Introduction to clinical research

India has become an attractive destination for outsourced pharmaceutical services. Drive for increased productivity & efficiency in the pharmaceutical industry Growth of the biotech sector and the virtual pharma model Proven success of other outsourcing plays Established track record in Business Process & IT outsourcing World leader in the generic and API sectors Intellectual Property protection enforcement has evolved Well trained, English speaking and computer savvy biomedical workforce Cost effective workforce willing and able to adhere meticulously to protocols and processes Large heterogeneous “urban centric” patient populations Global Trends Indian Industry Core Competencies

Drive for increased productivity & efficiency in the pharmaceutical industry

Growth of the biotech sector and the virtual pharma model

Proven success of other outsourcing plays

Established track record in Business Process & IT outsourcing

World leader in the generic and API sectors

Intellectual Property protection enforcement has evolved

Well trained, English speaking and computer savvy biomedical workforce

Cost effective workforce willing and able to adhere meticulously to protocols and processes

Large heterogeneous “urban centric” patient populations

The clinical development sector in India is enjoying rapid growth. Revenues from contract R&D for international sponsors was USD 100 M in 2005 Sector enjoying a 40% annual growth rate Nascent but dynamic CRO sector Quintiles India has been in operation for the past 5 years, with multiplication of resources Most global CROs have a presence in or alliance to access India Local CROs are gaining momentum but consolidation is inevitable Pharmaceutical sponsors are ramping up their clinical operations in India Pfizer, Aventis and Eli Lilly are ahead of the rest Altana, Merck & Co and GSK are catching up - India’s Clinical Development Sector -

Revenues from contract R&D for international sponsors was USD 100 M in 2005

Sector enjoying a 40% annual growth rate

Nascent but dynamic CRO sector

Quintiles India has been in operation for the past 5 years, with multiplication of resources

Most global CROs have a presence in or alliance to access India

Local CROs are gaining momentum but consolidation is inevitable

Pharmaceutical sponsors are ramping up their clinical operations in India

Pfizer, Aventis and Eli Lilly are ahead of the rest

Altana, Merck & Co and GSK are catching up

What is clinical research? Organized research on human beings intended to provide adequate information on the drug use as a therapeutic agent on its safety and efficacy. Also referred to as Clinical trial management

Organized research on human beings

intended to provide adequate information on the drug use as a therapeutic agent on its safety and efficacy.

Also referred to as Clinical trial management

Clinical research - position in drug development Drug development Discovery research Formulation and development Clinical development(trials) Commercialization

Drug development

Discovery research

Formulation and development

Clinical development(trials)

Commercialization

India offers pharmaceutical services at various stages of the value chain. Target Identification & Validation Lead Generation & Optimisation Pre-Clinical Development Ph I Ph II & III Contract Manufacturing Less developed academic expertise Investment incongruity Pharmaceutical Value Chain with Offshoring Opportunities Medicinal Chemistry Custom chemical synthesis Molecular Modelling Virtual Screening Pharmaco-kinetics Animal Testing Toxicology Bioequival-ence Limited first in man studies Clinical Trials Data Management Central Lab Biostats APIs Formulations Finished product Clinical trial supplies

Less developed academic expertise

Investment incongruity

Medicinal Chemistry

Custom chemical synthesis

Molecular Modelling

Virtual Screening

Pharmaco-kinetics

Animal Testing

Toxicology

Bioequival-ence

Limited first in man studies

Clinical Trials

Data Management

Central Lab

Biostats

APIs

Formulations

Finished product

Clinical trial supplies

Why do we need clinical trials? new drugs for new uses of existing drugs, medical devices, new drug delivery systems etc.

new drugs

for new uses of existing drugs,

medical devices,

new drug delivery systems etc.

Why do we need clinical trials? Evidence to prove the efficacy and safety in human beings. Only a well designed clinical study on a defined population can give meaningful results- (positive or negative) about any therapeutic intervention

Evidence to prove the efficacy and safety in human beings.

