FDA 发布 MAPP 5241.3 Rev. 1，修订仿制药 ANDA 良好评估实践
MAPP 5241.3 Rev. 1 Good Abbreviated New Drug Application Assessment Practices
FDA 药品审评与研究中心发布 MAPP 5241.3 Rev. 1，修订仿制药 ANDA 良好评估实践，修订版自 2023 年 10 月 6 日起生效。文件为配合 GDUFA III，重新明确一级评估人、二级评估人、分支主管和分部主任的职责，规定主管在无特殊情况下不评估 ANDA，分支主管通常不进行三级评估。
文件反映 GDUFA III 后 FDA 对仿制药 ANDA 评估职责与流程的调整，可供对比审评分工变化。
PDF 文字版；图形和原始排版请参阅官方 PDF。
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5241.3 Rev. 1
POLICY AND PROCEDURES
OFFICE OF GENERIC DRUGS
Good Abbreviated New Drug Application Assessment Practices
Table of Contents
PURPOSE ..............................................................................1
BACKGROUND .....................................................................1
POLICY .................................................................................4
RESPONSIBILITIES ...........................................................4
PROCEDURES .....................................................................5
REFERENCES ......................................................................8
DEFINITIONS ......................................................................8
EFFECTIVE DATE ..............................................................9
CHANGE CONTROL TABLE............................................9
PURPOSE
This Manual of Policies and Procedures (MAPP) revises the good abbreviated new drug
application (ANDA) assessment practices for the Office of Generic Drugs (OGD) and the
Office of Pharmaceutical Quality (OPQ) to increase their operational efficiency and
effectiveness, with a goal of decreasing the number of review cycles needed to approve
ANDAs that meet the requirements for approval.
BACKGROUND
Under the Generic Drug User Fee Amendments of 2012 (GDUFA I), 1 the Food and Drug
Administration (FDA) implemented a restructuring of the ANDA assessment program.
As part of this restructuring, FDA adopted performance goals for the review of ANDAs;
overhauled the generic drug program’s business processes; developed and implemented
an integrated ANDA review information platform; reorganized OGD; established OPQ
to, among other things, integrate the ANDA quality assessment; and hired and trained
over 1,000 employees. As a direct result of this restructuring, FDA’s efficiency, and
output from ANDA review improved, including issuance of complete response letters as
well as increased ANDA approvals.
1 Food and Drug Administration Safety and Innovation Act (Public Law 112-144).
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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MANUAL OF POLICIES AND PROCEDURES
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The generic drug user fee program was reauthorized through the Generic Drug User Fee
Amendments of 2017 (GDUFA II) 2 on August 18, 2017. As outlined in the GDUFA
Reauthorization Performance Goals and Program Enhancements Fiscal Years 2018-2022
(GDUFA II Commitment Letter), 3 the GDUFA II ANDA review program instituted
substantial program enhancements at every major stage of the ANDA development and
review timeline, including: product development, pre-submission, filing, mid-review, late
review, post-complete response letter, and approval/tentative approval, with the goal of
reducing the number of assessment cycles necessary for approval.
Most recently, the generic drug user fee program was reauthorized as part of the
Continuing Appropriations and Ukraine Supplemental Appropriations Act, 2023. 4 As
described in the GDUFA Reauthorization Performance Goals and Program
Enhancements Fiscal Years 2023-2027 (GDUFA III commitment letter) applicable to this
latest reauthorization, 5 FDA has agreed to performance goals and program enhancements
regarding aspects of the generic drug assessment program that build on previous
authorizations of GDUFA. New enhancements to the program are designed to maximize
the efficiency and utility of each assessment cycle, with the intent of continuing to reduce
the number of assessment cycles for ANDAs and facilitating timely access to generic
medicines.
ANDAs typically undergo primary and secondary assessment by the OGD and OPQ
technical disciplines (i.e., bioequivalence, labeling, and quality) to determine whether
they meet the requirements for regulatory approval. OGD and OPQ’s consistent and
targeted focus should continue to be on evaluating and analyzing submitted data and
information to determine whether the application meets the requirements for approval
and documenting that determination. To reinforce the policy and procedural changes set
forth in this MAPP, OGD and OPQ will continue to use the term assessment in place of
review. See Definitions below.
Although nothing in the previous version of this MAPP altered the regulatory
requirements for ANDA approval, it made three significant changes to FDA’s ANDA
assessment practices.
Those changes were to:
• Establish that assessment teams should, when available, use templates and
assessment tools provided by the disciplines that focus the primary assessment of
2 Food and Drug Administration Reauthorization Act of 2017 (Public Law 115-52).
3 This agreement is available at
https://www.fda.gov/downloads/ForIndustry/UserFees/GenericDrugUserFees/UCM525234.pdf.
4 See Division F, Title III of the Continuing Appropriations and Ukraine Supplemental Appropriations Act,
2023 (Public Law 117-180).
5 The GDUFA III commitment letter is available at https://www.fda.gov/media/153631/download.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5241.3 Rev. 1
bioequivalence, quality, 6 or labeling data or information on the critical attributes
of the application. These critical attributes templates and assessment tools help
guide assessors to convey:
o Their determination of whether the application meets the requirements for
approval
o Their message to applicants, when applicable, explaining the deficiency,
why a major or minor amendment is necessary to respond to that
deficiency (e.g., by referencing guidance documents), and what missing or
additional information is needed to support an approval decision
• Clarify the roles and responsibilities of primary assessors, secondary assessors,
and division directors (who, under this MAPP, no longer perform the role of a
typical tertiary assessor). This clarification is intended to reduce duplicative and
unnecessary work to increase FDA’s efficiency and effectiveness.
• Establish that OGD and OPQ will clearly communicate to applicants what
deficiencies must be corrected for their ANDAs to be approved. This
communication is intended to enable applicants to develop high-quality re-
submissions and to reduce the number of subsequent cycles for approval.
Collectively, these changes were intended to expand access to generic medicines and
enable OGD and OPQ experts to focus more of their attention on novel or challenging
scientific and policy issues associated with the development and assessment of generic
drug products.
FDA published the previous version of this MAPP concurrently with the guidance for
industry Good Abbreviated New Drug Application Submission Practices. 7 This guidance
highlights common, recurring deficiencies that may delay approval of an ANDA and
makes recommendations to applicants on how to avoid these deficiencies. The guidance
and this MAPP build upon the success of the generic drug user fee program to help
reduce the number of assessment cycles for an ANDA to attain approval.
This MAPP was developed by OGD and OPQ in close collaboration with both offices’
senior technical discipline leadership and staff.
6 FDA takes a risk-and science-based approach to product quality assessment by: 1) encouraging
implementation of risk-based approaches that focus Agency attention on critical areas and 2) ensuring that
assessment policies are based on advanced pharmaceutical science.
7 For the most recent version of a guidance, check the FDA Drugs guidance web page at
https://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/default.htm.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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POLICY
• The ANDA assessment determines whether an ANDA meets the requirements for
approval. Requirements for approval 8 are primarily specified in relevant statutory
provisions and regulations, while guidance documents may provide clarity on the
existing requirements or recommendations on how to meet these requirements.
• Critical attributes templates and assessment tools developed by the technical
disciplines structure the primary assessment, eliminate unnecessary
documentation, and focus the assessment on whether the application meets the
regulatory requirements for approval. Use of these templates and assessment
tools helps to increase the efficiency and consistency of the primary assessment
within a discipline and improves the ease of the secondary assessment.
• Primary assessors, secondary assessors, branch chiefs (OPQ) and division
directors (supervisors) have distinct and complementary roles and responsibilities.
• OGD and OPQ will clearly explain to applicants the deficiencies that must be
addressed to obtain ANDA approval.
RESPONSIBILITIES
• Primary assessors assess the ANDA, draft communications to the ANDA
applicant, recommend whether the ANDA meets the regulatory requirements for
approval and document the assessment.
• Secondary assessors validate primary assessments and communications as being
consistent with current policies and procedures.
• Absent unique circumstances, supervisors do not assess ANDAs. Instead,
supervisors focus on managing practices and assessment consistency within the
branch or division and are available for consultation by assessors.
