FDA 483 - Rentschler Biopharma SE - February 15, 2022

On February 11, 2022, an FDA inspection observed deficiencies in the simulated fill process for a (b)(4) drug substance into (b)(4) bottles. The pump dispensing the drug substance lacked an RPM specification and documentation of its setting. The bottle capping process, performed by hand, did not apply the manufacturer's recommended torque of (b)(4), failing to ensure an integral seal.

Discoloration was noted on (b)(4) and (b)(4) below the (b)(4) assembly, with an unknown root cause and no formal risk assessment or corrective action. Laboratory procedures for endotoxin testing lacked a time limit. The (b)(4) drug substance excipient, (b)(4), was not adequately controlled, with no risk or analytic assessment of potential (b)(4) formation.

Equipment and facility systems lacked adequate validation. Seven (b)(4) incubators had no chamber distribution or penetration profile assessments. (b)(4) hold tanks for (b)(4) lacked validation for hold time from a microbiological control perspective, and no procedure described the hold time limit. (b)(4) stored in (b)(4) areas were not validated for their storage conditions. A sanitized (b)(4) system lacked hold time validation. Routine requalification of worst-case loads was absent. Cleaning validation for parts washer performance failed acceptance criteria in two studies, with a third experiencing mechanical failure, not