FDA releases long-overdue guidance on content and format of OTC drug submissions

More than a year late, the FDA today unveiled a new draft guidance document that explains how sponsors of Over-the-Counter Monograph Order Requests (OMORs) – a relatively new type of application created in 2020 – should format these applications, including the information to be provided. While the guidance may be new, the document mostly relies on long-established standards.

Regulatory Background and Context

• Nonprescription drugs, also known as over-the-counter (OTC) drugs, are regulated differently than traditional prescription drugs. Until recently, the FDA relied on a monograph process through which firms could bring OTC drugs to market without FDA approval so long as it adhered to pre-set terms under the monograph. The monographs functioned as rule books for specific classes of OTC drugs, describing active ingredients, doses, indications, labeling and tests requires for covered OTC products to be generally recognized as safe and effective (GRASE).
• However, the Coronavirus Aid, Relief, and Economic Security Act (CARES Act) included provisions to overhaul OTC drug regulation. Under Section 3851 of the CARES Act, the monograph rulemaking process was replaced with an administrative one, similar to the way the FDA already regulates other products. The FDA will follow these procedures for both agency-initiated operations (e.g., developing or amending a monograph) or sponsor-initiated operations (e.g., requesting an addition or change to a monograph through an OTC Monograph Order request, or OMOR).
• The CARES Act was accompanied by a user fee agreement “commitment letter,” the Over-the-Counter Monograph User Fee (OMUFA) Program Performance Goals and Procedures.
• Buried within the OMUFA Commitment and Goals Letter is a section requiring that Over-the-Counter Monograph Order Requests (OMORs) be submitted “using content and format recommendations described in the guidance for industry Nonprescription Sunscreen Drug Products – Content and Format of Data Submissions,” an existing guidance which was seen as a useful stopgap measure for future submissions.
• However, the letter went on to say that the FDA should also release a new guidance document on the content and format of OMORs explicitly applicable to all OTC products. That guidance was supposed to be published by April 1, 2022, with a final guidance to be published by October 1, 2023.
• But that date came and went without FDA publishing any guidance on the content or format of OMORs. As several experts in OTC products told AgencyIQ, the absence of the guidance and the failure of FDA to meet this specific obligation had been puzzling, especially since the guidance document was intended to be something of a foundational document to ensure high-quality submissions.

The guidance document

• Now, though, the FDA has finally unveiled its draft guidance document on the format and content of OMORs. The 22-page draft guidance document describes how the FDA intends to make use of the Common Technical Document (CTD) format – an ICH standard that is currently also used for prescription drugs – with specific requirements for OMORs. (We should note that since the CARES Act requires the electronic submission of OMORs, we’re really talking about the electronic Common Technical Document, or eCTD).
• Unlike most guidance documents, this one includes language indicating requirements, rather than just recommendations. As FDA explains, “The OMOR must be submitted to FDA in the form and manner specified by the Agency.” (Emphasis added). Only if the FDA believes that the OMOR is “sufficiently complete and formatted” appropriately will FDA begin its “substantive review.” That’s unusual, since most FDA guidance documents are only able to offer recommendations.
• The guidance recommends that OMORs be organized into a five-module CTD submission, taking into account FDA’s other guidance documents related to the CTD. As FDA notes, “The recommendations provided in these guidance documents are also applicable to OMORs.” However, the agency also notes that because CTDs are intended to apply to many different types of products (i.e., prescription products and biologics), not all headings and subheading will be pertinent to all OMORs. In such cases, the sponsor of the application “should indicate that no information is being submitted for a given module or a section or subsection of a module.”
• Most of the guidance is relatively straightforward and talks about the exact requirements of each section of the OMOR CTD submission, including related documents. For example, the OMOR should have a comprehensive table of contents, a cover letter, administrative information about the sponsor and certain legally required information, references to prior data or meetings with the FDA, and proposed labeling. Each of these has associated sub-requirements as well that FDA wants to see.
• OTC drug manufacturers are likely to benefit greatly from the fact that FDA isn’t starting from scratch on these requirements and recommendations. The guidance makes extensive reference to prior CTD submission guidelines, such as the International Council for Harmonization’s (ICH) M4 series of guidance documents related to the CTD and quality, safety and efficacy. In many of those cases, sponsors are advised to follow the recommendations contained within those guidance documents, rather than have the FDA offer new OMOR-specific ones. As a result, the guidance is mostly a high-level overview of OMOR content and format requirements.
• However, there are a few elements within the guidance which speak to OMOR-specific requirements. For example, on Page 13 of the guidance the FDA talks about where to include “consumer behavior studies” and information regarding safe nonprescription marketing and use of the OTC drug within the CTD (Module 5 for both).

Analysis

• We’re mostly expecting that industry will approve of this guidance, with the exception of how late FDA was in releasing it. The prior FDA-recognized guidance on this topic included highly similar recommendations, including the use of the CTD and general information. However, the new guidance is significantly expanded and is likely to be more helpful. We will be curious to see if industry requests that FDA include additional information, or if they believe that the guidance is specific enough.
• Speaking of late guidance, that’s something that may be of concern to industry going forward. FDA has been relatively slow to hire new staff under its OMUFA program. According to the agency’s FY2022 OMUFA Performance Report, FDA only hired 13 staff in FY2021 when it anticipated hiring 30 staff. While FDA hired the remaining 17 in 2022, as well as another 19 staff (against a projected 24 staff), the delays in hiring of key review staff mean it’s not just guidance that could experience delays, but the review of OMOR applications as well.

To contact the author of this analysis, please email Alec Gaffney ( [email protected])
To contact the editor of this analysis, please email Kari Oakes ( [email protected])

Key Documents and Dates

Over-the-Counter Monograph Order Requests: Format and Content