Interchangeability of biological products in the Brazilian Unified National Health System (SUS): the main regulatory challenges

Abstract: Biological products have sparked a worldwide therapeutic revolution. However, the high cost of these products threatens health systems’ sustainability. The development of copies is considered an economic alternative, but due to the products’ complexity, many concepts used in generic drugs do not apply. Interchangeability between biologicals poses a regulatory challenge. This essay discusses the main regulatory challenges for establishing criteria for interchangeability between new biologicals and their copies in the scope of the Brazilian Unified National Health System (SUS), considering the guidelines adopted by the world’s main drug regulatory agencies concerning interchangeability and the prevailing Brazilian regulatory framework on this issue. Concerns related to the interchangeability of biologicals include automatic substitution, nomenclature, pharmacovigilance, immunogenicity, and extrapolation of therapeutic indications and clinical data from new biologicals to their copies. While the clinical success and economic benefits of switching from new biologicals to their biosimilars have already been observed, the heterogeneity between countries in the regulatory barriers to the approval of copies of biologicals should be taken into consideration during the regulation of interchangeability of biologicals in Brazil.

摘要：生物制品引发了全球性的治疗革新。然而，此类产品的高昂成本正威胁着全球医疗体系的可持续性。开发生物制品仿制品被视作一种经济替代方案，但由于该类产品结构复杂，仿制药所适用的诸多理论与规范并不适用于生物制品。生物制品间的可互换性是一项监管难题。本文围绕巴西统一国家卫生系统（SUS）框架下，确立新型生物制品与其仿制品可互换性标准的主要监管挑战展开论述，参考了全球主要药品监管机构发布的可互换性指导原则，以及巴西当前针对该问题的现行监管框架。与生物制品可互换性相关的核心关切要点包括自动替换、命名规范、药物警戒、免疫原性，以及将新型生物制品的治疗适应症与临床数据外推至其仿制品的相关问题。尽管将新型生物制品切换至其生物类似药的临床成效与经济效益已得到验证，但在巴西开展生物制品可互换性监管工作时，仍需考虑各国在生物制品仿制品审批监管壁垒方面存在的异质性。