FDA 483 - Cantrell Drug Company - March 22, 2018

The FDA Form 483 details multiple deficiencies at a compounding facility producing sterile injectable drug products. Investigations into unexplained discrepancies did not extend to other potentially affected products. The quality control unit failed to adequately investigate environmental monitoring (EM) excursions and trends, including viable organism recoveries on laptop keyboards in ISO-7 areas (Aspergillus spp., Staphylococcus auricularis, Staphylococcus spp.) and from employee gowns. Corrective actions for these issues were inadequate, and nearby products in ISO-5 hoods were not rejected.

Viable organisms (Staphylococcus hominis, Talaromyces rugulosus, Sclerotinia sclerotiorum) were also found in ISO-5 laminar flow hoods, with no identified root cause, and a plenum space above the ISO-7 cleanroom was not periodically cleaned. Smoke studies in August 2017 confirmed turbulent flow and stagnant air in ISO-7 gowning rooms, and technicians wore "street" shoes with fiber cloth covers inside the cleanroom.

The firm lacked an internal protocol to track and trend results from a third-party consultant reviewing batch records, and failed to include or reference email documentation of deficiencies found by the consultant. The firm did not follow its change control procedure for the differential pressure monitoring system, and its procedure for monitoring classified areas failed to require documentation of daily control chart reviews and conclusions.

An instrument used for sterility testing produced anomalous negative control results without investigation or trending. Out-of-specification (OOS) results from a contract testing