Mode and dosage time in polyethylene glycol precipitation process influences protein precipitate size and filterability

• DOI: 10.1016/j.procbio.2022.01.017
• Publication Date: 2022-01-21T16:18:44Z
• Authors: Maria del Carme P...; Jean-Luc Beulay; Eric Valery; Alois Jungbauer; Peter Satzer
• Keywords: Filtration (mathematics); Particle (ecology)

Precipitation has gained interest as alternative to the costly protein A chromatography for monoclonal antibody purification. Traditional precipitation processes are based on direct addition of precipitant in a single dose, with limited control co-precipitation impurities and not considering batch-to-batch variations. We propose gradual dosage polyethylene glycol prevent resulting floc size. used focused beam reflectance measurement demonstrate that PEG6000 time final concentration significantly changes particle size distribution (PSD). demonstrated stepwise was superior conventional batch PEG precipitation, improving product yield purity by factor 4 HCP removal, samples pre-treated CaCl2 caprylic acid. studied 3D structure precipitates fractal dimension showed exhibited different compactness density depending time, filterability tangential flow filtration depth filtration. To switch from continuous addition, needs be considered due its high impact process performance. Focused (FBRM) can adjust methodology improve quality attributes inform about design further purification steps.