USP Verification of compendial procedures
美国药典35版USP 1226 VERIFICATION OF COMPENDIAL PROCEDURES
882〈1226〉 Verification of Compendial Procedures / General Information USP 35terial to which the procedure is applied. Although complete 〈1226〉 VERIFICATION OF revalidation of a compendial method is not required to ver-ify the suitability of v a procedure v USP35 under actual condi-COMPENDIAL PROCEDUREStions of use, some of the analytical performance characteris-tics listed in chapter 〈1225〉, Table 2, may be used for the verification process. Only those characteristics that are con-sidered to be appropriate for the verification of the particu-The intent of this general information chapter is to pro-lar v procedure v USP35 need to be evaluated. v The process of vide general information on the verification of compendial assessing the suitability of a compendial analytical test pro-procedures that are being performed for the first time to cedure under the conditions of actual use may or may not yield acceptable results utilizing the personnel, equipment,require actual laboratory performance of each analytical per-and reagents available. This chapter is not intended for ret-formance characteristic.v USP35 The degree and extent of the roactive application to already successfully established labo-verification process may depend on the level of training and ratory procedures. The chapter Validation of Compendial Pro-experience of the user, on the type of procedure and its cedures 〈1225〉 provides general information onassociated equipment or instrumentation, on the specific characteristics that should be considered for various test cat-procedural steps, and on which article(s) are being tested.egories and on the documentation that should accompany v Verification should assess whether the compendial proce-analytical procedures submitted for inclusion in USP–NF. Ver-dure is suitable for the drug substance and/or the drug ification consists of assessing selected analytical performance product matrix, taking into account the drug substance’s characteristics, such as those that are described in chapter synthetic route, the method of manufacture for the drug 〈1225〉, to generate appropriate, relevant data rather than product, or both, if applicable. Verification should include repeating the validation process.an assessment of elements such as the effect of the matrix Users of compendial analytical procedures are not re-on the recovery of impurities and drug substances from the quired to validate these procedures when first used in their drug product matrix, as well as the suitability of chromato-laboratories, but documented evidence of suitability should graphic conditions and column, the appropriateness of de-be established under actual conditions of use. In the United tector signal response, etc.v USP35States, this requirement is established in 21 CFRAs an example, an assessment of specificity is a key pa-211.194(a)(2) of the current Good Manufacturing Practice rameter in verifying that a compendial procedure is suitable regulations, which states that the “suitability of all testing for use in assaying drug substances and drug products. For methods used shall be verified under actual conditions of instance, acceptable specificity for a chromatographicuse.”method may be verified by conformance with system suita-Verification of microbiological procedures is not covered bility resolution requirements (if specified in the in this chapter because it is covered in USP general test v procedure).v USP35 However, drug substances from different chapters Antimicrobial Effectiveness Testing 〈51〉, Microbiologi-suppliers may have different impurity profiles that are not cal Examination of Nonsterile Products: Microbial Enumeration addressed by the compendial test procedure. Similarly, the Tests 〈61〉, Microbiological Examination of Nonsterile Products:excipients in a drug product