8 Note that filing reviews for ANDAs are covered by CDER MAPP 5200.14, Filing Review of Abbreviated
New Drug Applications, available at https://www.fda.gov/about-fda/center-drug-evaluation-and-research-
cder/cder-manual-policies-procedures-mapp.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5241.3 Rev. 1
PROCEDURES
1. Original ANDAs
A. Primary Assessors
• Focus on information that is necessary to ensure that the ANDA meets the
regulatory requirements for approval for their specific discipline.
Information that is not needed to make a regulatory decision in assessing
the ANDA is not relevant.
• Use the technical discipline’s critical attributes templates and assessment
tools, when available, to assess whether the ANDA meets the regulatory
requirements for approval. These templates and assessment tools may
constitute the primary assessment documentation or may be incorporated
within an assessment document.
• Reference in the assessment the location of the information under
assessment (e.g., URL, section, and page number), evaluate the
information, and document their assessment and conclusion. When
necessary, may use summary tables and bullet points to convey relevant
information or findings.
• Assess the submission and related documentation proportionate to (1) the
novelty, complexity, and level of potential risk to quality posed by product
attributes or process characteristics and (2) whether the decision could
establish a precedent or new policy.
If primary assessors have questions about the appropriate extent of their
assessment and documentation, they should consult the secondary assessor
or the supervisor.
• Refrain from copying and pasting ANDA content into the assessment
template or document unless it is essential or more efficient to do so.
Rather, as appropriate, primary assessors should briefly summarize the
information or reference the information location.
• Make an initial determination as to whether any potential consults will be
necessary and whether there are complex issues that require prioritization
or the involvement of multiple disciplines.
• When deficiencies, information gaps or discrepancies are identified during
the assessment cycle, draft information requests or deficiencies to be
conveyed to the applicant in a mid-cycle letter.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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• Will not attempt to rewrite, reorganize, or reassemble the ANDA as it is
the ANDA applicant’s responsibility to submit a high-quality and
complete ANDA in the appropriate submission format as described in
FDA’s guidance for industry Good ANDA Submission Practices. 9
• Recommend approval if the ANDA meets the regulatory requirements for
approval upon completion of the assessment (of the original ANDA
submission and amendments containing responses to any information
requests/deficiency letters).
• If the ANDA application (including any amendments containing responses
to information requests and deficiency letters) does not meet the
regulatory requirements for approval, draft the outstanding deficiencies
that must be corrected for the ANDA to be approvable. 10
• If the communication is a discipline review letter, follow discipline
procedures regarding next steps for issuing the letter. If the
communication is a complete response letter, notify the secondary
assessor.
B. Secondary Assessors
• Provide scientific and regulatory oversight of primary assessments,
specifically to ensure the quality of the technical assessment, the quality of
the communication to the applicant, and consistency with similar
assessments and current policies and procedures.
The extent of the secondary assessment should be calibrated as appropriate
considering the experience, knowledge, expertise, and quality of the work
product of the primary assessor; the novelty, complexity, and level of
potential risk to product quality or product performance; and whether the
decision would establish a precedent and/or change in policy. For
example, when the primary assessor is a new employee, the secondary
assessment may warrant more oversight or time for discussion about key
issues.
• Will not redo the primary assessment. If the secondary assessor identifies
shortcomings in the primary assessment, the primary assessor should
receive coaching or additional training, as appropriate.
9 See also FDA guidance for industry “Providing Regulatory Submissions in Electronic Format — Certain
Human Pharmaceutical Product Applications and Related Submissions Using the eCTD Specifications”
(February 2020, Rev. 7).
10 For quality-related deficiencies, see MAPP 5016.8, Communication Guidelines for Quality-Related
Information Requests and Deficiencies.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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• Confirm, as appropriate per discipline procedures, that the communication
to the applicant references the application and explains what deficiencies
must be corrected for the ANDA to be approvable. Ensure, as appropriate
per discipline procedures, that primary assessors:
o Included in discipline review letters and complete response letters a
reference to a specific location within the ANDA to provide a point of
reference for the deficiency
o Identified any omitted information or explained the problem with
information submitted
o Explained the actions necessary to resolve the deficiency (including
alternative approaches, if applicable)
o Explained why the requested information or revision is needed (i.e.,
the communication should clearly reference the ANDA and explain
what deficiencies must be corrected for the ANDA to be approvable
and why a major or minor amendment is necessary to respond to each
deficiency (e.g., by referencing regulations, compendia, MAPPs, and
guidance documents))
• After determining concurrence with the primary assessment, moves the
ANDA to the next step culminating in a regulatory action.
