The warning letter dated May 12 came following a US Food and Drug Administration (FDA) inspection at the Irvine, California facility in May 2016.
Among the GMP violations cited by the Agency, B. Braun Medical’s quality control unit at the facility was pulled up on failures in investigating product defect complaints and manufacturing deviations related to 76 field alert reports (FAR) filed for parenteral drugs produced on the firm’s partial additive bag (PAB), Excel, and Titan XL lines.
“Of these FAR, 44 were related to customer complaints regarding visible particulate matter and leaking intravenous (IV) bags,” the Agency noted.
“While you opened investigations into these significant complaints, some investigations have been open for extended periods without resolution. Your failure to conduct prompt and thorough investigations, including ensuring CAPA effectiveness, prolonged patient exposure to potential hazards posed by defective products.”
While B Braun had implemented some measures to investigate customer complaints of bag leakage and mould contamination increased in its PAB line, for instance by increasing the in-process leak test pressure to improve the detection of PAB top-cap corner leaks, the Agency said the quality unit failed to ensure the test was adequate to detect these leaks and written procedures had not been updated.
“Container-closure integrity is imperative to ensure sterility of parenteral drugs, and manufacturing operations should be designed to prevent visible particle contamination.”
Pinhole Leak Detector
The firm was also accused of failing to routinely calibrate, inspect, or check according to a written program designed to assure proper performance of equipment used in the manufacture, processing, packing, and holding of a drug product.
For example, a Pinhole Leak Detector Machine used during inspection of finished drug products manufactured on PAB Line was not deemed adequately qualified:
“You lacked adequate qualification studies to demonstrate that the equipment is capable of detecting pinholes leaks. Corner pinholes comprise a large proportion of defects seen in your rejected PAB products. Some of these pinholes are as small as 127 microns. However, you qualified your equipment to detect pinholes greater than or equal to (b)(4) microns, approximately four times as large as known defects in your bags.”
The FDA inspected the facility in 2013, 2014, and 2015, and noted the 2016 inspection – which resulted in the warning letter – cited the same or similar GMP violations.