警告信精选W194W156中英文版

1、FDA Warning Letters, Form 483 Observations, Establishment Inspection ReportsFDA警告信，483缺陷表，检查报告Important: Warning letters should be interpreted in the context of full content. Just looking at extracts may be misleading. And sometimes they include good advice from the FDA not mentioned in the extracts

2、.重要的警告信可能会用完整的上下文内容来解释。只看摘要可能会导致误解。有时候完整的内容会包含摘要中没有包括的来自FDA的建议。W-194Keywords: GLP, raw data, reason for change, responsibilities of QAU, integrity of study data关键词：GLP, 原始数据，变更理由，质保责任，研究数据的完整性 Primary Deviations: Incomplete study records, no reason for change of study records, QAU not fulfilled its

3、responsibilities, raw data, no assurance of the quality and integrity of study report, no final study report, no or inadequate testing and calibration of equipment 主要错误：研究数据不完全，没有理由地改变研究记录，质保未履行职责，原始数据，研究报告的质量和完整性没有保证，没有最终研究报告，检测和仪器检验没有或不够。 Examples: - Failure of the study director to assure that al

4、l experimental data were accurately recorded and verified and document the reason for any change in the entries- For study xxx your study director failed to assure that dosing were accurately recorded to confirm that study animals received protocol-specified doses of the vehicle.- Failure of QAU to

5、assure that reported results in the final study report accurately reflected the raw data- Failure of QAU to maintain written and properly signed records of each periodic inspection- Failure to identify the test and control articles with appropriate characteristics in the final report- Failure to ade

6、quately test, calibrate, and/or standardize all equipment used the generation, measurement and assessment of data 事例：研究主管未能保证所有的实验数据被准确记录，也未能确认任何条目的变更理由并记录。为研究xxx，你们的研究主管未能保证准确记录剂量以确保试验动物接受研究草案中规定的剂量质保未能保证最终研究报告中的结果准确反映原始数据质保未能在阶段性的检查中持续填写记录并适当签名在最终研究报告中没有用合适的特定的格式来鉴别测试和控制内容没有对产生，测量及评估数据的设备进行足够的测试，校

7、准和/或标准化W-193Keywords: Batch records, method validation, cleaning validation, equipment calibration 关键词：批记录，方法验证，清洁验证，设备校准 Primary Deviations: Incomplete batch records, insufficient documentation of method validation, inadequate documentation of laboratory equipment calibration, shipment of APIs to U

8、S from non certified manufacturing site 主要错误：批记录不完整，方法验证文件不够，实验室设备校准文件不充分，从未经确认的生产地点向美国出货 Examples: - Batch production records do not include complete information relating to the production and control of each API batch- Method validation documentation did not include appropriate data to verify that

9、 the analytical method produced accurate and reliable data- Production equipment was not adequately cleaned and was not maintained in a good state of repair - Laboratory equipment calibration was not adequately documented. 事例：批生产记录没有包括与每个批次的生产与控制相关的完整信息方法验证文件没有包含适当的数据以确认分析方法能产生准确和可靠数据生产设备清洁不够，且在修理状态

10、下没有维修实验室设备校准没有被完全记录 W-192Keywords: Data security, raw data, passwords, laboratory software关键词：数据安全性，原始数据，密码，实验室软件  Primary deviations: no individual passwords, ability to overwrite raw data.   主要错误：没有个人密码，可以改写原始数据  Examples: - Validation of the (brand name) laboratory s

11、oftware used to control instruments, generate data, perform calculations, and store data from raw material and finished product testing failed to demonstrate adequate security. Analysts have the ability to overwrite original data, and are not required to utilize the protection of individual password

12、s. - The corresponding EIR further states: During discussions and lab demonstrations, it was determined that neither system prevents analysts from overwriting original raw data. A review of the software validation showed initial failures for modules demonstrating the ability to delete or overwrite d

13、ata. Documentation in the validation report stated that this capability could not be changed. During the laboratory demonstration, I observed the statement, "Data will be overwritten" with the option to ignore this. - In addition to the ability to overwrite original data, the analysts are

14、not required to utilize the protection of passwords since they are considered to have "limited access". I stated that each analyst needs to have their own password to access the system to help ensure data security and to track the usage by individuals.   事例：用来控制设备，产生数据，进行校准， 储存原料

15、和成品检验数据的实验室软件的验证中没有论证安全性。分析人员能够改写原始数据。没有要求对个人密码进行保护相对应的EIR状态：在讨论和实验室论证中发现，系统并不能防止分析人员改写原始数据。软件验证回顾表明记录数据删除和数据改写的模块最初就失灵了。验证报告文件中表明这种能力不能被改变。在实验室论证中，我看到不予理会“数据可以被修改”的声明。除了修改原始数据的能力外，分析人员没有要求保护密码，尽管他们也认为登陆要受到控制。我建议每个分析人员都需要用自己的密码来登陆系统以确保数据安全及跟踪个人使用情况W-191Keywords: Vendor software, software validation关

16、键词：供应商软件，软件验证  Primary deviations: vendor supplied computer software not validated,   主要错误：供应商提供未经验证的软件  Examples:   事例-The performance of the computer software has not been verified. Specifically your firm has not verified your computer software program in al

17、l aspects of their donor referral operations to ensure that electronic records are trustworthy, accurate and reliable. The related EIR further explained: The firm uses a computer software program called (brand name) that is manufactured by (vendor name). 计算机软件性能未经确认，特别是你公司未确认所有捐赠转诊方面的计算机软件程序以确保电子纪录是

18、可信，准确和可靠的。相关的EIR解释：公司使用某公司生产的某软件。- During the inspection, I asked if the computer software has been validation to assure that it performs for it's intended use. I was told that the software was validated by the manufacturer. The managing director provided me a copy of the letter the received

19、 from (the vendor). The letter indicated that the software was validated. She also the gave me a copy of validation information that was obtained from (the vendor) during the inspection.在检查中，我问计算机软件是否已验证，确保能实现预计的功能。答案是软件已由生产商验证。管理者提供了一份供应商的信件的复印件。信件表明软件已验证。在检查中，她还提供了从供应商处获得的验证信息的拷贝。- I told the mana

20、ging director I still need to see what they have done to validate the system since the computer was making a decision to accept or reject potential donors. The managing director and the Manager of the Communications Center told me that they were unaware they the company had to validate the software

21、because it was validated by (the vendor) and that was their reason for purchasing the version of software instead of the COTS (Commercial Off The Shelf) version of the software that is also manufactured by (the vendor).  我告诉管理者，由于由计算机决定接受或拒绝可能的捐赠者，所以我需要了解他们如何验证系统。管理者和交流中心的经理告诉我他们没有意识到他们必须对

22、供应商验证过的软件进行验证。他们购买这个版本的软件而不是商业现成版，也是因为这个版本的软件供应商已经验证过（商业现成版也由同一供应商生产）。W-190Keywords: IQ, OQ, PQ, retrospective validation, legacy systems, no review of electronic records关键词：IQ,OQ,PQ, 回顾性验证，遗赠系统，没有电子纪录的回顾  Primary deviations: no validation of legacy systems, no formal change control. no de

23、sign control for customized software elements, no review of electronic records 主要错误：没有遗赠系统的验证，没有正式的变更控制，没有对定制的软件要素进行设计控制，没有电子纪录的复核  Examples: 事例：- No IQ, OQ or PQ has been performed throughout the life of the system. No validation reports have been generated historically. 在系统的整个使用周期中没有进行IQ

24、,OQ,PQ。没有验证报告。- Current efforts to retrospectively validate the system have progressed through the approval of an IQ protocol, however, this protocol has not yet been executed. OQ and PQ efforts have not yet been developed as part of these current validation efforts.现在的努力是对系统进行回顾性验证，已批准IQ草案，但还未实施。OQ

25、,PQ还未作为现阶段验证的一部分。- The (system) has not been maintained under established procedures for change control. This is true throughout the life of this software application. 系统没有在已建立的变更程序下进行维护。在整个软件使用过程中都是如此。- The firm has failed to generate or maintain design control documentation sufficient to define al

26、l customized elements making up the (system) configuration (i.e., functional or structural design documentation defining all program making up (the system)该公司未能产生或维护足够的设计控制文件以定义所有构成系统的定制的要素（比如：定义构成系统的所有程序的功能性或结构性设计）- Electronic records generated during manufacture of APIs were not reviewed prior to

27、release of validation lots or for any lots manufactured thereafter to include the most recently released API lot. 在验证批或之后生产的任何批次放行前没有复核在生产APIs过程中产生的电子记录。最近放行的批次也是如此。W-189Keywords: Microsoft Excel, Microsoft Word, Off-the-shelf software, Validation关键词：微软Excel, 微软 Word, 现成软件  Primary deviati

28、ons: Off-the shelf software not validated 主要错误: 现成软件没有验证  Examples: 事例：Failure to assure that when computers or automated data processing are used as part of the production or quality system the manufacturer shall validate computer software for its intended use according to an established

29、protocol, as required by 21 CFR 820.70(i). 没有按照21 CFR 820.70(i)要求制定草案来确保作为生产或质量系统的一部分的计算机或自动数据处理会被验证，以满足计划的使用目的。- Electronic records are used but there was no software validation. 使用电子记录但软件未经验证。- No procedures are established to validate for its intended purpose the Microsoft Word or Microsoft Excel

30、 software used in creating and maintaining nonconformance records, product return records, internal audit corrective records, or corrective action records. 没有制定程序来验证微软Excel和微软 Word 软件，这些软件计划用在产生或维持不符合记录，产品退回记录，内部审计纠正记录或整改记录。W-188Keywords: Laboratory, Electronic Audit Trail, Chromatographic integrati

31、on关键词：实验室，电子审计追踪，色谱综合性能  Primary deviations: No or inadequate electronic audit trail, no audit trail for chromatographic reintegration 主要错误：没有或电子审计追踪不够，没有色谱完整性能审计追踪  Examples: 事例：- Operations that could affect the integrity of chromatographic data files are not controlled by elec

32、tronic audit trails that maintain who, why and what was changed to any given sample record能够影响色谱数据文件的操作没有被电子审计追踪控制，这种跟踪是显示任何样品纪录为什么以及怎样被改变的。- There are no records of user transactions when data is deleted, copied, renamed or purged当数据被删除，复制，重命名或者清除时没有使用者操作记录。- The firm can not determine if reintegra

33、tion of a sample occurred once or several times。公司没有决定样品重组是进行一次还是几次。W-187Keywords: Stability Testing, Quality Control Unit, Laboratory investigations, electronic audit trail, automated computer time-out, method validation, method transfer 关键词：稳定性测试, 质控，实验室调查。电子审计追踪，计算机自动暂停，方法验证，方法转移  Prima

34、ry deviations: Electronic audit trail not reviewed, electronic audit trail does not identify the the person who made the change, no automated computer time-out, operators and supervisors can delete raw data, raw data from contract testing labs not reviewed, proper functioning of established methods

35、not verified after modifications, no follow-up on unknown chromatographic peaks, failing impurity results not reported, no or inadequate training, responsibilities of quality control unit not in writing, inadequate cleaning and maintenance of equipment, no or inadequate failure investigation 主要错误：电子

36、审计追踪未复核，电子审计追踪不能识别谁作了修改。没有计算机自动暂停，操作员和主管可以删除原始数据，没有复核合同实验室过来的数据，已建立方法的适当的功能在方法修改后未经确认，没有继续跟进未知色谱峰，没有报告不合格的杂质结果，没有培训或培训不够，没有写明质控的职责，设备清洁和维护不够，没有故障调查或调查不够  Examples: 事例：- Appropriate controls are not exercised over computers or related systems to assure that changes in master production and

