首页 > 资讯 > FDA着手对仿制药物理属性差异进行问卷调查

出自识林

2014-10-15 Lachman CONSULTANTS

FDA在今日的联邦公告上公布，FDA将对患者和药剂师进行问卷调查，以获得者两个团体对于同一药品仿制产品的特定属性差异的看法。完整FR通知请见这里。

该问卷随仿制药办公室去年12月发布的关于仿制药大小、形状和颜色的指南接踵而至。FDA已收到许多患者和医疗机构在最初从品牌产品替换成仿制药（当初始替换发生时）或后续替换到其他仿制药生产商的产品时，关于仿制药物理属性不同方面差异的投诉和反馈。从历史上看，FDA从未真正监管过这些属性，除非引发一些明显的安全问题，FDA允许仿制药申请人有显著的自由空间来选择其产品设计。在Hatch-Waxman法案通过之后，仿制药厂商开始更加一致的在一些属性上制造差异，以努力避免商业外观侵权并围绕专利设计。随着时间的推进，今天的FDA显然认为（而且是理所当然如此）仿制产品属性的这些变化可能影响用药的顺应性或（至少）引发了关于药剂师是否能配发合适药物的问题。尽管辅有警告标签以及药剂师在配发时提供的咨询或其他信息，这些产品的差异（或因它们可能产生的混乱）仍可能发生。当产品替换发生时，患者继续质疑颜色、大小或形状的改变，他们可能会担心药物强度错误或配发错误的药品。吞咽较大药片或胶囊的问题也可能导致对处方服药的较差的顺应性或不顺应。

FDA在FR通知中表示，他们计划进行这些调查“为提供更多的信息帮助指导监管机构或药房实践，我们计划对药剂师和患者关于仿制药产品药片外观改变的看法和经验进行调查。”

对药剂师的问卷设计用于获取当配送的仿制药在生产时发生变更，药剂师对仿制药颜色、大小和形状改变的看法，以及药剂师所观察到的患者对这些变化的反应。

药剂师问卷将面向在传统社区药店环境下实践的全国范围的药剂师。FDA的目标是调查足够多的药剂师以获得1000份完成的问卷。问卷大约需要药剂师花费20分钟的时间完成。

患者问卷调查将分成两组通过电话完成，一组是50岁及以上患有特定慢性病并采取特定治疗类药物的患者（例如，抗癫痫、高血压、抑郁症、HIV药物）。第二组患者将来自于国家患者数据库中至少患有一种慢性疾病，他们的药物中一个属性已经改变有待研究。

看来，FDA正试图量化这些变化的引入可能对患者处方药物治疗的顺应性产生影响的问题，并可能找出特定类型或治疗类别的药品对于这类变化会给患者带来最大的麻烦。根据这些研究结果，FDA会回顾和/或修订其有关仿制药变更的政策，并可能增加对产品同一性的要求，或者如果他们发现某些改变不会影响药物治疗顺应性，减少企业的负担。

这是FDA和行业正在处理的非常令人困惑的问题。对患者安全性和有效性的影响是非常重要的，但来自FDA的明确指导对于仿制药企业高效开发寻求FDA批准的产品也是必要的。如果在产品开发过程中规则发生变化，显然，企业将被迫从头做起修改FDA可能反对的特定属性。政策可能根据调查结果发生变化吗？当然！法规还会远远落后吗？很有可能！我们所能作的就是等待和观望范式转换向对原研产品的真正“复制”。

Lachman CONSULTANTS - Bob Pollock先生 2014-10-14
校译：识林-椒 2014-10-14

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Patients and Pharmacists to be Surveyed by FDA on Their Perception of Differences in Attributes of Generic Products
Written by Bob Pollock • October 14, 2014

FDA announced in today's Federal Register (FR) that they will conduct a survey of patients and pharmacists to gain an understanding of both groups' perception of certain attributes of differences in generic medicines for the same drug product. See the full FR notice here.

This survey comes on the heels of Office of Generic Drug Guidance (OGD) on size, shape and color of generic products ( here), issued last December. FDA has received complaints and feedback from numerous patient and health care providers on various aspects related to differences in the physical characteristics of generics when they are initially switched from the brand name product (when initial substitution occurs) as well as when switching to other generic manufacturers of the product on subsequent refills. Historically, FDA never really regulated such attributes and it has permitted generic applicants significant leeway to choose their product design unless it posed some obvious safety issue. Generic firms began developing differences in these attributes more consistently after the passage of the Hatch-Waxman Act in an effort to avoid trade dress infringement and to design around patents. As time marched on, FDA today clearly believes (and rightfully so) that these changes in attributes of generic products may impact on the medication compliance or (at a minimum) raises a question about whether the appropriate medication have been dispensed by the pharmacist. These product differences (or the resultant confusion they may cause) seem to occur despite the auxiliary warning labels, and counseling or other information provided by the pharmacist at time of dispensing. Patients continue to question color, size, or shape changes when product substitutions are made, and, if the tablet or capsule is substantially smaller or larger than what they have been getting, they may worry that the wrong strength of medication or wrong drug has been dispensed. Problems with swallowing a larger tablet or capsule could also lead to poor compliance or noncompliance with prescribed medication regimens.

FDA says in the FR notice that they intend to conduct these surveys “[T]o 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.”

The survey for pharmacists is designed to obtain both the pharmacist's perception of changes in color, size, and shape of generic medications when a change is made in the manufacturing of the generic product dispensed, as well as the pharmacist’s view of the reactions of their patients to such changes.

The pharmacist survey will enroll a national cohort of pharmacists who practice in traditional community pharmacy settings. FDA's goal is to survey enough pharmacists to obtain 1000 completed surveys. The survey is estimated to take about 20 minutes for the pharmacist to complete.

Patient surveys will be conducted by phone in two groups – patients 50 years of age or older that have certain chronic conditions and take certain therapeutic categories of drug products (e.g., antiepileptic hypertension, depression, HIV drugs). A second group of patients will be derived from a national database of patients with at least one chronic disease whose medication has changed in one of the attributes to be studied.

It appears that FDA is attempting to quantify problems that such changes introduce that may effect the patient's compliance with prescription drug therapy, and possibly to identify specific types or therapeutic categories of drug products for which such changes are most troublesome to patients. Depending on the results of the study, FDA could review and/or revise its policy on generic product changes and may either increase requirements on sameness of products or lessen the burden on industry if they find that certain changes do not impact drug therapy compliance.

This is a very perplexing issue that the Agency and industry are dealing with. The impact on patient safety and efficacy are of paramount importance but clear guidance from FDA is necessary for the generic industry to efficiently develop the products for which it will seek FDA approval. If the rules change in the process of product development, then clearly the industry may be forced to go back to the drawing board to revise the specific characteristic to which FDA may object. Could the policy change based on the result of the survey? Certainly! Could regulation be far behind? Quite possibly! All we can do is wait and see as the paradigm shifts more towards a true “copy” of the innovatory product.