Information Packages: CBER

Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants

Guidance for Industry

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

February 2016

Procedural

OMB Control No. XXXXXX

Expiration Date XXXXXX

See additional PRA statement in section XV of this guidance.

Formal Meetings Between the FDA and Biosimilar Biological Product Sponsors or Applicants

Guidance for Industry

Additional copies are available from:

Office of Communications, Division of Drug Information

Center for Drug Evaluation and Research

Food and Drug Administration

10001 New Hampshire Ave., Hillandale Bldg., 4th Floor

Silver Spring, MD 20993-0002

Tel: 855-543-3784 or 301-796-3400; Fax: 301-431-6353; Email: [email protected]

http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

or

Office of Communication, Outreach, and Development

Center for Biologics Evaluation and Research

Food and Drug Administration

10903 New Hampshire Ave., Bldg. 71, rm. 3128

Silver Spring, MD 20993-0002

Tel: 800-835-4709 or 240-402-7800; Email: [email protected]

http://www.fda.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/default.htm

U.S. Department of Health and Human Services

Food and Drug Administration

Center for Drug Evaluation and Research (CDER)

Center for Biologics Evaluation and Research (CBER)

February 2016

Procedural

TABLE OF CONTENTS

I. INTRODUCTION 1

II. BACKGROUND 2

III. MEETING TYPES 3

IV. PARTICIPATION IN the FDA’S BIOSIMILAR BIOLOGICAL PRODUCT DEVELOPMENT PROGRAM 5

V. MEETING PROCEDURES 6

A. Biosimilar Initial Advisory Meeting 6

B. BPD Type 1 Meeting 6

C. BPD Type 2 Meeting 6

D. BPD Type 3 Meeting 6

E. BPD Type 4 Meeting 7

VI. MEETING REQUESTS BY SPONSORS OR APPLICANTS 7

VII. ASSESSING MEETING REQUESTS 9

A. Meeting Denied 9

B. Meeting Granted 10

VIII. RESCHEDULING MEETINGS 10

IX. CANCELLING MEETINGS 11

X. MEETING PACKAGE CONTENT AND SUBMISSION 12

A. Timing of Submission 12

B. Where and How Many Copies of Meeting Packages to Send 12

C. Meeting Package Content 13

XI. PREMEETINGS AND COMMUNICATIONS WITH SPONSORS OR APPLICANTS 14

XII. PROCEDURES FOR THE CONDUCT OF MEETINGS 15

XIII. DOCUMENTATION OF MEETINGS 15

XIV. RESOLUTION OF DISPUTE ABOUT MEETING MINUTES 15

XV. PAPERWORK REDUCTION ACT OF 1995 16

Formal Meetings Between the FDA and Biosimilar

Biological Product Sponsors or Applicants

Guidance for Industry¹

This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not create any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.

I. INTRODUCTION

This guidance provides recommendations to industry on formal meetings between the Food and Drug Administration (FDA) and biosimilar biological product sponsors or applicants. The Biosimilar User Fee Act of 2012 (BsUFA), enacted as part of the Food and Drug Administration Safety and Innovation Act (FDASIA), amended the Federal Food, Drug, and Cosmetic Act (the FD&C Act) to authorize a new user fee program for biosimilar biological products.^2,3 The FDA has committed to meeting certain performance goals set forth in a letter from the Secretary of Health and Human Services to the Chairman of the Committee on Health, Education, Labor, and Pensions of the Senate and the Chairman of the Committee on Energy and Commerce of the House of Representatives.⁴ The performance goals include meeting management goals for formal meetings that occur between the FDA and sponsors or applicants during the development phase of a biosimilar biological product. The FDA encourages sponsors and applicants to use the meetings described in this guidance to optimize product development and facilitate submission of marketing applications.

For the purposes of this guidance, formal meeting includes any meeting that is requested by a sponsor or applicant following the request procedures provided in this guidance and includes meetings conducted in any format (i.e., face-to-face meeting, teleconference, or videoconference).

This guidance reflects a unified approach to all formal meetings between sponsors or applicants and the FDA for biosimilar biological product development (BPD) programs. This guidance is intended to assist sponsors or applicants in generating and submitting a meeting request and the associated meeting package to the FDA for biosimilar biological products intended to be submitted under 351(k) of the Public Health Service Act (PHS Act). This guidance does not apply to meetings associated with new drug applications or abbreviated new drug applications under section 505 of the FD&C Act or to biologics license applications (BLAs) under section 351(a) of the PHS Act.⁵

This guidance discusses the principles of good meeting management practices (GMMPs) and describes standardized procedures for requesting, preparing, scheduling, conducting, and documenting such formal meetings.

