Periodic Reporting for period 1 - BIOPURE (Biopharmaceuticals purification by continuous membrane-assisted crystallization achieving lower cost and intensified processes)
Reporting period: 2023-06-01 to 2024-05-31
Biological medicines are therapies that contain one or more active ingredients produced or extracted from a biological system. For example, biological drugs are monoclonal antibodies (mAbs), some vaccines, blood components, hormones and many other biomolecules. Among the biological drugs, the most interesting from the therapeutic point of view are mAbs.
Whole antibodies, or their Fab fragments, are capable of recognizing and specifically binding proteins, or, in some cases, other organic molecules such as peptides, polysaccharides, glycoproteins, lipids, or nucleic acids, called antigens or epitopes. In virtue of their specific binding and subsequent neutralization of the target involved in the pathological state, mAbs are used in the treatment of tumours, inflammations, infectious events, cardiovascular diseases, rejection following organ transplants.
Industrially, mAbs are produced in batch bioreactors in the downstream processing (DSP) step. Then, they are purified to achieve biopharmaceutical quality standards by means of purification platforms consisting in a sequence of unitary operations which include centrifugation, filtration, affinity chromatography with protein-A, ion exchange chromatography (cation/anion), viral inactivation, ultrafiltration, diafiltration. The major limitation of this technological approach consists in the high cost of the protein-A based resin and the large amount of chemicals that are used for the regeneration of the chromatographic column after each purification step. This has an unsustainable economic and environmental impact that has to be mitigated to allow a larger portion of the world’s population to take the benefits of such therapies at affordable costs.
In this context, BIOPURE project has the overall purpose to deliver a step change in monoclonal antibodies purification through the implementation of radically new and disruptive technology based on membrane-assisted crystallization (MAC), for the recovery and purification of monoclonal antibodies in the solid state directly from clarified cell culture fluids (CCCF). The proposed approach has the potential to replace the protein A chromatographic step by an inexpensive, robust, environmentally sustainable and easily scalable process. By achieving the main objective of BIOPURE, it is expected that the adoption of membrane-assisted method for mAb-products purification will provide a breakthrough advancement in terms of productivity efficiency via continuous manufacturing, and cost reduction via process intensification. In this respect, BIOPURE promises to lower manufacturing and purchase of equipment costs with a smaller footprint. It simplifies logistic chains and enhances environmental sustainability by avoiding extensive use of chemicals, compared to the standard chromatography-based platforms. It opens the doors to new possibilities and biomedicines so far too challenging economically or technologically. As end result, the citizens will have access to a more affordable and diverse selection of new generation biomedicines.
Whole antibodies, or their Fab fragments, are capable of recognizing and specifically binding proteins, or, in some cases, other organic molecules such as peptides, polysaccharides, glycoproteins, lipids, or nucleic acids, called antigens or epitopes. In virtue of their specific binding and subsequent neutralization of the target involved in the pathological state, mAbs are used in the treatment of tumours, inflammations, infectious events, cardiovascular diseases, rejection following organ transplants.
Industrially, mAbs are produced in batch bioreactors in the downstream processing (DSP) step. Then, they are purified to achieve biopharmaceutical quality standards by means of purification platforms consisting in a sequence of unitary operations which include centrifugation, filtration, affinity chromatography with protein-A, ion exchange chromatography (cation/anion), viral inactivation, ultrafiltration, diafiltration. The major limitation of this technological approach consists in the high cost of the protein-A based resin and the large amount of chemicals that are used for the regeneration of the chromatographic column after each purification step. This has an unsustainable economic and environmental impact that has to be mitigated to allow a larger portion of the world’s population to take the benefits of such therapies at affordable costs.
In this context, BIOPURE project has the overall purpose to deliver a step change in monoclonal antibodies purification through the implementation of radically new and disruptive technology based on membrane-assisted crystallization (MAC), for the recovery and purification of monoclonal antibodies in the solid state directly from clarified cell culture fluids (CCCF). The proposed approach has the potential to replace the protein A chromatographic step by an inexpensive, robust, environmentally sustainable and easily scalable process. By achieving the main objective of BIOPURE, it is expected that the adoption of membrane-assisted method for mAb-products purification will provide a breakthrough advancement in terms of productivity efficiency via continuous manufacturing, and cost reduction via process intensification. In this respect, BIOPURE promises to lower manufacturing and purchase of equipment costs with a smaller footprint. It simplifies logistic chains and enhances environmental sustainability by avoiding extensive use of chemicals, compared to the standard chromatography-based platforms. It opens the doors to new possibilities and biomedicines so far too challenging economically or technologically. As end result, the citizens will have access to a more affordable and diverse selection of new generation biomedicines.
