regulation of medical devices celia m. witten, ph.d., m.d. director division of general, restorative...

Regulation of Medical DevicesRegulation of Medical DevicesCelia M. Witten, Ph.D., M.D.Celia M. Witten, Ph.D., M.D.

DirectorDirectorDivision of General, Restorative Division of General, Restorative

andandNeurological DevicesNeurological Devices

Office of Device EvaluationOffice of Device EvaluationFood and Drug AdministrationFood and Drug Administration

RHAIRRHAIR

Society for Academic Emergency Society for Academic Emergency MedicineMedicine

Boston, MassachusettsBoston, Massachusetts

May 31, 2003May 31, 2003

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OutlineOutline

Who we areWho we are Device typesDevice types Paths to marketPaths to market Temperature control devicesTemperature control devices Clinical study regulationClinical study regulation

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FDA

CVM CFSCAN CDRH CBER CDER

OST OSM OSB ODE OHIP OC OIVD

DAGID

DCD

*DGRND

DOED

DRARD

Who We Are

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Device Examples Device Examples

Neuroembolization devicesNeuroembolization devices Deep brain stimulatorsDeep brain stimulators Neurodiagnostic devices (EEG, Neurodiagnostic devices (EEG,

EMG)EMG) Neurosurgical shuntsNeurosurgical shunts Muscle stimulatorsMuscle stimulators Neurovascular stentsNeurovascular stents

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Regulatory Review:Regulatory Review: Pathways to Market Pathways to Market

Premarket Notification 510(k)Premarket Notification 510(k) Premarket Approval Application Premarket Approval Application

(PMA)(PMA) Product Development Protocol Product Development Protocol

(PDP)(PDP) Humanitarian Device Exemption Humanitarian Device Exemption

(HDE)(HDE) De Novo ClassificationDe Novo Classification

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Premarket Notification Premarket Notification 510(k)510(k)

Substantial EquivalenceSubstantial Equivalence Predicate Device (legally Predicate Device (legally

marketed, not subject to PMA)marketed, not subject to PMA) ComparisonComparison

– same intended use andsame intended use and– same technological characteristics orsame technological characteristics or– different technological characteristics different technological characteristics

andand– as safe and effective as predicateas safe and effective as predicate

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Premarket Application Premarket Application (PMA)(PMA)

…”…”reasonable assurance of reasonable assurance of safety and effectiveness”…safety and effectiveness”…

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Regulatory Path Regulatory Path ExamplesExamples

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Hydrocephalus ShuntsHydrocephalus Shunts

510(k) (substantial equivalence)510(k) (substantial equivalence) Comparison to predicateComparison to predicate Standards:Standards:

– ASTM F647ASTM F647– ISO 7197ISO 7197

Materials/biocompatibilityMaterials/biocompatibility For new/unusual designs, may need a For new/unusual designs, may need a

clinical study forclinical study for– InfectionInfection– Revision/causesRevision/causes– Failures/failure modesFailures/failure modes

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Intracranial Neurovascular Intracranial Neurovascular StentsStents

Class III (PMA/HDE/PDP)Class III (PMA/HDE/PDP) 2 HDE’s approved2 HDE’s approved

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Deep Brain StimulationDeep Brain Stimulation

Class IIIClass III PMA approval for essential PMA approval for essential

tremor and Parkinson’s tremor and Parkinson’s disease symptoms disease symptoms

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Clinical Study Clinical Study RegulationRegulation

FFD&C Act gives FDA the FFD&C Act gives FDA the authority to regulate authority to regulate investigational devices:investigational devices:

To To encourageencourage the discovery the discovery and development of new and development of new devicesdevices

Maintain Maintain optimum freedomoptimum freedom for for scientific investigationsscientific investigations

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Section 520(g)Section 520(g)of the Actof the Act

Requires IRB approval for all Requires IRB approval for all clinical investigationsclinical investigations

Requires informed consent Requires informed consent from all subjects unless from all subjects unless emergency useemergency use

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IDE RegulationIDE Regulation(Part 812)(Part 812)

Allows an unapproved device to be Allows an unapproved device to be shipped for clinical evaluation:shipped for clinical evaluation:

Identifies sections of the Act from Identifies sections of the Act from which IDEs are exemptwhich IDEs are exempt

