美國FDA分析方法驗證指南中英文對照（六）

XI. METHODOLOGY

Sections II through IX provide general information on the submission of analytical procedures and methods validation information, including validation characteristics. Additional information on certain methodologies is provided below.

XI． 方法學

II章到第IX章提供了分析方法和分析方法驗證資料方面的基本信息，包括驗證項目。下文就一些具體的方法給出了說明：

A. High-Pressure Liquid Chromatography (HPLC)

The widespread use of HPLC analytical procedures and the multitude of commercial sources of columns and packings frequently have created problems in assessing comparability. Many of the following points may also apply to other chromatographic analytical procedures.

A．高效液相色譜(HPLC)

HPLC分析方法的廣泛應用及色譜柱和柱填充的眾多來源都經常會給可比性評估帶來很多問題。如下這些要點中，很多都適用于其它色譜分析方法。

1. Column

The following characteristics are useful for defining a particular column and, if known, should be included in the analytical procedure description. If method development has indicated that columns from only one commercial source are suitable, this information should be included as part of the analytical procedure. If more than one column is suitable, a listing of columns found to be equivalent should be included.

1.色譜柱

在定義某一色譜柱時，如下這些性質是很有用的，也應當要包括在分析方法描述中。如果分析方法開發表明只有某一商業來源的色譜柱是適用的，則在分析方法中應當要包括這些資料。如果有多種色譜柱都是適用的話，則應當要包括等效色譜柱列表。

a. Column Parameters  色譜柱參數

• Material: glass, stainless steel, plastic  材質：玻璃，不銹鋼，塑料
• Dimensions: length, inner diameter 尺寸：長度，內徑
• Frit size  熔封尺寸
• Filter type  過濾類型
• Precolumn and/or guard column type, if used  預柱和/或保護柱（如使用）

b. Packing Material  色譜柱填充物

• Particle type: size, shape, pore diameter  顆粒類型：尺寸，形狀，孔徑
• Surface modification (e.g., bonded surface type, surface coverage, percentcarbon, additional silylation) 表面修飾(如：鍵合表面類型，表面覆蓋，碳比例，甲硅烷基化作用)
• Recommended pH range for column use  適用的柱pH范圍

2. System Suitability Testing

Each analytical procedure submitted should include an appropriate number of system suitability tests defining the critical characteristics of that system. Criteria for all system suitability testing should be provided. The system suitability tests listed below are defined in CDER=s reviewer guidance on Validation of Chromatographic Methods (November 1994).

2.系統適應性研究

CDER的評審官指南：色譜方法的驗證(1994年11月) 中對如下這些系統適應性實驗進行了定義：

• Tailing factor  拖尾因子
• Relative retention  相對保留時間
• Resolution   分離度
• Relative standard deviation (RSD)   相對標準偏差
• Capacity factor   容量因子
• Number of theoretical plates  理論塔板數

The RSD is normally performed at the beginning of the run. However, for assays with lengthy run times or as otherwise justified by the applicant, the reported average may be taken from injections at the beginning and end of the run, or at the beginning, middle, and end of the run.

If an internal standard is used, the minimum acceptable resolution between theinternal standard and one or more active ingredients should be specified. If theanalytical procedure is used to control the level of impurities, the minimum resolution between the active ingredient and the closest eluting impurity, or the two peaks eluting closest to each other, should be given.

一般來說，在儀器開始運行時，進行進樣精密度實驗，計算其相對標準偏差。然而，對于運行時間很長的分析，或申請者另有理由說明，則可以在運行的開始和結束時，或在運行的開始，中間和結束時進樣，然后報告其平均值。

如果用到了內標物，則應當要標明內標物與活性成分(單個或多個)之間的分離度的最低可接受值。如果該分析方法是用于控制雜質水平的，則應當要說明活性成分和最鄰近雜質組分，或每兩相鄰組分的分離度最小可接受值。


3. Operating Parameters

The sequence of injection of blanks, system suitability standards, other standards, and samples should be defined. Flow rates, temperatures, and gradients should be described.Complete details should be provided for the preparation of the mobile phase,including the order of addition of the reagents and the methods of degassing andfiltration. The effect of adjustments in mobile phase composition on retention times should be included in the analytical procedure. The rationale for the use ofprecolumns and/or guard columns should be provided and justified. Any specialrequirements, such as the use of inert tubing or injection valves, should be specified.

