Markovic Ingrid
Expert Opin Drug Saf. 2007 Sep;6(5):487-91. doi: 10.1517/14740338.6.5.487.
Leachables are chemical entities that migrate spontaneously from the final container closure system, packaging components and/or processing equipment under recommended conditions of product use and storage. Unlike leachables, extractables are generated under exaggerated temperature and time conditions in the presence of an appropriate solvent. Increasing evidence suggests that leachables may pose a safety risk by causing toxicity, carcinogenicity, immunogenicity and/or endocrine dysregulation. These substances may also alter product physico-chemical properties via interaction with the active pharmaceutical ingredient or the excipients in product vehicle, thereby adversely affecting the final product quality. The evaluation of leachable compounds begins with a thorough identification of extractable compounds released from the production and packaging components under exaggerated conditions. The set of observed extractables helps to identify possible targets to be monitored in a subsequent leachables study over extended time periods. Although extractables and leachables also present a challenge for the safe use of device components (e.g., metered dose inhalers, dry powder inhalers, nasal spray devices or various implants), this review focusses on a safety risk assessment for specified therapeutic biological protein products. Regulatory, safety and scientific considerations in evaluating extractables and leachables are discussed, along with strategies for the analytical identification, quantification and monitoring.
可浸出物是指在产品使用和储存的推荐条件下，从最终容器密封系统、包装组件和/或加工设备中自发迁移的化学物质。与可浸出物不同，可提取物是在适当溶剂存在下，于夸张的温度和时间条件下产生的。越来越多的证据表明，可浸出物可能通过导致毒性、致癌性、免疫原性和/或内分泌失调而构成安全风险。这些物质还可能通过与活性药物成分或产品载体中的辅料相互作用，改变产品的物理化学性质，从而对最终产品质量产生不利影响。可浸出化合物的评估始于对在夸张条件下从生产和包装组件中释放的可提取物化合物进行全面鉴定。观察到的可提取物集有助于确定在后续更长时间的可浸出物研究中可能需要监测的目标。尽管可提取物和可浸出物也给设备组件（如定量吸入器、干粉吸入器、鼻喷雾装置或各种植入物）的安全使用带来挑战，但本综述重点关注特定治疗性生物蛋白产品的安全风险评估。文中讨论了评估可提取物和可浸出物时的监管、安全和科学考量，以及分析鉴定、定量和监测的策略。
