The Pharma Professional
An industry focused learning program for students of
pharmaceutical sciences
Session 1
22nd February 2014
NIPER Hyderabad
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Outline
Industry snapshot and key trends
What the industry expects from you
Program overview and expectations
Session 1 : The drug development sector
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HOW READY ARE YOU?
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Let’s find out….
Name 3 different business segments of the pharma
industry
How many generic brands does the Indian pharma
industry have in its portfolio?
What was the market size of the Indian pharma industry
in 2011?
Which is the largest segment of the Indian pharma
industry?
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INDUSTRY SNAPSHOT AND KEY TRENDS
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Global pharma market is around 850bn and growing at 7%
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US, Europe, & Japan – constitute around 80% of the market
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Portfolio and market size – Indian pharma industry
USD 15.6 bn in 2011
USD 35.9 bn in 2016 (forecast)
Accounts for over 10% of global
pharmaceutical production
Over 60,000 generic brands
across 60 therapeutic categories
Manufactures more than 400
different APIs
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Key business segments
APIs
CRAMS
Formulations
Biosimilars
Novel drug discovery
• USD 8.7 bn export market in 2010
• India expected to become 2nd largest producer globally
• More than 1000 players
• USD 7 bn market
• Prescription and OTC drugs
• Double digit growth over next 5 years
• USD 600 mn market in 2012-13
• Govt. planning to allocate USD70 mn for local players
• Only focused players
• Collaborative research models
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Key trends
• Current spend is 2% on turnover
• Likely to increase due to introduction of product patents R&D
• India becoming a hub for clinical trials
• Market worth USD 485 mn in 2012, projected CAGR of 17% to 2015
Clinical research
• Thriving export market
• Strong presence in generic space Exports
• Several multinationals establishing partnerships and JVs with Indian companies to develop new drugs
• GSK-DRL, Pfizer-Aurobindo key examples Collaborations
• Introduction of product patents in 2005
• India has reiterated commitment to IP protection Product patents
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Functional distribution of human resources in pharma
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Typical career map
Qualifications Experience Typical profile Functions
Vocational/12th
standard
0 years Operators/Workmen Production
B.Pharm/BSc 0 years Trainees Production/QC/Sales
M.Pharm/MSc 0 years Trainees R&D and allied
functions
B.Pharm/BSc 3-5 years Supervisors Production/QC/Sales
M.Pharm/MSc 3-5 years Managers R&D and allied
functions
BPharm/MPharm 5+ years Group
Leads/Managers
Various
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WHAT THE INDUSTRY EXPECTS FROM YOU
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Technical and business expectations
Strong understanding of business models and
commercial awareness
Understanding of production environment and
compliance requirements
Understanding of quality management practices
Application of intellectual property and regulatory affairs
from industry perspective
Working in interdependent R&D environments
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Behavioral expectations
Strong business communication skills and task
orientation
Advanced presentation and team skills
Ability to be proactive and work under minimal
supervision
Ability to generate new ideas and improve existing
processes
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Program overview
An industry focused learning program for the
pharmaceutical industry
40 hours of hands-on modules designed to enable
students to understand industry skills
Robust assessment and certification
Aligned with your placement objectives
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What we expect from you
Regular attendance – 100%
Assignments to be completed on time
Participate fully in interactive sessions
Certification subject to:
Attendance
Class participation
Quality of assignments
The business of drug development
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Outline
Overview and key trends
The drug development lifecycle
Key phase gates and deliverables
Key functions and responsibilities
Organization and team structures
Cross functional interactions and challenges
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OVERVIEW AND KEY TRENDS
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Drug development is progressive elaboration
Is there an unmet Medical need?
What targets to work on?
Do we have the right molecule?
Does it work in animals?
Is it safe in animals?
Is it safe in humans?
Does it work in humans?
Does it work in clinic?
