美国FDA分析方法验证指南中英文对照（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． 方法学

II章到第IX章提供了分析方法和分析方法验证资料方面的基本信息，包括验证项目。下文就一些具体的方法给出了说明：

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．高效液相色谱(HPLC)

HPLC分析方法的广泛应用及色谱柱和柱填充的众多来源都经常会给可比性评估带来很多问题。如下这些要点中，很多都适用于其它色谱分析方法。

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.色谱柱

在定义某一色谱柱时，如下这些性质是很有用的，也应当要包括在分析方法描述中。如果分析方法开发表明只有某一商业来源的色谱柱是适用的，则在分析方法中应当要包括这些资料。如果有多种色谱柱都是适用的话，则应当要包括等效色谱柱列表。

a. Column Parameters  色谱柱参数

• Material: glass, stainless steel, plastic  材质：玻璃，不锈钢，塑料
• Dimensions: length, inner diameter 尺寸：长度，内径
• Frit size  熔封尺寸
• Filter type  过滤类型
• Precolumn and/or guard column type, if used  预柱和/或保护柱（如使用）

b. Packing Material  色谱柱填充物

• Particle type: size, shape, pore diameter  颗粒类型：尺寸，形状，孔径
• Surface modification (e.g., bonded surface type, surface coverage, percentcarbon, additional silylation) 表面修饰(如：键合表面类型，表面覆盖，碳比例，甲硅烷基化作用)
• Recommended pH range for column use  适用的柱pH范围

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.系统适应性研究

CDER的评审官指南：色谱方法的验证(1994年11月) 中对如下这些系统适应性实验进行了定义：

• Tailing factor  拖尾因子
• Relative retention  相对保留时间
• Resolution   分离度
• Relative standard deviation (RSD)   相对标准偏差
• Capacity factor   容量因子
• Number of theoretical plates  理论塔板数

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.

一般来说，在仪器开始运行时，进行进样精密度实验，计算其相对标准偏差。然而，对于运行时间很长的分析，或申请者另有理由说明，则可以在运行的开始和结束时，或在运行的开始，中间和结束时进样，然后报告其平均值。

如果用到了内标物，则应当要标明内标物与活性成分(单个或多个)之间的分离度的最低可接受值。如果该分析方法是用于控制杂质水平的，则应当要说明活性成分和最邻近杂质组分，或每两相邻组分的分离度最小可接受值。


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.操作参数

应当要确定空白溶液，系统适应性实验用标准溶液，或其它标准溶液和样品溶液的进样顺序。应当要对流速，温度和梯度洗脱进行描述。

需详细说明流动相的配制，包括试剂的添加顺序，去气和过滤的方法。分析方法中应当要说明流动相组成的调整会对保留时间所产生的影响。如使用了预柱和/或保护住的话，则要进行说明并提供给出合理性解释。如有任何其它要求，如使用了惰性管(inert tubing)或进样阀(injection valve)，都应当要对此进行说明。



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．气相色谱(GC)

在GC分析方法描述中，至少要包括如下内容。如分析方法中用到了其它的一些参数，对此也应当要进行说明。如果分析方法开发表明只有某一商业来源的色谱柱是适用的，则在分析方法中应当要包括这些资料。如果有多种色谱柱都是适用的话，则应当要包括等效色谱柱列表。

1. Column  色谱柱

• Column dimensions: length, internal diameter, external diameter  色谱柱尺寸：柱长，内外径
• Stationary phase   固定相
• Column material (e.g., silica, glass, stainless steel)  柱填充料(比如：硅酸，玻璃，不锈钢)
• Column conditioning procedure   柱调节程序

2. Operating Parameters  操作参数

• Gases: purity, flow rate, pressure   载气：纯度，流速，压力
• Temperatures: column, injector, detector (including temperature program, if used)   温度：色谱柱，进样器，检测器(包括升温程序，如用到的话)
• Injection (e.g., split, splitless, on-column)   进样：(比如：分流，不分流，柱头进样(On-column injection)
• Detector   检测限
• Typical retention time and total run time   典型保留时间和总运行时间

