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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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Why? - Mid-Term Strategy
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
Why? - Mid-Term Strategy
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
US Drug Delivery - Frost & Sullivan 2008
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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
Rank 1 Rank 2 Rank 3 Rank 4 Rank 5
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%)
US Drug Delivery - Frost & Sullivan 2008
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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
Rank 1 Rank 2 Rank 3 Rank 4 Rank 5
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.)
US Drug Delivery - Frost & Sullivan 2008
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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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What?Define Regulatory Strategy
Evaluate & compare the proposed syringe system to approved materialsProtects the drug
product?Introduce a new
material?Need drug product
formulation changes?
Regulatory considerations – Major change to regulatory market approval . . . Manageable
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What?Define Regulatory Strategy
Evaluate & compare the proposed syringe system to approved materials
Need supporting clinical data?
Protects the drug product?Introduce a new
material?Need drug product
formulation changes?
Safety or efficacy effect?New indication?New route of
administration?
Regulatory considerations – Major change to regulatory market approval . . . Manageable
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What?Define Regulatory Strategy
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
material?Need drug product
formulation changes?
Safety or efficacy effect?New indication?New route of
administration?
Define stability requirementsExecute stability
protocolAnalyze stability
data
Regulatory considerations – Major change to regulatory market approval . . . Manageable
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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
Extractables/Leachables
Accelerated
Long Term
Indication
Administrationroute
Degradation profile
Impurityprofile
Liquid
Lyophilized
FormulationStudy
StabilityStudy
ClinicalStudy
REGULATORY STRATEGY
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How?
Filing
Container/Closure
Extractables/Leachables
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:
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For information about Baxter BioPharma Solutions, please visit our website at www.baxterbiopharmasolutions.com