Formal Meetings Between the FDA and Biosimilar Biological
Transcript Of Formal Meetings Between the FDA and Biosimilar Biological
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)
November 2015 Procedural
OMB Control No. 0910-0802 Expiration Date 9/30/2018
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 240-402-8010; 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)
November 2015 Procedural
TABLE OF CONTENTS
I. II. III. IV.
V.
A. B. C. D. E.
VI. VII.
A. B.
VIII. IX. X.
A. B. C.
XI.
XII. XIII. XIV. XV.
INTRODUCTION............................................................................................................. 1 BACKGROUND ............................................................................................................... 2 MEETING TYPES ........................................................................................................... 3 PARTICIPATION IN THE FDA’S BIOSIMILAR BIOLOGICAL PRODUCT DEVELOPMENT PROGRAM ....................................................................................... 5 MEETING PROCEDURES............................................................................................. 6
Biosimilar Initial Advisory Meeting............................................................................................. 6 BPD Type 1 Meeting...................................................................................................................... 6 BPD Type 2 Meeting...................................................................................................................... 6 BPD Type 3 Meeting...................................................................................................................... 6 BPD Type 4 Meeting...................................................................................................................... 7
MEETING REQUESTS BY SPONSORS OR APPLICANTS..................................... 7 ASSESSING MEETING REQUESTS............................................................................ 9
Meeting Denied .............................................................................................................................. 9 Meeting Granted .......................................................................................................................... 10
RESCHEDULING MEETINGS ................................................................................... 10 CANCELLING MEETINGS......................................................................................... 11 MEETING PACKAGE CONTENT AND SUBMISSION.......................................... 12
Timing of Submission .................................................................................................................. 12 Where and How Many Copies of Meeting Packages to Send .................................................. 12 Meeting Package Content............................................................................................................ 13
PREMEETINGS AND COMMUNICATIONS WITH SPONSORS OR APPLICANTS ................................................................................................................. 14 PROCEDURES FOR THE CONDUCT OF MEETINGS.......................................... 15 DOCUMENTATION OF MEETINGS......................................................................... 15 RESOLUTION OF DISPUTE ABOUT MEETING MINUTES................................ 15 PAPERWORK REDUCTION ACT OF 1995.............................................................. 16
Contains Nonbinding Recommendations
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
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 Glossary of the guidance for industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. (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.) 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/Approv alApplications/TherapeuticBiologicApplications/Biosimilars/UCM281991.pdf.
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Contains Nonbinding Recommendations
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 products. 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.
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.
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Contains Nonbinding Recommendations
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 Biosimilar Biological Product Development (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
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.
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Contains Nonbinding Recommendations
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.
7 When final, this guidance will represent the FDA’s current thinking on this topic.
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Contains Nonbinding Recommendations
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
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.
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Contains Nonbinding Recommendations
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.
13 See section 744H(a)(1)(E) of the FD&C Act. 14 Id.
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Contains Nonbinding Recommendations
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).
15 See http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/de fault.htm#Addresses.
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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)
November 2015 Procedural
OMB Control No. 0910-0802 Expiration Date 9/30/2018
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 240-402-8010; 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)
November 2015 Procedural
TABLE OF CONTENTS
I. II. III. IV.
V.
A. B. C. D. E.
VI. VII.
A. B.
VIII. IX. X.
A. B. C.
XI.
XII. XIII. XIV. XV.
INTRODUCTION............................................................................................................. 1 BACKGROUND ............................................................................................................... 2 MEETING TYPES ........................................................................................................... 3 PARTICIPATION IN THE FDA’S BIOSIMILAR BIOLOGICAL PRODUCT DEVELOPMENT PROGRAM ....................................................................................... 5 MEETING PROCEDURES............................................................................................. 6
Biosimilar Initial Advisory Meeting............................................................................................. 6 BPD Type 1 Meeting...................................................................................................................... 6 BPD Type 2 Meeting...................................................................................................................... 6 BPD Type 3 Meeting...................................................................................................................... 6 BPD Type 4 Meeting...................................................................................................................... 7
MEETING REQUESTS BY SPONSORS OR APPLICANTS..................................... 7 ASSESSING MEETING REQUESTS............................................................................ 9
Meeting Denied .............................................................................................................................. 9 Meeting Granted .......................................................................................................................... 10
RESCHEDULING MEETINGS ................................................................................... 10 CANCELLING MEETINGS......................................................................................... 11 MEETING PACKAGE CONTENT AND SUBMISSION.......................................... 12
Timing of Submission .................................................................................................................. 12 Where and How Many Copies of Meeting Packages to Send .................................................. 12 Meeting Package Content............................................................................................................ 13
PREMEETINGS AND COMMUNICATIONS WITH SPONSORS OR APPLICANTS ................................................................................................................. 14 PROCEDURES FOR THE CONDUCT OF MEETINGS.......................................... 15 DOCUMENTATION OF MEETINGS......................................................................... 15 RESOLUTION OF DISPUTE ABOUT MEETING MINUTES................................ 15 PAPERWORK REDUCTION ACT OF 1995.............................................................. 16
Contains Nonbinding Recommendations
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
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 Glossary of the guidance for industry Scientific Considerations in Demonstrating Biosimilarity to a Reference Product. (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.) 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/Approv alApplications/TherapeuticBiologicApplications/Biosimilars/UCM281991.pdf.
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Contains Nonbinding Recommendations
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 products. 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.
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.
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Contains Nonbinding Recommendations
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 Biosimilar Biological Product Development (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
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.
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Contains Nonbinding Recommendations
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.
7 When final, this guidance will represent the FDA’s current thinking on this topic.
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Contains Nonbinding Recommendations
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
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.
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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.
13 See section 744H(a)(1)(E) of the FD&C Act. 14 Id.
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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).
15 See http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/de fault.htm#Addresses.
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