STACY SHOLLENBERGER
Senior Manager, Process Analytical Technology, Merck KGaA, Darmstadt, Germany

Abstract

Process Analytical Technology (PAT) offers significant opportunities to improve process understanding and optimize product quality in biopharmaceutical manufacturing. Aim of the article is to provide an overview on PAT with a special focus on bioprocesses and highlight how Raman spectroscopy, in particular, is well-suited for applications in the biopharma sector due to its non-destructive nature, high molecular specificity, and ability to analyze multiple analytes simultaneously. These capabilities enable real-time monitoring of complex bioprocess solutions, facilitating optimization of product attributes and supporting process efficiency throughout the biopharmaceutical manufacturing workflow. Overall, PAT, with its emphasis on Raman spectroscopy, enhances process understanding and helps ensure consistent and high-quality biopharmaceutical production while also optimizing processes and saving time and resources.

WHAT IS PAT?
Process Analytical Technology (PAT) is a regulatory framework defined by the Food and Drug Administration (FDA) with the main intention to foster innovation and encourage the implementation of more efficient approaches in pharmaceutical development, manufacturing and quality assurance (1). The aim is to build quality into the products instead of testing the quality of the product at the end of the process, thus introducing the principle of Quality by Design (QbD) – a science-driven, risk-based approach supported also by the International Council for Harmonization (ICH) (2-6).

The application of PAT opens opportunities for a deeper process understanding and the development of dynamic manufacturing processes with real-time monitoring, real-time assurance, and real-time release. Key to PAT implementation is the identification of critical material attributes (CMAs) and critical process parameters (CPPs) that impact critical quality attributes (CQAs). The development of appropriate analytical methods to monitor sources of variability allows for real-time control of the process, maintaining the desired product quality withi ...