美国FDA分析方法验证指南中英文对照
美国FDA生产过程(工艺)验证总则指南中英文版
GUIDELINEON GENERAL PRINCIPLES OFPROCESS VALIDATIONMay, 1987Prepared by: Center for Drugs and Biologics andCenter for Devices and Radiological HealthFood and Drug AdministrationMaintained by: Division of Manufacturing and Product Quality (HFN-320)Office of ComplianceCenter for Drugs and BiologicsFood and Drug Administration5600 Fishers LaneRockville, Maryland 20857General Principles of Process Validation May 1987GENERAL PRINCIPLES OF PROCESS VALIDATIONI. PURPOSEThis guideline outlines general principles that FDA considers to beacceptable elements of process validation for the preparation ofhuman and animal drug products and medical devices.II. SCOPEThis guideline is issued under Section 10.90 (21 CFR 10.90) and isapplicable to the manufacture of pharmaceuticals and medicaldevices. It states principles and practices of generalapplicability that are not legal requirements but are acceptable tothe FDA. A person may rely upon this guideline with the assurance of its acceptability to FDA, or may follow different procedures.When different procedures are used, a person may, but is notrequired to, discuss the matter in advance with FDA to prevent theexpenditure of money and effort on activities that may later bedetermined to be unacceptable. In short, this guideline listsprinciples and practices which are acceptable to the FDA for theprocess validation of drug products and medical devices; it doesnot list the principles and practices that must, in all instances,be used to comply with law.-1-This guideline may be amended from time to time. Interestedpersons are invited to submit comments on this document and anysubsequent revisions. Written comments should be submitted to the Dockets Management Branch (HFA-305), Food and Drug Administration,Room 4-62, 5600 Fishers Lane, Rockville, Maryland 20857. Receivedcomments may be seen in that office between 9\a.m. and 4\p.m.,Monday through Friday.III. INTRODUCTIONProcess validation is a requirement of the Current GoodManufacturing Practices Regulations for Finished Pharmaceuticals,21 CFR Parts 210 and 211, and of the Good Manufacturing PracticeRegulations for Medical Devices, 21 CFR Part 820, and therefore, isapplicable to the manufacture of pharamaceuticals and medicaldevices.Several firms have asked FDA for specific guidance on what FDAexpects firms to do to assure compliance with the requirements forprocess validation. This guideline discusses process validationelements and concepts that are considered by FDA as acceptableparts of a validation program. The constituents of validationpresented in this document are not intended to be all-inclusive.FDA recognizes that, because of the great variety of medicalproducts (drug products and medical devices), processes and-2-manufacturing facilities, it is not possible to state in onedocument all of the specific validation elements that areapplicable. Several broad concepts, however, have generalapplicability which manufacturers can use successfully as a guidein validating a manufacturing process. Although the particular requirements of process validation will vary according to such factors as the nature of the medical product (e.g., sterile vsnon-sterile) and the complexity of the process, the broad concepts stated in this document have general applicability and provide an acceptable framework for building a comprehensive approach to process validation.DefinitionsInstallation qualification - Establishing confidence that process equipment and ancillary systems are capable of consistently operating within established limits and tolerances.Process performance qualification - Establishing confidence thatthe process is effective and reproducible.Product performance qualification - Establishing confidence through appropriate testing that the finished product produced by aspecified process meets all release requirements for functionalityand safety.-3-Prospective validation - Validation conducted prior to thedistribution of either a new product, or product made under arevised manufacturing process, where the revisions may affect the product's characteristics.Retrospective validation - Validation of a process for a product already in distribution based upon accumulated production, testing and control data.Validation - Establishing documented evidence which provides a high degree of assurance that a specific process will consistentlyproduce a product meeting its pre-determined specifications and quality attributes.Validation protocol - A written plan stating how validation will be conducted, including test parameters, product characteristics, production equipment, and decision points on what constitutes acceptable test results.Worst case - A set of conditions encompassing upper and lowerprocessing limits and circumstances, including those withinstandard operating procedures, which pose the greatest chance ofprocess or product failure when compared to ideal conditions. Such conditions do not necessarily induce product or process failure.-4-IV. GENERAL CONCEPTSAssurance of product quality is derived from careful attention to anumber of factors including selection of quality parts andmaterials, adequate product and process design, control of theprocess, and in-process and end-product testing. Due to thecomplexity of today's medical products, routine end-product testingalone often is not sufficient to assure product quality for severalreasons. Some end-product tests have limited sensitivity.1 Insome cases, destructive testing would be required to show that themanufacturing process was adequate, and in other situationsend-product testing does not reveal all variations that may occurin the product that may impact on safety and effectiveness.2The basic principles of quality assurance have as their goal theproduction of articles that are fit for their intended use. These1 For example, USP XXI states: "No sampling plan for applyingsterility tests to a specified proportion of discrete unitsselected from a sterilization load is capable of demonstrating withcomplete assurance that all of the untested units are in factsterile."2 As an example, in one instance a visual inspection failed to detecta defective structural weld which resulted in the failure of aninfant warmer. The defect could only have been detected by usingdestructive testing or expensive test equipment.-5-principles may be stated as follows: (1) quality, safety, and effectiveness must be designed and built into the product; (2) quality cannot be inspected or tested into the finished product;and (3) each step of the manufacturing process must be controlled to maximize the probability that the finished product meets all quality and design specifications. Process validation is a key element in assuring that these quality assurance goals are met.It is through careful design and validation of both the process and process controls that a manufacturer can establish a high degree of confidence that all manufactured units from successive lots will be acceptable. Successfully validating a process may reduce the dependence upon intensive in-process and finished product testing. It should be noted that in most all cases, end-product testingplays a major role in assuring that quality assurance goals are met; i.e., validation and end-product testing are not mutually exclusive.The FDA defines process validation as follows:Process validation is establishing documented evidence which provides a high degree of assurance that a specific process will consistently produce a product meeting its pre-determinedspecifications and quality characteristics.-6-It is important that the manufacturer prepare a written validation protocol which specifies the procedures (and tests) to be conducted and the data to be collected. The purpose for which data are collected must be clear, the data must reflect facts and becollected carefully and accurately. The protocol should specify a sufficient number of replicate process runs to demonstrate reproducibility and provide an accurate measure of variability among successive runs. The test conditions for these runs should encompass upper and lower processing limits and circumstances, including those within standard operating procedures, which pose the greatest chance of process or product failure compared to ideal conditions; such conditions have become widely known as "worst case" conditions. (They are sometimes called "most appropriate challenge" conditions.) Validation documentation should include evidence of the suitability of materials and the performance and reliability of equipment and systems.Key process variables should be monitored and documented. Analysisof the data collected from monitoring will establish thevariability of process parameters for individual runs and willestablish whether or not the equipment and process controls areadequate to assure that product specifications are met.