Predictive Nature of High-Throughput Assays in ADC Formulation Screening

Utilization of high-throughput biophysical screening techniques during early screening studies is warranted due to the limited amount of material and large number of samples. But the predictability of the data to lon-ger-term storage stability is critical as the high-throughput methods assist in defining the design space for the longer-term studies. In this study, the biophysical properties of two ADCs in 16 formulation conditions were evaluated using high-throughput techniques. Conformational stability and colloidal stability were eval-uated by determining Tm values, kD, B22, and Tagg. In addition, the samples were placed on stability and the extent of aggregate formation over the 8-week interval was determined. The rank order of the 16 different formulations in the high-throughput assays was compared to the rank order observed during the stability studies to assess the predictive capabilities of the screening methods. It was demonstrated that similar rank orders can be expected between high-throughput physical stability indicating assays such as Tagg and B22 and traditional aggregation by SEC data, whereas conformational stability read-outs (Tm) are less pre-dictive. In addition, the high-throughput assays appropriately identified the poor performing formulation conditions, which is ultimately what is desired of screening assays. & COPY; 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.

Automated summary

This study evaluated the biophysical properties of two ADCs in 16 formulation conditions using high-throughput techniques and verified the predictive capabilities of the screening methods through stability studies. The results showed that high-throughput stability indicators, such as Tagg and B22, have similar ranking abilities as traditional methods like SEC data in assessing aggregate formation, while conformational stability indicators (Tm) are less predictive. Additionally, the high-throughput assays effectively identified poor performing formulation conditions, which is the ultimate goal of screening assays.