(699c) A PAT Story – Classical Approaches and Recent Developments

It has been more than 20 years ago, when the FDA launched their initiative on process analytical technology (PAT) [1]. Since then pharmaceutical manufacturing approaches have changed significantly. Continuous approaches have more and more substituted the traditional batch paradigm including flow synthesis of the drug substance and turn-key lines for solid dosage products. Modular, high-speed and end-to-end manufacturing have been implemented, together with personalized manufacturing. In its first decade PAT was mainly used for data collection to increase process understanding and to support quality control at a low level control strategy [2] by substituting or supporting off-line in-process controls. With the requirements of integrated process routes, the objective of PAT has changed to deliver information for real-time process control actions and for real-time release testing (RTRT). In addition, many PATs have been developed for specific applications and the related critical quality attributes (CQAs).

This talk will give an overview on the state of the art application of PAT. Examples of novel PAT tools will be shown, but also PAT in a wider field of view. Soft sensors will be presented, which are not only a surrogate for classical hard sensors, but rather an essential part of a comprehensive in-line monitoring strategy. By combining data from equipment, univariate and multi-variate sensors, CQAs like the dissolution profile can be predicted, which are conventionally only accessible via time- and cost-intensive laboratory analysis. Feeding closed-loop controllers , PAT becomes an enabler for the highest level control strategy. Finally, a digital RTRT strategy will be presented, in which comprehensive data from a fully integrated continuous manufacturing line is matched with specific amounts of product. At the end of the manufacturing cycle, the complete history of process conditions is digitally available for each specific amount of product.

[1] United States Food and Drug Administration, CDER, 2004. Guidance for industry, PAT—A Framework for Innovative Pharmaceutical Development, Manufacturing, and Quality Assurance. Rockville.

[2] Yu, L.X., Amidon, G., Khan, M.A., Hoag, S.W., Polli, J., Raju, G.K., Woodcock, J., 2014. Understanding Pharmaceutical Quality by Design. AAPS J. 16, 771-783. doi: 10.1208/s12248-014-9598-3.