3.操作參數

應當要確定空白溶液，系統適應性實驗用標準溶液，或其它標準溶液和樣品溶液的進樣順序。應當要對流速，溫度和梯度洗脫進行描述。

需詳細說明流動相的配制，包括試劑的添加順序，去氣和過濾的方法。分析方法中應當要說明流動相組成的調整會對保留時間所產生的影響。如使用了預柱和/或保護住的話，則要進行說明并提供給出合理性解釋。如有任何其它要求，如使用了惰性管(inert tubing)或進樣閥(injection valve)，都應當要對此進行說明。



B. Gas Chromatography (GC)

At a minimum, the following parameters should be included in the description of a GC procedure. Additional parameters should be specified if required by the analytical procedure. If method development has indicated that columns from only one commercial source are suitable, this information should be included as part of the analytical procedure. If more than one column is suitable, a listing of columns found to be equivalent should be included.

B．氣相色譜(GC)

在GC分析方法描述中，至少要包括如下內容。如分析方法中用到了其它的一些參數，對此也應當要進行說明。如果分析方法開發表明只有某一商業來源的色譜柱是適用的，則在分析方法中應當要包括這些資料。如果有多種色譜柱都是適用的話，則應當要包括等效色譜柱列表。

1. Column  色譜柱

• Column dimensions: length, internal diameter, external diameter  色譜柱尺寸：柱長，內外徑
• Stationary phase   固定相
• Column material (e.g., silica, glass, stainless steel)  柱填充料(比如：硅酸，玻璃，不銹鋼)
• Column conditioning procedure   柱調節程序

2. Operating Parameters  操作參數

• Gases: purity, flow rate, pressure   載氣：純度，流速，壓力
• Temperatures: column, injector, detector (including temperature program, if used)   溫度：色譜柱，進樣器，檢測器(包括升溫程序，如用到的話)
• Injection (e.g., split, splitless, on-column)   進樣：(比如：分流，不分流，柱頭進樣(On-column injection)
• Detector   檢測限
• Typical retention time and total run time   典型保留時間和總運行時間

3. System Suitability Testing

Appropriate system suitability criteria should be defined and included in all analytical procedures.

If an internal standard is used, the minimum acceptable resolution between the internal standard and one or more active ingredient should be specified. If the analytical procedure is used to control the level of impurities, the minimum resolution between the active ingredient and the closest eluting impurity, or the two peaks eluting closest to each other, should be given.

The RSD is normally performed at the beginning of the run. However, for assays with lengthy run times or as otherwise justified by the applicant, the reported average may be taken from injections at the beginning and end of the run, or beginning, middle, and end of the run.

3.系統適應性實驗

在所有的分析方法中都應當要有適當的系統適應性要求。

如采用國內標準，則應滿足內標和一個或多個組分的最小分離度要求。如果該分析方法是用于控制雜質水平的，則應當要說明活性成分和最鄰近雜質組分，或每兩相鄰組分的分離度最小可接受值。

一般來說，在儀器開始運行時，進行進樣精密度實驗，計算其相對標準偏差。然而，對于運行時間很長的分析，或申請者另有理由說明，則可以在運行的開始和結束時，或在運行的開始，中間和結束時進樣，然后報告其平均值。


C. Spectrophotometry, Spectroscopy, Spectrometry and Related Physical Methodologies

These analytical procedures include, but are not limited to, IR spectrophotometry, near IR spectrophotometry (NIR), UV/visible spectrophotometry (UV/Vis), atomic emission and atomic absorption, NMR, Raman spectroscopy, MS, and XRD.

Spectrometric analytical procedures may not be stability-indicating. The bias of the analytical procedure should be evaluated by comparing it with a chromatographic procedure, where appropriate. When manually operated equipment is used, the description of the analytical procedure should include an acceptance criterion for the amount of time that may elapse between sampling and reading. Appropriate system suitability and/or calibration testing is recommended. Validation criteria should include specificity (demonstrating no interference of placebo), linearity, repeatability, intermediate precision, and robustness.

