3990511

Mixing characterization for low pH viral inactivation across scales: Challenges to replicating poor mixing at benchtop-scale

Date
March 19, 2024
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Low pH virus inactivation (VI) is a widely used step in the downstream purification of monoclonal antibodies. Affinity eluate pH is lowered by an acidic titrant, held for a minimum time to inactivate acid-labile viruses, then neutralized prior to further processing. For proteins which are prone to low pH aggregation, scale-up poses significant challenges, as poor mixing can result in aggregate formation. Developing a small-scale model would reduce both the amount of material, and the turnaround time required to assess the impact of poor mixing on product quality. 95% blend time was used as the scaling parameter instead of power per unit volume due to the geometric differences of the vessels and agitators between the large and small scales.

In this work, a variety of equipment used for low pH virus inactivation, ranging from 50mL to 1000L scale, was characterized using 95% blend time It was shown to be effective method in de-risking processing performance when scaling mixing from 1000L to 50L. However, mixing conditions which were shown to have an impact on product quality could not be reproduced at the benchtop scale (< 100mL). The insights from these experiments will be used to highlight the challenges that can be encountered when trying to model mixing at benchtop scale and propose mitigation strategies which can be leveraged when developing a low pH virus inactivation process.

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