definiens: means ( a ) with respect to a BLA or NDA, the accep tance by FDA of such BLA or NDA for substantive review, which can b e evidenced by Takeda ’s receipt of notice from FDA of such acceptance or other evidence that FDA has comm enced its substantive review, ( b ) with respect to a Drug Approval Application filed with the EMA, the receip t by Takeda of a letter from the EMA with respect t o such Drug Approval Application indicating that there has been a positive outcome of the EMA ’s validation of such Drug Approval Application and ( c ) with respect to a Drug Approval Application filed with the PMDA in J apan, the acceptance by PMDA of such Drug Approval Applic ation for substantive review, which can be evidence d by Takeda ’s receipt of notice from PMDA of such accept ance or other evidence that PMDA has commenced its substantive review