There’s no question that drug pricing is one of the most important issues in health care right now, and while such pricing considerations are outside FDA’s statutory mandate, it has not stopped FDA from trying to address pricing issues through enhancing drug competition (see, for example, our discussions of the Drug Competition Action Plan and the Biosimilar Competition Action Plan). To that end, FDA has attempted to limit exclusivity awards in an effort to facilitate generic access, by, for example, requiring proof of clinical superiority for Orphan Drug Exclusivity (Depomed) or by limiting the definition of active ingredient to active moiety (Vascepa). But courts have not necessarily agreed with FDA’s interpretation of its governing statute (the FDCA). In some of these instances—Depomed serving as a prime example—Congress has not hesitated to step in.
Most recently, the Senate passed legislation amending the definition of “active ingredient” with respect to New Chemical Entity (“NCE”) exclusivity, presumably in an attempt to address the Vascepa litigation. In a case that we followed closely in 2015, Amarin challenged FDA’s determination that its Vascepa Capsules (icosapent ethyl) was not entitled to New Chemical Entity exclusivity based on FDA’s theory that Vascepa’s “active ingredient” is a component of a mixture that makes up the “active ingredient” of Lovaza, a previously approved drug. FDA opined that when a mixture is well-characterized and components of that mixture have been identified as both the active ingredient and the active moiety in another product, a component of that mixture is not eligible for NCE exclusivity because it contains a previously approved active ingredient or moiety. The key legal issue in that case was framed as “whether the prior approval of a drug product, the active ingredient of which is a complex mixture of constituents, constitutes approval of each constituent as an active ingredient so as to preclude NCE exclusivity for a new drug product in which one of those constituents alone is the active ingredient.” Central to this dispute was the definition of “active ingredient” as compared to “active moiety” in the context of mixtures. While the statute offers NCE exclusivity for a new “active ingredient,” FDA regulations offer it for a new “active moiety.” And while the distinction is often inconsequential, it becomes relevant for poorly characterized or well characterized mixtures. As we explained back in 2015, Judge Moss was not too convinced by FDA’s conflation of active moiety and active ingredient, noting that it contradicts the plain language of the statute and is inconsistent with other provisions (and application of those provisions) of the statute.
Presumably with this decision in mind, Congress is granting FDA permission to conflate those definitions in a recent bill passed by the Senate in mid-March 2021. S.415, entitled “An Act to amend the [FDCA] with respect to the scope of new chemical exclusivity” strikes the term “active ingredient” throughout the drug provisions set forth in section 505 of the FDCA and inserts “active moiety.” Under this new definition, an active moiety approved in a mixture of an active ingredient can now block a component of that active moiety used alone as an active ingredient from obtaining NCE exclusivity. This bill gives FDA the discretion it relied upon in the Vascepa litigation to make narrower NCE exclusivity decisions and therefore further restrict awards of such exclusivity and bolsters any denials by further review of an Advisory Committee. Though, practically, the bill will have little effect, active ingredients composed of “mixtures” can no longer rely on Judge Moss’s decision. Further, this new definition of “active ingredient” refers all new active moieties to an Advisory Committee for review unless FDA provides a reason not to do so. Theoretically, this will ensure that all NCE determinations—well characterized active ingredient or otherwise—are consistent.
In a different but related bill, Congress attempts to address biological product pricing through further education about biosimilars. In S.164, “Advancing Education on Biosimilars Act,” Congress provides authority for FDA to maintain and operate a website providing educational materials regarding biosimilars and interchangeable biosimilars. The bill also requires FDA to publish the action package and summary review of each approved biologic and biosimilar. It’s not clear how this bill would change the status quo. Firstly, under the bill, the provision of educations resources is optional, as the bill uses the term “may” rather than “shall.” Secondly, FDA already engages in this type of education on its website and as part of its Biosimilars Competition Action Plan. And FDA already publishes the summary basis of approvals for (at least some) biologics and biosimilars, which you can access through the Purple Book, in its drug database. Perhaps this a response to the rampant misinformation about the quality of biosimilars, but, again, it’s not entirely clear how this will help.
Both S.415 and S.164 have cleared the Senate and are up for review in the House of Representatives.