An OTC monograph drug is a nonprescription, over-the-counter (or OTC) drug that may be marketed without an approved drug application under section 505 of the FD&C Act if it meets the requirements of section 505G of the FD&C Act, as well as other applicable requirements.

Simply stated, an OTC monograph is a "rule book" for each therapeutic category establishing conditions, such as active ingredients, uses (indications), doses, route of administration, labeling, and testing under which an OTC drug is generally recognized as safe and effective (GRASE).

In 1972, FDA established the Over the Counter (OTC) Drug Review to evaluate the safety and effectiveness of nonprescription, OTC drug products marketed in the United States before May 11, 1972. The OTC Drug Review established conditions under which OTC drugs were generally recognized as safe and effective (GRASE) and not misbranded. These GRASE conditions were described in OTC drug monographs for each OTC therapeutic drug class. Prior to enactment of the CARES Act, the OTC Drug Review relied on a three-phase public rulemaking process to establish monographs.

For more information on the OTC Drug Review prior to enactment of the CARES Act, see the FDA webinar titled The Monograph reform is here! Learn what to expect and how to prepare.

The CARES Act, enacted on March 27, 2020, includes important reforms that modernize the way OTC monograph drugs are regulated in the United States. Specifically, the CARES Act replaces the rulemaking process with an administrative order process for issuing, revising, and amending OTC monographs. The CARES Act also provides FDA the authority to assess and collect user fees dedicated to OTC monograph drug activities. FDA anticipates that this user fee program will provide additional resources to help the agency conduct these important regulatory activities in a timely manner and ultimately help provide the public with access to innovative OTC monograph drugs.

Despite FDA's successes in providing consumers with access to a wide variety of safe and effective OTC monograph drugs, challenges the over 50-year old OTC Drug Review process became apparent. The biggest challenges of the OTC Drug Review prior to the CARES Act included:

• Burdensome, multistep rulemakings to establish or amend monographs;
• FDA lacked adequate resources to devote to rulemaking process;
• Delays in finalizing monographs;
• Limited, burdensome process for innovation (e.g., new combinations of ingredients or new dosage forms);
• Delays in responding to safety issues; and
• Challenges in keeping pace with evolving science and changing market conditions.

OTC Monograph Reform is expected to accomplish the following:

• Improve the process by replacing rulemaking with administrative orders;
• Improve efficiency, timeliness, and predictability;
• Facilitate innovation;
• Establish a process to rapidly address safety issues;
• Finalize pending monographs; and
• Provide FDA with user fees to support OTC monograph drug activities.

Yes, the Over-the-Counter Monograph User Fee Program Performance Goals and Procedures document outlines the performance and procedural goals and other commitments agreed to by the agency for purposes of this user fee program. These goals apply to aspects of the over-the-counter monograph drug review program that are important for facilitating timely access to safe and effective medicines regulated under the OTC drug monograph system, and to implementing the OTC monograph policy reforms.

During the first three years of OTC Monograph Reform, essentially all effective review capacity has been consumed by current external mandates, safety activities, and OTC Monograph Reform implementation and infrastructure development activities. Beginning in Years 4 and 5 (and to a limited extent in Year 3), FDA expects to have built sufficient effective review capacity to begin to have timelines and performance goals for review activities expected to be part of the steady state of a monograph review program.

FDA is committed to meeting the timelines and performance goals and to continuous improvement of its performance.

The CARES Act gives FDA the authority to issue an administrative order that adds, removes or changes GRASE conditions for an OTC drug monograph.

Either industry or FDA can initiate the administrative order process. A request by industry to initiate the administrative order process is called an OTC Monograph Order Request (OMOR) and can be made by a requestor, which is defined in the CARES Act as any person or group of persons marketing, manufacturing, processing, or developing a drug.

As FDA issues each proposed or final administrative order, FDA will publish the order at "Administrative Orders" on OTC Monographs@FDA. Additionally, FDA will also publish a notice of availability of each proposed and final administrative order in the Federal Register.

Yes. After issuance of a proposed administrative order, there will be a public comment period. The public will receive at least 45 calendar days (and potentially longer depending on the subject of the proposed order) to submit comments on the proposed administrative order. When FDA issues the proposed order, the agency will provide Information on how the public should submit their comments and the duration of the comment period.

