Comparative Physicochemical and Biological Characterisation of the Similar Biological Medicinal Product Teriparatide and Its Reference Medicinal Product

Abstract

Background In January 2017, the European Commission approved Terrosa ® (company code RGB-10) as one of the first biosimilar medicinal products of teriparatide for the same indications as for the reference medicinal product Forsteo ® (Lilly France S.A.S.), which has been on the market in the European Union since 2003. The active pharmaceutical ingredient of the reference medicinal product is the biologically active 1-34 fragment of the endogenous human parathyroid hormone [PTH(1-34)]. It is one of the three bone anabolic agents used in the treatment of osteoporosis promoting bone formation and preventing fragility fractures. Objective The objective of this paper is to summarise the results of the comparative analysis of representative batches of both the RGB-10 drug product and the reference medicinal product performed by physicochemical and in vitro biological methods. Methods A series of state-of-the-art analytical methods were applied in a comparative head-to-head manner for testing the similarity in respect to purity, content, structure and potency. Results Based on the results of the comprehensive physicochemical and biological characterisation, RGB-10 proved to be highly similar to the reference medicinal product with respect to the critical quality attributes investigated. Conclusion The results of the quality comparability study demonstrated similarity of RGB-10 to the reference medicinal product, providing the scientific basis for conducting a specifically designed clinical programme, and supported registration of the Marketing Authorisation Application of RGB-10 in the EU.

Analytical Similarity Assessment of Biosimilars: Global Regulatory Landscape, Recent Studies and Major Advancements in Orthogonal Platforms

“…However, there have been limited studies involving the use of X-ray crystallography (XRC), a traditional technique for protein structural studies at the near-atomic level, as it works well only with proteins that can be crystallized, it requires expensive instrumentation, trained operators, and extensive time for analysis ( Lerch et al, 2020 ). If we look at the evolution of HOS assessment in biosimilarity studies ( Figure 4 ), the timeline is peppered with multiple orthogonal techniques such as single dimension NMR ( Visser et al, 2013 ; Sörgel et al, 2015 ; Montacir et al, 2017 ), multi-dimension NMR ( Shekhawat et al, 2019 ; Bor Tekdemir et al, 2020 ; Kovács et al, 2020 ), HDX-MS ( Cho et al, 2016 ; Brokx et al, 2017 ; Brown et al, 2019 ), IM-MS ( Fang et al, 2016 ; Montacir et al, 2017 , 2018 ), antibody conformational array ( Jung et al, 2014 ; Hong et al, 2017 ), aptamer-based enzyme linked apta-sorbent assay ( Wildner et al, 2019 ), and small angle X-ray scattering (SAXS) ( Narvekar et al, 2020 ) ( Supplementary Table S4 ). Of these, NMR has emerged as the new gold standard for HOS assessment with more than 10 published biosimilarity studies published with either 1D, or 1D and 2D as a part of the analytical platform ( Supplementary Table S4 ).…”

Management of medication‐related osteonecrosis of jaw: Comparison between icariin and teriparatide in a rat model

“…These effects of icariin are all related to the pathophysiology of MRONJ and indicate the potential therapeutic effect on MRONJ. Meanwhile, the other agent which promotes the remodeling of bone through binding and activation of the PTH‐R1 receptor, 14 teriparatide, has been reported to be able to stimulating bone formation by osteoblasts and subsequently bone resorption by osteoclasts 15,16 . The application of teriparatide for treatment of MRONJ has achieved some success where the negative effects of BPs were eliminated 17 …”