can vary widely among manu-Tests for Specified Microorganisms 〈62〉, Sterility Tests 〈71〉, and facturers and may have the potential to directly interfere in general information chapter Validation of Microbial Recov-with the procedure or cause the formation of impurities that ery from Pharmacopeial Articles 〈1227〉.are not addressed by the compendial procedure. In addi-tion, drug products containing different excipients, antioxi-Change to read:dants, buffers, or container extractives v may affect the re-covery of the drug substance from the matrix.v USP35 In these cases, a more thorough assessment of v the matrixeffects v USP35 may be required to demonstrate suitability of VERIFICATION PROCESSthe v procedure v USP35 for the particular drug substance or product. Other analytical performance characteristics such as vThe verification process for compendial test procedures is an assessment of the limit of detection or quantitation and the assessment of whether the procedure can be used for its precision for impurities procedures may be useful to demon-intended purpose, under the actual conditions of use for a strate the suitability of the compendial v procedure v USP35specified drug substance and/or drug product matrix.v USP35under actual conditions of use.Users should have the appropriate experience, knowledge,Verification is not required for basic compendial test pro-and training to understand and be able to perform the cedures that are routinely performed unless there is an indi-compendial procedures as written. Verification should be cation that the compendial procedure is not appropriate for conducted by the user such that the results will providethe article under test. Examples of basic compendial proce-confidence that the compendial procedure will perform suit-dures include, but are not limited to, loss on drying, residue ably as intended.on ignition, various wet chemical procedures such as acid If the verification of the compendial procedure is not suc-value, and simple instrumental v determinations v USP35 such as cessful, and assistance from USP staff has not resolved the pH measurements. However, for the application of already problem, it may be concluded that the procedure may not established routine procedures to compendial articles tested be suitable for use with the article being tested in that labo-for the first time, it is recommended that consideration be ratory. It may then be necessary to develop and validate an given to any new or different sample handling or solution alternate procedure as allowed in the General Notices . The preparation requirements.alternate procedure may be submitted to USP, along with the appropriate data, to support a proposal for inclusion or replacement of the current compendial procedure.Change to read:VERIFICATION REQUIREMENTSVerification requirements should be based on an assess-ment of the complexity of both the procedure and the ma-USP 35General Information / 〈1227〉 Validation of Microbial Recovery883culture preparation. The conditions of organism preparation 〈1227〉 VALIDATION OF and storage must be standardized for the neutralizer evalua-tion and should reflect the conditions of the antimicrobial MICROBIAL RECOVERY FROM assay.The specific conditions of the test, including buffers used, PHARMACOPEIAL ARTICLES water, light conditions, and temperature, must be repro-duced in the validation study. All test conditions also shouldbe standardized and performed in the validation study ex-actly as performed in the test.This chapter provides guidelines for the validation of The conditions of microbial recovery are among the most methods for the estimation of the number of viable micro-crucial in accurately estimating the number of microorgan-organisms, for the detection of indicators or objectionable isms present in a test solution. The first consideration is the microorganisms, for the validation of microbiological meth-recovery medium used to support the growth of survivors. ods used in antimicrobial effectiveness testing, and for the This concern is discussed in detail below. The second con-sterility testing of Pharmacopeial articles. It is generally un-sideration is the incubation conditions. Optimal conditions derstood that if a product possesses antimicrobial properties for growth must be present to ensure complete growth and because of the presence of a specific preservative or because reproducible results.of its formulation, this antimicrobial property must be neu-tralized to recover viable microorganisms. This neutralizationmay be achieved by the use of a specific neutralizer, by METHODS OF NEUTRALIZING dilution, by a combination of washing and dilution, or by ANTIMICROBIAL PROPERTIESany combination of these methods.The tests under Antimicrobial Effectiveness Testing 〈51〉, Ste-Three common methods are used to neutralize antimicro-rility Tests 〈71〉, and Microbial Enumeration Tests 〈61〉 and bial properties of a product: (1) chemical inhibition, (2) dilu-Tests for Specified Microorganisms 〈62〉 require the validation tion, and (3) filtration and washing.of recovery methods. To ensure that the results of the testsare credible, neutralization of antimicrobial properties of thetest solution is required before estimating the number of Chemical Inhibitionviable microorganisms.Table 1 shows known neutralizers for a variety of chemicalantimicrobial agents and the reported toxicity of some INFLUENTIAL FACTORSchemical neutralizers to specific microorganisms. However,despite potential toxicity, the convenience and quick action Several factors affect the measurement of a test solution’s of chemical inhibitors encourage their use. Chemical inhibi-antimicrobial activity, and these must be considered in the tion of bactericides is the preferred method for the antimi-validation design. They include the nature of the microor-crobial efficacy test. The potential of chemical inhibitors ganisms used as challenge organisms, the preparation of the should be considered in the membrane filtration and the inoculum of challenge organisms, the specific conditions of direct transfer sterility tests. Antibiotics may not be suscepti-the test, and the conditions of recovery. These factors also ble to neutralization by chemical means, but rather by enzy-affect the validation of recovery methods for aqueous or matic treatment (e.g., penicillinase). These enzymes may be nonaqueous products, irrespective of their antimicrobial used where required.properties; thus, all test methods should be validated withthese factors in mind.The nature of the challenge microorganism exerts a Dilutionstrong effect upon the response to the antimicrobial agent,and so upon the neutralization required for recovery. Repre- A second approach to neutralizing antimicrobial proper-sented among these organisms in compendial tests are ties of a product is by dilution, because the concentration of Gram-positive bacteria, Gram-negative bacteria, yeasts, and a chemical bactericide exerts a large effect on its potency. molds. Each organism to be used in the test must be in-The relationship between concentration and antimicrobial cluded in the validation.effect differs among bactericidal agents but is constant for a The preparation of the inoculum of challenge microorgan-particular antimicrobial agent. This relationship is exponen-isms also affects the testing of products having antimicrobial tial in nature, with the general formula:properties. The growth and preparation of the challenge or-ganism determines the physiological state of the cell. This Cηt = kstate has a direct influence on the results of any test ofantimicrobial efficacy. Microbial tests do not use individual in which C is the concentration; t is the time required to kill cells; rather, populations of cells are harvested for study. The a standard inoculum; k