FDA警告信翻译
W-185
Keywords: Software and computer system validation, back-up, limited access, audit trail, data encryption, accurate copies
?Primary deviations: Inadequate storage and back-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.
?Examples:
-Failure to store records so as to minimize deterioration, prevent loss
and back up of automated data processing systems
- The electronic data did not correlate with the paper records; you had
not established an electronic data back-up procedure; and finally, data
was copied onto the server from one system to the next via floppy:
therefore, no limited access or data protection had been established
- You failed to encrypt and/ or physically secure your data back-up
system to comply with the requirements to prevent deterioration or
deletion of the analyzer data
- Failure to adequately validate the intended use of this PC and its
software
- The dedicated PC [redacted] attached to the [redacted] was not
secure in that access to the data on [redacted] was not granted by a
unique username and password or equivalent method
- 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] 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.
- your response and have concluded that it is inadequate because no
system validation was conducted to ensure accuracy, reliability,
consistent intended performance, and the ability to discern invalid or
altered records
关键词：软件和计算机系统的验证，备份，权限限制，审核追踪，数据加密，精确复制
?主要偏差：不适当的存储和备份，无法区分有效的或经更改的电子记录，无需唯一的用户ID和密码就可访问计算机记录，没有进行验证或验证不适当，电子记录的复制不准确。
?举例：
-无储存记录使得耗损减到最低，无对自动数据处理系统进行备份和防止
数据遗失。
-电子数据与纸面纪录不相符；没有建立电子数据备份程序；数据通过软
盘在服务器上从一个系统复制到另一个系统：然而，没有进行数据的保护和访问限制。
-无对数据备份系统进行加密和/或采取物理安全措施以保护分析数据不
被损毁或删除，以符合相关要求。
-没有针对PC及其软件预期的使用目的进行充分的验证。
-专门［］用于的PC在数据存取方面不安全，［］没有通过使用唯一用
户名和密码或其他等效的方法对数据存取进行限制。
-没有电子数据相关的正式文件规定由谁负责收集分析结果，如数名质量
控制人员在［］中进行过存取；也没有文件规定不能对研究数据进行软件的修改，如没有审核追踪能力；以及电子数据与纸面记录不相符。
-没有对系统进行验证，以确保系统的准确性，可靠性，与预期性能的一
致性，以及系统具有对无效或经修改的纪录的识别能力。
W-184
Keywords: IRB, clinical investigations, review procedures
?Primary deviations: Failure to follow required written procedures, failure to use expedited review procedures.
?Examples:
- Review of the inspection report indicates that the IRB failed to follow
written procedures for conducting initial and continuing review of
research
- 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.
- 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.
- Failure to use expedited review procedures only for certain kinds of
research involving no more than minimal risk or for minor changes in
approved research [21 CFR 56.110]
- Failure to ensure that the IRB reviewed proposed research at
convened meetings at which a majority of the members of the IRB were present
关键词：IRB（Institutional Review Boards），临床研究，回顾程序?Primary deviations: Failure to follow required written procedures, failure to use expedited review procedures. 主要偏差：没有遵循必需的书面程序，没有使用畅通的回顾程序。
W-183
Keywords: Clinical trials, investigational plan, investigator agreement ?Primary deviations: Missing records, inaccurate data corrected,
unapproved deviation from investigational plan, no or inadequate ?Examples:
- Failure to ensure adequate monitoring of the investigation
- Data were missing and inaccurate data was corrected for Subject
[redacted]
- Failure to secure the investigator's compliance with the signed
investigator agreement, the investigational plan, applicable FDA
regulations, and any other conditions of approval imposed by the
reviewing IRB or FDA
- There are repeated deviations from the investigational plan, spanning
several years, with no apparent steps taken to bring the clinical
investigators into compliance, which indicates failure to ensure
investigator compliance
关键词：临床试验，研究计划，调查人员协议
?主要偏差：记录丢失，修改过的不准确数据，与研究计划不符的未经批准的偏差，没有或不充分。
?举例：
-没有确保对研究进行充分的监控。
-Data were missing and inaccurate data was corrected for Subject
[redacted]
W-182
Keywords: Method validation, USP, standard methods, stability testing,
method documentation, change control, OOS, batch records ?Primary deviations: Failure to validate changed USP standard methods, missing validation for stability indicating methods, insufficient
documentation of test methods, insufficient documentation of changes,
no follow-up of oos situations, failure to release products that do not
meet USP requirements, incomplete batch records
?Examples:
- Your firm uses USP methods to analyze your products, but changes
have been made to the USP methods and no validation has been
performed. For example, for Migrazone Capsules, the USP uses three
different wavelengths to analyze the three active ingredients. Your firm
changed the method to use [redacted] of or all three actives and no
validation of the new procedure was performed.
