FDA CRL - SHANDONG LUYE PHARMACEUTICAL CO., LTD

The FDA issued a Complete Response Letter (CRL) to Shandong Luye Pharmaceutical Co., Ltd. for its New Drug Application (NDA 212849) for Rykindo (risperidone) extended-release injectable suspension, submitted March 28, 2019, under section 505(b)(2) of the Federal Food, Drug, and Cosmetic Act. The agency identified significant deficiencies preventing approval. Major concerns include clinical safety issues, specifically unanticipated high drug concentration spikes observed in patients during a pivotal study. These spikes, up to five times higher than average, raise serious safety concerns. Shandong Luye must conduct a root-cause analysis and detail how such events would be prevented commercially. Product quality deficiencies were also noted, including inadequate in vitro drug release acceptance criteria and insufficient bridging data between clinical and commercial product batches, with observed differences in drug release profiles. The FDA denied a biowaiver for additional strengths, citing unresolved clinical pharmacokinetic concerns and a lack of complete in vitro drug release data. Lastly, the Use-Related Risk Analysis was deemed incomplete as it failed to identify the critical risk of users not re-suspending the microspheres after reconstitution. Shandong Luye Pharmaceutical Co., Ltd. must address these issues with comprehensive data and justifications to secure approval.