Dr Dilip Pawar 1

Clinical Research in Clinical Research in IndiaIndia

Drivers for changing Drivers for changing perceptionsperceptions

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

Fellow Of American Society Of Clinical PharmacologyFellow Of American Society Of Clinical Pharmacology

Director & Chief Scientific AdvisorDirector & Chief Scientific Advisor Institute of Clinical Research Education and ResearchInstitute of Clinical Research Education and Research

Chief Executive Officer & Global Medical DirectorChief Executive Officer & Global Medical Director Drug Research Laboratory; MUMBAI, INDIADrug Research Laboratory; MUMBAI, INDIA

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WELCOME

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INDIAINDIA

LIFE EXPECTANCY

68 YEARS

EXPENDITURE ON HEALTH

6%OF GDP

(1.2% Government Spend)

POPULATION

URBAN 345 million

Total 1 billion

BIRTH RATE 27 per 1000

DEATH RATE 8 per 1000

INFANT MORTALITY77 per 1000

•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

URBAN LITERACY

MALES 82%

FEMALES 64%

INDIAINDIA

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58

0

20

40

60

80

100

120

1947

32

1998

62

1980

2020

72

Life Expectancy

Life SpanLife Span

42

1991

119

2025

Pop

ula

tion

>65

yea

rs (

mill

ion

)

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218 mn1990 (846 mn) 2000 (1000mn)

340 mn

2025 (1400 mn)

URBAN POPULATION

PREVALENCE OF ILLNESS

Prevalence of Illness

10% 22%

15-60 years > 60 years• Rapid recruitment

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

Population – Pronounced Population – Pronounced

Rural to Urban MigrationRural to Urban Migration

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DIS

EA

SE

S O

F D

EV

EL

OP

ING

CO

UN

TR

IES

PROBLEMS OF REPRODUCTIVE HEALTH

ACUTE INFECTIOUS DISEASES

NUTRITIONAL DISEASES

•Varied Disease Patternsof developing and developed world

Epidemiologic Transition DIS

EA

SE

S O

F D

EV

EL

OP

ED

WO

RL

D

AIDS

CHRONIC DISEASES

LIFESTYLE-RELATED

CARDIO-VASCULAR

CANCERS

DEGENERATIVE DISEASES

Changing Disease Changing Disease PatternsPatterns

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Changing Disease Changing Disease PatternsPatterns Cardiovascular diseasesCardiovascular diseases Degenerative neurological Degenerative neurological

diseasesdiseases Diabetes Diabetes CancerCancer Psychiatric illnesses Psychiatric illnesses Gastro Intestinal DisordersGastro Intestinal Disorders Infectious Diseases Infectious Diseases Tropical diseasesTropical diseases

Patient PopulationPatient Population 8 million Epileptics8 million Epileptics 40 million Asthmatics40 million Asthmatics ~34 million Diabetics~34 million Diabetics 8-10 million HIV +ve8-10 million HIV +ve 3 million Cancer patients3 million Cancer patients > 2 million Cardiac deaths> 2 million Cardiac deaths 1.5 million Alzheimer 1.5 million Alzheimer

patients patients 1 million PD patients1 million PD patients 15% Hypertensive15% Hypertensive 1% Schizophrenia patients1% Schizophrenia patients

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

Diseases and PatientsDiseases and Patients

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

Aryans from Central Asian steppes – 1500 BCAryans from Central Asian steppes – 1500 BC(pale skinned and light-eyed)(pale skinned and light-eyed)

Greeks (Yavanas)Greeks (Yavanas) ScythiansScythians ParthiansParthians Iranians (Persians)Iranians (Persians)

Also Turks, Huns, Chinese, EthopiansAlso Turks, Huns, Chinese, Ethopians

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

Today Caucasians 80% Dravidians 20%

• Ethnic diversity

- majority Caucasian

India – Ethnic India – Ethnic DiversityDiversity

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The ‘Language’ The ‘Language’ AdvantageAdvantage