In general, FDA’s guidance documents do not establish legally enforceable responsibilities. Instead, guidances describe the Agency’s current thinking on a topic and should be viewed only as recommendations, unless specific regulatory or statutory requirements are cited. The use of the word should in Agency guidances means that something is suggested or recommended, but not required.

II. BACKGROUND

Each year, FDA review staff participate in many meetings with biosimilar biological product sponsors or applicants who seek advice relating to the development and review of biosimilar biological products. Because these meetings often represent critical points in the regulatory and development process, it is important that there are efficient, consistent procedures for the timely and effective conduct of such meetings. The GMMPs in this guidance are intended to provide consistent procedures that will promote well-managed meetings, and ensure that such meetings are scheduled within a reasonable time, conducted efficiently, and documented appropriately.

III. MEETING TYPES⁶

There are five types of formal meetings that can occur between sponsors or applicants and FDA staff to discuss development of a biosimilar biological product:

1. Biosimilar Initial Advisory meeting: A Biosimilar Initial Advisory meeting is an initial assessment limited to a general discussion regarding whether licensure under section 351(k) of the PHS Act may be feasible for a particular product, and, if so, general advice on the expected content of the development program. This meeting type does not include any meeting that involves substantive review of summary data or full study reports. However, preliminary comparative analytical similarity data from at least one lot of the proposed biosimilar biological product compared to the U.S.-licensed reference product should be provided in the meeting package. The analytical similarity data should be sufficient to enable the FDA to make a preliminary determination as to whether licensure under section 351(k) of the PHS Act may be feasible for a particular product, and to provide meaningful advice. A general overview of the development program, including synopses of results and findings from all completed studies and information about planned studies, also should be provided.

Extensive analytical, nonclinical, and/or clinical data are not expected to be provided based on the expected stage of development of the proposed biosimilar biological product. If the sponsor or applicant is seeking targeted advice on the adequacy of any comparative data or extensive advice for any aspect of an ongoing biosimilar development program, a different meeting type should be requested.

2. BPD Type 1 meeting: A BPD Type 1 meeting is a meeting that is necessary for an otherwise stalled BPD program to proceed. Examples of a BPD Type 1 meeting include:

• Meetings to discuss clinical holds: (1) in which the sponsor or applicant seeks input on how to address the hold issues; or (2) in which a response to hold issues has been submitted, and reviewed by the FDA, but the FDA and the sponsor or applicant agree that the development is stalled and a new path forward should be discussed

• Special protocol assessment meetings that are requested after receipt of an FDA letter in response to protocols submitted under the special protocol assessment procedures as described in section VI of the BsUFA goals letter

• Meetings to discuss an important safety issue, when such an issue is identified and the FDA and the sponsor or applicant agree that the issue should be discussed

• Dispute resolution meetings as described in 21 CFR 10.75 and 312.48, and in section IV of the BsUFA goals letter, and the draft guidance for industry and review staff Formal Dispute Resolution: Appeals Above the Division Level⁷

3. BPD Type 2 meeting: A BPD Type 2 meeting is a meeting to discuss a specific issue (e.g., proposed study design or endpoints) or questions where the FDA will provide targeted advice regarding an ongoing BPD program. This meeting type can include substantive review of summary data, but does not include review of full study reports.

4. BPD Type 3 meeting: A BPD Type 3 meeting is an in-depth data review and advice meeting regarding an ongoing BPD program. This meeting type includes substantive review of full study reports or an extensive data package (e.g., detailed and robust analytical similarity data), FDA advice regarding the similarity between the proposed biosimilar biological product and the reference product based on a comprehensive data package, and FDA advice regarding the need for additional studies, including design and analysis, based on a comprehensive data package.

• Examples of a BPD Type 3 meeting submission include:

• Comprehensive analytical similarity data that permit the FDA to make a preliminary evaluation of analytical similarity during development. The level of analytical data provided should be similar to what the sponsor or applicant intends to submit in a 351(k) BLA (e.g., full study reports and/or datasets that support the full study reports).

• Full study report(s) for a clinical study(ies).

• Based on the data and/or datasets and results reported in the full study reports, the FDA encourages the sponsor or applicant to provide an update on the development plan of the proposed biosimilar biological product. Examples of topics the sponsor or applicant can address as part of a BPD Type 3 meeting in addition to the in-depth data submitted include the following:

• Proposal for any planned additional studies

• Proposal for extrapolation

5. BPD Type 4 meeting: A BPD Type 4 meeting is a meeting to discuss the format and content of a biosimilar biological product application or supplement to be submitted under section 351(k) of the PHS Act. Although the proposed content of the application will be discussed, this meeting type does not include substantive review of summary data or full study reports.

Sponsors or applicants are not required to request meetings in sequential order (i.e., Biosimilar Initial Advisory meeting, BPD Type 2, BPD Type 3, then BPD Type 4). The meeting type requested depends on the stage of the development program and/or the advice being sought. Although the FDA would most likely grant one Biosimilar Initial Advisory meeting and BPD Type 4 meeting for a particular biosimilar biological product, sponsors or applicants can request, as appropriate, as many BPD Type 2 and Type 3 meetings as needed to support ongoing development of a biosimilar biological product.

IV. PARTICIPATION IN the FDA’S BIOSIMILAR BIOLOGICAL PRODUCT DEVELOPMENT PROGRAM

As stipulated by statute, a sponsor or applicant must pay a biosimilar biological product development fee (BPD fee) to participate in the FDA’s BPD program to receive a BPD Type 1, 2, 3, or 4 meeting for a product.⁸ There is no fee for a Biosimilar Initial Advisory meeting. The BPD fee is an annual per-product fee, not a per-meeting or per-review activity fee. There are three types of BPD fees: the initial BPD fee, the annual BPD fee, and the reactivation fee. The initial BPD fee is due on the date a sponsor or applicant submits an investigational new drug application (IND) for an investigation that the FDA determines is intended to support a biosimilar biological product application for a product, or within 5 calendar days after the FDA grants the sponsor’s or applicant’s request for a BPD Type 1, 2, 3, or 4 meeting for that product, whichever occurs first.⁹

After a sponsor or applicant has paid the initial BPD fee, beginning in the next fiscal year, an annual BPD fee will be assessed for the product until the sponsor or applicant submits a marketing application that is accepted for filing, or discontinues participation in the BPD program for that product.¹⁰ If a sponsor or applicant has discontinued participation in the BPD program for a product and wants to again engage with the FDA on development of the product as a biosimilar biological product, the sponsor must pay a reactivation fee to resume participation in the BPD program for that product.¹¹ The reactivation fee is due on the date the sponsor submits an IND for an investigation that the FDA determines is intended to support a biosimilar biological product application for the product, or within 5 calendar days after the FDA grants the sponsor’s or applicant’s request for a BPD Type 1, 2, 3, or 4 meeting for the product, whichever occurs first.¹²

Section 744H(a)(1)(E) of the FD&C Act establishes the consequences of failure to pay BPD fees. With respect to meetings, if the FDA grants a request for a BPD Type 1, 2, 3, or 4 meeting for a product, and the granting of the meeting request triggers an obligation to pay an initial BPD fee or a reactivation fee for the product, the meeting will be cancelled if the sponsor or applicant fails to pay the fee within 5 calendar days after the meeting is officially granted.¹³ Additionally, if a sponsor or applicant is in arrears with respect to an annual BPD fee for a product, the FDA will deny the sponsor’s or applicant’s request for a BPD Type 1, 2, 3, or 4 meeting for that product, and cancel any scheduled BPD meetings for that product.¹⁴

V. MEETING PROCEDURES

Each meeting type is subject to different procedures, as described below.

A. Biosimilar Initial Advisory Meeting

Biosimilar Initial Advisory meetings should be scheduled to occur within 90 calendar days of FDA receipt of a written meeting request and meeting package. If a sponsor or applicant requests a meeting date that is beyond 90 days from the date of the request receipt, the FDA will work with the sponsor or applicant to determine the earliest agreeable date.

B. BPD Type 1 Meeting

If sponsors or applicants are considering submission of a request for a BPD Type 1 meeting, they should first contact the relevant division in either the Center for Biologics Evaluation and Research (CBER) or the Center for Drug Evaluation and Research (CDER) to discuss the suitability of the request. BPD Type 1 meetings should be scheduled to occur within 30 calendar days of FDA receipt of a written meeting request and meeting package. If a sponsor or applicant requests a meeting date that is beyond 30 days from the date of the request receipt, the FDA will work with the sponsor or applicant to determine the earliest agreeable date.

C. BPD Type 2 Meeting

BPD Type 2 meetings should be scheduled to occur within 75 calendar days of FDA receipt of a written meeting request and meeting package. If a sponsor or applicant requests a meeting date that is beyond 75 days from the date of request receipt, the FDA will work with the sponsor or applicant to determine the earliest agreeable date.

D. BPD Type 3 Meeting

BPD Type 3 meetings should be scheduled to occur within 120 calendar days of FDA receipt of a written meeting request and meeting package. If a sponsor or applicant requests a meeting date that is beyond 120 days from the date of the request receipt, the FDA will work with the sponsor or applicant to determine the earliest agreeable date.

E. BPD Type 4 Meeting

BPD Type 4 meetings should be scheduled to occur within 60 calendar days of FDA receipt of a written meeting request and meeting package. If a sponsor or applicant requests a meeting date that is beyond 60 days from the date of the request receipt, the FDA will work with the sponsor or applicant to determine the earliest agreeable date.

VI. MEETING REQUESTS BY SPONSORS OR APPLICANTS

To make the most efficient use of FDA resources, before seeking a meeting with CBER or CDER, sponsors or applicants should consider other sources of information applicable to their product development program, such as FDA and International Conference on Harmonisation guidances. Written correspondence to request such a meeting should be submitted to the sponsor’s or applicant’s application (e.g., IND, BLA) through the controlled document system.¹⁵

If there is no application, the request should be submitted to either the appropriate CDER division director with a copy sent to the division’s chief of project management staff or to the office director/division director of the appropriate product office within CBER. Before submitting any meeting request by fax or email when there is no application, the sponsor or applicant should contact the appropriate product office within CBER, or the appropriate division or the Biosimilars Program staff within CDER, Office of New Drugs, to determine to whom the request should be directed, how the request should be submitted, and the appropriate format for the request, and to arrange for confirmation of receipt of the request. This contact reduces the possibility that faxed or emailed requests will be overlooked because of the volume of faxes and emails received daily by FDA staff. Faxed or emailed requests should be sent during official business hours (8:00 a.m. to 4:30 p.m. EST/EDT) Monday through Friday (except Federal government holidays).

A meeting request for the development of a proposed biosimilar biological product with multiple indications that span multiple review divisions should be submitted to the division that has regulatory oversight of the reference product.

The meeting request, regardless of the submission method, should include adequate information for the FDA to assess the potential utility of the meeting and to identify FDA staff necessary to discuss proposed agenda items. The meeting request should include the following information:

1. The product name.

2. The application number (if applicable).

3. The proposed proper name (or proper name if post-licensure).

4. The structure (if applicable).

5. The reference product name.

6. The proposed indication(s) or context of product development.

7. The meeting type being requested (i.e., Biosimilar Initial Advisory meeting, BPD Type 1, 2, 3, or 4 meeting). The rationale for requesting the meeting type should be included.

8. A brief statement of the purpose of the meeting. This statement should include a brief background of the issues underlying the agenda. It also can include a brief summary of completed or planned studies or data that the sponsor or applicant intends to discuss at the meeting, the general nature of the critical questions to be asked, and where the meeting fits in overall development plans. Although the statement need not provide detailed documentation of trial designs or completed studies and clinical trials, it should provide enough information to facilitate understanding of the issues, such as a small table that summarizes major results.

9. A list of the specific objectives/outcomes the requester expects from the meeting.

10. A proposed agenda, including estimated times needed for discussion of each agenda item not to exceed the total allotted meeting time.

11. A list of questions, grouped by discipline. Each question should be precise, and there should be a brief explanation of the context and purpose of the question.

12. A list of all individuals with their titles and affiliations who will attend the requested meeting from the sponsor’s or applicant’s organization, including consultants and interpreters.

13. A list of FDA staff, if known, or disciplines, asked to participate in the requested meeting. Note that requests for attendance by FDA staff who are not otherwise essential to the application’s review may affect the ability to hold the meeting within the specified time frame of the meeting type being requested. Therefore, when attendance by nonessential FDA staff is requested, the meeting request should state whether a later meeting date is acceptable to the requester to accommodate the nonessential FDA attendees.

14. Suggested dates and times (e.g., morning or afternoon) for the meeting that are within or beyond the appropriate time frame of the meeting type being requested. Nonavailability dates and times also should be included.

15. The proposed format of the meeting (i.e., face-to-face, teleconference, or videoconference).

The sponsor or applicant should define in its written meeting request the specific areas of input requested from CBER or CDER. A well-written meeting request that uses the above components as a guide can help the FDA understand and assess the utility and timing of the meeting related to product development or review. Although CBER or CDER will determine the final meeting type (i.e., Biosimilar Initial Advisory meeting, or BPD Type 1, 2, 3, or 4 meeting), the sponsor or applicant should provide its meeting type assessment as it relates to the product’s development. The list of sponsor or applicant attendees and the list of requested FDA attendees can be useful in providing or preparing for the input needed at the meeting. However, during the time between the request and the meeting, the projected attendees can change. If there are changes, an updated list of attendees with their titles and affiliations should be provided to the appropriate FDA contact at least 1 week before the meeting.

The objectives and agenda provide overall context for the meeting topics, but it is the list of questions that is most critical to understanding the kind of information or input needed by the sponsor or applicant and to focus the discussion, should the meeting be granted. Each question should be precise and include a brief explanation of the context and purpose of the question. The questions submitted within a single meeting request should be limited to those that can be reasonably answered within the allotted meeting time, taking into consideration the complexity of the questions submitted.

VII. ASSESSING MEETING REQUESTS

The meeting request should be accompanied by the meeting package (see section X., Meeting Package Content and Submission, for additional information regarding the content of the meeting package). This ensures that the FDA will have adequate information to assess the potential utility of the meeting and prepare for the meeting. If the meeting package is not submitted to the appropriate division with the meeting request, the meeting request will be considered incomplete and the FDA generally will deny the meeting. The CBER or CDER division director or designee who receives a meeting request will determine whether to hold the meeting and will respond to the sponsor or applicant by granting or denying the meeting within 14 calendar days of receipt of the request and meeting package for a BPD Type 1 meeting, and within 21 calendar days of receipt of the request and meeting package for a Biosimilar Initial Advisory meeting or a BPD Type 2, 3, or 4 meeting.

A. Meeting Denied

If a meeting request is denied, notification to the sponsor or applicant will include an explanation of the reason for the denial. Denials will be based on a substantive reason, not merely on the absence of a minor element of the meeting request or a minor element of the meeting package. For example, as noted in section IV., Participation in the FDA’s Biosimilar Biological Product Development Program, the FDA will deny a BPD Type 1, 2, 3, or 4 meeting if the sponsor or applicant is in arrears with respect to an annual BPD fee for that product.¹⁶ Additionally, a meeting can be denied because it is premature for the product development stage or is clearly unnecessary. However, if a sponsor or applicant is not in arrears with respect to an annual BPD fee for a product, requests for BPD Type 1, 2, 3, and 4 meetings for that product will be honored except in the most unusual circumstances.

Following denial of a meeting, a subsequent request to schedule the meeting will be considered as a new request (i.e., a request that merits a new set of time frames as described in section V., Meeting Procedures).

B. Meeting Granted

If a meeting request is granted, CBER or CDER will notify the sponsor or applicant in writing of the decision and schedule the meeting by determining the meeting type, date, time, length, place, format (i.e., a scheduled face-to-face meeting, teleconference, or videoconference), and expected FDA participants. All of the scheduling information will be forwarded to the sponsor or applicant as soon as possible following the granting notification, and within the specified BsUFA timelines.

The Center (i.e., CBER or CDER) may determine that a different meeting type is more appropriate and it may grant a meeting of a different type than requested (e.g., if a sponsor or applicant requests a Biosimilar Initial Advisory meeting for a product, but the Center determines that a BPD Type 3 meeting is more appropriate, the FDA may grant a BPD Type 3 meeting instead of a Biosimilar Initial Advisory meeting).

As described in section IV., Participation in the FDA’s Biosimilar Biological Product Development Program, if the FDA grants a request for a BPD Type 1, 2, 3, or 4 meeting for a product, the sponsor or applicant may be required to pay an initial BPD fee or a reactivation fee for the product within 5 calendar days.¹⁷

VIII. RESCHEDULING MEETINGS

Occasionally, circumstances arise that necessitate the rescheduling of a meeting either by the FDA or the sponsor or applicant. If a meeting needs to be rescheduled, it should be rescheduled as soon as possible after the original date. A new meeting request should not be submitted and new time frames should not be set for rescheduled meetings. Sponsors or applicants and the FDA should take reasonable steps together to avoid rescheduling meetings. For example, if an attendee becomes unavailable, a substitute can be identified, or comments on the topic that the attendee would have addressed can be forwarded to the sponsor or applicant following the meeting. It will be at the discretion of the appropriate division whether the meeting should be rescheduled depending on the specific circumstances.

The following situations are examples of when a meeting can be rescheduled. This list includes representative examples and is not intended to be an exhaustive list.

• The review team determines that additional information is needed from the sponsor or applicant for the FDA to address the sponsor’s or applicant’s questions or other important issues for discussion, and it is possible to identify the additional information needed and arrange for its submission in a timely manner.

• Essential attendees are no longer available for the scheduled date and time because of an unexpected or unavoidable conflict or an emergency situation.

