medical device development and entrepreneurship presented by: t. kim parnell, ph.d., p.e. the pec...
TRANSCRIPT
Medical Device Development and Entrepreneurship
Presented by:
T. Kim Parnell, Ph.D., P.E.The PEC Group
www.parnell-eng.com
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Introduction
• Overview
• Medical Device Development
• Device Startups
• Consulting
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Medical Device Applications
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Some Device Fields…
• Cardiovascular
• Orthopaedic
• Sleep disturbances
• Vascular closure
• Cosmetic
• Etc.
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AAA DevicesAbdominal Aortic Aneurysm
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AAA Device
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Coronary Artery Disease
• Stents are used as scaffolds to hold open the artery
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Finite Element Analysis (FEA)
• Design
• Life prediction
• FDA requirements
• Can shorten the design cycle
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FEA & Testing
• Finite element analysis (FEA) and physical testing are complementary
• A comprehensive program needs to include both components
• With judicious experimental validation, FEA can be used to reduce the amount of physical testing that is needed and shorten the design cycle
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The Challenge for Medical Device Development
• Reduce development time
• Increase confidence of success
• Avoid surprises and delays
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Prototype Development• Physical prototype
Cost and lead time is often a limitation Essential for animal testing and
determining needed characteristics Want to reduce the number of design iterations
that are prototyped
• Virtual prototype Assess more design options Compare alternatives
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Testing Is Essential for:
• Detailed characterization of the material; Getting data needed for the analysis
• Fatigue testing taking into account surface finish, processing steps
• Validation
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Nitinol Stent FEA
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Stent FEA
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Stent FEA
• Rolldown Expansion
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Stent FEA
• Rolldown Expansion
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Creative Strategies in Medical Devices510(K) vs PMA?
• 510(K) Concept of equivalence May 28,1976 Medical Devices Amendments to the FDA Pro’s
• Speed• Lower risk
Con’s • Low barriers to entry• 510(K) with clinical trials
• PMA – Pre Market Approval Clinical trials for safety and efficacy of device Pro’s – barriers to entry Con’s – time, expense and risk
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Medical Device Development
• Needs Assessment • Research • Intellectual property • Biomedical ethics • Brainstorming • Assessing Clinical and Market Potential • Developing patent strategies • Prototyping
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Value of Execution
• Ref: Rich Ferrari
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Consulting Implications
• Reduced fees for equity? Incentive Upside potential
• Need some assessment of the company Capitalization Burn rate
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Resources
Startups & Business
• SVEBP www.siliconvalleypace.com
• Stanford BUS16 continuingstudies.stanford.edu
• TVC www.techventures.org
• TEN www.tensv.org
• Girvan Institute www.girvan.org
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Resources (cont)
Medical Device• Stanford Biodesign innovation.stanford.edu
• BioDesign Network mdn.stanford.edu
• NanoBioConvergence www.nanobioconvergence.org
• DeviceLink www.devicelink.com/mddi
• TCT www.tctmd.com
• Vulnerable Plaque www.vp.org
• Vascular News www.CXvascular.com
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Summary
• Many opportunities in medical devices Entrepreneurs Consultants
• Increasingly multi-disciplinary
• Technology can be applied to advantage
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Carotid Stent
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• Introduction Simulation vs. Testing What are the issues?
• Benefits of Synergizing Simulation and Testing
• Illustrations & Case Studies• Conclusions• Questions??
Outline of Presentation
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Sensitivity by Analysis
• Material
• Tolerance
• Variability of the body/target environment
• Atypical applications
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Validation of Model by Test
• Analysis of tensile test to confirm ability to predict material behavior
• Validation tests for stents might include: Flat plate loading Radial expansion Radial compression
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Example:
Flat Plate Loading Using Contact
Note: This “pinching” loading mode is distinct from “radial” loading
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Are the Assumptions Satisfied?
