Adaptation to high throughput batch chromatography enhances multivariate screening.
High throughput process development offers unique approaches to explore complex process design spaces with relatively low material consumption. Batch chromatography is one technique that can be used to screen chromatographic conditions in a 96-well plate. Typical batch chromatography workflows examine variations in buffer conditions or comparison of multiple resins in a given process, as opposed to the assessment of protein loading conditions in combination with other factors. A modification to the batch chromatography paradigm is described here where experimental planning, programming, and a staggered loading approach increase the multivariate space that can be explored with a liquid handling system. The iterative batch chromatography (IBC) approach is described, which treats every well in a 96-well plate as an individual experiment, wherein protein loading conditions can be varied alongside other factors such as wash and elution buffer conditions. As all of these factors are explored in the same experiment, the interactions between them are characterized and the number of follow-up confirmatory experiments is reduced. This in turn improves statistical power and throughput. Two examples of the IBC method are shown and the impact of the load conditions are assessed in combination with the other factors explored.
Biologics Process Development, Bristol-Myers Squibb, Bloomsbury, NJ, USA. gregory.barker@bms.com.
Gregory A
GA
Barker
Biologics Process Development, Bristol-Myers Squibb, Bloomsbury, NJ, USA.
Joseph
J
Calzada
Biologics Process Development, Bristol-Myers Squibb, Bloomsbury, NJ, USA.
Sibylle
S
Herzer
Biologics Process Development, Bristol-Myers Squibb, Bloomsbury, NJ, USA.
Siegfried
S
Rieble
D001709:Biotechnology; D002845:Chromatography / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods*; D015999:Multivariate Analysis; D011994:Recombinant Proteins
D011994:Recombinant Proteins
High throughput process development (HTPD); Iterative batch chromatography; Multivariate screening; Purification process development; Resin screening