Ensuring the Consistency of Biosimilars

Abstract

Background: Biological products are subject to constant reappraisal by regulatory agencies and pharmaceutical companies once they have entered the market, since every improvement in their manufacturing process has the potential to alter the basic properties of these molecules.

Methods: Narrative review focusing on scientific literature as well as legal documents from regulatory agencies.

Results: Evaluating the impact of each manufacturing change of these drugs requires rigorous analyses in proportion to the anticipated risk of inducing more or less molecular micro-heterogenicity. There are currently more than 30 biosimilars of TNF-α blockers at different stages of testing, each with a specific manufacturing process. Although the initial demonstration of biosimilarity is now a well-established exercise, it does not guarantee that successive manufacturing changes will not result in a widening gap between drifted/evolved innovators and drifted/evolved biosimilars, as well as among the different biosimilars of a given original biologic.

Conclusion: Given the structural complexity of TNF-α blockers-as well as of other biologic drugs included in the armamentarium of systemic inflammatory diseases-regulatory agencies should make available to the practitioner, in a simple and constantly updated way, all available data regarding quality standards of both original molecules and biosimilars. Furthermore, they should strive to guarantee that, once a compound has received approval, it maintains a level of consistency throughout its commercial life in order to maintain and increase confidence in these valuable drugs.

Keywords: Biosimilars; TNF-α blockers; patient safety.; quality control; regulation; standards; therapeutic equivalency.