; and (ii) designated in such a system as an article regulated by the Secretary (which may include regulation as a drug, a device, a dietary supplement, or other product that is regulated under this Act); and (B) is an ingredient that presents significant public health concern and is, or contains— (i) an active ingredient in a drug— (I) that is approved under section 505 or licensed under section 351 of the Public Health Service Act; or (II) for which— (aa) an investigational use exemption has been authorized under section 505(i) of this Act or section 351(a) of the Public Health Service Act; and (bb) a substantial clinical investigation has been instituted, and such investigation has been made public