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Development of a new process analytical technology based on an innovative nanoplasmonic detection array for monitoring glycosylation of monoclonal antibodies

Periodic Reporting for period 1 - PATGlycoPrint (Development of a new process analytical technology based on an innovative nanoplasmonic detection array for monitoring glycosylation of monoclonal antibodies)

Período documentado: 2019-05-01 hasta 2021-04-30

During the production of biopharmaceuticals, monitoring and controlling critical quality attributes and process parameters is central to ensure that the products meet the regulatory requirements with respect to safety and quality and to facilitate efficient and cost-effective production. An important goal of the biopharmaceutical industry is to lower the production costs, increase quality and sustainability in production of biologics and to reduce time-to-market of new drugs by improving the monitoring and controlling capabilities. The FDA (U.S. Food and Drug Administration) and the EMA (European Medicine Agency) since 2004 have encouraged the biopharma industry to apply process analytical technology (PAT) for real-time or near real-time bioprocess monitoring to improve testing efficiency and reduce rejects and re-processing. Traditional analytical equipment and procedures are expensive and time consuming and not suitable for real-time/near real-time applications. Despite large efforts from the research community as well as industry to develop techniques to implement PAT into bioproduction, challenges remain, and significant improvements are still highly desirable.
The main goal of the research project is to develop a new analytical technology that allows real-time or near real-time monitoring and control of bioproduction. The intended objective is to develop a sensor technology for detection and monitoring of glycosylation of monoclonal antibodies (mAbs) and other pharmaceutical glycoproteins in real-time. Throughout the project´s lifetime, the objective are also expanded to other bioprocess key performance indicators and critical quality attributes, including bioproduct titer and IgG aggregation. Currently, no commercially available instrument can fulfil the criteria of a PAT for real-time on-line/in-line measurements of these attributes. The host institute (Linköping University, Sweden) has previously developed a novel sensor technology using replaceable sensor chips based on gold nanoparticles (AuNPs). With a simple and flexible configuration, the sensor system is expected to facilitate real-time analysis of antibody quality attributes and can be used as a PAT for monitoring and control of bioprocesses. A parallel goal of the project is to support the researcher to resume the research activity after a career break as well as to enhance the opportunities for future employments in both academic and industrial sectors by equipping the researcher with new knowledge, skills, and networks.
The cost and time required for the development of an approved biopharmaceutical, including mAb, have been estimated to 1.2 billion dollars and 8 years, respectively. Treatment using mAbs can cost thousands of dollars per month for cancer treatment. This cost is unaffordable for many people and limits the application of these improved treatments. The success of the project will in turn contribute to lowering the cost for the patients and reduce pressure on strained health care budgets.
The action has been successfully implemented at the Laboratory of Molecular Materials (www.m2lab.se) for two years following the proposed work packages and the Gantt chart. We developed a reliable sensor system that could allow rapid at-line measurements of product titer and facilitate on-line IgG monitoring. The analysis time was reduced significantly from hours when using other traditional methods to only a few minutes with our sensor. The scientific discoveries and the results of the project up to date have laid a solid foundation for further research and development and received large interest from the biosensor community and very positive feedback from the biopharma industry. On top of that, the action provided an excellent opportunity for the researcher to carry out the research and acquire new knowledge and skills that assuredly promoted the researcher´s future career.
The research was conducted according to five proposed work packages (WPs) with adjustments over the course of the project. In WP1 and 3, we focused on developing and optimizing nanoplasmonic sensors to measure product titer, aggregation and glycosylation. In WP2, we synthesized and validated two different peptide libraries for screening and discovering new novel peptides that can be used for glycosylation detection. WP4 and 5 were for project management, dissemination, and exploitation of the results.
The research results of the work have so far been presented as one conference contribution, one open-access journal article, and two manuscripts in preparation. The research data acquired during the project is expected to contribute to one more conference abstract and two scientific papers with some additional data which will be collected after the fellowship. The developed sensor technology was also successfully tested in an industrial setting for a related therapeutic protein, a single-domain antibody (dAb), in different process steps up to pilot scale. Furthermore, the research work was also presented in three division seminars at the host and showcased in “European Researchers´ Night’ for a public audience. In addition, the researcher actively joined seminars held by the Grants Office of the host University to share her experience about the Marie Curie Fellowship. Finally, to increase the accessibility and reusability of the research results, poster presentation and data sets used in the published article were shared on the Zenodo repository.
For project management and knowledge transfer, the host provided significant support to the researcher with helpful feedbacks from weekly discussions and three meetings with industrial collaborators to adjust the plan and act on problems encountered during the project. To expand knowledge, networking and other research skills, the researcher attended four workshops about advanced bioproduction, grant writing, and career development as well as participated in teaching and supervising a Master student. Throughout the project, the researcher was able to engage and collaborate with several small and large companies including ArgusEye, Cytiva, and BioInvent. After the fellowship, the researcher will be hired by the host with another employment contract and continue with the current work and apply for more grants.
The research action goes beyond the state of the art by developing a sensor system that facilitate real-time monitoring and control of the bioprocess of therapeutic antibodies. Up to date, we have successfully developed and evaluated the sensor containing a single channel for bioprocess monitoring. The developed sensor greatly overcome the current technology limitation by 1) significantly shortening the analysis time from hours to immediately or only a few minutes 2) enabling feasibility of on-line/in-line measurement due to the small size and the simplicity of the optical sensor set-up; 3) reducing the instrumentation cost. On a short perspective, the work is expected to have an immediate impact on both the biosensor research community and industry by presenting novel means to achieve rapid and cost-effective techniques for on-line/in-line real-time monitoring of bioprocesses. On a longer and broader perspective, a successful project can significantly reduce costs in the production of therapeutic proteins, enable more rapid development of biosimilars, and therefore give more people possibilities to receive therapeutic treatments.
Performing experiments at the LSPR corner
First publication is added to the m2LAB´s information board
Testing of the sensor system in a pilot-scale antibody purification
Preparation of sensor chips