16/17 May 2023
An FDA inspection in February 2022 at Calgene BioPharma, LCC in Baltimore, a subsidiary of Emergent BioSolutions, resulted in a serious Warning Letter by the FDA on August 10, 2022. Warning Letters by FDA reference appropriate chapters in 21 CFR Part 211. In this case, chapters 21 CFR 211.67(a) and (b) and 21 CFR 211.113(b). Part 1 dealt with particulate contaminants. Part 2 of the news addresses inadequate cleanroom behaviour by company employees.
"Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b))."
The inspector observed inadequate aseptic working techniques by operators while performing interventions during production. Observations included the following:
What was further criticised:
Overall, the FDA lacked a robust concept of operations with appropriate procedures and also sufficient staff discipline.
The firm's response that it had made appropriate improvements in its programme to monitor personnel in the aseptic area was not sufficient for the FDA. From FDA's perspective, what was missing was:
Further expected is an independent evaluation with regard to:
It is expected that a detailed remediation plan with appropriate timelines will be prepared and submitted for this purpose.
Overall a very serious Warning Letter which puts the company's global ability to manufacture in accordance with GMP under scrutiny. Repeated deviations to an inspection in 2021 were criticised. The inefficient quality system with regard to cGMP was also criticised, in particular the lack of an efficient quality oversight system. The "recommendation" of qualified consultants indicates that the FDA does not expect an adequate internal solution to the problems. Corresponding sanctions in case of non-fulfilment of the demands were considered.
Source: FDA Warning Letter to Cangene BioPharma, LLC dba Emergent BioSolution dated10/8/2022.