The biopharmaceutical sector is now a billion-dollar industry providing prevention, treatment and sometimes even cures to severe indications. This sector is segmented in multiple product classes including vaccines and cell and gene therapies. Even though these products have a track record of proven efficiency, the global supply of these life-saving biologics faces significant challenges—one of the greatest being supply.

 

Supply shortages are affecting the quality of life of millions of people, as these result in failure to adequately treat patients and, in the case of vaccines, failure to meet disease eradication targets. Challenges surrounding the global supply of biopharmaceuticals differ across product classes: for example, while vaccines have been routinely manufactured and distributed since their first introduction over 200 years ago, current processes for vaccine manufacture typically rely on outdated expensive technology with low flexibility to respond to market fluctuations. On the other hand, in gene therapies, the fast growth of this sector has not allowed for technology innovation to keep up, and most manufacturing processes rely on non-scalable technologies. This poses a critical issue as products approach the later stages of the clinical trials pathway and in time, commercialization.

 

 

The challenges related to the supply of biopharmaceuticals highlighted above seem to have a common root: technical innovation, as adequate technology advancements are needed to reduce footprint and enhance scalable, robust and cost-effective manufacture of biologics. In order to address the current gaps in technology availability in the biotherapeutics sector, Univercells has designed a next-generation platform for biotherapeutics manufacture: The NevoLine biomanufacturing platform.

 

This disruptive platform uses technological innovation to achieve cost-effective manufacture of biologics in a modular format. The principles of process intensification, chaining and automation are combined in self-contained modules to drastically reduce facility footprint, and capital and operational expenditures. These modules can be configured with product- and process-specific containment levels as well as number of particles per cubic meter environments, enabling bespoke solutions to customer-specific applications. The modules can be adapted and assembled to fit different process requirements and can be adjusted onsite at any point in order to facilitate multi-product manufacture.

 

The NevoLine platform is compatible with various modular facility designs to enable rapid deployment of ‘end-to-end’ manufacturing solutions to rapidly respond to new market needs and speed market access.

 

At the core is the scale-X bioreactor, a high-cell-density structured fixed-bed bioreactor, which enables intensified cell cultures to be performed through media recirculation or media perfusion. The scale-X bioreactor portfolio supports product development and commercialization at different stages with different configurations (surface area per bioreactor) and capacity up to 600 sq m of area for cell growth within a 70-liter bioreactor.

 

The first application of this platform was a configuration for the manufacture of a trivalent Sabin strain inactivated poliomyelitis virus (sIPV) vaccine using Vero cells. The work was performed under a grant from the Bill & Melinda Gates Foundation with consortium partners, Batavia Biosciences and Natrix (Merck Millipore). Poliomyelitis (polio) is an infectious disease that can cause debilitating paralysis or death, and for which there is no effective treatment available, making prevention through immunization the best strategy to overcome it. At the start of the project, the supply gap for polio was 50 million doses.

 

 

The NevoLine platform consists of three interconnected modules containing selected equipment and single-use items for the production, purification and inactivation of a live polio virus vaccine. Given the biosafety level required for this application, isolators were used as modules. The interconnected modules contain the entire production sequence up to bulk drug substance preparation. In-line decontamination of liquid waste and the thermal/VHP decontamination of solid waste take place outside the modules. The unit operations carried out within each of the three modules are:

 

•          Upstream (USP) module: Cell culture in the scale-X bioreactor, infection and concentration

•          Downstream (DSP) module: Clarification and purification

•          Inactivation (INAC) module: Virus inactivation

 

The initial experimental results attained with the intensified process designed to be integrated into the NevoLine platform have demonstrated a superior performance in harvest titers and DSP yields with respect to current processes. These results, combined with the additional benefits of the design of the NevoLine platform, resulted in a COG reduction of 2 to 5-fold and a CAPEX reduction of up to 10-fold.

 

The high success observed in this first application resulted in Univercells receiving the CPhI Award for Excellence in Pharma: Bioprocessing & Manufacturing during CPhI Worldwide 2019 in Frankfurt, Germany last October. The team at Univercells is working on various applications of the platform, as well as concepts for other targets with the most advanced project being in gene therapy products.