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.系统适应性实验

在所有的分析方法中都应当要有适当的系统适应性要求。

如采用国内标准，则应满足内标和一个或多个组分的最小分离度要求。如果该分析方法是用于控制杂质水平的，则应当要说明活性成分和最邻近杂质组分，或每两相邻组分的分离度最小可接受值。

一般来说，在仪器开始运行时，进行进样精密度实验，计算其相对标准偏差。然而，对于运行时间很长的分析，或申请者另有理由说明，则可以在运行的开始和结束时，或在运行的开始，中间和结束时进样，然后报告其平均值。


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，光谱法和相关的物理方法

(IR)，近红外光谱(NIR)，紫外可见光谱(UV/Vis)，原子发射光谱/原子吸收光谱，核磁共振(NMR)，拉曼光谱，质谱(MS)和X-射线衍射(XRD)。

光谱分析方法可能没有稳定性指示能力。必要的话，可能通过与色谱方法的比较来评估光谱分析方法的偏差。如果用到了手动仪器的话，则分析方法描述中应当要有取样(sampling)和读数(reading)之间时间差的可接受标准。建议使用适当的系统适应性实验和/或校准实验。验证标准中应当要包括专属性 (说明没有空白干扰)，线性，重复性，中间精密度和耐用性。


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：毛细管电泳(CE)

对于一个毛细管电泳分析方法，至少要指明下述参数。如分析方法需要的话，还要包括其它参数。若方法开发研究表明只有某一商业来源的毛细管是适用的话，则在分析方法描述中需包括该信息。如果有多种毛细管柱都是适用的，则要列表说明所有的等效毛细管柱。

1. Capillary  毛细管柱

• Capillary dimensions: length, length to detector, internal diameter, external diameter   毛细管尺寸：长度，至检测器长度，内径，外径
  
• Capillary material   毛细管材质
• Capillary internal coating (if any)   毛细管内部涂层(如果有的话) 
  

2. Operating Parameters  操作参数

• 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)   毛细管制备过程：第一次使用前，第一次进样前，每次进样前（比如，用100mmol的氢氧化钠冲洗，或用电流缓冲液冲洗）
• Running buffer: composition, including a detailed preparation procedure with the order of addition of the components    电泳缓冲液：组成，包括详细的制备程序及各组分的添加次序。
• Injection: mode (e.g., electrokinetic, hydrodynamic), parameters (e.g.,voltage, pressure, time)    进样：形式（电动的，水力的），参数（比如，电压，压力，时间等）
• Detector    检测器
• Typical migration time and total run time    典型的迁移时间和总运行时间
• Model of CE equipment used   CE仪器型号
• Voltage (if constant voltage)  电压（如果是恒压的话）
• Current (if constant current)   电流（如果是恒流的话）
• Polarity (e.g., polarity of electrode by detector)   极性（比如，检测器电极的极性）
  

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.系统适应性实验

每个分析方法都应当要有适当的系统适应性实验以确定该系统的关键参数。是否包括其它参数，这由申请者来决定。

如用到了内标物，则至少要指明内标物和一个或多个活性组分间分离度的最小可接受值。若该分析方法是用于控制杂质水平的话，则要说明活性组分的最接近流组分间的最小可接受分离度，或每两邻近组分间的最小可接受分离度。



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

旋光度用于测定多糖类物质的纯度，通过单色光（钠光）的偏振，但事实上已扩展到使用任一波长的光源。

如不在钠光谱的波长测定的话，则要给出选择该波长的理由，并要对比在钠D和所选用波长下的旋光度。循环二色性图谱能达到这个目的。除了 USP<781>中的规定之外，旋光度测定程序还应当要包括溶剂，浓度，及水溶液所要调节到的pH值。所用仪器和条件都要能适用于消旋物或光学异构体的结构确认。

光学异构体纯度可以用异构体过量(e.e.) 来表示，举例如下：

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：

和分别是较多光学异构体和较少光学异构体的量。对于消旋物来说，该值为0，若为纯的光学异构体，则为100%。若为中间浓度，则将其表示为中间值；比如，97：3的e.e为94%。

推荐进行适当的系统适应性实验和/或校准实验。验证项目应当包括专属性和中间精密度。



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：和粒径分析相关的分析方法：

对于有些原料药和制剂的质量控制和官方评审来说，粒径分析是个很重要的因素。

和其它分析方法，比如HPLC相比，粒径分析方法的验证是不尽相同的。然而，在给验证进应用到标准混合物。

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.