-7-Finished product and in-process test data can be of value inprocess validation, particularly in those situations where qualityattributes and variabilities can be readily measured. Wherefinished (or in-process) testing cannot adequately measure certainattributes, process validation should be derived primarily fromqualification of each system used in production and fromconsideration of the interaction of the various systems.V. CGMP REGULATIONS FOR FINISHED PHARMACEUTICALS Process validation is required, in both general and specific terms,by the Current Good Manufacturing Practice Regulations for FinishedPharmaceuticals, 21 CFR Parts 210 and 211. Examples of suchrequirements are listed below for informational purposes, and arenot all-inclusive.A requirement for process validation is set forth in general termsin section\211.100 -- Written procedures; deviations -- whichstates, in part:"There shall be written procedures for production and processcontrol designed to assure that the drug products have theidentity, strength, quality, and purity they purport or arerepresented to possess."-8-Several sections of the CGMP regulations state validationrequirements in more specific terms. Excerpts from some ofthese sections are:Section 211.110, Sampling and testing of in-processmaterials and drug products.(a) "....control procedures shall be established to monitor theoutput and VALIDATE the performance of those manufacturingprocesses that may be responsible for causing variability in thecharacteristics of in-process material and the drug product."(emphasis added)Section 211.113, Control of Microbiological Contamination.(b) "Appropriate written procedures, designed to preventmicrobiological contamination of drug products purporting to besterile, shall be established and followed. Such proceduresshall include VALIDATION of any sterilization process."(emphasis added)VI. GMP REGULATION FOR MEDICAL DEVICESProcess validation is required by the medical device GMPRegulations, 21 CFR Part\820. Section 820.5 requires everyfinished device manufacturer to:"...prepare and implement a quality assurance program that isappropriate to the specific device manufactured..."-9-Section 820.3(n) defines quality assurance as:"...all activities necessary to verify confidence in the qualityof the process used to manufacture a finished device."When applicable to a specific process, process validation is anessential element in establishing confidence that a process willconsistently produce a product meeting the designed qualitycharacteristics.A generally stated requirement for process validation is containedin section\820.100:"Written manufacturing specifications and processing proceduresshall be established, implemented, and controlled to assure thatthe device conforms to its original design or any approvedchanges in that design."Validation is an essential element in the establishment andimplementation of a process procedure, as well as in determiningwhat process controls are required in order to assure conformanceto specifications.Section 820.100(a)(1) states:"...control measures shall be established to assure that thedesign basis for the device, components and packaging iscorrectly translated into approved specifications."-10-Validation is an essential control for assuring that thespecifications for the device and manufacturing process areadequate to produce a device that will conform to the approveddesign characteristics.VII. PRELIMINARY CONSIDERATIONSA manufacturer should evaluate all factors that affect productquality when designing and undertaking a process validation study.These factors may vary considerably among different products andmanufacturing technologies and could include, for example,component specifications, air and water handling systems,environmental controls, equipment functions, and process controloperations. No single approach to process validation will beappropriate and complete in all cases; however, the followingquality activities should be undertaken in most situations.During the research and development (R&D) phase, the desiredproduct should be carefully defined in terms of itscharacteristics, such as physical, chemical, electrical and-11-performance characteristics.3 It is important to translate theproduct characteristics into specifications as a basis fordescription and control of the product.Documentation of changes made during development providetraceability which can later be used to pinpoint solutions tofuture problems.The product's end use should be a determining factor in thedevelopment of product (and component) characteristics andspecifications. All pertinent aspects of the product which impacton safety and effectiveness should be considered. These aspects3 For example, in the case of a compressed tablet, physicalcharacteristics would include size, weight, hardness, and freedomfrom defects, such as capping and splitting. Chemicalcharacteristics would include quantitative formulation/potency;performance characteristics may include bioavailability (reflectedby disintegration and dissolution). In the case of blood tubing,physical attributes would include internal and external diameters,length and color. Chemical characteristics would include rawmaterial formulation. Mechanical properties would include hardness and tensile strength; performance characteristics would includebiocompatibility and durability.-12-include performance, reliability and stability. Acceptable rangesor limits should be established for each characteristic to set upallowable variations.4 These ranges should be expressed inreadily measurable terms.The validity of acceptance specifications should be verifiedthrough testing and challenge of the product on a sound scientificbasis during the initial development and production phase.Once a specification is demonstrated as acceptable it is importantthat any changes to the specification be made in accordance withdocumented change control procedures.VIII. ELEMENTS OF PROCESS VALIDATIONA. Prospective ValidationProspective validation includes those considerations that should bemade before an entirely new product is introduced by a firm or whenthere is a change in the manufacturing process which may affect theproduct's characteristics, such as uniformity and identity. Thefollowing are considered as key elements of prospective validation.4 For example, in order to assure that an oral, ophthalmic, orparenteral solution has an acceptable pH, a specification may beestablished by which a lot is released only if it has been shown tohave a pH within a narrow established range. For a device, aspecification for the electrical resistance of a pacemaker leadwould be established so that the lead would be acceptable only ifthe resistance was within a specified range.-13-1. Equipment and ProcessThe equipment and process(es) should be designed and/or selectedso that product specifications are consistently achieved. Thisshould be done with the participation of all appropriate groupsthat are concerned with assuring a quality product, e.g.,engineering design, production operations, and quality assurancepersonnel.a. Equipment: Installation QualificationInstallation qualification studies establish confidence thatthe process equipment and ancillary systems are capable ofconsistently operating within established limits andtolerances. After process equipment is designed orselected, it should be evaluated and tested to verify thatit is capable of operating satisfactorily within theoperating limits required by the process.5 This phase ofvalidation includes examination of equipment design;determination of calibration, maintenance, and adjustmentrequirements; and identifying critical equipment featuresthat could affect the process and product. Informationobtained from these studies should be used to establishwritten procedures covering equipment calibration,maintenance, monitoring, and control.5 Examples of equipment performance characteristics which maybe measured include temperature and pressure of injectionmolding machines, uniformity of speed for mixers,temperature, speed and pressure for packaging machines, andtemperature and pressure of sterilization chambers.-14-In assessing the suitability of a given piece of equipment,it is usually insufficient to rely solely upon therepresentations of the equipment supplier, or uponexperience in producing some other product.6 Soundtheoretical and practical engineering principles andconsiderations are a first step in the assessment.It is important that equipment qualification simulate actualproduction conditions, including those which are "worstcase" situations.6 The importance of assessing equipment suitability based uponhow it will be used to attain desired product attributes isillustrated in the case of deionizers used to producePurified Water, USP. In one case, a firm used such water tomake a topical drug product solution which, in view of itsintended use, should have been free from objectionablemicroorganisms. However, the product was found to becontaminated with a pathogenic microorganism. The apparentcause of the problem was failure to assess the performanceof the deionizer from a microbiological standpoint. It isfairly well recognized that the deionizers are prone tobuild-up of microorganisms--especially if the flow rates arelow and the deionizers are not recharged and sanitized atsuitable intervals. Therefore, these factors should havebeen considered. In this case, however, the firm reliedupon the representations of the equipment itself, namely the"recharge" (i.e., conductivity) indicator, to signal thetime for regeneration and cleaning. Considering the desiredproduct characteristics, the firm should have determined theneed for such procedures based upon pre-use testing, takinginto account such factors as the length of time theequipment could produce deionized water of acceptablequality, flow rate, temperature, raw water quality,frequency of use, and surface area of deionizing resins.