Scale-up of batch manufacturing operations in the pharmaceutical industry often presents technical challenges and various risks. In this work, a case study describing the use of a discrete element method (DEM) model to study a batch blending process is described. This model was developed to (1) gain insight into undesirable blend uniformity results observed during the manufacture of a recent drug product registration batch and (2) to assess the risk associated with scaling-up the process. During execution of the pilot-scale registration batch, the team had observed the presence of a sub-potent region of the blend that was insufficiently mixed in addition to variability in the potency of stratified samples. The model has confirmed that poor blending is to be expected in this particular bin and visually depicts the presence of a “dead zone” where mixing does not occur due to the particular processing conditions used in the operation of this blender. The model also revealed that, by employing certain modifications to the process, a uniform blend could be achieved in this equipment. To assess the risk in scaling-up this process, the blending performance in the commercial scale bin was predicted to be satisfactory. Results from the commercial scale batch confirm that a well-mixed blend is in fact achieved in this equipment. The use of process models such as this enable scientists and engineers to better understand the process and the associated risks which help to enable successful drug product development and scale-up.
Professional Development Hours
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