April 1, 2013, the Food and Drug Administration (FDA) announced the availability of a new draft guidance addressing the procedures for requesting and conducting meetings on the topic of biosimilar product development and approval. The draft guidance, entitled Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants, provides “principles of good meeting management practices (GMMPs)” and establishes “standardized procedures for requesting, preparing, scheduling, conducting, and documenting” formal meetings between members of the biosimilars industry and FDA.1
The draft guidance comes as part of FDA’s implementation of the Biologics Price Competition and Innovation Act of 2009, which established the 351(k) approval pathway for biosimilar products. FDA’s past guidance documents addressing the 351(k) pathway have encouraged biosimilar product sponsors to meet with FDA in the early phases of the application process, advising sponsors to “establish a schedule of milestones that will serve as landmarks for future discussions with the Agency.”2 In 2012, the nature and scope of FDA’s interactions with biosimilar product sponsors received additional attention after enactment of the Biosimilar User Fee Act, which led to the establishment of five specific types of meetings between sponsors and the Agency that may take place as part of a biosimilar development program.3
FDA’s new draft guidance addresses these five meeting types and reviews the definitions and timelines previously described in the Agency’s draft biosimilars user fee commitment letter.4 The draft guidance also applies more generally to any meeting that a sponsor requests in compliance with the procedures articulated in the guidance, whether conducted in a face-to-face, teleconference, videoconference, or any other format.
“Already, the extensive amount of information that FDA has requested be included in meeting packages and requests has fueled concerns that the 351(k) pathway, which was intended to be ‘abbreviated,’ will in practice prove to be anything but.”
Pursuant to the guidance, a meeting request should include a written submission specifying the issues for which FDA’s input is desired. It should include sufficient information to allow FDA to assess the utility of the meeting, and should enable FDA to identify the staff whose participation will be required. In particular, the meeting request should include fifteen elements:
- The product name;
- The application number (if there is currently an application);
- The proposed proper name (or, if post-licensure, the established proper name);
- The product structure (if applicable);
- The reference product name;
- The proposed indication(s) or context of product development;
- The meeting type requested (a Biosimilar Initial Advisory meeting or a BiologicalProduct Development (BPD) Type 1, 2, 3, or 4 meeting), along with the rationalefor requesting this meeting type. The final determination as to the type ofmeeting conducted will be made by FDA;
- A brief statement of the purpose of the meeting, including a brief background ofthe underlying issues. The sponsor may also provide a brief summary of studiesand clinical trials (planned or completed), relevant data, the potential role of themeeting in the overall development plan, and “the general nature of the criticalquestions to be asked”;
- A list of the specific objectives or outcomes the requester expects from the
- A proposed agenda, including estimated times needed for each agenda item; A list of questions, which should be precise, “grouped by discipline,” and
- accompanied by a brief explanation of each question’s context and purpose;
- A list of individuals from the sponsor’s organization as well as consultants who
- will attend the requested meeting, identified with their titles and affiliations. FDA
- acknowledges that this list may change between the time of the meeting request
- and the time when the meeting is held, and states that an updated list should be
- provided at least one week prior to the meeting;
- A list of FDA staff or disciplines whose participation is requested;
- Suggested meeting dates and times; and
- The proposed meeting format, such as face-to-face or via teleconference.6
In addition to addressing these items, the meeting request should be paired with a “meeting package”; indeed, FDA will deem a meeting request incomplete and will generally deny the request if no meeting package accompanies the request. FDA advises that the meeting package ought to “provide information relevant to the product, development stage, and meeting type requested,” and should identify “known or expected difficult design and evidence issues,” such as the potential selection of doses, study populations, or endpoints that differ from those studied for the licensure of the reference product.7 The guidance further directs that, in addition to much of the same information included in the meeting request, the meeting package should contain:
- A description of the dosage form, route of administration, dosing regimen (including duration and frequency and duration), and presentation(s) of the product;
