Abstract
Establishing comparability of the originator and its biosimilar at the structural and functional level, by analyzing so-called quality attributes, is an important step in biosimilar development. The statistical assessment of quality attributes is currently in the focus of attention because both the FDA and the EMA are working on regulatory documents for advising companies on the use of statistical approaches for strengthening their comparability claim. In this paper, we first discuss "comparable" and "not comparable" settings and propose a shift away from the usual comparison of the mean values: we argue that two products can be considered comparable if the range of the originator fully covers the range of the biosimilar. We then introduce a novel statistical testing procedure (the "tail-test") and compare the operating characteristics of the proposed approach with approaches currently used in practice. In contrast to the currently used approaches, we note that our proposed methodology is compatible with the proposed understanding of comparability and has, compared to other frequently applied range-based approaches, the advantage of being a formal statistical testing procedure which controls the patient's risk and has reasonable large-sample properties.
Highlights
Biologics are large-molecule drugs that have brought life-changing improvements to the health of patients in many important disease areas
This is expected since the focus of the Tier 1-test (T1-test) is on the mean value, but it is still a highly undesirable feature if a range type hypothesis is considered
The rate of comparability claims is high in Scenario 3 and the rate of comparability claims in this situation is increasing with an increasing sample size and reaches 100% for N = 100
Summary
Biologics are large-molecule drugs that have brought life-changing improvements to the health of patients in many important disease areas. The establishing of comparability at the quality/ analytical level, i.e., demonstrating the similarity of the biosimilar and the originator at the structural and functional level, is generally seen as the first and most important step for the approval of biosimilars [2]. There is still an ongoing controversial discussion on the question of if and how statistical approaches can be used for supporting the comparability claim. This is evident by the fact that the FDA has withdrawn its published draft guidance on this topic after reviewing the received comments [3]
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