OBJECTIVE: Biologic drug molecules such as antibodies are exposed to the physiological stress conditions of pH 7.4 and 37°C during their long circulation lifetime in vivo. The stress on biologic molecules in vivo is more severe compared to that under typical storage conditions of low pH formulation and cold temperature. Chemical degradation of critical residues such as asparagine may occur in vivo, leading to potential loss of biological activity. This study describes a physiologically relevant and convenient in vitro PBS stress condition of pH 7.4 and 40°C for pre-clinical stability screening of biologic molecules. METHODS: As benchmarks, multiple commercial antibodies (alirocumab, evolocumab, golimumab, ramucirumab, and trastuzumab) were tested in parallel for formulation stability at storage and accelerated temperature conditions and for physiological stability at pH 7.4 and 40°C stress both for 3-4 weeks. The stressed antibodies were monitored for chemical modification and target binding, without requiring affinity purification. RESULTS: The major CDR chemical modifications observed in PBS-stressed commercial antibodies were deamidations of asparagine residues. Although slight decreases in target binding were observed for two antibodies, the affinities overall remained strong after PBS stress. CONCLUSIONS: This benchmarking study of commercial antibodies would be useful as a guide to screen discovery-stage biologic molecules both for drug product stability at formulation pH under storage and accelerated temperature conditions and for physiological stability under in vivo-mimicking pH and temperature stress condition.