美國FDA分析方法驗證指南中英文對照（三）

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 competent analyst to reproduce the necessary conditions and obtain results comparable to the applicant=s. Aspects of the analytical procedure that require special attention should be described.

VI．　NDA，ANDA，BLA和PLA中分析方法的內容和格式

NDA，ANDA，BLA和PLA中所提交的任一分析方法都應當要有詳細的描述，以使合格的分析人員能重現出所需的實驗條件并獲得和申請者相當的實驗結果。應當要敘述分析方法中需要特殊注意的地方。

If the analytical procedure used is in the current revision of the USP/NF or other FDA recognized standard references (e.g., 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 211.194).

如果所用的分析方法是USP/NF或其它FDA認可參考文獻（如，<<AOAC國際方法匯編>>）中且所參考的分析方法未經過修改的話，則需提供該分析方法的參引，而不用提供該分析方法的描述（21 CFR 211.194）。

A description of analytical procedures from any other published sources should be provided, because the referenced sources may not be readily accessible to the reviewer.

對于從其它公開發表的文獻上獲得的分析方法，應當要對其進行敘述，因為評審官可能并不能很方便的獲得這些文獻。



A. Principle

A statement of the principle of the analytical procedure should be included. For example, separation is based on isocratic reversed phase HPLC with detection by UV.

A．基本方法

HPLC進行分離的，檢測器為UV檢測器。


B. Sampling

 　The number of samples (e.g., vials, tablets) selected, how they are used (i.e., as individual or composite samples), and the number of replicate analyses per sample should be described.

B．取樣

需要敘述的有：所選樣品的數目（比如，瓶，片等），它們是如何使用的（也就是，單獨的或是混合樣品），每個樣品分析的重復次數。


C. Equipment and Equipment Parameters

A listing of all equipment (e.g., instrument type, detector, column type, dimensions) should be included, as well as a list of equipment parameters (e.g., flow rate, temperatures, run time, wavelength settings). A drawing representing the experimental configuration (e.g., illustrating positions for a spray pattern analytical procedure) should be provided, when appropriate.

C．儀器和儀器參數

需要敘述的有：儀器列表（比如，儀器類型，檢測器，柱子類型，尺寸等）和儀器參數（比如，流速，溫度，運行時間和設定波長等）。如果必要的話，還要提供實驗結構示意圖（比如，闡述噴灑式分析方法的位置）。


D. Reagents

A list of reagents and their grades (e.g., USP/NF, American Chemical Society (ACS) Analytical Reagent) should be included. If in-house or modified commercial reagents are used, directions for their preparation should be included. Unstable or potentially hazardous reagents should be identified, and storage conditions, directions for safe use, and usable shelf life for these reagents should be specified.

D．試劑

需要敘述的有：試劑列表及其相應的規格（比如：USP/NF，美國化學社（ACS）分析試劑）。如果使用的是自制試劑或更改過的商業試劑，則應當要有其制備方法。對于不穩定的或有潛在危險的試劑，應標明其儲存條件，安全使用說明和使用周期。


E. System Suitability Testing

System suitability test parameters and acceptance criteria are based on the concept that the equipment, electronics, analytical operations, and samples to be analyzed constitute an integrated system. System suitability testing ensures that the system is working properly at the time of analysis. Appropriate system suitability criteria should be defined and included in the analytical procedure.

E．系統適應性實驗

系統適應性實驗參數和合格標準是建立基礎是：儀器，電子元件，分析操作和待測樣品是個不可分割的整體。系統適應性實驗確保系統在樣品分析的時候能很好地運行。在分析方法中應當要包括適當的系統適應性合格標準。

All chromatographic analytical procedures should include system suitability testing and criteria. Parameters typically used in system suitability evaluations are defined and discussed in the CDER reviewer guidance on Validation of Chromatographic Methods (November 1994).

所有的色譜分析方法都應當要有系統適應性實驗及相應的合格標準。CDER評審官指南<<色譜分析方法的驗證>>（1994年11月）對用于評估系統適應性的典型參數進行了定義和討論。

System suitability testing is recommended as a component of any analytical procedure, not just those that involve chromatographic techniques. Regardless of the type of analytical procedure, testing should be used to confirm that the system will function correctly independent of the environmental conditions. For example, titration analytical procedures should always include the evaluation of a blank (commonly referred to as a blank titration).