Teaching - Medical, Nursing & Pharmacy

Communication with Regulatory Authorities

• Hospital Management

• Source documents

Labeling of Medicines

ENGLISH

Languages - 15 official languagesHindi - National language

- Mother tongue of 30% of people

English - Language for communication

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Medical Practice in Medical Practice in IndiaIndia

Multiple systems Multiple systems AyurvedaAyurveda Other traditional Indian systems Other traditional Indian systems Homeopathy Homeopathy Western system; most widely Western system; most widely

practiced practiced Multiple systems of therapiesMultiple systems of therapies

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Pharmaceutical industry- Pharmaceutical industry- PastPast

Clinical trials not mandatory till Clinical trials not mandatory till 19871987

Market of branded genericsMarket of branded generics No incentive for research No incentive for research Innovator companies indifferentInnovator companies indifferent Local industry not serious about Local industry not serious about

clinical trials clinical trials No data exclusivity & patent No data exclusivity & patent

protectionprotection

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Medical professionMedical profession

Did not question source of Did not question source of references references

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

needs needs

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IRBsIRBs

Very few in numberVery few in number Mainly reviewed animal studies & Mainly reviewed animal studies &

post graduate thesespost graduate theses Not US FDA compliant Not US FDA compliant No SOPs No SOPs Not much attention paid to ICFNot much attention paid to ICF Patient reimbursement not Patient reimbursement not

permitted permitted

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Why Not India until recently?Why Not India until recently?

High importation duty (55%)High importation duty (55%) No provision in drug laws for No provision in drug laws for

global studies global studies No incentive for PI’s; academic No incentive for PI’s; academic

institutions suspicious of institutions suspicious of cliniciansclinicians

No Data ExclusivityNo Data Exclusivity Long start up times Long start up times

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Changing perceptionsChanging perceptionsand a new environmentand a new environment

Drivers:Drivers: WTO WTO Need to globalizeNeed to globalize Encourage Private public Encourage Private public

partnershippartnership Intense lobbying by MNCsIntense lobbying by MNCs Shift of focus of the indigenous Shift of focus of the indigenous

industry; from process to product industry; from process to product Economic senseEconomic sense

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OUTSOURCING OPPORTUNITIES - INDIA

Outsourcing Opportunities -

India

Bulk Drugs&

FormulationsManufacturing

BioinformaticsBiostatistics

SoftwareDevelopment

ContractMarketing &

Sales

International Clinical

Trials

Technical Services

HerbalsNeutraceuticals

ContractR&D

MedicinalChemistry

Plant Machinery

&Pharma

Equipment

PrimaryPackaging Materials

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Why India Now?Why India Now?

No importation dutyNo importation duty Patent act amended; IPR in place Patent act amended; IPR in place Data Exclusivity – Data Exclusivity – Export procedures simplifiedExport procedures simplified Drug laws amended to permit Drug laws amended to permit

global studies global studies

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Why India…..Why India…..

GCP compliant IRB’s GCP compliant IRB’s Untapped patient populationUntapped patient population English business languageEnglish business language GCP guidelines ICH compliant GCP guidelines ICH compliant Start up time reduced to 8-12 Start up time reduced to 8-12

weeks weeks CAP certified central labsCAP certified central labs

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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 ClassEpidemiological Transition of

Disease - Patterns changing

• Good connectivity• Increasing use of IT and Internet• Transfer of ECGs and Imaging - now routineHealth Insurance expansion

- private participation emphasis on preventive care

Good Courier Systems within India and to other countries

Clinical Trial EnvironmentChange Drivers

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Skilled workforce with

domain expertiseHigh quality research

Therapeutic Expertise Technology support

Maintenance of time schedules

Shortening time to market

INDIA

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Regulatory milestonesRegulatory milestones

Mandatory clinical trials for the first Mandatory clinical trials for the first applicant – 1987applicant – 1987

