; (2) a disease or condition that poses a threat of epidemic or pandemic; or (3) a disease or condition associated with morbidity that has a substantial impact on day-to-day functioning. (c) Standard of review for approval (1) Requirements An application for provisional approval under this section may be approved only if the Secretary determines that— (A) there is substantial evidence of safety for the drug, such that there is evidence consisting of adequate and well-controlled investigations, including clinical investigations, by experts qualified by scientific training and experience to evaluate the safety of the drug involved, on the basis of which it could fairly and responsibly be concluded that the drug will have the effect it purports or is represented to have under the conditions of use prescribed, recommended, or suggested in the labeling or proposed labeling; and (B) there is relevant early evidence based on adequate and well-controlled investigations, including early-stage clinical investigations, to establish that— (i) the drug provides a positive therapeutic outcome