美国FDA分析方法验证指南中英文对照.docx

1、美国FDA分析方法验证指南中英文对照美国FDA分析方法验证指南中英文对照2012-03-05 10:37I. INTRODUCTIONThis guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug p

2、roducts.1. 绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered

3、in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。The principles also apply to drug subs

4、tances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with the center with productjurisdiction to prevent the expenditure of resources on preparing a submission that may later be determine

5、d to be unacceptable.这些原则同样适用于二类DMF所涉及的原料药和制剂。如果使用了其它方法，鼓励申请者事先和FDA药品评审中心的官员进行讨论，以免出现这种情况，那就是花了人力物力所准备起来的递交资料后来发现是不可用的。The principles of methods validation described in this guidance apply to all types of analytical procedures. However, the specific recommendations in this guidance may not be applic

6、able to certain unique analytical procedures for products such as biological, biotechnological, botanical, or radiopharmaceutical drugs.本指南中所述的分析方法验证的原则适用于各种类型的分析方法。但是，本指南中特定的建议可能不适用于有些产品所用的特殊分析方法，如生物药，生物技术药，植物药或放射性药物等。For example, many bioassays are based on animal challenge models, 39 immunogenici

7、ty assessments, or other immunoassays that have unique features that should be considered when submitting analytical procedure and methods validation information.比如说，许多生物分析是建立在动物挑战模式，免疫原性评估或其它有着独特特性的免疫分析基础上的，在递交分析方法和分析方法验证资料时需考虑这些独特的性质。Furthermore, specific recommendations for biological and immunoc

8、hemical tests that may be necessary for characterization and quality control of many drug substances and drug products are beyond the scope of this guidance document.而且，许多原料药和制剂的界定和质量控制所需的生物和免疫化学检测并不在本指南的范围之内。Although this guidance does not specifically address the submission of analytical procedure

9、s and validation data for raw materials, intermediates, excipients, container closure components, and other materials used in the production of drug substances and drug products, validated analytical procedures should be used to analyze these materials.尽管本指南并不专门叙述原料，中间体，赋形剂，包装材料及原料药和制剂生产中所用的其它物料的分析方

10、法及分析方法验证资料的递交，但是应该应用验证过的分析方法来分析检测这些物质。For questions on appropriate validation approaches for analytical procedures or submission of information not addressed in this guidance, applicants should consult with the appropriate chemistry review staff at FDA.对于本指南中未提及的关于分析方法验证和资料提交方面的问题，请向FDA相关的化学评审人员咨询。T

11、his guidance, when finalized, will replace the FDA guidance for industry on Submitting Samples and Analytical Data for Methods Validation (February 1987).本指南，一旦定稿，将取代FDA于1987年2月份发布的工业指南：分析方法验证所需提交的样品和分析资料。II. BACKGROUND Each NDA and ANDA must include the analytical procedures necessary to ensure the

12、 identity, strength, quality, purity, and potency of the drug substance and drug product, including bioavailability of the drug product (21 CFR 314.50(d)(1) and 314.94(a)(9)(i). II. 背景每个NDA和ANDA都必需包括必要的分析方法以确保原料药和制剂的认定，剂量，质量，纯度和效力，还包括制剂的生物利用度(21 CFR 314.50(d)(1) 和314.94(a)(9)(i)。FDA验证文件现场备查，可以不与DMF一

13、起交。Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability (21 CFR 211.165(e) and 211.194(a)(2).必须要有资料来论证所用的分析方法是符合一定的准确度和可靠性标准的。Methods validation is the process of demonstrating that analytical procedures are suitable for

14、 their intended use. The methods validation process for analytical procedures begins with the planned and systematic collection by the applicant of the validation data to support the analytical procedures.分析方法验证是论证某一分析方法适用于其用途的过程。分析方法的验证过程是从申请者有计划地系统性收集验证资料以支持分析方法开始的。Thereview chemist evaluates the

15、analytical procedures and validation data submitted in the NDA or ANDA. 审评化学家会对NDA或ANDA中的分析方法和验证资料进行评审。On request from FDA, an NDA or ANDA applicant must submit samples of drug product, drug substance, noncompendial reference standards, and blanks so that the applicants drug substance and drug produ

16、ct analytical procedures can be evaluated by FDA laboratories (21 CFR 314.50(e) and 314.94(a)(10).一旦FDA有要求，则NDA或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)(10)。The FDA laboratory analysis demonstrates that the analytical procedures are reproducible by laborator

17、y testing. The review chemists and laboratory analysts determine the suitability of the analytical procedures for regulatory purposes.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会从法规的角度确定该分析方法的适用性。FDA investigators inspect the analytical laboratory testing sites to ensure that the analytical procedures

18、 used for release and stability testing comply with current good manufacturing practices (CGMPs) (21 CFR part 211) or good laboratory 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

19、 description of the manufacturing methods, including analytical procedures, that demonstrate that the manufactured product meets prescribed standards of safety, purity, and potency (21 CFR 601.2(a) and 601.2(c)(1)(iv).每个BLA和PLA都必须要有详细的生产工艺描述，包括分析方法，以说明所生产的产品是符合规定睥安全，纯充和效力标准的(21 CFR 601.2(a) and 601.

20、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 their validation are submitted as part of the license applica

21、tion 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 81211.194(a)(2)。对于BLA，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 results of tests performed on the lots represen

22、ted by the submitted sample must be provided (21 CFR 601.2(a) and 601.2(c)(1)(vi). The review committee chair may request analytical testing by CBER laboratory analysts to evaluate the applicant=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)

23、(1)(vi)。评审委员会主席会要求CBER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 perspective. In general, validated analytical procedures should be used, irrespective of whether they are for in-process, release, acceptance, or stability testing. Each qua

24、ntitative analytical procedure should be designed to minimize assay variation.从验证的角度来看，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.

25、 Recommendations on information 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 NDA 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III到IX章和XI章给出

26、了所需提供资料方面的建议。向FDA实验室提供样品和递交NDA和ANDA中的分析方法验证资料的信息见第X章。III. TYPES OF ANALYTICAL PROCEDURES A. Regulatory Analytical Procedure A regulatory analytical procedure is the analytical procedure used to evaluate a defined characteristic of the drug substance or drug product. The analytical procedures in the

27、U.S. Pharmacopeia/National Formulary (USP/NF) are those legally recognized under section 501(b) of the Food, Drug, and Cosmetic Act (the Act) as the regulatory analytical procedures for compendial items. For purposes of determining compliance with the Act, the regulatory analytical procedure is used

28、.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 validated alternative a

29、nalytical 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 rational

30、e for its inclusion and identify its use (e.g., release, stability testing), validation data, and comparative data to the regulatory analytical 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 quantitati

31、ve analytical procedure that can detect the changes with time in the pertinent properties of the drug 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, without interference from degradation produ

32、cts, 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 for release testing, then an analytical procedure capable of qualitatively and quantitatively monitoring the impurities, including degradation products, should complement it. Assay analytical procedures for stability studies should be stability-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