Post-Preclinical Process Development for Inactivated and Recombinant SARS-CoV-2 Vaccines
The high-yield production of inactivated and recombinant vaccines against the SARS-CoV-2 virus necessitates the development of modern and effective bioprocesses. In this regard, optimization strategies for both upstream and downstream processes will be developed for the large-scale transition of vaccines whose R&D-stage production and purification have been conducted by the Health Biotechnology Institute of Türkiye.
Within the scope of this project, process optimization and critical process parameters for scale-up operations will be studied in detail. Following bioreactor inoculation and the production phase, cell culture performance will be evaluated using advanced analytical techniques. Furthermore, detailed cell culture procedures will be executed, and optimization of media and feeding strategies based on cellular metabolism will be ensured as part of this project.
The efficient recovery and purification of the vaccine agent from the cell culture environment represent the most critical stages of biopharmaceutical manufacturing. Purification strategies will be established to reduce high-molecular-weight aggregates, charge variants, residual DNA, host cell proteins, leached protein A, and viral particles. To achieve high levels of purity, large-scale chromatography techniques will be employed in addition to laboratory-scale procedures, aimed at removing cells from the supernatant via centrifugation and filtration and purifying the harvested cell culture fluid based on scale and facility capacity. For instance, the His-tag incorporated at the DNA level for the nasal vaccine enables the utilization of affinity chromatography within the process. Furthermore, to ensure absolute product safety, potential viruses will be eliminated through virus filtration.
One of the paramount product characteristics to be maintained throughout the process is stability. In addition to stability, the purity and quality of the final product will be rigorously determined through analyses conducted using large-scale instrumentation.