【正文】 edures and controls. Remendations 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(yàn)證資料應(yīng)當(dāng)擺在申請(qǐng)的分析方法和控制章節(jié)中提交。向 FDA實(shí)驗(yàn)室提供樣品和遞交 NDA和 ANDA中的分析方法驗(yàn)證資料的信息見(jiàn)第 X章。 USP/NF 中的分析方法是法定的用于藥典項(xiàng)目檢測(cè)的分析方法。 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 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 替代分析方法是申請(qǐng)者提出用于代替法定分析方法的分析方法。 If an alternative analytical procedure is submitted, the applicant should provide a rationale for its inclusion and identify its use (., release, stability testing), validation data, and parative data to the regulatory analytical procedure. 如果提交了替代分析方法，申請(qǐng)者還應(yīng)當(dāng)提供其理由，并標(biāo)明其用途（如，放行，穩(wěn)定性實(shí)驗(yàn)），驗(yàn)證資料及其與法定分析方法的對(duì)比資料。 A stabilityindicating assay accurately measures the active ingredients, without interference from degradation products, process impurities, excipients, or other potential impurities。 If an applicant submits a nonstabilityindicating analytical procedure for release testing, then an analytical procedure capable of qualitatively and quantitatively monitoring the impurities, including degradation products, should plement it. Assay analytical procedures for stability studies should be stabilityindicating, unless scientifically justified. 如果申請(qǐng)者遞交了用于放行檢測(cè)的非穩(wěn)定性指示分析方法，則應(yīng)當(dāng)要有能定性和定量地監(jiān)測(cè)雜質(zhì)，包括降解產(chǎn)物，的分析方法對(duì)其進(jìn)行補(bǔ)充。 IV. REFERENCE STANDARDS A. Types of Standards A reference standard (., primary standard) may be obtained from the USP/NF or other official sources (., CBER, 21 CFR ). If there are questions on whether a source of a standard would be considered by FDA to be an official source, applicants should contact the appropriate chemistry review staff. When there is no official source, a reference standard should be of the highest possible purity and be fully characterized. IV 標(biāo)準(zhǔn)品 A．標(biāo)準(zhǔn)品的類型 可以從 USP/NF處或其它官方 (比如說(shuō)， CBER， 21CFR )獲得標(biāo)準(zhǔn)品 (也就是一級(jí)對(duì)照品 )。如果沒(méi)有官方來(lái)源，則被用來(lái)作標(biāo)準(zhǔn)品的物質(zhì)應(yīng)當(dāng)要有盡可能高的純度，并得到充分界定。 B. Certificate of Analysis A certificate of analysis (COA) for reference standards from nonofficial sources should be submitted in the section of the application on analytical procedures and controls. For standards from official sources, the user should ensure the suitability of the reference standard. The standard should be stored correctly and used within the established use interval. B．分析報(bào)告單 對(duì)于非官方標(biāo)準(zhǔn)品，在申請(qǐng)的分析方法和控制章節(jié) 中應(yīng)當(dāng)要提供該標(biāo)準(zhǔn)品的分析報(bào)告單。應(yīng)當(dāng)正確儲(chǔ)存標(biāo)準(zhǔn)品并在已確定的時(shí)間段內(nèi)使用該標(biāo)準(zhǔn)品。非官方對(duì)照品要有盡 可能高的純度，并進(jìn)行充分地界定以確保其結(jié)構(gòu)，劑量，質(zhì)量，純度和效力。用于標(biāo)準(zhǔn)品界定的分析方法不應(yīng)僅僅是和先前的指定標(biāo)準(zhǔn)品進(jìn)行比較實(shí)驗(yàn)。應(yīng)當(dāng)要敘述制備標(biāo)準(zhǔn)品時(shí)所用的補(bǔ)充精制過(guò)程。建立純度的資料。 