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Abstract：
Objective: The aim was to critically evaluate well-established regulatory agencies mAb biosimilar guidelines for development and marketing authorization about quality, efficacy and safety and compare to BRICS-TM regulations to identify challenges. Materials and Methods: The current valid guidelines of EMA, WHO, USFDA, BGTD/HC, ICH, and BRICS-TM were obtained from official websites and comparative qualitative review was performed. Results: The review revealed that Health Canada uses mAb specific guidelines from EMA or USFDA when necessary. The BRICS agencies (except Russia) have incorporated some or most of the WHO SBP TRS and related annexes in similar national biotechnological/biological guidelines; however, gaps or insufficient information have been identified. The Russian Federation has issued general product registration guideline/s with very brief information about mAbs. The TMMDA (Turkey) has published an updated biosimilar guideline which parallels those of the EMA and the ones from WHO; however, no mAb specific guidelines are published. COFEPRIS (Mexico) has published a biotechnological/biological product registration guideline with no information about mAb. The SAHPRA biosimilar guideline has an annex on mAbs which focuses on non-clinical and clinical aspects. The comparative evaluation of BRICS-TM agencies indicates a gap pertaining to clarification for physico-chemical characterization, manufacturing process, overages and compatibility requirements between biological substances and excipients specifically on mAbs. In vitro assay requirements seem quite aligned with those of WHO, whereas in vivo studies mostly have disparity in terms of necessity, type of studies as well as design and criteria. Clinical safety and efficacy studies are indicated in emerging regulatory agencies, however detailed information pertaining to design, size of populations, requirements for primary and secondary endpoints, clarity and evaluation criteria differ. In general, BRICS-TM agencies allow extrapolation of indications provided that pre-defined conditions are met. Interchangeability, switching and substitution of biosimilars are not defined in most of BRIC-TM guidelines whereas South Africa, by law, allows neither interchangeability nor substitution. Pediatric research remains questionable across BRICS-TM. Conclusions: EMA, USFDA guidelines are broadly aligned with WHO and in addition, they also contain specific requirements pertaining to their own region. BRICS-TM has considerably less defined mAb specific biosimilar development and comparability parameters in their published guidelines.
摘要：
目标：目的是批判性地评估完善的监管机构mAb生物仿制药的开发和营销授权指南，疗效和安全性，并与BRICS-TM法规进行比较，以确定挑战。材料和方法：EMA的现行有效指南，WHO,USFDA,BGTD/HC,ICH,和BRICS-TM从官方网站获得，并进行了比较定性审查。结果：审查显示，加拿大卫生部在必要时使用EMA或USFDA的mAb特定指南。金砖国家机构（俄罗斯除外）已将部分或大部分WHOSBPTRS和相关附件纳入类似的国家生物技术/生物学指南；然而，已发现差距或信息不足。俄罗斯联邦已发布一般产品注册指南，其中包含有关单克隆抗体的非常简短的信息。TMMDA（土耳其）发布了更新的生物仿制药指南，该指南与EMA和WHO的指南相似；但是，尚未发布mAb特定指南。COFEPRIS（墨西哥）发布了一项生物技术/生物制品注册指南，没有有关mAb的信息。SAHPRA生物仿制药指南有一个关于单克隆抗体的附件，侧重于非临床和临床方面。BRICS-TM机构的比较评估表明，在物理化学表征的澄清方面存在差距，制造过程，生物物质和赋形剂之间的过量和相容性要求，特别是对单克隆抗体。体外测定要求似乎与世界卫生组织的要求相当一致，而体内研究大多在必要性方面存在差异，研究类型以及设计和标准。临床安全性和有效性研究表明在新兴的监管机构，然而，有关设计的详细信息，人口的大小，主要和次要端点的要求，清晰度和评价标准不同。总的来说,金砖国家TM机构允许在满足预定条件的情况下推断适应症。互换性,大多数BRIC-TM指南中没有定义生物仿制药的转换和替代，而南非，根据法律,既不允许互换性，也不允许替代。整个BRICS-TM的儿科研究仍然存在疑问。结论：EMA，美国食品和药物管理局的指导方针与世卫组织大致一致，此外，它们还包含与自己地区有关的具体要求。BRICS-TM在其发布的指南中对mAb特异性生物类似药开发和可比性参数的定义要少得多。
