美国FDA分析方法验证指南中英文对照

ANDA

的申请者必须提交制剂，原料药，非药 典对照品和空

白以使

FDA

实验室能对 申请者所用分析方法进行评审

(21 CFR 314.50(e) and 314.94(a)(1

0))

。

The FDA laboratory analysis demonstrates that the analytical procedures ar

e reproducible by laboratory testing. The review chemists and laboratory analys

ts determine the suitability of the analytical procedures for regulatory purpos

es.

FDA

实验室的 分析会论证该分析方法在实验室内是可以重现的。

审评化学家和实验室分析家

FDA investigators inspect the analytical laboratory testing sites to ensur

e that the analytical procedures used for release and stability testing comply

with current good manufacturing practices (CGMPs) (21 CFR part 211) or good lab

oratory practices (GLPs) (21 CFR part 58), as appropriate.

FDA

检查官会对分析实验室进行检查确保用于放行和稳定性实验的分析方法符合现行

的

GMP

（

21CFR part 211)

和

GLP (21 CFR part 58)

。

Each BLA and PLA must include a full description of the manufacturing meth

ods, including analytical procedures, that demonstrate that the manufactured pr

oduct meets prescribed standards of safety, purity, and potency (21 CFR 601.2(a)

and 601.2(c)(1)(iv)).

< br>每个

BLA

和

PLA

品是符 合规定睥安全，纯充和效力标准的

(21 CFR 601.2(a) and 601.2(c)(1)(iv))

。

Data must be available to establish that the analytical procedures used in

testing meet proper standards of accuracy and reliability (21 CFR 81211.194(a)

(2)). For BLAs, PLAs, and their supplements, the analytical procedures and thei

r validation are submitted as part of the license application or supplement and

are evaluated by the review committee.

必须要 有资料证明所用的分析方法是符合一定的准确度和可靠性要求的

(21 CFR 812 1

1.194(a)(2))

。对于

B LA

，

PLA

及它们的补充，在所提交 的许可证申请中应当要有分析方法

和方法验证这部分的资料，审评委员会会对这部分资料 进行评审。

Representative samples of the product must be submitted and summaries of r

esults of tests performed on the lots represented by the submitted sample must

be provided (21 CFR 601.2(a) and 601.2(c)(1)(vi)). The review committee chair m

ay request analytical testing by CBER laboratory analysts to evaluate the appli

cant=s analytical procedures and verify the test results.

需提供代表性样品及该样品所代表批号的检测结果总结

(21 CFR 601.2(a) and 601.2

(c)(1)(vi))

。

评审委员会主席会要求

CBER

< br>实验室的分析人员进行分析实验对申请者的分析

方法进行评估，并确认其分析结果 。

All analytical procedures are of equal importance from a validation perspe

ctive. In general, validated analytical procedures should be used, irrespective

of whether they are for in-process, release, acceptance, or stability testing.

Each quantitative analytical procedure should be designed to minimize assay va

riation.

从验证的角度来看，

< br>所有的分析方法有着同样的重要性。

一般来说，

应当要应 用已验证过的

分析方法，

而不论其是被用于过程控制，

放行，合格或稳定性实验。高等每个定量分析方法

时都应当要减少其分析 误差。

Analytical procedures and validation data are submitted in the sections of

the application on analytical procedures and controls. Recommendations on info

rmation to be submitted are included in sections III through IX and XI of this

guidance. Information on submission of the methods validation package to the ND

A or ANDA and samples to the FDA laboratories is provided in section X.

分析方法和验证资料应当摆在申请的分析方法和控制章节中提交。

本指南的第

到

I

X

XI

章给出了所需提供资料方面的建议。

向

FDA

实验室提供样品和递交

和

ANDA

中

的分析方法验证资料的信息见第

X

章。

III.

TYPES

OF

ANALYTICAL

PRO

CEDURES

A. Regulatory Analytical Procedure A regulatory analytical procedure is th

e analytical procedure used to evaluate a defined characteristic of the drug su

bstance or drug product. The analytical procedures in the U.S. Pharmacopeia/Nat

ional Formulary (USP/NF) are those legally recognized under section 501(b) of t

he Food, Drug, and Cosmetic Act (the Act) as the regulatory analytical procedur

es for compendial items. For purposes of determining compliance with the Act, t

he regulatory analytical procedure is used.

III

分析方法的类型

A.

法定分析方法

法定分析方法是被用来 评估原料药或制剂的特定性质的。

USP/NF

中的分析方法是 法定

的用于药典项目检测的分析方法。为了确认符合法规，需使用法定分析方法。

B. Alternative Analytical Procedure

An alternative analytical procedure is an analytical procedure proposed by

the applicant for use instead of the regulatory analytical procedure. A valida

ted alternative analytical procedure should be submitted only if it is shown to

perform equal to or better than the regulatory analytical procedure.

B.

替代分析方法

替代分析方法是申请者 提出用于代替法定分析方法的分析方法。只有当一替代分析方

法相当于或优于法定分析方 法时，才可以应用验证过的替代分析方法。

If an alternative analytical procedure is submitted, the applicant should

provide a rationale for its inclusion and identify its use (e.g., release, stab

ility testing), validation data, and comparative data to the regulatory analyti

cal procedure.

如果提交了替 代分析方法，申请者还应当提供其理由，并标明其用途（如，放行，稳定性实

验），验证 资料及其与法定分析方法的对比资料。

C. Stability-Indicating Assay

A stability-indicating assay is a validated quantitative analytical proced

ure that can detect the changes with time in the pertinent properties of the dr

ug substance and drug product.

