FDA否定请愿并修订鲁比前列酮BE指南
出自识林
FDA否定请愿并修订鲁比前列酮BE指南
笔记 2015-07-22 2015年7月17日,发布修订版的指南草案鲁比前列酮的生物等效性建议,对2010年版本进行了修订。原研药AMITIZA的生产商,Sucampo制药去年递交了公民请愿,17日当天FDA公布了否定回复信Citizen Petition Denial Response from FDA CDER to Sucampo Pharma Americas LLC 鲁比前列酮胶囊介绍: FDA在2006年1月首次批准了AMITIZA胶囊(NDA 021908),鲁比前列酮(lubiprostone)是一种前列腺素E1衍生物,可选择性激活位于胃肠道管腔侧表皮细胞膜上的2型氯离子通道(CIC-2),增加肠液的分泌和肠道的运动性。AMITIZA胶囊适用于成人慢性特发性便秘(CIC)、成人慢性非癌痛阿片诱导性便秘(OIC)的治疗。此外,AMITIZA还适用于18岁以上女性便秘型肠易激综合征(IBS-C)的治疗。 到目前为止,美国还没有这个产品的ANDA获批。中国有5家按化3.1申报临床的,其中一家进口注册的在2015年6月获得临床批件。 Sucampo制药递交的公民请愿简介: 2010年8月的鲁比前列酮生物等效性(BE)草案 2014年1月,Sucampo递交了公民请愿,认为:只在CIC成人患者进行研究,不能推断在OIC、IBS-C患者的效果,2010年的指南草案不能充分保证ANDA能与AMITIZA的所有适应症有相同的安全性。
参考: Bob Pollock对此事的评论: 此次修订的建议实际上使鲁比前列酮仿制药批准途径变得容易了。 FDA在否定回复信中这样表述:
FDA也在否定回复信中详细解释了这个决定的理由。当Sucampo认为:因为80-125%的范围,仿制药血药浓度会与RLD有25%的差别时,FDA纠正了这个观点,FDA表述:
之前的BE研究结果表明,仿制药事实上与原研会有3.5-4%差别,可能用两批原研药检测也会有这样的结果。 只有与RLD Q1/Q2产品,FDA允许进行一个PK研究,和一个严格的比较溶出度检测。对其他主要作用机制是在胃肠道局部效果的口服给药产品,FDA也是这样的态度。如果产品与RLD Q1和Q2不相同,FDA建议在检测计划中增加:CIC患者身上进行的临床终点的BE研究。 仿制药办公室将继续评价BE研究的要求,基于得到的新信息和科学数据,将经常修订BE指南。 参考: 编译:识林-榕 2015-07-22 Bob Pollock 's comments: FDA Denies Petition and Revises Bioequivalence Guidance for Lubiprostone However, its revised recommendations (here) actually made the path to approval for a duplicate version of the drug potentially easier for generic entrants. The FDA stated in its petition denial letter (here) that:
FDA also explained its rationale for its decision in detail in the denial letter and also set the record straight when the innovator noted that, because of the 80-125% confidence interval, that concentration of the generic lubiprostone could be 25% different than that of the reference listed drug (RLD). FDA noted that:
Previous studies of BE results show that generics actually differ by only 3.5-4%, a result that would be expected if two lots of the innovator product were tested against themselves. The FDA is permitting a pK study only if the generic product is Q1 and Q2 is the same as the RLD, along with a rigorous comparative dissolution testing protocol. This is a position that FDA has taken for other orally administered products whose primary mechanism of action is based on its local effect in the GI tract. If however, the products are not Q1 and Q2, then the FDA is recommending that a BE study with clinical endpoints in chronic idiopathic constipation also be included in the testing regimen. The Office of Generic Drug continues to evaluate its requirements for BE testing and often revises its guidance based on new information and scientific data that becomes available. |