Type and Extent of Information on (Potentially Critical) Quality Attributes Described in European Public Assessment Reports for Adalimumab Biosimilars.

Ali M Alsamil,Helga Gardarsdottir,Thijs J Giezen,Hubert G Leufkens,Toine C Egberts

doi:10.3390/ph14030189

Abstract

Regulatory approval of biosimilars predominantly relies on biosimilarity assessments of quality attributes (QAs), particularly the potentially critical QAs (pCQAs) that may affect the clinical profile. However, a limited understanding exists concerning how EU regulators reflect the biosimilarity assessments of (pC)QAs in European public assessment reports (EPARs) by different stakeholders. The type and extent of information on QAs and pCQAs in EPARs were evaluated for seven adalimumab biosimilars. Seventy-seven QAs, including 31 pCQAs, were classified and assessed for type (structural and functional attributes) and extent (biosimilarity interpretation and/or test results) of information in EPARs. Reporting on the QAs (35–75%) varied between EPARs, where the most emphasis was placed on pCQAs (65–87%). Functional attributes (54% QAs and 92% pCQAs) were reported more frequently than structural attributes (8% QAs and 22% pCQAs). About 50% (4 structural and 12 functional attributes) of pCQAs were consistently reported in all EPARs. Regulators often provided biosimilarity interpretation (QAs: 83% structural and 80% functional; pCQAs: 81% structural and 78% functional) but rarely include test results (QAs: 1% structural and 9% functional and pCQAs: 3% structural and 9% functional). Minor differences in structural attributes, commonly in glycoforms and charge variants, were often observed in adalimumab biosimilars but did not affect the functions and clinical profile. Despite the variability in reporting QAs in EPARs, the minor observed differences were largely quantitative and not essentially meaningful for the overall conclusion of biosimilarity of the seven adalimumab biosimilars.

Highlights

Biological drugs have become important treatment options for numerous diseases, including cancer and inflammatory diseases [1]
Rapporteurs from 11 member states prepared the initial European public assessment reports (EPARs) of the seven adalimumab biosimilars
The present study evaluated the type and extent of information on quality attributes (QAs) and potentially critical QAs (pCQAs) reported in EPARs by EU regulators for seven adalimumab biosimilars approved in Europe as of November 2020

Summary

Introduction

Biological drugs have become important treatment options for numerous diseases, including cancer and inflammatory diseases [1]. After patent expiration of the reference biologicals, biosimilars contribute to improved patient access to treatment due to competition, resulting in lower prices. Biosimilars are, generally, not exact replications of the reference biological but are highly similar [4]. The leading regulatory and health authorities in highly regulated markets, such as the European Medicines Agency (EMA), the United States Food and Drug Administration (US FDA), and the World Health Organization (WHO), have established frameworks and guidelines for the development, assessment, and approval of biosimilars [5,6,7,8]. Biosimilar development and regulatory approval predominantly rely on demonstrating the biosimilarity to the reference biological, which involves a stepwise comparability assessment

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