EXPLORE
DISCOVER
DEVELOP
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Generic
formulation
Brand
Bulk drug
Reward-risk profile
Risk
Rew
ard
Innovation
NDDS
NCE
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Making a drug – long, risky and expensive
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Key facts
It takes 10-15 years to develop a new drug
The pharma industry currently spends over USD135
billion every year on R&D
In 2011, 35 new drugs were launched out of more than
3200 compounds in development
In 2007-2011, the number of NCEs/NBEs launched fell
to 149 from 196 a decade earlier
It costs an average of USD 1.38 billion to develop a
single new drug
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THE DRUG DEVELOPMENT
LIFECYCLE
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The drug development lifecycle
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Overview of key processes and timelines
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Novel drug development– the moving parts
Understanding the biological pathways that the drug
modulates
Creativity in the design of molecules
The correct balance of efficacy and safety
High rate of failures
Opportunity costs of tying up investment capital
Much higher for the pharmaceutical industry
Primarily influenced by long gestation periods for a
research project
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Where does the money go?
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Challenges of pharma product development
Complex development process
Long duration and high development costs
Multiple activities, multiple resources
High degree of technical uncertainty
High degree of market uncertainty
Dependencies among candidates
Regulatory requirements/limitations
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KEY PHASE GATES AND
DELIVERABLES
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Reproducible API scale-up and optimization of process suitable for preparation
of DS for pre-IND work
Complete pre-formulation package
MoA established
Selectivity established against unwanted pharmacologically related side effects
Complete pharmacological in vivo profiling via intended RoA in relevant animal
models
Safety pharmacology established, safety margin defined
Optimized PK and metabolic properties in approved formulation and intended
RoA
Adequate exposure for tox studies in at least 2 species
PK/PD correlation established in animal models
Compound patent filing covering all indications
Phase gates to enter regulatory safety studies
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Candidate drug to be a single stereoisomer (preferably achiral), absence of
active metabolites
Acceptable physicochemical properties and pre-formulation performance
Process in place for manufacture of API for Phase I
Satisfactory outcome of regulatory tox studies
Expected therapeutic dose in man finalized
Potency, efficacy and selectivity as per defined TPP
All DMPK properties optimized, prediction of human PK with clear
pharmacology and toxicology correlations
Finalized clinical TPP
Draft protocols for Phase I studies, and regulatory strategy upto PoC
Phase gates to enter Phase I
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Solid phase drug product/API consistent within process chemistry and
compatible with proposed excipients
Animal ADME package completed
Established PK/PD correlation and adequate dose exposure
Efficacy profile as per agreed TPP
Adequate safety margin established with 13 week studies, no genotox
liabilities
Acceptable safety, tolerability and exposure from Phase I studies
Draft protocols for Phase II studies, and updated regulatory strategy
Phase gates to enter Phase II
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Human dosage formulation finalized
Adequate safety margins established in animal models to support longer
duration of dosing in humans for Phase III
Satisfactory outcome from immunotox studies
Human ADME package completed
PoC established in humans
Phase gates to enter Phase III and beyond
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KEY FUNCTIONS AND
RESPONSIBILITIES
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Multiple functions involved
Molecular
biology
Exploration Discovery Optimization Safety Clinical
Development
Regulatory
Approval
Bioinformatics
Pharmacology
Medicinal
Chemistry
Toxicology
Analytical
Chemistry
Formulation
Pharmaco
kinetics
Clinical
Development
Regulatory
Expertise
Marketing
Process
Chemistry
Statistics
Legal
Expertise
Biochemistry
Project
Management
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Reproducible API scale-up and identifying suitable process for drug
substance
Establishing validated analytical methods
Ensuring material characterization for safety studies
Pre-formulation and formulation development including polymorph screening
and stability
Providing stable drug product with minimum accelerated stability data
Key responsibilities - CMC
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Establishing PK/PD correlations in animal models
Predicting the expected therapeutic dose in humans using non-clinical data
and correlations
Optimizing PK and metabolic properties in the approved formulation
Animal ADME and human ADME packages
Key responsibilities – Biology and DMPK
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Updating TPP with recommendations on clinical relevance
Developing and updating the clinical plan with protocol synopses one phase
in advance
Developing protocols for clinical studies
Conducting clinical studies - monitoring for safety, efficacy and adverse
