Crystallization Process Development

API crystallization processes are often difficult to reproduce and especially challenging to scale. If not done well, crystal size distributions can vary, requiring additional processing to ensure uniformity and can cause down-stream processing issues such as filterability and formulation challenges. To develop a scalable crystallization process, it’s critical to evaluate crystallization dynamics across the various phases of API development. This provides maximum control over impurities, polymorphic forms, particle size, and agglomeration.

Cambrex takes a phase-appropriate approach to crystallization process development. Our initial crystallization development efforts typically focus on early-stage API, often following screening studies, with a focus on delivering a fit-for-purpose crystallization process that will result in a target form with high yields, purity, appropriate particle properties and process efficiency. As the molecule advances and specifications and constraints become tighter, we shift our attention to optimization/robustness studies (Design of Experiment, or DoE) of existing crystallization processes, drying studies, and formulation development. After launch, our experts remain available to support crystallization operations, often in a troubleshooting capacity.

We apply the same principles to peptide crystallization. As a CDMO with expertise in bringing complex molecules to the market, we understand that peptides are particularly challenging when it comes to crystallization process development. Successful scale-up relies on a robust crystallization process to control the thermodynamic and kinetic factors that impact the solid form.

Everything begins with our crystallization scientists and engineers, who bring decades of experience to every project. At their disposal are the latest modelling software and process analytical tools to understand how bench-scale processes will perform on much larger scales in the plant. Using our expertise in statistical design and modelling, our team is able to gain an in-depth understanding of the critical process parameters of the crystallization, understanding the operating space and ensuring process robustness. Our development programs are tailored to final APIs or process intermediates.