Reporting of quality attributes in scientific publications presenting biosimilarity assessments of (intended) biosimilars: a systematic literature review

Abstract

Last years, more than 46 unique biosimilars were approved by EMA and/or US-FDA following patent expiration of reference products. Biosimilars are not identical like generics, but highly similar versions where demonstrating biosimilarity of quality attributes (QAs) to a reference product is the basis of development and regulatory approval. Information on QAs assessed to establish biosimilarity may not always be publicly available, although this information is imperative to understand better the science behind biosimilars approval. This study aims to identify QA types reported in publications presenting biosimilarity assessments of (intended) biosimilars over time. English full-text publications presenting biosimilarity assessments of QAs for (intended) biosimilars between 2000 and 2019 identified from PubMed and EMBASE. Publication characteristics and QAs classified into: structural (physicochemical properties, primary structure, higher-order structures (HOSs), post-translational modifications (PTMs), and purity and impurities) and functional (biological and immunochemical activities) were extracted from publications. Seventy-nine publications were identified (79% open-access, 75% industry-sponsored, 62% including unapproved biosimilars, and 66% involving antibodies). Reporting frequencies varied for QA types: biological activity (94%), physicochemical properties (81%), PTMs (79%), primary structure (77%) purity and impurities (73%), HOSs (58%), and immunochemical activity (41%). The number of publications increased from 6 (7%) during 2009-2011 to 62 (79%) during 2015-2019. Eighteen (28%) publications reported all QA types relevant to an active-biological-substance. Reporting of most QA types increased over time that most evidenced by immunochemical activity (from 0% to 47%) which occured after EMA monoclonal antibody (mAbs) guidline in 2012 and more publications on mAbs later on when compared to earlier period. Biosimilarity assessments of QAs have been published in peer-reviewed publications for about 60% of approved biosimilars. Publishing biosimilarity assessments and reporting QAs over time appears to be affected by regulatory actions that occurred in 2012-2015, including regulatory approval and development of regulatory guidelines for biosimilars. Availability of a complete, publicly accessible and unbiased biosimilarity assessment of QAs, as part of a trusted and transparent regulatory process, will contribute to increased confidence and acceptance of biosimilars in clinical practice.