November 1-5, 2015
Process Analytical technologies (PAT) are a key component to fully leverage the success of continuous manufacturing. The timely measurement of critical quality attributes and critical process parameters assures that the desired product quality is being consistently manufactured and non-conforming material being identified. PAT tools can be utilized to meet the expectations for in-process monitoring, and allows for identification and isolation of rejected in-process materials. It further supports process development, as continuous and fast response of process to factor changes allows efficient experimentation and increases process understanding within the range of conditions studied during development. Ultimately, PAT will allow Real Time Release (RTR), reduces cost, timelines and manufacturing risk.
The presentation will address a comprehensive PAT concept for the overall continuous biomanufacturing process, through various novel and existing analytical technologies, which is addressing the critical needs of the process. The talk will elaborate on multiple upstream and downstream PAT examples, with one of them being the concept of utilizing online UPLC for multiple attributes throughout the process. The online measurement of titer for the monitoring of the ProA purification load will be presented in a case-study. In this study, the PATROL UPLC Process Analysis System from Waters was directly connected to the load feed-stream of an ÄKTA chromatography system for ProA purification. Continuous sampling and monitoring of titer has been successfully demonstrated.
A separate example will present an innovative approach of measuring pH through spectral measurements. Though potentiometric pH probes are commonly used in downstream processes, the drawbacks of the need for periodic recalibration (with consequent risk of product stream contamination), susceptibility to human calibration error, and slow response time, are of concern for sterile, continuous manufacturing systems over long periods of time. The presentation will address the proof of concept of measuring pH spectrally as alternative approach, which can be performed sterile and does not require frequent calibration. By using benign colorless extrinsic chromophores at low concentration, we demonstrated the feasibility of measuring pH within the desired accuracy (±0.10) as PAT application during low pH virus inactivation.
Eike Zimmerman, Jeff Goby, and Anoushka Durve, "PAT concepts for the process monitoring and control of continuous biomanufacturing" in "Integrated Continuous Biomanufacturing II", Chetan Goudar, Amgen Inc. Suzanne Farid, University College London Christopher Hwang, Genzyme-Sanofi Karol Lacki, Novo Nordisk Eds, ECI Symposium Series, (2015). http://dc.engconfintl.org/biomanufact_ii/96