1. Pharmaceutical Industr y &
Clinical Research: Basic Intro
Dr. Bhaswat S. Chakraborty

2. Global Pharmaceutical Market
• The global pharmaceutical market research has been done by
many companies
– All indicate a significant growth of pharma market in 2010-2011.
– The forecasting indicates pharmaceutical market growth of about 4
- 6% in 2010-2011.
– >$850 Billion
– Expected to grow at a 4 - 7% compound annual growth rate
(CAGR) through 2013.
– >$975 billion by 2013

3. Global Top 20 Pharmaceutical Companies
Revenue in $
Rank Company
Million(2010)
01 Johnson & Johnson 61,897
02 Pfizer 50,009
03 Abbott 30,764
04 Merck & Co. 27,428
05 Eli Lilly & Co. 21,836
06 Bristol-Myers Squibb 21,634
07 Amgen 14,642
08 Gilead Sciences 7,011
09 Mylan 5,093
10 Genzyme 4,516

4. Indian Pharmaceutical Market
 3rd largest (after US and European) generic market in volume, 14 th in
value
 India currently holds only ~2% share, but it has been growing at approximately
10% per year
 India is a leader in generic drugs and active pharmaceutical ingredients (API)
 Now seeking to become a major player in outsourced clinical research as well as
contract manufacturing and research
 There are ~100 U.S. FDA-approved manufacturing facilities in India, more than
in any other country outside the U.S
 In 2010, almost 30% of all Abbreviated New Drug Applications (ANDA) to the
FDA have been filed by Indian companies
 India’s share of the global generics market is ~33% now

5. Top 10 Pharmaceuticals in India, as of 2010
Revenue 2010 Revenue 2010
Rank Company
(Rs crore) (Rs billion)
1 Cipla 4,198.96 41.989
Ranbaxy (Taken over by
2 4,162.25 41.622
Daiichi Sankyo in 2008)
3 Dr. Reddy's Laboratories 3,763.72 37.637
4 Sun Pharmaceutical 2,463.59 24.635
5 Lupin Ltd 2,215.52 22.15
6 Aurobindo Pharma 2,081.19 20.801
GlaxoSmithKline
7 1,773.41 17.734
Pharmaceuticals Ltd
8 Cadila Healthcare 1,613 16.13
9 Aventis Pharma Limited 983.80 9.838
10 Ipca Laboratories 980.44 9.8044

6. Growth in Indian Domestic
Market
Revenue in US$ Billion

7. Dynamic Continuum of Drug
Discovery

8. Clinical Research
• Clinical research is a branch of medical science that determines the safety and
effectiveness of
– Medications
– Medical devices (including surgicals)
– Diagnostic products and treatment regimens intended for human use.
• These may be used for prevention, treatment, diagnosis or for relieving
symptoms of a disease
• Ethical research, overseen and regulated by local and other pertinent
Government authorities
• Regulators and Ethics committees review the research prior to conduct as
well as after completion of a study
• Clinical research is often understood by four phases of Clinical Trials (Phase I
– IV)

9. Global Clinical Research
Environment Today
• Large, multinational clinical trials preferred over smaller, local trials
– Pharmaceutical and biotechnology companies to accelerate development
timelines
– Under tighter budgets and resource constraints
• Multinational trials aim to increase access to treatment of naïve subjects by
enlisting sites outside of major markets, and to drive cost savings
• After a steep learning curve in the 1990’s, most large pharmaceutical
companies and CROs now have systems for large, multinational
studies:
– Hardware and IT infrastructure harmony
– Support in multiple languages
– Responding to regulators’ queries from several countries arriving at the
same time
• Successful management of large, multinational clinical studies are more
common now than before
• Certain aspects, however, still require constant oversight to avoid
serious mistakes.

