The goal of this study will be to development a process to manufacture the oil-based raw material with PAT implementation.

The COVID-19 pandemic reminds us that, first, global pandemics are significant threats to population health and material standard of living and, second, evidently not enough is being done to prevent pandemics. Future pandemics are likely if the system of pandemic preparedness is not improved. The first step to ensure we are ready for the next viral outbreak is to understand how the current system functions: who is funding this system and who is conducting the basic and applied R&D into diagnostics and vaccines? Which viruses are being targeted?

The current key challenges in manufacturing of pharmaceuticals in general and vaccines in particular is the lack of rapid measurements for monitoring the processes in real time, lack of understanding of the correlation between operating conditions to the productivity of antigens composing the vaccines and contaminations that affect the purification processes.

Sanofi Pasteur has established a cutting-edge facility for the production of different types of vaccines in Toronto. This state-of-the-art facility is comprised of various complex mixing operations, which play significant role in the vaccine production. Currently, there is lack of sufficient information about the hydrodynamics of these mixing units for the process validation. In this project, computational fluid dynamics and tomography will be utilized to characterize and optimize the operations of mixing units. The CFD model will be validated using tomography data.

The safety and quality of vaccine products are an integral requirement for all vaccine manufacturing and production. Most current tests are using laboratory equipment that requires trained personnel, equipment qualification, method validation, manual sampling, and testing at various stages of product manufacturing. However, the off-line testing is slow, often requires significant volume of material for testing and requires extensive maintenance and upkeep of many different analytical instruments. This is both expensive and time consuming.

The objective is to develop an in-line Process Analytical Technology (PAT) tool to monitor viability and biomass levels at the fermentation stage bacterial organisms.
The Master student will be engaged in the development of the PAT tool for deployment into a state-of-the-art vaccine manufacturing facility. The student will use benchtop tools such as flow cytometry to monitor the bacterial fermentation process and develop correlations to the inline measurements.

The current project will assemble a library of molecules known as single-chain variable fragment (scFv) antibodies to treat COVID-19. The scFv antibodies will neutralize the SARV-CoV-2 coronavirus that causes COVID-19 by targeting its spike (S) glycoprotein. ScFv antibodies offer numerous advantages compared to other treatment alternatives such as small-molecule drugs and monoclonal antibodies, and are arguably the cheapest and most efficacious option to fight the pandemic.

The goal of this study will be to characterize a SARS-CoV2 antigen and the formulated drug product that will contain SARS-CoV2 antigen and a squalene-based adjuvant under tight timeline to release the material for COVID-19 vaccine clinical trials.

Vaccine antigen production is a process that entails numerous variables. In order to have a consistent and robust process, monitoring of process parameters and controlling output variables within a certain range is the best practice. To accomplish this objective, analytical tools are used, on-line, off-line, at line. Real time monitoring of the processes is advantageous as operating parameters can always be adjusted to keep the process in check.

Monitoring the immuno-modulatory effects of vaccine formulations is critical for novel vaccine development. While animal models have been effective, increasing evidence suggests differences when translating to humans. We have designed a platform which uses fresh human whole blood coupled with a high-throughput single cell analysis, mass cytometry (CyTof Helios), to characterize and model the immune responses to vaccine formulations.