(645f) Application of Integrated Modeling Approach for Quality-By-Design (QbD) Process Development of Lyophilization

Lyophilization has been one of the most important unit operations in drug-product processes involving biologics as it affords low temperature drying to produce stable product that is amenable to storage and transportation. In order to achieve successful scale-up and technology transfer of a lyophilization process from laboratory to manufacturing, it is imperative to understand the scale-up issues/challenges, specifically the equipment performance (capabilities and limitations) and the differences in manufacturing environment. These need proactive considerations in the process design during the development stages. Computational fluid dynamics (CFD) provides inexpensive option to assess process equipment performance across scales.

In this work, CFD modeling was employed to study laboratory and manufacturing scale lyophilizers to understand the equipment performance differences arising from design differences and their impact on the process performance. CFD models were utilized to study and predict chamber pressure and temperature as well as flow patterns and velocities. Coupling CFD with the one-dimensional heat and mass balance was used to predict product temperature for a given formulation (Tg’/collapse temperature) for both laboratory scale as well as manufacturing scale lyophilizers. A safe operational design space was constructed for a lyophilizer and product combination and utilized for quality-by-design (QbD) of lyophilization cycle scale-up and tech-transfer. We present here the CFD study on four lyophilizers at different scales coupled with two different formulations. The model predictions were verified using appropriate experiments. The design space provides flexibility to change/operate without revalidation as well as explanations for parameters excursions during operations.

Kushal Sinha, Ehab Moussa, Deliang Zhou, Madeleine Witting, Nandkishor Nere, Sherwin Shang, Mario Hirth, Martin Bultmann, Nupur Dutta, Ted Tharp, Feroz Jameel and Martin Gastens are employees of AbbVie. The design, study conduct, and financial support for this research was provided by AbbVie. AbbVie participated in the interpretation of data, review, and approval of the publication.