ABSTRACT

As with all of pharmaceutical production, the regulatory environment for the production of therapeutics has been changing as a direct result of the US FDA-initiated Quality by Design (QbD) guidelines and corresponding activities of the International Committee for Harmonization (ICH). Given the rapid growth in the biopharmaceutical area and the comp

Introduction. Regulatory Perspective of Innovative Process Development Incorporating PAT Tools. ICH QII Guidelines, impact on PAT. Quality-by-Design, Knowledge Management and Continuous Improvement. PAT - Desired State in Biologics Manufacturing. Miniaturization of Measurement Systems and Technology for improved process understanding and rapid screening. Raw Material Characterization via PAT tools. Rapid Microbial Methods and PAT. Glycosylation monitoring for therapeutic protein manufacturing. Real-time Multivariate Process Monitoring, Control and Optimization. First-principles modeling in combination with PAT (improved process understanding). Spectroscopic methods for Biologics manufacturing monitoring and control. On-line HPLC Applications in Cell Culture and in Purification Processes. Process chemometrics, multivariate modeling and analysis. Soft-sensors and their applications in biologics manufacturing. In-line/At-line/On-line Analytics, Sterile Sampling Systems. Drug substance and drug product (incl. lyophilization) PAT tools. Limitations and challenges of current measurement systems in PAT framework. Current state-of-the art in PAT tools for measuring CQAs in near real-time and future research needs. NIH, NFS and NIST Research Directions towards enabling PAT tools for biologics manufacturing end-point monitoring, control and real-time release opportunities. New sensor technologies and its impact on PAT. PAT Business Case Development, Implementation Challenges and Benefits. PAT as a Manufacturing Excellence Contributor, Its Relations to Lean Manufacturing. Future Directions in PAT.