Monitoring Downstream Purification with Raman Spectroscopy using the ProCellics™ Raman Analyzer

Raman spectroscopy is a process analytical technology (PAT) with broad use in the biotech industry for its high selectivity and ability to monitor a variety of components simultaneously without impacting product quality. Traditionally, Raman spectroscopy has been focused on upstream processes to monitor nutrients, metabolites and cell composition, but significant interest has arisen in recent years in applying the technology in downstream unit operations such as tangential flow filtration. Raman spectroscopy offers in-line sensing and frequent measurement, enabling rapid decision making required for downstream process parameter adjustment. This webinar outlines the workflow of developing chemometric models for Raman spectroscopy and two case studies supporting implementation in TFF applications: Monitoring DMSO solvent clearance to below the 5000 ppm ICH guideline target following an antibody-drug conjugation reaction; and measuring highly concentrated mAb drug substance such as in final UF where high frequency intervals, low relative error and flow independence are key enablers.

Presented by Greg Voyta, Senior Engineer, Upstream Process Development at Merck

Greg Voyta is a Senior Engineer, part of the Upstream Process Development team at Merck His team supports process development and scale up of upstream technologies and his focus areas are cell retention systems and PAT technologies. Greg has over a decade of experience in the biotech industry, with previous roles in downstream MSAT and extensive experience in the virus filtration unit operation. Greg holds a Bachelors degree in Chemical Engineering from Worcester Polytechnic Institute.

ProCellics™ Raman Analyzer for ADC Solvent Clearance Monitoring during TFF

This talk highlights how, as a leading CTDMO, we are advancing the use of Process Analytical Technology (PAT) to gain deeper insight into our Antibody-Drug Conjugate (ADC) manufacturing processes. We will showcase how the ProCellics™ Raman Analyzer enables real-time monitoring of DMSO solvent clearance during a tangential flow filtration (TFF) process, which facilitates robust process control and ensures effective solvent removal. Building and optimizing the chemometric model through careful selection of offline data sets will be highlighted. In addition, the detailed kinetic data collected provides valuable insights to guide future process optimization.

Presented by Dr. Kim Nguyen, Senior Scientist, ADC Bioconjugation Template Innovation at Merck

Dr. Kim Nguyen has been working in the company for 9 years, first in Process and Analytical Development then in Innovation, focusing on analytical method development and optimization. Before she joined Merck, Dr. Nguyen had her postdoctoral training at the Washington University in St. Louis, performing research to evaluate radiopharmaceuticals for diagnosis and treatment of cancers. Dr. Nguyen has over 10 years of experience in analytical R&D, project management, technology transfer to GMP manufacturing.

ProCellics™ Raman Analyzer Supports Rapid Decision Making With Highly Concentration Drug Substance

Integrated biologics manufacturing offers productivity advantages over batch processing but requires advancement of robust in-line Process Analytical Technology (PAT) and digital monitoring capabilities. Downstream processing optimization is hindered by slow analytics when rapid decision-making on parameter adjustments is needed. This talk will share how the ProCellics™ Raman analyzer with flow cell can be used for in-line concentration measurement of highly concentrated drug substances exceeding 250 g/L. Traditional methods like UV-Vis spectroscopy face accuracy limitations with concentrated samples under small-scale development conditions. Raman spectroscopy addresses these challenges, requiring minimal sample volumes. Previous research demonstrated this system’s ability to accurately measure mAb concentrations (12-213 g/L) with 0.46% relative error and measurement intervals under 23 seconds. The system performs consistently across flow rates of 0.1-10 mL/min, typical for development work. This presentation will extend that application and explore the potential for a generic model applicable across various mAb and mAb-derived modalities.

Presented by Alexander Farris, Bioprocessing Engineer at Merck

Alexander Farris is currently a Bioprocessing Engineer on Merck’s PAT & Digital Applications R&D team, where he focuses on advancing ProCellics™ Raman Analyzer applications in downstream processing. Prior to joining Merck, Alex built a strong foundation in the biopharmaceutical industry by working in GMP manufacturing of viral vectors at Thermo Fisher Scientific’s CDMO and providing manufacturing and development support for various biologics projects at Bristol Myers Squibb. Alex holds a B.S. in Chemical Engineering from the University of Massachusetts, Amherst.

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The life science business of Merck KGaA, Darmstadt, Germany, operates as MilliporeSigma in the US and Canada. Merck KGaA, Darmstadt, Germany is a global science and technology company with more than 62,000 employees in 65 countries.