Thorough knowledge and control of impurities is an expectation for the registration of pharmaceuticals. Actual and potential impurity investigations are phased during drug development to acquire the appropriate information necessary to ensure drug safety from the standpoint of patient exposure to impurities. Regulatory expectations and common practices for the timing of impurity investigations during development are discussed. Investigations for synthetic drug substances include process-related impurities such as intermediates, by-products, mutagenic impurities, residual solvents, and elemental impurities. Stress or forced degradation studies are used to investigate degradation impurities for both drug substances and products. The goals of stress studies conducted at different phases of development are discussed. Protein products have related considerations for impurity investigations, but the nature of impurities and technologies used for determining them can be quite different compared to classical synthetic molecules. Considerations for protein product impurities are discussed with an emphasis on process impurities in monoclonal antibodies.

对杂质的透彻了解和控制是对药物注册的一种期望。从患者接触杂质的角度来看，在药物开发过程中会分阶段进行实际和潜在的杂质调查，以获取确保药物安全所需的适当信息。讨论了开发过程中杂质调查时间的法规要求和通用做法。对合成原料药的研究包括与过程有关的杂质，例如中间体，副产物，诱变杂质，残留溶剂和元素杂质。应力或强迫降解研究用于调查原料药和产品的降解杂质。讨论了在开发的不同阶段进行的压力研究的目标。蛋白质产品在杂质研究中具有相关考虑因素，但是与传统的合成分子相比，杂质的性质和用于确定杂质的技术可能会大不相同。讨论了蛋白质产品杂质的考虑因素，重点是单克隆抗体中的工艺杂质。