首页 > 资讯 > 对仿制药物理属性要求的探讨仍在继续

出自识林

2015-05-15

Lachman CONSULTANTS

仿制药占据了85%的市场，不同的仿制药厂商会提供形状、颜色、大小等物理属性各不相同的产品，这可能影响仿药的合规情况，引起患者混淆，甚至可能成为患者拒绝使用仿制药的理由。FDA于2014年进行过一项面向药剂师和患者的研究，以期了解他们对于仿制药在物理属性上与原研有差别的感受。FDA就此研究发布了联邦通告，介绍了研究的出发点、所收到的业界评论、以及相应给出的回复。考虑到FDA已经发布了《仿制药片剂、胶囊大小、形状和其它物理属性的指南》，我们无疑应对后续讨论以及可能的的监管变化保持关注。

FDA的目标可以概括如下：为指导监管政策并给药房运营工作提供额外的帮助，FDA针对药剂师和患者展开调查，希望了解他们对于片剂仿制药外观变化的感受与经验。这一调查旨在进一步了解片剂外观变化对处方疗效难顺应性（non-adherence）的影响。这或许有助于我们研究那些可能解释片剂外观变化与难顺应性关系的因素，包括其他可能改善仿制药安全与有效性的因素。

关于难顺应性，Bob先生曾经举过一个生动的例子。一位患者如在过去10年中一直服用某品牌药品，是一种胶囊形状总片重为300mg的薄膜包衣片，此时患者勉强可以吞下；现在，市售一种仿制药产品获得FDA批准并列为可替代（AB类）药品；然而，该药品的仿制版本为圆形、没有薄膜包衣、总片重为750 mg。药房虽然保证仿制药版本（即使大得多）与原研相比，具有相同的剂量规格，有严谨的试验证明治疗等效。但患者实际上需要吞咽一片超过两倍大小和片重的药片，这相当难以接受。（详见往期资讯功能性问题—新指南草案面世）

FDA所发布的联邦通告收到10份评论，其中最值得研究的部分以及FDA的相应回复摘录如附：

• 两家企业关注潜在的外观专利问题，因为仿制药和品牌药的外观将不再存在区别。有趣的是，FDA回应道该调查仅旨在了解医护人员与患者的看法，而不对外观相似作出强制要求，或者对现行法规作出任何调整。
• 类似的，另一企业认为“该调查虽然有助于FDA指导监管政策，但实际上属于国家药房部（State Boards of Pharmacy）所管辖的范畴”。FDA重申调查的目的仅是了解医护人员与患者对外观区别的看法，或许有助于指导针对患者或医师的教育项目，规避问题开启对话机制，而不是“意在指导药房运营工作”。
• 一评论者表示收集这些信息可能引发《健保流通与责任法案》（Health Insurance Portability and Accountability Act，HIPAA）相关问题。FDA对此保证，该研究得到了有关部门的批准，并交由熟悉程序的学术机构进行，并表示任何FDA人员都不会接触其中的个人信息。
• 还有一评论者指出必要的形状、颜色或其它物理外观属性的变化，可以避免患者和药剂师使用时的混淆。FDA对此情况表示了解，并表示已准备后续增加问题处理此问题。

评论与FDA回复的全文如附 原文

整理 识林-葳 2015-05-15
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英文原文

As we reported in October of 2014 (here), the FDA announced that it was proposing to conduct a study of pharmacist and patient perception of changes in the physical attributes of generic products. This study is being designed by an academic institution to measure the impact of changes in shape, size and color of generic products. With 85% of all products being dispensed generically, and with new first time generics or different suppliers of generic products being dispensed, changes in the physical attributes of the product the patient receives may impact compliance rates, cause confusion in the patient and in some instances even stop the patient from taking their medication altogether.

When FDA first published the Federal Register (FR) notice announcing the proposed study they asked for comments and today, as a prepublication in the FR the FDA repeated its goal in conducting the study and outlined the comments received and provided their responses to those comments.

This is an important issue as FDA has issued guidance on size and shape of solid oral dosage forms and has hinted at the possibility of further changes or requirements. The industry should review the survey results carefully and provide their comments on any FDA report associated with the findings of the survey.

The Agency’s goal is stated as follows: To provide additional information that may help guide regulatory policy or pharmacy business practices, we intend to conduct surveys of pharmacists and patients about their perceptions about and experiences with generic drug product pill appearance change. These surveys are intended to further our understanding of the relationship between changes in pill appearance and non-adherence to prescribed therapeutic regimens. The surveys may enable us to investigate factors that may explain the association between changes in pill appearance and nonadherence, including which factors could be modified to improve the safe and effective use of generic drugs.

There were 10 comments received in response to the initial FR notice. Some of the more relevant comments are summarized below along with a summary of the FDA response.

• Two companies addressed the issue of potential trade dress issues should the findings suggest that there should be no difference in appearance of brand and generic drugs. Interestingly, FDA responded that their goal is to obtain the perceptions of healthcare providers and patients, but not to mandate sameness in appearance or change any legal precedent or legal issue.
• In a similar vein, one commenter noted “that the survey findings may be used by FDA to guide pharmacy business practice, which is the jurisdiction of the State Boards of Pharmacy.” The FDA reiterated its position that the goal of the survey is to obtain perceptions relative to changes that may provide guidance as to educational programs for patients and practitioners to help avoid problems and to open the dialog and that they had “no intent on guiding pharmacy business practice”.
• One commenter expressed concern about gathering of data and potential HIPAA issues. FDA assured the commenter that the study is being conducted under approval of an institutional review board (IRB) and is being conducted by an academic institution familiar with appropriate procedures and indicated that no FDA staff will have access to personal information.
• One comment noted that variances in shape, color, or other physical appearance characteristics could actually help patients and pharmacists avoid confusion. FDA acknowledged this fact and noted that it has decided to include additional questions to address this issue.

A full list of comments and the full FDA responses can be accessed here.