37、control records are instituted only by authorized personnel没有对计算机系统或相关系统进行适当控制以确保只有经过授权的人才能制定主生产记录- The audit trail generated within xxx does not truly reflect the identity of the responsible individuals. Individuals have been able to log on to the system under an other individuals account and make

38、changes which then show up on the audit trail to the first individual. 在xxx产生的电子审计追踪不能真实反应责任人的身份。个人可以用其他人的账号登陆系统并作修改，电子审计追踪显示的是其他人作了修改。- Changes made by PERSON 1 are attributed to PERSON 2 on the (electronic) audit trail.第一个人作的修改在审计追踪上归于第二个人- The firm's review of laboratory data does not inc

39、lude the audit trail/revision history to determine if unapproved changes have been made. 公司实验室数据的复核没有包括用来决定是否有未经批准的变更的审计追踪/版本历史。- The xxx system computers in the lab do not time-out. If an employee fails to log off a computer and walks away other individuals can easily access the computer under the

40、first employees account.实验室中的Xxx 系统计算机不能自动暂停，如果一个员工没有退出计算机就走开的话，其他员工可以很容易地用第一个员工的账户进入计算机。-  The firm routinely assigned method validation chemists, lead chemist, and laboratory supervisors system administrator status with the ability to modify and delete raw data files in the HPLC data acq

41、uisition system 在HPLC数据获取系统中，公司已经验证的方法，分析人员，主分析师，实验室主管和系统管理员能够修改和删除原始数据文件。- Records maintained of any modifications of an established method employed in testing do not include the data to verify that the modification produced results that are at least as accurate and reliable for the material being

42、tested as the established method 在测试中使用的修改后方法的记录没有包括用来确认修改方法至少能产生和原有方法同样精确和可靠结果的数据。- The firm does not receive and review all raw data from contract testing laboratories 公司没有收到和复核来自合同实验室的所有数据。- The accuracy, sensitivity, specificity, and reproducibility of test methods have not been established and

43、documented检测方法的精确性，灵敏度，专属性和重复性未经验证并记录- The firm failed to perform finished product test method transfers for 34 products34个产品的成品检测方法转移没有进行- The firm has failed to perform method validations, method verifications, or method transfers for any of the laboratory test methods used to test active pharmace

44、utical ingredients 公司没有对用来检测APIs的所有实验室方法进行方法验证，确认或转移。W-186Keywords: Method validation, method transfer, process control procedure, sampling plans, test procedures关键词：方法验证，方法转移，过程控制程序，取样计划，检测程序  Primary deviations: Analytical methods transferred without method transfer or revalidation proto

45、col, no or inadequate product specifications, no or inadequate sampling plans. 主要错误：分析方法转移时无转移或再验证草案。没有产品规格或不全，没有取样计划或不合适  Examples: 事例：- Failure to establish production and process control procedures designed to assure your drug products have the required identity, strength, quality and p

46、urity. For example, the validation protocols for xxx and xxx do not provide assurance that the manufacturing process quality throughout the production process没有建立生产和过程控制程序以保证药品符合同一性，强度，质量和纯度方面的要求。例如：xxx 和 xxx的验证草案不能保证整个生产过程的生产质量- failure to establish scientifically sound and appropriate specificatio

47、ns, standards, sampling plans, and test procedure designed to assure products conform to appropriate standards of identity, strength, quality, and purity. For example, there is no scientific justification for testing 30 capsules for content uniformity during process validation. 没有建立听起来很科学很合适的规格，标准，取

48、样计划和测试程序以保证药品符合同一性，强度，质量和纯度方面的要求。例如：在验证过程中检测30个胶囊的装量差异没有科学依据。Failure to establish and document the accuracy, sensitivity and reproducibility of test methods employed. for example, methods that were validated at one facility and transferred to xxx site are being used without method transfer or revali