• Make adjustments/corrections as needed so that the model is predictive of the test
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Additional Information and Insight From Analysis
• Get information not available from device testing alone
• Internal conditions: stress levels, degree of plasticity, residual stress, transformation fraction
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Balloon Expandable Stent
• Basic steps: Roll-down for catheter insertion Inflation and Deployment Cyclic pulsation loading
• Fatigue testing of full device to FDA required 400M cycles is a long process
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Fatigue and Life Testing
• Long test times for full device
• Reduce testing of multiple design iterations
• Get insight more quickly
• Need both analysis and testing
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Cyclic Testing of Sub-specimen
• Before fatigue testing full device, get more information in less time with sub-specimen Higher loading frequency, reduced test time Cycle to failure for a range of loads Develop part-specific S/N data
• Extend with analysis, develop and interpret test conditions in terms of stress & strain
• Make predictions for full device
Stent Segment
Sub-specimen
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Stent Segment and Sub-specimen
Parnell, (2000)
Stent Segment Sub-specimen
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Material Testing: Elastic/Plastic
• Need more detail than basic data from manufacturer (for example, Min. Yield, Ultimate, Elongation)
• Elongation is sensitive to the gage length tested
• Reduction of area very useful, particularly for highly ductile materials
• Need full stress/strain curve with additional data like reduction of area
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Tensile Response of Elastic/Plastic Material
E’
E
D
CB
A
0
Proportional limit
Yield stress
Ultimate stress
Linear Plastic Strain hardening
Significant necking
True Stress
Eng. Stress
Anderson (2002), Biomaterials
Typical stress/strain curve for steels. Strains become localized when necking occurs. Standard elongation highly dependent on gage length. Measured area reduction gives correct local strain.
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Shape Memory Material (SMA) Applications
• Unique characteristics
• Large recoverable strain range
• Super elastic vs. Shape Memory (thermally activated)
• Self-expanding devices
• Conditions after partial unloading
• Load predictions
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Applications for Shape Memory Alloys • Materials that return to some shape upon
appropriate temperature change• Applications:
Medical
IndustrialApplications
Home Appliance
Accessories clothing
Sports
Communi-cation
ShapeMemory
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Shape Memory Material Properties
• DSC to determine transformation temperatures
• Tensile test
• Behavior as function of temperature
• Super elastic material behavior General features (T > Af )
Stress-induced martensite and reverse
• Shape memory (reverting to learned shape)
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NiTi Response to Temperature
T< Ms Shape Memory(residual strain recovered by heating)
Ms <T< Af Shape Memory(residual strain recovered by heating)
Af <T<Tc Superelastic (SIM)(full strain recovery)
T>Tc Plasticity before SIM(permanent residual strain)
As [K] Af [K] Ms [K] Mf [K]
188 221 190 128
Transformation Temperatures
Miyazaki, et.al., (1981)
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Variation of SMA Structures
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Pseudo-elastic behavior of SMATemperature induced phase transformation
Pseudo-elastic Stress-Strain Behavior
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Material Testing: Shape Memory Alloy
• Transformation temperatures (DSC or other)
• Stress/strain tensile curve with unloading
• Application may require tensile data at additional temperatures
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Temperature Dependent Material Behavior of Shape Memory Alloys
NiTi Stent
Nickel-Titanium alloys show temperature dependent material behavior. Shape memory effect (that deformed specimens, regained their original shape after a loading cycle) is observed at a certain temperature.
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Input:ASS AS
f SAS SA
f ,ASs
L To Cm Cs
ASf
SAf
,ASs
ASS
SAS
L
To
Cm
Cs
ASS
ASf
SAS
SAf
Input data for Mechanical SMA
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Differential Scanning Calorimetry (DSC)
Shaw & Kyriakides, (1995), (courtesy of M.-H. Wu )
•DSC can be used to determine transformation temperatures of shape memory materials
•Heating curve: As,Af
•Cooling curve: Ms,Mf
•Austenite is Cubic (BCC)
•Martensite is Monoclinic
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Shape Memory Effect (SME)
Shape memory effect is a consequence of a crystallographically reversible solid-solid phase transformation occurring in particular metal alloys (Ni – Ti, Cu based alloys).
This transition occurs between a crystallographically more-ordered phase (called austenite) and a crystallographically less-ordered phase (martensite).
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Stability for Martensite and Austenite Phases
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Vulnerable Plaque
• Morphology
• Tissue characteristics
• Tissue properties and geometry become important in evaluating device
Christensen, (2002)
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Inverse Analysis Problem
• Correlate material properties to measured behavior
• Use to estimate ranges of properties for tissue
• Example: estimation of vessel wall cyclic strains from cine PC-MRI data (Draney, et.al., 2002)
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Conclusions• Testing and analysis are complementary; Both are
essential• Use together for maximum benefit
Reduce number of physical prototypes Shorten development cycle Avoid surprises and delays
• Applicable in all fields: Electrical Mechanical Biomedical
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Overview• Biomedical industry
Overview Types of biotechnology innovations
• Biomedical Devices Synergy of Mechanical Engineering and Biomedical Technology Examples
• Entrepreneurship in Biomedical Industry Growth Trends in Healthcare and BioMedical Technology Business models for biotech start-ups Rise of outsourcing
• Why Lack of financial resources
• The good and bad Concerns regarding the FDA regulation
• Opportunities for Technology Consultants