FDA finalizes guidance on electronic submissions for OTC products

Background: Modernizing regulation of over-the-counter (OTC) products

• Nonprescription products, also called over-the-counter (OTC) products, must demonstrate the ability to be used safely and effectively without the supervision of a qualified healthcare professional. These products are regulated differently from traditional prescription drugs.
• The FDA’s regulatory paradigm for these products has undergone modernization in recent years following the passage of the Over-the-Counter Monograph Safety, Innovation, and Reform Act within the Coronavirus Aid, Relief, and Economic Security Act (CARES Act). The law made key changes to how nonprescription products are regulated and also established the Over-the-Counter Monograph Drug User Fee (OMUFA) program to support the agency’s activities in this space. [ Read AgencyIQ’s explainer on the CARES Act here.]
• Prior to CARES Act reforms, FDA relied on a monograph process through which firms could bring OTC drugs to market without FDA approval so long as they 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 required for covered OTC products to be generally recognized as safe and effective (GRASE).
• The new system replaced the monograph rulemaking process with an administrative process, allowing the FDA to approve a drug without first having to issue a proposed and final regulation for public comment. This enabled more efficient procedures for both agency- and sponsor-initiated operations. Additionally, if a change to a monograph is requested by the sponsor, the sponsor will be required to submit a new submission type called an OTC Monograph Order Request (OMOR).
• The law also required the electronic submission of OTC monographs and other OTC related submissions—a requirement intended to further increase efficiency. This includes the submission of OMORs, public comments to administrative orders, formal meeting requests and packages, dispute resolution requests, administrative hearing requests, record request responses, as well as updates to drug listing information.
• According to the OMUFA commitment letter, the FDA committed to the publication of a draft guidance on electronic monograph submissions by October 1, 2022, which must then be finalized by April 1, 2024.

FDA published draft guidance on electronic OTC submissions in late September 2022

• The draft guidance, Providing Over-the-Counter Monograph Submissions in Electronic Format, explained that OTC monographs should be submitted through the CDER NextGen Portal or through the OTC Monographs@FDA portal. Further, “For OTC monograph submissions not explicitly described in this guidance, interested parties should check the OTC Monographs@FDA portal to see whether FDA has provided instructions on how they should be submitted electronically. If FDA has not provided instructions on how an OTC monograph submission not explicitly described in this guidance should be submitted, contact FDA at druginfo@fda.hhs.gov.”
• What should be submitted to which portal? Per the draft guidance, OMORs, meeting requests and packages, formal dispute resolution requests, administrative hearing requests and responses to record requests should use the CDER NextGen portal. On the other hand, data, information and comments to a proposed or final order should use the OTC Monographs@FDA portal. Sponsors should continue to submit updates to drug listing information using FDA’s Electronic Drug Registration and Listing System (eDRLS).
• CDER NextGen portal requires an applicant to create an account and does not allow editing once submitted. As the draft guidance noted, the receipt date for an electronic OTC monograph is based on passing validation checks on file properties such as file size and a virus scan. If successfully submitted, the applicant will receive confirmation both in the portal and as email confirmation with the receipt date. The guidance warned: “The receipt date for an OTC monograph submission is the date on which the request is deemed to have arrived at FDA. The receipt date should not be confused with the date of FDA’s subsequent decision to file a request.” Questions related to the portal can be submitted to the agency via email.
• Sponsors should be aware the monograph order process is generally public. If any information is considered confidential, sponsors should follow instructions under the CDER NextGen portal or OTC Monographs@FDA portal on how to submit confidential information.
• The draft guidance received a single comment from the Consumer Healthcare Products Association (CHPA) with mostly technical requests. CHPA asked for clarification for the file types and maximum file sizes accepted by each portal, along with more communication regarding workarounds (e.g., compressed files) and reasons for failed uploads. “Sponsors should know in advance if their file sizes will need additional CDER assistance prior to submission,” CHPA wrote, continuing, “A submission rejection because of file size limitation may lead to confusion and may ultimately cause the sponsor to miss their submission timeline date.” The organization also requested additional information in the guidance regarding portal accounts, particularly asking for further instruction if an individual does not have a secure email or certain other identifying information.

Now, FDA has finalized this document with minor changes

• The draft guidance was brief and generally limited in content, and the final version is no different. Published July 25, 2024, the final guidance retains the vast majority of content from its predecessor, with a handful of wording changes and additional explanations. For example, rather than listing the information that should be submitted to different portals in paragraph form, the guidance now includes bulleted lists to increase readability.
• The biggest change: the guidance contains many references to the CDER NextGen Portal Reference Guides. In places where the draft guidance encouraged sponsors to reference FAQ sites or email the agency directly, the guidance now provides links to reference guides that elaborate on information such as file naming conventions, acceptable file formats, and file size limitations. These guides represent a significant investment on FDA’s part in developing these resources. These address many of the questions raised by CHPA while giving FDA more leeway to update the guides as technology changes.
• That said, the final guidance adds expanded instructions on “next steps” for sponsors once a CDER NextGen Portal account is created. Per the guidance, the portal will lead submitters through the process to establish a monograph file (MGF), which involves submission of a Pre-Assignment Request. Once this is reviewed, an MGF number is assigned, and the OTC monograph submission may proceed.
• What’s next? With this guidance publication, FDA has fulfilled its commitment under OMUFA. Still, the agency is over three months late on the timeline set in the commitment letter. A couple of additional guidances agreed to under the user fee program have yet to be finalized, though they are likely to be forthcoming in the coming months. First, the agency agreed to finalize guidance on formal meetings between FDA and sponsors or requestors for OMUFA ingredients and drug products, which was released in draft form in February 2022 [ See AgencyIQ analysis here.]. Final guidance was expected in July 2023, according to the commitment letter performance goals. and the most recent update Second, a draft guidance on best practices for appeals of decisions regarding a monograph was published in June 2023 [ See AgencyIQ analysis here], targeted for finalization in February 2024 in the commitment letter.

Featuring previous research by previous AgencyIQ researcher Kedest Tadesse.

To contact the author of this item, please email Amanda Conti ( aconti@agencyiq.com).
To contact the editor of this item, please email Jason Wermers ( jwermers@agencyiq.com).

Key Documents and Dates

• Final Guidance: Providing Over-the-Counter Monograph Submissions in Electronic Format
• FDA Docket No.: FDA-2022-D-2059