The recommendation – which is set out in long awaited draft guidance today – is that sponsors should submit data from a switching study, or studies, to the US Food and Drug Administration (FDA) in order to deem a biosimilar interchangeable with its reference product.
“The main purpose of a switching study or studies is to demonstrate that the risk in terms of safety or diminished efficacy of alternating or switching between use of the proposed interchangeable product and the reference product is not greater than the risk of using the reference product without such alternation or switch,” the Agency says in the guidelines.
“A switching study or studies should evaluate changes in treatment that result in two or more alternating exposures (switch intervals) to the proposed interchangeable product and to the reference product.”
Under existing laws, the Food and Drug Administration (FDA) deems a biosimilar product interchangeable if a sponsor can prove it is “expected to produce the same clinical result as the reference product in any given patient” and that switching is safe.
However, prior to today’s draft guidance the US agency had not defined how a sponsor must go about generating such proof.
Certain switching studies have already been undertaken, most prominently the Norwegian government led 'NOR-SWITCH' study which found last October Celltrion's Remsima was not inferior to its reference biologic, J&J's Remicade (infliximab).
However, using a non-US licensed comparator product would not be appropriate in a switching study, the guidance says, as it is possible the proposed interchangeable product and the non-US reference product have “subtle differences in levels of specific structural features.”
Because of these subtleties, “there is uncertainty as to whether the results observed in a switching study using a non-US licensed comparator product would also be observed if the US licensed reference product had been used instead.”
Furthermore, the FDA claims there may be numerous versions of non-US comparator products each with possible subtle differences in levels of structural features.
“The goal of a switching study or studies is to determine a biosimilar product’s interchangeability with a reference product that is licensed for use in US clinical settings, thus establishing interchangeability with a product that patients will not receive in the United States would generally not be appropriate.”
Today's publication will be welcomed by industry which had expected recommendations to be published last year.