C：分光光度法，光譜法和相關的物理方法

(IR)，近紅外光譜(NIR)，紫外可見光譜(UV/Vis)，原子發射光譜/原子吸收光譜，核磁共振(NMR)，拉曼光譜，質譜(MS)和X-射線衍射(XRD)。

光譜分析方法可能沒有穩定性指示能力。必要的話，可能通過與色譜方法的比較來評估光譜分析方法的偏差。如果用到了手動儀器的話，則分析方法描述中應當要有取樣(sampling)和讀數(reading)之間時間差的可接受標準。建議使用適當的系統適應性實驗和/或校準實驗。驗證標準中應當要包括專屬性 (說明沒有空白干擾)，線性，重復性，中間精密度和耐用性。


D. Capillary Electrophoresis (CE)

At a minimum, the parameters listed below should be specified for a capillary electrophoretic analytical procedure. Additional parameters may be included as required by the procedure.

If method development has indicated that capillaries from only one commercial source are suitable, this information should be included as part of the analytical procedure. If more than one capillary is suitable, a listing of capillaries found to be equivalent should be included.

D：毛細管電泳(CE)

對于一個毛細管電泳分析方法，至少要指明下述參數。如分析方法需要的話，還要包括其它參數。若方法開發研究表明只有某一商業來源的毛細管是適用的話，則在分析方法描述中需包括該信息。如果有多種毛細管柱都是適用的，則要列表說明所有的等效毛細管柱。

1. Capillary  毛細管柱

• Capillary dimensions: length, length to detector, internal diameter, external diameter   毛細管尺寸：長度，至檢測器長度，內徑，外徑
  
• Capillary material   毛細管材質
• Capillary internal coating (if any)   毛細管內部涂層(如果有的話) 
  

2. Operating Parameters  操作參數

• Capillary preparation procedure: procedure to be followed before the first use, before the first run of the day, before each run (e.g., flush with 100 millimolar sodium hydroxide, flush with running buffer)   毛細管制備過程：第一次使用前，第一次進樣前，每次進樣前（比如，用100mmol的氫氧化鈉沖洗，或用電流緩沖液沖洗）
• Running buffer: composition, including a detailed preparation procedure with the order of addition of the components    電泳緩沖液：組成，包括詳細的制備程序及各組分的添加次序。
• Injection: mode (e.g., electrokinetic, hydrodynamic), parameters (e.g.,voltage, pressure, time)    進樣：形式（電動的，水力的），參數（比如，電壓，壓力，時間等）
• Detector    檢測器
• Typical migration time and total run time    典型的遷移時間和總運行時間
• Model of CE equipment used   CE儀器型號
• Voltage (if constant voltage)  電壓（如果是恒壓的話）
• Current (if constant current)   電流（如果是恒流的話）
• Polarity (e.g., polarity of electrode by detector)   極性（比如，檢測器電極的極性）
  

3. System Suitability Testing

Each analytical procedure should include the appropriate system suitability tests defining the critical characteristics of that system. Other parameters may be included at the discretion of the applicant.

If an internal standard is used, the minimum acceptable resolution between the internal standard and one or more active ingredient should be specified. If the analytical procedure is used to control the level of impurities, the minimum resolution between the active ingredient and the closest eluting impurity, or the two peaks eluting closest to each other, should be given.

3.系統適應性實驗

每個分析方法都應當要有適當的系統適應性實驗以確定該系統的關鍵參數。是否包括其它參數，這由申請者來決定。

如用到了內標物，則至少要指明內標物和一個或多個活性組分間分離度的最小可接受值。若該分析方法是用于控制雜質水平的話，則要說明活性組分的最接近流組分間的最小可接受分離度，或每兩鄰近組分間的最小可接受分離度。



E. Optical Rotation

Optical rotation is used for the measurement of stereochemical purity. Visual polarimeters rely on a monochromatic source, which traditionally was sodium D, but has expanded to virtually any wavelength.

If measurements are to be made at a wavelength other than sodium D, an explanation for selecting the wavelength should be given, along with a comparison of the specific rotation at sodium D and the wavelength to be used. Circular dichroism (CD) spectra may suffice for this purpose. In addition to the provisions of USP <781>, procedures for measurement of specific rotation should include the solvent, concentration, and, for aqueous solutions, the pH to which the solution should be adjusted. The conditions and equipment should be shown to be suitable to confirm the stereochemical identity of a racemate or an enantiomer.

The enantiomeric purity can be expressed as enantiomeric excess (e.e.), using the following formula as an example:

E：旋光度

旋光度用于測定多糖類物質的純度，通過單色光（鈉光）的偏振，但事實上已擴展到使用任一波長的光源。

如不在鈉光譜的波長測定的話，則要給出選擇該波長的理由，并要對比在鈉D和所選用波長下的旋光度。循環二色性圖譜能達到這個目的。除了 USP<781>中的規定之外，旋光度測定程序還應當要包括溶劑，濃度，及水溶液所要調節到的pH值。所用儀器和條件都要能適用于消旋物或光學異構體的結構確認。

光學異構體純度可以用異構體過量(e.e.) 來表示，舉例如下：

e.e. = 100% * {{M} - [m]}/{[M] + [m]}

where [M] and [m] are the concentrations of the major and minor enantiomers, respectively. This yields values of zero for a racemate and 100 percent for a pure enantiomer. An intermediate concentration gives intermediate values; for example, 97:3 would give an e.e. of 94 percent.

Appropriate system suitability and/or calibration testing is recommended. Validation criteria should include specificity, and intermediate precision.

e.e. = 100% * {{M} - [m]}/{[M] + [m]}

式中：

和分別是較多光學異構體和較少光學異構體的量。對于消旋物來說，該值為0，若為純的光學異構體，則為100%。若為中間濃度，則將其表示為中間值；比如，97：3的e.e為94%。

推薦進行適當的系統適應性實驗和/或校準實驗。驗證項目應當包括專屬性和中間精密度。



F：Methodologies Relating to Particle Size Analysis

Particle size analysis is an important element for quality control and regulatory evaluation of certain drug substances and drug products. The normal concepts of validation may differ for particle size methodologies as compared to other analytical methodologies such as HPLC.However, a standard mixture may be used for calibration.

F：和粒徑分析相關的分析方法：

對于有些原料藥和制劑的質量控制和官方評審來說，粒徑分析是個很重要的因素。

和其它分析方法，比如HPLC相比，粒徑分析方法的驗證是不盡相同的。然而，在給驗證進應用到標準混合物。

Particle size evaluation can include characteristics of size, morphology, surface, and population of particles. The following parameters are useful for describing particle size analysis for characterization of drug substances and drug products.

粒徑分析可以包括尺寸特征，形態，表面和粒子群。如下這些參數對于描述界定原料藥或制劑所用粒徑分析時是很有用的。

1. Particle Size Methods

Types of particle size methods include, but are not limited to:

1．    粒徑分析方法

粒徑分析方法包括，但不局限于：

a. Nonfractionation methods that evaluate an entire population of particles  評估整個粒子群的非分級方法

• Microscopy (optical, electron)  顯微鏡檢查法
• Light scattering (dynamic, photon correlation, laser diffraction)  光散射（動態，光子相關，激光衍射）
• Electrozone sensing   電區感應
• Photozone sensing    輻照感應

b. Fractionation methods that use physical techniques to separate particles on the basis of size   根據粒子的尺寸進行分離的物理性分級方法

• Sieving    篩分
• Cascade impactor    階式碰撞采樣器
• Sedimentation    沉降法
• Size exclusion chromatography    尺寸排除色層分析法

2. Calibration and Validation Characteristics

To ensure proper instrument operation, the system should be calibrated according to the manufacturer's and/or the laboratory's specification, as appropriate.

The methods validation usually involves evaluation of intermediate precision and robustness. Assurance should be provided that the data generated are reproducible and control the product's quality. See additional information in sections V and VII.

2.校準和驗證

為確保儀器操作的準確性，應根據供應商和/或實驗規范對系統進行校準。

分析方法驗證經常會包括中間精密度和耐用性(robustness)的評估。應當要確保所得到的數據是可重現的，并能控制產品的質量。更多信息可參見第V和VII章。


G. Dissolution

The equipment used for dissolution is covered by USP <711> or USP <724>. The dissolution procedure description and validation should include the following.

G：溶出度

在USP<711>或USP<724>中說明了溶出度實驗所用的設備。溶出度實驗分析方法描述及其分析方法驗證中應當包括如下資料：

1. Dissolution Medium

A brief discussion of the reasons for selecting the medium.

