Leachables analysis from a closed connected single-use mAb purification process

Abstract

During a closed connected single-use monoclonal antibody (mAb) purification process, samples for leachables screening were gathered from two parallel processes (using different capturing chromatography), from perfusion culture to final storage bags. These samples were prepared and analyzed using screening methods for HS-GC-MS, GC-MS, LC-QToF/ESI pos and neg, to be able to identify a broad spectrum of leachables. The identified compounds were sorted into sample points from different steps of the mAb process, compared with available extractables data, and mapped from the process equipment used. It was therefore possible to compare leachables with extractables and at the same time follow the appearance and disappearance of leachables during the process. A large number of leachables could be detected, many which were predicted by the extractable mapping and explained by the utilized single-use equipment, e.g., several ethylene glycols and laurolactam, increasing after a filtrations but decreasing during the next process step. The data verifies that the purification process contains several sinks for leachables, which is a common assumption when risk-assessing extractables and leachables. The vast majority of identified leachables were removed as quickly as they were released, with the logical exception of leachables from the final storage bags plus the material and processes associated with the final step of the process.