Vaxxinity develops a heterologous COVID-19 vaccine, UB-612, aimed to boost the immunity stimulated after the primary vaccination. To date, clinical evidence supports UB-612 favorable safety profile and high immunogenicity across multiple SARS-CoV2 variants, including Omicron. Currently, UB-612 is tested in a Phase 3 pivotal study designed to compare head-to-head its safety and immunogenicity to several authorized COVID-19 vaccines based on mRNA, virus-vectored, and inactivated manufacturing platforms, administered as 3rd-dose boosters.

This discussion will focus on how Merck was able to rapidly advance an investigational SARS-CoV-2 vaccine based on the vesicular stomatitis virus platform used for the Ebola vaccine, ERVEBO. In this discussion, we detail the development of the purification process for this vaccine candidate. We will highlight areas where the platform was successfully adopted as well as additional measures that were needed for the SARS-CoV-2 vaccine candidate.

High-throughput (HTP) microscopy’s ability to measure cellular phenomenon in multiple cell culture models has advanced the utility of viral imaging with the advent of automation-friendly multi-modal imagers. The ability to automate cellular staining, and subsequent imaging, paired with the use of integrated liquid handling, has led to the development of faster HTP approaches that can supplement slower traditional virologic methods during clinical development.

The COVID pandemic and Industry 4.0 acceleration have highlighted the need for concrete solutions for agile vaccine manufacturing. For this talk, we will discuss recent trends, solutions and innovations that allow vaccine processing acceleration, including closed processing, modular facilities, and vaccine platform manufacturing.

Development of analytical methods to streamline real-time measurements during process development is a priority for the evolution of bioprocess manufacturing. Current methods to measure downstream processes are limited and therefore, in this study, the application of NIR and NMR spectroscopy were studied to quantify the aluminum content in adsorbed vaccine drug substance and drug product. NIR in-line capabilities using multivariate PLS and PCA analyses will be discussed.

Raman deployment in vaccine manufacturing is viewed as an advanced technology, aimed to increase overall efficiency, quality, innovation, and reliability. In combination with Raman-based regression models, efficiency increases with inline process characterization of metabolites, cell density, and titer in real time which can be viewed from any network laptop/desktop assuming the proper network integration and capabilities. Additionally, Raman deployment with regression models increase quality by enabling proactive issue resolution and reducing overall risk during new product introduction and tech transfer.

Many viral manufacturing processes for animal health have been transferred from the time consuming and higher risk adherent culture systems to more scalable suspension cell cultures. Growing demand and the need for efficient and economic processes drive the continuous search for innovations. This talk describes studies conducted at MSD Animal Health to evaluate the XCell ATF Technology for intensification of virus propagation on suspension cells.

Continuous processing is the holy grail for many industries and became popular for bioprocessing in the last decade, too. Intensification is a prerequisite to enable a step-wise transformation toward that goal. This presentation gives a comprehensive overview of strategies where and how to implement process intensification, quantifies the benefits like plant occupancy time, and optimizing capacity based on successful examples and case studies.

With the move to intensive processing there is a strong desire to understand the holistic impact of the manufacturing operation on the environment and the business efficiency. The latest process models evaluate facility efficiency (doses per unit volume of cleanroom), PMI, and total energy efficiency. Pre-release versions were used by Process Intensification team in NIIMBL to support sustainability assessments. By way of example, comparisons are made between standard fed-batch processes and intensified process options that include perfusion and continuous downstream operations at different scales. 

Purification of measles vector vaccines based on restricted access chromatography and ultrafiltration has all relevant elements for a platform process. MV vectors remain in the process stream and impurities bound to the stationary phase or depleted based on their smaller size during ultrafiltration. Since the flow-through step is very insensitive to the change of surface properties of the MV vector compared to a bind-elute step and ultrafiltration is a very generic unit operation. These methods are easily scalable, allow processing of large feed streams, and can be carried out semi-continuously within a fully integrated process.

The ambr250 HT is an important tool for bioreactor process development of vaccines and oncolytic viruses, as it allows for expedited experimentation due to ability to automate, reduced resourcing and staffing needs, and smaller footprint. Through this poster, a series of case studies from live virus/microcarriers, fermentation, or suspension mammalian cells are examined where the ambr250 HT was applied in an industrial setting to expand capabilities, increase efficiency, and shorten timelines. 

The provision of high-quality plasmid DNA is a requisite for the production of different vaccines like mRNA vaccines or protein-based vaccines. For this purpose, a generic approach for the fermentation process and the DSP steps has been developed which allows the production of the corresponding plasmid variants in high quality in a very flexible manner and in a short time.

Quality by Design (QbD) guidance for biopharmaceutical companies has been around for over a decade.  However, its implementation in vaccine development continues to be limited and fragmented in its application.  Furthermore, with the imminent publication of ICH Q14, QbD approaches will extend to analytical methods.  The approaches to be taken to generate suitable documentation, risk assessments and design of experiments to provide both process and analytical control strategies will be discussed.   

mRNA-based vaccines show a revolutionary prophylactic and therapeutic potential. However, both the mRNA itself and the nanocarrier used for its delivery place unique demands on the analytical methods used to ensure vaccine quality. We will show that MD-FFF is a very powerful, high-data-content methodology that nicely complements and extends beyond batch-phase techniques for physical, chemical and stability analysis of these next-generation vaccines in the industry setting.