Quality by digital design in action: a workflow for crystallisation and isolation

This paper exemplifies a Quality by Digital Design (QbDD) workflow for the crystallisation and isolation of active pharmaceutical ingredients (APIs). QbDD uses a digital first approach to improve manufacturability and sustainability whilst assuring product quality within practical constraints. This study uses three exemplar compounds (ibuprofen, lamivudine, and AZD0837), each of which presents a different challenge for crystallisation; these include agglomeration, solid state form, and slow growth rates, respectively. These cases are used to evaluate the benefits of the QbDD approach and identify gaps for future research. Results of this work show that the QbDD workflow reduces the number of physical experiments by 28% and the API material usage by 52-65% when compared to comparable API development processes not using this approach. This approach provides a route to practically implement and exploit the benefits of digital tools and overcome digital skill shortages. By exploiting digital tools for process simulation and optimisation, the workflow improves efficiency, even in complex cases where multiple workflow iterations are required. This workflow, therefore, paves the way for more sustainable and cost-effective API production and it promotes future standardisation of digital design in pharmaceutical development.