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

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

Medical Devices

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)

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

Medical Devices are Classified by Risk

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

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

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

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

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

Getting a Device to Market

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.

Premarket Approval Application (PMA)

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)

21 C.F.R. 814

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

Used for devices that will benefit patients with rare conditions (<4,000 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

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

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

Medical Device Research

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

Device Clinical Research

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

SR vs. NSR Determination

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

Significant Risk Definition

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

NSR Determination
No IDE application to FDA Considered to have an IDE Abbreviated requirements only

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

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

Access to Unapproved Devices

Early/Expanded Access
Emergency Use Compassionate Use Treatment Use Continued Access

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidanc e/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/uc m051345.htm

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/RunningClinic alTrials/GuidancesInformationSheetsandNotices/ucm118823.htm

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

http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidanc e/HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/uc m051345.htm#continuedaccess

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

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/DeviceRegulationandGuidance /HowtoMarketYourDevice/InvestigationalDeviceExemptionIDE/ucm 051345.htm#continuedaccess

Trials

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

Regulatory Differences in Trials

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

Regulatory Differences in Trials

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

Adverse Event Differences in Trials

Devices
21 C.F.R. 812.150(a)(1)

Drugs
21 C.F.R.312.32

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

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

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

Summary

CDRH Homepage www.fda.gov/cdrh CDRH Learn http://www.fda.gov/Training/CDRHLearn/ ucm162015.htm Device Advice www.fda.gov/cdrh/devadvice Computerized Systems http://www.fda.gov/downloads/Drugs/Gui danceComplianceRegulatoryInformation/ Guidances/UCM070266.pdf

Other References

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

Device Contacts for Questions