Table 1 Overview of FDA pathways

Compassionate use request

21 CFR 812.35-36 and Section 561 of the FD&C Act

For use of unapproved devices from clinical trials in patients that do not meet the study’s inclusion criteria

This pathway arose as part of the “Expanded Access” provision in the FDA Modernization Act of 1997. A compassionate use request allows for investigational devices to be used in emergency situations or for patients that do not meet a clinical trial’s inclusion criteria. FDA approval is required prior to implementation and can be obtained by having the sponsor submit an Investigational Device Exemption (IDE) supplement, including a description of why treatment is needed, why alternatives are unsatisfactory, any deviations from clinical protocol, as well as patient protection measures such as IRB approval, institutional clearance, informed consent, authorization from the IDE sponsor, and independent assessment by an uninvolved physician

Custom device exemption (CDE)

21 CFR 812.3(b) and Section 520(b) of the FD&C Act

For use of a customizable device due to the rarity of a patient’s medical condition or special need

This pathway arose in 1976 as an amendment to the Federal Food, Drug, and Cosmetic Act, and was expanded in 2012 under the FDA’s Safety and Innovation Act. Use of customizable devices “should represent a narrow category for which, due to the rarity of a patient’s medical condition or physician’s special need, compliance with premarket review requirements and performance standards under Sections 514 and 515 of the FD&C Act is impractical.” The device must be created in order to comply with an order of an individual physician, sufficiently unique that clinical investigation or performance standards would not apply. The customizable implant must be produced in quantities of less than 5 per year per device per patient

Humanitarian use device (HUD)

FD&C Section 520 (m)

For use of a device in treatment of a diagnosis which manifests in less than 4000 individuals per year in the United States

This pathway allows for exemption of scientifically based validation studies of efficacy mandated for standard premarket approval as long as there is enough information to suggest that the benefit is probably greater than the risk and no better alternative exists. Once a manufacturer has obtained an HDE approval for a specific device, IRB approval must be obtained from individual institutions, which may result in institutional device approval or necessitate IRB approval on a case-by-case basis

Premarket notification and premarket approval application

21 CFR 807.92(a)(3),862.9, 21 CFR 864.9

For devices to be used prior to marketing and sale

To obtain premarket approval for marketing and sale, there must be valid scientific evidence demonstrating the product is safe and effective. For premarket notification [510(k)], there must be evidence demonstrating a device is as safe as a currently legally marketed device. Many orthopaedic and implantable cardiac devices are approved via supplemental PMA pathways