![]() Biosimilarity must be substantiated by robust scientific evidence. To generate such evidence, a hypothesis of high similarity between a biosimilar candidate and the original reference medicine should be verified through well‐established and validated methodologies that aim to identify all the potential relevant physicochemical differences, but are also capable of detecting even clinically meaningless differences. The acceptable difference level between the biosimilar candidate and the reference medicine is determined to a qreat extent by a thorough assessment of multiple batches of the reference biologic. ![]() Indeed, no approved biological medicine, whether original or not, is structurally identical to itself, due to an intrinsic batch‐to‐batch variability that can be enhanced by manufacturing changes. ![]() Although different batches of reference biological compounds are not identical to each other, they may be considered essentially equal and therapeutically indistinguishable. Therefore, there is a clinically acceptable range of inherent structural heterogeneity for any biological product. 2, 3 As a consequence, many patients have likely been treated with structurally slightly different versions of any given reference biomedicine, which constitutes a de facto switch of insignificant therapeutic concern. The approach used to substantiate biosimilarity represents a refinement of the procedures that have been securely applied for decades to batches of biologics that are subject to manufacturing changes, 4 but also to the very precise discrimination between native and non‐native proteins during the monitoring of doping in sports. Indeed, the differentiation between an endogenously produced protein, such as erythropoietin, and an externally administered version, such as epoetin alfa or beta, requires extremely sophisticated laboratory techniques. 5, 6 The experience in analysing differences among batches of original biological agents has shown that no clinical comparison of efficacy and safety can match the accuracy and sensitivity of a stringent physicochemical and functional comparability. The rigorous regulation applied to the intrinsic variability of original biologics has thus been extended to the pioneering guidance regarding biosimilar‐to‐originator comparability put forth by the European Medicines Agency (EMA). 7 The magnitude of acceptable physicochemical differences between biosimilars and their corresponding reference biologics can confidently be assessed in the laboratory, where the differences in critical quality attributes must be shown not to exceed the batch‐to‐batch variability of the reference biologic. In addition to analytical comparability, biosimilarity is further supported by the demonstration of comparable pharmacokinetic, and possibly pharmacodynamic, clinical data. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |