Alsamil Ali M, Giezen Thijs J, Egberts Toine C, Leufkens Hubert G, Gardarsdottir Helga
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Faculty of Science, Utrecht University, 3584 CG Utrecht, The Netherlands.
Pharmaceutical Product Evaluation Directorate, Drug sector, Saudi Food and Drug Authority, Riyadh 13513-7148, Saudi Arabia.
Pharmaceuticals (Basel). 2021 Feb 25;14(3):189. doi: 10.3390/ph14030189.
Regulatory approval of biosimilars predominantly relies on biosimilarity assessments of quality attributes (QAs), particularly the potentially critical QAs (pCQAs) that may affect the clinical profile. However, a limited understanding exists concerning how EU regulators reflect the biosimilarity assessments of (pC)QAs in European public assessment reports (EPARs) by different stakeholders. The type and extent of information on QAs and pCQAs in EPARs were evaluated for seven adalimumab biosimilars. Seventy-seven QAs, including 31 pCQAs, were classified and assessed for type (structural and functional attributes) and extent (biosimilarity interpretation and/or test results) of information in EPARs. Reporting on the QAs (35-75%) varied between EPARs, where the most emphasis was placed on pCQAs (65-87%). Functional attributes (54% QAs and 92% pCQAs) were reported more frequently than structural attributes (8% QAs and 22% pCQAs). About 50% (4 structural and 12 functional attributes) of pCQAs were consistently reported in all EPARs. Regulators often provided biosimilarity interpretation (QAs: 83% structural and 80% functional; pCQAs: 81% structural and 78% functional) but rarely include test results (QAs: 1% structural and 9% functional and pCQAs: 3% structural and 9% functional). Minor differences in structural attributes, commonly in glycoforms and charge variants, were often observed in adalimumab biosimilars but did not affect the functions and clinical profile. Despite the variability in reporting QAs in EPARs, the minor observed differences were largely quantitative and not essentially meaningful for the overall conclusion of biosimilarity of the seven adalimumab biosimilars.
生物类似药的监管批准主要依赖于质量属性（QA）的生物相似性评估，尤其是那些可能影响临床特征的潜在关键质量属性（pCQA）。然而，对于欧盟监管机构如何在不同利益相关者的欧洲公共评估报告（EPAR）中体现（pC）QA的生物相似性评估，人们了解有限。对七种阿达木单抗生物类似药的EPAR中QA和pCQA的信息类型和范围进行了评估。对77个QA（包括31个pCQA）进行了分类，并评估了EPAR中信息的类型（结构和功能属性）和范围（生物相似性解释和/或测试结果）。EPAR之间关于QA的报告（35%-75%）各不相同，其中最强调的是pCQA（65%-87%）。功能属性（54%的QA和92%的pCQA）的报告频率高于结构属性（8%的QA和22%的pCQA）。所有EPAR中一致报告了约50%的pCQA（4个结构属性和12个功能属性）。监管机构经常提供生物相似性解释（QA：结构属性83%，功能属性80%；pCQA：结构属性81%，功能属性78%），但很少包括测试结果（QA：结构属性1%，功能属性9%；pCQA：结构属性3%，功能属性9%）。在阿达木单抗生物类似药中经常观察到结构属性的微小差异，通常是糖型和电荷变体方面的差异，但这些差异并不影响功能和临床特征。尽管EPAR中关于QA报告存在差异，但观察到的微小差异在很大程度上是定量的，对于七种阿达木单抗生物类似药的生物相似性总体结论而言并非本质上有意义。
