Berkshire Sterile Manufacturing, LLC – FDA EIR, Apr 13, 2018

An FDA pre-approval inspection of Berkshire Sterile Manufacturing, Inc. (BSM) was conducted from March 26 to April 13, 2018. The inspection, carried out under Compliance Program 7346.832 for sterile-filled small volume parenteral drugs, focused on BSM's readiness for commercial manufacturing of ANDA 210714 Isosulfan Blue Injection. This was the first FDA inspection for the contract manufacturer. The inspection revealed several significant issues, leading to a six-item FDA Form 483.

Key violations included a failure to consistently follow established quality procedures, deficiencies in cleaning, disinfection, and environmental monitoring practices, and a failure to calibrate critical manufacturing equipment in a timely manner. The firm also did not adequately establish the reliability of its critical component suppliers, as analytical evaluation to verify certificates for sterility or endotoxin levels was missing. Furthermore, an in-process bioburden test method was not validated prior to use, with validation activities occurring concurrently with the inspection. Other observations included an incomplete autoclave qualification and a lack of open-door recovery studies for stability chambers.

In response to the identified deficiencies, BSM management committed to submitting a written response to the FDA Form 483 within 15 business days, detailing their proposed corrective actions.