Optimization‐based framework for resin selection strategies in biopharmaceutical purification process development

Liu, Songsong; Gerontas, Spyridon; Gruber, David; Turner, Richard; Titchener‐Hooker, Nigel J.; Papageorgiou, Lazaros G.

doi:10.1002/btpr.2479

Cited by 7 publications

(1 citation statement)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hughson, Cruz, Carvalho, and Castilho () utilized STP operation for rapidly purifying a labile glycoprotein without the use of intermediate hold tanks. Liu et al () designed a two‐step integrated polishing train for the removal of fragments and aggregates from a recombinant Fc‐fusion protein. Recently, we used a custom in silico tool to generate and rank integrated, straight‐through processes for efficient HCP removal from Pichia pastoris‐ derived feed stocks (Timmick et al, ).…”

Section: Introductionmentioning

confidence: 99%

A combined screening and in silico strategy for the rapid design of integrated downstream processes for process and product‐related impurity removal

Vecchiarello

Timmick

Goodwine

et al. 2019

Biotech & Bioengineering

View full text Add to dashboard Cite

Integrated designs of chromatographic processes for purification of biopharmaceuticals provides potential gains in operational efficiency and reductions of costs and material requirements. We describe a combined method using screening and in silico algorithms for ranking chromatographic steps to rapidly design orthogonally selective integrated processes for purifying protein therapeutics from both process-and product-related impurities. IFN-α2b produced in Pichia pastoris containing a significant product variant challenge was used as a case study. The product and product-related variants were screened on a set of 14 multimodal, ion exchange, and hydrophobic charge induction chromatography resins under various pH and salt linear gradient conditions. Data generated from reversed-phase chromatography of the fractions collected were used to generate a retention database for IFN-α2b and its variants. These data, in combination with a previously constructed process-related impurity database for P. pastoris, were input into an in silico process development tool that generated and ranked all possible integrated chromatographic sequences for their ability to remove both process and product-related impurities. Top-ranking outputs guided the experimental refinement of two successful three step purification processes, one comprising all bind-elute steps and the other having two bind-elute steps and a flowthrough operation. This approach suggests a new platform-like approach for rapidly designing purification processes for a range of proteins where separations of both process-and product-related impurities are needed. K E Y W O R D Shigh throughput process development, integrated downstream processing, mixed mode chromatography, process development tool, protein chromatography, straight-through processing

show abstract

Section: Introductionmentioning

confidence: 99%

A combined screening and in silico strategy for the rapid design of integrated downstream processes for process and product‐related impurity removal

Vecchiarello

Timmick

Goodwine

et al. 2019

Biotech & Bioengineering

View full text Add to dashboard Cite

show abstract

An impurity characterization based approach for the rapid development of integrated downstream purification processes

Timmick

Vecchiarello

Goodwine

et al. 2018

Biotech & Bioengineering

View full text Add to dashboard Cite

In this study, we describe a new approach for the characterization of process-related impurities along with an in silico tool to generate orthogonal, integrated downstream purification processes for biological products. A one-time characterization of process-related impurities from product expression in Pichia pastoris was first carried out using linear salt and pH gradients on a library of multimodal, salt-tolerant, and hydrophobic charge induction chromatographic resins. The Reversed-phase ultra-performance liquid chromatography (UPLC) analysis of the fractions from these gradients was then used to generate large data sets of impurity profiles. A retention database of the biological product was also generated using the same linear salt and pH gradients on these resins, without fraction collection. The resulting two data sets were then analyzed using an in silico tool, which incorporated integrated manufacturing constraints to generate and rank potential three-step purification sequences based on their predicted purification performance as well as whole-process "orthogonality" for impurity removal. Highly ranked sequences were further examined to identify templates for process development. The efficacy of this approach was successfully demonstrated for the rapid development of robust integrated processes for human growth hormone and granulocyte-colony stimulating factor.

show abstract

High throughput process development workflow with advanced decision-support for antibody purification

Stamatis

Goldrick

Gruber³

et al. 2019

Journal of Chromatography A

View full text Add to dashboard Cite

Optimization‐based framework for resin selection strategies in biopharmaceutical purification process development

Cited by 7 publications

References 50 publications

A combined screening and in silico strategy for the rapid design of integrated downstream processes for process and product‐related impurity removal

A combined screening and in silico strategy for the rapid design of integrated downstream processes for process and product‐related impurity removal

An impurity characterization based approach for the rapid development of integrated downstream purification processes

High throughput process development workflow with advanced decision-support for antibody purification

Contact Info

Product

Resources

About