依维莫司片两个不同BE指南的警示
出自识林
依维莫司片两个不同BE指南的警示
笔记 2016-07-04 Lachman CONSULTANTS 2016年6月最近更新的具体产品的生物等效性（BE）指南中，有一篇关于依维莫司（Everolimus）的BE指南（RLD 021560），该指南涵盖了治疗器官排斥反应中的药物使用。之前的指南文件（2011年3月首次发布，2012年6月修订）适用于肿瘤适应症的不同产品（RLD 022334）。 两个指南文件都提供了排除性语言，并概述了BE建议适用的适应症。 新指南提供了全重复实验设计，并允许使用标度生物等效性方法限定参照药品（RLD）的可变性，根据指南，Everolimus具有低到中度个体间变异。FDA还在新指南中承认，该特定产品具有窄治疗范围，因此反映了相对于该药品用于器官排斥的其它BE指南，并指出“低于治疗浓度可能导致严重的治疗失败”。 尽管指南应用于何种RLD已经非常清楚，但研究人员必须确保选择适当的指南以走向正轨。很有可能一个ANDA申请人阅读了用于肿瘤的产品的旧指南，错误地认为这些建议可能也适用于器官排斥产品，尽管原指南文件中做出了声明。申请人应牢记FDA已经对很多药品采取更严格的立场，包括对窄治疗指数的药品以及缓释和/或复杂产品。不要以为一个产品的一种BE建议将始终适用于另一个产品。也许可以向OGD发送受控函询问，尤其是对于像这样的在FDA发布指南之前的特殊情况。 Lachman CONSULTANTS - Bob Pollock先生 Important Note: There Are Two Different Everolimus Bioequivalence Guidance Recommendations – Be Careful Which You Rely Upon By Bob Pollock | June 28, 2016 原文地址 In the most recent update of the bioequivalence (BE) recommendations, there is a new Guidance for the conduct of BE studies for Everolimus dated June 2016. This specific Guidance covers the use of the drug in treating organ rejection ((here Both Guidance documents provide the exclusionary language and outline to which indication the recommendation applies. The new Guidance provides for a fully replicated design and permits a scaled BE approach to the limits of variability of the reference listed drug (RLD) product, which, according to the Guidance, has “low-to-moderate within-subject variability.” FDA also acknowledges in the new Guidance that this particular product has a narrow therapeutic range, and thus, mirrors other BE Guidances relative to drug products for organ rejection and notes that “sub-therapeutic concentration leads to serious therapeutic failures.” Even though it is clear which Guidance should be used for which RLD, one must take care in making sure you have selected the appropriate Guidance to put you on the right track. It is possible that an ANDA applicant that reads the old Guidance for the product for oncology may have thought, erroneously, that those recommendations might also apply to the organ rejection product despite the disclaimer in the original Guidance document. One should always keep in mind that FDA has taken a more stringent position on many drugs, for narrow therapeutic index drug, as well as modified-release and/or complex products. Do not assume that one recommendation for one product will always apply to another. Perhaps a Controlled Correspondence to OGD would be in order, especially for an unusual situation such as this prior to FDA issuing a Guidance. |
)). A previous Guidance document (initially issued in March 2011 and then revised in June 2012) covers a different product where the indication is for oncology ((