-15-Tests and challenges should be repeated a sufficient numberof times to assure reliable and meaningful results. Allacceptance criteria must be met during the test orchallenge. If any test or challenge shows that theequipment does not perform within its specifications, anevaluation should be performed to identify the cause of thefailure. Corrections should be made and additional testruns performed, as needed, to verify that the equipmentperforms within specifications. The observed variability ofthe equipment between and within runs can be used as a basisfor determining the total number of trials selected for thesubsequent performance qualification studies of theprocess.7Once the equipment configuration and performancecharacteristics are established and qualified, they shouldbe documented. The installation qualification shouldinclude a review of pertinent maintenance procedures, repairparts lists, and calibration methods for each piece ofequipment. The objective is to assure that all repairs canbe performed in such a way that will not affect the7 For example, the AAMI Guideline for Industrial EthyleneOxide Sterilization of Medical Devices approved 2 December 1981, states: "The performance qualification should includea minimum of 3 successful, planned qualification runs, inwhich all of the acceptance criteria are met.....(5.3.1.2.).-16-characteristics of material processed after the repair. Inaddition, special post-repair cleaning and calibrationrequirements should be developed to prevent inadvertentmanufacture a of non-conforming product. Planning during the qualification phase can prevent confusion duringemergency repairs which could lead to use of the wrongreplacement part.b. Process: Performance QualificationThe purpose of performance qualification is to providerigorous testing to demonstrate the effectiveness andreproducibility of the process. In entering the performance qualification phase of validation, it is understood that theprocess specifications have been established and essentially proven acceptable through laboratory or other trial methods and that the equipment has been judged acceptable on thebasis of suitable installation studies.Each process should be defined and described with sufficient specificity so that employees understand what is required.-17-Parts of the process which may vary so as to affectimportant product quality should be challenged.8In challenging a process to assess its adequacy, it isimportant that challenge conditions simulate those that willbe encountered during actual production, including "worstcase" conditions. The challenges should be repeated enoughtimes to assure that the results are meaningful andconsistent.8 For example, in electroplating the metal case of animplantable pacemaker, the significant process steps todefine, describe, and challenge include establishment andcontrol of current density and temperature values forassuring adequate composition of electrolyte and forassuring cleanliness of the metal to be plated. In theproduction of parenteral solutions by aseptic filling, thesignificant aseptic filling process steps to define andchallenge should include the sterilization anddepyrogenation of containers/closures, sterilization ofsolutions, filling equipment and product contact surfaces,and the filling and closing of containers.-18-Each specific manufacturing process should be appropriatelyqualified and validated. There is an inherent danger inrelying on what are perceived to be similarities betweenproducts, processes, and equipment without appropriatechallenge.9c. Product: Performance QualificationFor purposes of this guideline, product performancequalification activities apply only to medical devices.These steps should be viewed as pre-production qualityassurance activities.9 For example, in the production of a compressed tablet, afirm may switch from one type of granulation blender toanother with the erroneous assumption that both types have similar performance characteristics, and, therefore,granulation mixing times and procedures need not bealtered. However, if the blenders are substantiallydifferent, use of the new blender with procedures used forthe previous blender may result in a granulation with poorcontent uniformity. This, in turn, may lead to tabletshaving significantly differing potencies. This situationmay be averted if the quality assurance system detects theequipment change in the first place, challenges the blender performance, precipitates a revalidation of the process, and initiates appropriate changes. In this example,revalidation comprises installation qualification of the newequipment and performance qualification of the processintended for use in the new blender.-19-Before reaching the conclusion that a process has beensuccessfully validated, it is necessary to demonstrate thatthe specified process has not adversely affected thefinished product. Where possible, product performancequalification testing should include performance testingunder conditions that simulate actual use. Productperformance qualification testing should be conducted usingproduct manufactured from the same type of productionequipment, methods and procedures that will be used forroutine production. Otherwise, the qualified product maynot be representative of production units and cannot be usedas evidence that the manufacturing process will produce aproduct that meets the pre-determined specifications andquality attributes.1010 For example, a manufacturer of heart valves receivedcomplaints that the valve-support structure was fracturingunder use. Investigation by the manufacturer revealed thatall material and dimensional specifications had been met butthe production machining process created microscopicscratches on the valve supporting wireform. These scratchescaused metal fatigue and subsequent fracture. Comprehensivefatigue testing of production units under simulated useconditions could have detected the process deficiency.In another example, a manufacturer recalled insulin syringesbecause of complaints that the needles were clogged.Investigation revealed that the needles were clogged bysilicone oil which was employed as a lubricant duringmanufacturing. Investigation further revealed that themethod used to extract the silicone oil was only partiallyeffective. Although visual inspection of the syringesseemed to support that the cleaning method was effective,actual use proved otherwise.-20-After actual production units have sucessfully passed product performance qualification, a formal technical review should be conducted and should include:o Comparison of the approved product specifications and the actual qualified product.o Determination of the validity of test methods used to determine compliance with the approved specifications.o Determination of the adequacy of the specification change control program.2. System to Assure Timely RevalidationThere should be a quality assurance system in place which requires revalidation whenever there are changes in packaging, formulation, equipment, or processes which could impact on product effectiveness or product characteristics, and whenever there are changes in product characteristics. Furthermore, when a change is made in raw material supplier, the manufacturer should consider subtle, potentially adverse differences in theraw material characteristics. A determination of adverse differences in raw material indicates a need to revalidate the process.-21-One way of detecting the kind of changes that should initiate revalidation is the use of tests and methods of analysis whichare capable of measuring characteristics which may vary. Such tests and methods usually yield specific results which go beyond the mere pass/fail basis, thereby detecting variations within product and process specifications and allowing determination of whether a process is slipping out of control.The quality assurance procedures should establish the circumstances under which revalidation is required. These may be based upon equipment, process, and product performance observed during the initial validation challenge studies. It is desirable to designate individuals who have the responsibilityto review product, process, equipment and personnel changes to determine if and when revalidation is warranted.。
美国FDA分析方法验证指南中文译稿[1]
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1II. 背景 (2)III. 分析方法的类型 (3)A. 法定分析方法 (3)B. 可选择分析方法 (3)3 C. 稳定性指示分析 (3)IV. 对照品……………………………………………………………………………4A. 对照品的类型 (4)B. 分析报告单 (4)C. 对照品的界定 (4)V. IND 中的分析方法验证 (6)VI. NDA, ANDA, BLA 和PLA 中分析方法验证的内容和格式 (6)A. 原则 (6)B. 取样 (7)C. 仪器和仪器参数 (7)D. 试剂 (7)E. 系统适应性实验 (7)F. 对照品的制备 (7)G. 样品的制备 (8)H. 分析方法 (8)L. 计算 (8)J. 结果报告 (8)VII. NDA，ANDA,BLA 和PLA 中的分析方法验证 (9)A．非法定分析方法 (9)1．验证项目 (9)2. 其它分析方法验证信息 (10)a. 耐用性 (11)b. 强降解实验 (11)c. 仪器输出/原始资料 (11)3．各类检测的建议验证项目 (13)B．法定分析方法 (15)VIII. 统计分析…………………………………………………………………………15A. 总则 (15)C. 统计 (16)IX. 再验证 (16)X. 分析方法验证技术包：内容和过程……………………………………………17A. 分析方法验证技术包 (17)B. 样品的选择和运输 (18)C. 各方责任 (19)XI. 方法………………………………………………………………………………20A. 高效液相色谱(HPLC) (20)B. 气相色谱(GC) (22)C. 分光光度法，光谱学，光谱法和相关的物理方法 (23)D. 毛细管电泳 (23)E. 旋光度 (24)F. 粒径相关的分析方法 (25)G. 溶出度 (26)H. 其它仪器分析方法 (27)附件A：NDA，ANDA，BLA 和PLA 申请的内容 (28)附件B：分析方法验证的问题和延误 (29)参考文献……………………………………………………………………………………30术语表………………………………………………………………………………………32This guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products.1. 绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。
准备FDA认证前检查中英文对照文档
? When is the ANDA reviewed by FDA?
