FDA 483 Observations in 503B Outsourcing Facilities

In this issue, we will continue our review of FDA 483 observations in 503B outsourcing facilities; specifically, we will look at two categories of observations: "Environmental Monitoring" and "Cleaning, Disinfecting, and Deactivation."

ENVIRONMENTAL MONITORING (EM)

• Your firm failed to conduct investigations related to all mold recoveries during environmental monitoring.
• Your firm failed to conduct surface samples as outlined in your firm's written procedure.
• Your firm failed to justify the reduction of environmental monitoring frequencies of yeast and mold plates per your firm's written procedure.
• Your firm's written procedure for EM during aseptic operations is not representative of your firm's most challenging and/or stressful conditions.
• The firm does not have scientific justification for not monitoring environmental conditions throughout manufacturing operations with the ISO-5 LAF hood.
• The firm does not monitor the differential pressure of the ISO-5 LAF hood during manufacturing operations.
• Non-viable air sampling is not conducted during production.
• An unclassified room utilized during the production of sterile drug products, does not undergo routine environmental monitoring.
• Alarm systems to monitor for potential breaches in air quality are currently not employed.
• Alarms for monitoring the pressure differentials for the cleanroom are not handled according to the firm's written procedure.
• The monitoring for non-viable particulates is not located in close proximity to the aseptic operator.

CLEANING, DISINFECTING, AND DEACTIVATION

• Aseptic processing areas are deficient regarding the system for cleaning and disinfecting the room and equipment to produce aseptic conditions.
• Your firm has not established a cleaning validation to assure your cleaning process removes chemical and microbial residues on the equipment used in your aseptic operations.
• Your ISO-5 cleaning procedure does not address cleaning the inside of the acrylic view screens and front surfaces with the ISO-5 laminar air flow space.

More next week.