Team's Andrew Pocock delivered this presentation at the PDA Parenterals 2012 conference in Barcelona on November 7th 2012.

1. Lowering the Hurdles in
PDA: A Global
Device Selection for
Biologics
Association
Andy Pocock – Team Consulting
7th November 2012

2. Who are Team Consulting?
Focus on medical devices to meet the needs of patients and healthcare
professionals worldwide for over 25 years
Drug delivery Surgical devices Critical care Regenerative
medicine
Over 40 parenteral device projects & developments including:
• autoinjectors, injector pens
• needle free devices
• wearable/large volume devices
• safety needles/safety syringes
• vaccine delivery systems
• dual chamber devices

3. Lowering hurdles?
Understand
the challenges
Awareness of
the process
What are the
requirements
Don’t get caught out by the wrong device choice…

4. Agenda
1. Some background and drivers to the biologics sector
– Market pull & delivery challenges
1. Selection process and key criteria
– What to consider during selection
1. Attributes for a successful delivery device for biologics
– ‘Ideal’ vs. ‘Essential’ characteristics

5. 1. Device Selection for Biologics
Some background:
Market Pull / Delivery Challenges

6. The drug delivery device ‘system’
Drug Delivery Primary
Device Container Drug Patient
• The primary container and delivery device are the ‘drug to patient interface’
• This is the key interface in the system, as there is limited control over the patient /
user actions
• The device choice (and design) is the opportunity to get it ‘right’ for the patient
and reduce the occurrence of use-related errors

7. Why adopt new drug delivery technology?
Survey of industry experts, small/medium sized drug companies, drug delivery specialists:
– User compliance – convenience and ease of use may help
– Differentiation – competition for market share driving product positioning via
delivery means (i.e. device type and design)
– Life Cycle Management – using device characteristics to extend product life
Shand.B – University of Cambridge / Simpson.I - Team Consulting.
2007

8. Biologics – Market Pull
• Increasing numbers of biologically derived
therapeutics in development
— monoclonal antibodies (mAbs) aimed at
the treatment of chronic illnesses –
Cancer, RA, MS Emerging
Vs.
• Global biologic sales expected to reach Developed?
US$166 billion by 2015*
— $64 billion from off-patented drugs
• Growth in Biosimilars following patent
expiry of many biologics e.g.
— Herceptin, Roche
— Enbrel, Amgen
— Humira, Abbott
*IMS Health 2007 & 2009, Evaluate Pharma, Sandoz analysis 2010

9. Biologics – Implications for injection devices 1
*in-Pharma Technologist.com –
February 2012
• Increasing competition within Biologics
market requires differentiation by delivery
means
— Diversification of device type/design to
meet particular user requirements
FDA - Guidance for Industry on
• Significant market drive toward self- Biosimilars
administration •Q.I.4. Can a proposed biosimilar product
— To contain costs and improve convenience
have a delivery device or container
closure system that is different from its
• Subcutaneous delivery is easily accessible reference product?
by patient and can accommodate
infrequent, regular regimens (e.g. weekly - •“Yes, some design differences in the
monthly) delivery device or container closure system
used with the proposed biosimilar product
may be acceptable”

10. Biologics – Implications for injection devices 2
• Heightened safety demands due to ‘home Dosing regime
use’ leading to more sophisticated, simple
to use, safer devices
— Single use, disposable (combination)
— Needle protection (needle retraction /
shielding) Formulation factors
• Focus on compliance - convenience,
usability etc.
Administration
• Minimise patient anxiety & pain
— Finer needles, concealed needles and/or
automatic insertion
— Needle-free devices
— Larger volume, slow release ‘wearable’
devices

11. Biologics – Implications for injection devices 3
Higher payloads of active biologic to achieve
the required therapeutic dose, leading to
(potentially):
•Larger volumes (1ml+ )
— Additional challenges of pain associated
with larger injected volumes, rate of
delivery etc.
•Higher viscosities (≈30cP)
— Stretching the ‘power’ budget required
— Challenging the robustness of primary • “The results show that increasing the volume from
0.5 to 1.0 mL increases the pain significantly.”
container and delivery mechanism • “Pain is subjective and highly variable, trending up
even in small volumes”
• “The volume should generally be less than 1.0 mL if
injected into thigh (SC)”
Source: Jorgensen et al, The Annals of
Pharmacotherapy: Vol. 30, No. 7, pp. 729-732, 1996

12. Self-Injection Spectrum
Pre-filled & Safety Auto injectors Wearable / electronically
Syringe & vial dual chamber syringes & Pen injectors enabled devices
More complex user task? Increased technical sophistication
Why the interest in anything more complex than a ‘standard’
prefilled syringe?

