AOP Orphan Pharmaceuticals AG – FDA CRL

The FDA issued a Complete Response Letter (CRL) to AOP Orphan Pharmaceuticals GmbH for its New Drug Application (NDA 217202) for landiolol injection, filed under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The agency found the application unacceptable in its present form. Key deficiencies included unresolved issues related to product quality, specifically concerning the drug product and manufacturing. The proposed prescribing information required significant revisions to meet regulatory content and formatting requirements (e.g., 21 CFR 201.56(a) and (d), 201.57), including submission in Structured Product Labeling (SPL) format. Additionally, the proprietary name proposed for the drug was deemed unacceptable. A comprehensive safety update, encompassing new clinical data, updated exposure information, worldwide safety experience, and translated foreign labeling, was also required as per 21 CFR 314.50(d)(5)(vi)(b). A crucial postmarketing requirement, if the NDA were approved, involves conducting an *in vitro* assessment to evaluate the potential inhibitory effect of landiolol and its M1 metabolite on multiple drug transporters (e.g., P-gp, BCRP, OATP1B1, OATP1B3, OCT2, MATE1, MATE2-K, OAT1, OAT3) to address potential drug-drug interactions. AOP Orphan Pharmaceuticals GmbH must address all identified deficiencies and resubmit the application or take other actions available under 21 CFR 314.110 within one year.