Antibody drug conjugates (ADCs) form a relatively new class of biopharmaceuticals which attracts a lot of attention throughout the industry due to its high potential for cancer therapy. Despite continued industrial and academic research and development efforts, clinical success has been limited so far. This can be attributed to the complex nature of the compounds, which are aiming to combine the specificity of a monoclonal antibody (mAb) and the cell-killing capacity of small molecule drugs. Especially for site-specific conjugations, a multi-step process including a buffer exchange is often needed for covalent linkage of antibody and drug via a linker. Despite the range of parameters that have to be investigated, high-throughput methods are scarcely used so far in the field of ADCs.<br/><br/>In this work, a model system, consisting of a mAb and a non-toxic fluorophore as pseudo-drug, was used to develop a high-throughput platform for a site-specific multi-step conjugation process on a liquid-handling station. A high-throughput solid-phase buffer exchange was successfully incorporated for reagent removal by utilization of a batch cation exchange step. For conjugate characterization, a high-throughput compatible reversed phase chromatography method with a runtime of 7 min per sample was developed. The potential of the platform was shown by performing a kinetics case study, where the high-throughput approach was successfully confirmed with results in larger scale. Due to the degree of automatization and parallelization, the platform is capable of reducing process development efforts significantly. This study could promote the use of HTS in conjugation process development, where the wide range of parameters to be screened would make it a standard tool.

Establishing a high-throughput process development platform for an antibody conjugation process

255th National Meeting (2018)

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