify, innovate, and adapt technology to our own needs in order to better address the burden of neglected tropical diseases. Research capacity building is an approach that starts with people and their needs; till recently, most of the clinical trials were conducted without a properly designed and reviewed protocol. Data collection and recording were not stipulated and lacked appropriate supervision and monitoring; good clinical and laboratory practices and standard operating procedures were absent; while adverse reaction detection and reporting mechanisms and ethical issues too were not addressed properly during planning and conducting of the trial.

Major areas
Capacity-building requires examination of interventions that develop the abilities, behaviour, relationships and values that enable an organization to carry out complex tasks. The central most are notions of time, human resources, management of change and most important, sustainability. Some of the critical components include: Understanding institutional priorities Initiating faculty discussions (dept. chairs)

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Clinical Research Advisory Committee Attending to the relationship between stakeholders (e.g., medical school and clinical system) Honestly examine current infrastructure & metrics.

Focus areas
Formation of Ethics Committees or institutional Review Boards: it is vital for these committees to be constituted and follow the procedures of ICH GCP guidelines Members should be trained in ICH GCP guidelines

Principal Investigators: Should be encouraged by the institutions to actively participate in early phase drug development studies for Indian as well as MNC companies.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

The medical institutions should identify clinical research as an important area to attract funding by the pharmaceutical industry.

ICMR leading medical institutions

The Indian Council of Medical Research (ICMR) is the premier national agency for the formulation, promotion and conduct of biomedical research in India. The mandate and policies of the ICMR coincide with the national health policies. The Council not only plans and promotes medical research in the current and emerging health problems of the country but is also expected to build a strong cadre of skilled biomedical scientists. One of the major mandates of the Council is to augment capacity strengthening of the institutions involved in both basic and clinical sciences. With India becoming the largest pool of diabetics and cancer patients, its hardly surprising that it is fast becoming the global outsourcing hub for hosting clinical trials. Thus, concerned over the rights and safety of volunteers, the Indian Council of Medical Research (ICMR) has launched a first-of-its-kind national survey of over 1,000 scientific institutions and medical colleges to assess their ethics committees. The survey will also throw light on the status of the ethics committees on these institutions, whether they function properly so as to accredit them.

Training need for Clinical trials

Since clinical research is a highly specialized job function it requires specific skill-sets to carry out various operations. To carry out these functions effectively, there is a need of training at the level of medical institutions. Specialized training requirements include training on clinical trial process, Standard Operating Procedures (SOPs), GCP and applicable regulatory guidelines. Requirements for individual stakeholders may vary based on his responsibility but some of the training elements remain common for all the stakeholders. There are reputed institutions for training such as the Academy for Clinical Excellence and Institute of Clinical Research India. WHO-CDSCO (Central Drugs Standard Control Organization) has launched GCP training programmes. These programmes cover foundations of GCP, amended Schedule Y, ethics and consent process and responsibilities of the investigators and the sponsors. The response to pilot programmes in Mumbai for all four stake holders - sponsors, investigators, ethics committees, and regulators - has been enthusiastic. This programme, which will be soon rolled out to other cities, provides the much needed government boost to the academia- industry training efforts. All of us are aware of the importance of good laboratory practices and good clinical practices. Compliance to these is a standard requirement. If one doesnt comply, they will not be doing

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White Paper onGlobal Clinical Trials in India Prospects and Challenges

business. It depends on all the stakeholders to see that only quality service providers exist. The Government of India, industry associations and other stakeholders are initiating various programmes for drawing attention to GCP and GLP awareness and compliance by CROs. Even online programmes are available through various service providers. These programmes are proving fruitful.

Collaborative work
Many big hospitals are also contributing plenty of patients to the clinical trials done by these companies. While Sagar Apollo hospital has a tie-up with Clinigene, Lotus Labs has signed an MoU with St Johns Medical College for multiple phase clinical studies and has also set up a clinical research facility in the medical college campus. Lotus Labs has an association with around 20 hospitals in the country for these studies and so do other CROs. The Academy for Clinical Excellence (ACE), set up by Asian Clinical Trials, a group company of Hyderabad-based Suven Lifesciences and Pfizer, is based in Mumbai. It offers various course options to pursue in clinical research. By having a partnership with the Bombay College of Pharmacy, ACE aims to provide a one-stop-shop for all the training needs of the clinical research professionals in the country.

