This is mainly for Pharma R&D but the principles apply to all specialities.

1. RESEARCHERS’ SKILL
DEVELOPMENT
PROCESS
FOCUS ON PHARMACEUTICAL
R&D
Dr. Bhaswat S. Chakraborty
Sr. VP & Chair, R&D Core Committee
Cadila Pharmaceuticals Ltd.
1
Presented at the DSIR Seminar “Essential Skills for
the 21st
Century Researcher,” GTU, Ahmedabad,
January 7, 2016

2. CONTENTS
 Discovering & Developing New Drugs: Main Factors for Skill
Development
 Education and Qualifications
 Discovery & Development
 Lead Compound to Regulatory Approval
 Regulatory Approval to Marketing
 Drug DD & Other R&D Scientists
 Adaptation of a Fresh Graduate in his/her R&D Roles
 Some Essential Skills
 Team playing
 Finding a Mentor
 Notes on working in Big Pharma R&D
 Demystifying Myths
 Concluding Remarks
2

3. 3
New Medicine Marvels

4. IMPACT OF NEW MEDICINES IN LAST
100 YRS
 Human life expectancy has doubled in both developed and
developing economies
 One of the main reasons: better medicines than before
 In some cases a better QoL
 Backbone of effective and safe medicines
 Research in the areas drug discovery, preclinical, formulation
development and clinical studies
 However, last two decades have seen very high cost of drug
R&D
 ~couple of billion US dollars
 Despite this intimidating expense and the patents-warfare, R&D
for good medicines are on
 Good medicines are still being discovered and developed
4
Chakraborty B.S. (2012) PharmaTech, 3: 22-26

5. MAIN FACTORS IN SKILL
DEVELOPMENT: PHARMA R&D
 Educational Qualification
 Awareness of the field
 Right environment
 Beginners’ knowledge and ability
 Adaptation
 Coaching and mentoring
 Gaining experience
 Taking leadership and responsibility
 Team playing
 Supervisory and managing abilities
5

6. SKILL
 An ability and capacity acquired through deliberate systematic, and
sustained effort to smoothly & adaptively carryout complex
activities or job functions involving ideas (cognitive skills), things
(technical skills) and/or people (interpersonal skills)
6
COMPETENCE
o A cluster of related abilities, commitments, knowledge, and
skills that enable a person (or an organization) to act effectively in
a job or situation.
o Competence indicates sufficiency of knowledge and skills that
enable someone to act in a wide variety of situations.
KNOWLEDGE
 Knowledge is the theoretical or practical understanding of a
subject. For example, an employee might have knowledge of the
ADME used in early drug development
A fine line between skills and abilities (learned or innate)

7. Bell M, Science Careers, March 19, 2004
COMMON DRUG DISCOVERY
DISCIPLINES
7

8. DRUG DD & OTHER R&D
SCIENTISTS
 Most of the pharmaceutical R&D scientists have a post graduate
training from a recognized academic institution in their respective
fields
 About 10% of these individuals are PhD, MD & MVSc degree
holders
 Other requirements include high IQ, goal setting, problem solving
and team playing skills
 Can also be gifted with a high EQ or MBA degree (necessary for
management positions)
 An eye for details and writing expressly in technical English
 Inclination for experiments, hypothesis generation
 Training in research methologies
 ….
8
Chakraborty B.S. (2013) PharmaTech, 4: 18-20

9. DISCOVERING & DEVELOPING
NEW DRUGS: OVERVIEW
 Highly time and cost intensive
 Three stages:
 Discovery: Identifying new compounds that help
treat disease
 Development: Administering the new drug to
animals and humans to make sure it is safe and
effective
 Manufacturing: Producing the new drug in large
quantities for distribution
9

10. DRUG DISCOVERY
 Selection and characterization of the target disease
 Disease must be well understood and characterized
 Protein (usually) associated with the disease can be targeted by a
lead compound with desirable properties
 Which may cure the disease or control it
 With HTS robotics, data processing and control softwares, liquid
handling devices, and sensitive detectors, a researcher can now
conduct millions of chemical, genetic or pharmacological tests in
few days
 Such in silico molecular modeling is actually a tremendous
acceleration of the drug discovery process
 40 years to understand the cholesterol biosynthesis pathway to develop
the statin drugs – those that inhibit the enzyme HMG-CoA reductase, the
rate limiting step in cholesterol biosynthesis
 But 3 yrs for a molecular-level understanding of the role of the HER-2
receptor in breast cancer to develop Herceptin® 10
Chakraborty B.S. (2012) PharmaTech, 3: 22-26

