Ilisa Bernstein, PharmD, JD
President, Bernstein Rx Solutions, LLC

ACNU in a nutshell

In the waning days of 2024, FDA issued a final rule that is intended to increase consumer access to nonprescription (OTC) drugs. The final “ACNU rule” has been decades in the making. ACNU is “additional condition for nonprescription use.” Under the new regulatory framework, an OTC drug can be marketed without a prescription if the applicant (the company seeking approval to market the drug) implements one or more extra steps to ensure appropriate self-selection and/or appropriate actual use by the consumer, without an intervention by a health care provider. Simply, there soon will be “OTC drugs with ACNUs” in the marketplace.

The final rule provides examples of these additional steps, or conditions, such as requiring the patient to answer a questionnaire and provide proof that they answered correctly, demonstrating that the product is right for them. For example,  after successfully completing a questionnaire, the patient may be issued a QR code from the app or website to show at the point of sale when they buy the product. This provides a pathway for OTC marketing of products that may otherwise have been only available by prescription to ensure safe and effective use. The questions would be those that a consumer would be able to answer to help in self-selection, such as identifying other drugs they are on to prevent a drug-drug interaction, important allergy information, results from lab tests, or symptoms.

Approval of a nonprescription drug with an ACNU

The final rule establishes requirements for what needs to be submitted to FDA by the applicant, the elements of the additional condition, what must be on the labeling, and postmarketing reporting requirements. The applicant has to demonstrate how the ACNU ensures appropriate self-selection and/or actual use, including what the labeling will include, actions the consumer will take to demonstrate appropriateness, data or other information supporting the ACNU, and how the ACNU will be operationalized.

For generic drugs, the applicant submits their own application with the required information, referring to a reference listed drug’s (RLD) approved ACNU. Generic sponsors are permitted to operationalize the ACNU differently than the sponsor for the RLD. More on that below.

Of particular note is that there may be a prescription and nonprescription version of the same drug with the same active ingredient, dose, or formulation, that are both marketed. The final rule includes a lengthy legal analysis supporting FDA’s view that there can be nonprescription and prescription versions in the marketplace if there are meaningful differences in the marketing of the product – which the ACNU provides. This is a departure from FDA policy to date and a point of contention for manufacturers and confusion for pharmacies, providers, and maybe even consumers. Not to mention the issues it will likely create for payors.

Reporting of ACNU failures

The applicant of the product is responsible for surveillance, evaluation, and reporting of ACNU failures to FDA. As such, there will be monitoring in the marketplace to ensure appropriate ACNU implementation by the FDA and the sponsor. Retail sellers and consumers can report failure of an ACNU to the applicant. For example, if the ACNU is an online questionnaire, failures might be related to the website not working, the website not included or illegible on the product label, or the inability of retail sellers able to check at point of sale for the ACNU. Not only will manufacturers need processes and procedures to manage the ACNU failure reporting requirements, but a best practice for retailers will be to also have processes and procedures in place and staff trained in order to ensure that a product is not sold without verifying successful completion of the ACNU self-attestation.

Importantly, an OTC with an ACNU is misbranded if the ACNU is not implemented or operationalized in compliance with the approval requirements. This could put retailers in jeopardy of compliance and enforcement action if the product is sold without the consumer demonstrating successful completion of the ACNU self-attestation.

Labeling information on an ACNU product

The labeling of the product must include specific statements with instructions on how to access the ACNU to ensure that a consumer will know if they must complete an ACNU before purchasing the product. One statement will be in a yellow banner with bold black type on the principal display panel of the immediate container surface that the consumer is likely to see when looking for information about the product. For example, it may say “To check if this drug is safe for you, go to [insert website, phone number, kiosk, etc.]” The label may also state “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…”

Completing the ACNU might create inconveniences for consumers. A consumer may be at the store looking for an OTC drug product, but they will not be able to purchase that product unless they complete the ACNU steps. This may be difficult. If someone does not have a mobile phone, does not have wifi access, or does not understand what steps they need to take, they will not be able to purchase that product until they complete the ACNU step. They may then end up purchasing a different product or leave the store without a medication.

On the other hand, completing the ACNU might be viewed as a hassle, yet a perfunctory step that could be gamed until the consumer gets the right outcome to buy the product, regardless of whether it is right for them.

ACNU issues at the point of sale

OTC drug products can be sold anywhere in the marketplace, not just at pharmacies. However, not all places where OTC drug products currently are sold have the ability to check the consumer proof that they successfully completed the ACNU self-attestation at the point of sale. Regardless of whether the seller is a pharmacy or another entity , this will require costly modifications to the point of sale systems in order to accommodate checking ACNU proof. Even more problematic is that there are no provisions to require standardized operationalization of the ACNU. Every product may have different ACNU methods, making it difficult to implement point of sale modifications. If a retailer is not able to verify the ACNU proof, they will not be able to sell the product to the consumer.

This is a déjà vu moment for FDA history buffs, reminiscent of early REMS requirements established for reference listed drugs and generics for those drugs. REMS (Risk Evaluation and Mitigation Strategy,) are drug safety programs required by FDA for applicants to implement in order to ensure safe and effective use of drug products that may pose serious safety concerns. Through years of trial and error, eventually shared system REMS were developed. These standardized the operationalization of REMS for a drug or drug class, including the RLD and generics, making processes more predictable and accessible for providers, patients, and applicants. While ACNU is a slightly different situation, the concept of standardizing operationalization of the ACNU could improve access and availability for patients.

OTC drugs with ACNUs will create additional confusion for consumers because they will have to check where the product is sold if they do successfully complete the ACNU. If a patient completes an ACNU for a particular manufacturer’s product, but the retailer only carries a different manufacturer’s version of that product, it is not clear if the retailer can accept successful completion of an ACNU for a different manufacturer’s version. Having a standardized or shared system would help in this situation as well. Pharmacies and other retailers should work with applicants to develop voluntary standardization for ACNU.