is a constant; and the concentration data generated from these studies are less variable if the cell exponent, η, is the slope of the plot of log t versus log C. populations are homogeneous. Liquid cultures or confluent Antimicrobial agents with high η values are rapidly neutral-growths on solid medium are best suited for reproducibleTable 1. Some Common Neutralizers for Chemical BiocidesNeutralizer Biocide Class Potential Action of BiocidesBisulfate Glutaraldehyde, Mercurials Non-Sporing BacteriaDilution Phenolics, Alcohol, Aldehydes, Sorbate —Glycine Aldehydes Growing CellsLecithin Quaternary Ammonium Compounds (QACs),BacteriaParabens, Bis-biguanidesMg+2 or Ca+2 ions EDTA—Polysorbate QACS, Iodine, Parabens—Thioglycollate Mercurials Staphylococci and SporesThiosulfate Mercurials, Halogens, Aldehydes Staphylococci。
USP-通则-61-62-71-1225--1226
<1225>V ALIDATION OF COMPENDIAL PROCEDURES药典规程的验证Test procedures for assessment of the quality levels of pharmaceutical articles are subject to various requirements. According to Section 501 of the Federal Food, Drug, and Cosmetic Act, assays and specifications in monographs of the United States Pharmacopeia and the National Formulary constitute legal standards. The Current Good Manufacturing Practice regulations [21 CFR (a)] require that test methods, which are used for assessing compliance of pharmaceutical articles with established specifications, must meet proper standards of accuracy and reliability. Also, according to these regulations [21 CFR (a)(2)], users of analytical methods described in USP-NF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Recognizing the legal status of USP and NF standards, it is essential, therefore, that proposal for adoption of new or revised compendial analytical procedures be supported by sufficient laboratory data to document their validity.用于评价药物质量水平的测试规程受到多种要求的影响。
201507FDA行业指南：分析方法验证（中英文）（下）
201507FDA行业指南：分析方法验证（中英文）（下）VII. STATISTICAL ANALYSIS AND MODELS 统计学分析和模型A. Statistics 统计学Statistical analysis of validation data can be used to evaluate validation characteristics against predetermined acceptance criteria. All statistical procedures and parameters used in the analysis of the data should be based on sound principles and appropriate for the intended evaluation. Several statistical methods are useful for assessing validation characteristics, for example, an analysis of variance (ANOVA) to assess regression analysis R (correlation coefficient) and R squared (coefficient of determination) or linear regression to measure linearity. Many statistical methods used for assessing validation characteristics rely on population normality, and it is important to determine whether or not to reject this assumption. There are many techniques, such as histograms, normality tests, and probability plots that can be used to evaluate the observed distribution. It may be appropriate to transform the data to better fit the normal distribution or apply distribution-free (nonparametric) approaches when the observed data are not normally distributed. Appropriate literature or text should be consulted for information on statistical procedures to use when developing new test methods, evaluating existing test methods or evaluating measurement system performance, as well as other general information on the interpretation and treatment of analytical data[18].The data analysis should be assured either by using appropriately validated software or independent verification for correctness.验证数据的统计学分析可以用于评估验证的属性是否符合预定的可接受标准。
方法验证 PPT课件
11.7.4 检测限（LOD） 检测限系指试样中的被分析物能够被检测 出的最低量。 药品的杂质测定，应通过测试确定方法的 检测限。 定量限（LOQ） 定量限系指试样中的被分析物能够被定量 测定的最低量，其测定结果应具有一定的 准确度和精密度。 杂质和降解产物用定量 测定方法研究时，应确定方法的定量限。
杂质检查主要用于控制主成分以外的杂质，如无 机杂质，有机杂质等。杂质检查分为限 度检查和定量测定两部分。用于限度检查的分析 方法验证侧重专属性、检测限和耐用性。用 于定量测定的分析方法验证强调专属性、准确度、 精密度、线性、范围、定量限和耐用性。 含量测定对准确度要求较高，因此所采用的分析 方法要求具有一定的专属性、准确度和 线性等要求。 中国药典 2010 版中规定了不同的检验项目需要 验证不同的内容，详见表 1。
11.7 方法验证内容 本章节内容除特殊标注外，主要依据中国药典 2010 附录 XIX A 药品 质量标准分析方法 验证指导原则。 11.7.1 准确度 准确度系指用该方法测定的结果与真实值或参考值接近的程度。一般 用回收率表示。准 确度应在规定的范围内测试。 A. 验证方法 准确度应在规定的范围内建立，至少用 9 个测定结果进行评价。例如， 设计 3 个不同浓 度，每个浓度各分别制备 3 份供试品溶液，进行测定。应报告已知加 入量的回收率（％）或 测定结果平均值与真实值之差及其相对标准偏差或可信限。 准确度是定量测定的必要条件，因此含量测定、杂质定量测定均需验 证准确度。原料药 与制剂所用的具体方法详见下表。
中间精密度 定义:在同一个实验室，不同时间由不同分 析人员用不同设备测定结果之间的精密度， 称为中间精密度。 验证方法:为考察随机变动因素对精密度的 影响，应设计方案进行中间精密度试验。 变动因素为不同日期、不同分析人员、不 同设备。
USP-1092-溶出度试验地开发和验证(中英文对照版).docx
（ 1092 ）溶出度试验的开发和验证【中英文对照版】INTRODUCTION前言Purpose目的The Dissolution Procedure: Developmentand Validation<1092> provides a comprehensive approach covering items to considerfordeveloping and validating dissolution procedures and the accompanyinganalytical procedures. It addresses the use of automation throughout the testand provides guidance and criteria for validation. Italso addresses thetreatment of the data generated and theinterpretation of acceptance criteriafor immediate- and modified-releasesolid oral dosage forms.溶出实验 :开发和验证（ 1092 ）指导原则提供了在溶出度方法开发和验证过程中以及采用相应分析方法时需要考虑的因素。
本指导原则贯穿溶出度实验的全部过程，并对方法提供了指导和验证标准。
同时它还涉及对普通制剂和缓释制剂所生成的数据和接受标准进行说明。
Scope范围Chapter <1092> addresses the development andvalidation ofdissolution procedures, with a focus on solid oral dosage forms.Many ofthe concepts presented, however, may be applicable to otherdosageforms and routes of administration. General recommendationsare given with theunderstanding that modifications of the apparatus and procedures as given in USPgeneral chapters need to be justified.<1092> 章节讨论了溶出度实验的开发和验证，重点是口服固体制剂。
201507FDA行业指南：分析方法验证（中英文）（上）
201507FDA行业指南：分析方法验证（中英文）（上）Analytical Procedures and Methods Validation for Drugs and Biologics药品和生物制品分析方法验证Guidance for Industry行业指南U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)July 2015Pharmaceutical Quality/CMCAnalytical Procedures and Methods Validation for Drugs and BiologicsGuidance for IndustryAdditional copies are available from:Office of Communications, Division of Drug InformationCenter for Drug Evaluation and ResearchFood and Drug Administration10001 New Hampshire Ave., Hillandale Bldg., 4th FloorSilver Spring, MD 20993Phone: 855-543-3784 or 301-796-3400; Fax: 301-431-6353 Email:****************.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidan ces/default.htmand/orOffice of Communication, Outreach and DevelopmentCenter for Biologics Evaluation and ResearchFood and Drug Administration10903 New Hampshire Ave., Bldg. 71, Room 3128Silver Spring, MD 20993Phone: 800-835-4709 or 240-402-7800Email:************.gov/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInf ormation/Guidances/default.htmU.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)July 2015Pharmaceutical Quality/CMCAnalytical Procedures and Methods Validation for Drugs and Biologics药物和生物制品分析方法验证Guidance for Industry[1]行业指南This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on this topic. It does not create any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. To discuss an alternative approach, contact the FDA staff responsible for this guidance as listed on the title page.本指南代表了FDA对本专题的当前想法。
USP401226药典的确认中英文对照
1226 VERIFICATION OF COMPENDIAL PROCEDURES 药典方法的确认The intent of this general information chapter is to provide general information on the verification of compendial procedures that are being performed for the first time to yield acceptable results utilizing the personnel, equipment, and reagents available.此章节的意图是对药典方法的确认提供基本资料，使用人员，设备和试剂使第一次进行运用药典方法以产生可接受的结果。
This chapter is not intended for retroactive application to already successfully established laboratory procedures. The chapter Validationof Compendial Procedures <1225>provides general information on characteristics that should be considered for various test categories and on the documentation that should accompany analytical procedures submitted for inclusion in USP–NF. Verification consists of assessing selected analytical performance characteristics, such as those that are described in chapter<1225>to generate appropriate, relevant datarather than repeating the validation process.此章节并不旨在对已经成功建立的实验室方法进行回顾性运用。
201507FDA行业指南：分析方法验证（中英文）（中）
201507FDA行业指南：分析方法验证（中英文）（中）A. Principle/Scope 原理/范围A description of the basic principles of the analytical test/technology (i.e., separation, detection); target analyte(s) and sample(s) type (e.g., drug substance, drug product, impurities or compounds in biological fluids).分析测试/技术（即分离、检测）基本原因的描述；目标分析物和样品类型（例如，原料药、制剂、杂质或生物流体中的化合物）。
B. Apparatus/Equipment 仪器/设备All required qualified equipment and components (e.g., instrument type, detector, column type, dimensions, and alternative column, filter type).所有需要的确认过的仪器和组件（例如，仪器类型、检测器、柱子类型、尺寸和可替代的柱子、过滤器类型）。
C. Operating Parameters 运行参数Qualified optimal settings and ranges (include allowed adjustments supported by compendial sources or development and/or validation studies) critical to the analysis (e.g., flow rate, components temperatures, run time, detector settings, gradient, head space sampler). A drawing with experimental configuration and integration parameters may be used, as applicable.确认过的优化的设置和范围（包括来自药典或研发和/或验证研究的允许调整），对于分析过程非常关键（例如，流速、部件温度、运行时间、检测器设置、梯度、顶空进样器）。
药品注册英语
药品注册用英语现在做注册资料经常会涉及英语表达，为了使我们写注册资料时的英语更纯正，希望各位达人能积极勇跃提供经常涉及的英语表达，使我们的注册水平更上一层楼。
我先抛砖引玉CEP：欧洲药典适应性证书certificate of suitability to monograph of European Pharmacopoeia。
是欧洲药典所收载的原料药的一种认证程序，用以确定原料药的质量可以用欧洲药典的方法加以控制。
这一程序适用于生产的和提取的有机或无机物质以及发酵生产的非直接基因产品。
DMF：Drug master File美国药物主文件档案。
是指提交给FDA的用于提供关于人用药品的生产设备、工艺或生产、工艺处理、包装和储存中使用的物料的详细的和保密的信息。
分为五种类型：I：生产地点、设备、操作程序和人员II：原料药、原料药中间体、生产原料药和中间体使用的物料和药品III：包装材料IV：赋形剂、色素、调味剂、香料或生产这些物质所用的物料V：FDA接受的参考信息EDMF：European Drug Master File欧洲药物主文件档案。
是指欧洲制剂申请中有关原料药信息的文件，又称原料药主文件档案（ASMF）。
EDMF 只有在制剂申请的支持下才能提交。
EDMF分为两部分：1．申请人部分（AP）：供制剂申请人使用的非保密信息；2. 限制部分（RP）：EDMF持有人认为是保密的信息。
EDMF的使用范围：1. 新原料药2. 已知的但欧洲药典或其成员国药典没有收载的原料药3. 欧洲药典或成员国药典已收载的原料药ANDA：Abbreviated New Drug Application 美国简略新药申请。
是FDA规定的仿制药申请程序。
Generic：仿制的，非特殊的API：Active Pharmaceutical Ingredient 原料药Dossier：文档，档案。
TSE：Transmitting animal Spongiform Encephalopathy agent 传播性动物海绵状脑病体Q7A：ICH（国际协调会议）原料药GMP 指南。
GMP分析方法验证
一. 法规对分析方法验证的要求 二. 分析方法验证定义和目的 三. 分析方法分类 四. 标准分析方法验证/确认 五. 分析方法验证类别和验证内容 六. 常见典型的验证参数/项目 七. 分析方法验证的程序 八. 方法再验证 九. 分析方法验证方案内容 十. 参考文献
一. 法规对分析方法验证的要求
❖ 目的：提供对药典分析方法确认的信息，这些方法 是第一次执行，使用适当的人员、设备、试剂，来 生成可接受的结果。而不是为了对已经成功确立的 实验室规程/方法进行追溯操作。
❖ 说明： （1）药典分析方法的使用者无须在初次使用药典方 法时对方法进行验证，但方法在实际使用条件下的 系统适应性的数据应当以文件形式记录。 （2）一些常规的药典测试方法无须确认:如干燥失重、 炽灼残渣、酸度、pH测定等。
四. 标准分析方法验证/确认
❖USP <1226> Verification of Compendial Procedures 药典分析方法确认
❖ 说明： （3）本规程不适用于微生物测试方法。 （4）如果药典方法确认不成功，并且USP员工
的协助也未能解决问题，则可推断此方法或许 并不适合在此实验室进行该供试品检测。因此 须当按照药典要求重新开发替代方法进行验证。
（二）欧盟GMP的额外要求 12.82 应在分析仪器/设备完成确认后，再着手 分析方法的验证。
12.83 对已验证分析方法的任何修改均应有完 整的记录，这类记录应包括修改的理由和充分 的数据，以证实经修改的方法与规定的方法同 样准确、可靠。
一. 法规对分析方法验证的要求
（三）ICH指南 关于分析方法验证部分内容见ICH Q2 A 、 Q2B, 这次培训主要也是根据ICH这个指南为依据， 具体内容见后面章节。
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<1226> Summary
Verification of microbiological procedures is not covered in this chapter because it is covered in other USP general chapters, <51> Antimicrobial Effectiveness <61> Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests <71> Sterility Tests <1227> Validation of Microbial Recovery From Pharmacopeial Articles
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<1226> Summary
The intent of this chapter is to provide general information to laboratories on the verification of compendial procedures that are being performed for the first time to yield acceptable results utilizing the laboratories’ personnel, equipment, and reagents. Not intended for retroactive application to already successfully established laboratory procedures. Verification consists of assessing selected Analytical Performance Characteristics, such as those which are described in chapter <1225>, to generate appropriate, relevant data rather than repeating the validation process.
