FDA 483 - Hybrid Pharma LLC - June 20, 2019

An FDA inspection conducted at Hybrid Pharma LLC, an outsourcing facility located in Deerfield Beach, FL, from May 20 to June 20, 2019, identified significant deficiencies in manufacturing practices. The FDA 483 report detailed numerous observations related to inadequate controls and procedures, crucial for ensuring drug product quality and sterility. Key violations included a lack of adequate validation for aseptic and sterilization processes, such as media fills failing to simulate worst-case conditions and the absence of endotoxin testing for intrathecal drug products. Environmental controls were also found deficient, with brown discoloration on HEPA filters and cleanroom walls, and ineffective cleaning efficacy studies. The facility also exhibited poor environmental monitoring, non-cleanable surfaces, and loose ceiling tiles in critical areas. Furthermore, the company lacked essential written procedures for production and process controls, leading to unvalidated drug product formulations and sterilization parameters. Laboratory records were incomplete, showing inadequately validated test methods and missing data for routine product release. The stability program was deficient, with no formal plan and reliance on trial batches for stability studies. Critical issues were also noted regarding quality control unit responsibilities not being formalized or followed, and a widespread lack of documented employee training for various functions, including visual inspection and GMP. Finally, drug product labels were found to be non-compliant, repeatedly missing the required "This is a compounded drug" statement. These observations indicate a failure to adhere to good manufacturing practices for sterile drug production. Hybrid Pharma LLC is required to address these findings and implement comprehensive corrective actions to ensure compliance and patient safety.