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

Area of Science:

• Pharmaceutical Manufacturing
• Process Chemistry
• Digital Transformation

Background:

• Traditional active pharmaceutical ingredient (API) development faces challenges in manufacturability and sustainability.
• Current processes often require extensive physical experimentation, leading to material waste and increased costs.
• Integrating digital tools can optimize API crystallization and isolation, improving efficiency and product quality.

Purpose of the Study:

• To exemplify a Quality by Digital Design (QbDD) workflow for API crystallization and isolation.
• To evaluate the benefits of QbDD in terms of experimental reduction and material savings.
• To identify areas for future research in digital pharmaceutical development.

Main Methods:

• Application of a QbDD workflow to three exemplar compounds with distinct crystallization challenges (agglomeration, solid-state form, slow growth).
• Utilizing digital tools for process simulation and optimization within the QbDD framework.
• Comparative analysis against traditional API development processes.

Main Results:

• The QbDD workflow reduced physical experiments by 28% compared to conventional methods.
• API material usage was decreased by 52-65% through the QbDD approach.
• Improved efficiency was observed, even in complex cases requiring multiple workflow iterations.

Conclusions:

• The QbDD workflow offers a practical route to implement digital tools in pharmaceutical development, addressing skill shortages.
• This approach leads to more sustainable and cost-effective API production.
• The study promotes the standardization of digital design in the pharmaceutical industry.