Protein Stress Testing

Forced degradation — also known as stress testing — is the deliberate exposure of a biotherapeutic to various stress conditions to induce degradation. The primary goal is to understand how a molecule may degrade during or after manufacturing by accelerating its chemical and physical changes under controlled conditions. These studies help identify degradation pathways and potential molecular liabilities early in development, informing risk assessments related to product quality, safety, and efficacy.

Despite their broad utility across the drug development lifecycle — from assay development and formulation design to manufacturing, storage, and clinical use — regulatory guidance on how to conduct forced degradation studies remains limited. At a minimum, testing is expected on both drug substance and drug product. The insights gained contribute to defining critical quality attributes (CQAs) aligned with the target product profile and support formulation strategies to mitigate degradation risks.