WEBINAR – March 26, 2009 Shoot for Share! From …...920752-00 1 SPEAKER: Raul Soikes Senior Director, Program Management Baxter BioPharma Solutions WEBINAR – June 25, 2009 Shoot

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SPEAKER: Raul Soikes

Senior Director, Program Management

Baxter BioPharma Solutions

WEBINAR – June 25, 2009

Shoot for Share!From Vial to Pre-filled Syringe

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Today we will address:

Why? Value proposition of moving to a pre-filled syringe

What? Regulatory plan to enable move

How? Process to move from vial (liquid or lyophilized) to syringe

Who? CMO qualifications

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WHY?

VALUE PROPOSITION

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Why?

Market drivenLine extension – Life cycle management

• New presentation• New administration route

Latest Technology / Market edge• Competition• Pharmacoeconomics

Customer drivenSafety- fewer manipulationsAccuracy- Dose deliveredQuality of life- self administered

Product drivenManufacturing

Less API waste → increased units filled → increased revenue

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Why? - Strategies to Improve the Value of a Biologic Molecule

Due to the inherent challenges of biologics, enhancements are difficult yet the market rewards improvements

Short-Term Strategy (6-18 Months)

Mid-Term Strategy (18-36 Months)

Long-Term Strategy (>36 Months)

Attach a safety device to a pre-filled syringe

Kit vials with a ready to use diluent syringe

Move from a stable liquid vial to a pre-filled syringe

Move from a vial orsyringe into anautoinjector or cartridge

Reformulate lyophilized vials into a liquid vial or pre-filled syringe

Develop sustained release formulation

Develop alternate route formulation

Short and Mid -Term strategies can help to differentiate a biologic molecule

Enhanced Packaging and Reformulation Give New Life to Biologics, Tom Polen, BioPharm International, October 2006

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Why? - Mid-Term Strategy

Teva Pharmaceutical Industries Ltd changes the presentation of Copaxone® from a dry vial preparation to a pre-filled syringe.

Copaxone PFS achieved rapid uptake in the US, with 64% of patients switching within the first three months from the dry vial formulation to the new formulation, and the remainder had switched within six months of launch.

Dry vial to Syringe – rapid uptake 64% switched in 3 months, remainder in 6 months after launch

10.1

17.219

21.5 22.724.2 24.3

8.2

11.7

4.7

0

5

10

15

20

25

30

2000 2001 2002 2003 2004 2005 2006 2007 2008

Copaxone PFS Copaxone Lyo Vial

Unit data in (M) Millions of units… 2003, patients had all but completely switched to PFS formulation

Unit data in (M) Millions of units… 2003, patients had all but completely switched to PFS formulation

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For patients, the switch reduced average preparation time from 235 seconds (reconstituted Copaxone) to 38 seconds, saving more than 20 hours over the course of a year.

The Copaxone® reformulation was priced at a premium as compared to the original formulation. In 2002 the premium started at 5%, however, by 2005 the price premium was 48.6%.

Premium pricing - from 5% in 2002 to 49% by 2005.

Preparation time reduced from 4 minutes to 38 seconds.

28.04 29.5533.33

37.8842.64

48.14

55.64

26.02 25.51

$0.00

$10.00

$20.00

$30.00

$40.00

$50.00

$60.00

2001 2002 2003 2004 2005 2006 2007 2008

Copaxone PreFilled Syringe Copaxone Lyo Vial

2002 Pricing -$26.02 Vial vs. $28.04 for PFS

2005 Pricing -$25.51 Vial vs. $37.88 for PFS

Unit pricing of Copaxone in $ USD

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Enbrel Presentation Mix

02,0004,0006,0008,000

10,00012,00014,000

2004 2005 2006 2007

Uni

ts (T

hous

ands

)

Vial (Kit) Syringe SureClick


Amgen, Inc. changed the presentation of Enbrel from a dry vial preparation to a pre-filled syringe. To further differentiate and add value, in 2006 Enbrel launched in an auto injector.

IMS Data

Overall Enbrel unit sales have remained stable, however revenue has increased due to the price premium the PFS and SureClick™ format.

Revenue increased due to price premium; unit sales stable

Enbrel WW Sales

0

1,000

2,000

3,000

4,000

5,000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

$ (M

illi

on

s)

Sales ROW Sales US Sales Japan

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Why? - Selecting a Drug Delivery TypeDoctors’ top factors : minimal side effects, patients ease of use, satisfaction, convenience, comfort. Three of five factors (underlined) impacted by product presentation.

Question:In order of importance, please select the top 5 factors that you consider when selecting a drug delivery type? (1= most important, 2=2nd most important, 3=3rd most important, etc.)