FDA什么时候审查ANDA
? After the ANDA holder files the ANDA ANDA 持有人将 ANDA归档后
? Because of backlogs, expect at least 6 month delay before reviewing 由于积压，预计至少延迟 6个月才能被审查
? Ensure that the ANDA or DMF submission is an accurate reflection of what is being done at the facility
确保ANDA或DMF中提交的是设施正在进行的情况的准确反应
Richard Needham, RFL Associates
? Ensure that data submitted in the ANDA or DMF submission is supported by raw data at the facility
确保在ANDA或DMF文件中提交的数据以设施的原始数据为依据
? Data and original records must be documented according to cGMP standards 原始数据和记录必须根据cGMP标准进行
? Two adjacent conference rooms 两个相邻的会议室
配备两个人通常是指
? Two Interpreters (provided by the firm, at present) 两名翻译员（目前由公司提供的）
? The interpreters are extremely important to the smooth running of the inspection 翻译员对于检查顺利进行是非常重要的
FDA清洁验证指南(中英文对照)
Validation of Cleaning Processes清洁工艺验证GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES清洁工艺验证检查指南Mike Ma Sort outXiao GangNote: This document is reference material for investigators and other FDA personnel. The document does not bind FDA, and does no confer any rights, privileges, benefits, or immunities for or on any person(s).注意：本指南是审计官和其他FDA人员的参考资料。
FDA不受本指南的约束，也没有授予任何人任何权利、特权、收益或豁免权。
1 of 14ContentI. INTRODUCTION 简介 (3)II. BACKGROUND 背景 (3)III. GENERAL REQUIREMENTS 常规要求 (5)IV. EVALUATION OF CLEANING VALIDATION清洁验证的评估 (6)V. ESTABLISHMENT OF LIMITS 确定限度 (11)VI. OTHER ISSUES 其他问题 (12)VII. REFERENCES 参考资料 (13)2 of 14Validation of cleaning procedures has generated considerable discussion since agency documents, including the Inspection Guide for Bulk Pharmaceutical Chemicals and the Biotechnology Inspection Guide, have briefly addressed this issue. These Agency documents clearly establish the expectation that cleaning procedures (processes) be validated.自从机构文件，包括化学原料药制剂检查指南和生物技术制剂检查指南简明的提及清洁验证规程以来，就对清洁规程验证产生了大量的讨论。
FDA最新版-药物分析程序及方法验证指导原则-中文翻译版
药品及生物制品的分析方法和方法验证指导原则目录1.介绍 (1)2.背景 (2)3.分析方法开发 (3)4.分析程序内容 (3)A.原则/范围 (4)B.仪器/设备 (4)C.操作参数 (4)D.试剂/标准 (4)E.样品制备 (4)F. .................................................................................................................... 标准对照品溶液的制备 (5)G.步骤 (5)H.系统适应性 (5)I.计算 (5)J.数据报告 (5)5.参考标准和教材 (6)6 分析方法验证用于新药，仿制药，生物制品和DMF (6)A.非药典分析方法 (6)B.验证特征 (7)C.药典分析方法 (8)7.统计分析和模型 (8)A.统计 (8)B.模型 (8)8.生命周期管理分析程序 (9)A.重新验证 (9)B.分析方法的可比性研究 (10)1.另一种分析方法 (10)2.分析方法转移的研究 (11)C.报告上市后变更已批准的新药，仿制药，或生物制品 (11)9.美国FDA 方法验证 (12)10.参考文献前言本指导原则草案，定稿后，将代表美国食品和药物管理局（FDA）目前关于这个话题目前的想法。
它不会创造或赋予或任何人的任何权利，不约束FDA 或公众。
您可以使用另一种方法，如果该方法符合适用的法律和法规的要求。
如果你想讨论一个替代方法，请与FDA 工作人员负责实施本指南。
如果你不能确定适当的FDA 工作人员，请拨打本指南的标题页上所列的电话号码。
介绍：该修订指南草案将取代行业2000 年的指导分析方法和方法验证草案，并最终确定后，也将取代1987 年美国FDA 行业指南《提交的样品和分析数据的方法验证》。
该草案提供了有关申请人如何提交分析程序和方法验证数据来支持说明原料药和制剂具有强度、质量、纯度和效用的文件。
准备FDA认证前检查中英文对照文档
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。
美国FDA分析方法验证指南中英文对照
I. INTRODUCTIONThis guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products.1. 绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。
This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。
这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。
The principles also apply to drug substances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with the center with product jurisdiction to prevent the expenditure of resources on preparing a submission that may later be determined to be unacceptable.这些原则同样适用于二类DMF所涉及的原料药和制剂。
FDA 行业指南 中英对照 待完成讲解学习
F D A行业指南中英对照待完成Guidance for IndustryContainer Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls Documentation行业指南人用药品及生物制品的包装容器和封装系统：化学，生产和控制文件指南发布者：美国FDA下属的CDER及CBER发布日期：May 1999TABLE OF CONTENTS目录I. INTRODUCTION介绍II. BACKGROUND 背景A. Definitions 定义B. CGMP, CPSC and USP Requirements on Containers and Closures. CGMP, CPSC和USP对容器和密封的要求C. Additional Considerations 其他需要考虑的事项III. QUALIFICATION AND QUALITY CONTROL OF PACKAGING COMPONENTS包装组件的合格要求以及质量控制A. Introduction 介绍B. General Considerations 通常要求C. Information That Should Be Submitted in Support of an Original Application for AnyDrug Product 为支持任何药品的原始申请所必须提供的信息D. Inhalation Drug Products 吸入性药品E. Drug Products for Injection and Ophthalmic Drug Products 注射剂和眼科用药F. Liquid-Based Oral and Topical Drug Products and Topical Delivery Systems 液体口服和外用药品和外用给药系统G. Solid Oral Dosage Forms and Powders for Reconstitution 口服固体剂型和待重新溶解的粉末H. Other Dosage Forms 其他剂型IV. POSTAPPROVAL PACKAGING CHANGES 批准后的包装变更V. TYPE III DRUG MASTER FILES 药品主文件第III类A. General Comments 总体评述B. Information in a Type III DMF 第III类DMF中包括的信息VI. BULK CONTAINERS 大包装容器A. Containers for Bulk Drug Substances 用于原料药的容器B. Containers for Bulk Drug Products 用于散装药品的容器ATTACHMENT A 附件AREGULATORY REQUIREMENTS 药政要求ATTACHMENT B 附件BCOMPLIANCE POLICY GUIDES THAT CONCERN PACKAGING 关于包装，所适用的政策指南ATTACHMENT C 附件CEXTRACTION STUDIES “提取性”研究ATTACHMENT D 附件DABBREVIATIONS 缩略语ATTACHMENT E 附件EREFERENCES 参考文献GUIDANCE FOR INDUSTRY1Container Closure Systems for Packaging Human Drugs and Biologics Chemistry, Manufacturing and Controls DocumentationI．INTRODUCTION介绍This document is intended to provide guidance on general principles2 for submitting information on packaging materials used for human drugs and biologics.3 This guidance supersedes theFDA Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics ,issued in February 1987 and the packaging policy statement issued in a letter to industry dated June 30, 1995 from the Office of Generic Drugs.4 This guidance is not intended to describe the information that should be provided about packaging operations associated with drug productmanufacture. 本文件目的是为递交人用药品和生物制品的包装信息提供总体原则指南。
201507fda行业指南：分析方法验证(中英文)(下)
201507 FDA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. Appropriateliterature 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。
中英文-美国FDA_GMP检查
执行FDA检查
Douglas A. Camer – Senior Policy Advisor CDER / Office of Compliance 药品审批研究中心 / 执法办公室 Division of Manufacturing and Product Quality International Compliance Branch China - June 2011
The CGMP Regulation CGMP 法规
• CGMP for Finished Pharmaceuticals 对于成品药的现行药品生产管理规范（CGMP） 21 CFR Parts 210 and 211 – Establish “what to” do, not “how to” 确定 “要做什么, 而不是“如何做” • Minimal standards 最低标准 • Maximum flexibility 最大的灵活性 • Specific enough to address problems 具体到足以解决问题 – e.g., Penicillin contamination control 例如，青霉素污染控制 • Technology neutral 技术中立 • Scalable 可扩展性
The Law says… 法律规定...
