The US Food and Drug Administration (FDA) has announced a final rule expanding the approval pathway for nonprescription drug products by allowing the approval of a nonprescription drug product with an “Additional Condition for Nonprescription Use” (ACNU). This rule aims to expand consumer access to certain nonprescription drugs—that would otherwise be available only via prescription—by permitting their retail sale with an additional condition beyond labeling, such as a digital questionnaire to help the consumer decide if the medication is right for them.
Traditionally, nonprescription drugs have been available to consumers without a prescription only if they can be used safely and effectively based solely on their labeling. However, FDA has recognized that some medications require additional safeguards to ensure proper use and appropriate self-selection without a healthcare provider’s (HCP) supervision but may not otherwise warrant prescription status, and that the additional safeguards can be achieved with modern technological advancements.
KEY PROVISIONS OF THE FINAL RULE
The final rule, published on December 23, 2024 and effective on January 27, 2025, establishes novel (and additional) requirements for a nonprescription drug product with an ACNU, including application, labeling, and post-marketing reporting requirements. The rule also clarifies how the legal concepts of “misbranding” and a “meaningful difference” between marketed drug products will apply to nonprescription drugs with an ACNU.
1. Application Requirements
Under the final rule, pharmaceutical companies may submit New Drug Applications (NDAs) for nonprescription drugs that include an ACNU, demonstrating that the proposed ACNU is necessary to ensure appropriate self-selection and/or use by consumers, where labeling information alone will not suffice. FDA will then evaluate whether the data submitted by the applicant establishes that the ACNU adequately mitigates risks associated with using the drug without HCP supervision.
In addition to adhering to the existing content and format requirements for an NDA, applicants seeking to market a nonprescription drug with an ACNU must include the following information: (1) the purpose of the ACNU; (2) data demonstrating the necessity of the ACNU to ensure safe and effective use without HCP supervision; (3) data and an explanation on how the ACNU ensures appropriate self-selection or appropriate actual use of the drug by consumers; (4) proposed labeling that describes the key elements of the ACNU; and (5) how the ACNU will be operationalized.
Abbreviated New Drug Application (ANDA) applicants provide somewhat different information—in lieu of data supporting the ACNU, ANDA applicants are to submit information demonstrating that the key elements of the ACNU are the same as the key elements of the ACNU for its reference listed drug.
2. Labeling Requirements
A nonprescription drug product’s labeling must conform to specific ACNU-related labeling requirements that clearly inform consumers about the ACNU and provide instructions on how to fulfill its conditions. For example, the drug product must bear the following statement (or a similar FDA-approved statement) on the principal display panel and the immediate container surface: “You must complete an extra step to see if this drug is safe for you before you use it. Do not take this drug without completing this step. See the Drug Facts Labeling for more information.”
3. Post-Marketing Reporting Requirements
Nonprescription drug manufacturers must monitor, evaluate, and report any “ACNU failures”—defined as either a failure associated with the implementation of a key element of the ACNU, or the operationalization of an ACNU. This requirement involves submitting reports of ACNU failures to FDA within 15 calendar days through the FDA Adverse Event Reporting System, among other tasks.
4. Misbranding and Enforcement
The final rule establishes that a nonprescription drug with an ACNU that is made available to consumers is considered misbranded (and thus would be subject to related enforcement actions) if the applicant fails to fulfill the ACNU requirements. As such, applicants must ensure that any ACNU follows the specific implementation and post-approval requirements set forth by FDA.
5. An ACNU Represents a Meaningful Difference from an Existing Prescription Drug
Finally, FDA has determined that the existence of an ACNU for a nonprescription drug constitutes a “meaningful difference” between the nonprescription drug and an otherwise identical, existing prescription version of the drug, thereby permitting simultaneous marketing of both. This “dual” marketing status is generally unavailable as it is prohibited by the Federal Food, Drug, and Cosmetic Act unless there is a meaningful difference between the two versions. In the preamble to the final rule, FDA defended this determination in the face of contrary comments made by certain members of the public during the rulemaking process.
Key Takeaways for Stakeholders
The ACNU framework presents new opportunities and responsibilities for various stakeholders. The final rule provides a clear pathway for pharmaceutical companies to expand their product lines by offering certain medications as nonprescription drug products with appropriate safeguards. However, to be successful, these companies must invest in (1) the development and validation of ACNUs, (2) the submission of comprehensive drug applications and related user fees, (3) coordination with FDA in effectively utilizing this pathway, and (4) efforts to ensure ongoing regulatory compliance and fulfillment of post-marketing requirements.
Depending on the success and utilization of this pathway, manufacturers may also experience shifting dynamics in the prescription and nonprescription marketplaces for their products. Given potentially uncertain financial returns and limited value of any three-year new clinical investigation exclusivity (given FDA’s stance on the simultaneous marketing of a prescription and nonprescription-ACNU pair), it remains to be seen how frequently we will see this pathway used to expand the nonprescription marketplace.
Retailers of nonprescription drugs may need to establish additional processes and procedures and implement systems or make other adjustments to allow for consumers’ fulfillment of the additional condition(s) under the ACNU for impacted products before purchase. Although FDA clarified that state-licensed pharmacists would not be necessary for completing the condition(s), the advent of ACNUs may further complicate the existing “behind the counter” shelf-space management by retailers.
CONCLUSION
This final rule by FDA represents a significant shift in the regulatory landscape, aiming to enhance consumer access to medications while maintaining safety standards. By establishing a drug application framework for certain additional drugs to be sold without a prescription, provided specific conditions are met by the consumer, FDA states that it seeks to improve public health outcomes and allow consumers to manage their health, often in a more cost-effective way.
Stakeholders across the healthcare sector must collaborate to ensure that any future ACNUs are implemented effectively so that the benefits of increased access are realized without compromising consumer safety and the efficacy of nonprescription drugs.