期刊
MABS
卷 10, 期 7, 页码 945-950出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2018.1505178
关键词
PAT; aggregation; MALS; chromatography; process control
For many protein therapeutics including monoclonal antibodies, aggregate removal process can be complex and challenging. We evaluated two different process analytical technology (PAT) applications that couple a purification unit performing preparative hydrophobic interaction chromatography (HIC) to a multi-angle light scattering (MALS) system. Using first principle measurements, the MALS detector calculates weight-average molar mass, M-w and can control aggregate levels in purification. The first application uses an in-line MALS to send start/stop fractionation trigger signals directly to the purification unit when preset M-w criteria are met or unmet. This occurs in real-time and eliminates the need for analysis after purification. The second application uses on-line ultra-high performance size-exclusion liquid chromatography to sample from the purification stream, separating the mAb species and confirming their M-w using a mu MALS detector. The percent dimer (1.5%) determined by the on-line method is in agreement with the data from the in-line application (M-w increase of approximately 2750 Da). The novel HIC-MALS systems demonstrated here can be used as a powerful tool for real-time aggregate monitoring and control during biologics purification enabling future real time release of biotherapeutics.
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