During the reference period, BIOPURE’s team interacted with industrial end-users, to understand their needs in mAbs production in terms of both process efficiency and product quality. This interaction was successfully finalized with the definition of a user requirement specification (URS) report, that served as guideline on the definition of the requirements for testing and demonstrating the BIOPURE prototype in relevant environment.
Based on prototype characteristics, the definition of the proper membrane module geometry and the maximum active membrane area to be used for each module in the prototype, has been designated. On these bases, the research team designed a semi-continuous system that is suitable to produce membranes of proper size and characteristics at the target scale. The synergistic interaction amongst the several expertise of the BIOPURE consortium, allowed to develop a digital twin of the physical prototype and the design of the working prototype, complemented by the soft sensor platform and control scheme.
During the reporting period, technical work was associated to a desktop market study to evaluate the current market landscape, identifying key trends, assessing competition, and understanding the potential market size for BIOPURE’s mAbs’ purification technology, and the identification and setting up of discussions with relevant biotechnology industry representatives to obtain market feedback and to communicate the technology. The feedback from industry experts and investors has confirmed the demand for BIOPURE’s technology and provided essential guidance for refining our product and business strategies. Once the business model and the commercialization vehicle had been defined, an initial business plan has been developed using the business model canvas approach.
A plan for communication and dissemination of project’s results has been delivered during the first reporting period, while the setting up of the BIOPURE website and the associated social-media accounts allowed to start communication activities of BIOPURE. Coordination & management activities comprised budget distribution to partners and progresses monitoring through regular consortium meetings and interaction between work packages and tasks leaders, together with continuous interaction with EC/EISMEA. A Data management plan was delivered during the working period as well.
Based on prototype characteristics, the definition of the proper membrane module geometry and the maximum active membrane area to be used for each module in the prototype, has been designated. On these bases, the research team designed a semi-continuous system that is suitable to produce membranes of proper size and characteristics at the target scale. The synergistic interaction amongst the several expertise of the BIOPURE consortium, allowed to develop a digital twin of the physical prototype and the design of the working prototype, complemented by the soft sensor platform and control scheme.
During the reporting period, technical work was associated to a desktop market study to evaluate the current market landscape, identifying key trends, assessing competition, and understanding the potential market size for BIOPURE’s mAbs’ purification technology, and the identification and setting up of discussions with relevant biotechnology industry representatives to obtain market feedback and to communicate the technology. The feedback from industry experts and investors has confirmed the demand for BIOPURE’s technology and provided essential guidance for refining our product and business strategies. Once the business model and the commercialization vehicle had been defined, an initial business plan has been developed using the business model canvas approach.
A plan for communication and dissemination of project’s results has been delivered during the first reporting period, while the setting up of the BIOPURE website and the associated social-media accounts allowed to start communication activities of BIOPURE. Coordination & management activities comprised budget distribution to partners and progresses monitoring through regular consortium meetings and interaction between work packages and tasks leaders, together with continuous interaction with EC/EISMEA. A Data management plan was delivered during the working period as well.
The proposed membrane-based technology has already been proved at the laboratory scale (TRL4) as a cheaper and easily scalable alternative to protein A chromatography for mAb purification. The current step is to demonstrate the generalized efficiency of the technology and scale it up to TRL6 through the design of a fully automatized prototype that will be operated continuously and capable of compliance with quality and regulations for biopharmaceutical productions. In addition to technological development, the new BIOPURE technology will be validated with real market players, leading to verifying the planned business model, the IPR management plan, and the associated financial planning included in the go-to-market strategy.
In this respect, as results beyond the state of the art in the reference period, several progresses have been reached by the BIOPURE’s team towards the design of the working prototype and the membrane production at the target scale. Furthermore, on the technology exploitation side, our understanding of the market landscape has been strengthened thanks to initial information gathered from industry discussions, positioning us well for successful market entry and growth, and the selection and verification of the business model and commercialisation vehicle to bring the technology to the market has been initialized.
In this respect, as results beyond the state of the art in the reference period, several progresses have been reached by the BIOPURE’s team towards the design of the working prototype and the membrane production at the target scale. Furthermore, on the technology exploitation side, our understanding of the market landscape has been strengthened thanks to initial information gathered from industry discussions, positioning us well for successful market entry and growth, and the selection and verification of the business model and commercialisation vehicle to bring the technology to the market has been initialized.