Biopharmaceutical manufacturing processes are inherently complex due to their nonlinear bioprocess dynamics, variability in batch operations and manufacturing schedule, raw materials involved, and automatic process control. A typical processed lot generates large amounts of data that need to be analyzed and interpreted for process troubleshooting and continuous improvement purposes in addition to product release. Multivariate batch process modeling, monitoring and control approaches in real-time are elaborated by providing industrial examples from the commercial manufacturing processes. Examples and opportunities in cell culture (e.g., bioreactor applications) and purification (e.g., large-scale chromatography) operations are summarized. Impact of process analytical technologies (PAT), soft-sensor development, first principles modeling applications and commercial-scale examples are presented. (C) 2010 Elsevier Ltd. All rights reserved.