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Regulatory Focus™ > News Articles > FDA’s Draft Biosimilar Interchangeability Guidance: Stakeholders Seek More Clarity

FDA’s Draft Biosimilar Interchangeability Guidance: Stakeholders Seek More Clarity

Posted 04 April 2017 | By Zachary Brennan 

FDA’s Draft Biosimilar Interchangeability Guidance: Stakeholders Seek More Clarity

As comments on the US Food and Drug Administration’s (FDA) draft guidance on biosimilar interchangeability begin to trickle in, stakeholders seem optimistic and appreciative of the agency’s draft though some suggest tweaks to FDA's recommendations for switching studies.


In January, FDA released its draft guidance on biosimilar interchangeability for consultation, noting that there is "no single data package that will work for all proposed interchangeable products."

The draft calls on companies to use so-called "switching studies" to determine whether alternating between a biosimilar and its reference product two or more times impacts the safety or efficacy of the treatment.

"Rather than being used only as a control, the comparator product is used in a switching study in both the active switching arm and the control non-switching arm," FDA writes. "Thus, using a non-US-licensed comparator product generally would not be appropriate."

FDA also says sponsors should consider the "totality of factors" for their product to determine the amount and type of data to demonstrate interchangeability.


While more comments are likely to be published in the docket before the 19 May deadline for submissions, the first nine reveal a range of opinions on switching studies and other areas where commenters are seeking more clarity.

The Ohio Public Employees Retirement System (OPERS), for instance, expressed concern with the burdens of FDA’s proposed requirements for conducting switching studies.

"These study requirements are burdensome in terms of the length of time required for review and substantial patient study size. They will delay patient access to interchangeable products as well as increase manufacturer costs that will ultimately be passed onto patients and healthcare purchasers," OPERS said, also noting concerns "about the FDA's recommendation that sponsors use a United States (U.S.) licensed reference product in a switching study or studies."

However, Michael Schweitz, MD, federal advocacy chair of the Coalition of State Rheumatology Organizations, said his group "strongly" agrees with FDA’s recommendation to not use non-US comparators, noting, "there may be differences between U.S. and international products, and even among international products. While these differences may be subtle, they could be sufficient to render them useless for a switching study designed to prove interchangeability for U.S. patients. We urge FDA to maintain this position."

Schweitz also praised FDA’s call to use actual patients in switching studies, as opposed to healthy volunteers, though he cautioned that "for rare diseases, the need to find real patients may create a hurdle that is unreachable for manufacturers." He urged FDA to take a similar approach as Health Canada and "require some clinical data for all indications especially when the pathophysiologic mechanisms involved in the diseases are clearly different."

The insurer Cigna, meanwhile, says it supports the use of switching studies, but seeks additional FDA guidance on the types of switching studies that may be used.

"In particular, we ask FDA to make clear to sponsors that studies need to demonstrate the performance of a proposed interchangeable against a reference product only. In cases where at least one interchangeable product is already available on the market, we ask FDA to specify that switching studies may use either the reference product or the approved interchangeable product as the approved comparator," Cigna writes.

The insurer also says FDA "should make clear that only one switching study is needed against either the original reference product or the approved interchangeable, but not both. Finally, we encourage FDA to add clarity about switching between biosimilars after they both have been proven interchangeable to the reference product. For example, will dispensing pharmacists be required to provide the same level of healthcare provider and patient notification when switching between biosimilars as when switching between a reference product and a biosimilar?"

Health service provider QuintilesIMS notes concerns related to the control of post-approval changes for interchangeable biosimilars, noting that "continued biosimilarity testing throughout the lifecycle of an interchangeable biosimilar product is not feasible, or desirable. Instead, QuintilesIMS strongly recommends applying the same approach to the evaluation of post approval changes to the interchangeable product as for any other biologic products."

QuintilesIMS also said its position is that "additional conditions of use for the reference product licensed, after the interchangeable product has been licensed, should be extrapolated to the interchangeable biosimilar with a scientific justification."

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