1．溶解媒介

簡要討論媒介選擇的理由。


2. Procedure  操作程序

A dissolution test consists of a dissolution procedure and method of analysis (automated on-line analysis or manual sampling followed by HPLC analysis). The written procedure should cover the following items:  

溶出度測試包括溶解步驟和分析方法（自動在線分析、或手動取樣然后進行HPLC分析）。書面程序應當要包括如下這幾點：

• Apparatus  儀器
• Preparation of standard    標準品的制備
• Preparation of sample   樣品的制備
• Method of analysis (e.g., UV, HPLC)    分析方法 (比如，UV，HPLC)
• Sampling procedure (e.g., intervals, filtration, handling of samples, dilutions)    進樣步驟（比如：間隔，過濾，樣品處理，稀釋）
• Calculations    計算
  
• Acceptance criteria    合格標準

Regardless of the method of analysis, system suitability criteria should be described.Blank and standard solution spectra or chromatograms should be included.

無論是用什么分析方法，都應當要有系統適應性實驗，并要有相應的合格標準。還應當要有空白溶液和標準溶液的光譜或色譜圖。


3. Validation Characteristics

Both the dissolution procedure and the method of analysis should be validated.

The time needed for the completion of the sample analysis should be stated in the procedure. Data should be submitted to support the stability of the dissolution sample during the procedure. If filters are used on-line or during sample preparation, appropriate recovery studies should be performed and documented and any bias should be addressed.

3. 驗證

無論是溶出程序，還是分析方法都應當要經過驗證。

在操作程序中應當要說明完成樣品分析所用的時間。還應當要有資料說明樣品在實驗過程中的穩定性。若進行了在線過濾或在樣品制備過程中進行了過濾，則應當要進行適當的回收實驗并整理成文件，需說明實驗過程中出現的所有偏差。


H. Other Instrumentation

1. Noncommercial Instrumentation

FDA encourages the development and use of the most appropriate instrumentation. However, the use of rare or exotic systems not only places an undue burden on the regulatory laboratory, but also may delay the validation process. When noncommercial instrumentation is used, the instrumentation should be capable of being constructed from commercially available components at a reasonable cost, if possible. For unique methodologies or instrumentation requiring contract fabrication, the applicant's cooperation with the FDA laboratories in helping facilitate duplication of the analytical procedure is important. In addition to design and equipment specifications, complete performance assessment procedures should be provided. Such systems may be found suitable for regulatory use.

H：其它儀器分析方法

1.非商業化儀器

FDA鼓勵開發和使用最恰當的儀器。稀有系統的使用不僅給官方實驗室帶來了過度的負擔，也會耽擱驗證過程。

若使用非商業化儀器，則應當盡可能地能以經濟的商業化配件組裝成實驗所用儀器。對于需要合同制造的特殊分析方法或儀器，申請者應當要和FDA實驗進行合作，以使該分析方法可以重現，這一點是非常重要的。除了需提供儀器設計和儀器規格之年，還應當要提供完整的性能評估程序。這樣的系統必須是適用的。

2. Automated Analytical Procedures

The use of automated analytical procedures, although desirable for control testing, may lead to delay in regulatory methods validation because FDA laboratories have to assemble and validate the system before running samples. To avoid this delay, applicants should demonstrate the equivalence of a manual procedure to the automated procedure based on the same principle whenever possible.

2.自動分析方法

自動分析方法的使用會導致官方分析方法驗證的延誤，即使是非常適用于檢測控制的，因為在樣品分析之前，FDA實驗室必須要對系統進行裝配和驗證。為了避免這類延誤，申請者應當盡可能論證在相同的原理基礎上，手動分析方法和該自動分析方法是相當的。

 

NDA, ANDA, BLA, AND PLA SUBMISSION CONTENTS

The information relating to analytical procedures and methods validation that should be submitted in NDAs, ANDAs, BLAs, and PLAs is identified below with a cross-reference to the section of this guidance that provides recommendations and/or discussion on the topics.

