Lee & Company – FDA 483, Feb 21, 2013

The FDA Form 483 details significant deficiencies at an unnamed facility manufacturing sterile drug products.

**Environmental Monitoring Deficiencies:** * Aseptic processing areas lack suitable procedures for monitoring ISO Class 5 environmental conditions. * No monitoring for viable and non-viable particles is conducted during aseptic filling; current practice involves static personnel, settling/contact plate, and non-viable particulate monitoring. * No dynamic studies exist to ensure filtered air flow patterns in the ISO Class 5 area.

**Sterilization Process Validation Issues:** * Procedures to prevent microbiological contamination lack validation of sterilization processes. * No qualification studies (e.g., [b] (4) studies) have been performed on [b] (4) used to sterilize vials, septums, equipment, and drug product, particularly with current loading patterns. * Sterilization of suspensions has not been validated. * The process for sterilizing empty vials and septums lacks established critical parameters (time, [b] (4) exposure) and loading patterns.

**Aseptic Technique and Media Fill Deficiencies:** * No written procedures establish operator aseptic technique (e.g., glove changes, sanitization frequency) during aseptic filling. * Media fill studies (SOP #7.1) are not representative of actual operations, using different vial sizes, colors, and lower fill volumes than routine production.

**Process Control and Stability