Unintended downstream consequences are likely to abound in the wake of the June 24, 2022 Dobbs decision that overruled Roe v. Wade, as Mintz attorneys have addressed in other contexts here and here Those looking ahead have raised concerns about women’s continued access to the wide array of birth control options that have been approved for use in the United States by the Food and Drug Administration (FDA). In an apparent ironic twist of timing, on July 11, 2022, Perrigo Company announced that one of its operating entities, HRA Pharma, had submitted an application to FDA to switch an existing prescription-only progestin birth control pill to over-the-counter (OTC) status. Should the application be approved in 2023 after completing the arduous agency review process, the product would represent the first OTC birth control pills authorized to be marketed in the U.S. And when such marketing approval is granted, we’ll know to what extent innovative conditions placed on the consumer side of the equation may have played a role in FDA’s ultimate decision.
Background on the FD&C Act
Some of you might be wondering here: given that so many other countries already have OTC birth control pills, and the benefit-risk profile for these somewhat-old drug products is so well characterized and understood, why has the United States been so slow to get to this point? At a fundamental level, the answer to this question lies in the structure of the Federal Food, Drug, and Cosmetic Act (FD&C Act), which identifies only two types of drug products – those that are not safe to use except under the supervision of a licensed health care provider due to toxicity or other risks of harm to the consumer (i.e., prescription drugs, also called Rx); and those that do not carry those kinds of risks and for which the applicant can demonstrate to FDA that consumers can correctly select and use the drugs based on written directions that are included in the product labeling (i.e., OTC drugs).
Given the bright lines around these two categories of drug products, birth control pills have historically been unable to come to market as OTC drugs due to concerns about women at heightened risk of developing blood clots taking such products without sufficient monitoring by a health care professional, because such risks cannot necessarily be managed by the prospective consumers solely using information in the Drug Facts Label (DFL). Accordingly, the argument has been that women cannot “self-select” an appropriate birth control pill product in an OTC setting, which means that such drugs have remained prescription-only under the current legal and regulatory framework. Self-selection in this context means that a consumer can make a decision whether or not use to use a drug product based on the information in the product’s DFL and their own personal medical history – a process all of us go through when picking which headache medication or allergy pills to purchase, or when deciding whether our child needs an anti-itch cream or an antibacterial ointment for their particular skin ailment.
This two-tier system of Rx or OTC drugs has caused consternation in the U.S. for years, if not decades, given the rapidly increasing prices of prescription drugs in the country and clear evidence of inequitable access to certain medical products depending upon an individual’s race, class, and social status. Among many other reviews and analyses that have been published in relation to this topic is the GAO’s 2009 report on the pros and cons of a third, so-called “behind-the-counter” (BTC) class of drugs. Although federal proposals for this kind of BTC category have been abandoned since that time, for a while they were all the rage. In the intervening 10+ years, FDA has sought to encourage more companies to do the work necessary to switch their drug products from Rx to OTC status by submitting results from consumer studies – such as label comprehension studies and actual use studies – to demonstrate that written instructions and the DFL alone can support consumers’ self-selection decisions and safe use of their drugs. Indeed, in 2019 the agency took the unprecedented step of developing and releasing “model” DFLs to support the switch of the critical opioid overdose-reversal drug naloxone to OTC status, but to date no company has accepted that invitation and submitted an application to move its Rx naloxone product over into nonprescription status. That being said, however, many other commonly used drug products have successfully “switched” from Rx to OTC status over the past 20 years, and the agency maintains a public list of those switches (most recently updated in March 2022).
This brief historical background should provide some context for our readers on why FDA’s newly proposed rule that would establish requirements for marketing nonprescription drug products with additional conditions for nonprescription use (ACNU) is making waves in the industry and has been so eagerly awaited – and why the changes proposed by the agency could come into play for Perrigo/HRA Pharma’s recently submitted OTC birth control pill application.
Summary of the ANCU Proposed Rule
In late June 2022 FDA released a proposed rule called Nonprescription Drug Product With an Additional Condition for Nonprescription Use in conjunction with a public announcement. The agency emphasized that its proposed regulatory changes are “intended to increase options for the development and marketing of safe and effective nonprescription drug products, which could improve public health by broadening the types of nonprescription drug products available to consumers.” Specifically, FDA is making clear that it is willing to accept new and innovative mechanisms for consumers to self-select an OTC drug product as long as the sponsor of that drug product designs and operationalizes an appropriate ANCU.
The agency explains that, definitionally, an ANCU is an FDA-approved condition that an “applicant must implement to ensure consumers’ appropriate self-selection or appropriate actual use, or both,” of the OTC drug product if the applicant and FDA determine that labeling alone is insufficient to ensure the drug’s safe and effective use. Examples of ANCUs included in the agency’s proposal include a tailored questionnaire that is available via mobile app or telephone that a prospective consumer would have to respond to in a certain way to in order to be able to purchase the OTC drug product, and a quiz that the consumer would have to take after reviewing the instructions for using the drug in order to confirm their full understanding of those instructions. The proposed rule also describes procedural aspects of submitting new drug applications and abbreviated new drug applications (used for generic versions of a drug) and what simultaneous marketing of Rx and OTC versions of the same drug would look like. FDA also requests comments on a variety of tangential issues that the agency and industry will have to grapple with when the envisioned framework becomes a reality; for example, FDA is seeking comment on whether patents claiming aspects of an ANCU approved for the innovator’s nonprescription drug should be listed in the Orange Book or whether such patent listings may have the potential to delay future generic entry of follow-on nonprescription products.
While it is unclear whether the Perrigo/HRA Pharma application for its OTC progestin-only birth control pills contains any form of proposal for an ANCU or how the sponsor would plan to implement or operationalize any such condition, the newly announced regulatory change is not the first time FDA has articulated that it’s willing to accept and consider proposals for OTC drug products that go beyond the four corners of the Drug Facts Label. In 2018 the agency published a brief draft guidance that articulated much the same policy, calling for either “additional labeling” to the DFL – such as informational leaflets or interactive video displays for consumers – or ANCU proposals that may be necessary for the safe and effective use of the OTC drug in question. In that 2018 guidance, the agency stated almost word for word what the current proposed rule says: “FDA believes the innovative approaches described in this guidance could lead to the approval of a wider range of nonprescription drug products, including drug products that may treat chronic conditions or other conditions for which the limitations of the DFL present challenges for adequate communication of information needed for safe and effective use without the supervision of a health care practitioner.”
The difference, of course, is that non-binding guidance articulated in a policy document can always change, whereas duly promulgated regulations are binding on both the industry and FDA. It may have been that the informal agency position set forth in that 2018 guidance did not provide most industry participants with the certainty and assurances they needed to submit such an “innovative” application for a new OTC drug product, since no such applications have been approved by FDA since that time and we’re not aware of any company announcing publicly that they had submitted such an application. Perhaps the anticipated future codification of FDA’s novel approach will encourage more companies to develop and attempt to operationalize ANCUs for commonly used chronic disease medications, like cholesterol-lowering statins, and commonly used preventive medications, like oral contraceptive pills. It will therefore be quite interesting to see the ultimate contours of any Perrigo/HRA Pharma marketing approval for its OTC birth control product and whether any such innovative conditions are incorporated into FDA’s authorization for this first-of-its-kind nonprescription drug product.
Stakeholder comments on the proposed ANCU rule should be submitted to the electronic docket by October 26, 2022.