The procedure for FDA to initiate an administrative order can be expedited when FDA determines:

• a drug poses an imminent hazard to public health; or
• a change in the labeling of a drug, class of drugs, or combination of drugs is reasonably expected to mitigate a significant or unreasonable risk of a serious adverse event associated with use of the drug.

The term "OTC monograph order request" (or OMOR) is defined in section 744L(7) of the FD&C Act and refers to a request for FDA to issue an administrative order under section 505G of the FD&C Act.

There are two types of OMORs: Tier 1 and Tier 2.

As described in section 744L(8) of the FD&C Act, a Tier 1 OMOR is any request not determined to be a Tier 2 OMOR.

Examples of Tier 1 OMORs include additions of:.

• 1. A new ingredient to a monograph that already has one or more ingredients that have been found to be GRASE.
• 2. A new indication to a monograph that already has one or more ingredients that have been found to be GRASE, and the new indication applies to one or more of the GRASE ingredients.
• 3. New monograph therapeutic category (each ingredient proposed for the new therapeutic category will be a separate OMOR).

As described in section 744L(9) of the FD&C Act, a Tier 2 OMOR is a request for:

• 1. Reordering of existing information in the drug facts label of an OTC monograph drug;
• 2. Addition of information to the "Other Information" section of the drug facts label of an OTC monograph drug (subject to certain limitations);
• 3. Modification to the "Directions for Use" section of the drug facts label of an OTC monograph drug, consistent with a minor dosage form change;
• 4. Standardization of the concentration or dose of a specific finalized ingredient within a particular finalized monograph;
• 5. Change to ingredient nomenclature to align with nomenclature of a standards-setting organization; or
• 6. Addition of an interchangeable term in accordance with section 330.1 of title 21, Code of Federal Regulations (or any successor regulations).

Based on program implementation experience or other factors found appropriate by FDA, FDA may also characterize any OMOR as a Tier 2 OMOR (including recharacterizing a request from Tier 1 to Tier 2) and publish such determination in a proposed order issued pursuant to section 505G of the FD&C Act.

In April 2023, FDA issued a draft guidance for industry titled Over-the-Counter Monograph Order Requests (OMORs): Format and Content. Please refer to the draft guidance for the agency's recommendations on the format and content of the information requestors should provide in an OMOR.

No. However, when nearing completion of the development program for an OMOR, FDA strongly encourages requestors to request a pre-OMOR submission meeting to present a summary of the data supporting the OMOR. In a pre-OMOR meeting, requestors can discuss the proposed format of the OMOR, obtain FDA feedback on the adequacy of the proposal for the OMOR submission, and discuss the appropriate categorization of the OMOR. The meeting should be sufficiently in advance of the planned submission of the OMOR to allow for a meaningful response to FDA feedback.

Requestors of OTC monograph drugs should submit an OMOR electronically through the CDER NextGen Portal.

Submitters need to have a CDER NextGen portal account to submit an OMOR in electronic format through the CDER NextGen portal. For information, go to the CDER NextGen portal website available at https://edm.fda.gov.

Yes, a requestor may submit an OMOR for FDA review. FDA will review the OMOR in accordance with timelines set forth in the OMUFA commitment letter.

Yes. This reference guide provides additional information about submitting an OMOR in the CDER NextGen Portal. This reference guide can also be accessed through the CDER NextGen Portal.

Section 505G of the Federal Food, Drug, and Cosmetic (FD&C Act), as added by the CARES Act, deemed final monographs and tentative final monographs, as described by that section, to be final orders. Among other things, section 505G describes final and tentative final monographs as being the most recently implemented version, including as modified by any proposed or final rule.

FDA ensured that the OTC monographs in the deemed final orders were appropriately harmonized, in terms of terminology and cross references (for example, since the monographs are no longer in the Code of Federal Regulations [CFR] the corresponding CFR citations and references have been updated to reflect a new order numbering system). FDA also included some other minor changes in the deemed final orders, such as consolidating professional use provisions into their own section within an OTC monograph, to provide stakeholders with more easily accessible information about the OTC monograph that is in effect for each therapeutic category.

The CARES Act established the deemed final orders, which were effective upon enactment of the CARES Act on March 27, 2020.