49、dation protocol,. 没有记录所采用方法的精确度，灵敏度和重复性。例如：在一个地点验证的方法转移到另一个地点时，没有进行方法转移或者再验证方案。W-185Keywords: Software and computer system validation, back-up, limited access, audit trail, data encryption, accurate copies关键词：软件和计算机系统验证，备份，限制登陆，审计追踪，数据加密，精确拷贝  Primary deviations: Inadequate storage and bac

50、k-up, missing ability to discern invalid or altered electronic records, access to computer records without unique user ID and password, no or inadequate validation, inaccurate copies of electronic records. 主要错误：不适当的存储和备份，不能辨别无效或改编的电子记录，没有个人专用的用户名和密码来访问计算机记录。电子记录拷贝不准确  Examples:事例 -Failure

51、to store records so as to minimize deterioration, prevent loss and back up of automated data processing systems 没有存储记录来最小化毁坏风险，预防丢失和数据自动处理系统的备份。-  The electronic data did not correlate with the paper records; you had not established an electronic data back-up procedure; and finally, data w

52、as copied onto the server from one system to the next via floppy: therefore, no limited access or data protection had been established电子数据与纸面记录不相关联，你们没有建立电子数据备份程序，数据从一个系统到另一系统的拷贝非常松散,所以没有限制登陆和保护数据。Failed to encrypt and/ or physically secure your data back-up system to comply with the requirements to

53、 prevent deterioration or deletion of the analyzer data没有给数据备份系统加密或物理保护以符合预防分析数据被毁坏和删除的要求。- Failure to adequately validate the intended use of this PC and its software没有充分验证计算机和软件的计划用途- The dedicated PC redacted attached to the redacted was not secure in that access to the data on redacted was not g

54、ranted by a unique username and password or equivalent method计算机上用于编写的功能在访问数据方面不安全，不是通过个人专用的用户名和密码或同等的方法。- there as no documentation associated with the electronic data for whom was responsible for collection of the analytical results as several quality control personnel have access to the redacted

55、no software changes in the study data could be detected as there was no audit trail capability; and finally, the electronic data did not correlate with the paper records.没有与电子记录相关联的谁负责收集分析结果和几个质量控制人员能够编辑的文件。在研究数据中没有软件变化可以被检测出，即没有审计追踪能力，最后电子数据与纸面记录不相关联。- your response and have concluded that it is in

56、adequate because no system validation was conducted to ensure accuracy, reliability, consistent intended performance, and the ability to discern invalid or altered records 你们已经做出系统验证不充分的结论，因为系统验证没有确保精确性，可靠性，持续使用能力和识别无效及更改记录的能力W-184Keywords: IRB, clinical investigations, review procedures关键词：IRB，临床研究

57、，复核程序  Primary deviations: Failure to follow required written procedures, failure to use expedited review procedures. 主要错误：没有遵循已定规程，没有采用官方的复核程序  Examples: 事例：- Review of the inspection report indicates that the IRB failed to follow written procedures for conducting initial and co

58、ntinuing review of research检查报告复核显示IRB没有遵循已定规程对研究进行起始复核和持续复核。- The IRB's written procedures state that "the IRB shall consist of thirteen (13) members." Since October 12, 2005, the IRB membership roster has listed only 12 members.IRB已定规程声明：IRB有十三个成员，但自从2005年10月12号开始，IRB成员表上只列了12个成员

59、。- The IRB's written procedures state that "meetings will be held on an as-needed basis, but no less than quarterly." However, the IRB records indicate that the IRB has met at intervals greater than three months on four occasions since August 2004.IRB已定规程声明：会议按需召开，但不少于每季度一次，IRB记录表明IRB从2004年8月以来有四次会议间隔在三个月以上。- Failure to use expedited review procedures only for certain kinds of research involving no more than minimal risk or for minor changes in approved resear