Factors influencing researchers' skill development process
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Transcript of Factors influencing researchers' skill development process
FACTORS INFLUENCING RESEARCHERS’ SKILL DEVELOPMENT PROCESSFOCUS ON PHARMACEUTICAL R&D
Dr. Bhaswat S. Chakraborty Sr. VP & Chair, R&D Core
CommitteeCadila Pharmaceuticals Ltd.
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Presented at the DSIR Seminar “Essential Skills for the 21st Century Researcher,” GTU,
Ahmedabad, January 7, 2016
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
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New Medicine Marvels
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 developed4
Chakraborty B.S. (2012) PharmaTech, 3: 22-26
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
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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)
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COMPETENCEo 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)
Bell M, Science Careers, March 19, 2004
COMMON DRUG DISCOVERY DISCIPLINES
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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 ….
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Chakraborty B.S. (2013) PharmaTech, 4: 18-20
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
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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
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DRUG DISCOVERY
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Chakraborty B.S. (2012) PharmaTech, 3: 22-26
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
DEVELOPMENT OF THE LEAD COMPOUNDS
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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
LEAD COMPOUND TO REGULATORY APPROVAL
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Chakraborty B.S. (2012) PharmaTech, 3: 22-26
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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
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 times18
Chakraborty B.S. (2013) PharmaTech, 4: 18-20
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
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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 team20
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 people21
Source: Booz & Company (2010)
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.
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Chakraborty B.S. (2013) PharmaTech, 4: 18-20
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
1. You don’t get to publishNot 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
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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
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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
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McCarthy R, Science Careers, March 19, 2004
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
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McCarthy R, Science Careers, March 19, 2004
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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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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THANK YOU VERY MUCH
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