(645e) Ibrance® Capsule Commercial Process: Designed for Robustness

The commercial manufacturing process of Ibrance® (palbociclib) capsules was redesigned to ensure the quality attributes met or exceeded the Quality Target Product Profile (QTPP). The optimized process was established based on parameter ranges from process understanding achieved through multivariate and univariate analysis of small scale development trials, and computational modeling tools. The registration stability and clinical supply manufacturing campaigns, were utilized to broaden the process parameter ranges, establish process understanding, and ultimately define the proven acceptable ranges for the commercial manufacturing process.

During the registration stability and clinical supply manufacturing campaigns, an edge of failure was identified for the quality attribute of stratified capsule dissolution. The impact on dissolution was only observed at the end of the encapsulation run. It was determined that the edge of failure was an encapsulation processing tail-end effect which was associated with the original design/operation of the encapsulator hopper and powder feed system. Three engineering design modifications were identified and implemented to remediate the issue, and subsequently tested in a number of additional clinical and commercial scale capsule batches. Optimization of the encapsulator hopper and feed system defined the equipment design modifications that ensure consistent product performance throughout the entire batch.