Laboratory of Pharmacology, Department of Pharmaceutical Sciences, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece.
BioDrugs. 2013 Jun;27(3):203-11. doi: 10.1007/s40259-013-0020-y.
Biologic medicinal products developed via rDNA technology as recombinant protein-based medicines that have been in clinical use since the early 1980s as original biopharmaceuticals have greatly contributed to the therapy of severe metabolic and degenerative diseases. The recent expiration of the data protection or patents for most of them created opportunities for the development of copy versions of original biopharmaceuticals with similar biologic activity (termed biosimilars). Production of these new products is expected to meet worldwide demand, promote market competition, maintain the incentives for innovation, and sustain the healthcare systems. The licencing of these products, however, relies on the experience gained with the original biopharmaceuticals. Critical issues related to this class of medicinal products include their terminology (to avoid confusion with generics and non-innovator copy versions that have not been tested according to the biosimilar guidelines), manufacturing, and regulation. The European Union (EU) has been the first to establish a regulatory framework for marketing authorization application (MAA) and has named these products biosimilars, a term also recently adopted by the US FDA. Unlike the conventional, more common small molecular weight human medicines and chemical generics, protein-based medicines exhibit higher molecular weight, complexity in structure and function that can be affected by changes in the manufacturing process. Therefore, biosimilars represent a relatively heterogeneous class of medicinal products that make their regulation quite challenging. According to the current understanding in the EU, a biosimilar is a copy version of an already authorized biopharmaceutical (or reference product) with similar biologic activity, physicochemical characteristics, efficacy, and safety, based on a full comparability exercise at quality, preclinical and clinical level to ensure similar efficacy and safety. Guidance has been provided through several Committee for Medicinal Products for Human Use (CHMP) guidelines as well as individual scientific advice requested from the European Medicines Agency (EMA) by various companies for the development and regulation of biosimilars. This review is mainly focused on the current status of regulation of biosimilars in the EU as well as on future challenges lying ahead for the improvement of the requirements needed for the marketing authorization of biosimilars. Emphasis is given on the quality requirements concerning these medicinal products (biologics).
通过 DNA 技术开发的生物医学产品作为重组蛋白类药物，自 20 世纪 80 年代初作为原生物制药进入临床使用以来，极大地促进了严重代谢和退行性疾病的治疗。最近，大多数原生物制药的数据保护或专利都已到期，这为具有相似生物活性的原生物制药的仿制版本（称为生物类似药）的开发创造了机会。这些新产品的生产预计将满足全球需求，促进市场竞争，保持创新激励，并维持医疗保健系统。然而，这些产品的许可依赖于原生物制药获得的经验。与这类药物相关的关键问题包括它们的术语（避免与根据生物类似药指南未经测试的仿制药和非创新者仿制版本混淆）、制造和监管。欧盟（EU）率先建立了营销授权申请（MAA）的监管框架，并将这些产品命名为生物类似药，美国 FDA 最近也采用了这一术语。与传统的、更常见的小分子人类药物和化学仿制药不同，基于蛋白质的药物表现出更高的分子量、结构和功能的复杂性，这些可能会受到制造工艺变化的影响。因此，生物类似药代表了一类相对异构的药物，这使得它们的监管极具挑战性。根据欧盟目前的理解，生物类似药是指已授权的生物制药（或参照产品）的仿制版本，具有相似的生物活性、理化特性、疗效和安全性，基于在质量、临床前和临床水平上的全面可比性研究，以确保相似的疗效和安全性。已经通过几个人用药物委员会（CHMP）指南以及欧洲药品管理局（EMA）应各公司的要求为生物类似药的开发和监管提供了个别科学建议。这篇综述主要集中在欧盟生物类似药监管的现状以及为改善生物类似药上市许可所需的要求而面临的未来挑战。重点放在这些药物（生物制剂）的质量要求上。
