bioavailability challenge 2013 - outsourcing dynamics for bioavailability

March 20th 2013

Outsourcing Dynamics for Bioavailability

Deepika Pramod ChopdaResearch Analyst - Life SciencesFrost & Sullivan

Bioavailability Challenge 2013

2

Focus Points

Challenges and Market Demands around Bioavailability

Overview—Current Scenario surrounding Bioavailability

Source: Frost & Sullivan analysis.

Shifting Trends–Bioavailability Outsourcing- CRO’s and CMO’s

Focus Points

Key Strategies and Conclusions

3

Overview—Current Scenario surrounding Bioavailability


Overview

Introduction

Demand

Competition

Outsourcing

Bioavailability is the rate of an active pharmaceutical ingredient absorbed from a drug product to an extent of it being available at the site of action.

Rise in disease incidence rate triggers the demand for new and improvised drug development, which directly accounts for the development of first stage of laboratory trials starting from bioavailability.

Despite the growth promising factors, this segment is effected by pricing pressures due to high laboratory procedure costs, in an economically constricted scenario.

Outsourcing has increasingly become a strategic move for most pharmaceutical and biotech companies intensifying the market opportunities for companies offering contract services primarily for cost effective reasons

4

Need for Bioavailability

Bioavailability – Need ?

To provide and estimate the

fraction of orally administered

drug dose that is absorbed into

the systemic circulation when

compared to the bioavailability for

a solution, suspension or

intravenous dosage form that is

completely available.

Useful information to

establish drug dosage

regimen and support drug

labeling, such as distribution

and elimination

Bioavailability studies

provide information on

performance of drug

formulation


5

Focus Points

Bioavailability- Challenges and Demands


Focus Points

6

Bioavailability- Challenges

• Controlling drug solubility and permeability is a

major challenge faced by the drug development

industry.

• Weak stability of the dissolved drug at the

physiologic pH.

• Intense presystemic metabolism

• Lengthy drug development programs due to high

inter-patient response variability increases costs,

thus poses as a challenge

• Controlling drug solubility and permeability is a

major challenge faced by the drug development

industry.

• Weak stability of the dissolved drug at the

physiologic pH.

• Intense presystemic metabolism

• Lengthy drug development programs due to high

inter-patient response variability increases costs,

thus poses as a challenge

Challenges


BCS Class I ~ 5%

BCS Class IV~20%

BCS Class II~70%

BCS Class III~5%

So

lub

ilit

y

Permeability High Low

High

Low

Note : BCS- Biopharmaceutics Classification System

Ref: L.Benet, Predicting drug disposition by Application of BDDCS, AAPS, 2008

New Chemical Entities

Response of Poor Water Soluble Drugs

7

Addressing the Challenges

Biological Approach

Pharmaceutics Approach

Pharmacokinetic Approach

Dissolution Enhancement


8

Bioavailability- Demands

• Comprehensive availability of products and

technologies supporting bioavailability

enhancement.

• Partnerships and collaboration between drug

discovery research companies and

manufacturing companies for improved drug

performance.

• Develop polymers to enhance drug solubility.

• Comprehensive availability of products and

technologies supporting bioavailability

enhancement.

• Partnerships and collaboration between drug

discovery research companies and

manufacturing companies for improved drug

performance.

• Develop polymers to enhance drug solubility.

Demands


Enhancing Bioavailability enhancing represented using a pro-drug design

Rev. Bras. Cienc. Farm. vol.40 no.3 São Paulo July/Sept. 2004

9

Addressing Demands

Using Hot Melt extrusion

Use of Spray-dried

Dispersions

Using Particle size Reduction

concept

Collaborations with contract research/man

ufacturing organizations


10

Focus Points

Shifting Trends–Bioavailability Outsourcing- CRO’s and CMO’s


Focus Points

11

Market Overview

Outsourcing Research /

Manufacturing

Outsourcing has increasingly become a strategic move for most pharmaceutical and biotech companies.

With manufacturing costs contributing to a major chunk of expenditure, pharmaceutical and biotech companies are considering contract manufacturing

The European Pharmaceutical Contract Manufacturing Market was estimated to be $11.20 billion in 2012, growing at rates of 10.4 per cent The European Contract Research market generated $6.58 billion in 2012, growing at rates of 8.5 per cent respectively.

. More than 80 per cent of the CMOs in Europe are located in the West – which includes Germany, the United Kingdom, France, Spain, Italy, and the Scandinavian and Benelux countries. ▪ Rise in CROs in the Eastern European and the Asian regions hinder Western European market growth due to economic constraints.

Contract Manufacturing Organizations (CMOs) and Contract Research Organizations (CROs) are equipped with the required expertise, resources, technology, and tools as a viable option to save cost and time. Independent services for pharmaceutical and biotechnology markets.


12

Research and Development

Discovery Research

Pre-clinical Development

Clinical Development

Drug Substance Production

Primary Process Development

Drug Substance Production

Formulated Drug Production

Dosage Form Develop- Ment

Dosage Form Production

Packing/ Ass-embly

Log-istics

More Important

Less Important

Outsourced Services

• Discovery Research

• Chemical Synthesis

• Pharmacology & Toxicology

• Clinical Trials

• Analytics

• Regulatory Support

• Process Development

• Formulation Development

• Drug Substance Production

• Dosage From Production

• Packaging

• Logistics

Outsourcing activities are well established along the whole pharmaceutical R&D and production value chain, from discovery research to packaging and logistics. Most of the outsourced services are used in one or more process steps of the value chain. In contrast to the traditional companies or Fully Integrated Pharmaceutical Companies (FIPCO), emerging pharmaceutical companies are focused on selected stages of the pharmaceutical value chain.

