Support Mounts for FDA to Waive Bridging Studies for Biosimilars
As part of FDA’s action plan on biosimilars, Commissioner Scott Gottlieb said in July the agency is “actively exploring" whether "in some circumstances" FDA can "facilitate the increased use of non-U.S.-licensed comparator products in certain studies to support" biosimilar applications.The change would allow biosimilar developers to purchase reference product to demonstrate biosimilarity from Europe or other region without further demonstrating that the EU-licensed and US-licensed reference products are similar.
Gottlieb explained in his action plan speech, echoing earlier comments, that biosimilar developers could cut costs by using biologic reference products sourced outside the US. And though some, like biosimilar developer Sandoz, are supporting this push from the commissioner, others representing the industry are pushing back in some circumstances.
PhRMA told Focus in a statement that it supports the adoption of analogous bridging study standards when non-US licensed comparators are used in innovator and biosimilar development programs.
“PhRMA is concerned, however, with proposals to waive bridging study requirements based on nonpublic information where a non-U.S. comparator is produced at the same facility as the reference product…in cases where this information is trade secret, FDA reliance on these trade secrets or disclosure of them to a biosimilar developer—either explicitly or implicitly through waiver of bridging study requirements—would raise serious issues under federal law and the Takings Clause,” the lobbying group said in a statement.
But Gillian Woollett, senior vice president of Avalere Health, confirmed to Focus that a proposal she co-authored in a May 2017 paper to waive certain bridging studies, “only requires public information - indeed the table in the paper on the clinical studies is all public. Hence no constitutional issues arise.”
Woollett's proposal calls for: “A greatly simplified basis for selecting a reference comparator, that does not require conducting new bridging studies,” which it says, “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 proposal also makes clear that bridging studies can be waived only when certain criteria are met, including when there is publicly available evidence that the selected reference biologic and the locally licensed product have been approved based on essentially the same original clinical safety, effectiveness and other data.
Sandoz, meanwhile, said it supports FDA’s considerations to enable the use of global reference products, but it acknowledged the challenges that need to be addressed – including the development of such criteria under which a global reference product may be used and related bridging studies waived.
“This approach could significantly reduce the complexity, duration and costs of biosimilar development as well as contribute to faster and broader patient access to these life-saving innovative medicines,” the company told Focus. “Additionally, enabling the use of global reference products could be useful for conducting head-to-head trials of reference biologics where comparator sourcing can be similarly challenging. We believe the concept of using global reference products conceivably applies to both biosimilar and interchangeable biologics.”