• Model development
  • Process development
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  • IEX
  • |
  • VLP

Model-based process development for virus-like particles

Computer-guided optimization of the purification of a virus-like particle

Ebola, malaria and influenza are highly pathogenic viruses and organisms that challenge the global health system. Virus-like particles (VLPs) are promising candidates in the fight against these diseases. VLPs are protein assemblies without any genetic material, which mimic the structure of viruses or present viral surface proteins. They are produced by recombinant systems such as bacteria, yeast, plant or insect cells. To remove host cell impurities after production, a suitable downstream process must be developed.

Graph to the case study Model-based process development for virus-like particles
Figure: Comparison of measured (dotted lines) and simulated (solid lines) UV measurements with a 30 CV salt gradient for complex VLP feedstock on the AEX membrane capsule. Feedstock was divided into 16 contaminant species (grey lines) and the product (red lines).

How to find an adequate purification process

There is no platform process available for purifying VLPs. The search for a fast and robust purification process is a challenge due to complex biological feedstock that contains components of unknown size and concentration. Currently, no downstream platform process exists for VLPs. In the given case study, an experimentally developed purification process for a Sf9-insect-cell-derived VLP is optimized via a model-based approach. Not only the experimental approach, but also the modeling of mass transfer is aggravated by the presence of uncertainties such as the unknown feed composition.

Process modeling based on UV absorption instead of molar concentration

The purification process was modeled by means of a lumped-rate model in combination with the stoichiometric displacement model. Measured UV peaks were then utilized to calibrate a model using an inverse peak fitting method. Using this method, it is possible to identify an arbitrary number of unknown parameters at the same time – in particular the unknown feed composition. Afterwards, the salt concentrations of a step elution process were varied to evaluate the effect on purity and yield and to identify an optimal process set-up.

Chromatography modeling is a valuable design tool for the process development of VLPs

In-silico process modeling and simulation were performed to control and predict the purification process of the VLPs. In a later optimization procedure, optimal process parameters were identified to enable the separation of the VLPs from the majority of impurities with minimal experimental effort.

See full paper “Modeling and simulation of anion-exchange membrane chromatography for purification of Sf9 insect cell-derived virus-like particles