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Career options in Clinical trials

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Most recently, India has become an attractive destination for contract research businesses because of the huge talent pool of investigators and clinical research (CR) professionals, in addition to other key enablers such as the lower cost of operations, availability of high quality infrastructure, facilitating regulatory support and increased outsourcing opportunities. Today India has produced 300 GCP trained investigators and approximately 600 trained CR (clinical research) professionals, who are successfully handling several global multi-centric studies. The career prospects in CR business continue to look positive from the growing number of studies being carried out and this conforms to the market estimates of several top analysts. McKinsey estimated that the Indian CR (clinical research) market will grow to US$1.5 billion in value by 2010. The growing industry scenario always demands good quality professionals to lead the business. India already has a talent pool of scientific personnel to handle the pharmaceutical manufacturing, chemistry, discovery, biotech and laboratory aspects of the business. But the profession of clinical research is entirely new to India and requires certain specific cognitive and communication skills. This new profession demands roles such as a clinical research associate, clinical team leader, project manager, managerclinical trial supplies, quality assurance manager, medical and regulatory affairs manager, data manager, data entry operator and head of clinical operations.

The emerging career

The CR business in India has created several career models for graduates and postgraduates. This gives a plethora of opportunities to professionals from science, phar macy, biotechnolog y and medical sciences streams to look for a promising future career. India has today approximately 6 lakh physicians, 4 lakh pharmacists, and 3 lakh bioscience graduates and postgraduates. Furthermore, the educational institutions in India generate a further 5060,000 graduates and postgraduates in different streams of science every year. There are five distinct career segments that have emerged as a result of the growth of the vibrant CR business. Each of these segments depicts the career pathways in a succinct manner for the CR career aspirants to assess his capability and choose one

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that best fits the potential. SEGMENT 1 describes the career pathways for medical graduates and post-graduates. This segment supports the clinical trial management in critical areas such as safety monitoring and management, regulatory submission and approval, medical writing, therapeutic training to the clinical operations, and study team. This segment is essentially the scientific and medical support arm of any organisation and contributes in an important way for the make or break decision making. SEGMENT 2 is very crucial, and is called the management arm of the CR business. This arm contributes to the bottom line of the CR business and constitutes 60%70% of the CR manpower. The professionals in great demand in this segment are the CRAs and Project Managers, who are essentially the field force and revenue earners for most CROs and pharma companies that are required for budgeting. SEGMENT 3 also plays a crucial role and is the analytical arm of the CR career model. The professionals involved in this segment have a statistical and programming back ground. They play a major role in the beginning of trial design and at the end to analyse and statistically interpret the data to derive conclusions. SEGMENT 4 is the support arm of the CR model. These individuals bring business, identify and recruit the right professionals, manage finance and provide training to the core teams. SEGMENT 5 the investigators, are the real lifeline of the CR business and they provide tremendous support as the study staff in the hospitalset up for patient care, follow-up, and compliance in clinical trials. Without their support, the CR business would not be able to operate.

White Paper onGlobal Clinical Trials in India Prospects and Challenges

Required skills
The success of the CR profession is dependent on an individuals level of knowledge and skill sets. Since it is an emerging business, Indias resource pool has had a limited exposure to GCP trials. The country lacks a mature pool of trained CR professionals with more than 1015 years of CR industry experience to handle complex issues in the CR business. There are relatively few senior professionals having work experience in global pharmaceutical companies that include the handling of global clinical trials. But nonetheless, India has a lot of professionals with the desired cognitive and communication skill sets required to manage the business. Among the cognitive skill sets, the most important ones are the knowledge of human anatomy and physiology, the science of disease and management, understanding of the drug development process, the regulatory framework of the country, and the applicable local and global guidelines. All these professionals need to be trained in GCP standards and should be interested in spending time and energy to participate in a CR. The Indian talent pool has the skill sets necessary to orient and train them quickly to meet the demand of any

