Protein Stability After Administration: A Physiologic Consideration.

Regulatory authorities and the scientific community have identified the need to monitor the in vivo stability of therapeutic proteins (TPs). Due to the unique physiologic conditions in patients, the stability of TPs after administration can deviate largely from their stability under drug product (DP) conditions. TPs can degrade at substantial rates once immersed in the in vivo milieu. Changes in protein stability upon administration to patients are critical as they can have implications on patient safety and clinical effectiveness of DPs. Physiologic conditions are challenging to simulate and require dedicated in vitro models for specific routes of administration. Advancements of in vitro models enable to simulate the exposure to physiologic conditions prior to resource demanding pre-clinical and clinical studies. This enables to evaluate the in vivo stability and thus may allow to improve the safety/efficacy profile of DPs. While in vitro-in vivo correlations are challenging, benchmarking DP candidates enables to identify liabilities and optimize molecules. The in vivo stability should be an integral part of holistic stability assessments during early development. Such assessments can accelerate development timelines and lead to more stable DPs for patients.