Research with FDA Regulated Devices

The FDA defines a medical device as an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related 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 diagnosing disease or other conditions, or in curing, mitigating, treating, or preventing disease in humans or animals
• Intended to affect the structure or any function of the body of humans or animals, and does not achieve its primary intended purposes through chemical action within or on the body and is not dependent on being metabolized for its primary intended purposes (21 U.S.C. 321(h))

Medical devices range from simple items like tongue depressors to highly complex programmable implanted devices like pacemakers. They also include in vitro diagnostic (IVD) products such as reagents, test kits, and blood glucose meters. Software functions can also be considered medical devices. Certain electronic products that have a medical use or make medical claims, such as diagnostic ultrasound products, x-ray machines, and medical lasers, are also considered medical devices.

Investigational devices are medical devices that are the object of a clinical investigation. This means that an objective of the study is looking at the safety and/or effectiveness of the device in some way.

All clinical investigations of devices must have an approved Investigational Device Exemption (IDE) or be exempt from the IDE regulations.

Please refer to the following to determine step by step if your study uses a medical device that is regulated by the FDA: FDA information sheet How to Determine if Your Product is a Medical Device.

IDE refers to the regulations under 21 CFR 812. An approved IDE means that the IRB (for nonsignificant risk devices) or the FDA (for significant risk devices) has approved the sponsor's study application and all the requirements under 21 CFR 812 are met. A list of relevant IDE Definitions and Acronyms is available on the FDA website.

Some clinical investigations of devices are exempt from the IDE requirements in 21 CFR 812 and are described in §812.2(c) of the IDE regulations. For the full list, please see FDA webpage describing the IDE Approval Process (specifically the section related to IDE Exempt Investigations.)

Human subjects research studies that involve the clinical investigation of a device are exempt from IDE regulations if they include:

• Legally marketed devices when used in accordance with FDA labeling
• Diagnostic devices that comply with the FDA labeling requirements in §809.10(c) and if the testing:
  • is noninvasive
  • does not require an invasive sampling procedure that presents significant risk
  • does not by design or intention introduce energy into a subject
  • is not used as a diagnostic procedure without confirmation by another medically established diagnostic product or procedure
• Consumer preference testing, testing of a modification, or testing of a combination of devices if the devices are legally marketed devices AND if the testing is not for the purpose of determining safety or effectiveness and does not put subjects at risk

When your research involves the clinical investigation of an investigational device, you must provide written justification in the protocol explaining why the device is exempt from the requirement for an IDE. Include this information in your Initial Review Submission to the IRB.

If the IRB does not agree that the device is exempt, they may require you to submit to the FDA for a formal determination before further review of the study. The FDA's decision on whether the device is exempt or requires an IDE is final.

If you seek guidance from the FDA for these determinations, they will provide you with an outcome letter. Include this letter in your Initial Review Submission.

If you are studying a medical device that is the object of a clinical investigation and it has not been determined to be exempt from the IDE regulations, your protocol is subject to the IDE regulations at 21 CFR 812.

An investigational device exemption (IDE) allows you to use an investigational device in a clinical study to collect safety and effectiveness data. Investigational use also includes clinical evaluation of certain modifications or new intended uses of legally marketed devices.

An approved IDE permits a device to be shipped legally for the purpose of conducting investigations without complying with other requirements of the Food, Drug, and Cosmetic Act that apply to devices in commercial distribution.

Investigations covered under the IDE regulation are subject to different levels of regulatory control based on the level of risk involved.

Significant Risk (SR) Device 

A SR device is an investigational device that:

• is intended as an implant and presents a potential for serious risk to the health, safety, or welfare of a subject.
• is for use in supporting or sustaining human life and represents a potential for serious risk to the health, safety, or welfare of a subject.
• is for a use of substantial importance in diagnosing, curing, mitigating, or treating disease or otherwise preventing impairment of human health and presents a potential for serious risk to the health, safety, or welfare of a subject.
  or
• otherwise presents a potential for serious risk to a subject.

Examples of SR devices include sutures, Electroconvulsive Therapy (ECT) devices, cardiac pacemakers, replacement heart valves, cochlear implants, biliary stents, plasmapheresis systems hydrocephalus shunts, endometrial ablation systems, extended wear contact lenses, and orthopedic implants.

Investigational devices that meet the definition of significant risk, and that do not qualify as exempt, must have both FDA and IRB approval. The sponsor must submit an IDE application to FDA and obtain approval prior to the PI's submission of the protocol for initial review by the NIH IRB.

Non-Significant Risk (NSR) Device

NSR (Non-Significant Risk) devices are devices that are not IND Exempt and do not pose a significant risk to human subjects. They are not subject to full IDE requirements and do not require an IDE application to be submitted to the FDA. However, the IRB must confirm the NSR determination at a full board meeting. In this case, these studies are subject to the abbreviated IDE requirements.

Sponsors are responsible for making the initial device risk determination. The PI must include this initial determination and the sponsor's explanation for why the device does not pose a significant risk in the protocol.

The FDA can help the sponsor, clinical investigator, and IRB in making the NSR determination, but no formal IDE application needs to be submitted unless the FDA later concludes that the device use is considered Significant Risk (SR).

Examples of medical devices the FDA considers nonsignificant risk devices include most daily-wear contact lenses and lens solutions, dental filling material, EEG recording devices, MRI devices within FDA parameters, and short-term use urological ("Foley") catheters.

Step-by-step process for determining if an IDE is required for a device study

Direct communication with the FDA is usually initiated by and is the responsibility of the study sponsor. As the site investigator, you should submit the following reports to the sponsor to provide them with the information they need to submit the required reports to the FDA:

• Unanticipated adverse device effects (UADE): You must submit to the sponsor and the reviewing IRB a report of any unanticipated adverse device effect as soon as possible but no later than 10 working days after you first learn of the UADE.
  
• Withdrawal of IRB approval: You must report to the sponsor a withdrawal of approval of the reviewing IRB within 5 working days.
  
• Annual Progress Reports: You must submit progress reports to the sponsor at regular intervals but no less than on a yearly basis. The contents of this report are dictated by the sponsor.
  
• Deviations from the investigational plan: You must notify the sponsor and the reviewing IRB of any deviation from the investigational plan to protect the life or physical well-being of a subject in an emergency. The notice must be provided as soon as possible but no later than 5 working days after the emergency occurred. If it is not an emergency, prior approval from the sponsor is required for changes in or deviations from the investigational plan. If the change or deviation may affect the scientific soundness of the investigational plan or the rights, safety or welfare of the subject, IRB approval must be obtained and, for SR investigations, the sponsor must obtain FDA approval by submitting an IDE supplement.
  
• Failure to obtain informed consent: If you use a device without obtaining informed consent, you must report the use to the sponsor and to the reviewing IRB within 5 working days after the use occurs.
  
• Final report: You must submit a final report to the sponsor within 3 months after termination or completion of the investigation.

The following policy outlines the NIH IRB reporting requirements that you must follow: