In the original Broadway show Hamilton, Leslie Odom, Jr. sang, “I want to be in the room where it happens.” The Food and Drug Administration let sponsors and requestors of over-the-counter (“OTC”) monograph drugs know how to be in the room where it happens when it issued a draft guidance this month on “Formal Meetings Between FDA and Sponsors or Requestors of Over-the-Counter Monograph Drugs.”¹ While the draft guidance is not legally binding on FDA (or industry), it provides the agency’s current thinking, so it’s worth a high-level review by companies developing or marketing OTC monograph drugs. For purposes of this Bulletin, we assume the reader understands the OTC monograph process, and will not discuss it here.

Background

• The CARES Act changes the regulatory framework for OTC monograph drug regulation.
• The CARES Act allows FDA to assess and collect user fees dedicated to OTC monograph drug activities.
• FDA must establish procedures under which requesters can meet with appropriate agency officials to obtain advice on the studies and other information necessary to support regulatory submissions, other matters relevant to the regulation of non-prescription drugs, and the development of new non-prescription drugs.
  • A requestor is “any person or group of persons marketing, manufacturing, processing, or developing a drug.”
• FDA must establish procedures to facilitate participation in joint meetings by multiple meeting requesters.
• The guidance does not apply to non-prescription drugs intended to be submitted as new drug applications, abbreviated new drug applications, or investigational new drug applications.
• Comments to the draft guidance must be submitted by April 8, 2022.

Meeting Types

• There are three types of formal meetings: Type X, Type Y, and Type Z.
• A Type X meeting is one that is necessary for a stalled OTC monograph order development program to proceed or a meeting that is necessary to address an important safety issue that needs immediate action.
• A Type Y meeting is intended for milestone discussions during the course of a development program and should generally occur not less than three months before the planned submission of an OTC Monograph Order Request (“OMOR”).²
  • A requestor may ask for a meeting when it has an interest in initiating an OMOR (i.e., a requester has not yet started an OTC monograph order development program).
  • When nearing completion of its development program for an OMOR, FDA recommends a pre-OMOR submission meeting to present a summary of the data supporting the OMOR and to take the following steps:
    • Discuss the proposed format for the OMOR.
    • Obtain FDA feedback on the adequacy of the proposal for the OMOR, such as the OMOR format and content, including presentation of data, the structure of the dataset, acceptability of data for submission, and the projected submission date of the OMOR.
    • Discuss the appropriate categorization of an OMOR (e.g., Tier 1 or Tier 2).
      • The law establishes two types of OMORs for user fee purposes: Tier 1 and Tier 2.
        • A Tier 1 OMOR is any OMOR not determined to be a Tier 2 OMOR. Examples of Tier 1 OMORs include additions of a new ingredient to a monograph that already has one or more ingredients that have been found to be Generally Recognized as Safe and Effective (“GRASE”) or a new monograph therapeutic category (each ingredient proposed for the new therapeutic category will be a separate OMOR).
        • A Tier 2 OMOR is, for example, a request for reordering of existing information in the Drug Facts label of an OTC monograph drug; addition of information to the “Other Information” section of the Drug Facts label of an OTC monograph drug (subject to certain limitations); modification to the “Directions for Use” section of the Drug Facts label of an OTC monograph drug, consistent with a minor dosage form change; and standardization of the concentration or dose of a specific finalized ingredient within a particular finalized monograph.

• A Type Z meeting is any meeting that is not a Type X or Type meeting.

Meeting Formats

• There are three meeting formats: face-to-face, teleconference/videoconference, and written response only (“WRO”).

Meeting Requests

• Requesters should consult publicly available information before asking for a meeting.
• To ask for a meeting, the sponsor must submit a written request to FDA electronically and include adequate information to assess the potential usefulness of the meeting and to identify which FDA staff should attend.
• The meeting request should include the following information:

1. The OMOR number, if applicable;
2. The product name, if applicable;
3. The relevant OTC monograph or, if an OTC monograph has not yet been established, the proposed therapeutic category;
4. The chemical name, established name, and/or structure;
5. Indications or proposed indications (uses);
6. The meeting type being requested (e.g., Type X, Type Y, or Type Z) and the rationale for requesting meeting type;
7. Suggested dates and times (e.g., morning or afternoon) for the meeting; and
8. A list of questions grouped by FDA discipline; for each question, there should be a brief explanation of the context and purpose of the question.