Identifies exempted investigations Identifies exempted investigations (e.g. cleared devices, IVDs)(e.g. cleared devices, IVDs)

Defines SR and NSR investigationsDefines SR and NSR investigations

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Significant Risk (SR) Significant Risk (SR) StudyStudy

Presents a potential serious risk to Presents a potential serious risk to the health, safety, and welfare of a the health, safety, and welfare of a subject and is:subject and is:– an implant; oran implant; or– life supporting or sustaining; orlife supporting or sustaining; or– of substantial importance in of substantial importance in

diagnosing, curing, mitigating, or diagnosing, curing, mitigating, or treating disease or preventing treating disease or preventing impairment of human healthimpairment of human health

FDA approval requiredFDA approval required

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Non-significant Risk Non-significant Risk StudiesStudies

FDA approval not neededFDA approval not needed Examples:Examples:

– MRI < 4 TeslaMRI < 4 Tesla– Urologic cathetersUrologic catheters– Low level biostimulation lasersLow level biostimulation lasers– LaparoscopesLaparoscopes

NSR devices can be SR studiesNSR devices can be SR studies

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Informed Consent: Informed Consent: Emergency UseEmergency Use

Must be reviewed and Must be reviewed and approved by the IRB and the approved by the IRB and the FDA prior to useFDA prior to use

May be waived when there is May be waived when there is a life-threatening situationa life-threatening situation– the subject cannot communicatethe subject cannot communicate– time is not sufficienttime is not sufficient– no available alternativeno available alternative– two physicians certify in writing two physicians certify in writing

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Informed Consent: Informed Consent: Emergency ResearchEmergency Research

Certain studies may not require Certain studies may not require informed consent when IRB agrees informed consent when IRB agrees thatthat– there is a life-threatening situation and there is a life-threatening situation and

currentcurrent

treatments are unsatisfactorytreatments are unsatisfactory– no timeno time– can’t identify subjects prospectively can’t identify subjects prospectively – community consultationcommunity consultation– public disclosurepublic disclosure

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When Are Clinical Data When Are Clinical Data Needed?Needed?

To support:To support: PMA, PDP or HDE (almost always)PMA, PDP or HDE (almost always) 510(k) (<10%)510(k) (<10%) New indication for an New indication for an approvedapproved

device (e.g., BPH for a urologic device (e.g., BPH for a urologic laser)laser)

Significant change to device, Significant change to device, especially Class III devicesespecially Class III devices

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Types of StudiesTypes of Studies

Sponsor-investigatorSponsor-investigator Manufacturer-sponsoredManufacturer-sponsored

– FeasibilityFeasibility– Pivotal, including sites outside Pivotal, including sites outside

the USthe US– Post-approvalPost-approval

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Feasibility TrialFeasibility Trial

Answer design-related questions Answer design-related questions that cannot be addressed by that cannot be addressed by bench/animal testingbench/animal testing

Modify device design &/or Modify device design &/or instructions for useinstructions for use

Preliminary safety dataPreliminary safety data No controlNo control Limited # pts/limited follow-upLimited # pts/limited follow-up

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Pivotal TrialPivotal Trial

Final design, indication for use, Final design, indication for use, and protocoland protocol

ControlledControlled Masked, if possibleMasked, if possible Primary/secondary endpointsPrimary/secondary endpoints Develop information for labelingDevelop information for labeling Statistical validity to show S & EStatistical validity to show S & E

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Post-ApprovalPost-Approval

May be required for PMA May be required for PMA approvalapproval

Designed to address specific Designed to address specific questionquestion

# of patients and duration # of patients and duration specified by FDAspecified by FDA

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Cooling Devices:Cooling Devices:Clinical Study Clinical Study

QuestionsQuestions How soon?How soon? How cold?How cold? How fast?How fast? How long?How long? How measured?How measured? Speed of rewarming?Speed of rewarming? Other treatments provided?Other treatments provided? Local versus systemic?Local versus systemic?

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Temperature Control Temperature Control DevicesDevices

Tool?Tool? Treatment?Treatment?

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Temperature Control Temperature Control DevicesDevices

Cooling BlanketsCooling Blankets Endovascular DevicesEndovascular Devices

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