Print Email Facebook Twitter Process analytical technique (PAT) miniaturization for monoclonal antibody aggregate detection in continuous downstream processing Title Process analytical technique (PAT) miniaturization for monoclonal antibody aggregate detection in continuous downstream processing Author Neves Sao Pedro, M. (TU Delft BT/Bioprocess Engineering) Klijn, M.E. (TU Delft BT/Bioprocess Engineering) Eppink, Michel H.M. (Byondis B.V., Nijmegen; Wageningen University & Research) Ottens, M. (TU Delft BT/Bioprocess Engineering) Date 2021 Abstract The transition to continuous biomanufacturing is considered the next step to reduce costs and improve process robustness in the biopharmaceutical industry, while also improving productivity and product quality. The platform production process for monoclonal antibodies (mAbs) is eligible for continuous processing to lower manufacturing costs due to patent expiration and subsequent growing competition. One of the critical quality attributes of interest during mAb purification is aggregate formation, with several processing parameters and environmental factors known to influence antibody aggregation. Therefore, a real-time measurement to monitor aggregate formation is crucial to have immediate feedback and process control and to achieve a continuous downstream processing. Miniaturized biosensors as an in-line process analytical technology tool could play a pivotal role to facilitate the transition to continuous manufacturing. In this review, miniaturization of already well-established methods to detect protein aggregation, such as dynamic light scattering, Raman spectroscopy and circular dichroism, will be extensively evaluated for the possibility of providing a real-time measurement of mAb aggregation. The method evaluation presented in this review shows which limitations of each analytical method still need to be addressed and provides application examples of each technique for mAb aggregate characterization. Additionally, challenges related to miniaturization are also addressed, such as the design of the microfluidic chip and the microfabrication material. The evaluation provided in this review shows why the development of microfluidic biosensors is considered the key for real-time measurement of mAb aggregates and how it can contribute to the transition to a continuous processing. Subject protein aggregationcontinuous biomanufacturingmonoclonal antibodiesMicrofluidicsprocess analytical technol- ogy (PAT) To reference this document use: http://resolver.tudelft.nl/uuid:3ea71f77-d5da-41b6-bf03-19d57fbef0cc DOI https://doi.org/10.1002/jctb.6920 ISSN 0268-2575 Source Journal of Chemical Technology and Biotechnology, 97 (9), 2347-2364 Part of collection Institutional Repository Document type review Rights © 2021 M. Neves Sao Pedro, M.E. Klijn, Michel H.M. Eppink, M. Ottens Files PDF jctb.6920.pdf 1.32 MB Close viewer /islandora/object/uuid:3ea71f77-d5da-41b6-bf03-19d57fbef0cc/datastream/OBJ/view