Shifting Trends of Pharmaceutical Outsourcing


Pharmaceutical R&D and Production Value Chain —The Shifting Trends of Pharmaceutical Outsourcing

13

FIPCO (Fully Integrated Pharma Co.)

ResearchTechnology

Manufacturing

Clinical andRegulatory

Sales andDistribution

CSO

CMO

CROs

Partnerships

Academia, Scientific, Institutions

R&D

Preclinical Support

Clinical Development

Manufacturing

Sales and Distribution

Preclinical CRO

VIPCO (Virtually Integrated Pharma Co.)

Source: Burrill & Co. and Frost & Sullivan analysis

Changing Business Models

Pharma/Biotech Industry: Changing Business Models (Global), 2012

14

Why Outsource ?

Why Outsource Bioavailability?

Increased drug demand from

pharmaceutical and biotech

marketExclusive product

offerings and services

Strict regulatory approvals

Use of metrics-driven processes for clinical trials and drug testing

Efficiency in time

Access to state-of-the-art research tools

to develop niche products

Increase in R&D

expenditure


15

• The cost of developing drug had increased to $1,318.0 million in 2006 from $802.0 million in 2001.

• Increasing R&D expenditure, coupled with lower NCE approvals, resulted in continuous decline in R&D productivity.

• R&D productivity declined from 51.0 percent in 2000 to a historic low of 17.0 percent in 2009.

• R&D investment increased manifold during these years, but the number of NMEs launched every year remained almost stable.

Pharmaceutical Market: Cost of Developing Drugs, Global, 1975, 1987, 2001 and 2006

Pharmaceutical Market: New FDA Approval and R&D Spending, Global, 2000-2011

Co

st

of

De

vel

op

me

nt

($ M

illio

n)

R&

D S

pen

din

g (

$ B

illio

n)

Year

Nu

mb

er

of

Ne

w F

DA

Ap

pro

va

ls

Year

Note: *Total NMEs + Biologicals


Rising Cost of Drug Development and Declining R&D Productivity

1975 1987 2001 20060

200

400

600

800

1,000

1,200

1,400

138

318

802

1,318

16

Breakdown of Outsourced Drug Development Activities

Fill-finish operations

Toxicity testing

Validation services

Plant maintainance services

Testing for Product characterisa-tion

Contract Research (laboratory)

Testing for other bio assays

Testing for lot release

Downstream operations

Upstream operations

0 5 10 15 20 25 30 35 40

34.5%

26.6%

23.1%

21.1%

20.7%

18.3%

18.1%

17.5%

15.0%

15.2%

Upstream produc-tion operations

Downstream Pro-duction Operations

Validation services

Fill-finish opera-tions

Testing for product characterisation

0 5 10 15 20 25 30 35

30.1%

27.8%

24.5%

24.8%

18.3%

Bioavailability Outsourcing : Per cent Breakdown of activities being outsourced (Europe), 2011

Bioavailability Outsourcing : Growth rates of segments likely to witness higher levels of outsourcing (Europe), 2012- 2018

Note: All figures are rounded. The base year is 2011. Source: Frost & Sullivan analysisNote: All figures are rounded. The base year is 2011. Source: Frost & Sullivan analysis

17

Focus Points


Focus Points

Key Strategies and Conclusions

18

Bioavailability Outsourcing—Key Success Factors


Competitive

Knowledge

Capital

Investments

Vision

&

Strategy

Scale-up

Production

Capabilities

Clinical &

Regulatory

Expertise

Marketing

& Sales

Skills

• Clearly defined long-term vision commitment and strategic fit.• Goals for in-house development marketing, and geographic focus.

• Competitive intelligence on bioavailability enhancement

• Competitor pipeline analysis competitor’s R&D investment strategy.

• Competitive regional benchmarking.

• Effective communication to the scientific community• Effective market activities for commercialization of biosimilars• Continuous promotional activities and marketing relationship with doctors, pharmacists etc.

• Technical know-how for

clinical development• Regulatory expertise on

guidelines such as EMEA,

FDA and pharmacovigilance

Expertise

• Stable multi-step reproducible manufacturing facilities

• Proper supply chain management• Standard testing control facilities

Success

• Healthy finance infrastructure for high upfront investments

• Ability to cope with high manufacturing, maintenance, and promotional costs

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Conclusion

The Last Word- Significance of Bioavailability

Dictating PK behaviour is essential for enhancing

bioavailability

Dictating PK behaviour is essential for enhancing

bioavailability

Partnerships with CRO‘s to reduce costs and

improve process efficiency

Partnerships with CRO‘s to reduce costs and

improve process efficiency

Drug dissolution- rate determining step for oral

absorption

Drug dissolution- rate determining step for oral

absorption

Alliances and jointly developed programs for

bioavailability enhancement- growing

trend

Alliances and jointly developed programs for

bioavailability enhancement- growing

trend

To build therapeutic efficacy in a drug

To build therapeutic efficacy in a drug

Bioavailability is the most important factor to

control drug formulation

Bioavailability is the most important factor to

control drug formulation

A shift towards outsourcing for bioavailability is expected to build in the future to shorten the duration of drug action for faster and effective results accomplished by market

expertise


20

For Additional Information

Deepika Pramod ChopdaResearch AnalystFrost & Sullivan – Life [email protected]

Thank You!Please contact for additional information.

Ranjith GopinathanProgram ManagerFrost & Sullivan – Life [email protected]

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