FDA 483 - Apothecure, Inc - April 16, 2013

The FDA Form 483 details numerous deficiencies observed during an inspection of a facility manufacturing sterile injectable drug products.

**Key Violations and Observations:**

* **Incomplete/Absent Investigations:** The firm failed to thoroughly investigate sterility (plate contamination or endotoxin) failures for at least 28 lots and potency failures for at least 45 lots of injectable drug products between March 2012 and March 2013. Three lots with inconclusive sterility results were distributed without further investigation. Investigations for at least 110 lots containing fibers/particulates were also not conducted. * **Aseptic Processing Deficiencies:** * Procedures to prevent microbiological contamination, including validation of aseptic processing, were not established or followed. * Sterilization processes for injectable drug products and components (e.g., vials, stoppers) were not validated (e.g., lack of temperature distribution/heat penetration studies for autoclaves, no integrity testing on post-filters). * Use of non-sterile components (e.g., non-sterile filter, non-shedding data for filter not provided). * Smoke studies in ISO 5 hoods were not conducted under dynamic conditions. * Poor aseptic technique observed (e.g., technician using non-sterile gloves, mask, gown in ISO 5 area; uncovered sterile product transferred through ISO 7 area; non-sterile glo