Computational prediction of blend time in a large-scale viral inactivation process for monoclonal antibodies biomanufacturing

Document Type

Article

Publication Date

1-1-2023

Abstract

Viral inactivation (VI) is a process widely used across the pharmaceutical industry to eliminate the cytotoxicity resulting from trace levels of viruses introduced by adventitious agents. This process requires adding Triton X-100, a non-ionic detergent solution, to the protein solution and allowing sufficient time for this agent to inactivate the viruses. Differences in process parameters associated with vessel designs, aeration rate, and many other physical attributes can introduce variability in the process, thus making predicting the required blending time to achieve the desired homogeneity of Triton X-100 more critical and complex. In this study we utilized a CFD model based on the lattice Boltzmann method (LBM) to predict the blend time to homogenize a Triton X-100 solution added during a typical full-scale commercial VI process in a vessel equipped with an HE-3-impeller for different modalities of the Triton X-100 addition (batch vs. continuous). Although direct experimental progress of the blending process was not possible because of GMP restrictions, the degree of homogeneity measured at the end of the process confirmed that Triton X-100 was appropriately dispersed, as required, and as computationally predicted here. The results obtained in this study were used to support actual production at the biomanufacturing site.

Identifier

85140470372 (Scopus)

Publication Title

Biotechnology and Bioengineering

External Full Text Location

https://doi.org/10.1002/bit.28264

e-ISSN

10970290

ISSN

00063592

PubMed ID

36224707

First Page

169

Last Page

183

Issue

1

Volume

120

Fund Ref

Bristol-Myers Squibb

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