Managing the Marriage: Device Development in a Pharmaceutical Environment


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  • Put into context of PFS 2010 conference…..
  • A number of things are different e.g. Development processes Pharma companies understand drug development People know what to look for, and what is likely to go wrong Very few pharma companies regularly go through the full device development process People are often learning about the process as they do it… … and may move on before the next device development Familiarity is required with a new set of regulatory constraints: Unlike for many products, the development of medical devices is very highly regulated Device designers (including many design consultancies) have often gained their experience outside of medical device development Inventors by their nature aren’t always good at playing by the rules (That’s why there are inventors.) User Issues After being dispensed, most drugs have to deal with the same environmental issues: temperature, time, oxygen, moisture loss, and then differences in patient physiology and genetic makeup… After being dispensed, most devices have to deal with patients… who represent a far more complex and creative environment Production Issues The manufacturing processes involved are totally different
  • WHAT ARE THE REALITIES OF DRUG DELIVERY DEVICE DEVELOPMENT? rigidities of regulatory industry - real challenge associated with late changes uncertainties of drug pipeline - demands flexibility 'right first time' risk focused quality imperative vs. reject drug batches (pre-PAT) - little opportunity to 'reject batches' and 'fix it on version 2' time pressure of the drug income before patent expiry We can summarise this as a pair of paired 'conflicts' … rigidity AND flexibility … right first time AND immense time pressure
  • Device development has many facets. Understand what doesn’t need to be in the plan Early front end development work can sometimes be best done outside of the full development controls Quick, iterative explorative work Generation of simple models that can be easily tested Requirement for rich feedback rather than ‘statistical proof’ The information is needed for ‘understanding the landscape’ and ‘direction setting’, when many variables need to be accommodated Use ‘Rolling Wave’ planning – detail what you need to, when you need to - but outline all key phases and milestones from the outset
  • The DHF typically includes: Design and development plan Design inputs, including product requirement specifications Design reviews Risk management Design output including design specifications Design verification and validation History of design changes (after start of change control)
  • Not everybody does it properly Generally because they don’t do medical device development day in, day out Plan before the project has started, not part way through A good plan allows clear communication of deliverables and responsibilities, in advance! Development plans are a regulatory requirement The final device can not be too much of a compromise or it won’t be competitive… or safe.. So, do need to burn some bridges at some point. Can’t be all things to all men,
  • There are many specifications to think about. Three key sets of documents form part of the development process: User Requirements Specification What the users will get from the product / device Typically validated through clinical trials Product Requirements Specification What the product / device will do (or not) Typically verified through design verification Design Specifications What the product / device is Allows the manufacturer to validate manufacturing processes
  • This is how the specification maps onto the waterfall development process. Specified requirements need to be verified or validated, so consider how you will do this as you create it Don’t specify something that you can’t verify or validate Be clear on who is responsible for verifying which requirements Good specifications (and a good risk management process) should lead to good verification and validation plans. Bad specifications, however ….
  • There are many different kinds of injector devices! So you will need to describe the one that you are developing This is where the specifications come in
  • Consideration of the requirements for two different therapies starts us on the process of working out what it is we need to know… what we need to design to… what are the USER needs
  • What about more detailed, product/technical requirements Some elements of specification can be fixed early. Others can not, so for development to be swift it needs to be flexible and remain as accommodating as possible for as long as possible The final device can not be too much of a compromise or it won’t be competitive… or safe..
  • Users (patients, carers, clinicians) are often overlooked in device development until late in the day Consider the user from the very beginning of the development process when it’s cheaper to get it right in order to identify major risks early on Consider the context of use Drug + User = predictable Device + User = less predictable….. You can just about get away with a change in component colour or an adjustment to the IFU, but significant changes to avoid potential use error are a big deal.