BE for subsequent applicants – 1987 BE for subsequent applicants – 1987 GCP committee formed – 1995 GCP committee formed – 1995 Ethical guidelines - 2000Ethical guidelines - 2000 GCP guidelines released – 2001GCP guidelines released – 2001 Drug laws amended to permit Drug laws amended to permit

simultaneous phase global trials - simultaneous phase global trials - 20052005

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Recipe for success in IndiaRecipe for success in India

MOH approval easy if US IND/ MOH approval easy if US IND/ EMEA application EMEA application

Understand PI behavior – Understand PI behavior – financial negotiations financial negotiations

Invest in training PIs, IRBsInvest in training PIs, IRBs Promote young, enthusiastic PIsPromote young, enthusiastic PIs

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Nascent but Fast Nascent but Fast GrowingGrowing

- India’s Clinical Development Sector -

Annual Revenues USD 120 M with 40% Annual Revenues USD 120 M with 40% growth in past year growth in past year

240 international studies recruiting subjects 240 international studies recruiting subjects = 1.2% of the total studies worldwide = 1.2% of the total studies worldwide

66% of international clinical trials are Phase 66% of international clinical trials are Phase IIIIII

207 sites FDA registered207 sites FDA registered 40,000 subjects participated in clinical trials 40,000 subjects participated in clinical trials

to date (<0.02% of population)to date (<0.02% of population)

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Regulatory bodyRegulatory body Approval Approval TimeTime

Drugs Controller Drugs Controller General of India General of India (DCGI)(DCGI)

Regulatory approval Regulatory approval for study conduct in for study conduct in IndiaIndia

4 weeks – FAST TRACK, 4 weeks – FAST TRACK, US,UK,CANADA,SWITZERLAUS,UK,CANADA,SWITZERLAND,GERMANY,EMEA, ND,GERMANY,EMEA, AUSTRALIA, JAPAN CTA AUSTRALIA, JAPAN CTA availableavailable

16 weeks, no 16 weeks, no documentation to support documentation to support successful US/EU CTA successful US/EU CTA

Drugs Controller Drugs Controller General of India General of India (DCGI)(DCGI)

Test license to import Test license to import trial suppliestrial supplies

2 weeks in addition2 weeks in addition

Ethics CommitteesEthics Committees Local Ethics Local Ethics committee approval committee approval by sitesby sites

6 – 8 weeks (in parallel)6 – 8 weeks (in parallel)

Total (parallel Total (parallel processing)processing)

-- 6-8 weeks – FAST TRACK6-8 weeks – FAST TRACK

16 weeks (track B)16 weeks (track B)

Directorate General of Directorate General of Foreign Trade (DGFT)Foreign Trade (DGFT)

Permission to export Permission to export blood samplesblood samples

Additional 2 to 4 weeksAdditional 2 to 4 weeks

Recent India Regulatory Reform Recent India Regulatory Reform makes Approvals Possible within 6 makes Approvals Possible within 6 weeks.weeks.

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Meticulously Following Prescribed Process Is Key.

Contract/LOI executedAll documentsreceived

Regulatory dossier

compilation

CDA signed,Site Selected,

Release Protocol

Consent Letter from PIs

Internal reviewof dossier

PI submits application

to ECreply to queries

Approvals from EC

Regulatory submission

to DCGI

Sponsor / CRO

Queriesfrom EC

Approvals from EC

to PI

Regulatory Approval

from DCGI

DGFTExport License

Application

Submission to DGFT

Export License Obtained

from DGFT

Regulatory & IRB Approval Process:India

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Deadline is deadline !

Don‘t set too ambitious Don‘t set too ambitious deadlinesdeadlines

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India — Gradually Building a India — Gradually Building a Track RecordTrack Record

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Differing DynamicsDiffering Dynamics

I.I. Clinical Trials on diseases of topicsClinical Trials on diseases of topics e.g. e.g. malaria, TB, leishmaniasis malaria, TB, leishmaniasis

Locations – usually outside urban Locations – usually outside urban areasareas

Benefits to India – likely / immediateBenefits to India – likely / immediate

II.II. Clinical Trials on diseases/ disorders of Clinical Trials on diseases/ disorders of aa primitive economy primitive economy e.g.e.g.

