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Medical Device ProductDevelopment Process
David FarrarHead of New TechnologiesXiros Ltd, Leeds, UK
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“Nothing is accomplished in thereal world unless it is adopted byindustry.Academic scientists do notmanufacture devices.A paper in Science cannot savelives.How to repay the taxpayerssupporting academic research?”
Buddy RatnerBiomaterials Scientist & Entrepreneur
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New Product Development
• Doing projects right• Project planning• Project Management• Stage-Gate
• Doing the right projects• Business Cases• Valuation• Portfolio Management
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Development Process – Stage-Gate
Stage 1Initiation/ Feasibility
Stage 2Concept/ Definition
Stage 3Design & Development
Verification & Validation
Stage 4Transfer tomanufacturing
Stage 5Regulatory
Launch
Gate1
Gate2
Gate3
Gate4
Gate5
Design Control/Design History File Technical FileBusiness Case
• Development process broken into key phases• Project reviewed by management team at end of each phase – Gate Review• Project must successfully pass through Gate before it can proceed to next
phase• Stops projects running out of control• Focuses team on what information/results are required
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Development ProcessStage Description/Activities
0: Idea creation/gathering • Brainstorming• Internal R&D• Technology scouting
• Literature review• Companies/Universities
1: Initiation/Feasibility • Initial proposal & business case • Initial proof-of-concept andprototypes
2: Concept/Definition • Full business case & project plan• Research Customer Requirements• Market evaluation• IP Review
• Initial regulatory plan• Manufacturing plan• Further develop/test prototypes
3: Design & Development • Define design inputs• Verification & Validation Plan• Further testing/development• Risk assessment• Develop/review manufacturing
process
• Develop/test final prototype• Design packaging/labelling• Update market, IP, regulatory
reviews etc.
4: Transfer to Manufacturing • Establish and validate process• Approve suppliers
• Document procedure• Train operators
5: Regulatory • Prepare Technical File• Regulatory submission
• Obtain regulatory approval
6: Post Launch • Surgeon training• Product/Process improvements
• Complaints• Post-market surveillance
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Stage 0: Where do ideas come from?
• Market pull– Identify an unmet clinical need and then find
technologies to address it• Technology Push
– Invent a new material, technology and thenidentify clinical needs it might satisfy
• Clinical Needs – literature, talking to surgeons,market research, observing surgery, clinicalconferences, feedback from sales reps etc.
• New Technologies – literature, brainstorming,internal R&D, technology scouting, approachesfrom universities/companies etc.
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Stages 1/2: Making the Case…
•Most companies will develop a “Business Case” beforeinvesting significantly in a new project.
– Justifies the resources/funding needed to bring a new product tomarket.
– Enables projects to be prioritised
• Portfolio Management
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Typical Business Case Content(or what you need to think about before you start tocommercialise a medical device)
•Product attributes/technicalspecification
•Value proposition
•Strategic fit
•Market (size, growth, penetration)
•Sales channels
•Competition
•Intellectual Property position(patent protection, freedom tosell)
•Development plan/costs
•Manufacturing plan & costs
•Regulatory route
•Clinical trials
•Reimbursement
•Health economic analysis
•Risk analysis
•Value/financials
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Value Proposition Case Study: HIPResurfacing System
•For the young, active patient withadvanced hip disease, hipresurfacing can be an alternatetreatment to total hipreplacement. The procedure oftenpermits a return to normal lifeactivities and more bone stock ispreserved than with a total hipreplacement.
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Patient Journey – Treatment for Osteoarthritis
Patient lifetime
Lifestyle changes/nutraceuticals
Qu
alit
yo
flif
e
Pharmaceuticals
IA-steroids
IA-hyaluronicacid
Total jointreplacement
Revision jointreplacement
Seve
rity
oft
he
dis
ease
Pain relief
Replacement
GAP
Resurfacing
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Stage 3: Developing and Testing
• Establish customer needs and define design inputs• Develop device to meet design input requirements• Test and record outputs of design.• “Verification and Validation”• Development process recorded in Design History File
• Need to demonstrate safety and efficacy – supporting dataneeded for any marketing claims
• Time and cost of this stage often dominated by in vivo andclinical testing
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FDA Waterfall DiagramHave wedesigned whatwe intended to?
Does what wehave designedwork?
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Case Study: Biological Safety Testing
• ISO10993– provides a framework for biological safety testing
– 20 parts covering characterisation, in-vitro and in-vivo testing
– Part of a wider risk management process
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ISO10993-1
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Case Study: Suture Anchor - Safety
• Suture anchor for repair ofthe rotator cuff (shoulder)
• Available in PEEK or in anovel bioresorbablecomposite material
• For purposes of ISO10993:– what category is the
device?– what is the contact
type?– What biological safety
testing is required(PEEK andbiocomposite)?