- Failure to follow your firm's written stability testing program as required by 21 CFR 211.166(a) in that your firm has no validation data to
demonstrate that the method used to analyze products for stability is
capable of detecting degradation of the products
- Your firm lacks complete written methods that fully describe the
procedures, equipment, parameters and specifications to be used in the analysis of individual products.
- Written instructions for analyzing products include cross outs and
changes to the instructions without any documentation as to why these
changes were made
- Review of chromatograms revealed that, in certain instances, out of
specification results which were recorded on the chromatograms had no corresponding reference or raw data recorded in the official laboratory
bound notebook. In these cases, the data was recorded in the notebook only when the sample was retested and results found to be within limits.
For example...
- Your firm has released products purporting to meet USP requirements when, in certain cases, they fail to meet such requirements. For
example ...
- Laboratory control results are not included in batch records as
required by 21 CFR 211.188(b)(5). Analytical results are only
maintained in laboratory notebooks
关键词：方法验证，USP，标准方法，稳定性测试，方法文档，变更控制，OOS，批记录
?主要偏差：没有验证经变更的USP标准方法，稳定性的指示方法没有经过验证，检测方法的文档不足，没有对OOS进行跟进，未能放行不符合USP要求的产品，批记录不完整。
?举例：
-使用了经过变更的USP的方法对产品进行了分析，但没有开展相关的验证工作。例如，对于Migrazone胶囊，USP使用了三个不同波长对三种
活性成分进行分析。但你公司对方法进行了修改，是用单一波长［］对所有三种活性成分进行分析，并且没有对新的程序进行验证。
-你公司制定的书面稳定性测试计划未能满足21 CFR 211.166(a)的要求，没有任何验证数据证明你公司用于分析产品稳定性的方法能检测出产品
的降解。
-你公司缺乏完整的书面方法，全面描述分析某一特定产品所使用的程序，仪器，参数和规格标准。
-没有对含有超出规格标准项目的分析产品以及变更规程的原因进行书面
的说明。
-回顾色谱图显示，在某些情况下，记录在色谱图上的超出标准的结果，
在正式的实验室绑定笔记本中没有对应的资料或者原始数据。在此情况
中，只有样品被重新检测时的数据被记录在笔记本上，重新检测的结果均符合标准要求。例如：…
-你公司放行了声称符合USP要求的产品，但某些情况下，它们未能符合相关的要求。例如：
-未遵循21 CFR 211.188(b)(5)的要求，将实验室质量控制的结果包含在
批记录中。分析结果仅仅在实验室笔记本中维持。
W-181
Keywords: Cleaning records, sampling plans, test procedures, building design
?Primary deviations: Failure to keep records for the maintenance, cleaning, and sanitizing of equipment. Failure to establish sampling
plans, test procedures, or laboratory control mechanisms for testing
your finished product Failure to have adequate building design.
?Examples:
-For example, your firm lacked an adequate assessment of the
cross-contamination risks posed by the manufacture of several potent
compounds (e.g. cytotoxic and hormone products, as well as other
products of high pharmacologic activity) at your facility.
- Failure to have adequate building design and construction used in
manufacture, processing, packing, or holding of drug products to
facilitate cleaning, maintenance, and proper operations
- There were no equipment cleaning records for several of the product
contact, multi-use formulation mixing rods. The investigators observed
that there was no evidence to demonstrate that the mixing rods were
dedicated to specific products.