findings
Key responsibilities – Clinical Development
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Providing guidance on TPP
Developing the regulatory strategy from IND to NDA
Review and compilation of all relevant data for regulatory filings
Key responsibilities – Regulatory
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Defining the expected safety margins for regulatory studies and establishing
parameters for safety decisions (MTD, NOAEL, etc)
Developing protocols for safety studies
Conduct of studies, review of data and recommendations on Go/No Go
parameters
Key responsibilities – Safety
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Providing commercial assessments with priority of label claims and
indications
Market forecasts to justify continuation of investment
Developing launch strategy and providing oversight to project teams
Providing strong patent positions and ensuring no infringements on
substance, delivery system, formulation, indication or manufacturing methods
Key responsibilities – Commercial and IP
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ORGANIZATION AND TEAM
STRUCTURES
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Overview of organization structures
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Core teams and extended teams for a focused approach
Core team members own the action items and work with support departments
to ensure the deliverable
Extended team members are invited to meetings as needed; project
information (status, issues etc.) will be shared with all team members
Extended team members get integrated into core team as project moves into
later stages of development
Key concepts
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Project Teams
Leadership
CMC
Staff
Staff
Clinical
Staff
Staff
Regulatory
Staff
Staff
Safety
Staff
Staff
PMO
Project Manager
Project Manager
Project coordination
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Project Teams : Illustration of structure
CORE TEAM:
Project leader (Clinical)
Project Manager
Safety
Biology
DMPK
Regulatory
CMC
EXTENDED TEAM:
AR&D
Commercial
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Leads a multi-disciplinary team to achieve common goals
Drives the project from a scientific and business perspective
Monitors the environment and proposes scope changes as appropriate
Provides a mechanism to anticipate and handle uncertainties
Key roles – Project/Program Leader
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Drives the project management process
Manages cross-functional teams to achieve common objectives
Works with stakeholders to agree scope, deliverables, budgets and resources
across projects
Manages scope and mitigates risk across projects
Establishes, reviews and maintains project plans and tracking mechanisms
Chairs and leads project team meetings and ensures accurate and adequate
discussion of issues and action items
Manages and resolves conflicts
Key roles – Project/Program Manager
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Serves as functional expert; provides technical expertise and makes decisions
on behalf of the function
Takes accountability for the project deliverables related to his/her function
Ensures availability of function resources for the delivery of objectives
Provides all data, information and reports as required by the project team in a
timely manner
Key roles – Team member
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70-80% of all work is outsourced
Core expertise such as clinical/regulatory strategy is retained in-house
CMC, safety/PK form the major components that are outsourced
Virtual organizations have a strong project leader /project manager interface
Virtual organizations
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CROSS FUNCTIONAL
INTERACTIONS AND CHALLENGES
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What is expected of cross functional teams?
Resource optimization
Integration between science and business
Cost effective planning
Optimized development processes
Robust risk management
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What are the challenges?
SCOPE MANAGEMENT
Scope definition – back-translating the commercial expectations into
deliverables
Lack of scientific precedence and translation between animal and human
testing
Changes in competitive landscape and regulatory policies
Impact assessment of scope changes is complex and variable
Project scopes often poorly articulated
Gaps in establishing change control mechanisms
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What are the challenges?
TIME MANAGEMENT
Multiple iterative loops between functions
At what level of granularity should the plan be baselined?
Significant assumptions made early on
Decision making is data driven – planning for additional scenarios in a cost
effective manner is a challenge
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What are the challenges?
RESOURCE MANAGEMENT
Research is skillset driven
Requires multiple levels of agreement to ensure commitment
Retention and transfer of knowledge
Prioritization of material and equipment in the absence of a robust portfolio
prioritization mechanism
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Group Assignment
Divide yourselves into groups of 5
Identify the top 3 R&D companies (by sales) in India
Find their R&D pipeline and R&D strategy
Write a 500 to 700 word assignment on these companies on the
following:
R&D strategy
Business model
R&D Pipeline
Assignment should be submitted as a Word document by Thursday
27th February 2014 to [email protected] with a cc to
your department head