This BioPhorum paper contains feedback on the USP bioreactivity monographs to plastics used for manufacturing, and the use of resources. It also comments on the potential in vitro tests that should be included, the removal of the implantation test and safety, the removal of Class I to VI, and the topics for omission or inclusion into the <1031> chapter outline. The expert feedback provided in these documents aims to support the USP and, ultimately, produce documents that improve patient safety – but with adequate use of finite analytical resources, which would not be the case with divergent expectations.
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This paper contains feedback on the USP document Bacterial Endotoxin Test (BET): A USP Comparability Study of Recombinant Reagents (Recombinant Factor C and Recombinant Cascade) to Lysate Reagents (LAL). The paper comments on issues such as the feasibility of testing the recommended matrix using four different recombinant reagents and four different lysate reagents, and that water post-deionization (low-purity) but before distillation/ultra-filtration (high-purity) is not representative of samples typically tested for bacterial endotoxins. It also questions whether industry will be able to provide known contaminated samples as these would be difficult to obtain and then compare.
Container closure integrity (CCI): Container closure integrity control versus integrity testing during routine manufacturing
In 2014 uncertainty around regulation for container closure and integrity testing (CCIT) fed a perceptible shift in mindset across the industry, causing some concern amongst many subject matter experts in biological manufacturers. Their concern was that gaps in guidance was enabling skewed expectations such that they would promote 100% CCIT for the release of drug product batches. This paper addresses this concern by re-stating the principles of CCI, qualification, process control and in-process testing to establish the framework within all effective container closure integrity programs. It concludes that performing 100% CCIT does not provide certainty that a process is well controlled and introduces an additional step that is not always necessary or suitable for the high processing speeds in the industry.