Bioconjugation Processing Techniques Utilizing DoE Methodology

Biopharmaceuticals are large complicated molecules requiring researchers to apply sophisticated Design of Experiment (DoE) methods to optimize the multi-attribute reaction conditions for antibody or other protein conjugate Drug Substance Intermediates. The Design of Experiment (DoE) methodology accelerates understanding of the effect that process conditions have on the reaction and often leads to improved yield, lower consumption of expensive raw materials, and shorter development cycles. Applying Design of Experiment (DoE) in process development can serve as the basis of the Quality-by-Design approach, which is of increasing importance.

Experiment (DoE) benefits are magnified through precise and automated control of critical parameters during protein activation, reduction, and conjugation. By proving that control over reaction conditions is highly repeatable, scientists gain confidence. Once process confidence is established, no additional repeat experiments are necessary to confirm the central composite DoE set of process parameters.  Depending on the reaction, numerous factors may be identified as critical, including pH, temperature, agitation speed, and addition rate, as well as the concentration, molar ratios, reducing agent, buffer, and reaction hold times.

Data-rich experiments provide comprehensive process understanding to help researchers make faster decisions to improve economic viability, reduce consumption of reduction, activation, or conjugate reagents to eliminate unnecessary process stages, and improve process stability and product purity. 

Deploying an automated biochemistry workstation enables researchers to conduct DoE methods under reproducible conditions, automatically record results, and control study protocols to establish critical process parameters. 

1. In-Situ Raman Spectrometer — in-situ analysis of multiphasic reactions, polymorphs
2. In-Situ FTIR Spectrometer — in-situ reaction kinetics, mechanisms and pathways
3. PVM® Particle Size Analyzer — inline imaging and analysis of particle formation and growth
4. FBRM® Particle Size Analyzer — inline particle size analysis with FBRM® technology
5. Automated Chemical Synthesis Reactor — enjoy unattended bioconjugation experiments suited for DoE studies for quick discovery of new pathways
6. Reaction Sampling System — automated reaction sampling from suspensions and multiphase reactions
7. Process Development Software, Modeling, and Simulation — support bioconjugation studies with powerful scale-up capability