2%

1%

1%

2%

2%

6%

8%

5%

6%

9%

11%

16%

9%

1%

2%

2%

3%

3%

5%

6%

9%

13%

10%

12%

15%

1%

2%

2%

1%

4%

9%

6%

7%

10%

10%

16%

1%

3%

5%

1%

6%

9%

11%

8%

12%

6%

6%

11%

3%

4%

3%

2%

4%

5%

3%

5%

3%

5%

7%

8%

9%

10%

11%

9%

10%

14%

7%

3%

3%

13%

3%

2%

6%

6%

4%

7%

1%

8%

Well designed device

Ease of cost reimbursement

Formulary tiering of product with the delivery form

Easy for doctor to administer

Higher drug absorption

Requested by patient

Speedy recovery

Low frequency of dosing

Bioavailability

Low cost

Rapid onset of action

Dose accuracy

Patient comfort

Patient convenience

Patient satisfaction

Easy for patient to use

Minimal side effects

US Drug Delivery - Frost & Sullivan 2008

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46%

3%

2%

6%

9%

2%

1%

15%

2%

12%

9%

12%

6%

13%

5%

16%

14%

7%

17%

2%

4%

14%

10%

10%

7%

5%

17%

3%

12%

13%

20%

10%

9%

8%

11%

7%1%3%

13%

19%

3%

15%

7%

9%

7%

6%

1%

16%

11%

6%

6%

2%

0% 10% 20% 30% 40% 50% 60% 70%

Easy to self administer

Size of device

Specific adverse side effects to device

Requested by patient

Cost to patient

Formulary Tiering of Product

Appealing appearance of device

Published Clinical Data

Does not require power source

Complexity of device

Has Reusable Component

Rank 1 Rank 2 Rank 3 Rank 4 Rank 5

Ease of self administering is the top reason for selecting a device type.

Question:For Device Driven Drug Delivery (Examples: Inhaler, Autoinjector), please select the top 5 factors that most influence your decision to prescribe the product to your patients?

Why? Selecting Drug Delivery Type - Physician


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37%

3% 6%

24%14%

1% 3% 4% 3% 2% 3%

26%

6%7%

16%

12%

3%13%

7%3% 5%

14%

10%

12%

13%

7%9%

5%8%

10%

11%

10%

13%

2%

7%8%

6%

8%

4%

10%12%

10%

10%

4%

9%

11%

10%

9%

10%12%

9%

12%

13%

0%10%

20%30%

40%50%60%

70%80%

90%100%

Easy to selfadminister

Size of Device

Specif ic adverse side

effects

Recommendedby

Physician

Out of Pocket Cost

Appealingappearance

Published Clinical data

Does not require

batteries /pow er source

Complexity ofdevice

Need torefrigerate drug portion

Reusable /Environment-ally Friendly


Why? Device Drug Delivery Method - Patient

Question:For Device Driven Drug Delivery what are the top 5 factors that you consider? (1=most important, 2=2nd most important, 3=3rd most important, etc.)

Top Factors are ease of self administration (37%) followed by Physician’s recommendation (24%)


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Why? Device Drug Delivery Method – Patient

26%10%

2% 8% 11% 10%2%

17%10%

20%

7%

5%

11%15%

3%

20%

1%

8%

17%

7%

16%13%

3%4%

4%

13%

8%

12%15%

15%

4%3%

6%

8%

9%

10%

14%8%

13%

7%

14%

3%

14%

1%

9%8%

15%

12%

13%

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Easy to selfadminister

Rapid Onset of Drug Action

Lowfrequency of

dosing

Minimal Sideeffects

NoDiscomfort /

Pain

Low Cost /InsuranceCo-Pay

Likelihood ofReimburse-

ment

VeryConvenient

Welldesigneddevice

My doctorprefers it

Must beadministeredby another

person


Ease of self administering is the most important factor for selecting drug delivery type followed by convenience.

Question:In order of importance, please select the top 5 factors that you consider when selecting a drug delivery type? (1= most important, 2=2nd most important, 3=3rd most important, etc.)


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WHAT?

REGULATORY STRATEGY

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What?Define Regulatory Strategy

Regulatory considerations – Major change to regulatory market approval . . . Manageable

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Evaluate & compare the proposed syringe system to approved materialsProtects the drug

product?Introduce a new

material?Need drug product

formulation changes?


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Evaluate & compare the proposed syringe system to approved materials

Need supporting clinical data?

Protects the drug product?Introduce a new



Safety or efficacy effect?New indication?New route of

administration?


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Evaluate & compare the proposed syringe system to approved materials

Need supporting clinical data?

Perform Stability protocol - New Dosage Form

Protects the drug product?Introduce a new



Safety or efficacy effect?New indication?New route of

administration?

Define stability requirementsExecute stability

protocolAnalyze stability

data


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HOW?

VIAL TO SYRINGE

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How?

FilingFormulationStudy

StabilityStudy

ClinicalStudy

REGULATORY STRATEGY

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How?

Filing

Liquid

Lyophilized

FormulationStudy

StabilityStudy

ClinicalStudy

REGULATORY STRATEGY

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How?