- Investigators observed black colored particles in at least one
evacuated sterile vial. The microbiologist performing sterility testing on
the vials was observed removing the vial with the black colored particles and replacing the vial. No sampling plan or test procedures were
available to justify replacement of the finished product evacuated vial. 关键词：清洁记录，取样计划，检测规程，建筑物设计
?主要偏差：未能保留维护，清洁和消毒设备的记录。未能建立取样计划，检测规程，或实验室控制机制对最终产品进行检测。建筑物设计不当。
?举例：
-例如，你公司对因在设施内生产几种强力成分（如，细胞毒素，荷尔蒙
产品以及其他高药理活性的产品）所引起的交叉污染的风险缺乏适当的评估。
-未能对用于生产，加工，包装，或暂缓处理药物产品的建筑物进行适当
的设计，以方便清洁，维护，和人员操作。
-没有针对数个与产品接触的点，多用途配方搅拌棒等设备的清洁记录。
调查人员观察到没有证据表明搅拌棒是专门用于特定的产品的。
-调查人员至少在一个空的无菌瓶中观察到黑色的微粒。对瓶子进行无菌
检测的微生物学家被观察到以另一个瓶子更换了带有黑色微粒的瓶子。没有可用的取样计划或检测规程证明更换最终产品的空瓶的正确性。
W-180
Keywords: Cleaning validation, quality control unit, failure investigation, oos, raw data, laboratory notebooks, input-output checking, retesting Primary deviations: Inadequate cleaning validation, quality control units failed adequate investigation, no or inadequate failure investigation, raw data not documented in laboratory notebooks, oos retesting without
supervisory approval, electronic data files not routinely checked for
accuracy, discrepancies in electronic data
Examples:
- Our investigators observed numerous instances where the quality
control unit failed to adequately investigate and resolve laboratory
deviations and out-of-specification test results involving drug products
that ultimately were released for distribution into interstate commerce
- Our investigators uncovered out-of-specification test results in
laboratory raw data that were not documented in laboratory notebooks, and found that products were released based on retesting without any
justification for discarding the initial out-of-specification test results.
- The chromatographic test data reflecting the out-of-specification test
results were not recorded in laboratory notebooks. Instead, a new
sample preparation was injected within the same chromatographic run
without supervisory approval, as required by your firm's SOP
- A review of the laboratory notebook shows the sample dilution value in the laboratory notebook was overwritten, without being signed and
dated.
- There was a failure to check for accuracy the inputs to and outputs
from the "Total Chrom Data Acquisition System," which is used to run
your firm's HPLC instruments during analysis of drug products. For
example, electronic data files were not routinely checked for accuracy
and, as mentioned in the above observations, our investigators found
numerous discrepancies between the electronic data files and
documentation in laboratory notebook.
关键词：清洁验证，质量控制单位，事故调查，OOS，原始记录，实验室笔记本，输入输出检查，重新检验
?主要偏差：不当的清洁验证，质量控制单位未进行适当的调查，没有或不充分的事故调查，原始数据没有记录在实验室笔记本上，OOS没有经过
管理者的批准就进行重新检验，没有对电子数据文件的准确性进行日常的检查，电子数据自相矛盾。
?举例：
-调查人员发现很多实例，说明质量控制单位未能充分调查和解决实验室
偏差和超出规格标准的检测结果，其中包括最终被放行及销售到各州的药物产品。
-调查人员发现超出规格标准的检测结果的实验室原始数据没有记录在实
验室笔记本中，并且发现产品的放行是基于重新检验的合格结果，而没有经过任何验证就丢弃了最初的超出规格标准的检测结果。
-色谱检测数据反映出超出规格标准的检测结果没有记录在实验室笔记本
中。取而代之的是一个新的样品制备，进样到同样的色谱中运行，没有按照你公司SOP的要求经得管理者的批准。
-对实验室笔记本的检查发现其中样品稀释值被改写过，并且没有相应的
签名和日期。
-你公司没有对分析药物产品的HPLC仪器所使用的“综合色谱数据采集
系统”进行输入和输出的准确性的检查。例如，电子数据文件没有进行日常的准确性检查，如上述观察项所提及的，调查人员发现很多电子数据文件与实验室笔记本记录的文档相矛盾的情况。
W-179
关键词：计算机验证，培训，文件控制，CAPA，根本原因
?主要偏差：计算机系统没有验证，没有识别培训需求，未能遵循文件控制的要求，没有或不当的CAPA程序，没有对CAPA活动的有效性进行验
证或确认。
?举例：
-没有建立和维持开展纠正和预防行动的程序。根据….的要求，该程序必须包括对纠正预防行动的确认或验证，以确保这些行动是有效的，同时不会产生负面的影响。
