Previous FDA Policy Delineating Prescription and OTC Status 

Prior to the Additional Condition for Non-prescription Use (ACNU) final rule, FDA regulations only allowed prescription (Rx) drug products to be either fully (“full Rx-to-over-the-counter [OTC] switch”) or partially (“partial Rx-to-OTC switch”; e.g., only specific strengths or indications) changed to non-prescription marketing status. This meant that a single product could not be simultaneously designated as a prescription and non-prescription product for all use cases.  

To switch a product to non-prescription status, sponsors would have had to demonstrate that the drug product was both efficacious and safe to use in a non-prescription setting and that the label contained sufficient information for consumers to use the drug safely and effectively without a healthcare professional’s supervision. The FDA provided guidance documents on label comprehension studies and self-selection studies for nonprescription drug products.  

This prior regulatory paradigm limited access to products as either prescription or nonprescription. This has been particularly impactful for certain classes of drugs for which availability via prescription and nonprescription could be considered safe and valuable.    

Provisions of the ACNU Final Rule  

On December 23, 2024, the FDA issued a final rule to broaden the types of prescription drug products that consumers can purchase OTC, and allow a drug to be marketed with both prescription and non-prescription status. The rule went into effect May 27, 2025, after its original implementation date of January 27, 2025, was postponed twice. 

The final rule offers manufacturers an approval pathway for a non-prescription drug with ACNU by allowing flexibility when labeling alone cannot convey the necessary information for consumer self-selection or appropriate actual use. Manufacturers would need to submit a new drug application (NDA) or an abbreviated new drug application (ANDA) detailing how the ACNU is operationalized and includes consumer studies. The ACNU would need to demonstrate a “meaningful difference” between the prescription drug product and its non-prescription counterpart.  

If the ACNU is accepted as a reasonable mechanism for consumer self-selection, it would be sufficient to account for a “meaningful difference” between the prescription drug and its non-prescription counterpart without any differences in the drug attributes (e.g., strength). 

Strategic Considerations for Manufacturers 

Manufacturers will need to carefully plan early if they intend to market their products with both prescription and non-prescription status. 

If a consumer is unable to appropriately self-identify for use of the product based solely on the label, manufacturers can propose a variety of different ACNU methods to bridge any gap between insufficient labeling and appropriate self-selection. For example, manufacturers can propose that before purchasing the nonprescription drug product, consumers would need to take a questionnaire on a display screen at a pharmacy kiosk or via an automated telephone response system. Consumers will know there is an extra step required before purchasing the drug product from the label. Manufacturers will need to consider what data is needed to show the safety of the drug product when offered OTC with an ACNU, and what ACNU methodology will be accepted by the FDA to ensure consumer adherence, proper self-selection, and clear labeling. 

There are multiple downstream market access implications, including market share and volume changes, pricing approaches, payer coverage determination, and consumer decision making.  Even if a manufacturer is not planning to submit an ACNU non-prescription application for their drug product, manufacturers will want to carefully observe potential market dynamic shifts for an entire class of drugs if one of the products does receive ACNU non-prescription marketing status. Drug classes that may be affected include antihistamines, analgesics, topical pain or itchiness relief creams, acid reducers, oral contraceptives, and potentially other drugs for common chronic diseases.  

Potential for Added Demand to Pharmacists 

Approval of an ACNU product also has implications for pharmacies, especially if the ACNU product or state law requires intervention by the dispensing pharmacy, such as storing the product behind the counter to facilitate counseling by a pharmacist or requiring a survey to be administered by a pharmacist. Pharmacies will want to consider if there will be an added burden for pharmacists to administer these drugs, if infrastructure changes will need to be made, and if every pharmacy will be providing access to these products. 

How Relevant Parties Can Prepare for Coming Changes 

The ACNU pathway has the potential to optimize patient access to drugs via two distinct routes associated with unique costs and health plan coverage. Manufacturers, payers, and pharmacies will need to thoroughly consider the various impacts on their organizations when determining the value of the ACNU pathway.  

Avalere Health’s regulatory, payer, and market access experts can help interested parties make informed decisions regarding utilization of this new pathway, as well as with execution of strategies. To discuss how Avalere Health can help industry stakeholders navigate this new approval pathway, connect with us.