建議系統適應性實驗應成為所有分析方法的一部分，而不僅僅是色譜分析方法。無論是哪類分析方法，都要采用實驗來證實該系統能不受環境條件的影響而正確地運行。比如說，滴定法一般來說需要進行空白實驗。


F. Preparation of Standards

Procedures for the preparation of all standard solutions (e.g., stock, working standard solutions, internal standards) should be included.

F．標準品的制備

要有所有標準品溶液（比如，儲備液，工作對照品溶液，內部對照品溶液）的配制方法。


G. Preparation of Samples

Sample preparation for individual tests should be clearly described. Specific details should be provided for unusual sample preparations (e.g., solid-phase extraction, derivatization).

G.操作過程

應當要按操作步驟對操作過程進行逐步敘述。敘述應當要適當包括如下信息：平衡時間，樣品進樣順序和系統適應性或啟動參數。需標明不常見的危險。


I. Calculations

Representative calculations, with a tabulation defining all symbols and numerical factors, and specific instructions for the calculation of degradation products and impurities should be included. Any mathematical transformations or formulas used in data analysis should be described in detail. These may include logarithmic transformations used to obtain a linear relationship from exponential data, or the use of multiple order regression analyses.

I．計算

應當要提供代表性計算公式，并要列表說明所有符號和數字系數，及計算降解產物和雜質的特殊使用說明。所有用于數據分析的數學轉換或公式應詳細描述。這些包括對數轉換以獲得指數數據的線性關系，或多元回歸分析的使用。


J. Reporting of Results

J.結果報告


1. General

The format used to report results (e.g., percent label claim, weight/weight, weight/volume, parts per million (ppm)) including the specific number of significant figures to be reported should be provided.

1．通則

應該規定關鍵計算步驟中的數字單位（例如，‘標簽’標示量的百分比，W/W，W/L，ppm等）


2. Impurities Analytical Procedures

The name and location/identifier (e.g., retention time (RT), relative retention time (RRT)) of impurities and the type of impurity (e.g., process, degradant, excipient degradant) should be included in the analytical procedures for impurities in the drug substance and drug product. The detection limit (DL) or quantitation limit (QL) should be stated, as appropriate. The DL or QL can be set using the drug substance's detection response.

2．雜質分析規程
在有關原料藥和產品的雜質檢測規程中，應當包括雜質的名稱和檢測位/標志（例如，保留時間RT，相對保留時間RRT），以及雜質的種類（比如工藝降解產物，賦形劑降解產物），如有可能，還應當指明檢測限DL或定量限QL。也可以在原料藥檢測中設置DL和QL。

Reporting of organic impurities should cover (1) specified identified impurities by name, (2) specified unidentified impurities by location/identifier, (3) any unspecified impurities, and (4) total impurities. The total organic impurities for the drug product or drug substance is the sum of all impurities equal to or greater than their individual QL.

See recommendations regarding appropriate QLs in FDA impurities guidances (see references). Inorganic impurities and residual solvents should also be addressed.

有機雜質的報告中，應當包括：1、有記載的已經過確認的雜質的名稱；2、有記載但未經過確認雜質的（檢測）位/標志；3、所有的沒有記載的雜質，以及；4、總雜質。總有機雜質是指所有達到或超過其自身定量限度的雜質的總量。在這里可以參考FDA雜質指南文章中有關判定定量限度的內容（看后面的參考）。無機雜質和溶劑的殘留，也應該被提到。

For the drug product, drug substance process impurities may be excluded from reporting if an acceptable rationale is provided in the sections on analytical procedures and controls. Drug product impurities from the drug product manufacturing process, packaging, and labeling should be addressed.

對于產品以及原料藥的工藝雜質也可以不包括在報告中，除非分析規程和控制環節中描敘了一個可以被接受的原則，那么，在產品制造和包裝過程中（包括貼簽）產生的雜質就要被提到。

The above reporting information may not be strictly applicable to all products (e.g., biological, biotechnological, botanical, radiopharmaceutical drugs), but any significant process and product-related impurities should be determined and reported.

并不是所有產品（比如，生物制劑、生物工藝制劑、植物制劑、放射制劑）的報告都必須嚴格按照以上談到的內容來寫，但是所有關鍵的工序以及產品相關的雜質都要有檢測和報告。