Exploring new strategies to manufacture enveloped viruses biopharmaceuticals

Current industrial bioprocesses for the production of virus based biopharmaceuticals are still anchored in technologies established decades ago, including the use of embryonated eggs for vaccines. In this very traditional industry, innovation is slow. The reasons for this are various: high safety regulations and development costs, no acceptance of side effects, and a conservative nature of the industry dominated by a few large companies, meaning there is less economic incentive to develop new vaccines and virus based manufacturing processes.

To help address this, it is recognised that more efficient bioprocessing platforms must be developed and used commercially, mirroring the developments in biopharmaceutical production of monoclonal antibodies. More effort in intensification and acceleration of bioprocesses for virus based biopharmaceuticals production will provide the ability to rapidly respond to outbreaks or pandemics, but also to respond to the recent breakthroughs in the fields of gene therapy, immune therapy, and diagnostics. The separation and purification costs in the biopharmaceutical industry can generally account for 40-70% of the total manufacturing costs and for almost half of the total energy use. There are different strategies to level off this high separation and purification cost. This project aims to develop and contribute to the improvement of the downstream processing (DSP) of virus based biopharmaceuticals, focusing on enveloped viruses, whose particular fragility poses a challenge to process development. It is somewhat startling that under current practices virologists generally do not consider the production process of newly developed antigens whilst process engineers lack knowledge on important virology issues pertinent to the process. To address this aspect, multidisciplinary teams in addressing these issues are required to support innovation in the area.

The main objective of the MANVIRUS project is the implementation of a single-column recycle chromatography that mimics the operation mode of continuous multicolumn chromatography, using new affinity chromatographic matrices for enveloped virus based biopharmaceuticals through sophisticated management and recycling of the mixed fractions exiting the chromatographic column. For this purpose, several concepts will be also considered during the different stages of the project: fundamental modelling, design of experiments (DoE), model-based process design, and implementation of novel analytical tools, Good Manufacturing Practices (GMP) compatibility, regulatory issues, and economic viability. Innovative analytical tools that enable the assessment of the product quality during the separation process will also be on the focus of this project and they will be applied to generate a better process and product knowledge to contribute for a more efficient manufacturing of enveloped viral-based biopharmaceuticals accelerating the time to the clinic. Overall, MANVIRUS endeavours improve enveloped virus based biopharmaceuticals separation with higher yields and titters while setting a more efficient chromatographic operation mode, crucial to support later the clinical-to-market transition.

The project work plan is highly collaborative and the main strength of the team is its multidisciplinary and combines proven knowledge in virus engineering, downstream process, chromatography, model-based control scale-up and biochemical characterization; all these skills are crucial for successfully carry out the proposal. Furthermore, the long experience of the team in partnering with bioprocess “tool providers” (Merck Life Sciences, GE Healthcare – Cytiva, Sartorius Stedim, Thermo Scientific and Pall Lifescience) will facilitate the final application of the project in biomanufacturing.