Unintended consequences downstream are likely to multiply in the wake of June 24, 2022 Dobbs decision which annulled Roe v. Wade, as Mintz’s attorneys have addressed in other contexts here and here. In an apparent ironic twist of timing, on July 11, 2022, the Perrigo Company announced that one of its operating entities, HRA Pharma, had submitted an application to the FDA to switch an existing progestogen-only contraceptive pill to an over-the-counter prescription. (OTC). If the application is approved in 2023 after completing the agency’s arduous review process, the product would represent the first over-the-counter birth control pills allowed to be marketed in the United States. And when such marketing authorization is granted, we will know to what extent innovative conditions placed on the consumer side of the equation may have played a role in the FDA’s final decision.
Background to the FD&C Act
Some of you may be wondering here: given that so many other countries already have over-the-counter oral contraceptives, and the benefit-risk profile of these somewhat old drugs is so well characterized and understood, why 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 unsafe to use, except under the supervision of a licensed healthcare provider due to toxicity or other risk of consumer harm (i.e. prescription drugs, also known as Rx); and those that do not carry this kind of risk and for which the applicant can demonstrate to the FDA that consumers can correctly select and use drugs based on the written instructions included in the product labeling (i.e., over-the-counter drugs).
Given the clear lines around these two classes of drugs, birth control pills have historically been unable to be marketed as over-the-counter drugs due to concerns about women at increased risk of developing blood clots taking such products without sufficient oversight by a healthcare professional, as these risks cannot necessarily be managed by potential consumers using only the information contained in the drug information label (DFL). As a result, the argument has been that women cannot ‘self-select’ an appropriate birth control pill in an over-the-counter setting, meaning these drugs have remained prescription-only under the current legal and regulatory framework. Self-selection in this context means that a consumer can decide whether or not to use a drug product based on the information in the product’s DFL and their own personal medical history – a process we all follow when choosing. headache medicine. or allergy pills to buy, or deciding if our child needs anti-itch cream or anti-bacterial ointment for their particular skin condition.
This two-tier system of Rx or over-the-counter drugs has caused consternation in the United States for years, if not decades, given the rapidly rising prices of prescription drugs in the country and the clear evidence of ‘unequal access to certain medical products based on an individual’s race, class and social status. Among many other reviews and analyzes that have been published on this topic is the GAO’s 2009 report on the pros and cons of a third class of so-called “behind the counter” (BTC) drugs. Although federal proposals for this kind of BTC category have since been dropped, they were all the rage for a while. Over the next 10 years, the FDA has sought to encourage more companies to do the work necessary to upgrade their pharmaceutical products from Rx status to OTC status by submitting the results of consumer studies – such as studies label comprehension and real-use studies – to demonstrate that written instructions and DFL alone can support consumers’ self-selection decisions and the safe use of their medications. Indeed, in 2019, the agency took the unprecedented step of developing and releasing “model” LDFs to support the move of naloxone, a critical opioid overdose reversal drug, to over-the-counter status. , but to date, no company has accepted this invitation and submitted a transfer request. its over-the-counter naloxone Rx product. That being said, however, many other commonly used drug products have successfully transitioned from Rx status to OTC status over the past 20 years, and the agency maintains a public list of these changes (most recent update in March 2022).
This brief history should provide some context to our readers as to why the FDA’s proposed new rule that would establish requirements for the marketing of over-the-counter pharmaceuticals with additional conditions for non-prescription (ACNU) use is making waves. in the industry and has been so eagerly awaited – and why the agency’s proposed changes might come into play for Perrigo/HRA Pharma’s recently submitted OTC birth control pill application.
Summary of ANCU’s Proposed Rule
In late June 2022, the FDA released a proposed rule called Non-prescription pharmaceutical product with an additional condition for non-prescription use together with a public announcement. The agency stressed that the regulatory changes it is proposing “are intended to increase options for the development and commercialization of safe and effective over-the-counter pharmaceuticals, which could improve public health by expanding the types of pharmaceuticals on sale.” freely available to consumers”. Specifically, the FDA makes clear that it is willing to accept new and innovative mechanisms for consumers to self-select an over-the-counter drug product as long as the sponsor of that drug product designs and operationalizes an appropriate ANCU.
The agency explains that, by definition, an ANCU is an FDA-approved condition that an “applicant must implement to ensure appropriate consumer self-selection or appropriate actual use, or both,” of the over-the-counter drug product if the applicant and the FDA determine that labeling alone is insufficient to ensure the safe and effective use of the drug. Examples of ANCUs included in the agency’s proposal include a personalized questionnaire available through a mobile app or phone that a potential consumer would have to answer in a certain way in order to purchase the drug over-the-counter, and a quiz that the consumer should take after reviewing the instructions for use of the medicine to confirm that they have understood these instructions. The proposed rule also outlines the procedural aspects of submitting New Drug Applications and Abbreviated New Drug Applications (used for generic versions of a drug) and what marketing Rx and OTC versions of the same drug at the same time would look like. The FDA is also seeking comments on a variety of collateral issues that the agency and industry will face as the envisioned framework becomes a reality; for example, the FDA is seeking comment on whether patents claiming aspects of an ANCU approved for the innovator’s non-prescription drug should be listed in the orange book or whether such patent listings may have the potential to delay the future entry of over-the-counter follow-on product generics.
While it is unclear whether the Perrigo/HRA Pharma application for its over-the-counter progestin-only contraceptive pills contains any form of ANCU proposal or how the sponsor plans to implement or operationalize such a condition, the Recently announced regulatory change is not the first time the FDA has said it is willing to accept and consider proposals for over-the-counter drug products that go beyond the four corners of the Drug Facts label. . In 2018, the agency issued brief draft guidelines that articulated much of the same policy, calling for either “additional labeling” at the DFL – such as informational brochures or interactive video displays for consumers – or ANCU proposals that may be necessary for safety and effectiveness. the use of the over-the-counter drug in question. In these 2018 guidelines, the agency stated almost verbatim what the current proposed rule says: “The FDA believes that the innovative approaches described in these guidelines could lead to the approval of a broader range of drugs in over-the-counter, including drugs that may treat chronic conditions or other conditions for which the limitations of the DFL present challenges for adequate communication of information necessary for safe and effective use without professional supervision. health.
The difference, of course, is that non-binding guidelines set forth in a policy document can always change, whereas duly promulgated regulations are binding on both industry and the FDA. The agency’s informal position set out in these 2018 guidelines may not have provided most industry participants with the certainty and assurances they needed to submit such an “innovative” application for a new over-the-counter drug because no such application has been approved. by the FDA since then and we are not aware of any company having publicly announced that they have submitted such an application. Perhaps the planned future codification of the FDA’s new approach will encourage more companies to develop and attempt to operationalize ANCUs for commonly used chronic disease medications, such as cholesterol-lowering statins, and commonly used preventative medications. used, such as oral contraceptive pills. It will therefore be very interesting to see the ultimate contours of any Perrigo/HRA Pharma marketing approval for its over-the-counter contraceptive product and whether such innovative conditions are incorporated into the FDA clearance for this first over-the-counter drug.
Stakeholder comments on ANCU’s proposed rule must be submitted to the electronic docket by October 26, 2022.