Rentschler Biopharma Inc. – FDA EIR, Dec 13, 2019

Rentschler Biopharma Inc. underwent an FDA inspection from December 4-13, 2019, as part of a Level II Good Manufacturing Practice (GMP) review under Compliance Program 7345.848 for biological drug products. The inspection revealed nine observations, primarily concerning the firm's quality and production systems for its biological drug substance manufacturing. Key violations included a failure to thoroughly review unexplained discrepancies, such as significant microbial excursions from personnel monitoring and the persistent recovery of unusual environmental isolates without adequate investigation into their source or the effectiveness of cleaning practices. Batch production and control records were found to be incomplete, lacking comprehensive manufacturing and control instructions. Instead, separate 'Process SOPs' dictated operations without being fully integrated or version-controlled within the batch records, making batch reconstruction and verification difficult. Further issues identified involved inadequate laboratory methods, specifically the absence of established hold times for streaked microbial plates prior to external identification, and deficient stability testing for sterile media and buffer solutions. Additional concerns encompassed insufficient controls for document issuance, inadequate equipment maintenance, various facility and GMP warehouse deficiencies, and a failure to ensure data accuracy and prevent omissions in records. Master production instructions also lacked complete details. In response, Rentschler Biopharma's management committed to providing a written response to the FDA's observations within 15 business days, outlining their corrective actions. Furthermore, the client, Takeda, was advised by the FDA to continuously monitor product potency data and report any necessary updates related to previously identified issues.