Information that should be included in the analytical procedures and controls sections

1. Reference standard information Section IV

• Analytical procedures Section III, VI
• Validation data Section VII
• Stress studies Section VII.A.2.c
• Instrument output/raw data for impurities Section VII.A.2.b
• Statistical analysis Section VIII
• Revalidation, as needed Section IX
  
  
  

NDA, ANDA, BLA 和PLA申請的內容

NDA，ANDA，BLA和PLA中遞交的分析方法和方法驗證相關資料如下所示。并標明了本指南中給出了相應建議和/或討論的章節的章節號。

在分析方法和控制 一章中需包括的資料：

• 標準品信息，第IV章
• 分析方法，第III，VI章
• 分析方法驗證資料，第VII章
• 強降解實驗，第VII.A.2.C章
• 雜質研究的儀器輸出/原始資料，第VII.A.2.b章
• 統計分析，第VIII章
• 必要的再驗證，第IX章

Information that should be included in the methods validation package5

• Contents of the MV Package Section XI
• Representative instrument output/data for stress studies Section VII.A.2.c
• Representative instrument output and raw data for initialand oldest sample of a batch Section VII.A.2.b

分析方法驗證中所需包括的資料：

• 分析方法驗證的內容，第XI章
• 強降解實驗的代表性儀器輸出/原始資料，第VII.A.2.C章
• 某一批次最初樣品和最老樣品的代表性儀器輸出/原始資料，第VII.A.2.b章

 

Information that should be included in the stability section

• Stress study designs and results Section VII.A.2.b
• Reference (volume and page number of submission)to instrument output and raw data submitted to the sectiondedicated to analytical procedures and controls Section VII.A 2.c

穩定性章節中所需包括的資料：

• 強降解實驗的實驗設計和實驗結果，第VII.A.2.b章
• 參考分析方法和控制章節中所遞交的的代表性儀器輸出/原始資料，第VII.A.2.C章
  
  
  

METHODS VALIDATION PROBLEMS AND DELAY  分析方法驗證的問題和延誤

Listed below are examples of common problems that can delay successful validation.   下文舉列說明了些會延誤成功驗證的常見問題。

• Failure to provide a sample of a critical impurity, degradation product, internal standard, or novel reagent    未能提供關鍵雜質，降解物，內標物或新試劑的樣品。
• Failure to submit well-characterized reference standards for noncompendial drugs    未能提供非藥典藥物的已界定標準品。
• Failure to provide sufficient detail or use of unacceptable analytical procedures. For example:  未能提供分析方法的詳細描述，或使用和了不可接受的分析方法。比如：

            --  Use of arbitrary arithmetic corrections  隨意使用數學校正

            --  Failure to provide system suitability tests  未能提供系統適應性實驗

            --  Differing content uniformity and assay analytical procedures without showing  equivalence factors for defining corrections as required by the current USP chapter <905>  Uniformity of Dosage Units    含量均一性分析和含量分析的分析方法是不一樣的，且未說明校正用的等效因子，而這是美國藥典第<905>章：劑型的均一性 所必需的。

           -- Failure to submit complete or legible data. For example: 未能提供完整清晰的數據。比如：
 
           -- Failure to label instrument output to indicate sample identity  未能標注儀器輸出

           -- Failure to label the axes  未能標注坐標



Inappropriate shipping procedures. For example:  不合理的運送方式。比如：

• Failure to properly label samples   未能正確標注樣品
• Failure to package samples in accordance with product storage conditions    未能根據產品儲存條件來包裝產品
• Inadequate shipping forms (e.g., missing customs form. for samples from outside the United States)    貨運不完備(比如，沒有國外樣品的報關單)
• Failure to describe proper storage conditions on shipping containers    未在運送包裝上標明適當的儲存條件

Acceptance Criteria: Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures. 
合格標準(Acceptance criteria)：分析結果的可接受數值限度，范圍。

Active moiety: The molecule or ion, excluding those appended portions of the molecule that cause the drug to be an ester, salt (including a salt with hydrogen or coordination bonds), or other noncovalent derivative (such as a complex, chelate, or clathrate) of the molecule, responsible for the physiological or pharmacological action of the drug substance (21 CFR 314.108(a)). The active moiety is the entire molecule or ion, not the active site.
活性成分(Active moiety)：原料藥中那些能起生理作用或藥理作用的分子或離子，不包括那些使該藥物分子成為酯，鹽(包括帶氫或配位鍵的鹽)，或其它非共價鍵衍生物(比如，絡合物，螯合物，或包合物)(21CFR 314.108(a)). 活性成分指的是整個分子或離子，而不是活性位置。

