View
21
Download
1
Category
Preview:
Citation preview
people.innovate.
Medical Device ProductDevelopment Process
David FarrarHead of New TechnologiesXiros Ltd, Leeds, UK
people.innovate.
“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
people.innovate.
New Product Development
• Doing projects right• Project planning• Project Management• Stage-Gate
• Doing the right projects• Business Cases• Valuation• Portfolio Management
people.innovate.
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
people.innovate.
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
people.innovate.
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.
people.innovate.
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
people.innovate.
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
people.innovate.
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.
people.innovate.
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
people.innovate.
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
people.innovate.
FDA Waterfall DiagramHave wedesigned whatwe intended to?
Does what wehave designedwork?
people.innovate.
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
people.innovate.
ISO10993-1
people.innovate.
people.innovate.
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)?
people.innovate.
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.
people.innovate.
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
people.innovate.
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
people.innovate.
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
people.innovate.
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?
people.innovate.
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?
people.innovate.
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
people.innovate.
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
people.innovate.
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?
people.innovate.
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
people.innovate.
Stage 6: Post Launch
• Surgeon training
• Product/Process improvements
• Complaints
• Post-market surveillance
people.innovate.
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
people.innovate.
Thank you for listening!
Recommended