IBBR/NIST BMD Seminar

“The role of Raman Spectroscopy in Vaccine Manufacturing” - Karin Balss, Scientific Fellow, Janssen Pharmaceuticals

Vaccines are critical to ensuring global health and prevention of many different diseases. Vaccines are now frequently manufactured in single use or stainless-steel bioreactors, analogous to monoclonal antibody productions. To meet large, global demand, the manufacturing of vaccines must be robust, scale-able, and transferrable to multiple manufacturing locations.

Modeling and PAT sensors have shown value in other cell cultivation processes such as monoclonal antibodies for real time fault monitoring and correction, predictive quality, optimizing yield, and improving process robustness. Raman sensing in production bioreactors provides real time information about nutrient feed, metabolites, biomass, and product yield. The technique is highly chemically specific and scalable from the lab to commercial scale and represents an all-inclusive chemical fingerprint of the bioreactor.

This seminar will highlight a few examples using Raman sensing and multivariate modeling for monitoring vaccine production. Using smart, multiplexed sensors with modeling in this way reduces risk of scale-up and technical transfers. We can see process faults in real time, advise on parameters to adjust, and have the immediate ability to compare batch evolution with historical batches. We anticipate that over time, the models will become performance and quality indicating and allow for facile comparisons of the process at each site and across scales. 

"Cell Therapy Product Characterization by Raman Spectroscopy" - Lifu Xiao, PhD, Janssen Research & Development LLC

Cell therapy therapeutics are complex products that require sophisticated product characterization methods during cell therapy product and manufacturing process development. Conventional bioassays are often based on specific labelling of cellular markers to report cell viability and density, cell identity and health, as well as specific biomolecules. These methods are highly informative but tend to be time consuming and costly. Raman spectroscopy can be a label-free, fast, and information-rich complementary technique to the conventional bioassays for cell therapy product characterization.

Here we present two proof-of-concept studies using Raman spectroscopy for cell therapy drug product characterization. In the first study, we correlated the acquired cellular Raman signals with the established flow cytometry markers associated with apoptosis of T cells detected during drug product cryopreservation. In the second study, we applied Raman to measure viable cell density and cell viability of T cells directly in formulation solutions without sampling. Our results demonstrate the potential of Raman spectroscopy for label-free and non-invasive measurements of T cell characteristics relevant to cell therapy product design and process control.