  • The device should fit the user, not the other way around. Interaction design is key, and requires detailed understanding of device function. This analytical thinking helps drive the empirical side – what are the objectives of the studies… what do the protocols need to cover
  • Users (patients, carers, clinicians) are often overlooked in device development until late in the day Consider the user from the very beginning of the development process when it’s cheaper to get it right in order to identify major risks early on Ensure a permanent presence on the development team of a human factors specialist, working closely with the industrial designers and engineers
  • IF you mess up your mobile phone design, you have another coming along in six months time… If you launch a dud device….. COST DIFFERENCES … the immense costs of drug development vs. "under-investment" in drug delivery device development?? The huge cost of product recall……
  • Managing the Marriage: Device Development in a Pharmaceutical Environment

    1. 1. Managing the Marriage: Device Development in a Pharmaceutical Environment Chris Hurlstone, Team Consulting Ltd. 3 rd Pre-filled Syringe Conference London, October 2010 © Team Consulting 2010
    2. 2. Marrying Drugs and Devices - what’s the problem? Pre-Filled Syringes, 2010, slide © Team Consulting 2010 <ul><li>Drug discovery: Dozens of scientists working year after year with the most sophisticated technology imaginable </li></ul><ul><li>Drug manufacture: Trillions of atoms being marshalled into amazingly complex molecules by the most careful, delicate manufacturing processes </li></ul><ul><li>Now all you need to do is just get the stuff into a person. Surely that’s the easy part... Isn’t it? </li></ul>
    3. 3. Drug development vs. Device development – a few clear differences… <ul><li>Development processes </li></ul><ul><li>Regulatory constraints </li></ul><ul><li>Production processes </li></ul><ul><li>User issues </li></ul><ul><li>The Culture! </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010
    4. 4. Drug development & Device development – conflicting requirements Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Can’t go to market with an unsafe product Need to be right first time but… Need to get to market as quickly as possible Drug pipelines can be uncertain Need to be flexible for as long as possible but… Need to work in a rigid regulatory framework For a successful ‘marriage’ these conflicts need to be resolved… … and that requires focus on some key aspects of device development
    5. 5. Paths to a successful marriage…. <ul><li>Plan your joint development </li></ul><ul><li>Understand important requirements </li></ul><ul><li>Consider the individual </li></ul><ul><li>Manage risk throughout </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010
    6. 6. Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Planning… Pilot manufacture / DVT Detailed Design Proof of Principle Industrialisation Opportunity Definition Concept Design <ul><li>User Requirements Specification </li></ul><ul><li>Design / technology research </li></ul><ul><li>Interaction design </li></ul><ul><li>Concept generation and work-shopping </li></ul><ul><li>Visualisation </li></ul><ul><li>Evaluation </li></ul><ul><li>IP investigation </li></ul><ul><li>Design review </li></ul><ul><li>Structured selection </li></ul><ul><li>Product Requirements Specification </li></ul><ul><li>Visualisation </li></ul><ul><li>User Interface </li></ul><ul><li>Instructions </li></ul><ul><li>3D CAD detailing </li></ul><ul><li>Cost analysis </li></ul><ul><li>Design Review </li></ul><ul><li>Engineering Analysis </li></ul><ul><ul><li>FEA </li></ul></ul><ul><ul><li>Tolerance analysis </li></ul></ul><ul><ul><li>DFMA </li></ul></ul><ul><li>Prototyping </li></ul><ul><li>Testing </li></ul><ul><li>User trials </li></ul><ul><li>Software verification </li></ul><ul><li>Beta electronics </li></ul><ul><li>Concept development </li></ul><ul><li>Proof of principle rigs </li></ul><ul><li>Test protocols and planning </li></ul><ul><li>Proof of principle testing </li></ul><ul><li>Top level user studies </li></ul><ul><li>Engineering analysis </li></ul><ul><li>Initial DFMA </li></ul><ul><li>Mathematical modelling </li></ul><ul><li>Simulations </li></ul><ul><li>Alpha electronics </li></ul><ul><li>Software development </li></ul><ul><li>PRS update </li></ul><ul><li>Assessment of user requirements and technical constraints </li></ul><ul><li>Feasibility research </li></ul><ul><li>Performance characterisation </li></ul><ul><li>Life Cycle Management </li></ul><ul><li>Direction setting investigation </li></ul><ul><li>Decision support </li></ul><ul><li>Generation of Market Requirements Specification / Design Brief </li></ul>1 2 3 4 5 Lead concept(s) selected POP testing complete Detailed design complete & frozen for tooling Pilot Design Verification Complete and approved Design & processes signed-off & approved for launch Major Milestones <ul><li>Tooling procurement </li></ul><ul><li>Testing / evaluation </li></ul><ul><li>Component reconciliation </li></ul><ul><li>Tool correction & modification </li></ul><ul><li>Process development </li></ul><ul><li>Assembly & test jigs and fixtures </li></ul><ul><li>DV plans & protocols </li></ul><ul><li>Design verification </li></ul><ul><li>User studies & pre-clinical trials </li></ul><ul><li>QC development & documentation </li></ul><ul><li>Design review </li></ul><ul><li>Production tooling design, build and validation </li></ul><ul><li>Production DVT </li></ul><ul><li>CAD database updates </li></ul><ul><li>Clinical Trials support </li></ul><ul><li>Manufacturing support </li></ul><ul><li>Assembly and test equipment </li></ul><ul><li>Process validation and qualification </li></ul><ul><li>Knowledge & technology transfer </li></ul>Risk management Programme Plan Risk Management Plan Product Risk Assessment System Risk Assessment User Risk Assessment Risk assessment & mitigation iterations Process Risk Assessment Regulatory Design Development Plan, Regulatory Strategy, Essential Requirements, Technical/Design History File, Clinical Input Device Development Documentation 0
    7. 7. Planning is NOT just about Gantt charts <ul><li>Design and Development Plan </li></ul><ul><li>Risk Management Plan </li></ul><ul><li>Human Factors Engineering Plan </li></ul><ul><li>Design Verification Plan </li></ul><ul><li>Validation Plan </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010 <ul><li>As a checklist: </li></ul><ul><ul><li>Study FDA 21 CFR 820.30 and ISO 13485:2003 </li></ul></ul><ul><ul><li>Think about your DHF & Technical File content </li></ul></ul>
    8. 8. Planning: everybody has their favourite do’s and don’ts Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Combining drug and device development plans efficiently will require flexibility, contingency and some work at risk. Only burn bridges when you have to!