13. 2. Device Selection for Biologics
Selection Process & Criteria

14. Selection as part of a development process?
Define Assess Options Implement Design Launch
Requirements
Contract Negotiation
Review landscape
TPP
TPP
Receive proposals
User
Needs Assess evidence Design Control Process
URS
URS and samples
Review capability
TPP
TPP
User
Needs URS
URS Review
Design
PRS
PRS
Input
Device Selected Design
Process
Design
Design
Verification Output DDS
DDS
Design Medical
Validation Device

15. Broad Commercial & Technical Criteria
Implementable?
Implementable?
Can technical,
Can technical,
industrialisation and
industrialisation and
regulatory issues be
regulatory issues be
overcome?
overcome?
Adaptable?
Adaptable?
Available?
Available? Can the device be adapted
Can the device be adapted
Is ititthe right device at the
Is the right device at the to suit delivery
to suit delivery
right price?
right price? requirements?
requirements?
Protectable?
Protectable? Acceptable?
Acceptable?
Can the device provide
Can the device provide Will the device be
Will the device be
sustained competitive
sustained competitive acceptable? (by patients,
acceptable? (by patients,
advantage?
advantage? HCP’s, payers etc.)
HCP’s, payers etc.)
Simpson.I – Team Consulting

16. Consideration during selection
8. Regulatory 1. Medical Condition (patient)
7. Technical Status 2. Treatment
6. Human Factors 3. Primary Drug Pack
Engineering (HFE)
5. Commercial and Operational 4. Marketing

17. Consideration during selection
1. Medical Condition (Patient)
• What do you know about the patient condition that might influence acceptance?
• What is the dexterity and cognitive ability of the target population?
• What is the dose frequency? Single or multi dose / Fixed or variable dose?
• What is the period of treatment i.e. chronic disease vs. short term treatment?
• Who will administer? Self (Home) or HCP (Hospital) administration?
• Are there specific safety requirements that need to be considered e.g. timer
lockouts?
2. Treatment (Drug)
• Will the device cope with the drug/treatment characteristics?
• What is the dose volume?
— An auto-injector is typically <1ml
• What is the drug viscosity?
• Is reconstitution required?
• Is injection time important for the therapy?
• What is the delivery depth?

18. Consideration during selection
3. Primary Packaging
•Which type of primary container will be used? Is it defined?
•Who will undertake filling and final device assembly?
•What are the challenges associated with the primary pack that
might influence device choice? E.g. for a PFS
— Removal force of needle shield
— Dimensional tolerances
— Break loose force and glide force variance
— Accommodation of PFS during auto-injection
— Use of a rigid needle shield or soft needle shield
•Does stability data exists for a primary container?
4. Marketing
• Will the delivery characteristics offer competitive advantage?
How adventurous do you need to be?
— What is expected the patient experience?
— What will be the perceived value of the device - ‘Me too’ or
unique design?
• How will the treatment be offered?
— Multiple devices to meet differing user requirements
— Device platform used for other treatments.

19. Consideration during selection
5. Commercial and Operational
• What type of commercial agreement is preferred ?
— Who owns what IP? What is being for license?
— Who owns the component tools?
— Who will undertake final fill and assembly?
• What are the timelines for clinical trials and product launch?
• What is the launch and scale up strategy?
• What is the cost per device / cost per dose?
6. Human Factors Engineering (HFE)
• Will the device be safe and effective to use by the intended user
FDA guidance
groups with a realistic level of training? ISO/IEC 62366 (incl. ANSI/AAMI HE74)
ANSI/AAMI HE75:2009
•FDA guidance on applying HFE in medical device design should influence
the process of device selection
— Regulatory submissions must show a sensible programme of HFE in identifying
and mitigating risk associated with use error
• Separate exploratory and summative studies will be required for each
medication and associated user group(s).

