Clinical Research in India

Drivers for changing perceptions

Dr Dilip Pawar
MD, PhD, MCSEPI, DPBM, DCA, MASCPT(USA), MASPET(USA), FCP(USA), MBA

Fellow Of American Society Of Clinical Pharmacology

Director & Chief Scientific Advisor Institute of Clinical Research Education and Research Chief Executive Officer & Global Medical Director Drug Research Laboratory; MUMBAI, INDIA
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WELCOME
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INDIA
POPULATION URBAN
LIFE EXPECTANCY
68 YEARS

345 million 1 billion

Total

EXPENDITURE ON HEALTH

INDIA
URBAN LITERACY MALES FEMALES 82% 64%

6%OF GDP

(1.2% Government Spend)

Fourth largest economy in the world

Second fastest growing economy in the world

Projected GDP growth rate 8% Healthcare, Pharma, Biotech, IT, BPO, telecom are fastest growing sectors

BIRTH RATE

27 per 1000

DEATH RATE

8 per 1000

INFANT MORTALITY 77 per 1000

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Life Span
Population >65 years (million)
2025
5

120 100 80 60
Life Expectancy

119

62 58 42

72

40 20

32

1947

1980

1998

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1991

2020

Population Pronounced Rural to Urban Migration

2000 (1000mn) 340 mn

218 mn

1990 (846 mn)

2025 (1400 mn)

Prevalence of Illness
10% 22%

Rapid recruitment
(20-30% time advantage if studies are conducted in India Ernst & Young)

15-60 years
URBAN POPULATION

> 60 years

PREVALENCE OF ILLNESS Dr Dilip Pawar 6

Changing Disease Patterns

DISEASES OF DEVELOPING COUNTRIES DISEASES OF DEVELOPED WORLD
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PROBLEMS OF REPRODUCTIVE HEALTH

AIDS CHRONIC DISEASES LIFESTYLE-RELATED CARDIO-VASCULAR CANCERS DEGENERATIVE DISEASES

ACUTE INFECTIOUS DISEASES

NUTRITIONAL DISEASES

Epidemiologic Transition
Varied Disease Patterns of developing and developed world Dr Dilip Pawar

Diseases and Patients

Changing Disease Patterns

Patient Population

Cardiovascular diseases Degenerative neurological diseases Diabetes Cancer Psychiatric illnesses Gastro Intestinal Disorders Infectious Diseases Tropical diseases

8 million Epileptics 40 million Asthmatics

~34 million Diabetics

8-10 million HIV +ve 3 million Cancer patients > 2 million Cardiac deaths 1.5 million Alzheimer patients 1 million PD patients 15% Hypertensive 1% Schizophrenia patients

India has diseases of the tropical world plus diseases of the developed countries
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India Ethnic Diversity

Successive waves of visitors / invaders from the North Dravidians driven southwards

Aryans from Central Asian steppes 1500 BC (pale skinned and light-eyed) Greeks (Yavanas) Scythians Parthians Iranians (Persians) Also Turks, Huns, Chinese, Ethopians
Today Caucasians Dravidians 80% 20%

Ethnic diversity - majority Caucasian

Later Portuguese, Dutch, French, Moghuls (Mongols), English

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The Language Advantage

Languages Hindi -

English

15 official languages National language Mother tongue of 30% of people Language for communication

Teaching - Medical, Nursing & Pharmacy

Hospital Management Source documents

ENGLISH

Communication with Regulatory Authorities

Labeling of Medicines

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Medical Practice in India

Multiple systems
Ayurveda Other traditional Indian systems Homeopathy Western system; most widely practiced

Multiple systems of therapies

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Pharmaceutical industry- Past

Clinical trials not mandatory till 1987 Market of branded generics No incentive for research Innovator companies indifferent Local industry not serious about clinical trials No data exclusivity & patent protection

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Medical profession
Did not question source of references Did not demand local evidence Patient care Ist priority Not familiar with GCP needs Did government funded research Lack of appreciation of mutual needs

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IRBs
Very few in number Mainly reviewed animal studies & post graduate theses Not US FDA compliant No SOPs Not much attention paid to ICF Patient reimbursement not permitted

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Why Not India until recently?

High importation duty (55%) No provision in drug laws for global studies No incentive for PIs; academic institutions suspicious of clinicians No Data Exclusivity Long start up times

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Changing perceptions and a new environment

Drivers:
WTO Need to globalize Encourage Private public partnership Intense lobbying by MNCs Shift of focus of the indigenous industry; from process to product Economic sense

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OUTSOURCING OPPORTUNITIES - INDIA

Contract R&D Medicinal Chemistry Bulk Drugs & Formulations Manufacturing Contract Marketing & Sales

International Clinical Trials Outsourcing Opportunities India

Technical Services

Plant Machinery & Pharma Equipment

Primary Packaging Materials

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Bioinformatics Biostatistics Software Development

Herbals Neutraceuticals

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Why India Now?