“to assure that such drug meets the requirements of this Act as to safety and has the identity and strength, and meets the quality and purity characteristics, which it purports or is represented to possess.‖ • “并保证符合其声称或据称的鉴别和含量、质量和纯度特征的现行药 品生产质量管理规范操作和管理。”
美国FDA 分析方法验证指南
美国FDA 分析方法验证指南（中文）U.S. Department of Health and Human ServicesFood and Drug AdministrationCenter for Drug Evaluation and Research (CDER)Center for Biologics Evaluation and Research (CBER)August 2000目录一、结论………………………………………………………..…………………二、背景……………………………………………………………..……….…..三、分析方法的类型…………………………………………………………….A. 法定分析方法……………………………………………………………B. 替代分析方法……………………………………………………………C. 稳定性指示分析…………………………………………………………四、标准品……………………………………………………………………….. A．标准品的类型……………………………………………………………B．分析报告单………………………………………………………………C．标准品的界定……………………………………………………………五、IND 中的分析方法验证……………………………………………………..六、NDA、ANDA、BLA 和PLA 中分析方法的内容和格式…………………A．基本方法…………………………………………………………………B．取样………………………………………………………………………C．仪器和仪器参数…………………………………………………………. D．试剂………………………………………………………………………E．系统适应性实验…………………………………………………………. F．标准品的制备……………………………………………………………..G.操作过程…………………………………………………………………….H.操作程序……………………………………………………………………I．计算…………………………………………………………………………J.结果报告……………………………………………………………………. 1．通则……………………………………………………………………2．杂质分析规程…………………………………………………………七、NDA，ANDA，BLA 和PLA 中的分析方法验证………………………….. A．非药典分析方法…………………………………………………………1. 验证项目……………………………………………………………2. 其它验证资料……………………………………………………….(1) 讨论可能会形成的异构体并讨论异构体的控制…………………..a. 耐用性…………………………………………………….b. 强降解实验………………………………………………c.仪器输出/原始资料………………………………………i. 有机杂质……………………………………………ii. 原料药……………………………………………….iii. 制剂………………………………………………….(2) 各类检测的推荐验证项目…………………………………………..a. 鉴别………………………………………………………....b. 杂质………………………………………………………..c. 含量………………………………………………………..d. 特定实验…………………………………………………….B．药典分析方法(21CFR 211.194(a)(2))…………………………………..八. 统计分析…………………………………………………………………….A．基本原则………………………………………………………………B:对比研究…………………………………………………………………C:统计………………………………………………………………………九、再验证………………………………………………………………………十、分析方法验证资料：内容和数据处理…………………………………….A．分析方法验证资料…………………………………………………….B：样品的选择和运输…………………………………………………….C：各方职责……………………………………………………………….1.申请人……………………………………………………………….2.化学评审官………………………………………………………….3.FDA 实验室………………………………………………………….4.检查官……………………………………………………………….十一、方法学……………………………………………………………………A．高效液相色谱(HPLC)………………………………………………….1.色谱柱……………………………………………………………….2.系统适应性研究…………………………………………………….3.操作参数…………………………………………………………….B．气相色谱(GC)………………………………………………………….1.色谱柱……………………………………………………………….2.操作参数……………………………………………………………..3.系统适应性实验……………………………………………………..C：分光光度法，光谱法和相关的物理方法………………………………D：毛细管电泳(CE)…………………………………………………………E：旋光度……………………………………………………………………F：和粒径分析相关的分析方法……………………………………………G：溶出度…………………………………………………………………..H：其它仪器分析方法………………………………………………………附录A……………………………………………………………………………….. 附录B……………………………………………………………………………….. 术语表……………………………………………………………………………….一、绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。
准备FDA认证前检查中英文对照
Purpose of a pre-Approval Inspection 认证前检验的目的
Ensure that data submitted in the ANDA or DMF submission is supported by raw data at the facility
确保在ANDA或DMF文件中提交的数据以设施的原始数据为依据
FDA什么时候审查ANDA
After the ANDA holder files the ANDA ANDA持有人将ANDA归档后
Because of backlogs, expect at least 6 month delay before reviewing 由于积压，预计至少延迟6个月才能被审查
The Company Presentation (30-45 minutes)
公司介绍（30-45分钟）
History of Business企业历史
When was it founded? By whom? 什么时候成立？由谁创建？
Important milestones during company development 公司发展中的重要里程碑
Name and title displayed at initial meeting 姓名和标题呈现在首次会议上
Name tags on uniform during inspection 检查期间所有姓名标签格式应统一
Consider also a handout with the following information for key people: 还考虑分发含有以下信息的资料给关键人员： ▪ Full name (and English surname if applicable) 全名（如果适用加上英文姓氏） ▪ Title 标题 ▪ Thumbnail photograph 照片缩图
FDA分析方法验证指南中文
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B．分析报告单 对于非官方标准品，在申请的分析方法和控制章节中应当要提供该标准品的分析报告
四、标准品
A．标准品的类型 可以从 USP/NF 处或其它官方(比如说，CBER，21CFR 610.20)获得标准品 (也就是一级
对照品)。如果不能确定一标准品的来源是否会被 FDA 认为是官方来源，申请者应当要向适 当的化学评审人员咨询。如果没有官方来源，则被用来作标准品的物质应当要有尽可能高的 纯度，并得到充分界定。
B．取样………………………………………………………………………
C．仪器和仪器参数…………………………………………………………………………
E．系统适应性实验………………………………………………………….
F．标准品的制备……………………………………………………………..
G.操作过程…………………………………………………………………….
H.操作程序……………………………………………………………………
I．计算…………………………………………………………………………
J.结果报告…………………………………………………………………….
1．通则……………………………………………………………………
C. 稳定性指示分析 稳定性指示分析是能检测出原料药或制剂的某些性质随着时间的延长而出现的变化的
定量分析方法。 稳定性指示分析能不受降解产物，工艺杂质，赋形剂或其它潜在杂质的影响而准确测定
其中的活性成分。 如果申请者递交了用于放行检测的非稳定性指示分析方法，则应当要有能定性和定量地
监测杂质，包括降解产物，的分析方法对其进行补充。稳定性试验中所用的含量分析方法应 当要有稳定性指示能力，除非有科学的理由能证明其合理性。
FDA临床试验常见词汇中译文对照
FDA临床试验常见词汇中译文对照Aaction letter 决定通知active comparator 活性药物对照组active control = AC 阳性对照，活性对照active ingredient 有效成分Active Substance Master File (ASMF) 欧洲药物主文件acute myocardial infarction 急性心肌梗死acute tibial fractures 急性胫骨骨折adalimumab (Humira) 阿达木单抗adaptive design 自适应设计adaptive randomization 自适应随机ADE = adverse drug event 药物不良事件Adenoviral Vectors 腺病毒载体adequate and well-controlled studies 充分严格的对照研究ADHD = Attention-deficit hyperactivity disorder注意力缺陷多动障碍; 注意力不足过动症; 多动症adhesion barrier product 防黏著产品adjuvant 助剂; 佐剂auxiliary;adjuvant therapy 佐药疗法，辅助疗法ADL = activities of daily living 日常生活活动能力ADME = absorption, distribution, metabolism, and excretion(药物)吸收、分配、代谢和排除ADR = adverse drug reaction 药物不良反应adrenal cortex 肾上腺皮质adrenal cortical hormone 肾上腺皮质激素adrenal gland 肾上腺adrenaline 肾上腺素adulterated devices 掺假器械adverse drug reaction = ADR药物不良反应adverse effect 副作用adverse event = AE 不良事件adverse medical events 不良医学事件adverse reaction (adverse event) 药物不良反应advisory 提醒advocacy and support groups 倡导和支持团体AE = adverse event 不良事件AERS = Adverse Event Reporting System 不良事件报告系统BBIMO Bioresearch Monitoring Program 生物研究监测bioavailability (F) 生物利用度biochemical drugs 生化药品biocides 生物杀灭剂; 杀生物剂biocompatibility 生物相容性biodegradable 生物分解bio-engineered, transgenic food 转基因食物bioequivalence; bioequivalent 生物等效应biofilm 细菌薄膜, 生物膜biologic 生物制品biological response modifiers BRM 生物应答调节剂biological therapeutic agents 生物治疗药剂biomarker 生物标志物biometrics 生物统计; 生物识别技术bion stimulator 生物体刺激器bionic knee 仿生膝关节biopharma: biopharmaceutical products 生物药物产品bipolar 双相燥郁症birth defect 出生缺陷, 新生儿缺陷, 先天缺陷BLA = biologic license application 生物制品许可申请blank control 空白对照blend uniformity analysis 混合均匀度分析blind 盲法blind codes 编制盲底blind review 盲态审核blinding method 盲法blinding/ masking 盲法，设盲blister packaging 泡罩包装; 水泡眼block 分段;层block size 每段的长度blocked randomization 区组随机Ccase history 病历case record form = CRF病例报告表/病例记录表case report form 病例报告表cash curve 现金曲线cash trap 现金陷阱; 现金套牢categorical variable 分类变量CLIA Clinical Laboratory Improvement Amendments临床实验室改进修订案clinical (human) data 临床数据clinical endpoint临床终点clinical equivalence 临床等效应clinical hold 临床试验暂停通知clinical investigator 临床研究者Clinical Pharmacists 临床药师Clinical Research Coordinator = CRC临床研究协调者clinical study 临床研究Clinical Study Application = CSA临床研究申请clinical study report 临床试验的总结报告clinical trial 临床试验clinical trial application = CTA 临床试验申请clinical trial exemption = CTX 临床试验免责clinical trial protocol = CTP 临床试验方案Clinical Trial Report = CTR临床试验报告clinically significant results 有临床意义cohort 队列cohort studies 队列研究co-investigator = CI合作研究者comparison 对照Compassionate Use 体恤使用competitive labeling 优越标签Complementary And Alternative Therapy 补充性和非传统治疗Complete response 完全有效compliance 遵守；对遵守法规情况的监管composite variable 复合变量Compression Test 压缩试验computer-assisted trial design= CATD计算机辅助试验设计Con Meds = concomitant medications 联合用药confidence interval 可信区间confidence level 置信水平Confidentiality Regarding Trial Participants 为试验参与者保密control对照control group 对照组controlled clinical trials 临床对照实验Controlled Trials 对照试验Critical Path 关键路径CRM = continual reassessment method 连续重新评估方法crossover design 交叉设计cross-over study 交叉研究crossover therapy 交叉治疗CRF = case report form 病例报告表dosage form 剂型dosage regimen 给药方案dose-ranging study 剂量范围研究dose-reaction relation 剂量－反应关系dose-related adverse reactions 剂量相关的不良反应double blinding 双盲double dummy 双模拟double dummy 双模拟double dummy technique 双盲双模拟技术double-blind study 双盲研究Double-Masked Study 双盲研究DRGs = Diagnosis Related Group System 疾病诊断相关分组drop out 脱落drop test 落震试验;跌落试验drug eluting coronary stents 药物洗脱支架drug product 药物产品drug substance 原料药drug-drug interaction56 药物-药物相互作用drug-food interaction 药物-食物的相互作用EEPS = Electronic Entry Processing System 电子录入处理系统effectiveness 疗效efficacy 有效性测定efficacy (Of a drug or treatment) 药效；药品疗效EEMEA = European Medical Evaluation Agency; European Agency for the Evaluation of Medicinal Products; European Medicines Agency 药物评价机构; 欧洲医药品管理局emergency envelope 应急信件Empiric Bayesian Multiple Gamma-Poisson Shrinker经验性贝氏法（伽玛泊松分布缩检法）empirical 经验性endpoint 终点endpoint criteria 终点指标factorial design 析因设计factorial trial 析因试验failure 无效，失败Fair Packaging and Labeling Act (1966) 公平包装和标签法False Claims Act 防制不实请求法false therapeutic claims 错误的疗效声明full analysis set 全分析集full factorial design 全因子试验法Iinclusion criteria 入选标准inclusion/exclusion criteria 入选/排除标准incremental exposure 食品中递增摄入量incubation period/latency period 潜伏期IND = Investigational New Drug 临床研究新药INDA = investigational new drug application NDA前申报阶段indemnity insurance 赔偿保险Independent Data Monitoring = IDM独立数据监察Independent Data Monitoring Committee = IDMC独立数据监察委员会independent ethics committee = IEC 独立伦理委员会indications 适应症investigational new drug = IND 临床研究新药investigational product 试验药物investigator 调研人员investigator's brochure = IB 研究者手册Mmasked 设盲mean absorption time = MAT(药物在体内的)平均吸收时间mean disintegration time = MDIT(药物在体内的)平均崩解时间Mean Dissolution Time = MDT (药物在体内的)平均释放时间Mean Residence Time = MRT(药物在体内的)平均滞留时间medical governance 医药治理Medicare 老年医疗保险制度；联邦老年医保medication guides (for patients) 用药指南Medicines Control Agency = MCA英国药品监督局Misbranding 错误标签; 冒牌Miscoding 编码错误missing value 缺失值mixed effect model 混合效应模式MLD = minimal lethal dose 最小致死剂量MoA = Mechanism of Action 作用机制;作用机理monitor 监查员monitoring plan监查计划monitoring report 监查报告MR = moderate response 好转MRA = Agreement on Mutual Recognition 相互承认协定MTD = maximal tolerance dose 最大耐受剂量multicenter trial 多中心试验multi-drug resistance 多药物抗药性multiple arm trials 多治疗组的试验mutual recognition procedure (EU) 相互承认程序OOS = Overall survival 总生存率Pparallel group design 平行组设计parameter estimation 参数估计parametric release 参数放行parametric statistics 参数统计方法patient file 病人档案patient global; pt global 病人总体评价patient history 病历per protocol ( PP) analysis 符合方案分析PFS = progression-free survival 无疾病进展存活率PGE = patient global evaluation 病人总体评价PHA = preliminary hazards analysis 预先危险分析pharmaceutical equivalence 药剂等效性pharmaceutics药剂学pharmacodynamics=PD 药物效应动力学; 简称药效学pharmacoepidemiology 药物流行病学pharmacokinetics = PK 药代动力学; 简称药动学pharmacology 药理学Pharmacovigilance105 药物警戒pharmacy 配药学PharMetrics claims database 索赔数据库PhRMA = Pharmaceutical Research and Manufacturers of America美国药物研究与生产商协会PIC=Pharmaceutical Inspection Convention 药品检查协定PIC/S Pharmaceutical Inspection Cooperation Scheme 药物检查合作计划pipeline assets 开发中产品PK = pharmacokinetics 药物代谢动力学; 药动学，药代动力学placebo 安慰剂placebo control 安慰剂对照placebo controlled study 安慰剂对照研究placebo effect 安慰剂效应PMA = premarket approval 上市前许可; 销售前批准PMCs = post marketing commitments 承诺药品上市后的继续研究PMDRA = Post Marketing Drug Risk Assessment 上市后药品风险评估(办公室) PMHx = Past Medical History 既往病史PMN = Premarket Notification 销售前通知PMS = Premenstrual syndrome 经前综合症POC (Proof-of-concept) Clinical Trials 概念证明POC = point-of-care testing 床旁分析polytomies 多分类pooled analysis = PA 荟萃分析postmarket surveillance 上市后监督post-marketing surveillance; postmarket safety surveillance 销售（上市）后监督power 把握度; 检验效能Pp = Process Performance 工序绩效Ppk = Process Performance Index 工序绩效指数precautions 慎用；注意事项precision 精密度preclinical (animal) data 临床前(动物实验)数据preclinical study 临床前研究predicate device = legally marketed device that is not subject to Premarket Approval (PMA)和已合法在市场上销售的且不需要做PMA“销售前批准”的Pre-market Approval (Application) = PMA上市前许可（申请）premarket notification 上市前通知pre-marketing surveillance 销售（上市）前监督preparing and submitting 起草和申报prescription drug 处方药preservation 保藏prevalence 患病率prevention trials预防试验primary (coronary) event 原位病变primary endpoint 主要终点primary mode of action = PMOA 首要作用模式primary variable 主要变量principal investigator = PI主要研究者Principles of Qualification 确认（验证）原则process controls 工艺控制process validation 工艺验证product codes 产品的号码product differentiation 产品差异化，产品特色化product license = PL 产品许可证product life cycle (PLC) 产品生命周期prognosis 预后progression-free survival = PFS 无进展生存progressive Disease PD 病情进展proof of principle study 原理循证研究propensity score 倾向性评分protocol 试验方案; 方案protocol amendment 方案补正prototype design 原型设计protozoa 原生动物门proven acceptable Range = PAR 确定可接受范围PTC = Product Technical