title: Application of multivariate data analysis for identification and successful resolution of a root cause for a bioprocessing application.
abstract: Multivariate Data Analysis (MVDA) can be used for supporting key activities required for successful bioprocessing. These activities include process characterization, process scale-up, process monitoring, fault diagnosis and root cause analysis. This paper examines an application of MVDA towards root cause analysis for identifying scale-up differences and parameter interactions that adversely impact cell culture process performance. Multivariate data analysis and modeling were performed using data from small-scale (2 L), pilot-scale (2,000 L) and commercial-scale (15,000 L) batches. The input parameters examined included bioreactor pCO2, glucose, lactate, ammonium, raw materials and seed inocula. The output parameters included product attributes, product titer, viable cell density, cell viability and osmolality. Time course performance variables (daily, initial, peak and end point) were also evaluated. Application of MVDA as a diagnostic tool was successful in identifying the root cause and designing experimental conditions to demonstrate and correct it. Process parameters and their interactions that adversely impact cell culture performance and product attributes were successfully identified. MVDA was successfully used as an effective tool for collating process knowledge and increasing process understanding.
authors.affiliation: Process Development, Amgen Inc, Thousand Oaks, California, USA.
authors.forename: Alime Ozlem
authors.initials: AO
authors.lastname: Kirdar
authors.forename: Ken D
authors.initials: KD
authors.lastname: Green
authors.forename: Anurag S
authors.initials: AS
authors.lastname: Rathore
mesh_terms: D000465:Algorithms; D018929:Cell Culture Techniques / Q000379:methods*; D002468:Cell Physiological Phenomena; D003198:Computer Simulation; D008954:Models, Biological; D015999:Multivariate Analysis