The regulation defines both "U.S. FDA-regulated device product" and "U.S. FDA-regulated drug product" in 42 CFR 11.10(a). This "FDA-regulated" concept is also part of the ACT definition under 42 CFR 11.10(a) and described in 42 CFR 11.22(b)(1)(ii)(C) and 42 CFR 11.22(b)(2)(iii) for an applicable device clinical trial and an applicable drug clinical trial initiated on or after January 18, 2017, respectively. The regulation further defines these specific concepts as data elements in 42 CFR 11.10(b)(38) ("Studies a U.S. FDA-regulated Device Product") and 11.10(b)(39) ("Studies a U.S. FDA-regulated Drug Product") and explains them as a device product "subject to" section 510(k), 515, or 520(m) of the Federal Food, Drug, and Cosmetic (FD&C) Act and a drug product "subject to" section 505 of the FD&C Act or section 351 of the Public Health Service (PHS) Act, respectively. The Checklist and Elaboration for Evaluating Whether a Clinical Trial or Study is an Applicable Clinical Trial (PDF) (June 2017) provides additional information about these definitions.
The Final Rule preamble addresses whether a studied product meeting the device definition is "subject to" section 510(k), 515, or 520(m) of the FD&C Act. The Final Rule preamble states: "[A] clinical study of a device product that is being conducted entirely outside of the United States (i.e., does not have any sites in the United States or in any U.S. territory) and is not conducted under an IDE may not be a clinical study of a device product subject to section 510(k), 515, or 520(m) of the FD&C Act and, therefore, is not an applicable device clinical trial, depending on where the device product being used in the clinical study is manufactured. … If the device product is manufactured outside of the United States or its territories, and the clinical study sites are all outside of the United States and/or its territories, the device product would not be considered to be subject to section 510(k), 515, or 520(m) of the FD&C Act." (81 FR 65013)
Therefore, a study record that (1) does not list "United States" (or a U.S. territory) for the Facility Information/Country data element, (2) lists "No" for the U.S. Food and Drug Administration IND or IDE data element, and (3) lists "No" for the Product Manufactured in and Exported from the U.S. data element, would indicate that a studied device product is not "subject to" section 510(k), 515, or 520(m) of the FD&C Act. For such a study, the responsible party would list "No" for the Studies a U.S. FDA-regulated Device Product data element and the study would not be considered an applicable device clinical trial. Note that even if the device product being studied had previously been approved or cleared by the U.S. FDA under section 510(k), 515, or 520(m) of the FD&C Act for marketing in the U.S., that responsible party would list "No" for the Studies a U.S. FDA-regulated Device Product data element because the particular device product used in that study is not subject to those sections of the FD&C Act.
The Final Rule preamble also addresses whether a studied product meeting the drug definition is "subject to" section 505 of the FD&C Act or section 351 of the PHS Act. The Final Rule preamble states: "[A] clinical investigation of a drug product (including a biological product) that is being conducted entirely outside of the United States (i.e., does not have any sites in the United States or in any U.S. territory) may not be a clinical investigation of a drug product or biological product subject to section 505 of the FD&C Act or section 351 of the PHS Act, and therefore not an applicable drug clinical trial, depending on where the drug product (including biological product) being used in the clinical investigation is manufactured. … If the drug product (including a biological product) is manufactured outside of the United States or its territories, the clinical investigation sites are all outside of the United States, and the clinical investigation is not being conducted under an IND, the drug product or biological product would not be considered to be subject to section 505 of the FD&C Act or section 351 of the PHS Act, and the clinical investigation would not be an applicable drug clinical trial." (81 FR 65015)
Therefore, a study record that (1) does not list "United States" (or a U.S. territory) for the Facility Information/Country data element, (2) lists "No" for the U.S. Food and Drug Administration IND or IDE data element, and (3) lists "No" for the Product Manufactured in and Exported from the U.S. data element, would indicate that a studied drug or biologic product is not "subject to" section 505 of the FD&C Act or section 351 of the PHS Act. For such a study, the responsible party would answer "No" to the Studies a U.S. FDA-regulated Drug Product data element and the study would not be considered an applicable drug clinical trial. Note that even if the drug or biologic product being studied had previously been approved by the U.S. FDA under section 505 of the FD&C Act or section 351 of the PHS Act for marketing in the U.S., that responsible party would list "No" for the Studies a U.S. FDA-regulated Drug Product data element because the particular drug or biological product used in that study is not subject to those sections of the FD&C Act or PHS Act.
Example: For a clinical study conducted entirely outside of the United States or its territories, in which the drug, biological, or device product is not studied under an IND or IDE, and the studied drug, biological, or device product is manufactured outside of the United States or its territories, then the studied product would not be considered "FDA-regulated" under the relevant condition in 42 CFR 11.22(b)(1)(ii)(C) and 11.22(b)(2)(iii). The responsible party of such a study would select "No" for the data elements of Studies a U.S. FDA-regulated Drug Product and/or Studies a U.S. FDA-regulated Device Product (42 CFR 11.28(a)(2)(i)(N) and (O)).
For additional information, also see:
National Institutes of Health (NIH): Checklist and Elaboration for Evaluating Whether a Clinical Trial or Study is an Applicable Clinical Trial (PDF) (June 2017)What is the definition of a drug, biological, or device product under investigation being "manufactured" in the United States?