11. 11

12. DRUG DISCOVERY
12
Chakraborty B.S. (2012) PharmaTech, 3: 22-26

13. DEVELOPMENT OF THE LEAD
COMPOUNDS

Only 3-4 lead compounds emerge per 2000 structures examined
 Subjected to preclinical efficacy and safety and toxicity testing
 The first in humans, viz. Phase I studies
 Human safety, maximum tolerated dose based on pharmacokinetics
(ADME – absorption, distribution, metabolism and elimination) of the
administered drug
 Also be a slight hint of human efficacy of the lead drug in some cases
 If the toxicity profile and tolerability of the drug are acceptable
 Tested in limited number of patients first (a Phase II study)
 finally in a substantial number of patients in epidemiologic setup
(Phase III study)
 Results from clinical trials are fed back to enhance the next round
of target selection and lead identification and optimization
 Highest goal of drug DD is that the drug is safe & effective
in its proposed use(s) & benefits outweigh the risks
13

14. DEVELOPMENT OF THE LEAD
COMPOUNDS
14
Figure 2: The lead compounds are screened in animals and then select lead
compounds, only a few, are taken to the subsequent clinical studies.
Chakraborty B.S. (2012) PharmaTech, 3: 22-26

15. LEAD COMPOUND TO
REGULATORY APPROVAL
15
Chakraborty B.S. (2012) PharmaTech, 3: 22-26

16. 16

17. REGULATORY APPROVAL TO
MARKETING
 At the end of Phase II, the FDA and sponsors try to come to an
agreement on Phase 3 conduct
 How often the FDA meets with a sponsor varies, but this is one of two
most common meeting points prior to NDA
 The other most common time is pre-NDA, right before an NDA is
submitted
 Phase III studies begin if evidence of effectiveness is shown in Phase II
 Ph III: more information about safety & effectiveness,
 Studying different populations and different dosage
 Using the drug in combination with other drugs
 N=Hundreds to about 3,000
 Results of Phase III studies provide the main evidence of efficacy
and safety in a Regulatory application
 Following the Regulatory approval the drug can be marketed in that
country
 Post-marketing study commitments (Phase IV) are conducted after the
FDA has approved a drug for marketing
17

18. ADAPTATION OF A FRESH
GRADUATE IN HIS/HER R&D ROLES
 R&D scientists are mostly concentrated in private sector
pharma business companies and some academic institutions
 400,000 people globally in pharma, biotech and medical devices R&D
 Majority get a job orientation following their graduation from academia
and only after joining their employment
 Formal training in on-going projects and SOPs by the minute stepwise
descriptions of processes and rigidity of specifications
 The hierarchy of reporting and the reality of owning the responsibilities
are also strikingly novel for most of the entry level scientists
 Challenge is to be a part of large multidisciplinary drug discovery &
development teams
 A suitable mentor can hold the hands of a fresh graduate during these
bewildering times 18
Chakraborty B.S. (2013) PharmaTech, 4: 18-20

19. TEN ESSENTIAL SKILLS FOR
R&D SCIENTIST IN PHARMA
 Strong background in domain subjects (slide7 )
 Solid training in a research laboratory
 Ability to handle large datasets and conduct expert data analysis
 Analytical thinker and critical problem solver
 Excellent time manager with the ability to work independently
 A technophile who’s neither afraid of technology nor enamored by
it
 Experience in working as part of a multidisciplinary research
team
 A knack for finding new drug discovery targets
 Ability to clearly recognize when your research project is taking
you down a dead end
 A leader skilled in interpersonal communication
19

20. FIVE ESSENTIAL SKILLS FOR
R&D MANAGEMENT
 Timeline management
 Finish projects and tasks on time
 Budget management
 Finish on or under budget
 Scope management
 Achieve the goals
 Customer satisfaction
 Meet or exceed stakeholder requirements
 Leadership & Team Building
 Build and maintain a productive work team
20

21. ADDITIONALLY &
ESPECIALLY
 Do a talent gap analysis – the gap between the number
of (current+potential) scientific leaders and the number
required
 Clearly differentiated roles for senior, middle, and
project managers
 A focus on the pivotal roles across the middle
 Developing critical skills within the middle
management group
 They define a compelling destination
 They connect beyond boundaries
 They apply multiple lenses to problem solving
 They exploit informal channels to engage their people 21
Source: Booz & Company (2010)

22. DEVELOPMENT OF TEAM PLAYING
SKILLS
 All pharma R&D activities are carried out in “team” set up these
days
 Teams could be mainly of three types:
 Management, operational and expertise
 Management teams have the roles of leading and co-ordinating
 Operational teams consist of actual delivery of projects and
problem solving oriented team players
 Experts give critical input and also provide depth expertise
wherever needed
 Desirable that there is no artificial competition and dissatisfaction
in one’s mind regarding her role
 If roles remain unclear, domineering and put-down behaviours by
certain role players become rampant at the cost of others.
22
Chakraborty B.S. (2013) PharmaTech, 4: 18-20