All administrative orders, including the deemed final orders are available at OTC Monographs@FDA. To access the administrative orders, go to OTC Monographs@FDA. Under the "Administrative Orders" banner, click on the desired link under the "Order ID" heading and follow the prompts.

FDA is also posting separate OTC monograph documents that contain up-to-date OTC monograph sections that incorporate the latest final administrative orders. This provides a convenient and easy reference point for stakeholders to view the current OTC monograph, especially as the administrative order process modifies existing deemed final orders. To access these OTC monograph documents, under the "OTC Monographs" banner, click on the desired link under the "OTC Monograph ID" heading and follow the prompts.

FDA intends to issue a notice to withdraw the regulations establishing final monographs in title 21 of the CFR at a later date, once all the relevant deemed final orders have been posted on FDA's OTC Monographs@FDA web portal (i.e., 21 CFR parts 331, 332, 333, 335, 336, 338, 340, 341, 343, 344, 346, 347, 348, 349, 350, 352, 355, 357, and 358). Prior to the withdrawal of such regulations, reference the OTC monographs posted in OTC Monographs@FDA, to the extent the corresponding deemed final order has been added to the portal.

The new public facing web-portal, OTC Monographs@FDA, is an important part of the infrastructure for the new processes under OTC monograph reform and, generally, will be used instead of regulations.gov.

The CARES Act in establishing a streamlined administrative order process for OTC monographs that is intended to improve efficiency, timeliness and predictability of the OTC monograph system requires all submissions related to the administrative order process to be in electronic format and all final orders issued by FDA to be available in a public repository. In addition, the OTC Monograph User Fee Program Performance Goals and Procedures (OMUFA goals document) calls for FDA to establish a public-facing IT dashboard and IT platform for publicly displaying OTC monograph information and for receiving electronic submissions, archiving review work, and generating reports.

As a first step in implementing the new IT systems discussed in the OMUFA goals document, FDA has posted the deemed final orders to the public-facing web portal, OTC Monographs@FDA, which is the "public facing IT dashboard" referenced in the OMUFA goals document. This new web portal, OTC Monographs@FDA, provides stakeholders with the ability to search for proposed and final administrative orders that add, remove or change conditions of an OTC monograph. OTC Monographs@FDA also facilitates the submission of comments and data from stakeholders for proposed administrative orders.

Initially, as we implement OTC monograph reform, a few proposed orders may also be posted on regulations.gov, in addition to OTC Monographs@FDA, due to the historical use of regulations.gov for specific therapeutic categories. Each individual proposed order and its accompanying Federal Register Notice of Availability will contain instructions on how to submit comments.

If the order incorporates material (such as an ISO standard) by reference and states that this material is available for inspection at FDA, contact druginfo@fda.hhs.gov for more information about how to inspect. Copies of a specified publication may also be available from its publisher.

For an antiperspirant drug product marketed under section 505G of the FD&C Act that demonstrates standard effectiveness (20 percent sweat reduction) or extra effectiveness (30 percent sweat reduction) over a 24-hour period, the labeling may include effectiveness claims that the product works for all day or 24 hours.

Antiperspirant drug products marketed under section 505G of the FD&C Act cannot make effectiveness claims that the product works for more than 24 hours..

OTC external analgesic drug products that are in a patch, plaster, or poultice dosage forms and conform with the provisions of section 505G(a)(3)(A) of the FD&C Act may currently be legally marketed without an approved application.

Laxative drug products containing bisacodyl and sennosides as active ingredients and conforming with the provisions of section 505G(a)(3)(A) of the FD&C Act may currently be legally marketed without an approved application.

FDA issued a draft guidance titled "Formal Meetings Between FDA and Sponsors or Requestors of Over-the-Counter Monograph Drugs" regarding formal meetings between FDA and sponsors or requestors of OTC monograph drugs (hereinafter referred to as "meeting requesters"). When finalized, this guidance will specify the procedures and principles for formal meetings between FDA and meeting requesters. It will describe procedures under which meeting requesters can meet with appropriate FDA officials to obtain FDA's advice on the studies and other information necessary to support submissions under section 505G of the FD&C Act, other matters relevant to the regulation of nonprescription drugs, and the development of new OTC monograph drugs. The guidance will also specify procedures to facilitate efficient participation in joint meetings by multiple meeting requesters and/or organizations nominated by them to represent their interests.