Appropriate chemical attribute information, such as structural formula, empirical formula, and molecular weight. Information to substantiate the proof of structure should include appropriate analytical tests, such as elemental analysis, infrared spectrophotometry (IR), ultraviolet spectrophotometry (UV), nuclear magic resonance spectroscopy (NMR), and mass spectrometry (MS), as well as applicable functional group analysis. Detailed interpretation of the test data in support of the claimed structure should be provided. 適當(dāng)?shù)幕瘜W(xué)性質(zhì)資料，比如結(jié)構(gòu)式，經(jīng)驗(yàn)式和分子量等。還應(yīng)當(dāng)要提供具體的結(jié)構(gòu)解析資料。 適當(dāng)?shù)奈锢沓?shù)，比如說(shuō)熔程，沸程，折射率，離解常數(shù) (pK值 )和旋光度。 For biotechnological/biological product reference standards, the remendations on characterization information above may apply and should be considered. However, additional and/or different tests would be important to assess physicochemical characteristics, structural characteristics, biological activity, and/or immunochemical activity. 至于生物技術(shù) /生物產(chǎn)品的標(biāo)準(zhǔn)品，應(yīng)當(dāng)要考慮上述建議，可能可以應(yīng)用。 Physicochemical determinations may include isoform, electrophoretic, and liquid chromatographic patterns, as well as spectroscopic profiles. Structural characterization may include a determination of amino acid sequence, amino acid position, peptide map, and carbohydrate structure. Biological and/or immunochemical activity should be assessed using the same analytical procedures used to determine product potency. 物理化學(xué)性質(zhì)包 括異構(gòu)體，電泳和液相色譜行為及光譜性質(zhì)等。確定生物和 /或免疫化學(xué)活性的分析方法應(yīng)當(dāng)要和用來(lái)確定產(chǎn)品效力的分析方法一樣。如果這些檢測(cè)需用于某些標(biāo)準(zhǔn)品的界定，生物和免疫化學(xué)檢測(cè)的分析方法驗(yàn)證方面的特殊建議并不在本指南的范圍之內(nèi)。所需的分析方法和方法驗(yàn)證方面的資料會(huì)隨著研究的階段變化而變化 (21 CFR (a)(7))。 General guidance regarding analytical procedures and methods validation information to be submitted for phase 2 or phase 3 studies will be provided in the FDA guidance for industry INDs for Phase 2 and 3 Studies of Drugs, Including Specified Therapeutic BiotechnologyDerived Products, Chemistry, Manufacturing, and Controls Content and Format, when finalized (draft guidance published April 1999). 第 2 和第 3 階段研究所需提交的分析方法和方法驗(yàn)證資料方面的指南，發(fā)起人將可以參考FDA的指南 ：藥 品（包括結(jié)構(gòu)確定的，有療效的，生物技術(shù)產(chǎn)品）第 1階段研究的 IND申請(qǐng)的 CMC內(nèi)容和格式（草案， 1999年 4月）。 VI. CONTENT AND FORMAT OF ANALYTICAL PROCEDURES FOR NDAs, 230ANDAs, BLAs, AND PLAs Any analytical procedure submitted in an NDA, ANDA, BLA, or PLA should be described in sufficient detail to allow a petent analyst to reproduce the necessary conditions and obtain results parable to the applicant=s. Aspects of the analytical procedure that require special attention should be described. VI． NDA， ANDA， BLA和 PLA中分析方法的內(nèi)容和格式 NDA， ANDA， BLA 和 PLA 中所提交的任一分析方法都應(yīng)當(dāng)要有詳細(xì)的描述，以使合格的分析人員能重現(xiàn)出所需的實(shí)驗(yàn)條件并獲得和申請(qǐng)者相當(dāng)?shù)膶?shí)驗(yàn)結(jié)果。 If the analytical procedure used is in the current revision of the USP/NF or other FDA recognized standard references (., AOAC International Book Of Methods) and the referenced analytical procedure is not modified, a statement indicating the analytical procedure and reference may be provided rather than a description of the method (21 CFR ). 如果所用的分析方法是 USP/NF或其它 FDA認(rèn)可參考文獻(xiàn)（如， AOAC