Stakeholders ask FDA for more clarity, predictability for nonprescription drugs

Stakeholders want the US Food and Drug Administration (FDA) to clarify and streamline regulatory requirements for sponsors of nonprescription over-the-counter (OTC) drugs. They also cautioned that the agency should avoid measures that could harm the generic drug industry, which could ultimately raise drug prices.

A top priority for FDA Commissioner Marty Makary is to lower healthcare costs, including promoting the approval of more nonprescription drugs. In December, the agency issued a request for comment on measures it can take to help bring more nonprescription drugs to market and on topics to be discussed at a public meeting scheduled this year on the issue.

Responding to the request, the drug lobby group PhRMA said that while it agrees with FDA's efforts to increase access to OTC drugs, it said that the agency's regulatory decisions should not be based on pricing considerations. Broadly speaking, the group said that any decisions to convert prescription drugs to OTC should be made in collaboration with the drug sponsor and advice from the external experts on the Nonprescription Drugs Advisory Committee (NDAC). Furthermore, it said that any policy should not come at the cost of current incentives to encourage sponsors to make Rx-to-OTC switches, and the agency should work with sponsors and use the additional condition for nonprescription use (ACNU) rule to achieve its goals.

"The best way effectively and efficiently to achieve Rx-to-OTC switches is for the Agency to work collaboratively with the sponsors of New Drug Applications (NDAs) for prescription products on plans for the sponsors to remove the prescription-only requirement," said PhRMA. "FDA should engage in regular consultation with NDA sponsors about prescription drug products that sponsors believe are good candidates for Rx-to-OTC switches.

"NDA sponsors have the most information about their products and are uniquely situated to determine whether and under what circumstances it would be appropriate to request a switch and to complete any actual-use or label-comprehension studies necessary to achieve a switch," the group added. "And it is the sponsors who must develop the evidence and drive the switch process to manage the risk of prematurely or inappropriately removing prescription safeguards."

PhRMA noted that currently, sponsors who want to convert a prescription drug to an OTC product must submit a supplemental new drug application (sNDA), which typically requires a clinical trial, thereby imposing additional costs on sponsors. In terms of current incentives to convert prescription drugs to OTC, the group noted that under the Food, Drug, and Cosmetic (FD&C) Act, Congress has mandated that when a new application is approved that requires a clinical trial, the sponsor is given three-year exclusivity and urged the agency to ensure that its policies do not affect that exclusivity incentive.

"One policy that will undermine this congressional incentive is simultaneous marketing of the switched nonprescription product alongside prescription versions of the same drug product following a full switch," said PhRMA. "When a drug is changed from prescription to nonprescription status, FDA must remove from the market the prescription drug product and any Abbreviated New Drug Applications (ANDAs) that reference that drug unless 'meaningful differences' (such as dosage form or strength) between the products exist.

"In the case of a full Rx-to-OTC switch, the Agency will undermine the powerful three-year exclusivity incentive if it fails to remove prescription ANDA holders’ products from the market or allows for simultaneous marketing of prescription drug product and a nonprescription drug product with an Additional Condition for Nonprescription Use," the group added.

The Association for Accessible Medicines (AAS) wrote to FDA about increasing access to OTC drugs and cautioned against any policies that could harm an already strained generic drugs industry. It warned that switching drugs to nonprescription status could potentially push generic drugs out of the market, decrease competition, and lead to drug shortages.

"As AAM has noted, the generic drug sector is facing severe economic fragility, and companies cannot keep absorbing escalating costs while facing sustained price deflation that rewards only the lowest cost products, threatening the industry’s long-term sustainability and supply reliability," said AAM. "Accordingly, policies intended to increase access to OTC drugs must be carefully designed and implemented to avoid unintended consequences that could actually undermine affordability, reduce insurance coverage, or weaken the robust generic prescription drug marketplace upon which patients rely."

AAM previously raised similar concerns when FDA proposed its ACNU rule and stated that, depending on how the agency implements it, the rule could create unnecessary barriers to generic drugs entering the market and burden generic drugmakers. Despite the concerns, it noted that the previous administration implemented the rule without any significant changes.

