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

http://www.encognitive.com/files/images/chemo-chemotherapy-side-effects-baldness.jpg

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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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


DRUG DISCOVERY

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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.


LEAD COMPOUND TO REGULATORY APPROVAL

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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


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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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


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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