Pharmacies may choose to put these products behind the counter, similar to pseudoephedrine products, which also require an extra step before purchase, but for a different reason. This raises pharmacy shelf space issues.

Companies marketing ACNU products may choose to only sell the product through a website and mail the product to the patient. This is not ideal if the consumer needs the medicine and cannot wait.

The prescription version is likely be subject to the Drug Supply Chain Security Act, DSCSA, however, the OTC version would be exempt. DSCSA covers prescription drugs, which imposes specific requirements for tracing and verifying product in the marketplace. Pharmacies that sell both the prescription and OTC versions will need to segregate these products in inventory to reduce confusion and potential mix-ups. This should be mitigated because the prescription and OTC versions will have different NDC numbers.

For patients who have been maintained on prescription versions of these products, there may be out of pocket cost savings for the OTC with ACNU version. Pharmacists should expect that when the marketing blitz happens for a product that is approved with an ACNU, patients will be asking for comparison pricing in order to save money. Because every prescription drug plan is different, this will entail a new inquiry for every patient, creating timely uncompensated diversions for an already busy pharmacy team.

When will we see these products in the marketplace?

There are no pending applications for ACNU products, but it is likely that sponsors have applications ready for submission for FDA to review. Given the newness of the program, it is expected that FDA will be working closely with applicants to forge new grounds in this new marketing category.

Although there are many unknows in the implementation and execution of FDA’s new framework for OTC drugs with ACNUs in the marketplace, it is exciting to have a new category of options for patients in their therapeutic toolbox.

The post FDA’s new regulatory framework for OTC drugs – with an ACNU twist first appeared on Bernstein Rx Solutions.

True to FDA’s mission, the new DSCSA exemption protects public health.

FDA gave drug supply chain stakeholders a bit more time to stabilize electronic connections with their trading partners as they implement the last stage of the Drug Supply Chain Security Act (DSCSA). With this move, FDA helped avert significant supply chain disruptions and delays in patient access to important medicines.

The DSCSA was passed in 2013, creating a stepwise approach to further secure our nation’s drug supply from counterfeit and other illegitimate drugs. The early stages of the law required paper or electronic tracing of drugs through the supply chain based on the lot number of the product. The final stage of the law requires implementation of secure, electronic exchange of information for tracing of each drug package with its own unique serial number as it moves through the supply chain. This is more complex because every trading partner must ensure that their data system can talk to their trading partner’s system and exchange data that matches the products and their serial numbers.

Without stable electronic connections between trading partners, the data about the product packages may not be complete and accurate, legally barring the buyer from accepting ownership of the product. If this happens, the buyer either has to quarantine the product and reconcile the data or refuse to accept the product and return to sender. This could create disruptions in drug availability, which ultimately will be felt by the patient at the pharmacy counter if they cannot get their needed prescription.

The supply chain was not ready last November, the statutory deadline, so FDA granted a year-long “stabilization period,” until November 27, 2024, to allow trading partners to stabilize their connections. FDA was serious when they said… “this is it” and at that time they did not plan on giving any further extensions.

More time truly was needed to stabilize connections

By mid-summer, concerns were bubbling up from manufacturers, wholesalers, and dispensers that they needed more time. The stabilization period was helpful to get most of the way there but, given the massive amount of prescription drugs moving through the supply chain each day, problems with even one percent of the daily transactions could create widespread disruptions.

FDA listened. They took these concerns seriously and did their due diligence. In July, FDA gave small dispensers two years to comply. FDA continued to listen. They attended and held meetings with stakeholders to hear the concerns, challenges, and efforts to comply.

FDA’s new exemption is measured and targeted. Manufacturers, wholesalers, and dispensers are only eligible for an exemption if they have taken steps to comply and have systems, processes, and connections with their trading partners. This gives them time to stabilize systems and troubleshoot issues of missing or erroneous data. Manufacturers have until May 27, 2025, wholesalers have until August 27, 2025, and dispensers with 26 or more full-time employees have until November 27, 2025. There’s no free pass if you were procrastinating and not making an effort. Also, by staggering the exemption period, the supply chain can follow the data and focus efforts in a downstream manner, stabilizing connections from manufacturer to wholesaler, then wholesaler to dispenser.

I know that many in the drug supply chain are celebrating right now, but don’t celebrate too long. As FDA said in their notice announcing the time-limited exemptions, “this should not be viewed as an excuse to delay implementation.” This is the supply chain’s last chance. If your trading partner is not ready and is not willing to work with you, then you should seriously consider finding a different supplier.

Yes, I’m a little biased, but credit is due to FDA

Some say DSCSA is a complicated law to understand and implement. It’s not, but I have a special fondness for the law and want to see implementation succeed. I was on the team at FDA in the early 2000’s calling for a drug track and trace system in the U.S., after counterfeit drugs were found in the drug supply. I helped lead FDA’s team working with Congress to pass DSCSA. I then led FDA’s implementation efforts until I retired from the agency in late 2019, continuing to advocate for responsible and practical implementation from the private sector. I’m a DSCSA cheerleader, shouting for implementation to get over the goal line.

I am excited to see this so close to the end and appreciate FDA’s recognition that extra time is needed to get it right and avoid disruptions. Rarely do government officials get public kudos, but in this case, patients, supply chain trading partners, and public health should be waving their DSCSA pom poms with thanks. FDA DSCSA team, thank you.

Ilisa Bernstein

President, Bernstein Rx Solutions, LLC

The post FDA’s DSCSA exemption is the right move first appeared on Bernstein Rx Solutions.