Vaccines are composed of large molecules with complex structures. Vaccine antigens are defined by their structurally derived product quality attributes. The process conditions used during manufacture may influence or impact those product quality attributes. The ability to predict and model the effects of process conditions on product quality prior to GMP manufacture is critical to the success of a technology transfer. Process development must, therefore, allow generating extensive knowledge about the impact of process conditions on product characteristics, in-depth experience with all of the operations at both the laboratory and commercial scale, and a deep understanding of how laboratory results translate to production performance. In that sense, expertise in process modelling is crucial for the successful development of vaccines processes. Effective scale-down models are designed to accurately predict the performance of production-scale runs, and thus allow rapid development and optimization of processes in preparation for scale up and transfer to the manufacturing facility. Once a process is transferred to manufacturing, the scale-down model is further used to support and rationalize the validation strategy and to assess the impact of process changes. This being said, the modelling and accurate scale-down definition of unit operations is not always obvious and straightforward. But once achieved, the benefits of such approach are multiple and in particular with regards to savings in terms of products, costs, time, ressources and commercial capacity. Using concrete examples of vaccine drug product and adjuvant formulation, the proposed presentation will show case-studies where Quality by Design approaches including scale-down modelling and design space definition were used to support not only the process development but also the full Process Performance Qualification (PPQ) strategy definition encompassing product impact, homogeneity validation and holding time validation. It will show how these approaches have increased the overall success of new product transfer in commercial facilities and will present some of the challenges encountered in the scale-down definition and the mitigation strategies implemented to ensure successful implementation.

Use of modelization and scale-down models to support drug product development and transfer to manufacturing facilities: Challenges and benefits

255th National Meeting (2018)

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