Investigational Software Guidance
Version Date: May 9, 2013
Under FDA regulations, software that meets the definition of a medical device is regulated in the same way as other medical devices. The IRB must make regulatory determinations regarding the use of medical device software in research. This guidance gives an overview of the information that study teams should include in protocol documents and ARROW applications for studies involving investigational software, to enable the Health Sciences IRB to evaluate the regulatory status of the software.
When is software considered an FDA-regulated device?
The FDA considers software a medical device if it is an instrument, apparatus, implement, machine, contrivance, implant, in vitro reagent, or other similar or related article, including any component, part, or accessory, which is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease (i.e. it meets the legal definition of a medical device in section 201(h) of the Federal Food Drug and Cosmetic Act). Software intended for these purposes is considered a medical device whether it is “standalone” software meant for use on a general-purpose computer/other device (such as an application for a handheld device), or it is a component of or accessory to another medical device (such as a magnetic resonance diagnostic device or computed tomography x-ray system).
When is software considered investigational?
As with any other FDA-regulated device, software is considered investigational when it is the object of research involving one or more subjects to determine its safety or effectiveness for a specific indication, which includes for example, software tested in a study which is newly developed or modified from existing software, or that is being studied for an indication different from its labeling.
Which device studies are subject to FDA investigation device exemption (IDE) regulations?
An IDE must be obtained from the FDA before beginning any study using investigational software except as follows:
- The study uses FDA approved or cleared devices when used or investigated in accordance with the indications in their labeling;
- The study uses only devices determined by the IRB to constitute non-significant risk (in this case, an IDE is presumed to exist under FDA regulations).
- The study uses only diagnostic devices, if the sponsor complies with applicable requirements in 21 CFR 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, and
- Is not used as a diagnostic procedure without confirmation of the diagnosis by another, medically established diagnostic product or procedure.
What information about investigational software should be included in the IRB protocol and application?
- A clear description of the investigational software on the study, how it differs from software cleared for use by the FDA, results of any previous research using the software, and the procedures for using the software. When the software is a component of or accessory for another device (such as an MR or CT scanner), describe how the software affects the standard operation of the device.
- A clear description of the intended use of the software on the study, including whether the purpose of the study is to test the software’s safety or effectiveness
- Safety measures for protection of subjects
- Whether the software is sponsored by the UW investigator or by an external party
- Whether information developed using the investigational software will be disclosed to subjects or other health care providers or used to manage subjects’ clinical care
How should the ARROW application be completed to identify research involving investigational software?
- Select “Devices” on the Special Considerations and Procedures page of the application
- In the Devices section, indicate whether an investigational device exemption (IDE) has been applied for or already assigned by the FDA. If the answer is “yes,” upload the IDE application or FDA determination letter where prompted.
- If you think that an IDE is not required for the study, indicate why on the Devices: No IDE page of the application. For most investigational software, the appropriate choice is “A letter from the sponsor is attached stating that the device is a non-significant risk device.” Where prompted, upload a document from the device sponsor describing why the software, as used on the study, does not pose significant risk as defined in 21 CFR 812.3(m)(4), or upload documentation from the FDA indicating that the FDA has determined the software to be non-significant risk when used in the setting proposed in the research study.
Who determines the risk level of an investigational software (or other device) study when an IDE is not sought?
The device sponsor makes an initial significant risk (SR) or non-significant risk (NSR) determination. Unless the FDA has previously made an SR or NSR determination applicable to the study, the IRB must decide if it agrees with the sponsor’s determination. The IRB’s determination is based on the risks of the device as it will be used on the study, and the nature of the harm that may result from the use of the device and/or from additional procedures associated with the device study. (Note that an SR / NSR determination is distinct from a minimal risk determination, and based on different criteria.)
FDA educational video “CDRH Regulated Software: An Introduction”
FDA Information Sheet: Guidance for IRBs, Clinical Investigators, and Sponsors: Significant Risk and Nonsignificant Risk Medical Device Studies
FDA "Off-Label" and Investigational Use Of Marketed Drugs, Biologics, and Medical Devices - Information Sheet
FDA Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices:
FDA Guidance for Industry and FDA Staff: Criteria for Significant Risk Investigations of Magnetic Resonance Diagnostic Devices