Swanson Steven James
translational Pharmacokinetics Pharmacodynamics (tPKPD), Genentech Inc., San Francisco, CA, United States.
Front Immunol. 2024 Dec 16;15:1401178. doi: 10.3389/fimmu.2024.1401178. eCollection 2024.
The FDA has released new draft guidance to standardize how immunogenicity of protein therapeutics is described in product labels. A key aspect to this new guidance is that companies should describe anti-drug antibodies that have clinical significance in addition to reporting ADAs' incidence. Factors to consider when determining clinical significance include if those antibodies have a significant effect on the drug's pharmacokinetics, pharmacodynamics, efficacy, and/or safety. While in many instances, the humoral response to protein therapeutics does not have any clinical significance, there are cases where there is a clinically significant effect and it is important to communicate this information to physicians and patients. This new guidance also delineates where immunogenicity information should be listed in product labels which should provide consistency in how this information is listed. There are many factors that contribute to a therapeutic's immunogenicity and determining clinical significance is both complex and challenging, requiring that companies perform thorough analyses with scientific rigor. The analysis that is now proposed to understand clinical significance of ADAs is a new concept and will require companies to develop a strategy for compliance. This manuscript sets forth some of the key considerations in answering this important question. One of the benefits that this new guidance will provide is a common approach for describing the immune response to therapeutics that will be located in a dedicated section of the label, providing valuable consistency across protein therapeutics. Section 12.6 in the Clinical Pharmacology portion of the label will contain the relevant immunogenicity information, which will make it much simpler to find immunogenicity information in product labels. This new guidance is currently being utilized for new protein therapeutics and companies are being requested to systematically revise the labels of previously approved drugs for compliance, although an absolute timeline for this has not been established as of this writing.
美国食品药品监督管理局（FDA）发布了新的指南草案，以规范蛋白质疗法的免疫原性在产品标签中的描述方式。这项新指南的一个关键方面是，公司除了报告抗药物抗体（ADAs）的发生率外，还应描述具有临床意义的抗药物抗体。在确定临床意义时需要考虑的因素包括这些抗体是否对药物的药代动力学、药效学、疗效和/或安全性有显著影响。虽然在许多情况下，对蛋白质疗法的体液反应没有任何临床意义，但在某些情况下会有临床显著影响，将此信息传达给医生和患者很重要。这项新指南还划定了免疫原性信息应在产品标签中列出的位置，这将使该信息的列出方式保持一致。有许多因素会导致一种疗法产生免疫原性，确定临床意义既复杂又具有挑战性，要求公司进行严谨的科学全面分析。目前提议用于理解ADAs临床意义的分析是一个新概念，将要求公司制定合规策略。本手稿阐述了回答这个重要问题的一些关键考虑因素。这项新指南将带来的一个好处是，采用一种通用方法来描述对疗法的免疫反应，该描述将位于标签的专门部分，为各种蛋白质疗法提供了宝贵的一致性。标签临床药理学部分的第12.6节将包含相关的免疫原性信息，这将使在产品标签中查找免疫原性信息变得更加简单。目前，这项新指南正用于新的蛋白质疗法，并且要求公司系统性地修订先前批准药物的标签以符合要求，不过截至撰写本文时尚未确定绝对的时间表。
