Investigators Weigh Differences in Biosimilar Quality Reporting

An attempt to understand whether regulatory and scientific sources are consistent with each other in their reporting of quality attributes (QAs) for biosimilars has demonstrated general conformance between these 2 sources of biosimilar information.

Reporting of biosimilar quality attributes (QAs) is “inconsistent but reasonably complementary” between regulatory and scientific publications, according to the study comparing European public assessment reports (EPARs) from the European Medicines Agency (EMA) with peer-reviewed scientific publications on biosimilars.

Investigators looked at the reporting of 2 general categories of biosimilar QAs: structural and functional. Structural qualities include amino acid sequence, which must be similar between biosimilars and their reference products. They also concern purity of the drugs and physicochemical properties. Functional QAs include immunochemical activity and biological activity, such as antibody binding to the target ligands necessary to achieve a clinical response.

QAs, therefore, “describe specific physical, chemical, biological or microbial properties” of a biosimilar, and although the aims of scientific and regulatory reporting differ, data on QAs should be consistent, according to the authors. ”Limited information” about the consistency and complementarity of QA reporting made this study necessary, they wrote.

“Along with the surge of biosimilars introduced to the European market over the last decade, the need for comprehensive and reliable information among decision makers (eg, clinicians, pharmacists, payers, and regulators) about the justification of biosimilarity has become pertinent,” the authors wrote.

The authors focused exclusively on adalimumab biosimilars for their study because the monoclonal antibody (mAb) to tumor necrosis factor alpha (TNF) “has the largest number of approved mAb biosimilars and the broadest spectrum of therapeutic indications among TNF-α inhibitors.” They studied the reporting of 77 different QAs (53 structural and 24 functional) from reports on 6 adalimumab biosimilars.

Functional vs Structural Attributes

The total number of individual QAs reported for adalimumab biosimilars in regulatory and scientific sources ranged from 47 to 60, and the number of QAs reported consistently by both source types varied by biosimilar, ranging from 28% to 75%. Overall, a greater number of QAs were reported in EPARs (range 36-57) compared with scientific publications (range 14-49).

In both EPARs and scientific publications, functional QAs were reported more frequently than structural QAs (96% vs 89%) and more consistently (88% vs 62%, respectively). The authors suggested the reason functional attributes were more frequently and more consistently reported could be that “they reflect the clinically relevant” mechanisms of action of the biologic drugs and are useful in predicting the outcomes of clinical studies.

For example, binding to and neutralizing TNF-ɑ are functional attributes relevant to adalimumab’s mechanism of action, and these QAs were reported consistently in both information source types for all 6 biosimilars.

Regulatory and scientific motives also may have much to do with the type and frequency of information that gets reported. “Regulators…may be more concerned with the consistency and accountability of decisions. Researchers, frequently affiliated with biosimilar companies, might be more focused on presenting positive news—that is, QAs with favorable results in terms of biosimilarity, such as highly similar attributes,” they wrote.

Biosimilarity Interpretation

The authors analyzed whether publications included test results, biosimilarity interpretation, or both for each QA. EPARs more commonly included a biosimilarity interpretation without test results compared with scientific publications. The 2 sources agreed, on average, on 90% (range 78%-100%) of QAs in their interpretations of biosimilarity.

The authors noted the QAs with agreement on biosimilarity interpretation “were frequently related to biological and immunochemical activity [functional QAs],” whereas, “the types of QAs with different biosimilarity interpretations in both sources were frequently related to [post-translational] modifications and biological activity.”

Recommendation: Consult Both Sources

The authors advised consulting both sources of information to obtain a “more complete reporting of the biosimilarity assessment” and “an improved understanding of how biosimilarity was established at the molecular level.”

According to the authors, there have been few previous assessments of “whether and how data presented in these 2 publicly available information sources overlap.” However, studies assessing the reporting of safety and efficacy data “have found substantial discord between regulatory reports and scientific publications.” Their study, they said, was probably the first to examine whether the reporting of QAs is consistent or complementary between regulatory and scientific sources.

The Need for Consistency

The authors argued bringing greater consistency to reporting of QAs between sources could ultimately contribute to increased acceptance and use of biosimilars by clinicians. “A comprehensive and consistently reported set of QAs is needed to understand the science behind regulatory approval and increase confidence in biosimilars in clinical practice,” they wrote.


Alsamil AM, Giezen TJ, Egberts TC, Leufkens HG, Gardarsdottir H. Comparison of consistency and complementarity of reporting biosimilar quality attributes between regulatory and scientific communities: an adalimumab case study. Biologicals. 2021;S1045-1056(20)30142-1. doi:10.1016/j.biologicals.2020.12.003

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