Enabling Faster, Better Medical Device Development and Evaluation with Modeling and Simulation Tina Morrison PhD

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Enabling Faster, Better Medical

Device Development and Evaluation

with Modeling and Simulation

Tina Morrison PhD

Office of Device Evaluation

Center for Devices and Radiological Health U.S. Food and Drug Administration

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Overview

•

CDRH’s Role in Public Health

•

Advancing Regulatory Science with Modeling and

Simulation

•

Moving Forward:

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What we do …

CDRH is responsible for regulating firms who manufacture,

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CDRH Mission

“The mission of the Center for Devices and

Radiological Health (CDRH) is to

protect and

promote the public health

. …We facilitate

medical device innovation by advancing

regulatory science

, providing industry with

predictable, consistent, transparent, and

efficient regulatory pathways, and

assuring

consumer confidence in devices marketed in

the U.S.

”

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Safety and Effectiveness

• There is reasonable assurance that a device is safe when it can be determined, based upon valid scientific evidence, that the probable benefits to health from use of the device for its

intended uses and conditions of use, when accompanied by

adequate directions and warnings against unsafe use, outweigh any probable risks

• There is reasonable assurance that a device is effective when it can be determined, based upon valid scientific evidence, that in a significant portion of the target population, the use of the

device for its intended uses and conditions of use, when

accompanied by adequate directions for use and warnings against unsafe use, will provide clinically significant results.”

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Medical Device Evaluation

•

Comprehensive evaluation of a marketing application for a

therapeutic medical device typically includes

valid

scientific evidence

from

four types of models

: animal,

bench, computational, and human.

•

Each model has its strengths and

limitations for predicting clinical

outcomes.

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Models and Their Advantages

*Computer modeling in medical devices, as compared to other industries, is nascent and is the one model with the most potential for refinement/improvement because the others are fairly mature.

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Medical Device Evaluation

•

CDRH believes that, when appropriate, the most

balanced evaluation strategy includes scientific evidence

from all four models.

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Medical Device Development

with Modeling and Simulation

The Total Product Life Cycle

VIRTUAL PROTOTYPING DESIGN OPTIMIZATION DESIGN IDEATION PREDICT FAILURES? PREDICT SUCCESS? ROOT CAUSE REDESIGNS

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Current Uses of Modeling in

Medical Device Applications

Computational Solid Mechanics

Stents / Heart Valve Frames / Occluders / Vena Cava Filters / Annuloplasty Rings / Dental Implants / Spine & Joint Implants / Bone Plates & Screws / Surgical Tools

 _{Determine the implant size in a device family that is expected}

to perform the worst under simulated in vivo conditions

o Reduces the amount of physical testing

o Calculate Safety Factors for static and cyclic loads  _{Evaluate the effect of manufacturing tolerances}  Predicate Comparison

 _{Demonstrate a modification (e.g., dimensional) is minor and}

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Current Uses of Modeling in

Computational Fluid Dynamics

Ventricular Assist Devices / Total Artificial Heart / Blood pumps / Heart Valves / Endovascular Grafts / Drug Eluting Devices

 Characterize the flow field by identifying regions of high shear

stress, wall shear stress, or areas of low flow or flow stagnation

o especially in regions that cannot be visualized on the bench

 _{Determine blood damage, thrombosis potential, and drug}

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Current Uses of Modeling in

Computational Electromagnetism

Passive and Active Cardiology Implants / Peripheral Implants / Joint and

Spinal Implants / Deep Brain Stimulators / MR-guided Interventional Devices  _{Simulate the radiofrequency energy absorbed by patients}

undergoing magnetic resonance imaging (MRI)

o Especially worst-case conditions that cannot be replicated in an

animal model and cannot be tested ethically in humans

 _{Radiofrequency-induced currents and heating of (external)}

devices for electrophysiological recordings

 Simulate the electric/magnetic field generated by a device

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Current Uses of Modeling in

Physiological Closed-Loop Controllers & Algorithms

Anesthesiology Devices / Artificial Pancreas / Neurodiagnostic Tools  Use the simulation as an alternative validation method to

demonstrate device performance and robustness

 In silico _{simulation model (control algorithm) of diabetes}

replaces in vivo animal testing for evaluating artificial pancreas

 _{Signal modeling (EEG source localizing software) for brain}

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Current Uses of Modeling in

Computational Thermal Mapping

Ablation Devices

 Determine the thermal field distributions generated by tissue

ablation devices (e.g., High Intensity Ultrasound, radiofrequency)

 _{Assess potential damage to surrounding tissue, organs and}

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• Reports typically (might) lack sufficient details for adequate assessment

• Analyses lack

 _{sensitivity and uncertainty analyses for crucial input} parameters

 adequate validation to support the use of the modeling and simulation

 _{elicitation of the consequence of the computational}

model being incorrect

•

In biomechanics, lack of complete understanding of

the physiological loads, relevant device-tissue

interactions, and variations in patient populations

Some

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Moving Forward:

