Virus-like particles (VLPs) and viral vectors (VVs) are revolutionizing medicine by offering targeted vaccines. Production of VLPs and VVs is costly and time consuming. One of the main reasons is that its purification by chromatography, the state-of-the-art technique, has performance drawbacks.
We are developing novel targeted surface-modified chromatographic materials for purification of these complex biopharmaceuticals. Ultra-high definition structured monoliths are being produced by post-modification of shapes produced by additive manufacturing (AM). We are using ceramic-based AM techniques with ~50 micrometer resolution to produce mechanically stable isoreticular monoliths for downstream processing of clarified bioreaction bulks of adenoviruses and retro-VLPs as model cases. The use of AM techniques was also applied also to design the flow distributors in the separation processes, precisely controlling the flow distribution. The project also designed novel continuous chromatographic methods to reduce time lags and thus production cost. The results showed that the design has to be tailored to the manufacturing process to achieve stringent specifications once that we are printing at the pixel-level. The modifications of 3D printed alumina possess some inherent difficulties that has to be overcome to make the process commercially available. The holistic approach taken by NESSIE can allow a fast and decentralized production of chromatographic substrates which are valuable to produce vaccines for the world population.
The project is the first international project that focuses on ultra-high resolution 3D printing of ceramic substrates to purify virus-like particles (VLPs). The solution provided by the project is applicable to generate a second-generation vaccine for the current pandemic.
The project produced isoreticular monoliths with enhanced flow and surface area properties. For that, the design, starting material and printing process has to be specifically adapted. The design output is an electronic file that can be used for optimization of the structure digitally. The produced materials are compatible with existing cartridges units. Regarding the process, new designs of flow distributors was also achieved and implemented in chromatographic units. A new simplified Simulated Moving Bed (SMB) technology was also developed to further enhance the productivity of the new 3D printed chromatographic material.
Virus-like particles (VLPs) and viral vectors (VVs) are used to produce targeted and safer vaccines. VPLs and VVs are produced in cell cultures and require downstream purification to generate safe materials. Chromatography has been widely employed in the downstream processing of VVs and VLPs.
The main goal of this project is to produce new structured adsorbents as selective chromatographic media to separate complex biopharmaceuticals. New customized surfaces will be attached to innovative shapes produced by ceramic-based additive manufacturing (AM). The main advantage is the possibility to tailor flow inside the column and adjust surface modifications. The mechanical properties will be improved by addition of ceramic oxide additives and tailoring the composition and shape of the structure. The surface properties will be tuned by addition and post-modification of nanoparticles to introduce multimodal functionality incorporating hydrophobicity and ion exchange. The final flow properties and selectivity of the new chromatographic structure will be tunned through optimization of different variables.
Lithography-based Ceramic Manufacturing will be used. Novel combinations of materials, modelling and process improvements will be developed to provide strength and increased post-modification possibilities. The target is to obtain an improved final distribution of post-modified nanoparticles with controlled dual functionality of hydrophobicity and ion exchange in the same chromatographic unit. The new chromatographic materials will be tested for downstream processing of clarified bioreaction bulks of adenoviruses and retro-VLPs as model cases. Based on the experimental data, new adsorber configurations will be developed to optimize the performance of the downstream process and to improve economic indicators.
The components of the project will be manufactured at TRL 5 even though the utilization of ceramic-based AM for this type of application has never been tested before.