FDA EIR - Cosmo S.p.A. - November 10, 2017

An FDA Pre-Approval Inspection of Cosmo S.p.A. in Lainate, Milan, Italy, was conducted from November 6-10, 2017. The inspection, carried out under Compliance Program Guidance Manual 7346.832, focused on the readiness for commercial manufacturing, conformance to application, and data integrity for their new drug product, (b) (4) Tablet. The company also manufactures LIALDA® and Uceris for the U.S. market. During the previous FDA inspection in 2015, the firm received a VAI classification; all noted deficiencies and required corrective actions from that inspection were confirmed as resolved. However, the current inspection resulted in a one-item FDA Form 483, Inspectional Observations, issued to Mr. Roberto Villa, Chairman. The primary violation identified was inadequate in-process control procedures for the new drug product. Specifically, the Master Batch Record for commercial production of (b) (4) Tablets only required a visual check to confirm (b) (4) after a critical manufacturing step, which the FDA deemed insufficient to ensure product quality, contrary to the more robust testing performed during validation. This observation aligns with regulatory requirements under 21 CFR 211.110(a)(3) regarding control procedures. Additionally, a discussion item concerned an inconsistent and unscientific method for ensuring standard solution samples reached room temperature before use, relying on analysts "feeling the bottle." The firm committed to providing a written response to the FDA 483 observation. For the discussion item, they provided data to establish a consistent equilibration time and plan to update their procedure accordingly.