FDA 发布 MAPP 5016.3 Rev. 1，规定含多肽或蛋白原料药产品质量评估的职责分工
MAPP 5016.3 Rev. 1 Responsibility for the Quality Assessment of Products Containing Peptide or Protein Drug Substances
FDA 药品质量办公室发布 MAPP 5016.3 Rev. 1，规定含多肽或蛋白原料药产品的质量评估职责在 OPQ 各下属办公室之间的分工。文件按原料药分子的氨基酸数目划分，≤40 个氨基酸的产品由 OPQA I 和 II 负责，≥41 个的由 OPQA III 负责，修订版 1 生效日期为 2023 年 6 月 21 日。
文件以氨基酸数目划分 FDA 药品质量办公室内部对多肽或蛋白原料药产品的质量评估职责，并列出各类申报的对应分工。
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 5016.3 Rev. 1
POLICY AND PROCEDURES
OFFICE OF PHARMACEUTICAL QUALITY
Responsibility for the Quality Assessment of Products Containing Peptide or
Protein Drug Substances
Table of Contents
PURPOSE ..............................................................................1
BACKGROUND ...................................................................2
POLICY .................................................................................3
PROCEDURES .....................................................................4
REFERENCES......................................................................4
EFFECTIVE DATE ..............................................................4
CHANGE CONTROL TABLE............................................5
ATTACHMENT ..................................................................6
PURPOSE
• This MAPP describes how the responsibility for the quality assessments 1 of
products containing peptide or protein drug substances will be divided among
the suboffices of the Office of Pharmaceutical Quality (OPQ). 2
• This MAPP serves as a guide for the Office of New Drugs and the OPQ
Office of Program and Regulatory Operations (OPRO) to direct submissions
and manage other interactions regarding the quality assessments among the
Office of Product Quality Assessment (OPQA) I, OPQA II, OPQA III, and
the Office of Pharmaceutical Manufacturing Assessment (OPMA).
• The policy and procedures described in this MAPP apply to the quality
assessments performed by OPQ for all original investigational new drug
applications (INDs), IND amendments, original new drug applications
(NDAs), original biologics license applications (BLAs), NDA and BLA
amendments, supplements to approved NDAs and BLAs, and emergency use
1
Original new drug applications (NDAs) and biologics license applications (BLAs) are assessed by an
integrated quality assessment team. Investigational new drug applications (INDs) and supplements to
applications are assessed by an application assessment team, which may not involve team members who
typically would be assigned to an integrated quality assessment team. For convenience, this MAPP uses
quality assessment throughout.
2
The assignment of responsibility for a quality assessment as described in this MAPP does not constitute
an Agency determination of whether a product is or is not a biological product or whether a product will be
regulated under the Public Health Service Act or the Federal Food, Drug, and Cosmetic Act.
Originating Office: Office of Pharmaceutical Quality
Effective Date: 12/11/2018; 6/21/2023 Page 1 of 6
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5016.3 Rev. 1
authorizations (EUAs) for products containing peptide and/or protein drug
substances.
• This MAPP does not apply to:
o Abbreviated new drug applications (ANDAs)
o Products containing an amino acid polymer that is used solely as an
excipient. 3
BACKGROUND
• Currently, OPQ suboffices including OPQA I, OPQA II, OPQA III, and
OPMA perform product quality assessments for products ranging in size and
complexity from small peptides to large glycoproteins. The manufacturing
processes used by sponsors and applicants for these products include, but are
not limited to, chemical synthesis, purification from a naturally occurring
biological source, and application of biotechnology.
• The Biologics Price Competition and Innovation Act of 2009 clarified the
statutory authority under which certain protein products will be regulated by
amending the definition of biological product in section 351(i) of the Public
Health Service Act (PHS Act) to include “a protein (except any chemically
synthesized polypeptide)” and describing procedures for submission of a
marketing application for certain biological products. 4 Section 605 of the
Further Consolidated Appropriations Act, 2020 (Public Law 116-94) 5
removed the parenthetical “(except any chemically synthesized polypeptide)”
from the category of protein in the definition of biological product in section
351(i)(1) of the PHS Act.
• FDA’s regulations in 21 CFR 600.3(h)(6) state that the term protein means
“any alpha amino acid polymer with a specific, defined sequence that is
greater than 40 amino acids in size. When two or more amino acid chains in
an amino acid polymer are associated with each other in a manner that occurs
in nature, the size of the amino acid polymer for purposes of this [definition]
will be based on the total number of amino acids in those chains, and will not
be limited to the number of amino acids in a contiguous sequence.”
3
The terms excipient and inactive ingredient often are used interchangeably. In this MAPP, excipient
means any inactive ingredient that is added intentionally to therapeutic and diagnostic products and is not
intended to exert therapeutic effects at the intended dosage, although it may act to improve product
delivery.
4
Sections 7001–7003 of the Patient Protection and Affordable Care Act (Public Law 111-148).
5
Public Law 116-94 is available for download here: https://www.govinfo.gov/link/plaw/116/public/94.