No importation duty Patent act amended; IPR in place Data Exclusivity Export procedures simplified Drug laws amended to permit global studies

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Why India..
GCP compliant IRBs Untapped patient population English business language GCP guidelines ICH compliant Start up time reduced to 8-12 weeks CAP certified central labs

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Clinical Trial Environment Change Drivers

Government and Regulatory Environment more conducive to clinical research GCP guidelines introduced by ICMR and DGHS Customs levies on clinical trial drug supplies eliminated Patent rules harmonised
Healthcare and Healthcare delivery improvements Tertiary Hospital Infrastructure GCP awareness Healthcare Industry - Rs.100,000 crores Growing demand by Middle Class Good connectivity Increasing use of IT and Internet Transfer of ECGs and Imaging - now routine

Epidemiological Transition of Disease - Patterns changing

Health Insurance expansion - private participation emphasis on preventive care

Good Courier Systems within India and to other countries Dr Dilip Pawar 20

High quality research

Skilled workforce with domain expertise

Maintenance of time schedules INDIA

Shortening time to market

Therapeutic Expertise
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Technology support
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Regulatory milestones
Mandatory clinical trials for the first applicant 1987 BE for subsequent applicants 1987 GCP committee formed 1995 Ethical guidelines - 2000 GCP guidelines released 2001 Drug laws amended to permit simultaneous phase global trials Dr Dilip Pawar 2005

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Recipe for success in India

MOH approval easy if US IND/ EMEA application Understand PI behavior financial negotiations Invest in training PIs, IRBs Promote young, enthusiastic PIs

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Nascent but Fast Growing

- Indias Clinical Development Sector

Annual Revenues USD 120 M with 40% growth in past year 240 international studies recruiting subjects = 1.2% of the total studies worldwide 66% of international clinical trials are Phase III 207 sites FDA registered 40,000 subjects participated in clinical trials to date (<0.02% of population)

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Recent India Regulatory Reform makes Approvals Possible within 6 weeks.

Regulatory body Drugs Controller General of India (DCGI) Approval Regulatory approval for study conduct in India

Time 4 weeks FAST TRACK, US,UK,CANADA,SWITZERLAND, GERMANY,EMEA, AUSTRALIA, JAPAN CTA available 16 weeks, no documentation to support successful US/EU CTA

Drugs Controller General of India (DCGI) Ethics Committees Total (parallel processing) Directorate General of Foreign Trade (DGFT)

Test license to import trial supplies Local Ethics committee approval by sites Permission to export blood samples
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2 weeks in addition 6 8 weeks (in parallel)

6-8 weeks FAST TRACK 16 weeks (track B)

Additional 2 to 4 weeks

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Meticulously Following Prescribed Process Is Key.

Regulatory & IRB Approval Process:India
CDA signed, Site Selected, Release Protocol Consent Letter from PIs PI submits application to EC reply to queries Queries from EC Approvals from EC

Contract/LOI executed All documents received

Sponsor / CRO

Approvals from EC to PI

Regulatory dossier compilation

Internal review of dossier

Regulatory submission to DCGI

Regulatory Approval from DCGI

DGFT Export License Application

Export License Obtained from DGFT

Submission to DGFT

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Dont set too ambitious deadlines

Deadline is deadline !
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India Gradually Building a Track Record

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Clinical Trials Outsourced to India

Differing Dynamics
I.

Clinical Trials on diseases of topics e.g. malaria, TB, leishmaniasis Clinical Trials on diseases/ disorders of a primitive economy e.g. Acute infections Nutrition-related Reproductive health-related AIDS Clinical Trials on diseases/ disorders of a developed economy e.g. Cardiovascular CNS including neurological degeneration and psychiatry Gastrointestinal Diabetes Cancers Dr Dilip Pawar AIDS

Locations usually outside urban areas Benefits to India likely / immediate Sponsors Industry and Others Locations urban and perirural Benefits to India likely / immediate

II.

III.

Sponsors Industry Locations urban Test molecules drugs in development Data for regulatory submission Benefits to India likely / immediate

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India offers Cost Saving Potential

Overall Indexed Clinical Trial Costs
India China Russia Australia US Spain Germany France UK Poland
0.77 0.71 1.09 0.4 0.73 1 0.93 1.2 0.56 0.52

0.2

0.4

0.6

0.8

1.2

1.4
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Source: FastTrack Systems Global Cost Databases Dr Dilip Pawar

Mckinsey Report
Indian CR market will grow to US $1.5 billion in value by 2010.

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Choose Good Investigators Need local understanding and global experience India has experienced Investigators Concern factors :

Using Investigator groups (some will be great, others might not) When inexperienced, assess willingness and motivation to learn and then train and retrain

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INDIA - Perceptions & Realities

Perception
GCP awareness absent or low

Reality

Many sites in India are trained in GCP now mandated by Government Various audits of the study show no adverse finding Data integrity in question In India US FDA has audited sites with no major comments Different languages cause English used for all healthcare-related confusion and escalate costs activities, systems, procedures and drug because of need to translate labels. Only patient-related documents need documents translation Telecommunication facilities good in urban Telecommunication poor areas. Connectivity good EDC studies Connectivity poor possible electronic transmission of ECG, imagings frequent.

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Is Clinical Research is an attractive Option for INDIA

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Key Messages
India is well placed to provide solutions for contemporary and future clinical research

Can facilitate affordable drug research Has required patient populations and qualified scientists and clinicians Has the information technology competitive advantage Has a regulatory framework which is moving towards regulatory harmonization The socio-economic transformation in urban India understands contemporary GCP requirements Rapid urbanisation and exposure to developed world facilitates cross-cultural understanding Product patents fromDr Dilip Pawar 1, 2005 January 35

The Opportunities ahead

In Clinical Research Opportunities are many Not Only in India but also internationally GRAB THE OPPORTUNITY.

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