20. Consideration during selection
7. Technical status
•What stage of development is the technology?
— Prototype?
— Proven for other drug products and partners?
•What evidence of development analysis and testing Is available?
•What is known of the delivery window characterisation – viscosities,
delivery time, volume etc.
•Evidence of formative HF studies / experience with intended patient
groups?
8. Regulatory
•For biosimilars… how close does delivery method need to be to the
reference product?
•How will the device be regulated? A medical device or a combination
product?
•The route for submission will affect the level of complexity and risk

21. 3. Device Selection for Biologics
Attributes for a successful delivery
device for biologics

22. Self-Injection Landscape – A Simplified Map
Syringe & Vial CSII Pumps CSII Patch Pumps
Syringe & Vial
POC fill
Safety Reusable Disposable Electromechanical
Glass or Plastic
Systems Autoinjectors Autoinjectors Reusable Injectors
RTF
Reusable Disposable Electromechanical Wearable Large Cartridge-Based
Pen Injectors Pen Injectors Reusable Injectors Volume Injectors CSII Pumps
Cartridge
Proprietary Dual-Chamber Disposable Wearable Large Needle Free
Polymer Packs Pen Injector Autoinjectors Volume Injectors Injectors
Other
Needle Free Cartridge
Dual-Chamber Syringe

23. Selection – Develop or License?
Develop Benefits
•Secure IP to maintain competitive advantage
1.Create own device (‘ground up’ development)
•No ‘fuss’ tailored development to meet your
based on new or expired IP own specific requirements
•Freedom to select the right manufacturing
process capabilities
License Benefits
2.Develop a device with licensed IP for a specific •More predictable / manageable technical risk,
combination of technical feature(s) from a device cost and timescale
supplier •Reduced time to market - partially developed
already
3.Licence and customise an existing device core •Known (sometimes proven) technology with
technology to meet particular user / delivery access to manufacturing capability
requirements •Early development costs spread across other
non-competing sectors
4.Licence use of an existing device with no •Allows pharma/biotech to retain focus on core
changes to device other than branding / colour competence
•Reduced risk of IP infringement

24. The ‘IDEAL’ device for Biologics...
Creating a positive user
An injector people are WILLING experience
to use
Co
o ry
mm
lat
gu
erc
Re
Appealing
ial
An injector people CAN use An injector that can be MANUFACTURED
to FUNCTION as intended
Safe and intuitive or ‘learnable’ Ensuring robustness and
in the hands of the user Technical reliability

25. Essential Attributes - Functionality
• Invite input from all stakeholders – the functional specification represents
all needs and expectations – there should be no surprises
• Even for an ‘off the shelf’ injector, understand how and why the device
design works and where its limits are
— Stress test functional samples - in labs and in user’s hands. Face up to
likely realities as early as possible
— Model, simulate, test and iterate mathematical and physical models
— Expect convergence within 10% after 3 iterative loops between the
empirical and theoretical
— For multi-feature, multi function components – identify critical
features/dimensions based on in-depth understanding of the design
• Beware - Simulation and functional prototypes provide guidance only
— Production versions represent reality
— Manufacturability and usability must be built in from project start

26. Essential Attributes - Manufacturability
• Begin dialogue early – involve a manufacturing partner at design layout level
and must be shared by ALL
• A sound tolerance allocation methodology enables predictable production
— it must reflect the manufacturing processes involved and their
capabilities
— it must support the high levels of functionality and performance
required
— dialogue between designer and manufacturer should prevent
misunderstandings
• Consider high volume component assembly and feeding constraints early
– Top-tip; If you can assemble it automatically you can do it manually but this
seldom applies vice-versa!

27. Essential Attributes - Usability
• Reduce physical and cognitive ‘delivery task’ burden by eliminating the
negatives:
— Avoid significant use-related risks
— Maximise ease of use
— Minimise delivery pain / anxiety
— i.e. some users want to be in ‘control’, others want ‘distance’
• Reduce the cognitive and emotional treatment ‘self management’
burden
— Add functionality to deal with forgetfulness, incomprehension
and/or fear
— Balance dose size, dose discomfort and dosing frequency

28. Conclusions
• Delivery of biologics represent a significant and growing demand for safe,
effective, patient centred injection devices
• Expectations and challenges for delivery performance is rapidly evolving
• Suppliers are responding with a vast choice of novel and sophisticated
technologies
• A rigorous selection process can help avoid downstream headaches and
significantly enhance the chance of market success
— Consider the device early in the process... even during development of the drug.

29. Acknowledgements
• Ben Turner
Thank you for your attention
• Mark DiCioccio
Andy Pocock
Head of Parenteral Drug Delivery
andrew.pocock@team-consulting.com
• Andy Fry www.team-consulting.com

30. Lowering the Hurdles in
PDA: A Global
Device Selection for
Biologics
Association
Andy Pocock – Team Consulting
7th November 2012