Complaints 药品技术投诉Qqualification system for licensed pharmacist 执业药师资格准入制度qualified health claims 有保留的健康宣称Qualified Person = QP 受权人quality assurance = QA质量保证quality assurance unit = QAU质量保证部门quality control = QC 质量控制quality management systems 质量管理体系quality of life trials or supportive care trials 生存质量试验quality risk management = QRM 质量风险管理quantitative risk assessment 量化风险评估Rrandomization 随机化randomized trial 随机化试验randomized, double blinded clinical trial 随机双盲对照研究range check 范围检查rating scale 量表RCT = randomized clinical trials 随机临床试验RCT = randomized controlled trial 随机对照试验RDE: remote data entry 远距数据输入ready-to-eat foods 即食食品reagents 试剂recall 召回; 强制回收RECIST = Response Evaluation Criteria in Solid Tumors 实体瘤的疗效评价标准reconditioning 整改; 货物重整理；货物重包装recycled plastics 可循环利用塑料制品reference product 参比制剂reference samples 标准样品regulatory methodology 质量管理方法regulatory methods validation 管理用分析方法的验证（FDA对NDA提供的方法进行验证）regulatory specification 质量管理规格标准（NDA提供）rejection 排异remote monitoring system 远程监测系统; 远程监控REMS = Risk Evaluation and Mitigation Strategies 风险评估和减缓战略risk 受害risk assessment (risk analysis + risk evaluation) 风险评估，论证risk classification 风险分类;Risk Communications Advisory Committee 风险交流咨询委员会risk evaluation (part of risk assessment) 风险评价risk/ benefit analysis 风险-获益分析risk-benefit ratio 效益/风险比route of administration 给药途径royalties 专利使用费RPN = Risk Priority Number 风险优先指数RR = Response rate 缓解率RSD = (intra-day and inter-day) relative standard deviations (日内和日间) 相对标准差Ssafety advisory 安全建议safety evaluation 安全性评价safety evaluators 安全性评估人员safety set 安全性评价的数据集screening trials 筛选性试验SD = standard deviation 标准(偏)差SE = substantial equivalence 实质上的等同Seal Strength Test 密封强度试验sequence 试验次序SFDA 129= State Food And Drug Administration 国家食品药品监督管理局SG & A= Sales, General and Administration 销售、管理和一般费用shaft 传动轴SHEA = Society for Healthcare Epidemiology of America 美国医院流行病学学会sheaths 护套shelf life 保存期限; 保质期SIC codes = Standard Industrial Classification codes 标准产业分类代码side effects 副作用significance level 显著性水平Significant Risk (SR) 显著的危险性simple randomization 简单随机simulation model 仿真模型single blinding单盲single-blind study 单盲研究single-masked study 单盲研究site assessment = SA现场评估site audit 试验机构稽查SMDA = Safe Medical Devices Act of 1990 1990年安全医疗器械法SMF = Site Master File 生产场所主文件sNDA = supplemental NDA 疗效补充新药上市申请sponsor-investigator = SI 申办研究者spontaneous reports; voluntary reports 药品不良反应自愿报告SPS = Agreement on the Application Of Sanitary and Phytosanitary Measures卫生与植物卫生措施实施协议;简称SPS协议SSI = surgical site infection 手术部位感染SSOPs = Sanitation Standard Operating Procedures 卫生标准操作程序standard curve 标准曲线standard deviation 标准偏差standard drug 标准药物standard operating procedure = SOP 标准操作规程standard treatment 标准治疗Standards Of Care131 医护标准State Food and Drug Administration = SFDA国家食品药品监督管理局statistic 统计量statistical analysis plan = SAP 统计分析计划statistical model 统计模型statistical significance 统计学意义statistical tables 统计分析表Statisticians in the Pharmaceutical Industry = PSI制药业统计学家协会steady-state Area Under the Curve = AUCss稳态药时曲线下面积/稳态血药浓度－时间曲线下面积stratified 分层study audit 研究稽查study endpoint 研究终点Study Personnel List = SPL研究人员名单study site研究中心study type 研究类型subchronic toxicity studies 亚慢性毒性研究subgroup 亚组sub-investigator 助理研究者subject 受试者subject diary = SD 受试者日记subject enrollment 受试者入选subject enrollment log = SEL受试者入选表Subject Identification Code List = SIC受试者识别代码表subject recruitment 受试者招募subject screening log = SSL受试者筛选表submission 申报；递交subspecialties, internal medicine 亚专科,内科substantial equivalence to legally marketed (predicate) device 和已合法在市场上销售的且不需要做PMA“销售前批准”的相似产品有实质上的等同Ttrain-the-trainer program 培训者培训计划treatment group 试验组treatment IND 治疗性试验性新药申请treatment trials 治疗性试验trial error 试验误差trial initial meeting 试验启动会议trial master file 试验总档案trial objective 试验目的trial site 试验场所TRICARE 军队医疗系统triple blinding 三盲two one-side test 双单侧检验UAE = unexpected adverse event 预料外不良事件unblinding 破盲;揭盲under reporting bias 少报偏差unexplained syncope 不明原因晕厥unresectable 不能手术切除variability 变异variable 变量WHO International Collaborating Center for Drug Monitoring(世界卫生组织)国际药物监测合作中心WHO International Conference of Drug Regulatory Authorities= WHO-ICDRAWHO国际药品管理当局会议WHO Programme for International Drug Monitoring = PIDMWHO 国际药物监测合作计划。
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）。
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。
中英文-美国FDA_GMP检查
More Records 更多的记录
• Process Validation 工艺验证 • Equipment Qualification 设备确认 • Computer System Validation 计算机系统验证 (Protocol and Executed Protocol) (方案和已执行方案)
Objectives of Inspection 检查的目标
• Conduct the inspection in accordance with FD&C Act and Current Good Manufacturing Practice (CGMP) Regulations 检查的执行依据《联邦食品，药品和化妆品法》(FD&C Act) 及现行 药品生产管理规范(CGMP) 条例 • Accomplish what is necessary per the established, supporting Compliance Policy Guidance Manual 检查执行的程度依据 符合性方针指导手册 – 7356.002 “Drug Manufacturing Inspections” 7356.002 “药品生产检查” • “Systems Approach” “系统化方法” • Accomplish necessary, additional questions/concerns listed in the inspection assignment (“For Cause” Inspection) 要完成必要的检查、其它问题/额外关注点见“追因”检查的检查任务 分配
The CGMP Regulation CGMP 法规
美国FDA人用药品中英文翻译
美国FDA人用药品中英文翻译美国FDA人用药品中英文翻译1.总则 GENERAL2. 新药 NEW DRUGS3. 试验用新药申请 INVESTIGATIONAL NEW DRUG APPLICATION4.为FDA批准上市新药的申请 APPLICATIONS FOR FDA APPROVAL TO MARKET A NEW DRUG5.诊断用放射性药品 DIAGNOSTIC RADIOPHARMACEUTICALS（奥咨达医疗器械咨询）6.罕见病药 ORPHAN DRUGS7.生物利用度与生物等效性要求 BIOAVAILABILITY AND BIOEQUIVALENCE REQUIREMENTS8.含有酒精的预期用于口部摄入的非处方药品 OVER-THE-COUNTER DRUG PRODUCTS INTENDED FOR ORAL INGESTION THAT CONTAIN ALCOHOL 9. 一般认为安全与有效以及不错误标识的非处方人用药品OVER-THE-COUNTER (OTC) HUMAN DRUGS WHICH ARE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED（只专注于医疗器械领域）10.用于非处方的人类使用的抗酸产品 ANTACID PRODUCTS FOROVER-THE-COUNTER (OTC) HUMAN USE11. 用于非处方的人类使用的抗胃肠气胀产品 ANTIFLATULENT PRODUCTS FOR OVER-THE-COUNTER HUMAN USE12. 用于非处方的人类使用的局部抗菌药品 TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE 13. 用于非处方的人类使用的止泻药品 ANTIDIARRHEAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE14. 用于非处方的人类使用的止吐药品 ANTIEMETIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE15. 用于非处方的人类使用的帮助夜间睡眠的药品 NIGHTTIME SLEEP-AID DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE16. 用于非处方的人类使用的兴奋药品 STIMULANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE17.