Abstract
The totality of evidence describes the sum of analytical, non-clinical and clinical studies used to justify regulatory approval of a biosimilar. The foundation of this approach is a detailed analytical comparison of the biosimilar and reference medicine to establish molecular sameness by use of physicochemical and functional assays. By leveraging established knowledge and experience that the reference medicine is safe, pure and potent, an abbreviated clinical program is sufficient to establish that the biosimilar is highly similar to the reference medicine and will exhibit the same safety and efficacy in all approved indications. The extent of clinical studies required for the demonstration of biosimilarity is product specific, depending on the degree of molecular similarity and remaining residual uncertainty following analytical (physico-chemical and functional) analyses. This chapter aims to illustrate the scientific basis for the “Totality of Evidence” concept and to provide insight into the role of clinical trials for the verification of biosimilarity, using real world examples.
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Declaration of Interest
The authors are employees of Sandoz, a division of Novartis, which develops, manufactures and markets biopharmaceuticals, including biosimilar medicines.
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Cohen, H.P., Lamanna, W.C., Schiestl, M. (2018). Totality of Evidence and the Role of Clinical Studies in Establishing Biosimilarity. In: Gutka, H., Yang, H., Kakar, S. (eds) Biosimilars. AAPS Advances in the Pharmaceutical Sciences Series, vol 34. Springer, Cham. https://doi.org/10.1007/978-3-319-99680-6_22
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