The regulations define "applicable clinical trial" (ACT) in 42 CFR 11.10(a) and in 42 CFR 11.22 describe which ACTs are subject to the registration requirements. A clinical trial or study initiated on or after January 18, 2017, that meets certain conditions in 42 CFR 11.22(b)(1) or (2) will be considered to meet the definition of an applicable clinical trial. One of these conditions is whether the drug, biological, or device product "under investigation is a Product Manufactured in and Exported from the U.S. or one of its territories for study in another country." (42 CFR 11.22(b)(1)(ii)(D)(2) and 42 CFR 11.22(b)(2)(iv)(B)) The regulations also define the "Product Manufactured in and Exported from the U.S." in 42 CFR 11.10(b)(15) as meaning "any drug product (including a biological product) or device product studied in the clinical trial is manufactured in the United States or one of its territories and exported for study in a clinical trial in another country."
The agency explained that the term "manufacture" is used as a "short-hand for all device [or drug] activities within FDA's jurisdiction." (81 FR 65011 (device), 81 FR 65014 (drug)) Therefore, any step in the manufacturing of the device or drug product (including device components, drug active ingredients, and packaging/labeling) that occurs in the United States (or one of its territories) would be considered "manufactured" in the United States.
In addition, the drug, biological, or device product "under investigation" as described in 42 CFR 11.22(b)(1)(ii)(D)(2) and 42 CFR 11.22(b)(2)(iv)(B) includes products that are used in the clinical trial in conjunction with, or compared to, each other. If a drug, biological, or device product is tested in conjunction with, or compared to, one or more other drug, biological, or device products (including a placebo or sham), then the products would be considered "under investigation" for purposes of this ACT condition.