23. FINDING A CAREER
MENTOR
 Mentor in Sanskrit is “Mantradata”
or giver of knowledge
 E.g, Krishna-Arjuna (ancient), Gandhi-
Neheru, Sir Humphry Davy- Michael
Faraday
 R&D mentor can inspire and give
insight in many career related issues
 Can explain difficult scientific concepts,
which can lay foundation of the
mentee’s understanding and save a
great deal of time and energy
 Help the young scientist to design a
difficult clinical trial or experiment and
solve problems
 Correct interpretation and scope of new
FDA & other Science guidances is
another insight that a mentor can give
23
Chakraborty B.S. (2013) PharmaTech, 4: 18-20

24. 1. You don’t get to publish
Not true. Most pharmaceutical companies strongly encourage publication of scientific
work and often link bonus payments to high publication levels.
2. You don’t get to go to conferences
Not true. Pharmaceutical companies generally encourage scientists from all levels
to attend key conferences as both delegates and presenters.
3. You just screen or make compounds all day
Not true. A drug discovery operation is made of many different disciplines and
involves many activities including a lot of basic research.
4. You are not free to follow your own interests or to be innovative
Not true on both counts. Innovation and creativity is strongly encouraged and
scientists spend significant time exploring new hypotheses and approaches
5. The science is not as good as in academia
Not true. Pharmaceutical companies claim many high-profile publications, patents
and groundbreaking concepts every year.
Bell M, Science Careers, March 19, 2004
THE FIVE MYTHS OF WORKING
FOR INDUSTRY
24

25. WHERE TO FIND AN
EMPLOYMENT?
 Large drug manufacturing and biotech companies in PBE
 Contract research organizations (CROs)
 Academic institutions
 Governmental agencies
 Regulatory
 Research
 Policy
 Laboratories developing new drug therapies
 Universities or hospitals
 Supervising clinical drug trials
 Manufacturing centers for large-scale production of medications
 Pre-Clinical CROs 25

26. BIG PHARMA & THE
PHARMACEUTICAL-BIOTECH
ECOSYSTEM (PBE)
 Big pharma is atop the ecosystem with capital and resources
needed to commercialize new drugs
 Their goal is to enrich their drug development pipeline,
leveraging their expertise in regulatory submission,
reimbursement, and commercialization of product
 They are the integrators, orchestrating the drug development
process with members of the ecosystem
 The ecosystem concept offers a richer context than established
supply chain models because the PBE is a dynamic, growing
environment
 Members can use funding from big pharma to build business that
potentially can compete against established companies
26
McCarthy R, Science Careers, March 19, 2004

27. PREPARING FOR A CAREER IN
THE PHARMA R&D
 First, increase the value of your skills so it can benefit yourself and
your employer
 Going to graduate school and training in laboratories with
intellectually stimulating environments
 Sometimes working as a technician in a university research laboratory
can be helpful
 Second, understand the dynamics of value shifts in the PBE.
 Develop an interest in technology management
 New concepts such as disruptive technology and open innovation are
changing the way established companies are developing new products
 Third, engage in dialogue with others who are more experienced
than you in this field
 And lastly, remain a lifelong student
 Genomics/proteomics revolution are just beginning
 Opportunities for technology-astute scientists are abound in future 27
McCarthy R, Science Careers, March 19, 2004

28. YOU MAY SPECIALIZE IN:
 Designing new drug therapies using natural or synthetic
(man-made) ingredients
 Discovering new ways to use existing drugs to treat different
types of disease
 Studying how disease affects the body and what causes some
people to develop certain types of disease
 Studying how the human body responds to medications, so
scientists can develop better, safer drugs Test drugs on animals
and humans to ensure safety and efficacy
 Determining the most effective formulation and dosage for a
specific drug
 Working on improving the drug manufacturing process
 Ensuring the consistent quality of prescription medications
 Advising corporations or government agencies, including the
Food and Drug Administration, on issues related to
pharmaceutical development
 Monitoring drug adverse reactions
 And many more areas....
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29. CONCLUDING REMARKS
 Main factors for skill development in Pharmaceutical R&D include
education, training, mentoring, adaptation and leadership
 The discovery a drug, small or large molecule, is an exciting &
complex process of studying its structure (along with thousand of
related structures), mechanism of action, and physicochemical
properties
 Safety and Efficacy are main concerns in Preclinical & Clinical
phases; CMC is the subject of API & formulations
 Pharmaceutical R&D scientists come from a vast array of
specializations within pharmacy, health sciences, chemistry and
biotechnology majors
 Specializations can be very refined and narrowly focused these
days
 Industry, Government and Academia are main employers
 Adaptation and continued education are key factors of success
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30. THANK YOU VERY
MUCH
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