A quality by design study applied to an industrial pharmaceutical fluid bed granulation

The pharmaceutical industry is encouraged within Quality by Design (QbD) to apply science-based manufacturing principles to assure quality not only of new but also of existing processes. This paper presents how QbD principles can be applied to an existing industrial pharmaceutical fluid bed granulation (FBG) process. A three-step approach is presented as follows: (1) implementation of Process Analytical Technology (PAT) monitoring tools at the industrial scale process, combined with multivariate data analysis (MVDA) of process and PAT data to increase the process knowledge; (2) execution of scaled-down designed experiments at a pilot scale, with adequate PAT monitoring tools, to investigate the process response to intended changes in Critical Process Parameters (CPPs); and finally (3) the definition of a process Design Space (DS) linking CPPs to Critical to Quality Attributes (CQAs), within which product quality is ensured by design, and after scale-up enabling its use at the industrial process scale.The proposed approach was developed for an existing industrial process. Through enhanced process knowledge established a significant reduction in product CQAs, variability already within quality specifications ranges was achieved by a better choice of CPPs values. The results of such step-wise development and implementation are described.

Graphical abstractThis paper reports how the Quality by Design (QbD) principles can be applied to an existing industrial pharmaceutical fluid bed granulation process, using a three-step approach. Process analytical technology was implemented and the data generated treated with multivariate data analysis techniques. First, the variability of the industrial process was investigated, generating new process knowledge. Second, designed experiments were performed at a pilot scale to investigate the process response to changes in the Critical Process Parameters (CPPs). Finally, a Design Space (DS) for the process was defined, linking CPP to Critical to Quality Attributes (CQAs) of the granules, and after scale-up enabling its use at the industrial scale. Within the DS, it is assured the desired quality of the granules consistently.Figure optionsDownload full-size imageDownload high-quality image (150 K)Download as PowerPoint slide