粒径分析可以包括尺寸特征，形态，表面和粒子群。如下这些参数对于描述界定原料药或制剂所用粒径分析时是很有用的。

1. Particle Size Methods

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

1．    粒径分析方法

粒径分析方法包括，但不局限于：

a. Nonfractionation methods that evaluate an entire population of particles  评估整个粒子群的非分级方法

• Microscopy (optical, electron)  显微镜检查法
• Light scattering (dynamic, photon correlation, laser diffraction)  光散射（动态，光子相关，激光衍射）
• Electrozone sensing   电区感应
• Photozone sensing    辐照感应

b. Fractionation methods that use physical techniques to separate particles on the basis of size   根据粒子的尺寸进行分离的物理性分级方法

• Sieving    筛分
• Cascade impactor    阶式碰撞采样器
• Sedimentation    沉降法
• Size exclusion chromatography    尺寸排除色层分析法

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.校准和验证

为确保仪器操作的准确性，应根据供应商和/或实验规范对系统进行校准。

分析方法验证经常会包括中间精密度和耐用性(robustness)的评估。应当要确保所得到的数据是可重现的，并能控制产品的质量。更多信息可参见第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>中说明了溶出度实验所用的设备。溶出度实验分析方法描述及其分析方法验证中应当包括如下资料：

1. Dissolution Medium

A brief discussion of the reasons for selecting the medium.

1．溶解媒介

简要讨论媒介选择的理由。


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:  

溶出度测试包括溶解步骤和分析方法（自动在线分析、或手动取样然后进行HPLC分析）。书面程序应当要包括如下这几点：

• Apparatus  仪器
• Preparation of standard    标准品的制备
• Preparation of sample   样品的制备
• 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)    进样步骤（比如：间隔，过滤，样品处理，稀释）
• Calculations    计算
  
• Acceptance criteria    合格标准

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

无论是用什么分析方法，都应当要有系统适应性实验，并要有相应的合格标准。还应当要有空白溶液和标准溶液的光谱或色谱图。


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. 验证

无论是溶出程序，还是分析方法都应当要经过验证。

在操作程序中应当要说明完成样品分析所用的时间。还应当要有资料说明样品在实验过程中的稳定性。若进行了在线过滤或在样品制备过程中进行了过滤，则应当要进行适当的回收实验并整理成文件，需说明实验过程中出现的所有偏差。


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：其它仪器分析方法

1.非商业化仪器

FDA鼓励开发和使用最恰当的仪器。稀有系统的使用不仅给官方实验室带来了过度的负担，也会耽搁验证过程。

若使用非商业化仪器，则应当尽可能地能以经济的商业化配件组装成实验所用仪器。对于需要合同制造的特殊分析方法或仪器，申请者应当要和FDA实验进行合作，以使该分析方法可以重现，这一点是非常重要的。除了需提供仪器设计和仪器规格之年，还应当要提供完整的性能评估程序。这样的系统必须是适用的。

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.自动分析方法

自动分析方法的使用会导致官方分析方法验证的延误，即使是非常适用于检测控制的，因为在样品分析之前，FDA实验室必须要对系统进行装配和验证。为了避免这类延误，申请者应当尽可能论证在相同的原理基础上，手动分析方法和该自动分析方法是相当的。

 

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申请的内容

NDA，ANDA，BLA和PLA中递交的分析方法和方法验证相关资料如下所示。并标明了本指南中给出了相应建议和/或讨论的章节的章节号。

在分析方法和控制 一章中需包括的资料：

• 标准品信息，第IV章
• 分析方法，第III，VI章
• 分析方法验证资料，第VII章
• 强降解实验，第VII.A.2.C章
• 杂质研究的仪器输出/原始资料，第VII.A.2.b章
• 统计分析，第VIII章
• 必要的再验证，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

分析方法验证中所需包括的资料：

• 分析方法验证的内容，第XI章
• 强降解实验的代表性仪器输出/原始资料，第VII.A.2.C章
• 某一批次最初样品和最老样品的代表性仪器输出/原始资料，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