C.

稳定性指示分析

稳定性指示分析是能 检测出原料药或制剂的某些性质随着时间的延长而出现的变化的

定量分析方法。

A stability-indicating assay accurately measures the active ingredients, w

ithout interference from degradation products, process impurities, excipients,

or other potential impurities

。

稳定性指示 分析能不受降解产物，工艺杂质，赋形剂或其它潜在杂质的影响而准确测

定其中的活性成 分。

If an applicant submits a non-stability-indicating analytical procedure fo

r release testing, then an analytical procedure capable of qualitatively and qu

antitatively monitoring the impurities, including degradation products, should

complement it. Assay analytical procedures for stability studies should be stab

ility-indicating, unless scientifically justified.

如果申请者递交了用于放行检 测的非稳定性指示分析方法，则应当要有能定性和定量

地监测杂质，

包括降解产物，

的分析方法对其进行补充。

稳定性试验中所 用的含量分析方法

应当要有稳定性指示能力，除非有科学的理由能证明其合理性。

IV

.

REFERENCE

STANDARDS

A. Types of Standards A reference standard (i.e., primary standard) may be

obtained from the USP/NF or other official sources (e.g., CBER, 21 CFR 610.20).

If there are questions on whether a source of a standard would be considered b

y FDA to be an official source, applicants should contact the appropriate chemi

stry review staff. When there is no official source, a reference standard shoul

d be of the highest possible purity and be fully characterized.

IV

标准品

A

．标准品的类型

< br>可以从

USP/NF

处或其它官方

(

比如说，

CBER

，

21CFR 610.20)

获得标准品

(

也就是一级

对照品

)

。如果不能确定一标准品的来源是否会被

FDA

认为是官方来源 ，申请者应当要向适

当的化学评审人员咨询。

如果没有官方来源 ，

则被用来作标准品的物质应当要有尽可能高的

纯度，并得到充 分界定。

A working standard (i.e., in-house or secondary standard) is a standard th

at is qualified against and used instead of the reference standard.

工作对照品

(

也就是内部标准品或二 级标准品

)

是根据一级对照品标定的，

并用来代替

一级对照品的。

B. Certificate of Analysis

A certificate of analysis (COA) for reference standards from non-official

sources should be submitted in the section of the application on analytical pro

cedures and controls. For standards from official sources, the user should ensu

re the suitability of the reference standard. The standard should be stored cor

rectly and used within the established use interval.

B

．分析报告单

对于非官方标准品，在申请的分析方法和控制章节中应当要提供该标准品的分析报告

单。

对于从官方获得的标准品，

用户应当要确保标准品的适用性 。

应当正确储存标准品并在

已确定的时间段内使用该标准品。< /p>

C. Characterization of a Reference Standard

Reference standards from USP/NF and other official sources do not require

further characterization. A reference standard that is not obtained from an off

icial source should be of the highest purity that can be obtained by reasonable

effort, and it should be thoroughly characterized to ensure its identity, stre

ngth, quality, purity, and potency.

C

．标准品的界定

< br>从

USP/NF

及其它官方来源获得的标准品是不需要进 一步界定的。

非官方对照品要有尽

可能高的纯度，并进行充分地 界定以确保其结构，剂量，质量，纯度和效力。

The qualitative and quantitative analytical procedures used to characteriz

e a reference standard are expected to be different from, and more extensive th

an, those used to control the identity, strength, quality, purity, and potency

of the drug substance or the drug product. Analytical procedures used to Draft

—

Not for Implementation characterize a reference standard should not rely sol

ely on comparison testing to a previously designated reference standard.

用于界定标准品的定性和定量分析方法应当 要不同于用于控制原料药或制剂的结构，剂量，

质量，

纯度和效 力的分析方法，

要比它们更深入。

用于标准品界定的分析方法不 应仅仅是和

先前的指定标准品进行比较实验。

Generally, this characterization information should include:

A brief description of the manufacture of the reference standard, if the

manufacturing process differs from that of the drug substance. Any additional

purification procedures used in the preparation of the reference standard shoul

d be described.

一般来说，界定资料应当要包括：

标 准品的简单工艺描述，如果其生产工艺是否于其相应的原料药的话。应当要叙述制

备标准 品时所用的补充精制过程。

Legible reproductions of the relevant spectra, chromatograms, thin-layer c

hromatogram (TLC) photographs or reproductions, and other appropriate instrumen

tal recordings.

Data establishing purity. The data should be obtained by usin

g appropriate tests, such as TLC, gas chromatography (GC), high- pressure liquid

chromatography (HPLC), phase solubility analysis, appropriate thermometric ana

lytical procedures, and others as necessary.

相关光谱图，

色 谱图，

TLC

照片及其它仪器输出的清晰复印件。

建立纯度的资料。

应当

要应用适当的检测方法来获得 这些资料，比如说

TLC

，

GC

，

HPLC

，相溶解分析，适当的热分

析方法及其它必要的分析方法。

Appropriate chemical attribute information, such as structural formula, em

pirical formula, and molecular weight. Information to substantiate the proof of

structure should include appropriate analytical tests, such as elemental analy

sis, infrared spectrophotometry (IR), ultraviolet spectrophotometry (UV), nucle

ar magnetic resonance spectroscopy (NMR), and mass spectrometry (MS), as well a

s applicable functional group analysis. Detailed interpretation of the test dat

a in support of the claimed structure should be provided.

适当的化学性质资料 ，比如结构式，经验式和分子量等。结构确证资料应当要包括适

当的分析测试，比如元素 分析，

IR

，

UV,NMR