Pavlovic Mira, Girardin Elizabeth, Kapetanovic Liliana, Ho Kowid, Trouvin Jean-Hugues
Scientific Advice Unit, Agence Française de Sécurité Sanitaire des Produits de Santé, Saint-Denis, France.
Horm Res. 2008;69(1):14-21. doi: 10.1159/000111790. Epub 2007 Dec 4.
The concept of similar biological medicinal products ('biosimilar' medicinal products) allows pharmaceutical companies to develop products based on an abridged dossier once the marketing protection of the 'reference' biological medicinal product has expired. A biosimilar medicinal product can be granted a marketing authorization provided that its similarity to a reference product is established in terms of quality, safety and efficacy (step-wise comparability exercise). A decision to launch a biosimilar medicinal product on the market is taken if it has a similar efficacy and comparable or better (less) immunogenicity than the chosen reference biological medicinal product. However, this decision is based on limited data and the comparability program may detect substantial differences in immunogenicity profiles but is likely incapable of detecting rare events. This is why clinical experience, through clinical trials and extensive pharmacovigilance programs, remains the most reliable way to assess the immunogenicity and tolerance profile of recombinant therapeutic proteins. Substitution of one biological medicinal product by a biosimilar medicinal product is not currently recommended before long-term clinical efficacy and safety have been acquired in all relevant populations. Here we review recent regulatory guidelines provided by EMEA and comment on the marketing authorizations and risk management plans of two recently approved biosimilar somatropins.
相似生物药品（“生物类似药”）的概念使制药公司能够在“参照”生物药品的市场保护期到期后，依据简略资料开发产品。只要生物类似药在质量、安全性和有效性方面（逐步进行可比性研究）与参照产品的相似性得以确立，就可授予其上市许可。如果生物类似药具有与所选参照生物药品相似的疗效且免疫原性相当或更佳（更低），则可做出将其投放市场的决定。然而，该决定基于有限的数据，可比性研究可能会发现免疫原性特征存在重大差异，但可能无法检测到罕见事件。这就是为什么通过临床试验和广泛的药物警戒计划积累临床经验，仍然是评估重组治疗性蛋白质免疫原性和耐受性特征的最可靠方法。在所有相关人群中获得长期临床疗效和安全性之前，目前不建议用生物类似药替代一种生物药品。在此，我们回顾了欧洲药品管理局（EMEA）近期发布的监管指南，并对两种最近获批的生物类似人生长激素的上市许可和风险管理计划进行评论。
