Collaborative Initiative to Accelerate Process Development

In the upcoming March issue of BioProcess International magazine, there is a great article by Emerson’s Greg McMillan and Michael Boudreau, Broadley-James’ Trish Benton, and the University of Texas at Austin’s Yang Zang. The article, PAT Tools for Accelerated Process Development and Improvement, describes the collaborative effort between Emerson, Broadley-James, and UT, “…to examine and quantify the potential for faster optimization of batch operating points, process design, and cycle times.” The specific objective of this collaboration:

…is to show that the impact of PAT can be maximized through the integration of dynamic simulation and multivariate analytics in a laboratory-optimized control system during product development.

Greg and Michael are putting many of the ideas they described in their book, New Directions in Bioprocess Modeling and Control: Maximizing Process Analytical Technology Benefits, into practice.

The authors outline the challenge for the 400 biotechnology medicines currently in development, which require overlapping and iterative stages for process development and commercialization. These stages include:

…cell line selection and development, media optimization, process conditions optimization and verification, scale-up, project definition, and plant design.

This team is working on beta tests using this new dynamic model and on-line data analytics and wants to make the results fully public to promote wide use and to advance these concepts and methodologies.

If you’re like me and not in the biotechnology field, much of the article may get a little deep. I did glean a few tidbits you might find useful. By creating a dynamic model, one of the big benefits to the team is the ability to speed up the model by up to 1000 times real-time. Whether you’re simulating the growth of mammalian cell lines or have another slow process, this can really help reduce trial and error time.

Another key is that the model, configuration, and tools can run in the “virtual plant” PC environment or can be downloaded to the automation system. With proper scale up factors:

…the embedded tools go readily from bench-top bioreactors to pilot plants and eventually industrial-scale bioreactors.

With the recognition by the FDA that quality cannot be tested into products, which led to the creation of the Process Analytical Technology (PAT) initiative, the authors discuss the role of analytics in their efforts.

Principal component analysis (PCA) and projection to latent structures (PLS) are two multivariate analysis techniques that can help analyze continuous and batch process operations. The authors’ beta test is focusing on the on-line use of these analytical techniques where PLS detects deviations in quality parameters and PCA detects abnormal operations from measured and unmeasured disturbances.

Given the importance of new product development for pharmaceutical and biotechnology manufacturers, anything to reduce the overall development time and build in quality monitoring as prescribed in PAT should be a welcome addition.

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