FDA 483 - Schering-Plough Products LLC - February 16, 2001

The FDA Form 483 details numerous deficiencies in laboratory investigations, quality systems, and manufacturing processes.

**Laboratory Investigations:** The facility's failure investigations are inadequate, characterized by re-testing without scientific justification until passing results are obtained, and a lack of corrective actions. Examples include investigations 00 EXTR-211 and 00 EXTR-200 for Theophylline pellets, where failing results were invalidated or not addressed with evidence-backed conclusions or corrective actions. Similar issues were found in investigations 00 Rmat-73, 00 Rmat-81, 00 Rmat-85, and 00 Rmat-89 for Ribavirin drug substance, where re-testing continued until passing results were achieved, leading to lot release. The potency OOS investigation 99-RMAT-23 for API Ribavirin USP was inadequate, with an attributed cause (shaker vs. sonic) not addressed in procedures or applied to other lots. Incorrect re-testing practices were also observed for Ribavirin 200 mg capsules, where OOS results were attributed to analyst inexperience, leading to multiple re-tests and eventual release. Stability OOS investigations 00-STAB-86 and 00-STAB-87 also involved multiple re-tests and invalidation of original data without sufficient justification. The analytical laboratory investigation SOP is inadequate for failing to require FDA