C. Branch Chiefs
• Ensure that the ANDA assessments within the branch are consistent and
adhere to practices and policies outlined in applicable regulations,
guidances, MAPPs, SOPs, and training documents.
• Do not perform tertiary assessments unless there are unique
circumstances. Do not redo primary or secondary assessments.
• Serve as a resource for assessors for consultation on novel, complex, or
high-risk products and policy- and precedent-setting decisions. 11 If the
branch chief identifies an emerging policy issue, they should notify the
division director and management, as necessary.
D. Division Director
11 In some cases, such as for unusually complex products or for precedent-setting decisions, the senior
scientific advisor (or equivalent) may be consulted instead of, or in addition to, the division director.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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• Ensures that the assessments within the division are completed in
accordance with practices and policies outlined in applicable regulations,
guidances, MAPPs, SOPs, and training documents.
• Serves as a resource for assessors for consultation on novel, complex, or
high-risk products and policy- and precedent-setting decisions. When
emerging policy or precedent-setting issues are identified, the division
director notifies relevant personnel (e.g., Immediate Office, the Office of
Generic Drug Policy, the Office of Policy for Pharmaceutical Quality), as
appropriate, and works collaboratively to resolve the issues.
2. Amendments
• Primary and secondary assessors focus their assessment on issues within the
narrow scope of the amendment.
They should not revisit resolved issues from the original ANDA submission
(except to the extent issues within an amendment are correlated to, and could
impact, resolved issues). In the assessment of an amendment, primary and
secondary assessors also should not address new issues outside the scope of or
unrelated to the issue raised in the prior communication for which the
amendment was submitted. This includes situations where the assessor was
reassigned the amendment for workload management reasons and did not
conduct the original assessment.
• If the amendment contains information not requested in or related to a
discipline review letter or complete response letter, FDA will act on the
unsolicited amendment by the later of the goal date for the original
submission/solicited amendment or the goal date assigned for the unsolicited
amendment.
REFERENCES
• CDER MAPP 4151.8 Rev.1 Equal Voice: Collaboration and Regulatory and
Policy Decision-Making in CDER (Effective Date: 04/12/22)
• FDA Guidance for Industry Good Abbreviated New Drug Application Submission
Practices (January 2022)
DEFINITIONS
• Assessment: The process of both evaluating and analyzing submitted data and
information to determine whether the application meets the requirements for
approval and documenting that determination.
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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• Primary assessment: The main technical and regulatory evaluation of submitted
data and information to determine whether the application meets the regulatory
requirements for approval.
• Secondary assessment: A higher level evaluation of the primary assessment to
ensure completeness and consistency with current policies and procedures.
• Critical attributes template: A discipline-specific template used to guide the
primary assessor’s evaluation of submitted data and information, identify the
regulatory requirements for approval, and capture the primary assessor’s
recommendation.
• Discipline review letter: A letter used to convey preliminary thoughts on
possible deficiencies identified by a discipline assessor and/or assessment team
for its portion of the pending application at the conclusion of the discipline
assessment.
• Complete response letter: A written communication to an applicant from FDA
usually describing all the specific deficiencies that the Agency has identified in an
ANDA (including pending amendments) that must be satisfactorily addressed
before the ANDA can be approved.
EFFECTIVE DATE
• This MAPP is effective upon date of publication.
CHANGE CONTROL TABLE
Effective Revision Revisions
Date Number
1/3/18 Initial N/A
10/6/2023 1 Updates to account for changes made by GDUFA III
Originating Office: Office of Generic Drugs and Office of Pharmaceutical Quality
Effective Date: 1/3/2018; 10/6/2023
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来源：FDA Pharmaceutical Quality Documents · fda.gov