FDA recently issued the notice “Safety and Effectiveness of Certain Naloxone Hydrochloride Drug Products for Nonprescription Use,” which the agency said aims to help facilitate the development of nonprescription naloxone drug products, including through the switch of certain naloxone drug products from prescription status to nonprescription status. This notice represents FDA’s first public discussion of Rx-to-OTC switches in recent memory, and is further novel in that the agency is very strongly encouraging, but stops short of forcing, an OTC switch. It’s clever of the agency to attempt to accomplish its goals of making naloxone drug products more readily accessible in light of the widespread opioid epidemic via Federal Register notice. The statute is explicit that the agency may “by regulation” remove drugs subject to the prescription dispensing requirements when the requirements are no longer necessary for the protection of the public health. So, the Federal Register notice encourages a switch in a way that’s about as far as possible for the agency to go without actually forcing a switch via a proposed rule — which has never happened and which could be challenging for FDA.

Also out of the ordinary, is that a couple years ago, in May 2020, FDA conducted its own labeling comprehension study of an OTC naloxone product and then published a model Drug Facts Label, which could be used on OTC naloxone drug product, with pictograms on how to use the drug. FDA published this 21 CFR 201.66-compliant drug facts label and did the study to support its use in the OTC-setting to encourage manufacturers to pursue approval of OTC naloxone products. And, this new Federal Register notice is the next push by the agency to strongarm a switch.

The Federal Register notice includes a preliminary assessment – notably conducted by the agency itself – that certain naloxone drug products may be approvable as safe and effective for nonprescription use. Typically sponsors initiate switches from prescription to OTC status and the onus is on them to prove the safety and efficacy in the OTC setting. FDA claims in the notice that it does not mandate an immediately effective switch to nonprescription/OTC availability for naloxone; instead, FDA is informing prescription naloxone drug product application holders of the possibility that the agency may soon make a conclusive determination, through approval of a nonprescription naloxone drug product, that such products are safe and effective for use without a prescription. However, to make its final determination, FDA said it needs additional data, such as product-specific data on the nonprescription user interface design, including packaging and labeling.

Accordingly, the notice requests comments on whether there is data to support safe and effective nonprescription use of higher dose naloxone products and on potential consequences of a switch from prescription to nonprescription status. The notice says more data are needed on the safety and efficacy for nonprescription use of higher dose naloxone products and naloxone supplied in other presentations (including vials, ampules or syringes without integrated needles) before a preliminary assessment with respect to those products can be reached.

FDA promotion of naloxone products

This notice continues FDA’s trend to increasing access to naloxone products. In September, FDA had issued an immediately in effect guidance to clarify that certain Drug Supply Chain Security Act requirements do not apply to distribution of naloxone to harm reduction programs during the Opioid Public Health Emergency. FDA has also required drug manufacturers for all opioid pain relievers and medicines to treat opioid use disorder to add new recommendations about naloxone to their prescribing information; and it recently extended the shelf life of naloxone nasal spray from 24 months to 36 months. In addition, last week, it was reported that FDA granted Emergent BioSolutions Inc. priority review for an OTC version of Narcan, giving the drug an expected approval date of March 29, 2023.  

In announcing the Federal Register notice, FDA lauded Naloxone as “a medicine that can help reduce opioid overdose deaths and when administered timely, usually within minutes of the first signs of an opioid overdose, can counter the overdose effects.” FDA Commissioner Robert M. Califf, M.D. said: “The agency will keep overdose prevention and reduction in substance use disorders as a key priority and area of intense strategic focus for action as rapidly as possible.”

Switching to nonprescription/OTC status

There are a myriad of issues to consider when developing, manufacturing, and marketing OTC drugs, as significant attention must be paid to compliance issues, including your product’s labeling and marketing claims. And several issues to consider when pursuing a switch, such as whether to seek a full or partial switch, what studies will be necessary to support a switch, and whether being granted 3-year exclusivity might be possible for the studies that support the switch. At Hogan Lovells, we have a broad range of experience helping drug companies understand the sophisticated and rapidly-evolving regulatory landscape for OTC pharmaceutical products. We regularly advise OTC drug manufacturers, marketers, and large retailers on Rx to OTC switches and on monograph compliance and product labeling, including Drug Facts.

For example, we advised clients earlier this year on how FDA issued a long-awaited proposed rule – titled “Nonprescription Drug Product with an Additional Condition for Nonprescription Use” (ACNU) – that [if finalized] would expand the universe of over-the-counter (OTC) drug products to include those with an additional condition for use beyond traditional drug-facts labeling alone. We summarized online here how the proposal would create a new category of products that we call “OTC+”: products that would not be dispensed by prescription, but would not rely solely on the product’s labeling for safe and effective use.

Pharmaceutical and biotechnology companies will want to consider whether their products may be eligible for OTC approval under the ACNU pathway, which we see as being particularly relevant for treatments for chronic conditions such as hyperlipidemia, diabetes, and hypertension. At Hogan Lovells, we also offer marketing strategies and counsel on the requirements for switching prescription products to OTC status. We further assist in product advertising, Hatch Waxman exclusivity related to OTC drug products, the regulatory status of long-marketed “legacy” products, adverse event reporting, and current Good Manufacturing Practice (cGMP) standards as applied to OTC drugs.

FDA is seeking comments on the naloxone Federal Register notice through January 17, 2023. If you have any questions on obtaining over-the-counter status for a drug product, or may wish to submit a comment on FDA’s naloxone notice, feel free to contact the Hogan Lovells attorney with whom you regularly work or the author of this alert.

Authored by Heidi Gertner