title: Multivariate statistical monitoring as applied to clean-in-place (CIP) and steam-in-place (SIP) operations in biopharmaceutical manufacturing.
abstract: Multivariate statistical process monitoring (MSPM) is becoming increasingly utilized to further enhance process monitoring in the biopharmaceutical industry. MSPM can play a critical role when there are many measurements and these measurements are highly correlated, as is typical for many biopharmaceutical operations. Specifically, for processes such as cleaning-in-place (CIP) and steaming-in-place (SIP, also known as sterilization-in-place), control systems typically oversee the execution of the cycles, and verification of the outcome is based on offline assays. These offline assays add to delays and corrective actions may require additional setup times. Moreover, this conventional approach does not take interactive effects of process variables into account and cycle optimization opportunities as well as salient trends in the process may be missed. Therefore, more proactive and holistic online continued verification approaches are desirable. This article demonstrates the application of real-time MSPM to processes such as CIP and SIP with industrial examples. The proposed approach has significant potential for facilitating enhanced continuous verification, improved process understanding, abnormal situation detection, and predictive monitoring, as applied to CIP and SIP operations.
authors.affiliation: Amgen Inc., Operations Improvement, Industrial Engineering, W. Greenwich, RI, 02817.
authors.forename: Kevin
authors.initials: K
authors.lastname: Roy
authors.forename: Cenk
authors.initials: C
authors.lastname: Undey
authors.forename: Thomas
authors.initials: T
authors.lastname: Mistretta
authors.forename: Gregory
authors.initials: G
authors.lastname: Naugle
authors.forename: Manbir
authors.initials: M
authors.lastname: Sodhi
mesh_terms: D001702:Biopharmaceutics; D001709:Biotechnology / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D015999:Multivariate Analysis; D013227:Steam; D013242:Sterilization / Q000379:methods*
chemical_list: D013227:Steam
keywords: biopharmaceutical manufacturing; clean-in-place; continued verification; multivariate statistical process monitoring; steam-in-place