BioMarin International Limited – FDA 483, May 2, 2017

An FDA inspection of BioMarin International Ltd.'s drug substance manufacturing facility in Ringaskiddy, County Cork, Ireland, was conducted from April 24, 2017, to May 2, 2017. The inspection revealed several observations concerning manufacturing quality and control. Key issues included an inadequate investigation into a prior deviation (88878) related to bioburden excursions. Specifically, the product impact evaluation was deemed insufficient, and the corrective and preventive action (CAPA) failed to establish proper sanitization frequencies for manufacturing skids after equipment interventions. This inadequacy subsequently contributed to new contamination events.

Furthermore, the microbial control for a specific manufacturing skid in the drug substance process was found to be inadequate. During the 2017 campaign, six lots of harvest fluid consistently exhibited elevated bioburden levels, with spore-forming microorganisms identified. Lastly, the facility lacked a formal protocol to verify the effectiveness of the sanitization solution during its storage for the skids used in the manufacturing process.

BioMarin International Ltd. is expected to address these observations by implementing comprehensive corrective and preventive actions to ensure effective microbial control, thorough deviation investigations, and robust sanitization protocols, thereby ensuring compliance with good manufacturing practices for drug substances.