Acute infectionsAcute infections Nutrition-relatedNutrition-related Reproductive health-relatedReproductive health-related AIDSAIDS

Sponsors – Industry and OthersSponsors – Industry and Others

Locations – urban and periruralLocations – urban and perirural

Benefits to India – likely / immediateBenefits to India – likely / immediate

III.III. Clinical Trials on diseases/ disorders of Clinical Trials on diseases/ disorders of a developed economya developed economy e.g. e.g.

CardiovascularCardiovascular CNS including neurological CNS including neurological

degeneration and psychiatrydegeneration and psychiatry GastrointestinalGastrointestinal DiabetesDiabetes CancersCancers AIDSAIDS

Sponsors – IndustrySponsors – Industry

Locations – urbanLocations – urban

Test molecules – drugs in developmentTest molecules – drugs in development

Data for regulatory submissionData for regulatory submission

Benefits to India – likely / immediateBenefits to India – likely / immediate

Clinical Trials Clinical Trials Outsourced to IndiaOutsourced to India

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India offers Cost Saving India offers Cost Saving PotentialPotential

Overall Indexed Clinical Trial Costs

0.77

1.09

0.71

1.2

0.93

1

0.73

0.4

0.52

0.56

0 0.2 0.4 0.6 0.8 1 1.2 1.4

Poland

UK

France

Germany

Spain

US

Australia

Russia

China

India

Source: FastTrack Systems Global Cost Databases

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Mckinsey ReportMckinsey Report

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

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India has experienced India has experienced InvestigatorsInvestigators

Concern factors :Concern factors : Using Investigator groups (some Using Investigator groups (some

will be great, others might not)will be great, others might not) When inexperienced, assess When inexperienced, assess

willingness and motivation to learn willingness and motivation to learn and then train and retrainand then train and retrain

Choose Good InvestigatorsChoose Good InvestigatorsNeed local understanding and Need local understanding and

global experienceglobal experience

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Perception Reality GCP awareness absent or low

Many sites in India are trained in GCP – now mandated by Government

Data integrity in question

Various audits of the study show no adverse finding In India US FDA has audited sites with no major comments

Different languages cause confusion and escalate costs because of need to translate documents

English used for all healthcare-related activities, systems, procedures and drug labels. Only patient-related documents need translation

Telecommunication poor Connectivity poor

Telecommunication facilities good in urban areas. Connectivity good – EDC studies possible – electronic transmission of ECG, imagings frequent.

INDIA - Perceptions & INDIA - Perceptions & RealitiesRealities

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Is Clinical Research is an Is Clinical Research is an attractive Option for INDIAattractive Option for INDIA

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Key MessagesKey MessagesIndia is well placed to provide solutions for India is well placed to provide solutions for contemporary and future clinical researchcontemporary and future clinical research

Can facilitate affordable drug researchCan facilitate affordable drug research Has required patient populations and qualified Has required patient populations and qualified

scientists and cliniciansscientists and clinicians Has the information technology competitive advantageHas the information technology competitive advantage Has a regulatory framework which is moving towards Has a regulatory framework which is moving towards

regulatory harmonizationregulatory harmonization The socio-economic transformation in urban India The socio-economic transformation in urban India

understands contemporary GCP requirementsunderstands contemporary GCP requirements Rapid urbanisation and exposure to developed world Rapid urbanisation and exposure to developed world

facilitates cross-cultural understandingfacilitates cross-cultural understanding Product patents from January 1, 2005Product patents from January 1, 2005

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The Opportunities aheadThe Opportunities ahead In Clinical Research Opportunities are In Clinical Research Opportunities are

manymany Not Only in India but also Not Only in India but also

internationallyinternationally GRAB THE OPPORTUNITY……. GRAB THE OPPORTUNITY…….

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