definiens: means ( i ) any event, circumstance, change, occurrence, development, condition or effect that has or would be expected to result in a material adverse change in, or material adverse effect on, ( A ) the condition ( financial or otherwise ), business, assets, Liabilities or result s of operations of Issuer and its Subsidiaries, taken as a whole, excl uding any such effect to the extent resulting from ( 1 ) changes in general economic conditions in the U.S., ( 2 ) change s or conditions generally affecting the industry in which Issuer and its Subsidiaries operate, ( 3 ) acts of war, sabo tage or terrorism involving the U.S. or ( 4 ) the ann ouncement of the transactions contemplated by this Agreement exc ept, in the case of clauses ( 1 ), ( 2 ) and ( 3 ), to th e extent not having a disproportionate effect on Issuer and its Subsidiaries, taken as a whole, relative to other p articipants in the industry in which Issuer and its Subsidiaries o perate, ( B ) Issuer ’s ability to consummate the tran sactions contemplated by this Agreement on or before the End Time or ( ii ) any material adverse determination by, or a material delay of a determination by, the FDA or an y other Governmental Authority or any Review Board, or any indication that any such entity or Review Board wil l make any material adverse determination or materi ally delay making any determination, with respect to the safet y or efficacy as shown in pre - clinical or clinical testing, approvability, labeling, contents of package insert, prescribing information, risk management profile, pre - approval inspection matters or requirements relating to the results of any pre - clinical or clinical testing, po st - market requirements or commitments, in each case, related to any of the Products