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Case Study: Suture Anchor - Efficacy
• What might we want to claim?
• Strength – Insertion and Pullout
• Bone Ingrowth
• Bioresorption and replacementby bone
Need to consider choice, relevance andjustificationof animal model as well as any mechanical/in-vitro testing.
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Clinical Trials• Likely to be needed for any
new/innovative product.
• Can be the most costly part ofthe development process.
• Need to consider:
– Acceptance of outcomemeasures
– Variability of patientpopulation
– Follow-up time needed
– Sample size
– Cost
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Stages of Clinical DevelopmentPhase I
Checkingfor safety
Phase II
Checkingfor efficacy
Phase III
Confirmationin large patient
population
Phase IV
Testing longterm safety in
diverse patientpopulation
Sample: 10-20healthyvolunteers
Risk:Unexpected sideeffects
Sample: about200 patients
Risk: Manyprojects fail inPhase II due toproduct notbeing aseffective asexpected
Sample: morethan 1,000people
Risk: Chance ofdetecting rareside effectsincreases withnumber ofpeople involved
Sample: real lifepatients – post-marketingstudies
Risk: Previouslyuntested groupsmay showadversereactions
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Case Study: Angiogenic Suture
• Suture for rotator cuff tears.• Contains small molecule active to stimulate repair.• Drug-device combination.
• Regulatory bodies required a clinical trial.• Primary objective to obtain safety data on the active
suture and the assess preliminary effectiveness of activesuture vs. control in patients undergoing rotator cuffrepair.
• 80 patients.• Primary outcome: rotator cuff integrity 6 months post-op.• Secondary outcomes include: RC integrity at 1, 3, 6, 12 &
52 weeks, change in cuff/shoulder assessments,rehabilitation time etc
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Case Study – Anti-microbial hip implant
• Infection rates 1-2%• Low incidence but devastating when it
happens• Incorporate antibiotics/antimicrobial surface• Potential “combination” product (drug-
device)• How many patients do you need in your
clinical trial to show a reduction?
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Case Study – Advanced In-GrowthSurfaces
• Improved in-growth surfaces to improvecementless fixation of implants
• Advanced porous surfaces• Active Surfaces e.g. BMP, bisphosphonate
– “Combination”• How long/how many patients for clinical
trial?
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Project Costs
Discovery Preclinicalstudies
Clinicaltrials
Proof-of-concept
Productdevelopment
ProjectCosts
ProjectRisks
Research- Personnel- Facilities- Materials- IP fees
Manufacturing- CAPEX- Tooling- Materials- Packaging
Commercialization- Distribution- Launch costs- Training / education- Sales commissions
Development- Prototype mftr- Preclinicals- Clinical studies- Regulatory fees
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Stage 4: Getting ready tomanufacture
• Design for manufacturing should start early inthe process – how will the product be made?
• Process needs to be robust, efficient and costeffective
• Establish and validate process, includingsuppliers
• Document procedures and train operators
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State 5:Regulatory Approval• Probably the biggest driver in determining
development route
• US FDA – 510(k) vs. PMA
• Europe – CE mark
• Focus on Safety, Efficacy and Quality
• Is the product safe? Do benefits outweighrisks?
• Does the product do what it claims?
• Are adequate manufacturing controls inplace?
• What testing is required?
• Are clinical trials necessary?
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2017 18 19 20 21 22 23 2024
Project C
Project B
Project A
Project TimelinesDiscovery Proof of
conceptLabtesting
Prototypedevelopment
Preclinicalevaluation
Clinicaltrials
Regulatoryapproval
Launch
Examples
Project C• Technically challenging, new product concept• Requires preclinical evaluation and clinical trials• Long regulatory route (class 3 - PMA)
Project B• Next generation product development• Demonstrate safety / efficacy in preclinical studies• Short regulatory route (class 2 - 510k)
Project A• Instrument modification• Demonstrate fit for purpose• Minimal regulatory requirements (class 1)
• Project timelines vary widely• Not all steps necessary in each case• Determined by regulatory pathways
(can be complex and uncertain!)• Consider requirements to show safety & efficacy
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Stage 6: Post Launch
• Surgeon training
• Product/Process improvements
• Complaints
• Post-market surveillance
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Challenges in product development
Appropriateregulatory body
Lack of clinicallyrelevant animalmodels
Ideascreening
Preclinicaltesting
Clinicaltrials
Regulatoryapproval
High cost
Largesample size
Acceptanceof outcomemeasures
Provingsafety
Country specificrequirements
Lengthy follow-up
High failurerate
Variability inpatient population
CrowdedIP space
…or how things get lost in translation
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Thank you for listening!