Only a well designed clinical study on a defined population can give meaningful results- (positive or negative) about any therapeutic intervention

Scope of clinical research? Total cost of the drug development 750-900 million US $ Total time taken for the drug development 9-10 years 2/3rds of the drug development cost and time is spent on clinical trials development

Total cost of the drug development

750-900 million US $

Total time taken for the drug development

9-10 years

2/3rds of the drug development cost and time is spent on clinical trials development

Regulatory guidelines today Drugs and cosmetics act 1947 SCHEDULE-Y Indian GCP GUIDELINES ICMR Guidelines WHO Guidelines ICH-GCP Guidelines

Drugs and cosmetics act 1947

SCHEDULE-Y

Indian GCP GUIDELINES

ICMR Guidelines

WHO Guidelines

ICH-GCP Guidelines

Clinical research -a multi-disciplinary approach Sponsor Investigators Monitors Auditors and the quality control personnel. Biostatisticians. Data management group. Regulatory Affairs. Reporting and Documentation medical writing. Business development group

Sponsor

Investigators

Monitors

Auditors and the quality control personnel.

Biostatisticians.

Data management group.

Regulatory Affairs.

Reporting and Documentation medical writing.

Business development group

Players in Clinical Research Industry Pharma companies Clinical/contract research organisations(CROs) Biotech companies Central diagnostic laboratories Clinical research training institutes

Pharma companies

Clinical/contract research organisations(CROs)

Biotech companies

Central diagnostic laboratories

Clinical research training institutes

NEW DRUG DEVELOPMENT PROCESS Drug discovery Synthesis Drug designing Target validation(Preliminary in-vitro screening) Pharmacological assays

Drug discovery

Synthesis

Drug designing

Target validation(Preliminary in-vitro screening)

Pharmacological assays

PRECLINICAL STUDIES Include studies conducted on Experimental animals for safety and efficacy .

Include studies conducted on Experimental animals for safety and efficacy

.

Toxicity studies Acute toxicity studies LD50 Sub- acute toxicity studies Chronic toxicity studies Special toxicity studies-carcinogenecity,teratogenecity genotoxicity, effects on fertility and reproduction

Acute toxicity studies LD50

Sub- acute toxicity studies

Chronic toxicity studies

Special toxicity studies-carcinogenecity,teratogenecity

genotoxicity,

effects on fertility and reproduction

PRECLINICAL STUDIES Efficacy studies In- vitro assays Studies conducted using only animal tissues or cells or enzyme systems In- vivo assays Experiments using whole animals

Efficacy studies

In- vitro assays

Studies conducted using only animal tissues or cells or enzyme systems

In- vivo assays

Experiments using whole animals

CLINICAL TRIAL PHASES Phase-I- Clinical pharmacology,safety of new drugs Phase-II -safety and efficacy of new drug in patients,exploratory trial. Phase-III -multicentric confirmatory trial. Phase-IV -post- marketing surveillance

Phase-I- Clinical pharmacology,safety of new drugs

Phase-II -safety and efficacy of new drug in patients,exploratory trial.

Phase-III -multicentric confirmatory trial.

Phase-IV -post- marketing surveillance

Who conducts the clinical trial? Investigators Principal investigator Co-investigator

Investigators

Principal investigator

Co-investigator

Who participates in the trial? Subjects Patients Healthy human volunteer

Subjects

Patients

Healthy human volunteer

Regulatory requirements Drugs and cosmetics act Schedule-Y DCGI Drug controller General of India US-FDA United states-Food and drug administration act. MHRA Medicinal and health care products regulatory agency

Drugs and cosmetics act

Schedule-Y

DCGI Drug controller General of India

US-FDA United states-Food and drug administration act.

MHRA Medicinal and health care products regulatory agency

MONITORING Overseeing the progress of a clinical trial Ensuring that it is conducted according to the protocol,GCP,SOPs and the regulatory requirements. Usually conducted by Clinical research associates.

Overseeing the progress of a clinical trial

Ensuring that it is conducted according to the protocol,GCP,SOPs and the regulatory requirements.

Usually conducted by Clinical research associates.

SUMMARY Clinical research is an integral part of drug development Unlike the past, today the process has gained a unique position due to the regulatory requirements and ethical guidelines available globally. Designing, conducting,monitoring, appropriate quality assurance and data management determine the success of the clinical research.

Clinical research is an integral part of drug development

Unlike the past, today the process has gained a unique position due to the regulatory requirements and ethical guidelines available globally.

Designing, conducting,monitoring, appropriate quality assurance and data management determine the success of the clinical research.

Major Players

Career Path

Career Pipeline