Norwood Daniel L, Nagao Lee M, Stults Cheryl L M
International Pharmaceutical Aerosol Consortium on Regulation and Science (IPAC-RS) 1500 K Street, NW, Suite 1100 Washington, DC 20005-1209.
PDA J Pharm Sci Technol. 2013 Sep-Oct;67(5):413-29. doi: 10.5731/pdajpst.2013.00934.
In 2006, the Product Quality Research Institute's (PQRI) Leachables and Extractables Working Group released a comprehensive and detailed recommendation document related to leachables and extractables for inhalation drug products. The document includes best pharmaceutical development practice recommendations regarding container closure/delivery system component composition and selection, controlled extraction studies, drug product leachables studies, and routine extractables testing for component release. Also included in the document are two safety-based thresholds for leachables in inhalation drug products, the qualification threshold (QT) and the safety concern threshold (SCT), the first such safety-based thresholds for leachables in any drug product type. A process was described for converting the SCT into an analytically useful threshold for leachables/extractables characterization, the analytical evaluation threshold (AET), with consideration of individual drug product dosing parameters and container closure system component characteristics. This commentary presents the history and evolution of this recommendation document starting from the propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler drug products, which helped prompt interest in inhalation drug product leachables, through the work process of the PQRI group. The overall positive acceptance of the PQRI recommendations is discussed, along with a brief summary of regulatory initiatives influenced by the recommendations. Also presented and discussed are certain key issues and questions that have arisen since the recommendation document was released. The extension and application of best practice recommendations to other high risk drug product types (e.g., large and small volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug Product Working Group, is introduced and considered.
The recommendation document released by the Product Quality Research Institute's (PQRI) Leachables and Extractables Working Group in 2006 includes the first safety-based thresholds for leachables in any drug product type, along with comprehensive best practice recommendations for inhalation drug product pharmaceutical development related to extractables and leachables. The best practice recommendations encompass a number of important functional areas, including container closure/delivery system component composition and selection, controlled extraction studies, drug product leachables studies, and routine extractables testing for component release. This commentary presents the history and evolution of this recommendation document starting from the propellant changeover (chlorofluorocarbons to hydrofluorocarbons) in metered dose inhaler drug products, which helped prompt interest in inhalation drug product leachables, through the work process of the PQRI group. The overall positive acceptance of the PQRI recommendations is discussed, along with a brief summary of regulatory initiatives influenced by the recommendations. Also presented and discussed are certain key issues and questions that have arisen since the recommendation document was released. The extension and application of best practice recommendations to other drug product types (e.g., large- and small-volume parenterals, ophthalmics), led by the PQRI Parenteral and Ophthalmic Drug Product Working Group, is introduced and considered.
2006年，产品质量研究所（PQRI）的可沥滤物与可提取物工作组发布了一份全面而详细的关于吸入药物产品可沥滤物与可提取物的推荐文件。该文件包括有关容器密封/给药系统组件组成和选择、受控提取研究、药品可沥滤物研究以及组件释放的常规可提取物测试的最佳药物开发实践建议。文件中还包括吸入药物产品中可沥滤物的两个基于安全性的阈值，即合格阈值（QT）和安全关注阈值（SCT），这是任何药品类型中首个此类基于安全性的可沥滤物阈值。描述了一个将SCT转换为用于可沥滤物/可提取物表征的分析有用阈值即分析评估阈值（AET）的过程，其中考虑了单个药品的给药参数和容器密封系统组件特性。本述评介绍了该推荐文件的历史和演变，从计量吸入器药品中的推进剂转换（从氯氟烃到氢氟烃）开始，这促使人们对吸入药物产品的可沥滤物产生兴趣，一直到PQRI小组的工作过程。讨论了PQRI建议的总体积极接受情况，以及受这些建议影响的监管举措的简要总结。还介绍并讨论了自推荐文件发布以来出现的某些关键问题。介绍并考虑了由PQRI注射剂和眼科药品工作组牵头将最佳实践建议扩展和应用于其他高风险药品类型（如大容量和小容量注射剂、眼科制剂）的情况。
产品质量研究所（PQRI）的可沥滤物与可提取物工作组2006年发布的推荐文件包括任何药品类型中首个基于安全性的可沥滤物阈值，以及与可提取物和可沥滤物相关的吸入药物产品药物开发的全面最佳实践建议。最佳实践建议涵盖多个重要功能领域，包括容器密封/给药系统组件组成和选择、受控提取研究、药品可沥滤物研究以及组件释放的常规可提取物测试。本述评介绍了该推荐文件的历史和演变，从计量吸入器药品中的推进剂转换（从氯氟烃到氢氟烃）开始，这促使人们对吸入药物产品的可沥滤物产生兴趣，一直到PQRI小组的工作过程。讨论了PQRI建议的总体积极接受情况，以及受这些建议影响的监管举措的简要总结。还介绍并讨论了自推荐文件发布以来出现的某些关键问题。介绍并考虑了由PQRI注射剂和眼科药品工作组牵头将最佳实践建议扩展和应用于其他药品类型（如大容量和小容量注射剂、眼科制剂）的情况。
