FDA 483 - KRS Global Biotechnology, Inc - August 31, 2016

An FDA Form 483 was issued to an outsourcing facility, identifying significant deficiencies in their sterile drug product manufacturing and quality systems.

**Key Violations and Observations:**

* **Microbiological Contamination Prevention:** Procedures for preventing microbiological contamination of sterile drug products were not followed. Media fills in 2015 were limited, and no validation or media fills were performed for the lyophilization process used for injectable products like L-Asparaginase. * **Sterilization Validation:** Sterilization processes for stoppers, glassware, tools, and drug products (e.g., Carmine 75 mg/mL vials) were not adequately validated. This included a lack of established and documented parameters for sterilization by heat. This is a repeated observation from a 2014 FDA-483. Batch records lacked documentation of sterilization parameters and confirmation. * **Depyrogenation:** The depyrogenation SOP did not include critical parameters. * **Aseptic Processing Area Deficiencies:** * **Cleaning and Disinfection:** The cleaning and disinfecting SOP lacked specified contact times, frequency, and rotational schedules for cleaning agents. A sporicidal disinfectant was not used in ISO 5 hoods, and cleaning logs did not document the disinfectant used. Mop heads and buckets were not dedicated to specific cleanroom areas, and their sterilization was not validated. * **Equipment Maintenance:** Compounding equipment in ISO 5 and