; or (ii) could compromise national security. (3) Review of denials An applicant whose application submitted under this section has been denied approval under this subsection may, by petition filed not more than 60 calendar days after the date on which the applicant receives notice of such denial, obtain review of the denial in accordance with section 587P. (f) Supplements to an approved application (1) Risk analysis Prior to implementing any modification to an in vitro clinical test, the holder of the application approved under subsection (e) for such test shall perform risk analyses in accordance with this subsection, unless such modification is included in the change protocol submitted by the applicant and approved under this section or exempt under section 587C. (2) Supplement requirement (A) In general If the holder of an application of an approved in vitro clinical test makes a modification to such in vitro clinical test, except as provided in subparagraph (C), or otherwise specified by the Secretary, the holder of the application approved under subsection (e) for an in vitro clinical test shall submit a supplemental application to the Secretary. The holder of the application may not implement such modification to the in vitro clinical test until such supplemental application is approved. The information required in a supplemental application is limited to what is needed to support the change. (B) Change protocols The holder of an approved application may submit under this paragraph a supplemental application to modify the change protocol for a test or to request a change protocol for a test. (C) Exceptions Notwithstanding subparagraphs (A) and (B), and so long as the holder of an approved application submitted under subsection (a) or (b) for an in vitro clinical test does not add a manufacturing site, or change activities at an existing manufacturing site, with respect to the test, the holder of an approved application may, without submission of a supplemental application, implement the following