10. Largest Registry of Clinical
Trials
• ClinicalTrials.gov (www.clinicaltrials.gov) is a registry and
results database of federally and privately supported clinical trials
conducted in the United States and around the world.
– currently contains 113,598 trials
– sponsored by the National Institutes of Health, other federal
agencies, and private industry
– Studies listed in the database are conducted in 176 countries
– 24 categories of diseases
– gives you information about a trial's purpose, who may participate,
locations, and contact phone numbers
– receives over 50 million page views per month 65,000 visitors daily

11. Map of All Studies in
ClinicalTrials.gov

12. What is a Clinical Trial (CT)?
• Biomedical or health-related research
in human beings following a pre-defined
protocol
• Clinical Trials mean both interventional
and observational types of studies
– Interventional studies have the research
subjects assigned by the investigator to a
treatment or other intervention, and their
outcomes are measured
– Observational studies are those in which
individuals are observed and their outcomes
are measured by the investigators

13. Different Types of CTs
 Treatment trials test experimental treatments, new combinations of drugs,
or new approaches to surgery or radiation therapy
 Prevention trials look for better ways to prevent disease in people who
have never had the disease or to prevent a disease from returning. These
approaches may include medicines, vaccines, vitamins, minerals, or lifestyle
changes
 Diagnostic trials are conducted to find better tests or procedures for
diagnosing a particular disease or condition
 Screening trials test the best way to detect certain diseases or health
conditions
 Quality of Life trials (or Supportive Care trials) explore ways to improve
comfort and the quality of life for individuals with a chronic illness.

14. Different Phases of CT
 Clinical trials are conducted in phases. The trials at each phase have a
different purpose and help scientists answer different questions:
In Phase I trials, researchers test an experimental drug or treatment in a
small group of people (20-80) for the first time to evaluate its safety,
determine a safe dosage range, and identify side effects.
In Phase II trials, the experimental study drug or treatment is given to a
larger group of people (100-300) to see if it is effective and to further
evaluate its safety.
In Phase III trials, the experimental study drug or treatment is given to
large groups of people (1,000-3,000) to confirm its effectiveness, monitor
side effects, compare it to commonly used treatments, and collect
information that will allow the experimental drug or treatment to be used
safely.
In Phase IV trials, post marketing studies delineate additional
information including the drug's risks, benefits, and optimal use.

15. Participation in Clinical Trials
 Participants in clinical trials can play a more active role in their own health
care, gain access to new research treatments before they are widely available, and
help others by contributing to medical research
 All clinical trials have guidelines about who can participate
 Inclusion/exclusion criteria
 The factors that allow someone to participate in a clinical trial are called "inclusion
criteria"
 Those disallow someone from participating are called "exclusion criteria“
 These criteria are based on such factors as age, gender, the type and stage of a disease,
previous treatment history, and other medical conditions
 A participant must qualify for the study by I/E
 Some studies need patients with illnesses, while others need healthy participants
 I/E not used to reject people personally

17. Benefits & Risks of Participating
in CT
 Benefits
 Clinical trials that are well-designed and well-executed
are the best approach for eligible participants to play an
active role in their own health care
 Gain access to new research treatments before they are
widely available
 Obtain expert medical care at leading health care
facilities during the trial
 Help others by contributing to medical research.
 Risks
 There are risks to clinical trials. There may be
unpleasant, serious or even life-threatening side effects
to experimental treatment
 The experimental treatment may not be effective for the
participant
 The protocol may require more of their time and
attention than would a non-protocol treatment,
including trips to the study site, more treatments,
hospital stays or complex dosage requirements

18. What Happens During a CT?
• Depends on the kind of trial being conducted
– The clinical trial team includes doctors and nurses as well as social workers and
other health care professionals
– They check the health of the participant at the beginning of the trial, give specific
instructions for participating in the trial
– They also monitor the participant carefully during the trial, and stay in touch
after the trial is completed
– Some CTs involve more tests and doctor visits than the participant would
normally have for an illness or condition
– For all types of CTs, the participant works with a research team
– A CT is most successful when the protocol is carefully followed and there is
frequent contact with the research staff

19. Opportunities for India

20. The Rise of Trial Outsourcing
Western
United States Europe Rest of world
1997 86% 9% 5%
1999 80% 9% 12%
2001 77% 10% 13%
2003 70% 11% 19%
2005 62% 13% 25%
2007 57% 14% 29%
•Source: Tufts Center for the Study of Drug Development analysis of FDA data

