In some cases, direct comparative clinical trials will be necessary; or (iii) In unusual cases, where neither greater safety nor greater effectiveness has been shown, a demonstration that the drug otherwise makes a major contribution to patient care. 21 C.F.R. § 316.3(a)(3). FDA provides no information, either in its regulations or otherwise during its decision- making process, regarding what is necessary to show “greater safety” or a “major contribution to patient care” (MC to PC) in order to obtain exclusivity.