-未能成功调查出与产品，程序，质量系统相关的违反21 CFR 820.100a)(2)要求的不符合项的原因。例如，下列程序中没有包含开展事故调查的内容：投诉处理，产品缺陷追踪和趋势，非一致性的物料和设备维修。
-当使用计算机或自动数据处理系统作为生产或质量系统的一部分时，未
能根据21 CFR 820.70(i)的要求对自动化过程进行生产和过程的控制。生产者必须根据一个已建立的方案对计算机软件预期的使用进行验证。例
如，数据库用于数据分析，数据追踪及趋势分析，包括投诉和服务器访问数据库，没有对其预期的使用进行验证。
-需要对CAPA进行验证或确认，但未能找到关于CAPA 440C的相关记
录文档。
W-178
关键词：正在进行的设备确认（PQ），规程，PQ，培训，质量控制单位，记录，事故调查
?主要偏差：没有或不当的性能确认，没有或不当的生产和过程控制书面程序，没有或不当的质量控制单位，未能开展调查，没有或不当的培训，没
有遵循程序，未能维持一个完整的设备校准记录。
?举例：
-未能根据为确保适当的性能而设计的书面程序[21 CFR 211.68(a)].对自
动化的、机械的或电子的设备进行日常的校准，检查或检验。
-特别是，你的低温泵系统没有按照一个书面的计划进行确认，以确保系
统的所有部分，包括泵、电源、电子部件、真空维持部分和低温夹套，每
次都将按照其预期的使用目的运转。
- Failure to establish adequate written procedures for production and
process control designed to assure drug products have the identity,
strength, quality and purity they purport or are represented to possess
未能建立充分适当的关于生产和过程控制的书面程序，以确保药物产品具
有其声称或有代表性的特性、浓度、质量和纯度。
-未能建立一个充分适当的质量控制单位，具有批准或否决所有药物产品
的职责和权限，同时具有复核生产记录的权限，以确保没有发生错误，或
者当发生错误时根据21 CFR 211.22(a)的要求进行全面的调查。特别是….
-质量控制单位的人员未能对装填设备以密封气缸的装填操作的事故展开
调查，违反21 CFR 211.192
-未能按照21 CFR 211.160(b)(4) a和211.194(d)的要求维持关于实验室
仪器周期性校准的完整记录。
W-177
关键词：生物等效性，研究数据的回顾性复核，分析方法，无程序，药物动力学概况，事故调查
?Primary deviations: invalid retrospective review of study data, inadequate documentation to demonstrate accuracy of analytical
methods, providing incorrect information to the FDA, missing studies in
retrospective review, lacking procedures for critical steps in
retrospective review, failure to investigate pharmacokinetic profiles with unexpected concentration results, no timely information of study
sponsors about invalid data. 主要偏差：无效的研究数据回顾性审核，无
充分适当的文件证明分析方法的准确度，提供了不正确的信息予FDA，
回顾性审核的研究缺失，回顾性审核的关键步骤没有程序…….
?Examples:
-Failure to demonstrate that the five year retrospective review is
effective and capable of discriminating between valid and invalid data
- Failure to assure that the analytical methods used for in vivo
bioavailability studies could accurately measure the actual
concentration of active drug ingredient, or its metabolite, achieved in the
body. "Long term use" is not a sufficient assurance of assay accuracy.
- For these reasons you have not demonstrated that the reported
concentration results in Study xxx are accurate.
- You provided incorrect incorrect information to FDA regarding the
status of undergoing retrospective review
- You failed to appropriately include studies in the retrospective review
- There is no assurance that reviews were conducted in accordance
with original or revised procedures
- You failed to investigate the cause of anomalous results, or re-assay
the affected samples. Contrary to your response, the frequency of
occurrence is not a justification for accepting anomalous study results
- Although you discontinued use of the xxx method in August 2005, you failed to inform study sponsors that the data generated with this method was invalid.
W-176
关键词：临床研究，受试者安全，受试者权利，人员管理，签名，回顾报告，记录维护
?Primary deviations: failure to protect the rights, safety, and welfare of subjects under care, failure to personally conduct or adequately
supervise the above references clinical trial, no evidence of lab report
review, failure ton conduct the study in accordance with the
investigational plan, failure to prepare and maintain adequate and
accurate records, failure to promptly report to the sponsor any adverse effect that may reasonably be regarded as caused by, or probably
cause by, the drug.
