PDA: A Global Association

Lowering the Hurdles in Device Selection for Biologics

Andy Pocock – Team Consulting7th November 2012

Drug delivery Surgical devices Critical care Regenerative medicine

Focus on medical devices to meet the needs of patients and healthcare professionals worldwide for over 25 years

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

Who are Team Consulting?

Lowering hurdles?

Don’t get caught out by the wrong device choice…

Understand the challenges

Awareness of the process

What are the requirements

Agenda

1. Some background and drivers to the biologics sector– Market pull & delivery challenges

2. Selection process and key criteria– What to consider during selection

3. Attributes for a successful delivery device for biologics– ‘Ideal’ vs. ‘Essential’ characteristics

1. Device Selection for Biologics

Some background:Market Pull / Delivery Challenges

• 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

Drug DeliveryDevice

PrimaryContainer Drug Patient

The drug delivery device ‘system’

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

Why adopt new drug delivery technology?

• Increasing numbers of biologically derived therapeutics in development

— monoclonal antibodies (mAbs) aimed at the treatment of chronic illnesses – Cancer, RA, MS

• Global biologic sales expected to reach 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

Biologics – Market Pull

*IMS Health 2007 & 2009, Evaluate Pharma, Sandoz analysis 2010

EmergingVs.

Developed?

• Increasing competition within Biologics market requires differentiation by delivery means

— Diversification of device type/design to meet particular user requirements

• Significant market drive toward self-administration

— To contain costs and improve convenience

• Subcutaneous delivery is easily accessible by patient and can accommodate infrequent, regular regimens (e.g. weekly - monthly)

Biologics – Implications for injection devices 1

FDA - Guidance for Industry on Biosimilars•Q.I.4. Can a proposed biosimilar product have a delivery device or container closure system that is different from its reference product?

•“Yes, some design differences in the delivery device or container closure system used with the proposed biosimilar product may be acceptable”

*in-Pharma Technologist.com – February 2012

• Heightened safety demands due to ‘home use’ leading to more sophisticated, simple to use, safer devices

— Single use, disposable (combination)— Needle protection (needle retraction /

shielding)

• Focus on compliance - convenience, usability etc.

• Minimise patient anxiety & pain — Finer needles, concealed needles and/or

automatic insertion— Needle-free devices— Larger volume, slow release ‘wearable’

devices

Biologics – Implications for injection devices 2

Dosing regime

Formulation factors

Administration

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

container and delivery mechanism

Biologics – Implications for injection devices 3

• “The results show that increasing the volume from 0.5 to 1.0 mL increases the pain significantly.”

• “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

Increased technical sophistication

Why the interest in anything more complex than a ‘standard’ prefilled syringe?

Self-Injection Spectrum

More complex user task?

Syringe & vialPre-filled &

dual chamberAuto injectors

& Pen injectorsWearable / electronically

enabled devicesSafety

syringes

2. Device Selection for Biologics

Selection Process & Criteria

Selection as part of a development process?

Assess Options Implement Design

UserNeeds

Design Input

DesignProcess

DesignOutput

MedicalDevice

DesignVerification

Review

DesignValidation

DDS

PRS

TPP

URS

Design Control ProcessUser

Needs

TPP

URS

Review landscape

Receive proposals

Assess evidenceand samples

Review capability

DefineRequirements

Device Selected

Con

tract

Neg

otia

tion

Launch

Broad Commercial & Technical Criteria

Available?Is it the right device at the

right price?

Protectable?Can the device provide sustained competitive

advantage?

Implementable?Can technical,

industrialisation and regulatory issues be

overcome?

Adaptable?Can the device be adapted

to suit delivery requirements?

Acceptable?Will the device be

acceptable? (by patients, HCP’s, payers etc.)

Simpson.I – Team Consulting

Consideration during selection

2. Treatment

1. Medical Condition (patient)

5. Commercial and Operational

8. Regulatory

4. Marketing

6. Human Factors Engineering (HFE)

7. Technical Status

3. Primary Drug Pack

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?

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.

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?

FDA guidanceISO/IEC 62366 (incl. ANSI/AAMI HE74)

ANSI/AAMI HE75:2009

6. Human Factors Engineering (HFE)

• Will the device be safe and effective to use by the intended user groups with a realistic level of training?

•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).

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

3. Device Selection for Biologics

Attributes for a successful delivery device for biologics

Self-Injection Landscape – A Simplified Map

Cart

ridge

RTF

Glas

s or P

lasti

cSy

ringe

& V

ial

POC

fill

Safety Systems

ReusablePen Injectors

ElectromechanicalReusable Injectors

CSII Pumps CSII Patch Pumps

Reusable Autoinjectors

DisposablePen Injectors

ProprietaryPolymer Packs

Needle Free Injectors

ElectromechanicalReusable Injectors

DisposableAutoinjectors

Wearable Large Volume Injectors

Cartridge-BasedCSII Pumps

Oth

er

Needle Free Cartridge

Dual-Chamber Syringe

Wearable Large Volume Injectors

DisposableAutoinjectors

Dual-ChamberPen Injector

Syringe & Vial

Selection – Develop or License?

Develop1.Create own device (‘ground up’ development) based on new or expired IP

Benefits•Secure IP to maintain competitive advantage•No ‘fuss’ tailored development to meet your own specific requirements•Freedom to select the right manufacturing process capabilities

License2.Develop a device with licensed IP for a specific combination of technical feature(s) from a device supplier

3.Licence and customise an existing device core technology to meet particular user / delivery requirements

4.Licence use of an existing device with no changes to device other than branding / colour

Benefits•More predictable / manageable technical risk, cost and timescale•Reduced time to market - partially developed already•Known (sometimes proven) technology with access to manufacturing capability•Early development costs spread across other non-competing sectors•Allows pharma/biotech to retain focus on core competence•Reduced risk of IP infringement

Appealing

An injector people are WILLING to use

An injector people CAN use An injector that can be MANUFACTURED to FUNCTION as intended

Regu

lator

y Comm

ercial

Technical

Creating a positive user experience

The ‘IDEAL’ device for Biologics...

Ensuring robustness and reliability

Safe and intuitive or ‘learnable’ in the hands of the user

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

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!

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

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.

• Ben Turner

• Mark DiCioccio

• Andy Fry

Acknowledgements

Thank you for your attention

Andy PocockHead of Parenteral Drug Delivery

andrew.pocock@team-consulting.comwww.team-consulting.com

PDA: A Global Association

Lowering the Hurdles in Device Selection for Biologics

Andy Pocock – Team Consulting7th November 2012