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.