Medical Device Development and Entrepreneurship

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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
  
• Pros
• Speed
• Lower risk
• Cons
• Low barriers to entry
• 510(K) with clinical trials
• PMA Pre Market Approval
• Clinical trials for safety and efficacy of device
• Pros barriers to entry
• Cons 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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Outline of Presentation

• Introduction
• Simulation vs. Testing
• What are the issues?
• Benefits of Synergizing Simulation and Testing
• Illustrations Case Studies
• Conclusions
• Questions??

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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

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Stent Segment and Sub-specimen
Sub-specimen
Stent Segment
Parnell, (2000)
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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
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

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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 gt Af )
• Stress-induced martensite and reverse
• Shape memory (reverting to learned shape)

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NiTi Response to Temperature
Tlt Ms Shape Memory(residual strain recovered
by heating) Ms ltTlt Af Shape Memory(residual
strain recovered by heating) Af ltTltTc
Superelastic (SIM)(full strain recovery) TgtTc
Plasticity before SIM(permanent residual strain)
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Variation of SMA Structures
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Pseudo-elastic behavior of SMA

• Temperature 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
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.
NiTi Stent
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Input data for Mechanical SMA
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Differential Scanning Calorimetry (DSC)

• 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

Shaw Kyriakides, (1995), (courtesy of M.-H. Wu )
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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