The US Food and Drug Administration (FDA) has issued final guidance, New Chemical Entity Exclusivity Determinations for Certain Fixed-Combination Drug Products to set forth a change in the agency’s interpretation of the five-year new chemical entity (NCE) exclusivity provisions as they apply to certain fixed-combination drug products (fixed-combinations). Historically, FDA has interpreted these provisions such that a fixed-combination was ineligible for five-year NCE exclusivity if it contained a previously approved active moiety, even if the product also contained a new active moiety (i.e., an active moiety that the agency had not previously approved). Recognizing that fixed-combinations have become increasingly prevalent in certain therapeutic areas (including cancer, cardiovascular, and infectious disease) and that these products play an important role in optimizing adherence to dosing regimens and improving patient outcomes, the FDA is revising its interpretation off certain fixed-combination products. FDA intends to apply the new interpretation from the date of this guidance’s publication. Therefore, the new interpretation will not apply to fixed-combination drug products that were approved prior to the publication of this guidance document.
Under the agency’s historical interpretation of the applicable statutory and regulatory provisions, the presence of a previously approved active moiety in a fixed-combination generally rendered the drug product ineligible for five-year NCE exclusivity. This outcome arose out of the agency’s interpretation of the word "drug" in certain provisions of the Federal Food, Drug, and Cosmetic Act and the term "new chemical entity" in the agency’s implementing regulations to mean "drug product." The FDA intends to instead interpret "drug" in the relevant provisions to mean "drug substance" or "active ingredient." This will allow a drug substance that meets the definition of new chemical entity to be eligible for five-year NCE exclusivity, even when it is approved in a fixed-combination with another drug substance that contains a previously approved active moiety. Accordingly, under the agency’s new interpretation, a drug substance would be eligible for five-year NCE exclusivity, provided that it meets the definition of a new chemical entity, regardless of whether that drug substance is approved in a single-ingredient drug product, in a fixed-combination with another drug substance that contains no other previously approved active moiety, or in a fixed-combination with another drug substance that contains a previously approved active moiety. For example, a fixed-combination drug product that contains a drug substance with a single, new active moiety would be eligible for five-year NCE exclusivity, even if the fixed-combination also contained a drug substance with a previously approved active moiety.