Presented by Catherine Parker, RN Consumer Safety Officer

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Medical Devices, Device Regulations, and Medical
Device Trials

• Presented by Catherine Parker, RN
• Consumer Safety Officer
• Division of Bioresearch Monitoring
• Office of Compliance
• Center for Devices and Radiological Health

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Objectives

• Define medical device
• Describe the classifications of devices
• Describe the ways a device can get to market
• Describe how medical device clinical trials
  differ from drug trials

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Medical Devices
4
Medical Device Definition

• An instrument, apparatus, implement, machine,
  contrivance, implant, in vitro reagent, or other
  similar article, including any component, part,
  or accessory which is
• Recognized in the official National Formulary, or
  the United States pharmacopeia, or any supplement
  to them
• Intended for use in the diagnosis of disease or
  conditions, or in the cure, mitigation,
  treatment, or prevention of disease in man or
  other animals
• Intended to affect the structure or any function
  of the body of man or other animals
• Which does NOT achieve its primary intended
  purposes through chemical action within or on the
  body of man or other animals and which is NOT
  dependent upon being metabolized for the
  achievement of its intended purposes.

• Definition of Device
• Food Drug and Cosmetic Act 201(h)

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The Important Points

• Device definition excludes products that
• Achieve their primary intended purpose through
  chemical action within the body
• Are dependent upon being metabolized for the
  primary achievement of their primary intended
  purposes

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Medical Devices are Classified by Risk
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Class I Devices

• General controls are sufficient to provide
  reasonable assurance of the safety and
  effectiveness
• Examples elastic bandages, examination gloves,
  and hand-held surgical instruments

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General Controls

• Prohibition against adulterated or misbranded
  devices
• Premarket notification 510(k) requirements
• Good Manufacturing Practices (GMPs)
• Labeling
• Registration of manufacturing facilities
• Listing of device types
• Record keeping
• Repair, replacement or refund

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Class II Devices

• .
• General controls alone are insufficient to assure
  safety and effectiveness, and existing methods
  are available to provide such assurances.
• Also subject to special controls
• Examples powered wheelchairs, infusion pumps,
  and surgical drapes

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Special Controls

• Performance standards (discretionary, voluntary
  national or international standard, recognized by
  rulemaking)
• Post-market surveillance
• Patient registries
• Development and dissemination of
  guidelines/guidances
• Design controls
• Recommendations and other appropriate actions
• Tracking requirements

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Class III Devices

• Insufficient information exists to determine that
  general and special controls are sufficient to
  provide reasonable assurance of the safety and
  effectiveness of such devices
• Such devices are
• Life sustaining or life supporting
• Substantial importance in preventing impairment
  of human health or
• Present unreasonable risk of illness or injury

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Getting a Device to Market
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Premarket Notification 510(k)
21 C.F.R. 807

• Used for devices that are substantially
  equivalent (SE) to a predicate device
• Manufacturer must notify FDA 90 days before
  proposing to market a device
• Burden is on the manufacturer to demonstrate that
  the device is SE.

The device is as safe and effective as an
existing marketed device.
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Premarket Approval Application (PMA)
21 C.F.R. 814

• Class III devices
• New types of devices
• Previously found not SE
• May require pre-clinical and clinical data
  obtained from an investigational device exemption
  (IDE)

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Humanitarian Device Exemption (HDE)
21 C.F.R. 814.100

• Used for devices that will benefit patients with
  rare conditions (lt4,000 per year)
• Application for HDE must demonstrate probable
  benefit
• Devices must be used under IRB approval
• Device must be available at cost

Vertical Expandable Prosthetic Titanium Rib By
Synthes
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Other ways to Market

• Product development protocol (PDP)
• An alternative to a PMA whereby the
  investigation of a device and the development of
  information necessary for its approval are merged
  into one regulatory submission
• De Novo classification pathway
• A streamlined reclassification process for
  devices that are low-risk but not SE. They would
  automatically be assigned a Class III status. The
  de novo pathway can get a novel low-risk device
  reclassified to Class I or II thus avoiding a PMA

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Custom Device
21 C.F.R. 812.3(b)

• It is different from devices available
• It is not available to, or used by other MDs or
  dentists
• It is not available in finished form for purchase
  or dispensing upon prescription
• It is not offered for commercial distribution
  through labeling or advertising

• It is intended for use by an individual patient
  named in the order form
• Made in a specific form for that patient or
• Made to meet the special needs of MD or dentist
  (i.e. tool)

http//www.fda.gov/downloads/RegulatoryInformation
/Guidances/UCM127067.pdf
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Medical Device Research
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Research Applications
21 C.F.R. 812

• Investigational Device Exemption (IDE)
• Approved by an IRB and, if applicable, FDA
• Informed consent from all subjects
• Labeling for investigational use only
• Monitoring of the study
• Submission of required reports and records
• Permits an unapproved device to be shipped
  lawfully

