对于生物制品来说，免疫原性至关重要。然而，参考生物制品的标签文件通常不会提及免疫原性影响，这使得生物仿制药的开发更具挑战性。我们旨在调查美国食品和药物管理局药物评价与研究中心（Center for Drug Evaluation and Research, United States Food and Drug Administration, USFDA）截至2022年3月13日批准的生物仿制单克隆抗体申请的评审报告中，生物仿制药和其相关参考生物制品免疫原性特征的比较评估。我们的研究涵盖了2016年4月5日至2021年12月17日期间批准的22个申请。大多数生物仿制药与参考产品之间的抗药物抗体（ADA）发生率和中和抗体（NAb）发生率的最大差异主要在±15%（-13.6%~12%）和±20%（-17.4%~17.1%，仅有-23.4%和66.7%两种极端值）之间。与抗肿瘤药物相比，免疫抑制剂中ADA-（11/11，100.0%对比8/10，80.0%）/NAb-（11/11，100.0%对比3/10，30.0%）阳性受试者较多，且前述发生率差异的分布更广。已获取可分析数据的生物仿制药与参考产品在药代动力学参数的影响上表现出高度一致性。可用的转换研究中未发现免疫原性的增加。大多数（16/22，72.7%）生物仿制药需满足与免疫原性无关的上市后要求。如有免疫原性差异，USFDA会综合评估临床后果相关的所有证据。可能需要额外的滴度和亚组分析信息来阐明免疫原性影响的关键属性，以及为生物仿制药开发形成具有成本效益的策略。本文章受版权保护，版权所有。

Immunogenicity is critical for biologics. However, reference biologics labeling documents do not necessarily mention immunogenicity impact, rendering the development of biosimilars more challenging. We aimed to investigate the comparative assessment of immunogenicity profiles between biosimilars and their respective reference biologics in the review reports of the biosimilar monoclonal antibody applications approved by the Center for Drug Evaluation and Research, United States Food and Drug Administration (USFDA) as of March 13, 2022, covering 22 applications approved between April 5, 2016 and December 17, 2021. The maximum differences in anti-drug antibody (ADA) and neutralizing antibody (NAb) incidences between biosimilars and reference products mostly fell within ±15% (-13.6%~12%) and ±20% (-17.4%~17.1%, except extreme values of -23.4% and 66.7%), respectively. In comparison with antineoplastic agents, more immunosuppressants had ADA- (11/11, 100.0% versus 8/10, 80.0%)/NAb- (11/11, 100.0% versus 3/10, 30.0%) positive subjects, and the distribution of the aforementioned incidence differences was wider. The investigated biosimilars with available data for analysis demonstrated a high degree of consistency with their reference products in terms of the impact on pharmacokinetic parameters. No increase in immunogenicity was found in available switching studies. Most (16/22, 72.7%) biosimilars were issued post-marketing requirements that were not directly related to immunogenicity concerns. The USFDA considered the totality of evidence assessing clinical consequences of immunogenicity differences, if any. Additional information on titers and subgroup analysis may be warranted to elucidate the critical attributes of immunogenicity impact and to aid in forming cost-effective strategies for biosimilar development.This article is protected by copyright. All rights reserved.