The Pharma Professional

An industry focused learning program for students of

pharmaceutical sciences

Session 1

22nd February 2014

NIPER Hyderabad

2 2

Outline

Industry snapshot and key trends

What the industry expects from you

Program overview and expectations

Session 1 : The drug development sector

3

HOW READY ARE YOU?

4 4

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?

5

INDUSTRY SNAPSHOT AND KEY TRENDS

6

Global pharma market is around 850bn and growing at 7%

7

US, Europe, & Japan – constitute around 80% of the market

8 8

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

9 9

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

10 10

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

11 11

Functional distribution of human resources in pharma

12 12

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

13

WHAT THE INDUSTRY EXPECTS FROM YOU

14 14

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

15 15

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

16 16

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

17 17

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

19 19

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

20

OVERVIEW AND KEY TRENDS

21 21

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

22 22

Generic

formulation

Brand

Bulk drug

Reward-risk profile

Risk

Rew

ard

Innovation

NDDS

NCE

23 23

Making a drug – long, risky and expensive

24 24

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

25

THE DRUG DEVELOPMENT

LIFECYCLE

26 26

The drug development lifecycle

27 27

Overview of key processes and timelines

28 28

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

29 29

Where does the money go?

30 30

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

31

KEY PHASE GATES AND

DELIVERABLES

32 32

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

33 33

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

34 34

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

35 35

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

36

KEY FUNCTIONS AND

RESPONSIBILITIES

37 37

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

38 38

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

39 39

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

40 40

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

41 41

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

42 42

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

43 43

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

44

ORGANIZATION AND TEAM

STRUCTURES

45 45

Overview of organization structures

46 46

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

47 47

Project Teams

Leadership

CMC

Staff

Staff

Clinical

Staff

Staff

Regulatory

Staff

Staff

Safety

Staff

Staff

PMO

Project Manager

Project Manager

Project coordination

48 48

Project Teams : Illustration of structure

CORE TEAM:

Project leader (Clinical)

Project Manager

Safety

Biology

DMPK

Regulatory

CMC

EXTENDED TEAM:

AR&D

Commercial

49 49

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

50 50

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

51 51

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

52 52

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

53

CROSS FUNCTIONAL

INTERACTIONS AND CHALLENGES

54 54

What is expected of cross functional teams?

Resource optimization

Integration between science and business

Cost effective planning

Optimized development processes

Robust risk management

55 55

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

56 56

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

57 57

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

58 58

59 59

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 support@learning-curve.co.in with a cc to

your department head