Crystallization Working Group

Despite the plethora of experience that exists in the area of pharmaceutical crystallization, considerable gaps persist that limit the efficiency of crystallization development across the industry.  Given the widespread application of crystallization and the importance of API phase and attribute control, opportunities to improve our collective approaches to crystallization process development are viewed as good investment targets.

The team formed in early 2015 as a subteam of the International Consortium for Innovation and Quality in Pharmaceutical Development Enabling Technologies Working Group and spent 2015 framing opportunities and sharing practices in the field of pharmaceutical crystallization. Nine knowledge sharing themes were covered.  In October 2015, the team held a face-to-face meeting to review the discussions from the year and prioritize a list of collaboration opportunities.  In 2016, that list was whittled down to six top projects and proposals were written for each.  The top project revolved around the development of user-friendly population balance modeling (PBM) tools which conveniently utilize data inputs typically collected during lab-scale crystallization experiments.  The team developed a Request for Information (RFI) for this project in July (available here) and is currently evaluating responses.

The work of this group focuses around pharmaceutical crystallization, with interests ranging from modeling to reactor design to experimental tools that allow for more relevant measurements to be taken.  Proposed projects currently being advanced include:

  • Online tool for 2D/3D PSSD, with ability to integrate easily into models. The group is evualuating existing tools and conducting discussions with the lead vendor in this area.
  • Easily accessible population balance model utilizing available PAT input. An RFI issued and lead candidates interviewed for this project.
  • Screening tools for impurity rejection via crystallization in the solvent selection and design stage. The group is  working with the lead vendor to evaluate a screening tool and evolve capabilities.
  • Model tools to predict polymorphs and de-risk potential for more stable polymorph. This is tentatively moving forward as a Crystal Structure Prediction project.

Other projects currently paused in advancement include:

  • Offline analytical tools for PSSD
  • "Ideal" crystallization platform
  • Automated sampling and manipulation of slurries for analysis
  • Commercial HT polymorph screening kit with standard set oftemplating materials
  • In-situ seeding techniques (templates, bubbles, lasers, etc.)
  • Need for PAT at CMOs
  • Development of techniques for assessing physical stability that do not involve high T/RH that product will not see
  • Digital design from molecule to rationally designed API