Nikolaos Dimitrios Psaraftis

University

Technical University of Denmark (DTU)

Company

Novo Nordisk A/S

Project title

Downstream impact of crystallization process in an API purification production: Characterization and sensitivity analysis of crystallization process and subsequent drying step.

Project description

A typical process for the core production of an API – Insulin consists of three main stages: fermentation, recovery and purification.
In the final step of the purification process the API is dried to prepare the active ingredient for formulation of the drug product. The incoming material of this step are crystals formed in the previous step, depending on the particle-structure formed by this process the properties of the slurry fed into the drying process can also change.
In the current state, while the quality of the product has not been impacted, observations on the performance and yield of the drying step have been experienced. Indications show them to be related to the crystallisation step. Due to these steps being the final steps of the purification process, experimenting with the process is undesired.
In lab scale it will be possible to examine how properties such as, temperature, pH, or salt concentration, in different phases of the crystallisation (e.g., nucleation and growth), impact the final crystals. The crystals can be re-dissolved and transferred to a lab scale freeze-drier to see how the drying process develops over time. By repeating the experiment with different property settings for the crystallization process, a sensitivity analysis of the drier’s performance can be executed with the objective is to better understand the design space for crystallization applied to downstream processing.