The regulations at 42 CFR 11.44(b) and 11.44(c) provide for the delayed submission of results information for an applicable clinical trial (ACT) with certification under certain conditions. Under 42 CFR 11.44(c), results information submission may be delayed if the responsible party of an ACT certifies that a studied FDA-regulated drug, biological, or device product was not approved, licensed, or cleared by FDA for any use before the primary completion date of the trial. The responsible party of such an ACT must also certify that the sponsor of the ACT intends to continue with product development and is seeking, or may seek at a future date, initial approval, licensure, or clearance by the FDA for the studied product. (Note: Results information is not required to be submitted if the drug, biological, or device product is not approved, licensed, or cleared by FDA for any use before the primary completion date of the ACT, and the primary completion date for the trial is before January 18, 2017.) Under 42 CFR 11.44(b) results information submission may be delayed if the responsible party certifies that the ACT sponsor, who is also the manufacturer of the FDA-regulated product, is seeking approval, licensure, or clearance of the new use being studied in that ACT for a product that previously has been approved, licensed, or cleared by the FDA and has filed or will file within 1 year an application or premarket notification for the new use being studied. A new use is one which is not included in the labeling of the approved, licensed, or cleared drug, biological, or device product.
The Final Rule preamble clarified that “drug product” and “biological product” refer to a finished product that is approved or licensed for marketing, and not to the active ingredients or active moiety in such a product. (81 FR 65070) Thus, “initial approval” (or “initial licensure”) in 42 CFR 11.44(c) pertains to the approval or licensure of an original New Drug Application (NDA), Abbreviated New Drug Application (ANDA), or Biologics License Application (BLA), whereas “new use” in 42 CFR 11.44(b) pertains to the approval or licensure of a supplemental NDA, ANDA, or BLA for an additional use for that particular drug product or biological product. (81 FR 65070)
Similarly, “device product” refers to a manufacturer’s particular “product” rather than a general “type” of device. (81 FR 65073) Thus, “initial approval” of a device product under sections 515 or 520(m) of the Federal Food, Drug, and Cosmetic (FD&C) Act pertains to the approval of an original Premarket Approval (PMA) or Humanitarian Device Exemption (HDE) (81 FR 65070) while “initial clearance” pertains to the clearance of a manufacturer’s original 510(k) submission for a particular device product. (81 FR 65071) Whereas “approval of a new use” pertains to the approval of a supplemental PMA under section 515 of the FD&C Act for an additional use for a particular device product (81 FR 65070), “clearance of a new use” pertains to the clearance of the same manufacturer’s subsequent 510(k) submission for an additional use for the same device product. (81 FR 65071)
If an ACT studies an FDA-regulated device product that has not been previously approved or cleared (does not have “initial approval” or “initial clearance”) by the U.S. FDA for one or more uses, then the responsible party is required to answer “Yes” to the Device Product Not Approved or Cleared by U.S. FDA data element under 42 CFR 11.28(a)(2)(i)(P). The Final Rule preamble also explains for this data element that “if a manufacturer’s original 510(k) submission for its particular device product has not been previously cleared, then that manufacturer’s device product would be considered a ‘device product not cleared by FDA,’ even if another manufacturer has already obtained 510(k) clearance of its device product within the same product type.” (81 FR 65042) The responsible party is required to update this data element under 42 CFR 11.64(a)(1)(ii)(M) within 15 calendar days after a change in approval or clearance status has occurred.
Also note that clinical trial registration information submitted for an ACT of a device product that has not been previously approved or cleared (does not have “initial approval” or “initial clearance”) is subject to the delayed posting provision at 42 CFR 11.35(b)(2)(i), which states that applicable device clinical trial registration information for a device product that has not been previously approved or cleared will be publicly posted not earlier than the date of FDA approval or clearance. The responsible party for the ACT may authorize public posting of the information prior to the date of FDA approval or clearance of its device product as specified at 42 CFR 11.35(b)(2)(ii) by answering “Yes” to the Post Prior to U.S. FDA Approval or Clearance data element under 42 CFR 11.28(a)(2)(i)(Q).