21. Outsourcing of CTs
• Outsourcing can be defined as “the strategic use of outside resources to
perform activities traditionally handled by internal staff and resources”
• The basic rationale behind outsourcing:
– In some cases, other companies can perform a service more effectively and at a
lower cost.
• In pharma, the outsourcing of R&D activities offer the greatest advantages
• Pharmaceutical companies face extreme rising costs to develop new
medicines, capacity constraints and longer R&D timelines
• CROs offer services that can help to alleviate these constraints and increase
efficiency and R&D effectiveness
• In the past decade, the global spending on new drug development has been
growing at an annual rate of 9.1%
• However, the spending on contract clinical services has been growing
nearly 50% faster – at an annual rate of 13.4%

22. Drivers of Outsourcing/offshoring
of CTs
• Developing countries have a high patient enrolment rate compared to
North America and Europe.
• High enrolment rates imply that clinical trials can be finished sooner,
meaning that the profits of patent exclusivity can be enjoyed for
longer.
• Other factors that determine the attractiveness of a country for the
conduct of clinical trials include
– a broad spectrum of diseases
– a more rapid approval of trials
– availability of human resources
– technical skills
– differing ethnic responses to drugs and cost advantages
– availability of a “treatment naïve population”
Van Huijstee M & Schipper I. 2011. Putting Contract Research Organisations on the Radar. Centre for Research on Multinational Corporations

23. Opportunities for CROs
 In the pharmaceutical sector, outsourcing of CTs offers the greatest advantages
because
 CT phase is the most labour intensive, time consuming and costly part of the drug
development process.
 Nearly 70% of the total R&D costs are spent on clinical trials
 CTs are a key factor in the rising R&D costs because today’s drug trials are larger and
more complicated on average and require more participants than ever before.
 Recruiting participants is becoming more difficult in western countries.
 In 2008, US pharma companies spent $32.2 billion on trials.
 Pharmaceutical companies are under pressure to bring more new drugs to the
market while at the same time they have to cut their R&D budgets.
 As a result, companies are increasingly outsourcing their R&D to CROs
 CROs offer services that can increase R&D effectiveness and at lower costs.
 Currently, about half of the clinical trial activities are outsourced to CROs.
 The CRO market is estimated to account for $24 billion in 2010.
Van Huijstee M & Schipper I. 2011. Putting Contract Research Organisations on the Radar. Centre for Research on Multinational Corporations

24. The CRO Market
Source: Business Insights, The CRO Market Outlook, Emerging markets, leading players and future trends, 2008

26. Growth of CRO Market in India

27. Multi-centric CTs in India
• Up to 7% of global Phase III and 3.2 percent of Phase II trials.
• The growth rate of the Indian clinical sector has been estimated as two
and a half times that of the global market.
• Today, most of the big pharmaceutical companies are conducting
multi-centric trials in India with some of them are here >15 years.
– Eli Lilly and Pfizer began their CTs here in 1995.
– This was followed by Sanofi-Aventis, Bayer, Novartis Astra Zeneca and Johnson
& Johnson in the last decade.
– Last 2-3 years have seen other big pharmaceutical companies, like, Merck
GlaxoSmithKline, Bristol-Myers Squibb and some of the larger biotechnology
companies, like Amgen and Biogen Idec.
• However, all leading global CROs have also set up services in India (as
seen before).
• India has about 30 established major CROs

29. Prioritization of CTs
• Prioritization can be had based on national interest and patient safety.
– Clinical trials have different types of risks associated with them.
– A placebo trial involving vulnerable population (including
socioeconomically vulnerable) will have a higher risk and may be given a
different priority.
– Higher risk trials need to have special monitoring and more intense review
– a “site’s” ability to safely conduct the trials and the pool from which trial
subjects are sought.
– A number of operational issues to implement such a system of priorities
need to be discussed and procedures developed.
– A working group to measure risk associated with “site capabilities” needs
to be constituted.
– This may be particularly relevant for approval of Phase 1 trials.
– Criteria for disallowing trials as well as guidelines for exceptions should be
specified.

30. •Thank You•