• The meeting request must include the following information:

1. A brief statement of the purpose of the meeting, including:
   • a brief background of the issues;
   • a brief summary of data that the requester intends to discuss at the meeting, the general nature of the critical questions to be asked, and where the meeting fits in the overall OTC monograph order development program; and
   • enough information to facilitate understanding the issues (e.g., a small table that summarizes major clinical trial results);
2. The proposed format of the meeting (e.g., face-to-face, teleconference/ videoconference, or WRO);
3. A listing of the specific objectives or outcomes the requester expects from the meeting;
4. A proposed agenda, including estimated times needed for discussion of each agenda item;
5. A statement of whether the requester intends to discuss information exempt from disclosure under the law;
6. A list of planned attendees from the meeting requester’s organization, which should include their names and titles, as well as the names, titles, and affiliations of consultants, if applicable;
7. A list of requested attendees or discipline representatives from the Center for Drug Evaluation and Research, with an explanation for the request (when attendance by non-essential FDA staff is requested, the request should include a rationale for these attendees and note whether a later meeting date is acceptable to the requester to accommodate the non-essential FDA attendees); and
8. The date that the meeting package will be sent to FDA by the meeting requester.

Assessing and Responding to Meeting Requests

• Requests for Type Y meetings will typically be granted.
• In general, FDA will not grant a requester more than one Type Y meeting to discuss a particular OTC monograph order development program or conditions of use for a particular OTC monograph.
• For WRO meetings, the notification will include the date FDA intends to send the written response.
• FDA provided the following tables about response times and meeting schedules.

Meeting Request Response Time Goals

Meeting Schedule or WRO Times

• If FDA denies a meeting request (which will be for substantive reasons), it will explain its decision in writing.
• A subsequent request to schedule the meeting will be considered a new
• FDA will deny a request for a meeting from a person subject to user fees, and there are outstanding fees to pay.
• The requester should submit the meeting package to FDA for each meeting type (including WRO) no later than the date specified below.

Meeting Requester Meeting Package Timelines

• The meeting package must be submitted electronically to FDA, and the meeting package should identify the subject of the meeting and the date and time of the meeting, if known.
• The meeting package should provide summary information relevant to the OTC monograph order development program or the regulation of the OTC monograph drug and any supplementary information needed for FDA to respond.
• Meeting packages generally should include the following information, preferably in the order listed below:

1. The OMOR number, if previously assigned;
2. The product name, if applicable;
3. The relevant OTC monograph, or if a relevant OTC monograph has not yet been established, the relevant therapeutic category;
4. Chemical name, established name, and/or structure;
5. United States Pharmacopeia active ingredient monograph, if applicable;
6. The indications or proposed indications (uses) or context of OTC monograph order development program;
7. The proposed tier of the OMOR (Tier 1 or Tier 2), if applicable;
8. Dosage form, route of administration, and dosing regimen (strength, frequency, and duration), if applicable;
9. A list of all individuals, with their titles and affiliations, who will attend the requested meeting from the organization, including consultants;
10. A background section that includes:
    • a brief history and information about the issues to be discussed at the meeting about the OTC monograph order development program, regulation of the OTC monograph drug, or OTC monograph drug development, including substantive changes in development plans and current status of development, and relevant communications with FDA; and
    • if applicable, a list of completed, ongoing, and planned studies;
11. A brief statement summarizing the purpose of the meeting;
12. A proposed agenda, including estimated times needed for discussion of each agenda item;
13. A list of the final questions for discussion grouped by FDA review discipline and with a brief summary for each question; in general, there should be no more than 10 questions listed consecutively, regardless of discipline; and
14. Data to support discussion, organized by FDA discipline and question; protocols, full study, and trial reports, or detailed data generally are not appropriate for meeting packages, and the summarized material should describe the results of relevant studies and clinical trials with some degree of quantification and any decision about clinical trials that resulted.