• After the meeting package is submitted but before preliminary responses are sent by the FDA, the sponsor or applicant sends CBER or CDER additional questions or data that are intended for discussion at the meeting and require additional review time.

• It is determined that attendance by additional FDA personnel not originally anticipated or requested are critical and their availability precludes holding the meeting on the original date.

IX. CANCELLING MEETINGS

When the FDA grants a request for a BPD Type 1, 2, 3, or 4 meeting for a product, the sponsor or applicant may be required to pay an initial BPD fee or a reactivation fee for the product within 5 calendar days.¹⁸ If the sponsor or applicant fails to pay the fee within the required time frame, the meeting will be cancelled.¹⁹ If the sponsor or applicant pays the initial BPD fee or reactivation fee after the meeting has been cancelled because of nonpayment, the time frame described in section V., Meeting Procedures, for the new meeting will be calculated from the date on which the FDA received the payment, rather than the date on which the sponsor or applicant originally submitted the meeting request.

Occasionally, other circumstances arise that necessitate the cancelling of a meeting. If a meeting is cancelled for reasons other than nonpayment of a required initial BPD fee or reactivation fee, the FDA will consider a subsequent request to schedule a meeting to be a new request (i.e., a request that merits a new set of time frames as described in sections V., Meeting Procedures, and VII., Assessing Meeting Requests). Both sponsors or applicants and the FDA should take reasonable steps to avoid cancelling meetings (unless the meeting is no longer necessary). Cancellation will be at the discretion of the appropriate division, and will depend on the specific circumstances.

The following situations are examples of when a meeting can be cancelled. This list includes representative examples and is not intended to be an exhaustive list.

• If the FDA grants the sponsor’s or applicant’s meeting request, but the sponsor or applicant subsequently fails to pay a required initial BPD fee, annual BPD fee, or reactivation fee within the time frame required under section 744H(a)(1)(A), (B), or (D) of the FD&C Act, as applicable.

• The sponsor or applicant determines that the written premeeting responses to its questions are sufficient for its needs and additional discussion is not necessary (see section XII., Procedures for the Conduct of Meetings). In this case, the sponsor or applicant should contact the CBER or CDER regulatory project manager to request cancellation of the meeting. The division will consider whether it agrees that the meeting should be cancelled. Some meetings can be valuable because of the discussion they generate and the opportunity for the division to ask about relevant matters, even if the premeeting communications seem sufficient to answer the sponsor’s or applicant’s questions. If the division agrees with the sponsor or applicant that the meeting can be cancelled, the division will document the reason for cancellation and the premeeting communication will represent the final responses and the official record of the meeting.

• The FDA determines that the meeting package is grossly inadequate. Meetings are scheduled on the condition that appropriate information to support the discussion has been submitted. Adequate planning by the sponsor or applicant should avoid this problem.

X. MEETING PACKAGE CONTENT AND SUBMISSION

Premeeting preparation is critical for achieving a productive discussion or exchange of information. Preparing the meeting package should help the sponsor or applicant focus on describing its principal areas of interest. The meeting package should provide information relevant to the discussion topics and enable the FDA to prepare adequately for the meeting.

A. Timing of Submission

As discussed in section VII., Assessing Meeting Requests, if the meeting package is not submitted with the meeting request to the appropriate division, the meeting request will be considered incomplete and the FDA generally will deny the meeting.

B. Where and How Many Copies of Meeting Packages to Send

An archival copy of the meeting package should be submitted to the relevant application (e.g., pre-IND, IND, or BLA); if there is no established application, the sponsor or applicant should contact the division for additional instructions. The FDA strongly encourages sponsors or applicants to submit the archival meeting package electronically according to the electronic submission formatting recommendations (see the draft guidance for industry Providing Regulatory Submissions in Electronic Format — General Considerations ).²⁰

The number of copies of a meeting package will vary based on the meeting. The responsible point of contact in the division will advise on the number of copies needed for the meeting attendees. To facilitate the meeting process, the FDA strongly suggests that copies of meeting packages provided in electronic format also be provided in paper.

C. Meeting Package Content

The meeting package should provide information relevant to the product, development stage, and meeting type requested (see section III., Meeting Types), in addition to any supplementary information needed to develop responses to issues raised by the sponsor or applicant or division. The meeting package should contain sufficient detail to meet the intended meeting objectives. For example, inclusion of raw data in addition to the derived conclusions may be appropriate in some situations. Similarly, merely describing a result as significant does not provide the division with enough information to give good advice or identify important problems the sponsor or applicant may have missed. FDA guidances identify and address many issues related to biosimilar biological product development and should be considered in planning, developing, and providing information needed to support a meeting with the FDA.²¹ If a product development plan deviates from current guidances, or from current practices, the deviation should be recognized and explained. Known or expected difficult design and evidence issues should be raised for discussion (e.g., selection of study populations, doses, or endpoints different from those studied for the reference product’s licensure; extrapolation of indications).

