Application of multivariate analysis toward biotech processes: Case study of a cell-culture unit operation

BIOT 112

Anurag S. Rathore, arathore@amgen.com and Alime Kirdar, akirdar@amgen.com. Amgen, Inc, One Amgen Center Drive, Thousand Oaks, CA 91320
This talk will focus on examination of the feasibility of using multivariate data analysis (MVDA) for supporting some of the key activities that are required for successful manufacturing of biopharmaceutical products. These activities include process scale-up, comparability, characterization and fault diagnosis. Multivariate data analysis and modeling were performed using representative data from small-scale batches (2L) and large-scale batches (2000L) manufactured with a cell-culture process. Several input parameters (pCO2, pO2, glucose, pH, lactate, ammonium ions) and output parameters (purity, viable cell density, viability, osmolality) were evaluated in this analysis. Score plots, loadings plots and VIP plots were utilized for assessing scale-up and comparability of the cell-culture process. Batch control charts were found to be useful for fault diagnosis during routine manufacturing. Finally, observations made from reviewing VIP plots were found to be in agreement with conclusions from process characterization studies demonstrating the value of MVDA as a tool for extracting process knowledge.