用于非处方的人类使用的感冒、咳嗽、过敏症药、支气管扩张以及平喘药品 COLD, COUGH, ALLERGY, BRONCHODILATOR, AND ANTIASTHMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE 18. 用于非处方的人类使用的内服的止痛、退热以及抗风湿药品INTERNAL ANALGESIC, ANTIPYRETIC, AND ANTIRHEUMATIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE19. 用于非处方的人类使用的局部的耳部药品 TOPICAL OTIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE20. 用于非处方的人类使用的肛肠药品 ANORECTAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE21.用于非处方的人类使用的皮肤保护药品 SKIN PROTECTANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE22. 用于非处方的人类使用的外部的止痛药品 EXTERNAL ANALGESIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE23. 用于非处方的人类使用的眼科药品 OPHTHALMIC DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE24.用于非处方的人类使用的止汗药品 ANTIPERSPIRANT DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE25. 用于非处方的人类使用的遮光药品 SUNSCREEN DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE [STAYED INDEFINITELY]26.用于非处方的人类使用的防龋药品 ANTICARIES DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE27. 用于非处方的人类使用的其他内服药品 MISCELLANEOUS INTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE28. 用于非处方的人类使用的其他外用药品 MISCELLANEOUS EXTERNAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE29. 一般认为安全与有效以及不错误标识的处方人用药品：用于研究的药品 PRESCRIPTION DRUGS FOR HUMAN USE GENERALLY RECOGNIZED AS SAFE AND EFFECTIVE AND NOT MISBRANDED: DRUGS USED IN RESEARCH30. 在用于非处方销售的药品与器械上关于警告的解释性声明INTERPRETATIVE STATEMENTS RE WARNINGS ON DRUGS AND DEVICES FOR OVER-THE-COUNTER SALE。
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I. INTRODUCTIONThis guidance provides recommendations to applicants on submitting analytical procedures, validation data, and samples to support the documentation of the identity, strength, quality, purity, and potency of drug substances and drug products.1. 绪论本指南旨在为申请者提供建议，以帮助其提交分析方法，方法验证资料和样品用于支持原料药和制剂的认定，剂量，质量，纯度和效力方面的文件。
This guidance is intended to assist applicants in assembling information, submitting samples, and presenting data to support analytical methodologies. The recommendations apply to drug substances and drug products covered in new drug applications (NDAs), abbreviated new drug applications (ANDAs), biologics license applications (BLAs), product license applications (PLAs), and supplements to these applications.本指南旨在帮助申请者收集资料，递交样品并资料以支持分析方法。
这些建议适用于NDA，ANDA，BLA，PLA及其它们的补充中所涉及的原料药和制剂。
The principles also apply to drug substances and drug products covered in Type II drug master files (DMFs). If a different approach is chosen, the applicant is encouraged to discuss the matter in advance with the center with product jurisdiction to prevent the expenditure of resources on preparing a submission that may later be determined to be unacceptable.这些原则同样适用于二类DMF所涉及的原料药和制剂。
如果使用了其它方法，鼓励申请者事先和FDA药品评审中心的官员进行讨论，以免出现这种情况，那就是花了人力物力所准备起来的递交资料后来发现是不可用的。
The principles of methods validation described in this guidance apply to all types of analytical procedures. However, the specific recommendations in this guidance may not be applicable to certain unique analytical procedures for products such as biological, biotechnological, botanical, or radiopharmaceutical drugs.本指南中所述的分析方法验证的原则适用于各种类型的分析方法。
但是，本指南中特定的建议可能不适用于有些产品所用的特殊分析方法，如生物药，生物技术药，植物药或放射性药物等。
For example, many bioassays are based on animal challenge models, 39 immunogenicity assessments, or other immunoassays that have unique features that should be considered when submitting analytical procedure and methods validation information. 比如说，许多生物分析是建立在动物挑战模式，免疫原性评估或其它有着独特特性的免疫分析基础上的，在递交分析方法和分析方法验证资料时需考虑这些独特的性质。
Furthermore, specific recommendations for biological and immunochemical tests that may be necessary for characterization and quality control of many drug substances and drug products are beyond the scope of this guidance document.而且，许多原料药和制剂的界定和质量控制所需的生物和免疫化学检测并不在本指南的范围之内。
Although this guidance does not specifically address the submission of analytical procedures and validation data for raw materials, intermediates, excipients, container closure components, and other materials used in the production of drugsubstances and drug products, validated analytical procedures should be used to analyze these materials.尽管本指南并不专门叙述原料，中间体，赋形剂，包装材料及原料药和制剂生产中所用的其它物料的分析方法及分析方法验证资料的递交，但是应该应用验证过的分析方法来分析检测这些物质。
For questions on appropriate validation approaches for analytical procedures or submission of information not addressed in this guidance, applicants should consult with the appropriate chemistry review staff at FDA.对于本指南中未提及的关于分析方法验证和资料提交方面的问题，请向FDA相关的化学评审人员咨询。
This guidance, when finalized, will replace the FDA guidance for industry on Submitting Samples and Analytical Data for Methods Validation (February 1987). 本指南，一旦定稿，将取代FDA于1987年2月份发布的工业指南：分析方法验证所需提交的样品和分析资料。
II. BACKGROUNDEach NDA and ANDA must include the analytical procedures necessary to ensure the identity, strength, quality, purity, and potency of the drug substance and drug product, including bioavailability of the drug product (21 CFR 314.50(d)(1) and 314.94(a)(9)(i)).II. 背景每个NDA和ANDA都必需包括必要的分析方法以确保原料药和制剂的认定，剂量，质量，纯度和效力，还包括制剂的生物利用度(21 CFR 314.50(d)(1) 和314.94(a)(9)(i))。
FDA验证文件现场备查，可以不与DMF一起交。
Data must be available to establish that the analytical procedures used in testing meet proper standards of accuracy and reliability (21 CFR 211.165(e) and 211.194(a)(2)).必须要有资料来论证所用的分析方法是符合一定的准确度和可靠性标准的。
Methods validation is the process of demonstrating that analytical procedures are suitable for their intended use. The methods validation process for analytical procedures begins with the planned and systematic collection by the applicant of the validation data to support the analytical procedures.分析方法验证是论证某一分析方法适用于其用途的过程。
分析方法的验证过程是从申请者有计划地系统性收集验证资料以支持分析方法开始的。
The review chemist evaluates the analytical procedures and validation data submitted in the NDA or ANDA.审评化学家会对NDA或ANDA中的分析方法和验证资料进行评审。
On request from FDA, an NDA or ANDA applicant must submit samples of drug product, drug substance, noncompendial reference standards, and blanks so that the applicant's drug substance and drug product analytical procedures can be evaluated by FDA laboratories (21 CFR 314.50(e) and 314.94(a)(10)).一旦FDA有要求，则NDA或ANDA的申请者必须提交制剂，原料药，非药典对照品和空白以使FDA实验室能对申请者所用分析方法进行评审(21 CFR 314.50(e) and 314.94(a)(10))。