To facilitate FDA review, the meeting package content should be organized according to the proposed agenda. The meeting package should be a sequentially paginated document (individual sections can be numbered separately, as long as there is an overall pagination covering the whole submission) with a table of contents, appropriate indices, appendices, cross references, and tabs differentiating sections. Meeting packages generally should include the following information:

1. The product name and application number (if applicable).

2. The proposed proper name (or proper name if post-licensure).

3. The structure (if applicable).

4. The reference product name.

5. The proposed indication(s) or context of product development.

6. The dosage form, route of administration, dosing regimen (frequency and duration), and presentation(s).

7. A list of all individuals, with their titles and affiliations, who will attend the requested meeting from the sponsor or applicant organization, including consultants and interpreters.

8. A background section that includes the following:

1. A brief history of the development program.

2. The status of product development (e.g., chemistry, manufacturing, and controls; nonclinical; and clinical, including any development outside the United States, as applicable).

9. A brief statement summarizing the purpose of the meeting.

10. A proposed agenda.

11. A list of questions for discussion grouped by discipline and with a brief summary for each question to explain the need or context for the question.

12. Data to support discussion organized by discipline and question. The level of detail of the data should be appropriate to the meeting type requested and the product development stage.

XI. PREMEETINGS AND COMMUNICATIONS WITH SPONSORS OR APPLICANTS

CBER and CDER hold internal meetings, including meeting with the Biosimilar Review Committee (BRC),²² to discuss meeting packages and to gain internal alignment on the preliminary responses to a sponsor’s or applicant’s questions. Our goal is to communicate these preliminary responses to the sponsor or applicant no later than 2 days before the scheduled meeting date. Communications before the meeting between sponsors or applicants and the FDA, including preliminary responses, can serve as a foundation for discussion or as the final meeting responses. Nevertheless, preliminary responses should not be construed as final unless there is agreement between the sponsor or applicant and the FDA that additional discussion is not necessary for any question (i.e., when the meeting is canceled because the sponsor or applicant is satisfied with the FDA’s preliminary responses), or a particular question is considered resolved allowing extra time for discussion of the more complex questions during the meeting. Preliminary responses communicated by the FDA are not intended to generate the submission of a new meeting agenda or new questions. If, however, a sponsor or applicant provides new data or a revised or new proposal, the FDA may not be able to provide comments on the new data or it may necessitate the submission of a new meeting request by the sponsor or applicant.

XII. PROCEDURES FOR THE CONDUCT OF MEETINGS

Meetings will be chaired by an FDA staff member and will begin with introductions and a statement of the agenda. Presentations by sponsors or applicants generally are not needed because the information necessary for review and discussion should be part of the meeting package. If a sponsor or applicant plans to make a presentation, the presentation should be discussed ahead of time with the CBER or CDER point of contact to determine if a presentation is warranted and ensure that CBER or CDER has the presentation materials ahead of the meeting if possible. All presentations should be kept brief to maximize the time available for discussion.

The length of the meeting will not be increased to accommodate a presentation. If a presentation contains more than a small amount of content distinct from clarifications or explanations of previous data and that were not included in the original meeting package submitted to CBER or CDER for review, FDA staff may not be able to provide comments on the new data.

Before the end of the meeting, FDA attendees and the sponsor or applicant attendees should summarize the important discussion points, agreements, clarifications, and action items. Generally, the sponsor or applicant will be asked to present the summary to ensure that there is mutual understanding of meeting outcomes and action items. FDA staff can add or further clarify any important points not covered in the summary and these items can be added to the meeting minutes. The summary can be done at the end of the meeting or after the discussion of each question.

XIII. DOCUMENTATION OF MEETINGS

Documentation of meeting outcomes, agreements and disagreements, issues for further discussion, and action items is critical to ensuring that this information is preserved for meeting attendees and future reference. FDA minutes are the official record of the meeting. The FDA intends to issue the official, finalized minutes to the sponsor or applicant within 30 days of the meeting.

