Application note: Downstream biopharmaceutical operations

This Kaiser application note focuses on real-time, in situ process understanding using a Raman-based PAT approach. Raman spectroscopy is uniquely useful for biotechnology ‘Quality by Design’ (QbD) applications because it enables fast, non-destructive monitoring and control…

This application note addresses three key issues:

• Real-time, in situ process understanding using a Raman-based PAT approach
• Testing and release of formulation buffers
• Quantitative monitoring of excipient and protein concentrations in downstream bioprocesses

Introduction

The Process Analytical Technology (PAT) initiative of the U.S. FDA provides a framework for implementing principles of “Quality by Design” (QbD), which promotes quality assurance through understanding and controlling the critical process parameters that affect a biologic product’s critical quality attributes. To this end, rapid, non-destructive spectroscopic methods offer significant monitoring and control options for bioprocess unit operations such as in situ monitoring of purification cycles, buffer identification, protein aggregation, product identification, and quality control.

Extending process understanding to downstream bioprocesses is vital to ensure high-quality biological products. Current research is focused on gaining a better understanding of biologic downstream steps by quantitatively measuring key analytes such as amino acids, sugars, and proteins. Similar technology has been used to trend nutrient and metabolite concentrations in situ and in real time during upstream bioprocessing stages3. Raman spectroscopy is uniquely useful for biotechnology QbD applications because it enables fast, non-destructive monitoring and control. The work presented here investigates the development and application of new bioprocess analytics in accordance with the aims of QbD.