The US FDA on Monday announced in a draft guidance that it’s revising its historical interpretation of the 5-year NCE exclusivity provisions to further incentivize the development of certain fixed-combination products.
Combination therapies have emerged as the standard of care in certain disease settings, particularly cancer, HIV, cardiovascular disease, and infectious disease and since finalizing its guidance on the development of two or more drugs for use in combination, the FDA has “concluded that a change in our position regarding the availability of 5-year NCE exclusivity for certain fixed-combinations would further incentivize the development of these important products.”
Historically, the FDA interpreted the term drug in the eligibility clause of the 5-year NCE exclusivity statutory provisions to mean drug product, not drug substance.
As far as how the FDA plans to incentivize such combo drugs, the agency said it intends to “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 5-year NCE exclusivity, even when it is approved in a fixed-combination with another drug substance that contains a previously approved active moiety.”
A moiety is a part or functional group of a molecule. Accordingly, a drug product would be eligible for 5-year NCE exclusivity if it contains a drug substance that meets the definition of a new chemical entity, regardless of whether that drug substance is approved alone or in a fixed-combination.
The available data on fixed-combination approvals supports this proposition. In the nearly 20 years since FDA finalized the regulations on exclusivity, the agency has approved 19 NDAs (new drug applications) for fixed-combinations containing at least one new active moiety. More than half of these NDAs have gained approval within the last 7 years.
If the new interpretation is adopted, FDA intends to apply it prospectively so this guidance will not apply to fixed-combination drug products that were approved prior to adopting the new interpretation.
In 2013, the Agency was petitioned to revise its current interpretation of the 5-year NCE exclusivity provisions and the petitioners made several contentions in support of their conclusion that FDA’s current interpretation of the 5-year NCE exclusivity provisions discourages the development of new active moieties in fixed-combinations with previously approved active moieties.
Among other things, the petitioners stated that FDA’s existing interpretation “might encourage an applicant to submit an NDA for a single-entity product before it submits an NDA for a fixed-combination to secure 5-year NCE exclusivity for the single entity and protect the later-approved fixed-combination with that exclusivity under the umbrella policy.”
“This might lead to suboptimal drug development strategies, especially in light of the increasing importance of fixed-combinations,” the FDA says.