Endotoxin Test Concerns of Biologies Part II:Developing New Tools

摘要

Bacterial Endotoxin Test (BET) users seek ways to overcome low endotoxin recovery (LER) from direct spikes into undiluted biologies. These studies have come about from Chen's initial observation that Control Standard Endotoxin (CSE) spikes, when placed into undiluted biologies, buffers, and other constituents often cannot be recovered. By changing the endotoxin spike requirement from diluted product to undiluted product, users will unsurprisingly encountertest interference; what is unexpected from Chen's LER finding is that recovery sometimes cannot be improved by dilution. This is indicative of a still undefined binding phenomenon. Chen originally dismissed protein binding as a mechanism of LER as placebo with no protein of the same formulation also exhibited a low endotoxin spike recovery problem. However, we should not assume that the binding phenomenon with protein and without protein demonstrate the same mechanism of spike loss.