To assess whether a clinical trial using a radiation-emitting product “Studies a U.S. FDA-regulated Device Product” for purposes of the applicable device clinical trial definition in 42 CFR 11.10(a), 42 CFR 11.10(b)(38), and 42 CFR 11.22(b)(ii)(C), consider whether the following conditions apply:
(1) the product meets the definition of a device under section 201(h) of the Federal Food, Drug, and Cosmetic Act (FDA&C Act); and
(2) the clinical trial “studies” a device product subject to section 510(k), 515, or 520(m) of the FD&C Act.
For this assessment, the first question is whether the product meets the “device” definition at section 201(h) of the FD&C Act, which is how the regulation at 42 CFR 11.10(a) defines “device”. FDA has additional authority over radiation-emitting products under sections 531 – 542 of the FD&C Act; some are also devices, some are not. The assessment of whether a radiation-emitting product is a “device” under section 201(h) of the FD&C Act is largely dependent on its intended use. A radiation-emitting product such as external beam radiation used in a clinical trial would very likely be a “device” under 201(h) of the FD&C Act since it would likely be intended for use in the treatment, diagnosis, cure, prevention, or mitigation of disease or other conditions, and/or intended to affect the structure or function of the body.
If the product is a device under section 201(h) of the FD&C Act, then the second question is whether the clinical trial studies a device product subject to section 510(k), 515, or 520(m) of the FD&C Act. In explaining the “applicable device clinical trial” definition in 42 CFR 11.10(a), the Final Rule preamble clarifies that a “device product is considered to be subject to section 510(k), 515, or 520(m) of the FD[&]C Act if any of the following is required before it may be legally marketed in the United States: (1) A finding of substantial equivalence under section 510(k) permitting the device product to be marketed, (2) an order under section 515 of the FD[&]C Act approving a pre-market approval application for the device product, or (3) an HDE [or Humanitarian Device Exemption] under section 520(m) of the FD[&]C Act”. (81 FR 65012). In addition, for the clinical trial to be an “applicable device clinical trial,” the trial must meet the definition at 42 CFR 11.10(a), its primary purpose must be other than a feasibility study, and it must meet one of the following conditions: (1) at least one study facility is located in the U.S. (or a U.S. territory); (2) the study is conducted under a U.S. Investigational Device Exemption (IDE); or (3) the device product is manufactured in and exported from the U.S. (or a U.S. territory). (42 CFR 11.22(b)(1)(ii)).
Many radiation-emitting device products are subject to section 510(k) of the FD&C Act and some are subject to section 515 of the FD&C Act. If the product is a medical device intended to benefit patients in the treatment or diagnosis of a disease or condition that affects or is manifested in not more than 8,000 individuals in the United States per year, it may meet the requirements for a humanitarian use device under section 520(m) of the FD&C Act. FDA’s regulation in 21 CFR Part 892 describes the legal status (i.e., “classification”) of specific radiology devices, including diagnostic and therapeutic devices. For example, magnetic resonance diagnostic devices and medical charged-particle radiation therapy systems are designated in 21 CFR 892.1000 and 21 CFR 892.5050, respectively, as Class II devices (as defined in 21 CFR 860.3(c)(2)) and are subject to section 510(k) of the FD&C Act. In addition, an individual radiology device that is classified as a “high risk” class III device or has been found by FDA to be not substantially equivalent (NSE) to an existing Class I, II, or III device must generally be approved by FDA under section 515 of the FD&C Act before marketing.
The Final Rule preamble also explains that radiation-emitting products can be subject to the requirements in 42 CFR Part 11: “For example, a clinical trial for which a responsible party indicates the Intervention Type is ‘radiation,’ ‘genetic,’ or ‘procedure’ could in fact be an applicable device clinical trial studying a device product subject to section 510(k), 515, or 520(m) of the FDC Act (e.g., an x-ray device, a genetic test, or a surgical instrument).” (81 FR 65040).
In addition, the Final Rule preamble explains that when considering whether a clinical trial “studies” a device product, the responsible party should consider whether (a) the study is designed to examine the effect or performance of an FDA-regulated device product or differences in the intended use, for example, variations in frequency of use, method of administration, design specifications, and other characteristics (e.g., used in one or more, but not all, arms in a multi-arm study); and/or (b) at least one pre-specified primary or secondary outcome measure reflects a characteristic, effect, or performance of an FDA-regulated device product (e.g., need for replacement or maintenance of the device). (81 FR 65040) If either (a) or (b) are true, this would support that the clinical trial “studies” the device product.
