Pharmacia & Upjohn Company LLC – FDA 483, Oct 9, 2013

During an inspection conducted from September 30 to October 9, 2013, the FDA issued a Form 483 to Pharmacia & Upjohn Company LLC's drug manufacturing facility in Kalamazoo, MI. The observations highlight significant deficiencies in the company's remediation process for its ATNAA auto-injector product, particularly concerning quality control and compliance with regulatory expectations. Key issues included a lack of robust validation for the ATNAA remediation process, which failed to consistently detect and remove units with insufficient atropine levels. The process design itself was deemed inadequate, as it did not properly evaluate critical variables like plunger dislodgement or establish appropriate weight check limits for pralidoxime. Furthermore, operators performing visual inspections and remediation tasks were not adequately qualified or trained according to written procedures and validation protocols. The facility also failed to follow its own written process validation protocols, and investigations into product discrepancies, such as particulate matter, were insufficient. Deficiencies in batch records, including the failure to identify personnel performing critical steps, were also noted. Additionally, contract non-conformances included the improper application of ISO 2859-1 sampling rules and a lack of documented random sampling. Missing "R" marks on remediated pouches, indicating an incomplete inspection, further underscored the quality system breakdown. These observations underscore a need for comprehensive corrective and preventive actions to ensure product quality and regulatory compliance.