美國FDA分析方法驗證指南中英文對照（一）

美國FDA分析方法驗證指南中英文對照（http://www.drugfuture.com/library/ShowArticle.asp?ArticleID=69）

I. INTRODUCTION

This 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 products.

1. 緒論

本指南旨在為申請者提供建議，以幫助其提交分析方法，方法驗證資料和樣品用于支持原料藥和制劑的認定，劑量，質量，純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 in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.

本指南旨在幫助申請者收集資料，遞交樣品并資料以支持分析方法。這些建議適用于NDA，ANDA，BLA，PLA及其它們的補充中所涉及的原料藥和制劑。

The principles also apply to drug substances 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 product jurisdiction to prevent the expenditure of resources on preparing a submission that may later be determined to be unacceptable.

這些原則同樣適用于二類DMF所涉及的原料藥和制劑。如果使用了其它方法，鼓勵申請者事先和FDA藥品評審中心的官員進行討論，以免出現這種情況，那就是花了人力物力所準備起來的遞交資料后來發現是不可用的。

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 applicable 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驗證的原則適用于各種類型的分析方法。但是，本指南中特定的建議可能不適用于有些產品所用的特殊分析方法，如生物藥，生物技術藥，植物藥或放射性藥物等。

For example, many bioassays are based on animal challenge models, 39 immunogenicity assessments, or other immunoassays that have unique features that should be considered when submitting analytical procedure and methods validation information.
比如說，許多生物分析是建立在動物挑戰模式，免疫原性評估或其它有著獨特特性的免疫分析基礎上的，在遞交分析方法和分析方法驗證資料時需考慮這些獨特的性質。

Furthermore, specific recommendations for biological and immunochemical 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，許多原料藥和制劑的界定和質量控制所需的生物和免疫化學檢測并不在本指南的范圍之內。

Although this guidance does not specifically address the submission of analytical procedures 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.

盡管本指南并不專門敘述原料，中間體，賦形劑，包裝材料及原料藥和制劑生產中所用的其它物料的分析方法及分析方法驗證資料的遞交，但是應該應用驗證過的分析方法來分析檢測這些物質。

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.

對于本指南中未提及的關于分析方法驗證和資料提交方面的問題，請向FDA相關的化學評審人員咨詢。

This 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，將取代FDA于1987年2月份發布的工業指南：分析方法驗證所需提交的樣品和分析資料。

II. BACKGROUND

Each NDA and ANDA must include the analytical procedures necessary to ensure the 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

每個NDA和ANDA都必需包括必要的分析方法以確保原料藥和制劑的認定，劑量，質量，純度和效力，還包括制劑的生物利用度(21 CFR 314.50(d)(1) 和314.94(a)(9)(i))。

FDA驗證文件現場備查，可以不與DMF一起交。

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)).

必須要有資料來論證所用的分析方法是符合一定的準確度和可靠性標準的。

Methods validation is the process of demonstrating that analytical procedures are suitable for 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.

分析方法驗證是論證某一分析方法適用于其用途的過程。分析方法的驗證過程是從申請者有計劃地系統性收集驗證資料以支持分析方法開始的。

The　review chemist evaluates the analytical procedures and validation data submitted in the NDA or ANDA.

審評化學家會對NDA或ANDA中的分析方法和驗證資料進行評審。

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 applicant's drug substance and drug product analytical procedures can be evaluated by FDA laboratories (21 CFR 314.50(e) and 314.94(a)(10)).

一旦FDA有要求，則NDA或ANDA的申請者必須提交制劑，原料藥，非藥典對照品和空白以使FDA實驗室能對申請者所用分析方法進行評審(21 CFR 314.50(e) and 314.94(a)(10))。

The FDA laboratory analysis demonstrates that the analytical procedures are reproducible by laboratory testing. The review chemists and laboratory analysts determine the suitability of the analytical procedures for regulatory purposes.
FDA實驗室的分析會論證該分析方法在實驗室內是可以重現的。審評化學家和實驗室分析家會從法規的角度確定該分析方法的適用性。

FDA investigators inspect the analytical laboratory testing sites to ensure that the analytical procedures 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檢查官會對分析實驗室進行檢查確保用于放行和穩定性實驗的分析方法符合現行的GMP（21CFR part 211)　和GLP (21 CFR part 58)。

Each BLA and PLA must include a full 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)).

每個BLA和PLA都必須要有詳細的生產工藝描述，包括分析方法，以說明所生產的產品是符合規定睥安全，純充和效力標準的(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 their validation are submitted as part of the license application or supplement and are evaluated by the review committee.

必須要有資料證明所用的分析方法是符合一定的準確度和可靠性要求的(21 CFR 81211.194(a)(2))。對于BLA，PLA及它們的補充，在所提交的許可證申請中應當要有分析方法和方法驗證這部分的資料，審評委員會會對這部分資料進行評審。

Representative samples of the product must be submitted and summaries of results 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 may request analytical testing by CBER laboratory analysts to evaluate the applicant=s analytical procedures and verify the test results.

需提供代表性樣品及該樣品所代表批號的檢測結果總結(21 CFR 601.2(a) and 601.2(c)(1)(vi))。評審委員會主席會要求CBER實驗室的分析人員進行分析實驗對申請者的分析方法進行評估，并確認其分析結果。

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 quantitative analytical procedure should be designed to minimize assay variation.
從驗證的角度來看，所有的分析方法有著同樣的重要性。一般來說，應當要應用已驗證過的分析方法，而不論其是被用于過程控制，放行，合格或穩定性實驗。高等每個定量分析方法時都應當要減少其分析誤差。

Analytical procedures and validation data are submitted in the sections of the application on analytical procedures and controls. 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.

分析方法和驗證資料應當擺在申請的分析方法和控制章節中提交。本指南的第III到IX章和XI章給出了所需提供資料方面的建議。向FDA實驗室提供樣品和遞交NDA和ANDA中的分析方法驗證資料的信息見第X章。