Sanquin Plasma Products – FDA Warning Letter, Jun 4, 2013

The FDA issued a Warning Letter to Sanquin Plasma Products and C.A.F. – D.C.F. following inspections from May-June 2013, citing significant deviations from CGMP requirements in the manufacture of the licensed biological product Cinryze.

At Sanquin Plasma Products, violations included failure to withhold components until quality control testing (e.g., bioburden testing of incoming batches from C.A.F.-D.C.F.), failure to follow test procedures leading to incorrect tests and OOS results attributed to human error, and failure to follow stability testing programs (e.g., missed start times and testing time points). Significant deviations in intermediate manufacturing included uninvestigated recurring filtration blockages, ineffective CAPAs for container leaks and production deviations (e.g., broken stirrers), and lack of procedures for investigating process adjustments during nanofiltration. Process validation deficiencies were noted for nanofiltration time, filter changes, and mixing speeds. The company also failed to perform leachable/extractable studies for storage containers, inadequately validated container sealing processes, and lacked adequate segregation of intermediates. Laboratory control issues included failure to follow bioburden testing SOPs and uninitiated/delayed OOS investigations. Equipment deficiencies included lack of or inadequate preventive maintenance for sealing equipment and freezers.

At C.A.F. – D.C.F., violations included inadequate investigation of 44 rejected batches due to endotoxin failures, failure to investigate