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growing business. The senior professionals have utilised the transferable skills of related businesses to understand the needs of the CR industry.
White Paper onGlobal Clinical Trials in India Prospects and Challenges

Strengthening CR through training

Training is another important parameter for ensuring success in any profession. This is extremely important for the CR industry too, since it is a new industry in India. Naturally, there is a considerable emphasis on the training staff to equip them with knowledge and the necessary skills to handle global projects. Many local and global training institutes, such as; The Academy of Clinical Excellence (ACE) Institute of Clinical Research (ICR), Kriger Research Institute, Kundnani College of Pharmacy, Bioinformatics Institute of India, and Other similar organisations, have started full-time, short-term, diploma courses, class room based and/or online, in CR management. ACE, through its support from industry professionals, conducts certificate and postgraduate diploma courses to train professionals on the foundations of clinical research and GCP, ethics committee members, and other topics. ACE has trained 700 professionals on short-term programs and awarded 100 professionals with post graduation diplomas. These professionals are graduates in life science, pharmacy, medical, ayurvedic, and homeopathic streams and work as CRAs, study coordinators, quality assurance, study managers in CROs, pharma companies, and hospitals in India. ACE also hosted ACRP examinations in India in 2004 where many CR professionals were certified. Another institute in Mumbai, SIES Institute of Management, Nerul, has introduced a full-time module on CR management as a part of their PG Diploma in Pharmaceutical management. From 60 students this year, approximately 15%-20% have chosen to pursue CR careers in CROs and pharma companies. Global organisations like MDS, Barnett International, Thomson Centerwatch, ACRP, etc. are also exploring the possibility of expanding their training programs in India to support the growing demand for quality training.

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Career attraction
The CR business is largely driven and managed by people. A company with good, qualified, experienced, and trained people demonstrates sufficient credibility and capability to attract projects from sponsors. However, a sudden rise in the demand for trained and skilled professionals by many CROs and pharma companies has increased the salary levels and expectations of professionals. Despite this, the cost of skilled professionals in India is still low in comparison to its western counterparts. A clinical trial monitor typically earns approximately 10%15% of his U.S./European

White Paper onGlobal Clinical Trials in India Prospects and Challenges

counterpart. As many growing number of global companies are setting up their operations in India and as demands for the skilled professionals are also increasing, salary levels will no doubt rise dramatically over the next few years. The approximate per patient investigator fees in a complex oncology trial is US$2,000 in India; it is more than double this figure in Russia, 3-4 times higher in Europe, which is again more than 7 times higher in USA. It is definitely attractive for the sponsors and CROs to increase their headcount in India in order to run more trials in comparison to their set up costs elsewhere. This is a promising situation for CR professionals, including investigators, when compared to alternative job options or compensations available in India. Besides the salary and compensations, many recruiters have started offering bonuses and stock options as added incentives to retain professionals. Besides the fast bucks, the CR profession encourages professionals by providing them with the opportunity to work in a global environment by providing them global systems, infrastructure, and facilities.

Future requirement
This growth area of the healthcare industry requires 10,000 trained persons every year. However, only 1,000 persons are trained and certified annually. As per industry estimates, the requirement will grow to over 50,000 over the next five years. India, however, may not be able to make the most of this multi-million dollar opportunity due to the absence of trained manpower. Only three big players Institute of Clinical Research India, Academy for Clinical Excellence and Bioinformatics Institute of India train professionals for clinical research. With demand far outstripping supply, it seems to be a win-win situation for the clinical research associates.

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Future Outlook
White Paper onGlobal Clinical Trials in India Prospects and Challenges

In the past, clinical research was predominantly conducted in the West. However, it is likely to hold a good future world over. Developing countries such as India, China, those in Latin America and South East Asia are increasingly becoming capable of catering to the growing needs of the industry. With the increasing business opportunities in these future markets, pharmaceutical companies are devising tailor-made strategies for the developing countries which include exploiting the potential for clinical research.

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