Filing

Container/Closure

Extractables/Leachables

Accelerated

Long Term

Liquid

Lyophilized

FormulationStudy

StabilityStudy

ClinicalStudy

REGULATORY STRATEGY

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How?

Filing

Container/Closure


Accelerated

Long Term

Indication

Administrationroute

Degradation profile

Impurityprofile

Liquid

Lyophilized

FormulationStudy

StabilityStudy

ClinicalStudy

REGULATORY STRATEGY

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How?

Filing

Container/Closure


Accelerated

Long Term

Indication

Administrationroute

Degradation profile

Impurityprofile

Liquid

Lyophilized

Formulation

Container/Closure

StorageConditions

FormulationStudy

StabilityStudy

ClinicalStudy

REGULATORY STRATEGY

ClinicalData

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How?

Attribute* Move From Liquid Vial Move From Lyo VialContainer/Closure Similar? Leverage previous extractable/leachable studies.

Functionality: siliconization may be needed.

Formulation No change. Change from freeze-dried powder to liquid.

Storage Conditions No change.

Stability Study: 3 months comparative accelerated and long term of at least 1 batch (3 may be required).

Clinical Study: If degradation profile or impurities profile change.

May change

Stability Study: 3 months comparative accelerated and long term data on 3 batches.

Clinical Study: If degradation profile or impurities profile change.

Pre-filled syringe filing details:

* Indication and Administration Route changes need clinical data

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WHO?

CMO REQUIREMENTS

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Who?

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Who? Choosing your CMO . . .

Capability

Qualification

Capacity

Experience

CMOof

Choice

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Experience

Experience

Regulatory

Technical

Product type

Regulatory Global and local compliance Audit history Regulatory review and

approval process

Technical Product Scope Seasonal Campaign Market/Industry Presence

Product Type Small Molecules Biologicals

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Capability

Capability

Resources

Physical

Personnel

Resources Part of global company Redundancy Multidisciplinary

Physical Facility Aseptic Formulation Cold Chain Management

Personnel Education Training Experience

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Qualification

Qualification

GMP

Policies

Registration

Good Manufacturing Practices Compliance Documentation Training Audit

Company Policies Business Quality Regulatory Manufacturing

Registration National entities Regulatory Agencies

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Capacity

Capacity

Equipment

Laboratory

“Foot Print”

Equipment Preparation Formulation Fill, Lyophilization, & Cap Packaging

Laboratory Environmental monitor Product specific test Compendial testing

“Foot Print” Multiple lines Aseptic areasWaste treatment Supporting equipment

and processes

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Vial to Pre-filled Syringe:

Why? Value Proposition• Market – differentiation, premium pricing• Customer – safety, accurate dosing, self-administration• Product – less API waste → more units filled

What? Regulatory Strategy• Evaluate and compare syringe system to current presentation• Need supporting clinical data?• Perform stability study

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Vial to Pre-filled Syringe:

How? Vial to Syringe• Container/Closure - extractables/leachables• Formulation – liquid to liquid? Lyo to liquid?• Storage Conditions – stability study, degradation profile• Filing – clinical study? Stability supporting data

Who? CMO requirements• Experience• Capability• Qualification• Capacity

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References

1Moving to a Pre-Filled Syringe: Stability Considerations – A Regulatory Perspective. Raenel Gibson, RAC Regulatory Affairs Manager, Baxter Pharmaceutical Solutions LLC. Presented at the PDA “The Universe of Pre-filled Syringes and Injection Devices”, San Diego, CA, October 6-7, 2008.

2Financial Model For Converting From a Vial To a Pre-filled Syringe. Michael Borlet, Director of Marketing, Baxter Pharmaceutical Solutions LLC. Presented at the PDA “The Universe of Pre-filled Syringes and Injection Devices”, San Diego, CA, October 6-7, 2008.

Copaxone is a registered trademark of Teva Pharmaceutical Industries Ltd.

Baxter is a trademark of Baxter International Inc.

Enbrel is a trademark of Immunex Corporation

PFS is a trademark of Pharmacia & Upjohn Company

SureClick is a trademark of Amgen Inc.

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Shoot for Share: From Vial to Pre-Filled Syringe

• Thank you for participating in this complimentary webinar.

• If you have further questions or would like to contact me:Raul Soikes, Senior Director,

Program ManagementBaxter BioPharma SolutionsPhone 812-355-5247E-mail:

[email protected]

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For information about Baxter BioPharma Solutions, please visit our website at www.baxterbiopharmasolutions.com

mailto:[email protected]�

http://www.baxterbiopharmasolutions.com/�

Documents

WEBINAR – March 26, 2009 Shoot for Share! From …...920752-00 1 SPEAKER: Raul Soikes Senior Director, Program Management Baxter BioPharma Solutions WEBINAR – June 25, 2009 Shoot