Lowering the Hurdles in Device Selection for Biologics
Lowering the Hurdles inPDA: A GlobalDevice Selection forBiologicsAssociationAndy Pocock – Team Consulting7th November 2012
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 medicineOver 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
Lowering hurdles? Understandthe challengesAwareness of the processWhat are therequirements Don’t get caught out by the wrong device choice…
Agenda1. Some background and drivers to the biologics sector – Market pull & delivery challenges1. Selection process and key criteria – What to consider during selection1. Attributes for a successful delivery device for biologics – ‘Ideal’ vs. ‘Essential’ characteristics
1. Device Selection for Biologics Some background: Market Pull / Delivery Challenges
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
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
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
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”
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
Biologics – Implications for injection devices 3Higher payloads of active biologic to achievethe 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
Self-Injection Spectrum Pre-filled & Safety Auto injectors Wearable / electronicallySyringe & 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?
2. Device Selection for Biologics Selection Process & Criteria
Selection as part of a development process? Define Assess Options Implement Design LaunchRequirements 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
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 adaptedIs 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
Consideration during selection 8. Regulatory 1. Medical Condition (patient) 7. Technical Status 2. Treatment6. Human Factors 3. Primary Drug PackEngineering (HFE) 5. Commercial and Operational 4. Marketing
Consideration during selection1. 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 selection3. 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 thatmight 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 selection5. 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 influencethe 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 selection7. 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 patientgroups?8. Regulatory•For biosimilars… how close does delivery method need to be to thereference product?•How will the device be regulated? A medical device or a combinationproduct?•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 Syringe & Vial CSII Pumps CSII Patch PumpsSyringe & Vial POC fill Safety Reusable Disposable ElectromechanicalGlass 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
Selection – Develop or License?Develop Benefits •Secure IP to maintain competitive advantage1.Create own device (‘ground up’ development) •No ‘fuss’ tailored development to meet yourbased on new or expired IP own specific requirements •Freedom to select the right manufacturing process capabilitiesLicense Benefits2.Develop a device with licensed IP for a specific •More predictable / manageable technical risk,combination of technical feature(s) from a device cost and timescalesupplier •Reduced time to market - partially developed already3.Licence and customise an existing device core •Known (sometimes proven) technology withtechnology to meet particular user / delivery access to manufacturing capabilityrequirements •Early development costs spread across other non-competing sectors4.Licence use of an existing device with no •Allows pharma/biotech to retain focus on corechanges to device other than branding / colour competence •Reduced risk of IP infringement
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 intendedSafe and intuitive or ‘learnable’ Ensuring robustness and in the hands of the user Technical reliability
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.
Acknowledgements• Ben Turner Thank you for your attention• Mark DiCioccio Andy Pocock Head of Parenteral Drug Delivery firstname.lastname@example.org• Andy Fry www.team-consulting.com
Lowering the Hurdles inPDA: A GlobalDevice Selection forBiologicsAssociationAndy Pocock – Team Consulting7th November 2012