【文章內容簡介】 準品是不需要進一步界定的。非官方對照品要有盡 可能高的純度，并進行充分地界定以確保其結構，劑量，質量，純度和效力。 The qualitative and quantitative analytical procedures used to characterize a reference standard are expected to be different from, and more extensive than, 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 Analytical procedures used to Draft — Not for Implementation characterize a reference standard should not rely solely on parison testing to a previously designated reference standard. 用于界定標準品的定性和定量分析 方法應當要不同于用于控制原料藥或制劑的結構，劑量，質量，純度和效力的分析方法，要比它們更深入。用于標準品界定的分析方法不應僅僅是和先前的指定標準品進行比較實驗。 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 should be described. 一般來說，界定資料應當要包括： 標準品的簡單工藝描述，如果其生產工藝是否于其相應的原料藥的話。應當要敘述制備標準品時所用的補充精制過程。 Legible reproductions of the relevant spectra, chromatograms, thinlayer chromatogram (TLC) photographs or reproductions, and other appropriate instrumental recordings. Data establishing purity. The data should be obtained by using appropriate tests, such as TLC, gas chromatography (GC), highpressure liquid chromatography (HPLC), phase solubility analysis, appropriate thermometric analytical procedures, and others as necessary. 相關光譜圖，色譜圖， TLC照片及其它儀器輸出的清晰復印件。建立純度的資料。應當要應用適當的檢測方法來獲得這些資料，比如說 TLC， GC， HPLC，相溶解分析，適當的熱分析方法及其它必要的分析方法。 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. 適當的化學性質資料，比如結構式，經驗式和分子量等。結構確證資料應當要包括適當的分析測試，比如元素分析， IR， UV,NMR和 MS，及適用的官能團分析。還應當要提供具體的結構解析資料。 A physical description of the material, including its color and physical form. Appropriate physical constants such as melting range, boiling range, refractive index, dissociation constants (pK values), and optical rotation. A detailed description of the analytical procedures used to characterize the reference standard. 物理性質的描述，包括顏色和物理形態(tài)。 適當的物理常數，比如說熔程，沸程，折射率，離解常數 (pK值 )和旋光度。用于界定標準品的分析程序的詳細敘述。 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 /生物產品的標準品，應當要考慮上述建議，可能可以應用。然而，其它確定物理化學性質，結構特性，生物活性和 /或免疫化學活性的補充檢測和 /或其它檢測將是非常重要的。 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. 物理化學性質包 括異構體，電泳和液相色譜行為及光譜性質等。結構界定可能包括氨基酸序列，氨基酸組成，縮氨酸圖和碳水結構。確定生物和 /或免疫化學活性的分析方法應當要和用來確定產品效力的分析方法一樣。 These can include animalbased, cell culturebased, biochemical, or ligand/receptorbinding assays. While these tests may be needed for plete characterization of certain reference standards, specific remendations for validation of biological and immunochemical tests are not contained in this guidance document. 這些分析方法可以包括基于動物的，細胞培養(yǎng)的，生物化學的或配位體 /接受體螯合的分析方法。如果這些檢測需用于某些標準品的界定，生物和免疫化學檢測的分析方法驗證方面的特殊建議并不在本指南的范圍之內。 V. METHODS VALIDATION FOR INDs For an investigational new drug, sufficient information is required in each phase of an investigation to ensure proper identification, quality, purity, strength, and/or potency. The amount of information on analytical procedures and methods validation necessary will vary with the phase of the investigation (21 CFR (a)(7)). V． IND中的分析方法驗證 對于 IND而言，每個階段的研究都需要有足夠的資料以確保合適的認定，質量，純度，劑量和 /或效力。所需的分析方法和方法驗證方面的資料會隨著研究的階段變化而變化 (21 CFR (a)(7))。 For general guidance on analytical procedures and methods validation information to be submitted for phase 1 studies, sponsors should refer to the FDA guidance for industry on Content and Format of Investigational New Drug Applications (INDs) for Phase 1 Studies of Drugs, Including Well Characterized, Therapeutic, BiotechnologyDerived Products (November 1995). 關于在第 1階段研究所需提交的分析方法和方法驗證資料方面的指南，發(fā) 起人可以參考 FDA的指南 ：藥品（包括結構確定的，有療效的，生物技術產品）第 1階段研究的 IND申請的內容和格式（ 1995年 11 月）。 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（包括結構確定的，有療效的，生物技術產品）第 1階段研究的 IND申請的 CMC內容和格式（草案， 1999年 4月）。 All analytical procedures should be fully developed and validation pleted when the NDA, ANDA, BLA, or PLA is submitted. 在遞交 NDA， ANDA， BLA或 PLA時，所有的分析方法都應當要開發(fā)出來，并得到驗證。 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 o