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