Modeling and Simulation at CDRH

•

Initiatives

•

Research

•

Partnerships

•

Guidance

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 _{sensitivity and uncertainty analyses for crucial input}

parameters

 adequate validation to support the use of the modeling and

simulation

•

In biomechanics, lack of complete understanding of

Some

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FDA Guidance

1. Reporting Computational Modeling Studies in Medical Device Regulatory Submissions (DRAFT)

 Main body discusses the purpose of computational

modeling and simulation in regulatory submissions

 _{Main body presents recommendations for reporting}

different elements of the computational modeling study

 There are six subject matter appendices

o Fluid & Mass Transport, Solid Mechanics, Electromagnetism,

Control Loops, Thermal Transport, and Ultrasound

 DRAFT guidance is expected to be available for public

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 _{sensitivity and uncertainty analyses for crucial input} parameters

 adequate validation to support the use of the modeling and simulation

•

In biomechanics, lack of complete understanding of

Some

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Partnerships – ASME V&V 40

•

Subcommittee of ASME V&V Committee

 _{More information in Track 11 (11-4) from 4:00-6:00 PM}

• Charter: Provide procedures to standardize verification and validation (V&V) for computational modeling of medical devices

• Developing a general methodology for industry and

academia for creating a V&V plan and to assess credibility of computational model in a particular context of use

• Subgroups working on general methodology, solid

mechanics, fluid mechanics and some device specialties (e.g., cardiovascular, orthopedics)

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DRAFT Credibility Strategy

Risk Assessment Matrix

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Upcoming FDA Public Workshop

•

CDRH is leading the effort to make V&V40

applicable

to regulatory submissions

•

June 11-12, 2013

– FDA will lead a workshop that will

focus specifically on regulatory issues with

computational modeling

 Day 1: Library of Models and Data

 Day 2: Strategy to Assess Credibility of Computational

Modeling

o Email [email protected] if you wish to participate

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FDA Guidance

2. Strategy to Assess Credibility Computational Modeling Studies for Regulatory Submissions (DRAFT)

 _{Content is currently being drafted}

 The strategy is intended to create a framework for

determining the risk associated with using a

computational model in a specific context of use to

inform decision making and for determining ‘how much’ V&V is necessary to support the model in that context of use.

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 _{sensitivity and uncertainty analyses for crucial input}

parameters

 adequate validation to support the use of the modeling and

simulation

•

In biomechanics, lack of complete understanding of

Some

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Initiatives – The VPP

a) Develop computer models using radiological imaging data from healthy and diseased

anatomy;

b) Integrate with these models physiological, clinical and engineering data to promote development of complete physiological

models and simulations that can be used in the development and evaluation of medical devices; and,

c) create an open-source library of validated computer models and data easily accessible to industry developers, clinicians, and

Components of the Virtual

Physiological Patient

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1. Virtual Human Heart • Valves

• Ventricular Assist Devices

2. Complete Peripheral Vasculature • Endovascular Grafts • Stents 3. Bone Body • Joint Replacements 4. Model Mind • Neurosurgical Tools • Revascularization Post-stroke

Initiatives – The VPP

Components of the Virtual Physiological Patient

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Library of Models and Data

Public compendium of anatomic and physiologic data A shared point of reference might improve

understanding of the model attributes and

limitations and will enable the model to evolve as data accumulates.

Discrete computer models and simulations validated for regulatory evaluation

Selective use of high value models will improve predictability and consistency in the regulatory review process.

Peer-reviewed by experts in academia, government and industry

Ensure robust verification and validation, including periodic assessment.

Initiatives – The VPP

Components of the Virtual Physiological Patient

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Tortuosity, Bending & Twisting Rotor Design Inlet Outlet

Research – The VPP

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Partnerships – MDIC

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Get more information:

Call for Technical Papers and Posters

September 11-13, 2103, Marriott Conference Center, University of Maryland

Technical Papers and Posters will be presented in the following areas:

• The Role of Experiment in Modeling

• Computational Models as a Medical Device

• Consortium-Based Model Development and Validation • How Good is Good Enough?

• Imaging in Modeling and Simulation Development

• Lessons From More Mature Industries (Aerospace, Automotive, etc.): How Did They Do It???

• Novel Computational Methods • Patient Specific Modeling • Population Modeling

• Predictive Reliability Modeling • Probabilistic Modeling

• Surgical Simulation

Happy Hour in DC at the famous Old Ebbitt Grill Visit the White House, the Capitol and numerous free museums 1st_{ASME/FDA Frontiers in Medical Devices}

Applications of Computer Modeling and Simulation

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Future Directions

•

Digital Patients

•

Virtual Clinical Trials

•

Personalized Medicine

•

MDIC Subcommittee on

computational modeling

FDA NIH INDUSTRY ACADEMIA _CM NSF NIST NASA DARPA MDIC

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If you want to discuss

• how modeling and simulations fits into the device evaluation

strategy for your product,

• your validation strategy to support your computational model, • how to determine if your model/simulation is a medical device, • or, if you want to get involved with ASME V&V 40

Send an email to:

[email protected] Office of Device Evaluation

Enabling Faster, Better Medical Device Development and Evaluation via

Modeling and Simulation: CDRH perspective