20
Device Clinical Research

• Significant risk (SR)
• IDE submission
• Non-Significant risk (NSR)
• Abbreviated requirements
• IDE exempt

21
SR vs. NSR Determination

• Decision based on use of device in study IDE
  submission
• Sponsor makes initial assignment
• IRB makes determination
• FDA can disagree

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Significant Risk Definition

• Decision based on use of device in study
• IDE application
• Sponsor makes initial assignment
• IRB makes determination
• FDA can disagree

23
NSR Determination

• No IDE application to FDA
• Considered to have an IDE
• Abbreviated requirements only

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Abbreviated Requirements
21 C.F.R. 812.2(b)

• Labels device
• Obtains IRB approval
• SR vs. NSR determination
• Ensures informed consent
• IRB may waive documentation of consent if
  minimal risk

• Monitors study
• Maintains records
• Makes reports
• Ensure CI maintains records and makes reports
• Refrains from promotion and other practices

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IDE Exempt Device Research
21 C.F.R. 812.2(c)

• In commercial use before May 28, 1976
• SE to device in commercial use before May 28,
  1976 and used or investigated for labeled
  indication
• In vitro diagnostics (IVDs)
• Consumer preference testing
• Solely for veterinary or lab animal use

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Access to Unapproved Devices
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Early/Expanded Access

• Emergency Use
• Compassionate Use
• Treatment Use
• Continued Access

http//www.fda.gov/MedicalDevices/DeviceRegulation
andGuidance/HowtoMarketYourDevice/InvestigationalD
eviceExemptionIDE/ucm051345.htm
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Emergency Use

• Life-threatening or serious condition with no
  alternative
• Before or during an IDE
• FDA approval not required
• Report to the IRB within 5 days
• Report to the Sponsor and/or FDA

http//www.fda.gov/ScienceResearch/SpecialTopics/R
unningClinicalTrials/GuidancesInformationSheetsand
Notices/ucm118823.htm
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Compassionate Use

• Serious condition with no alternative
• Before or during an IDE study
• FDA approval required

http//www.fda.gov/MedicalDevices/DeviceRegulation
andGuidance/HowtoMarketYourDevice/InvestigationalD
eviceExemptionIDE/ucm051345.htmcontinuedaccess
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Treatment Use
21 C.F.R. 812.36

• Life-threatening or serious disease
• No alternative
• Controlled clinical trial
• Sponsor pursuing marketing approval
• FDA approval required

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Continued Access

• Public health need or
• Preliminary evidence that the device will be
  effective with no significant safety concerns
• Occurs after the completion of the clinical
  trial
• FDA approval required

http//www.fda.gov/MedicalDevices/DeviceRegulation
andGuidance/HowtoMarketYourDevice/InvestigationalD
eviceExemptionIDE/ucm051345.htmcontinuedaccess
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Trials
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Regulatory Similarities in Trials

• FDA approval required before test articles can be
  shipped
• IDE or IND
• FDA regulations specify sponsor and clinical
  investigator responsibilities
• 21 CFR 812 and CFR 312

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Regulatory Differences in Trials

• Devices Investigator agreement generated by
  the sponsor per 21 CFR 812.43(c)
• Drugs Statement of Investigator - Form 1572

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Regulatory Differences in Trials

• Contract Research Organizations (CRO)
• Device regulations are silent about them
• Drug regulations define transfer of obligations
  to CRO

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Adverse Event Differences in Trials

• Drugs
• CI report any adverse effects that may
  reasonably be regarded as caused by, or probably
  caused by, the drug.
• Sponsors notify FDA of any unexpected fatal or
  life-threatening event within 7 calendar days

• Devices
• CI report any unanticipated adverse device
  effects (UADE)
• Sponsors report results of an evaluation of a
  UADE to FDA and all reviewing IRBs within 10
  working days

21 C.F.R. 812.150(a)(1)
21 C.F.R.312.32
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Medical Device Trials

• Subject population usually in the 100s rather
  than 1000s
• No phases Feasibility then pivotal study
• Blinding is less common
• Controls vary
• No placebo rather sham, active, historical
• CI training often critical (e.g. Human Factors)
• IRBs play a critical role

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Summary
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Other References

• CDRH Homepage
• www.fda.gov/cdrh
• CDRH Learn
• http//www.fda.gov/Training/CDRHLearn/ucm162015.ht
  m
• Device Advice
• www.fda.gov/cdrh/devadvice
• Computerized Systems
• http//www.fda.gov/downloads/Drugs/GuidanceComplia
  nceRegulatoryInformation/Guidances/UCM070266.pdf

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Device Contacts for Questions

• Questions related to compliance
• Cathy Parker, Office of Compliance, Division of
  Bioresearch Monitoring, 301-796-5553
• Questions pertaining to SR/NSR
• Office of Device Evaluation
• Program Operation Staff 240-276-4040
• IRB or Human Subject Protections Marian Serge,
  301-796-5644