Why is <1226> needed?
21 CFR 211.194(a)(2): “users of analytical methods described in USP–NF are not required to validate the accuracy and reliability of these methods, but merely verify their suitability under actual conditions of use. Response to industry inquiries First draft published in PF31(2). Republished in PF32(4)
P, L
P, LOQ
S, LOD
P
S
P, L -----
P S, LOQ S, LOQ
--S, LOD S, LOD
-------
--S S
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P=Precision; S=Specificity; L=Linearity; LOD=Limit of Detection; LOQ=Limit of Quantitation;
Full validation
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Case study – Sodium Chloride
Acidity or alkalinity— To 20 mL of the solution prepared for the test for Appearance of solution, add 0.1 mL of bromothymol blue TS: not more than 0.5 mL of 0.01 N hydrochloric acid or 0.01 N sodium hydroxide is required to change the color of this solution. Loss on drying <731>—Dry the test material at 105º for 2 hours: it loses not more than 0.5% of its weight, determined on about 1.000 g of sample. Limit of bromides— To 0.5 mL of the solution prepared for the test for Appearance of solution, add 4.0 mL of water, 2.0 mL of pH 4.7 phenol red TS, and 1.0 mL of chloramine T solution (0.1 mg per mL), and mix immediately. After 2 minutes, add 0.15 mL of 0.1 N sodium thiosulfate, mix, dilute with water to 10.0 mL, and mix. The absorbance of this solution measured at 590 nm, using water as the comparison liquid, is not greater than that of a Standard solution, concomitantly prepared, using 5.0 mL of a solution containing 3.0 mg of potassium bromide per L and proceeding as above, starting with the addition of 2.0 mL of pH 4.7 phenol red TS (0.010%). Heavy metals, Method I <231>: 5 ppm
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<1226> Summary
Application: titrations, chromatographic procedures (related compounds, assay, limit tests), spectroscopic tests, etc. General tests do not typically require verification (water, heavy metals, residue on ignition, etc.)
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Category III
Category IV
P=Precision; S=Specificity; L=Linearity; LOD=Limit of Detection; LOQ=Limit of Quantitation;
Data Elements for Verification of Dosage Forms
Verification process
There are no general Validation protocols There are no general Verification protocols
Verification
DEGREE OF VERIFICATION
Perform the test as written
New USP Chapter: <1226> Verification of Compendial Procedures
Horacio N. Pappa, Ph.D. Senior Scientist Department of Standards Development
CVG-TPD 2006 INTERNATIONAL CONVENTION October 5-6, 2006 (Toronto, Ontario, Canada)
பைடு நூலகம்
The Analytical Process
PROCESS Laboratory Sample
Sample preparation Aliquout
<1058> Analytical Instrument Qualification Measurement <1225> Validation of Compendial Procedures <1226> Verification of Compendial Procedures <1010> Analytical data - interpretation and treatment Reportable value
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Data Elements for Verification of Drug Substances and Excipients
This table was deleted in the current proposal
Technique Category I Category II Quantitative HPLC/GC Spectro. or colorimet. Titration TLC Gel Electro. P P P ----P, S, LOQ P, LOQ P S, LOQ S, LOQ Limit Test S, LOD S, LOD --S, LOD S, LOD ----------S S --S S
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<1225> Validation of Compendial Procedures
Performance Characteristic
Category I
Category II Quant Limit Test * No Yes Yes No No *