Preliminary Responses

• Preliminary responses are not final unless there is an agreement between the two parties that additional discussion is not necessary.
• Preliminary responses are not intended to generate the submission of new information or new questions; if a requester provides new data or a revised or new proposal, FDA may not be able to provide comments on the new information, and the requester may need to submit a new meeting request to receive feedback on the new information.
• FDA will send the requester its preliminary responses to the questions in the meeting package no later than five calendar days before the meeting date for Type Y and Type Z meetings; FDA will generally not send preliminary responses for Type X meetings.
  • If the requester continues to want a meeting after receiving FDA’s preliminary responses, the requester should send FDA a revised agenda indicating which questions are resolved and unresolved.

Rescheduling Meetings

• If a meeting must be rescheduled, it should be done as soon as possible after the original date; a new meeting request should not be submitted.

Canceling Meetings

• Failure to pay required fees will result in FDA canceling a previously scheduled meeting; if the requester pays the required fee after the meeting has been canceled because of nonpayment, FDA will consider a subsequent request to schedule a meeting to be a new request, and the goal timeline for FDA’s response will be calculated from the date of the subsequent request.
• FDA can cancel a meeting if the meeting package is not received by the agency within the specified timelines, the meeting package is inadequate, the meeting package and questions are substantively different from the original request and no longer meet the criteria for the meeting granted, or the meeting requester determines that preliminary responses to its questions are sufficient.

Meeting Minutes

• FDA intends to issue the official, finalized minutes to the requester within 30 calendar days after the meeting.
• FDA minutes will describe the important agreements, disagreements, issues for further discussion, and action items from the meeting in bulleted format.
• FDA may communicate additional information in the final minutes that was explicitly communicated during the meeting or that provides further explanation of discussion topics; the final minutes will make clear this additional information from the discussion that occurred during the meeting.

Joint Meetings

• Multiple meeting requesters may want to combine efforts and have a formal meeting with FDA to discuss studies and other information necessary to support OTC monograph order submissions, matters relevant to the regulation of OTC monograph drugs, or OTC monograph drug development where they have a common interest. These formal meetings with multiple meeting requesters are known as joint meetings.
• A joint meeting may be requested for Type X, Type Y, and Type Z meetings.
• FDA provides the following examples where a joint meeting is appropriate:
  • A Type Y meeting to discuss overall data requested to support a positive GRASE determination after FDA has stated its intent to make a final GRASE determination for a particular monograph ingredient or other monograph condition of use.
  • A Type X meeting to discuss safety concerns with a marketed OTC monograph drug.
• Meeting requesters may consider forming an OTC monograph industry working group (“OTC IWG”) to work together on issues of common interest.
• If an OTC IWG is formed, the OTC IWG should designate a single point of contact (“POC”) to represent the OTC IWG in communications with FDA. The POC should facilitate all communication between FDA and the OTC IWG about the joint meeting, be responsible for all submissions related to the joint meeting, and serve as the point person for FDA.
• The POC can request a joint meeting on behalf of the OTC IWG.
• In addition to the information that should be submitted in the meeting request, it should include:
  • the meeting being requested is a joint meeting;
  • appropriate documentation of the formation of the OTC IWG and a list of its members, including organizations nominated by meeting requesters to represent their interests; and
  • the name of the POC and documentation of POC designation.
• In addition to the information that should be submitted in the meeting package, it should include any specific topics of discussion that should not be discussed because the OTC IWG has not agreed to share information protected from disclosure.

Confidentiality of Information Submitted to FDA in Connection With Formal Meetings

• A formal meeting is not open to the public to attend. Only the requester or, for joint meetings, the group of meeting requesters and their representatives, may attend the meeting.

AGG Observations

• The draft guidance provides detailed information on what FDA expects to see in request packages and the timing of meetings; there is transparency in the process.
• With any meeting request, companies should provide as much information as possible to obtain useful FDA feedback and maximize the meeting time.
• While one might want to be in “the room where it happens,” FDA holds the keys to the entrance and whether your stay (in this case, your proposal) is welcome.

[1] FDA issued the guidance to explain section 505G of the Federal Food, Drug and Cosmetic Act, 21 U.S.C. § 355h. Section 505G of the FDC Act was added by the Coronavirus Aid, Relief, and Economic Security Act (CARES Act).

[2] The term OMOR is defined in the law and refers to a request for FDA to issue an administrative order under Section 505G of the FDC Act. There are two Tiers of OMORs, discussed further in this Bulletin.