【正文】 I. INTRODUCTION This guidance provides remendations 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(yàn)證資料和樣品用于支持原料藥和制劑的認(rèn)定，劑量，質(zhì)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 remendations 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(bǔ)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(jìn)行討論，以免出現(xiàn)這種情況，那就是花了人力物力所準(zhǔn)備起來的遞交資料后來發(fā)現(xiàn)是不可用的。 The principles of methods validation described in this guidance apply to all types of analytical procedures. However, the specific remendations 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(yàn)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(chǎn)品所用的特殊分析方法，如生物藥，生物技術(shù)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(zhàn)模式，免疫原性評估或其它有著獨(dú)特特性的免疫分析基礎(chǔ)上的，在遞交分析方法和分析方法驗(yàn)證資料時需考慮這些獨(dú)特的性質(zhì)。 Furthermore, specific remendations 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(zhì)量控制所需的生物和免疫化學(xué)檢測并不在本指南的范圍之內(nèi)。 Although this guidance does not specifically address the submission of analytical procedures and validation data for raw materials, intermediates, excipients, container closure ponents, 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(chǎn)中所用的其它物料的分析方法及分析方法驗(yàn)證資料的遞交，但是應(yīng)該應(yīng)用驗(yàn)證過的分析方法來分析檢測這些物質(zhì)。 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(guān)于分析方法驗(yàn)證和資料提交方面的問題，請向 FDA相關(guān)的化學(xué)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(fā)布的工業(yè)指南： 分析方法驗(yàn)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 (d)(1) and (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(rèn)定，劑量，質(zhì)量，純度和效力，還包括制劑的生物利用度 (21 CFR (d)(1) 和 (a)(9)(i))。 FDA驗(yàn)證文件現(xiàn)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 (e) and (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(zhǔn)確度和可靠性標(biāo)準(zhǔn)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(yàn)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(yàn)證過程是從申請者有計劃地系統(tǒng)性收集驗(yàn)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(xué)家會對 NDA或 ANDA中的分析方法和驗(yàn)證資料進(jìn)行評審。 On request from FDA, an NDA or ANDA applicant must submit samples of drug product, drug substance, nonpendial reference standards, and blanks so that the applicant39。s drug substance and drug product analytical procedures can be evaluated by FDA laboratories (21 CFR (e) and (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(shí)驗(yàn)室能對申請者所用分析方法進(jìn)行評審 (21 CFR (e) and (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(shí)驗(yàn)室的分析會論證該分析方法在實(shí)驗(yàn)室內(nèi)是可以重現(xiàn)的。審評化學(xué)家和實(shí)驗(yàn)室分析家會從法規(guī)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 ply 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(shí)驗(yàn)室進(jìn)行檢查確保用于放行和穩(wěn)定性實(shí)驗(yàn)的分析方法符合現(xiàn)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 (a) and (c)(1)(iv)). 每個 BLA和 PLA都必須要有詳細(xì)的生產(chǎn)工藝描述，包括分析方法，以說明所生產(chǎn)的產(chǎn)品是符合規(guī)定睥安全，純充和效力標(biāo)準(zhǔn)的 (21 CFR (a) and (c)(1)(iv))。 Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reli