Originating Office: Office of Pharmaceutical Quality
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5016.3 Rev. 1
• FDA considers any amino acid polymer composed of 40 or fewer amino acids
to be a peptide and not a protein. 6
POLICY
• OPQ will divide the responsibilities for the quality assessments of products
containing peptide or protein drug substances among the suboffices (OPQA
I, OPQA II, OPQA III, and OPMA) based on whether the size of the drug
substance molecule is either ≤40 amino acids or ≥41 amino acids, regardless
of its method of manufacture (whether chemically synthesized, purified from
a naturally occurring biological source, or biotechnologically derived).
• Additional considerations for determining the responsibility for the quality
assessments of products containing peptide or protein drug substances are
described below:
o For a combination product 7 that contains both a protein drug substance as
a constituent part and a non-protein drug substance as a constituent part
and for which the responsibility for the quality assessment of the
constituent parts falls to different OPQ sub-offices, the quality
assessment will be a collaborative effort within OPQ.
o For a product in which the drug substance is composed of a mixture of
identified protein and/or peptide components, 8 the amino acid polymer
component with the greatest number of amino acids will be used to
determine where the responsibility in OPQ for the quality assessment.
o For a product in which a drug substance is composed of an amino acid
polymer, but the above scenarios do not apply, the responsibility in OPQ
for the quality assessment will be determined on a case-by-case basis.
o OPQ suboffices will collaborate with each other when multiple offices
have expertise that could contribute to the quality assessments of these
products including policy, review, and/or inspectional issues.
o OPQ suboffices will address and resolve, if possible, any disputes
concerning the responsibility for the quality assessments of these products.
If a resolution cannot be obtained, the matter will be brought to the OPQ
6
See the proposed rule, “Definition of the Term ‘Biological Product’” (“FDA proposes to consider any
polymer composed of 40 or fewer amino acids to be a peptide and not a protein.”) (83 FR 63817, December
12, 2018, codified at 21 CFR 600.3(h)(6)).
7
See the definition of combination product at 21 CFR 3.2(e).
8
For example, a product in which the drug substance is composed of a mixture of peptides and/or proteins
extracted from a plant part or an animal tissue.
Originating Office: Office of Pharmaceutical Quality
Effective Date: 12/11/2018; 6/21/2023 Page 3 of 6
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5016.3 Rev. 1
Deputy Director of Science.
PROCEDURES
• OPRO will use the criteria summarized in the table in the attachment and any
applicable additional considerations described above when requesting
assessor assignments, directing submissions, and managing other interactions
regarding the responsibilities for the quality assessments for INDs, NDAs,
BLAs, and supplements (including amendments) submitted for products
containing peptide or protein drug substances.
• OPQ suboffices will provide information to help OPRO decide which OPQ
suboffice is responsible for the quality assessment, when requested by
OPRO.
• OPQ will use established procedures and responsibilities for the
implementation of this MAPP.
REFERENCES
• Draft guidance for industry and review staff Good Review Management
Principles and Practices for New Drug Applications and Biologics License
Applications (September 2018) 9
• MAPP 4150.1 Role and Procedures of the CDER Ombudsman
• MAPP 4151.8 Rev. 1 Equal Voice: Collaboration and Regulatory
and Policy Decision-Making in CDER
• 21 CFR 600.3, Definitions
EFFECTIVE DATE
• This MAPP is effective upon date of publication.
9
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 guidance web page at https://www.fda.gov/regulatory-
information/search-fda-guidance-documents.
Originating Office: Office of Pharmaceutical Quality
Effective Date: 12/11/2018; 6/21/2023 Page 4 of 6
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5016.3 Rev. 1
CHANGE CONTROL TABLE
Effective Date Revision Revisions
Number
12/11/2018 N/A Initial
6/21/2023 1 Updated policy and procedures to conform to Section 605 of
the Further Consolidated Appropriations Act, 2020 and the
codification of 21 CFR 600.3(h)(6). Other updates are also
included to reflect current policy and procedures.
N/A N/A 2/13/2025 Administrative changes to reflect changes made to
OPQ’s suboffices’ names consistent with the 2024 OPQ
reorganization.
Originating Office: Office of Pharmaceutical Quality
Effective Date: 12/11/2018; 6/21/2023 Page 5 of 6
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MANUAL OF POLICIES AND PROCEDURES
CENTER FOR DRUG EVALUATION AND RESEARCH MAPP 5016.3 Rev. 1
ATTACHMENT
Responsibilities for Quality Assessments of Products Containing Peptide or
Protein Drug Substances
Size (Expressed Submission Typea Responsible OPQ
in Number of Subofficeb
Amino Acids)
IND OPQA I and II
Treatment IND or treatment OPQA I and II and
protocol OPMA
OPQA I and II and
Original NDA
≤40 OPMA
OPQA I and II and
Supplement to approved NDA
OPMA
OPQA I and II and
EUA
OPMA
IND OPQA III
Treatment IND or treatment
OPQA III and OPMA
protocol
≥41
Original BLA OPQA III and OPMA
Supplement to approved BLA OPQA III and OPMA
EUA OPQA III and OPMA
a
Submission types include amendments.
b
Assignments also apply to meetings that occur under respective submission types.
Originating Office: Office of Pharmaceutical Quality
Effective Date: 12/11/2018; 6/21/2023 Page 6 of 6
来源：FDA Pharmaceutical Quality Documents · fda.gov