稳定性章节中所需包括的资料：

• 强降解实验的实验设计和实验结果，第VII.A.2.b章
• 参考分析方法和控制章节中所递交的的代表性仪器输出/原始资料，第VII.A.2.C章
  
  
  

METHODS VALIDATION PROBLEMS AND DELAY  分析方法验证的问题和延误

Listed below are examples of common problems that can delay successful validation.   下文举列说明了些会延误成功验证的常见问题。

• Failure to provide a sample of a critical impurity, degradation product, internal standard, or novel reagent    未能提供关键杂质，降解物，内标物或新试剂的样品。
• Failure to submit well-characterized reference standards for noncompendial drugs    未能提供非药典药物的已界定标准品。
• Failure to provide sufficient detail or use of unacceptable analytical procedures. For example:  未能提供分析方法的详细描述，或使用和了不可接受的分析方法。比如：

            --  Use of arbitrary arithmetic corrections  随意使用数学校正

            --  Failure to provide system suitability tests  未能提供系统适应性实验

            --  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样的，且未说明校正用的等效因子，而这是美国药典第<905>章：剂型的均一性 所必需的。

           -- Failure to submit complete or legible data. For example: 未能提供完整清晰的数据。比如：
 
           -- Failure to label instrument output to indicate sample identity  未能标注仪器输出

           -- Failure to label the axes  未能标注坐标



Inappropriate shipping procedures. For example:  不合理的运送方式。比如：

• Failure to properly label samples   未能正确标注样品
• Failure to package samples in accordance with product storage conditions    未能根据产品储存条件来包装产品
• Inadequate shipping forms (e.g., missing customs form. for samples from outside the United States)    货运不完备(比如，没有国外样品的报关单)
• Failure to describe proper storage conditions on shipping containers    未在运送包装上标明适当的储存条件

Acceptance Criteria: Numerical limits, ranges, or other suitable measures for acceptance of the results of analytical procedures. 
合格标准(Acceptance criteria)：分析结果的可接受数值限度，范围。

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)：原料药中那些能起生理作用或药理作用的分子或离子，不包括那些使该药物分子成为酯，盐(包括带氢或配位键的盐)，或其它非共价键衍生物(比如，络合物，螯合物，或包合物)(21CFR 314.108(a)). 活性成分指的是整个分子或离子，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.
检测限(Detection limit)：分析方法的检测限指的是样品中被分析物能被检测出的最低量，但并不需要定量检测。

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)).
制剂(Drug product)：成品剂型，比如，片剂，胶囊，或包含某一原料药成分的溶液，通常还会有其它的一些组分，但这也不是必须的。(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)).

原料药/活性成分(Drug substance/active ingredient): 能在疾病的诊断，治疗上，缓解，处理或预防中起到药理作用或其它直接作用的成分，也包括能影响人体的结构和功能的成分。原料药不包括那些在该原料药的合成过程中所用到的中间体。这个术语还包括那些在制剂生产过程中为产生化学变化的的组分，或以改变后的形式存在的制剂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，而其它成分均与某一制剂保持一致的剂型。

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样品中的被分析物可在适当的精密度和准确度下被定量检测出的最低量。检测量是低含量组分样品定量分析的一个参数，特别是用于杂质和/或降解物的测定。

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

试剂(Reagent): 在分析方法中用于检测，测量，检查或分析其它物质的物质。

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.

规格(specification): 质量标准(也就是，检测项，分析方法和合格标准)，提供在已批准的申请中以确认原料药，制剂，中间体，原辅料，试剂和其它组分，包括容器密闭系统，和过程控制物料的质量。

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.

加样(Spiking): 往标准，样品或空白中加入少量已知量的已知物，特别是用于确认某一分析方法的性能或对仪器进行校准。

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.

稳定性指示分析(Stability-indicating assay): 可以检测出原料药和制剂的相关属性(如，活性成分，防腐剂的量) 随着时间延长而产生的变化。稳定性指示分析能不受降解物，工艺杂质，赋形剂或其它潜在杂质的影响对活性成分进行测定。

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

工作对照品(Working standard): 根据一级标准品进行确认的对照品，并用以代替一级对照品。(也被称之为内部对照品或工作对照品)。