XIV. RESOLUTION OF DISPUTE ABOUT MEETING MINUTES

This section refers to disputes regarding the accuracy and sufficiency of the minutes. A sponsor or applicant who objects to the accuracy of the minutes or who needs additional clarification of the meeting minutes issued by the FDA should contact the assigned FDA point of contact. This process addresses issues with the meeting minutes only. If a sponsor or applicant needs to discuss additional issues that were not addressed at the meeting, it should submit a correspondence or a new meeting request.

If, after following up as described above, there are still significant differences in the sponsor’s or applicant’s and the FDA’s understanding of the content of the official meeting minutes, the sponsor or applicant should notify the FDA in writing with respect to specific disagreements. The sponsor or applicant should submit the correspondence to its application or, if there is no application, forward a letter to the office director/division director of the responsible division, with a copy to the point of contact describing the concerns.

The sponsor’s or applicant’s concerns will be taken under consideration by the division and the office director if the office director was present at the meeting. If the minutes are deemed to accurately and sufficiently reflect the meeting discussion, the point of contact will convey this decision to the sponsor or applicant and the minutes will stand as the official documentation of the meeting. If after discussions with the sponsor or applicant the FDA deems it necessary to effect a change to the official minutes, the changes will be documented in an addendum to the official minutes. The addendum will also document any continued sponsor or applicant objections.

XV. PAPERWORK REDUCTION ACT OF 1995

This guidance contains information collection provisions that are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520).

The time required to complete the information collection for a meeting request and information package is estimated to average 15 hours and 30 hours per response, respectively, including the time to review instructions, search existing data sources, and gather the data needed, and complete and review the information collection. Send comments regarding this burden estimate or suggestions for reducing this burden to:

Food and Drug Administration, Center for Drug Evaluation and Research, Office of New Drugs, Attention: Document Control Room, 5901-B Ammendale Road, Beltsville, MD 20705.

An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB control number. The OMB control number for this information collection is XXXXX (expires XXXXX).

1 This guidance has been prepared by the Center for Drug Evaluation and Research (CDER) in cooperation with the Center for Biologics Evaluation and Research (CBER) at the Food and Drug Administration.

2 For the statutory definition of biosimilar and biological product and definitions of selected terms used in this guidance, see the terminology section of the draft guidance for industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. (When final, this guidance will represent the FDA’s current thinking on this topic. For the most recent version of a guidance, check the FDA Drugs guidance Web page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.) For the statutory definition of biosimilar biological product application, see section 744G(4) of the FD&C Act.

3 Sections 401-408 of FDASIA, adding sections 744G, 744H, and 744I to the FD&C Act.

4 The BsUFA goals letter, which is titled “Biosimilar Biological Product Authorization Performance Goals and Procedures Fiscal Years 2013 Through 2017,” is available on the FDA’s Web site at http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/TherapeuticBiologicApplications/Biosimilars/UCM281991.pdf.

5 For information on meetings for new drug applications and 351(a) BLAs, see the guidance for industry Formal Meetings Between the FDA and Sponsors or Applicants. We update guidances periodically. To make sure you have the most recent version of a guidance, check the FDA Drugs guidance Web page at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.

6 The meeting types and goal dates for BPD meetings were developed by the FDA in consultation with public and industry stakeholders as directed by the Biologics Price Competition and Innovation Act of 2009 (BPCI Act). For more information about BsUFA and the fee criteria for BPD meetings, refer to the BsUFA Web page at http://www.fda.gov/ForIndustry/UserFees/BiosimilarUserFeeActBsUFA/default.htm.

7 When final, this guidance will represent the FDA’s current thinking on this topic.

8 See section 744H(a)(1)(E) of the FD&C Act.

9 See section 744H(a)(1)(A) of the FD&C Act.

10 See section 744H(a)(1)(B) of the FD&C Act.

11 See section 744H(a)(1)(D) of the FD&C Act.

12 Id.

13 See section 744H(a)(1)(E) of the FD&C Act.

14 Id.

15 See http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/default.htm#Addresses.

16 See section 744H(a)(1)(E) of the FD&C Act.

17 See section 744H(a)(1)(A) and (D) of the FD&C Act.

18 See section 744H(a)(1)(A) and (D) of the FD&C Act.

19 See section 744H(a)(1(E) of the FD&C Act.

20 When final, this guidance will represent the FDA’s current thinking on this topic.

21 See the draft guidances for industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product, Quality Considerations in Demonstrating Biosimilarity to a Reference Protein Product, and Biosimilars: Questions and Answers Regarding Implementation of the Biologics Price Competition and Innovation Act of 2009. When final, these guidances will represent the FDA’s current thinking on these topics.

22 For more information about the BRC, refer to the Web page on implementation of the BPCI Act at http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/ucm215089.htm.

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