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Rapid optimization of processes for the integrated purification of biopharmaceuticals
Author(s) -
Crowell Laura E.,
Rodriguez Sergio A.,
Love Kerry R.,
Cramer Steven M.,
Love J. Christopher
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27767
Subject(s) - elution , column (typography) , process development , yield (engineering) , process (computing) , chromatography , quality by design , computer science , in silico , process optimization , process engineering , chemistry , biochemical engineering , materials science , engineering , telecommunications , biochemistry , frame (networking) , environmental engineering , particle size , metallurgy , gene , operating system
Straight‐through chromatography, wherein the eluate from one column passes directly onto another column without adjustment, is one strategy to integrate and intensify manufacturing processes for biologics. Development and optimization of such straight‐through chromatographic processes is a challenge, however. Conventional high‐throughput screening methods optimize each chromatographic step independently, with limited consideration for the connectivity of steps. Here, we demonstrate a method for the development and optimization of fully integrated, multi‐column processes for straight‐through purification. Selection of resins was performed using an in silico tool for the prediction of processes for straight‐through purification based on a one‐time characterization of host‐cell proteins combined with the chromatographic behavior of the product. A two‐step optimization was then conducted to determine the buffer conditions that maximized yield while minimizing process‐ and product‐related impurities. This optimization of buffer conditions included a series of range‐finding experiments on each individual column, similar to conventional screening, followed by the development of a statistical model for the fully integrated, multi‐column process using design of experiments. We used this methodology to develop and optimize integrated purification processes for a single‐domain antibody and a cytokine, obtaining yields of 88% and 86%, respectively, with process‐ and product‐related variants reduced to phase‐appropriate levels for nonclinical material.