Office of Clinical Pharmacology, Office of Translational Sciences, US Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD, 20993, USA.
Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, 10903 New Hampshire Ave., Silver Spring, MD, 20993, USA.
Ther Innov Regul Sci. 2020 Nov;54(6):1363-1371. doi: 10.1007/s43441-020-00161-z. Epub 2020 May 16.
Communicating the clinical impact of immunogenicity in labeling is important for safe and effective use of certain prescription products. Current U.S. Food and Drug Administration (FDA) guidance does not provide comprehensive recommendations on the communication of clinical impact of immunogenicity in labeling. To understand current labeling practice, we evaluated the immunogenicity data and clinical impact information in labeling of selected prescription products.
We created a database of 71 therapeutic biologics and drug products that had an immunogenicity assessment initially approved by FDA's Center for Drug Evaluation and Research between 2014 and 2018. We analyzed the content and format of immunogenicity information (e.g., anti-drug antibody incidence and/or immunogenicity impact on pharmacokinetics (PK), safety, and/or effectiveness) in the most recent approved labeling.
Immunogenicity information was in the ADVERSE REACTIONS section in 98% of the reviewed labeling. Immunogenicity impact on PK was reported in 52% of the labeling, typically within the ADVERSE REACTIONS section, but supportive PK data were often not included in the CLINICAL PHARMACOLOGY section. Additionally, the immunogenicity impact on safety and/or effectiveness was communicated in 70% of the labeling, with 23% clearly communicating the effect as clinically meaningful, and 10% providing actionable recommendations.
Most of the reviewed labeling includes immunogenicity information within the ADVERSE REACTIONS section. However, there is inconsistency in providing supportive PK data and high variability in reporting immunogenicity impact on safety and effectiveness in labeling. Development of a communication framework that allows for consistent inclusion of immunogenicity impact statements in labeling could improve how immunogenicity risk is conveyed in prescription drug labeling.
在标签中传达免疫原性的临床影响对于某些处方药的安全有效使用非常重要。目前，美国食品和药物管理局（FDA）的指导意见并未就标签中免疫原性的临床影响的沟通提供全面建议。为了了解当前的标签实践，我们评估了选定处方药标签中的免疫原性数据和临床影响信息。
我们创建了一个数据库，其中包含了 71 种治疗性生物制剂和药物产品，这些产品的免疫原性评估最初是由 FDA 药物评估和研究中心在 2014 年至 2018 年期间批准的。我们分析了最近批准的标签中免疫原性信息的内容和格式（例如，抗药物抗体的发生率和/或免疫原性对药代动力学（PK）、安全性和/或疗效的影响）。
在审查的标签中，98%的标签都包含了免疫原性信息。52%的标签报告了免疫原性对 PK 的影响，通常在不良反应部分，但临床药理学部分通常不包括支持性 PK 数据。此外，70%的标签传达了免疫原性对安全性和/或疗效的影响，其中 23%明确将影响描述为具有临床意义，10%提供了可操作的建议。
大多数审查的标签都在不良反应部分中包含了免疫原性信息。然而，在提供支持性 PK 数据方面存在不一致性，并且在标签中报告免疫原性对安全性和疗效的影响方面存在很大的可变性。制定一个沟通框架，允许在标签中一致地包含免疫原性影响声明，可以改善处方药标签中免疫原性风险的传达方式。
