On March 3, 2026, the U.S. Food and Drug Administration (FDA) announced the publication of its new draft guidance “New Clinical Investigation Exclusivity (3-Year Exclusivity) for Drug Products: Questions and Answers” ("NCIE Draft Guidance"). The new draft guidance (1) describes the statutory and regulatory criteria for eligibility; (2) clarifies common questions about the criteria; (3) provides model language for requesting exclusivity; and (4) clarifies FDA's decision-making and notification processes for 3-year exclusivity. The draft guidance does not address the scope of 3-year exclusivity, which has been addressed in a number of citizen petition responses and court decisions and often is a complex, fact-intensive inquiry.
Background
The Drug Price Competition and Patent Restoration Act of 1984 (Hatch-Waxman Amendments), among other substantial changes, created incentives for the development of new drugs and new uses of previously approved drugs through market exclusivity periods and patent-term extensions. The incentives include a 3-year period of exclusivity for an approval of a new condition of use for a drug containing a previously approved active moiety that generally is supported by a new clinical investigation essential to approval. The exclusivity prevents approval of 505(b)(2) new drug applications (NDAs) and abbreviated new drug applications (ANDAs) for the new condition of use protected by the exclusivity.
To receive 3-year exclusivity, an application (or supplement) must meet the following conditions:1
- The application is for a drug, which includes an active moiety that has been approved in another 505(b) application; and
- The application contains reports of new clinical investigations that are:
- .Not bioavailability studies;
- Essential to the approval of the application (or supplement); and
- Were conducted or sponsored by the applicant.
FDA defines many of the terms relevant to 3-year exclusivity at 21 CFR 314.108 and provides a general description of how to request 3-year exclusivity at 21 CFR 314.50(j)(4). However, questions often arise regarding whether a study fits within the definition of “new clinical investigation,” whether the clinical investigation was essential to approval, whether the investigation was conducted or sponsored by the applicant, and what certifications and supporting information must be provided to establish exclusivity. The new draft guidance provides some clarity on those questions.
Three-year exclusivity criteria
“New clinical investigation”
The draft guidance clarifies that the drug product studied in the clinical investigation does not necessarily need to be the same as the drug product approved in the application to potentially qualify for exclusivity. FDA uses the example of a clinical investigation for a granule formulation supporting approval for a tablet formulation, which can be crushed and administered similarly to the granule formulation to illustrate this point.
The draft guidance also memorializes FDA’s position that a clinical investigation that includes a pharmacokinetic (PK) assessment does not automatically preclude eligibility. In the draft guidance, FDA recognizes that studies may have multiple purposes and that an investigation evaluating bioavailability in conjunction with an assessment of a safety and/or efficacy endpoint to support approval may be eligible. However, FDA clarifies that a study incorporating routine safety monitoring but primarily conducted for the purposes of determining bioavailability is unlikely to qualify.
Additionally, FDA addresses when data from a cohort or treatment arm in a previously submitted study that is distinct from the originally approved population may be considered “new” for eligibility purposes, even where the results of at least one other cohort or treatment arm were previously relied on for approval of an application. FDA outlines the following factors as relevant to this determination:
- whether there is an acceptable scientific or medical reason for the separate cohort or treatment arm;
- whether the separate cohort or treatment arm evaluates different patient populations and/or different drug products; and
- whether the separate cohort or treatment arm was prespecified in the protocol.
FDA indicates that a wholesale rejection of such data would “elevate form over substance,” and provides insight into FDA’s motivations for potentially accepting “new” data from an “old” study. Sponsors considering eligibility for 3-year exclusivity should consider whether the investigation submitted for approval fits within this framework.
Essential to approval
FDA states that the trial must be “vital” to the application. In other words, without the new clinical investigation, FDA would not have sufficient information to approve the application. To make this case, an applicant should submit the following:
- a list of all published studies relevant to the conditions for which the applicant is seeking approval;
- a certification that the applicant has searched the scientific literature, that the list is complete and accurate to the best of the applicant’s knowledge, and in the applicant’s opinion, such published studies and/or reports do not provide a sufficient basis for approval without the new clinical investigation submitted as part of the NDA; and
- an explanation as to why the studies and/or reports are insufficient.
Conducted or sponsored by the applicant
An applicant should submit the following in support of its assertion that it meets this definition:
- provide the IND number under which the new clinical investigation that is essential to the approval of its NDA was conducted; or
- provide certification and information sufficient to show that the applicant or its predecessor in interest provided substantial support for the clinical investigation(s) that is essential to approval by either:
- providing a certified statement from a certified public accountant that the applicant or its predecessor provided more than 50% of the cost of the study; or
- an explanation of why FDA should consider the applicant to have met the requirement even if it (or its predecessor) did not provide 50%+ of the financial contribution to the study.
FDA further clarifies that to show that this requirement is met based on the acquisition of exclusive rights to a study, the applicant should provide a certified statement that the applicant acquired such exclusive rights, along with any relevant supportive documentation. FDA will look at the “totality of the information” to determine whether an applicant has acquired exclusive rights to a study.
Process for requesting 3-year exclusivity
Building upon its regulations, FDA outlines the specific information to be included in any 3-year exclusivity request, including its correct placement in Module 1 of the NDA. The appendix to the draft guidance includes representative language for making such a request.
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There is an opportunity to submit comments on the draft guidance, preferably within 60 days following publication in the Federal Register (i.e., by May 4, 2026).
[1] 21 USC 355(c)(3)(E)(iii) and (iv), 355(j)(5)(F)(iii) and (iv).
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