Clinical Trial in India, Prospects & Challenge

8/3/2019 Clinical Trial in India, Prospects & Challenge

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White Paper on

Global Clinical Trials in India

Prospects and Challenges

Federation of Indian Chambers of Commerce & Industry


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WhitePaperonGlobalClinicalTrialsinIndiaPros

pectsandChallenges

Cygnus Business Consulting & Research4th & 5th Floors, Astral Heights, Road No. 1, Banjara Hills, Hyderabad-500034, India

Tel: +91-40-23430203-07, Fax: +91-40-23430208, E-mail: [email protected]

Website: www.cygnusindia.com

Disclaimer: All information contained in this repor t has been obtained from sources believed to be accurate byCygnus Business

Consulting & Research (Cygnus). While reasonable care has been taken in its preparation, Cygnus makes no representation or

warranty, express or implied, as to the accuracy, timeliness or completeness of any such infor mation. The information contained

herein may be changed without not ice. All information should be considered solely as statements of opinion and Cygnus will not

be liable for any loss incurred by users from any use of the publication or contents


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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

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

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.


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Table of Contents

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

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


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Introduction

India is fast emerging as a favoured destination for clinical trials by global pharmaceutical andbiotech 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 drug applications are nearly 4,000.

Approximately 90,000 clinical trials were performedglobally 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


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lobalClinicalTrialsinIndia

ProspectsandChallenges

Opportunities and Operational Deficiencies

for Clinical Trial in India

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 post-

marketing 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.

H igher 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


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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.

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 countriesare 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 ofinnovation 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.


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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. Anumber 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.

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 elegantclinical trials that will

test concepts rather than simply compareproducts. 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 UnitedStates 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


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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.

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.


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Regulatory framework for conducting Stem

Cell, tissue engineering, vaccines, molecular

diagnostic products Research in India

Stem Cells

Stem Cell is acell 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.

ResearchSince 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


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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 cellscould be more useful for repairing of tissues damaged by injury or disease.

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 E ngineering

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.


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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.

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 (E S 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


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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 micro-

organism 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.


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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 requestadditional 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.

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


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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 PCR-

related 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 moleculardiagnostics.


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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Strengthening Institutional Ethics at par with

Global BenchmarkSince 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 Researchusing H uman 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.

Role of Research Body

The quality of an ethical consultation rests on the IECs

ability to provide a forum for open discussion of the

medical, moral, and legal issues surrounding a difficult

situation. The authority, whether institutional, moral, or

legal, of an ethics consultant and an IEC, is limited. The

Academy supports the view that the recommendations

from an ethics consultation are advisory only, with all

parties to a disagreement taking full responsibility for

their own actions. Improved communication, clarification

of differences and available options, and careful

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 incomposition. 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.

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.

IEC Members

1. Chairperson

2. One or two basic medical scientists.

3. One or two clinicians from variousInstitutes

4. One legal expert or retired judge

5. One social scientist / rep. of NGO

6. One philosopher / ethicist / theologian7. One lay person from the community

8. Member Secretary


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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

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 guidelinesin 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.

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


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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.

Areas for strengthening

Effectiveness of IE Cs: 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

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, educationof 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 principlesof 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 thelarger IEC.

6. IECs within a general hospital setting should ensure an adequate degree of

multidisciplinary expertise for addressing ethicalissues specific to pediatrics.

** V Mohanan N air: Civil S urgeon, G eneral H ospital, Thiruvananthapuram, Kerala 69501 1, I ndia. Douglas K M artin: A ssistant Professor, D epartment of H ealth Policy, Management

and E valuation and the Joint Centre for Bioethics, University of Toronto, Canada.


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legal scholars and ethicists. Most medical schools do not offer bioethics courses. Typically, well-

known people are nominated as IEC members. Finally, in the Indian context, lay persons can be

intimidated in the presence of more powerful scientific members.

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 internationalreputed 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.

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 releaseinto 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 orguidelines 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 E ngineering 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.

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 large-

scale 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.

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


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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.

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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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.

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 seriouslyexamined.

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


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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:

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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Capacity building in clinical research at

medical institutionsThe 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)

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


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Principal Investigators: Should be encouraged by the institutions to actively participate in early

phase drug development studies for Indian as well as MNC companies.

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 outvarious 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 trainingprogrammes. 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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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 ofHyderabad-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

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 careerThe CR business in India has created

several career models for graduates

and postgraduates. This gives a

plethora of opportunities to

professionals from science,

pharmacy, biotechnology and

medical sciences streams to look for

a promising future career. India has

today approximately 6 lakhphysicians, 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.

SEGMEN T 1describes 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.

SEGMEN T 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, andcompliance in clinical trials. Without their support, the CR business would not be able to operate.

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.

Strengthening CR through trainingTraining 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.

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


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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 inEurope, 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

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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Clinical Trial in India, Prospects & Challenge

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