Final Report Summary - AIMS (Advanced Interactive Materials by Design)
The integrated project AIMS was targeted at the design of a new class of interactive materials for use in the pharmaceutical, chemical and bio-industries. A real breakthrough in the improvement of production processes for complex molecules, e.g. large proteins cannot be achieved by incremental research, as shown by the presentation of material and process design cycles. Only the integration of material sciences and process development can significantly lower the costs for downstream-processing, which accounts for a large part of the production costs and is still considered a bottleneck in the production of bio-molecules.
Novel materials for selective purification are composed of functional elements (ligands) that interact with target molecules and structures for separation processes (supports) that are designed to ensure a high efficiency of the related purification techniques (chromatography, membrane separation, extraction). An innovative design approach will allow tailoring the material properties to the customers' needs and perceptions. This will cause a paradigm shift from sole material use to material design within the process development cycle and thus drastically enhance the process efficiency at an early stage.
To reach its overall objectives above, AIMS was divided into six individual sub-projects (SPs) and three different cycles. The sub-projects were linked to ensure an optimum exchange of knowledge and technology:
- SP1: Material processing dealt with support structures, sorbents and the scale-up of material production.
- SP2: Material functionalisation comprised the different aspects of material-product interaction like ligand design, processing and immobilisation.
- The crosslinking project SP3: Material parameter design created the necessary interface between material and process by relating structural material parameter with material performance. It implies up-to-date methods, such as molecular modelling, kinetic studies or mass transfer phenomena, to predict an optimum material texture.
- SP4: Material utilisation considered the three different unit operations chromatography, membrane separation and extraction, to ensure a variety of options for both, material application and process optimisation.
- SP5: Process design and optimisation dealt with a final experimental evaluation of the overall material performance under process conditions and the formation and validation of a generic method for process development, design and optimisation. It also acted as a link to the consumer by providing an optimised process with materials, tailored to its special needs.
- SP6: Knowledge transfer and integration generated appropriate links between the technical sub-projects on various levels. The main focus was to ensure proper knowledge management (including intellectual property rights (IPRs)) inside the consortium, to disseminate project results, and to evaluate the wider social impacts of the AIMs project.
The establishment of a web-platform, found at http://www.aimseu.de with a secure area provided a powerful tool for internal communication, which allows an easy exchange of documents, the announcement of upcoming events, the provision of up-to-date mailing lists, and the access to all project deliverables.
Even though the protein A benchmark technology significantly advanced since the start of the AIMS project and is even declared as a well-established industrial standard for purifying monoclonal antibodies by the major provider of protein A resins, concern of pharmaceutical companies increase to be depended on the availability of protein A materials.
The development of new materials started with commercially available benchmark materials, which have been evaluated to allow an assessment of the progress in terms of material and process improvement. Three generations of improved affinity materials have been developed for all different unit operations. Thorough investigation of the materials with a real cell supernatant led to a continuous improvement of material performance and created a database that can be used for the development of new affinity materials. The development of a new SartoAIMs protein A affinity membrane has to be highlighted since it shows a manifold improved capacity for IgG in comparison to commercially available benchmark materials. Affinity materials with mimetic ligands also reached a maturity comparable to benchmark materials available at the beginning of the project and thus represent an alternative to protein A.
Reliable quantitative correlation between material structure and performance were established for ion-exchange materials. Together with the availability of a new chromatographic resin FractoAIMs, which possesses a higher mechanical stability and can be produced according to target structural parameters bead size, pore size, surface area and ligand density, this facilitates a real 'material-by-design' approach to tailor the material properties to the needs of the individual application. This approach has successfully been applied to the specific design of an ion-exchange material for the continuous chromatographic purification.
In addition to the development and evaluation of new materials, the modelling strategies for the individual purification technologies improved significantly. All three unit operations have been modelled successfully and the level of detail and accuracy in predicting the process behaviour reflect the technical maturity of the technology. Suitable software interfaces have been developed which allow for an easy exchange of data between the detailed unit operation models and the generic process model. An experimentally validated molecular model allows assessing the interaction of support, linker, ligand, and product and is thus ideally suited to promote the design of new materials.
Two continuous alternatives to the current protein A technology have been considered for the purification of monoclonal antibodies within the AIMs project. The multi-column solvent gradient purification process shows a performance that is comparable with purification concepts that use protein A as a capture step but uses much cheaper ion-exchange resins as the stationary phases. These results led to the foundation of the company ChromaCon AG, as a supplier of high performance chromatographic process solutions. Aqueous two-phase extraction is also on the way to become a real alternative to existing purification technologies. Even without using an affinity system, a counter-current multistage extraction process has reached a global recovery yield of 80 % at a removal of 79 % of the impurities and leaving room further improvements.