- A background section including a brief history of the development program and a description of the development status (including chemistry, manufacturing and controls, nonclinical, and clinical information); and
- Data to support discussion organized by discipline and question. The level of detail required will depend on the development stage of the product and the requested meeting type.8
FDA Assessment of Meeting Requests
Once a meeting request and package has been submitted, FDA will grant or deny the request within (1) fourteen calendar days of receipt, if the request is for a BPD Type 1 meeting, or; (2) twenty-one calendar days of receipt, if the request is for a Biosimilar Initial Advisory meeting or a BPD Type 2, 3, or 4 meeting. A denial will rest on a “substantive reason”; failure to comply with a “minor element” of the meeting request or meeting package requirements will not result in denial.9 A meeting may be denied if it is premature for the current stage of product development, is clearly unnecessary, or if the applicant or sponsor is in arrears with respect to an annual BPD fee for this product; however, absent such deficiencies, requests for BPD Type 2, 3, and 4 meetings for that product “will be honored except in the most unusual circumstances.”10
If the request is denied, FDA will explain the reason for its decision. Subsequent attempts to schedule the meeting will be treated as new requests, subject to new timelines. If the request is granted, the sponsor will be notified in writing, and FDA will determine “the meeting type, date, time, length, place, format (i.e., a scheduled face-to-face meeting, teleconference, or videoconference), and expected FDA participants.”11
After granting a meeting request, FDA may provide preliminary responses to the questions posed in the submitted materials. However, the draft guidance cautions that these responses should not be considered final unless FDA and the sponsor agree otherwise.
Procedures for the Conduct of Meetings
When the meeting is conducted, it will be chaired by an FDA staff member. Before it is completed, participants will summarize “the important discussion points, agreements, clarifications, and action items” from the meeting.12 FDA notes that the sponsor will typically be asked to provide this summary, in order “to ensure that there is mutual understanding of meeting outcomes and actions” between the parties.13 In addition, FDA advises that meeting presentations will not generally be required, as all information necessary for discussion should have already been submitted in the meeting package. Accordingly, meetings will not be lengthened so as to accommodate presentations. If the sponsor nonetheless desires to make a presentation, it should contact FDA in advance to determine whether the presentation is warranted and to provide copies of the presentation materials.
The final sections of the draft guidance address the documentation of meetings and the resolution of disputes about meeting minutes. FDA minutes will serve as the official meeting records, and will be provided to all meeting participants within thirty days of the meeting. Any objections to the accuracy of the minutes, or requests for clarification, should be directed to the assigned FDA point of contact. If significant differences in the understandings of the FDA and the sponsor persist, the sponsor is instructed to describe the specific disagreements to FDA in writing. The relevant FDA division will then evaluate these concerns. If FDA decides to change the minutes, the changes will be input as an addendum, which will also address any remaining concerns of the sponsor; if FDA determines that the minutes do not require revision, the sponsor will be notified and the minutes will continue to serve as the official meeting documentation.
In addition to the particulars described above, the draft guidance includes information regarding the canceling or rescheduling of meetings. It also provides instructions with respect to pagination, the use of tabs, the inclusion of a table of contents, and other specifics of meeting package formatting, organizing, and method of submission.14 Companies currently engaged in or considering development of a biosimilar product are advised to review these details closely.
Already, the extensive amount of information that FDA has requested be included in meeting packages and requests has fueled concerns that the 351(k) pathway, which was intended to be “abbreviated,” will in practice prove to be anything but. The draft guidance has also been criticized for leaving a number of critical questions unanswered. Nonetheless, the procedures described may help FDA satisfy its goals with respect to its timelines for responding to and satisfying meeting requests. The procedures will also provide ample opportunity for sponsors to demonstrate whether and what types of human trials may be necessary for the approval of their products. Interested parties who would like to submit comments on the draft guidance are advised to do so by May 31, 2013, to ensure consideration prior to preparation of the final version of the guidance.