Mechanistic modeling of cation exchange chromatography scale‐up considering packing inhomogeneities

Abstract

In process development and characterization, the scale-up of chromatographic steps is a crucial part and brings a number of challenges. Usually, scale-down models are used to represent the process step, and constant column properties are assumed. The scaling is then typically based on the concept of linear scale-up. In this work, a mechanistic model describing an anti-Langmuirian to Langmuirian elution behavior of a polypeptide, calibrated with a pre-packed 1 ml column, is applied to demonstrate the scalability to larger column volumes up to 28.2 ml. Using individual column parameters for each column size, scaling to similar eluting salt concentrations, peak heights, and shapes is experimentally demonstrated by considering the model's relationship between the normalized gradient slope and the eluting salt concentration. Further scale-up simulations show improved model predictions when radial inhomogeneities in packing quality are considered.

Standardized approach for accurate and reliable model development of ion‐exchange chromatography based on parameter‐by‐parameter method and consideration of extra‐column effects

“…which is the basis of the self-association isotherm. [40,[54][55][56] However, the current interpretation was in conflict with the previously accepted explanation based on the same molecular weight.…”

“…For the system where the mole fraction of monomers was twice that of dimers, [ 8,34 ] the relationship can be rewritten as ν D + σ D ≈ 2( ν M + σ M ), which is the basis of the self‐association isotherm. [ 40,54–56 ]…”

“…Model reliability plays a crucial role in enhancing the dependability of model-assisted decisionmaking. Model-assisted decision-making has found widespread applications in the field of IEC, such as process optimization, [37] process characterization, [38] process scale-up, [25,39,40] and process control. [41] It is essential to consider the normativity and standardization of model development in IEC processes.…”