(548e) Integrated Reaction Modeling and Process Evaluation in the Development of Bioconjugation Technology Platform

Bionconjugation is utilized in the formation of diverse classes of biotherapeutics such as conjugate vaccines, polymer-based biologic conjugates and antibody-drug conjugates.  The development of an industrial bioconjugation process is thus inherently complex and time consuming.  Important areas considered include the conjugation system (selection of carrier and active agent or payload), the type of linker used to connect the carrier to the active agent, and the conjugation reactions.  Reaction kinetic modeling and reaction engineering have been found to play a beneficial role in the development of the conjugation step when used in concert with the experimental process evaluation.  In this work, two similar linkers were studied, first on their hydrolytic stability then incorporated into the kinetic modeling of the overall conjugation reactions.  Both a model protein and a virus like particle (VLP) were used for the conjugation.  The developed model for VLP conjugation fitted the experimental data well and enables rapid evaluation of various operating schemes and process optimization.