A Critical Analysis of the FDA's Omics-Driven Pharmacodynamic Biomarkers to Establish Biosimilarity

Abstract

Demonstrating biosimilarity entails comprehensive analytical assessment, clinical pharmacology profiling, and efficacy testing in patients for at least one medical indication, as required by the U.S. Biologics Price Competition and Innovation Act (BPCIA). The efficacy testing can be waived if the drug has known pharmacodynamic (PD) markers, leaving most therapeutic proteins out of this concession. To overcome this, the FDA suggests that biosimilar developers discover PD biomarkers using omics technologies such as proteomics, glycomics, transcriptomics, genomics, epigenomics, and metabolomics. This approach is redundant since the mode-action-action biomarkers of approved therapeutic proteins are already available, as compiled in this paper for the first time. Other potential biomarkers are receptor binding and pharmacokinetic profiling, which can be made more relevant to ensure biosimilarity without requiring biosimilar developers to conduct extensive research, for which they are rarely qualified.

Keywords: FDA; biosimilars; glycomics; omics technology; pharmacodynamic biomarkers; pharmacokinetics; proteomics; receptor binding.

Figure 1

The number of biosimilars approved in the EU and US (as of June 2023) shows a downward trend (source: FDA and EMA).

Figure 2

Cost distribution of testing of 246 biosimilars approved in the US, EU, and Japan from 2006 to 2021 [3].