Microbial Fermentation Scale Down Model Qualification – A Case Study

Development, characterization, and validation studies may be carried out using a scale-down model designed and operated using conditions, raw materials, and process parameters representative of the intended manufacturing-scale process. It is important to understand the degree to which the scale-down model represents the manufacturing-scale process, including any differences that might exist, as this may have an impact on the relevance of information (e.g. process parameter ranges derived during characterization studies, criticality of a process parameter) derived from the models. This case study will describe a scale-down model qualification effort intended to support a design space claim within a Quality by Design (QbD) submission. Discussion will include: 1) study design considerations; 2) defining practically significant differences between the scale-down model and manufacturing-scale process responses; 3) statistical analyses and outcomes; and 4) application and relevance of scale-offsets for predicting manufacturing-scale performance. In addition, some examples of frequent sources of offsets between scales will be discussed.