In terms of opportunities to improve access to nonprescription drugs, AAM recommended that FDA use targeted pathways for nonprescription drugs instead of indiscriminately approving nonprescription drugs that could undermine trust in the OTC drug approval system. It also recommended that the agency reassess its "meaningful difference" standard to allow prescription and nonprescription drugs on the market simultaneously, so patients can use their insurance or buy OTC drugs, depending on their needs and affordability.

Several stakeholders said FDA's current regulations and requirements are challenging and unpredictable for drugmakers developing nonprescription drugs. The US Chamber of Commerce said consumer study requirements, including label comprehension and self-selection studies used to demonstrate that consumers can use a nonprescription drug without their healthcare provider's supervision, are not always clear or consistently applied. It said that, ultimately, the requirements can lead to uncertainty and increased drug development risk for sponsors.

"The Chamber believes that updating and clarifying FDA’s consumer study guidance and engagement practices presents a meaningful opportunity to expand access to nonprescription drugs while maintaining the Agency’s longstanding commitment to safety and effectiveness," said the Chamber. "With respect to Label Comprehension Studies, FDA should consider clarifying expectations for study objectives and outcomes, including how the Agency evaluates whether consumers adequately understand key health information necessary for safe and effective use.

"FDA should also provide additional guidance on study population considerations, including how studies should be designed to reflect the intended user population and how results from individuals unlikely to use the product should be interpreted," it added. "Similarly, with respect to Self-Selection Studies, FDA should consider providing greater clarity on how self-selection decisions are evaluated, including how clinically appropriate factors may be considered when assessing whether consumers can correctly determine product suitability."

Echoing the Chamber, the Consumer Health Products Association (CHPA) wrote to FDA, stating that its evidentiary expectations for nonprescription drug sponsors were unclear, unpredictable, and overly burdensome. It said that its members consistently report significant uncertainty about the requirements for consumer‑behavior studies, including Label Comprehension (LC), Self-Selection (SS), and Actual Use Trials (AUT).

"FDA’s current guidance and practice often lacks transparent criteria for determining when consumer behavior studies are pivotal and what constitutes success, leading to rework and delays," said CHPA. "The absence of such clarity, particularly for self‑selection and AUT studies, leads to repeated FDA requests and delays.

"Compounding these challenges is the Agency often does not evaluate OTC performance (as assessed in consumer studies) against real world prescription utilization patterns, which demonstrate imperfect adherence, variable counseling, and inconsistent comprehension," the group added. "CHPA urges FDA to recalibrate expectations to real-world Rx comparators, apply weighted, product specific endpoints focused on selection, use, and stop use/ask a doctor actions, and limit endpoints to behaviors resulting in clinically meaningful outcomes or risks."

CHPA also raised concerns about the ACNU rule and said the simultaneous prescription and nonprescription with additional conditions marketing provision in the rule is unlawful and unnecessary. The group asked FDA to remove the provision and leave the rest of the rule in place.

CHPA added that FDA's responses to clarifications from nonprescription drug sponsors are often sent piecemeal and late in their drug development. They also noted that sponsors are often faced with new requirements after initiating key studies.

"CHPA urges unified, timely feedback across reviewers both within individual development programs and consistent advice to different sponsors, as underscored by recent changes in law," said CHPA. "Furthermore, FDA should reduce its reliance on ‘Written Responses Only,’ which limits real‑time clarification and impedes programs addressing urgent or seasonal needs."

CHPA also raised concerns that sponsors are frequently asked by the FDA to resubmit all draft labeling, often multiple times during the product development, which is overly burdensome. The group said that instead of asking for the same draft labeling multiple times, the agency should focus on critical safety messages in OTC product labeling and formalize the use of representative labeling during the review process.

Public comments

Stakeholders ask FDA for more clarity, predictability for nonprescription drugs

Related topics

Recommended content

Welcome to the new RAPS Digital Experience