?W-175Examples:
- You did not adhere to the applicable statutory requirements and FDA
regulations governing the conduct of clinical investigations
- Because this subject had a history of peptic ulcer disease and an
incident of gastrointestinal bleeding she was at substantial risk for GI
bleed related to treatment with aspirin.
- The record does reflect that you reviewed the subject screening
assessments and related subject records in accordance with the
protocol
- You delegated certain study tasks to an individual not qualified to
perform such tasks
- You permitted an individual with no medical training to evaluate
laboratory results for clinical significance. The lab reports were not
co-signed by you, therefore thee is no indication that you reviewed them - The case history did not contain any other documents to validate the
subject's enrollment and completion of clinical investigation
W-175
关键词：过程验证，软件验证，设计确认，SOPs，外来产品控制，投诉处理?主要偏差：验证工艺的参数监测和控制程序不充分不适当，工艺控制程序
不充分不适当，对外来产品的控制和文件记录的程序不充分不适当，投诉处理程序不充分不适当，没有或不当的软件
?举例：
-未能建立并维持用于监测和控制验证工艺的参数的程序，以确保能持续地满足特定的要求。
-当工艺流程不能通过后来的检查和检测充分确认时，则应当对该程序进行高保险系数的验证，并根据已建立的程序进行批准。
-验证活动和结果，包括批准验证的日期及负责人的签名和适合于验证主要设备的场所，均必须进行文件记录。例如，你公司没有对在XXX设备中使用的软件进行验证。XXX设备有一个用特殊软件编程的微处理器，用于控制XXX和改变XXX。未能提供用于验证该设备的程序，以确保该设备符合预先定义的用户需求和预期的使用，也没有对软件进行验证。
-未能建立和维持那些定义和控制生产方式的过程控制程序，包括文件架构、标准操作规程（SOPs）以及方法。
-未能建立和维持用于安装好的设备的验收程序，以确保安装好的设备所生产的每一批产品均符合要求。
-未能建立和维持关于外来产品验收的程序，包括接收或否决的文件。
-未能建立和维持由一个正式指定的单位接收、回顾和评价投诉的适当的投诉处理程序。
W-174
关键词：CAPA，投诉，培训，仪器校准，工艺验证，公认的产品测试?主要偏差：没有执行培训程序，没有或不充分不适当的仪器校准和检查程
序，没有工艺验证和监控的程序，没有建立和执行CAPA程序，没有维持投诉文件，所有购买或接收的产品和服务的说明书没有进过确认。
?举例：
-未能建立、执行和控制程序，确保用于生产和测量的仪器设备进行了准确度的日常校准、检查和检测。特别是，没有维持天平、生产熔炉以及填充设备的检测、检查、调节和校准的记录。
-未能确保维持投诉文件，也未能做到所有口头的和书面的投诉从接收开始均被记录在案，并以统一的和及时的方式处理。
-未能建立、执行和控制用于验证生产工艺以及控制和监测工艺参数的程序，
-未能执行和控制相关程序，确保所有购置的或接收的产品和服务符合规定的要求。
- 未能建立、执行和控制关于纠正和预防行动的程序
- 未能确保识别培训需求的培训程序被执行和培训的行动被文件化记录
W-173
关键词：合约实验室的审核，分析报告，质量单位的职责，保留样品，API，重包装，容器密封系统，等价
?主要偏差：未对合约实验室进行审核，未对供应商COAs的真确性进行验证，没有保存保留样品，容器密闭系统的等效性没有文件记录?举例：
- 没有通过在你包装的场所对APIs进行周期性全检验的方式验证供应商
COAs的真确性。
-未对开展外来API检验的合约实验室进行审核。你的SOPs中指出应每
两年进行一次相关的审核。
-未维持书面的程序，描述适用于质量控制单位的职责和规程。
-没有保存重新包装的每批API的保留样品。有数宗实例显示你公司接收
到了关于产品完整性的投诉。你公司未能针对这些重新包装的APIs的投诉开展全面调查，因为没有可用于检测的保留样品。
-你没有证明重包装APIs的容器密封系统与接收时APIs的密封系统是等
效的。
W-172
Keywords: failure investigations, contract laboratory, repair, passwords, audit trail, security, method change, signatures on test results, power failure
关键词：失败调查，维修，审核，密码，安全，方法变更，测试结果的签名，失败
?Primary deviations: insufficient written records of failure investigations, investigations not extended to other batches, missing HPLC peak not
investigated, no investigation regarding HPLC malfunctions requiring
external repair, impact of power failure not investigated, laboratory
records not signed by the analyst, analyst not identified, failure to use
group passwords to log-on to computer systems, changes of methods
by authorized persons not ensured, no review of audit trail, contract
laboratory not qualified
?主要偏差：失败调查的书面记录不充分，调查没有沿伸到其他的批次，?没有调查HPLC缺少的峰，没有调查HPLC的故障，没有调查电的功率，分析者没有签名，分析者不能被确定，不能保证方法的更改得到授权人的
认可。合同实验室没有进行资格确认。
?Examples:
?举例：
- Written records are not always made of investigations into
unexplained discrepancies, nor did investigations of unexplained
discrepancies extend to other batches of the same drug product or
other drug products that may have been associated with the specific
failure or discrepancies
?- The reference standard injection following assay and content uniformity testing of xxx, failed to show any peaks due to a leaking
column. There was no documented investigation of this deviation, there was no assessment of the impact of the leaking column on the xxx
analysis or any other analysis conducted with the same column, and the observation was made during the previous inspection, yet no
