; and (iii) to evaluate the analytical validity and clinical validity of such test. (3) Conditions of approval (A) In general An investigational use application with respect to significant risk tests shall only be approved if each of the following conditions is met: (i) The risks to the subjects of the in vitro clinical test are outweighed by the anticipated benefits to the subjects and the importance of the knowledge to be gained, and adequate assurance of informed consent is provided in accordance with paragraph (5)(A)(iii). (ii) The proposed labeling for the in vitro clinical test involved clearly and conspicuously states For investigational use . (iii) Such other requirements the Secretary determines to be necessary for the protection of the public health and safety as long as the requirements do not unduly delay investigation after finding that the results of such investigation establish sufficient data to support clinical or analytical validity. (B) Certain significant risk in vitro clinical tests for an unmet need As a condition of approval under this paragraph, the Secretary shall not impose a limit on the sample size for a significant risk in vitro clinical test that meets the requirements of section 587C, as long as such test is developed within a laboratory that is certified to conduct high-complexity testing under section 353 of the Public Health Service Act. (4) Coordination with investigational new drug applications Any requirement for the submission of a report to the Secretary pursuant to an investigational new drug application involving an in vitro clinical test shall supersede the reporting requirement in paragraph (2)(B), but only to the extent the requirement with respect to the investigational new drug application is duplicative of the reporting requirement under such paragraph. (5) Investigation plan requirements (A) In general With respect to an investigational plan submitted under paragraph (2)(A), the sponsor submitting such plan shall— (i) in the case of such a plan submitted to an