Department of Pharmacology, CIBERehd, School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Spain.
Department of Biochemistry and Molecular Biology II, CIBERehd, School of Pharmacy, Instituto de Investigación Biosanitaria ibs.GRANADA, University of Granada, Spain.
Pharmacol Res. 2018 Jul;133:251-264. doi: 10.1016/j.phrs.2018.01.024. Epub 2018 Feb 8.
Biosimilars are copies of reference biological drugs, developed as the patents for original biologicals expire. They are thus developed to replicate an original biological medicine just a generics are intended to replicate a chemically-synthesized medicine; however, there are important technical and regulatory differences between the two. Unlike chemical drugs, molecular identity cannot generally be established for any two biological drugs. Accordingly, their pharmacological properties cannot be assumed to be the same. This is due to the complexity of the production of biologicals and to the presence of minor natural variations in the molecular structure (collectively known as microheterogeneity). Further, biological production yields slightly different versions of the drug over time, particularly when changes are introduced in the production process. In this case the prechange and postchange versions of the biological are analyzed in what is called a comparability exercise. The comparable versions thus validated are considered not to have any significant differences at the clinical level. Likewise, biosimilars are not identical copies but comparable versions of the original biological drug, also validated through a comparability exercise, although of a much broader scope. Although current knowledge about biosimilars has increased significantly, they still arise a number of controversies and misconceptions, particularly regarding issues like extrapolation of indications, immunogenicity and substitution. This review deals with concepts and controversies in the biosimilar field.
生物类似药是参照原研生物药开发的，随着原研生物药专利的到期而产生。它们旨在复制原研生物药物，就像仿制药旨在复制化学合成药物一样；但是，两者之间存在重要的技术和监管差异。与化学药物不同，一般来说，不能确定任何两种生物药物的分子身份是否相同。因此，不能假定它们的药效相同。这是由于生物药物的生产复杂，并且分子结构中存在较小的天然变异（统称为微观不均一性）。此外，生物药物的生产随着时间的推移会产生略有不同的药物版本，特别是在生产过程中引入变化时。在这种情况下，会对生物药物的变更前和变更后版本进行分析，这称为可比性研究。经过验证的可比版本在临床水平上被认为没有任何显著差异。同样，生物类似药并不是原研生物药物的完全相同的复制版本，而是经过可比性研究验证的可比版本，尽管范围更广。尽管目前对生物类似药的了解有了显著增加，但它们仍然存在一些争议和误解，特别是在适应证外推、免疫原性和替代等问题上。这篇综述涉及生物类似药领域的概念和争议。