investigation was conducted.
?- There was no documented investigation regarding HPLC malfunctions requiring external repair. Both HPLC xxx and xxx required repair in June 2005; however there is no documentation regarding whether the
malfunctions impacted any analyses, and if so, what the corrective
actions were regarding those analyses.
?- Power failures occurred during analyses of xxx. Investigations did not document the impact on the analyses, any re-testing or resampling, or if the power outage impacted any other analyses
?- Laboratory records fail to include the initials or signature of the person who performs each laboratory test [21 CFR § 211.194(a)(7)].
Specifically, laboratory analysis records for analyses performed on
HPLC xxx and xxx do not indicate which analyst performed the
injections.
?- Failure to maintain complete records of any modification of an established method employed in testing [21 CFR § 211.194(b)].
Specifically, the records of laboratory methods stored in the xxx
computer system do not include the identity of the person initiating
method changes.
?- Appropriate controls are not exercised over computers or related systems to assure that changes in analytical methods or other control records are instituted only by authorized personnel
?- Laboratory managers (QC and R&D) gained access to the xxx computer system through a common password. Analysts were not
required to use individual passwords; they operated the system
following the login by the laboratory managers.
?- Due to the common password and lack of varying security levels, any analyst or manager has access to, and can modify any HPLC analytical
method or record. Furthermore, review of audit trails is not required.
?- Failure to follow written procedures applicable to the quality control, unit [21 CFR § 211.22(d)]. Specifically, the contracted laboratories
responsible for performing analyses on Active Pharmaceutical
Ingredients and other drug components, used in the finished drug
products, such as LOD, nitrogen content; microbial limits, and specific
rotation, have not been qualified by the quality unit as per your firm's
written procedures.
W-171
Keywords: Complaints, service, repair, design, risk assessment
关键词：投诉，服务，纠正，设计，风险评估
?Primary deviations: Service records not maintained, inadequate handling of complaints, not all possible risks identified and documented ?主要偏差：服务记录不完整，投诉处理不合适，所有可能的风险没有被识别和备案。
Examples:
举例：
- Failure to establish and maintain procedures to ensure that the design requirements relating to a device are appropriate and documented
缺乏建立和维护程序已保证涉及一个设备设计要求和文件证明
- Your firm failed to identify, approve, and document appropriate design inputs prior to the start of its formal design of the Frye Adjusting Instrument
你们公司未能识别、批准、Frye校准器械
- Failure to establish and maintain procedures for validating the device design to ensure that the device conforms to user needs and intended uses
为能为设备设计确认建立程序用以保证这些设备满足使用者的需要
- Your firm failed to adequately identify and document all possible risks associated with your device and document the results of your firm's risk analysis
在你们公司风险分析中未能从分的识别和说明所有可能存在与设备相关的风险- Failure to establish and maintain complaint handling procedures for receiving, reviewing, evaluating, and documenting complaints by a formally designated unit
缺乏建立和维护一个从接受、评论、评估、归档投诉处理程序正式指定个体
- Failure to maintain service reports for serviced devices, as required by 21 CFR § 820.200(d). For example, your firm failed to maintain service reports for each device returned to your firm for servicing or repair (e.g. the name of the device, the date of service, the individual(s) servicing the device, the service performed, and the test and inspection data).