    9. 9. Understanding Requirements – Device Specifications Pre-Filled Syringes, 2010, slide © Team Consulting 2010 URS PRS Design Specs
    10. 10. Specifications - The waterfall diagram Pre-Filled Syringes, 2010, slide © Team Consulting 2010 We need to think in particular about how key requirements can differ for similar devices User Needs Design Input Design Process Design Output Medical Device Design Verification Design Validation Review URS PRS Design Specs
    11. 11. Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Cartridge-based Injectors (multi or single dose) Pre-filled Syringe-based Injectors (single dose, not multi-dose) Reloadable (Reusable) Disposable Flexpen (NN) Preotact (Ypsomed) Autopen (OM) NovoPen 4 (NN) EasyPOD (Merck Serono) SymlinPen (Ypsomed) RediPen (BD) DUAL CHAMBER CARTRIDGE PEN (for lyophilised drugs) Penlet (Haselmeier) (not on market) SimpleJect (OM) SureClick (SHL) Humira pen (OM) Epipen (Meridian ) Humalog Pen (EL) EpiCard (Intelliject) Autoject II (OM) Snapdragon (OM) Leva (B&O) BD auto-injector
    12. 12. Specifications – drugs and devices…. Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Growth hormone Migraine Reusable Disposable Single dose Multi dose IM SC Regular Unpredictable / emergency Frequent Infrequent Self injection Third party injection Home Portable Fixed dose Variable dose Manual needle insertion Auto needle insertion Manual delivery Auto delivery
    13. 13. Specifications – key technology elements Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Some elements of device technology are strongly influenced by drug properties (e.g. stability, viscosity), so can only be confirmed when the formulation is fixed Needle Sterility Dose Control Depth Control Power Source Safety Interlocks Trigger Mechanisms Delivery Indication Needle Safety Reset Mechanisms Primary Drug Packaging Others are primarily driven by the needs of the user . You probably know who they are... but do you know what they will do ?!
    14. 14. The User… Pre-Filled Syringes, 2010, slide © Team Consulting 2010 … is a primary source of risk … is unpredictable … needs worrying about from Day 1. Usability is very hard to change at the last minute!
    15. 15. Combine analytical and empirical approaches Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Empirical Analytical
    16. 16. Human Factors Engineering to HE75 Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Full Spectrum of User Research Human Factors Engineering on device developments Opportunity Definition Phase Uncover Unexpressed User Needs Ethnographic Research Market Research Core Empirical Method Core Analytical Method Main image from AAMI HE75:2009
    17. 17. HFE: making what is safe, not what is ‘nice’ Pre-Filled Syringes, 2010, slide © Team Consulting 2010 For medical devices, being right first time is an imperative
    18. 18. Manage Risk Throughout <ul><li>Risk Management is like gravity. </li></ul><ul><li>Not just a good idea - it’s the law. </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Flowchart from ISO 14971:2009
    19. 19. The Risk Management Plan <ul><li>Defines responsibilities for risk management </li></ul><ul><li>Defines the scope </li></ul><ul><li>Defines risk assessment and mitigation tools and processes </li></ul><ul><li>Defines the severity of generic hazards, and other risk rating guidelines </li></ul><ul><li>Ensures the risk assessment process is sufficiently independent of the design process </li></ul><ul><li>Conforms to ISO 14971:2009 </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010
    20. 20. Manage Risk Throughout <ul><li>Risk Management for devices needs to consider a range of perspectives </li></ul><ul><ul><li>The ‘ User ’ or ‘ Application ’ </li></ul></ul><ul><ul><li>The ‘ Product ’ or Design ’ </li></ul></ul><ul><ul><li>The Manufacturing Process & Supply Chain </li></ul></ul><ul><li>Different techniques are appropriate at different stages, including </li></ul><ul><ul><li>Hazard Analysis </li></ul></ul><ul><ul><li>Fault Tree Analysis </li></ul></ul><ul><ul><li>FMEA/FMECA </li></ul></ul><ul><li>Risk mitigation is a critical part of design verification and validation, but should be starting much sooner </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010
    21. 21. In summary <ul><li>The right plan </li></ul><ul><li>The right specifications </li></ul><ul><li>User focus </li></ul><ul><li>Managed risk </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010 Flexibility in a rigid environment Managing cultural differences Minimising compromise The right first time imperative For a well managed marriage… and hopefully a happy one!
    22. 22. <ul><li>For further information, please contact </li></ul><ul><li>Chris Hurlstone </li></ul><ul><li>Tel: +44 (0)1799 532 741 </li></ul><ul><li>Email: [email_address] </li></ul>Pre-Filled Syringes, 2010, slide © Team Consulting 2010