The dream team for complying with Quality-by-Design: High throughput process development techniques and process modeling
Quality-by-Design demands can be fulfilled via mechanistic process understanding and/or a massive expansion of the database – for example, via high-throughput techniques such as batch chromatography. Mechanistic models strongly depend on model parameters which are commonly determined based on experimental data from lab-scale column runs.
Quantification of adsorber characteristics: column scale vs. batch systems
To improve the implementation of a process at different stages during its development, the same model should be applied for all scales and formats. Precise and uniform measurements of different column characteristics, such as ionic capacity, are necessary to allow a model-based scale comparison. The standard technique for determining the ionic capacity in column scale is acid-base titration. As this approach requires an in-line conductivity trace, the method is not applicable for high-throughput experimental systems such as batch chromatography.
Measuring histidine capacity to determine ionic capacity
An alternative method which can be used in both column and batch chromatography is the measurement of the total histidine capacity. The results of this non-invasive photometric method are comparable to conventional acid-base titrations in column scale.
Improved predictions of breakthrough using histidine-corrected parameters
By means of the presented method, the batch adsorber volumes could be corrected to generate more precise modeling parameters. Implementing these parameters, a column breakthrough curve could be modeled in ChromX from a single condition batch adsorption isotherm. Additionally, the presented case study can be extended to batch kinetics and batch bind-and-elute experiments.
With this approach, the importance of batch data in conventional and in-silico process development is increased.