New process concepts have been developed that exploit the full potential of the new materials and purification technologies. These concepts were tested under real process conditions in a mini-plant set up not only to assess their performance as an alternative to the existing protein A platform technology, but also to give valuable information for a generic process design methodology that considers all successful AIMs technologies. The combination of two MCSGP units that operate with different stationary phases allows completing the required MAB purification with only two steps excluding virus inactivation. This goes along with a reduction by a factor of three in the total purification costs.
Novel materials for selective purification are composed of functional elements (ligands) that interact with target molecules and structures for separation processes (supports) that are designed to ensure a high efficiency of the related purification techniques (chromatography, membrane separation, extraction). An innovative design approach will allow tailoring the material properties to the customers' needs and perceptions. This will cause a paradigm shift from sole material use to material design within the process development cycle and thus drastically enhance the process efficiency at an early stage.
To reach its overall objectives above, AIMS was divided into six individual sub-projects (SPs) and three different cycles. The sub-projects were linked to ensure an optimum exchange of knowledge and technology:
- SP1: Material processing dealt with support structures, sorbents and the scale-up of material production.
- SP2: Material functionalisation comprised the different aspects of material-product interaction like ligand design, processing and immobilisation.
- The crosslinking project SP3: Material parameter design created the necessary interface between material and process by relating structural material parameter with material performance. It implies up-to-date methods, such as molecular modelling, kinetic studies or mass transfer phenomena, to predict an optimum material texture.
- SP4: Material utilisation considered the three different unit operations chromatography, membrane separation and extraction, to ensure a variety of options for both, material application and process optimisation.
- SP5: Process design and optimisation dealt with a final experimental evaluation of the overall material performance under process conditions and the formation and validation of a generic method for process development, design and optimisation. It also acted as a link to the consumer by providing an optimised process with materials, tailored to its special needs.
- SP6: Knowledge transfer and integration generated appropriate links between the technical sub-projects on various levels. The main focus was to ensure proper knowledge management (including intellectual property rights (IPRs)) inside the consortium, to disseminate project results, and to evaluate the wider social impacts of the AIMs project.
The establishment of a web-platform, found at http://www.aimseu.de with a secure area provided a powerful tool for internal communication, which allows an easy exchange of documents, the announcement of upcoming events, the provision of up-to-date mailing lists, and the access to all project deliverables.
Even though the protein A benchmark technology significantly advanced since the start of the AIMS project and is even declared as a well-established industrial standard for purifying monoclonal antibodies by the major provider of protein A resins, concern of pharmaceutical companies increase to be depended on the availability of protein A materials.
The development of new materials started with commercially available benchmark materials, which have been evaluated to allow an assessment of the progress in terms of material and process improvement. Three generations of improved affinity materials have been developed for all different unit operations. Thorough investigation of the materials with a real cell supernatant led to a continuous improvement of material performance and created a database that can be used for the development of new affinity materials. The development of a new SartoAIMs protein A affinity membrane has to be highlighted since it shows a manifold improved capacity for IgG in comparison to commercially available benchmark materials. Affinity materials with mimetic ligands also reached a maturity comparable to benchmark materials available at the beginning of the project and thus represent an alternative to protein A.
Reliable quantitative correlation between material structure and performance were established for ion-exchange materials. Together with the availability of a new chromatographic resin FractoAIMs, which possesses a higher mechanical stability and can be produced according to target structural parameters bead size, pore size, surface area and ligand density, this facilitates a real 'material-by-design' approach to tailor the material properties to the needs of the individual application. This approach has successfully been applied to the specific design of an ion-exchange material for the continuous chromatographic purification.
In addition to the development and evaluation of new materials, the modelling strategies for the individual purification technologies improved significantly. All three unit operations have been modelled successfully and the level of detail and accuracy in predicting the process behaviour reflect the technical maturity of the technology. Suitable software interfaces have been developed which allow for an easy exchange of data between the detailed unit operation models and the generic process model. An experimentally validated molecular model allows assessing the interaction of support, linker, ligand, and product and is thus ideally suited to promote the design of new materials.
Two continuous alternatives to the current protein A technology have been considered for the purification of monoclonal antibodies within the AIMs project. The multi-column solvent gradient purification process shows a performance that is comparable with purification concepts that use protein A as a capture step but uses much cheaper ion-exchange resins as the stationary phases. These results led to the foundation of the company ChromaCon AG, as a supplier of high performance chromatographic process solutions. Aqueous two-phase extraction is also on the way to become a real alternative to existing purification technologies. Even without using an affinity system, a counter-current multistage extraction process has reached a global recovery yield of 80 % at a removal of 79 % of the impurities and leaving room further improvements.
New process concepts have been developed that exploit the full potential of the new materials and purification technologies. These concepts were tested under real process conditions in a mini-plant set up not only to assess their performance as an alternative to the existing protein A platform technology, but also to give valuable information for a generic process design methodology that considers all successful AIMs technologies. The combination of two MCSGP units that operate with different stationary phases allows completing the required MAB purification with only two steps excluding virus inactivation. This goes along with a reduction by a factor of three in the total purification costs.