Detection Limit: The detection limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be detected, but not necessarily quantitated as an exact value.
檢測限(Detection limit)：分析方法的檢測限指的是樣品中被分析物能被檢測出的最低量，但并不需要定量檢測。

Drug Product: A finished dosage form, for example, a tablet, capsule, or solution that contains a drug substance, generally, but not necessarily, in association with one or more other ingredients (21 CFR 314.3(b)).
制劑(Drug product)：成品劑型，比如，片劑，膠囊，或包含某一原料藥成分的溶液，通常還會有其它的一些組分，但這也不是必須的。(21 CFR 314.3(b))。

Drug Substance/Active Ingredient: An active ingredient that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease or to affect the structure or any function of the human body. The active ingredient does not include intermediates used in the synthesis of such ingredient. The term includes those components that may undergo chemical change in the manufacture of the drug product and be present in the drug product in a modified form. intended to furnish the specified activity or effect (21 CFR 210.3(b)(7) and 314.3(b)).

原料藥/活性成分(Drug substance/active ingredient): 能在疾病的診斷，治療上，緩解，處理或預防中起到藥理作用或其它直接作用的成分，也包括能影響人體的結構和功能的成分。原料藥不包括那些在該原料藥的合成過程中所用到的中間體。這個術語還包括那些在制劑生產過程中為產生化學變化的的組分，或以改變后的形式存在的制劑中以完成某一功能或作用的成分。(21 CFR 210.3(b)(7)和314.3(b))。

Placebo (or Blank): A dosage form. that is identical to the drug product except that the drug substance is absent or replaced by an inert ingredient or a mixture of the drug product excipients quantitatively equivalent to those found in the drug product dosage form.
空白(Placebo or blank)：指不含活性成分，或用惰性成分代替了活性成分，而其它成分均與某一制劑保持一致的劑型。

Quantitation Limit: The quantitation limit of an individual analytical procedure is the lowest amount of analyte in a sample that can be quantitatively determined with suitable precision and accuracy. The quantitation limit is a parameter of quantitative assays for low levels of compounds in sample matrices, and is used particularly for the determination of impurities and/or degradation products.

定量限(Quantitation limit): 分析方法的定量限指的是樣品中的被分析物可在適當的精密度和準確度下被定量檢測出的最低量。檢測量是低含量組分樣品定量分析的一個參數，特別是用于雜質和/或降解物的測定。

Reagent: For analytical procedures, any substance used in a reaction for the purpose of detecting, measuring, examining, or analyzing other substances.

試劑(Reagent): 在分析方法中用于檢測，測量，檢查或分析其它物質的物質。

Specification: The quality standards (i.e., tests, analytical procedures, and acceptance criteria) provided in an approved application to confirm the quality of the drug substances, drug products, intermediates, raw materials, reagents, and other components including container closure systems, and in-process materials.

規格(specification): 質量標準(也就是，檢測項，分析方法和合格標準)，提供在已批準的申請中以確認原料藥，制劑，中間體，原輔料，試劑和其它組分，包括容器密閉系統，和過程控制物料的質量。

Spiking: The addition of a small known amount of a known compound to a standard, sample, or placebo, typically for the purpose of confirming the performance of an analytical procedure or the calibration of an instrument.

加樣(Spiking): 往標準，樣品或空白中加入少量已知量的已知物，特別是用于確認某一分析方法的性能或對儀器進行校準。

Stability-Indicating Assay: A validated quantitative analytical procedure that can detect the changes with time in the pertinent properties (e.g., active ingredient, preservative level) of the drug substance and drug product. A stability-indicating assay accurately measures the active ingredients without interference from degradation products, process impurities, excipients, or other potential impurities.

穩定性指示分析(Stability-indicating assay): 可以檢測出原料藥和制劑的相關屬性(如，活性成分，防腐劑的量) 隨著時間延長而產生的變化。穩定性指示分析能不受降解物，工藝雜質，賦形劑或其它潛在雜質的影響對活性成分進行測定。

Working Standard: A standard that is qualified against and used instead of the reference standard (also known as in-house or secondary standard).

工作對照品(Working standard): 根據一級標準品進行確認的對照品，并用以代替一級對照品。(也被稱之為內部對照品或工作對照品)。