Implementation of QbD principles requires defining acceptable ranges for critical quality attributes (CQAs) and performing process characterization studies to determine acceptable process parameter ranges that ensure that these CQA acceptable ranges are met. For cell culture and purification unit operation process characterization studies, CQA Target Ranges (CQA-TRs) are established for identification of critical process parameters and assessment of acceptable product quality. These CQA-TRs are derived from Drug Substance release acceptance criteria.  For CQAs that are impacted by the downstream manufacturing process, CQA-TRs may also be established through process linkage studies.  With this approach, unit operations are challenged with higher levels of these quality attributes than would be generated when operated within the target process parameter ranges. The process linkage assessment confirms the capability of the manufacturing process to produce product with acceptable levels of the quality attribute, even when challenged at worst-case CQA levels.  The work presented will describe how data was leveraged from process linkage studies executed at small-scale, as well as from manufacturing-scale runs, to establish CQA-TRs for the Drug Substance manufacturing process of a monoclonal antibody.  The application of any relevant scale or assay offsets to the CQA-TRs, which were established during qualification of the scale-down model, will also be presented.

Process linkage approach for establishing critical quality attribute target ranges

251st National Meeting (2016)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.