; or (C) otherwise presents a potential for serious risk to the health of a human subject. (d) Review of applications (1) In general The Secretary may issue an order approving an investigation as proposed, approving it with conditions or modifications, or disapproving it. (2) Failure to act Unless the Secretary, not later than 30 calendar days after the date of the submission of an application for an investigational use exemption that meets the requirements of subsection (c), issues an order under paragraph (1) and notifies the sponsor submitting the application, the application shall be treated as approved as of such date without further action by the Secretary. (3) Denial The Secretary may deny an investigational use application submitted under this subsection if the Secretary determines that the investigation with respect to which the application is submitted does not conform to the requirements of subsection (c). A notification of such denial submitted to the sponsor with respect to such a request shall contain the order of disapproval and a complete statement of the reasons for the Secretary’s denial of the application. (e) Withdrawal of exemption (1) In general The Secretary may, by administrative order, withdraw an exemption approved under this section with respect to an in vitro clinical test, including an exemption treated as approved based on the Secretary’s failure to act pursuant to subsection (d)(2), if the Secretary determines that an investigation conducted under such an exemption does not meet the applicable conditions under subsection (c)(3) for such exemption. (2) Opportunity to be heard (A) In general Subject to subparagraph (B), an order withdrawing an investigational use exemption granted under this section may be issued only after the Secretary provides the sponsor of the in vitro clinical test with an opportunity for an informal hearing. (B) Exception An order referred to in subparagraph (A) with respect to an investigational use exemption granted under this section may be issued on a