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

Schering-Plough Products L.L.C. in Manati, PR, received an FDA Form 483 from a February 1-16, 2001 inspection, citing significant deficiencies in manufacturing and quality systems, indicative of non-compliance with Current Good Manufacturing Practices (CGMP).

Key observations included widespread inadequate process validation. Products such as Gentocin Veterinary Solution, Afrin nasal sprays, and Nasonex Nasal Spray had validations based on insufficient batches, failed acceptance criteria (e.g., Nasonex 123% potency), or used outdated processes.

Product quality and impurity control were critically deficient. Gentocin Otic Solution was contaminated with Dicyclohexy] Phthalate from label adhesive since 1999, without proper risk assessment. The firm failed to test for impurities in several Active Pharmaceutical Ingredients (APIs), including Gentamicin Sulfate, releasing non-conforming batches and discontinuing testing. Unknown degradation products exceeding USP limits were also noted in finished products.

Organizational controls also failed. Supplier audits were not conducted per schedule. A particularly concerning practice involved invalidating out-of-specification results for Diazoxide by retrospectively changing specifications. Batches of Gentocin Veterinary Solution failing specific gravity tests were released despite unaddressed prior investigations. Furthermore, persistent consumer complaints since 1998 regarding non-functional Nasonex Nasal Spray delivery systems had not led to corrective actions or safety assessments.

Schering-Plough must thoroughly address these observations, implementing robust corrective and preventive actions to ensure consistent product quality, safety, and regulatory compliance.