A ‘Global Reference’ Comparator for Biosimilar Development

Abstract

Major drug regulators have indicated in guidance their flexibility to accept some development data for biosimilars generated with reference product versions licensed outside their own jurisdictions, but most authorities require new bridging studies between these versions and the versions of them licensed locally. The costs of these studies are not trivial in absolute terms and, due to the multiplier effect of required repetition by each biosimilar sponsor, their collective costs are substantial. Yet versions of biologics licensed in different jurisdictions usually share the same development data, and any manufacturing changes between versions have been justified by a rigorous comparability process. The fact that a biosimilar is usually expected to be licensed in multiple jurisdictions, in each case as similar to the local reference product, confirms that minor analytical differences between versions of reference biologics are typically inconsequential for clinical outcomes and licensing. A greatly simplified basis for selecting a reference comparator, that does not require conducting new bridging studies, is proposed and justified based on the shared data of the reference product versions as well as the proof offered where biosimilars have already been approved. The relevance of this proposal to the interchangeability designation available in the US is discussed.