21 CFR § 820.200(d)规定未能完善维护服务报告，例如，你们公司没有完善被
送回维修设备的服务报告（例如：设备名称，维修时间，设备维修单位，维修的履行、测试与检测时间）
- Your firm failed to document the results of its analysis or evaluation of emails of complaints and service reports in order to identify existing and potential causes of nonconforming product. You stated that you mentally evaluated complaints and servicing or repairs of returned devices but that you had not documented any evaluations.
W-170
Keywords: process control, change control, training, product identification
关键词：过程控制，更改控制，培训，产品鉴别
?Primary deviations: no adequate production and process controls, inadequate change control, no performance verification after the
change, missing records of communication, training not documented ?主要偏差：生产和过程控制不够，更改控制不合适，在更改后没有进行验证，
?没有信息记录，没有培训文件。
?Examples:
?举例:
- Failure to establish and maintain adequate production and process
controls that include documented instructions, standard operating
procedures (SOP), and methods that define and control the manner of
production
?没有建立或者没有合适的产品和过程控制，其中包括文件的教育，标准操作规程，方法的详细说明和操作的方式。
- Failure to establish and maintain procedures for changes to a
specification, method, process, or procedure, including verification or
validation of such changes
?没有建立和者拥有为一规格、方法、步骤或程序更改的程序，包括这些更改的确认或确认。
- Failure to promptly remove obsolete documents from all points of use
没有将已经废除的文件迅速从使用单位回收。
?- Your firm changed the xxx Cooler-Heater device's internal timer setting in two instances. The reason for the changes, the review and
approval for the changes, and the effective date of the changes were
not documented
你们公司更改了XXX冷却器---加热器设备的内部计时器设置，但是更改的原因、评论和批准及生效日期都没有文件。
?- Your firm failed to conduct, document, and maintain the results of the verification testing of each change o determine whether or not each
change affect operations and performance specifications
你们公司未能管理、证明、维护每一次更改决定确认测试结果
?- Your firm failed to maintain records of communication with the specification developer to document who initiated and authorized the
changes, the signature of the approving individual(s), the approval date, and an effective date of each approved change
在规格标准的建立和更改时，没有由责任人参与的维护记录。
?- Failure to establish and maintain procedures for identifying product during all stages of receipt, production, distribution, and installation to
prevent mixup
你没有建立相关的文件保证在产品的接受、生产、分发时避免混淆。
?- Your firm stated that three individual employees involved in the assembly of the xxx Cooler-Heater devices had been trained but that
your firm could not provide any documentation of their training.
?声称三个冷却器---加热器设备相关的人员已经得到培训，但是你们公司不能提供关于他们培训的文件。
W-169
Keywords: Buildings, equipment cleaning, maintenance, calibration, laboratory controls, records, signature, failure investigation
关键词：厂房，设备清洗，维修，校准，实验室管理，记录，签名，失败调查?Primary deviations: Inadequate buildings, no or inadequate maintenance and cleaning of equipment, insufficient intervals for
equipment calibration, inadequate laboratory controls, test procedures
not followed, incomplete laboratory records, initials or signature of a
second review person missing, inadequate failure investigation ?主要背离：建筑物不适合，没有或缺乏设备维护和清洗，设备校准的时间间隔不合理，使实验管理不规范，测试程序没有被遵循，实验室记录不完善，测试者或复核者都没有签名，失败调查不充分。
?Examples:
?举例：
-Buildings used in manufacture of injectable products are not always
maintained in a good state of repair,
?生产血管注射剂的厂房没有一个好的维护规定。
-Equipment and utensils are not always cleaned, maintained and
sanitized at appropriate intervals to prevent malfunction or
contamination
设备和器材被清洗、维护、清洁在间隔时间不合理。
?- The calibration of instruments was not always conducted at suitable intervals
在适当的时间没有进行仪器的校准。
?- Deviations from written procedures not justified
没有证实书面程序的背离
?- Test procedures were not always followed
测试程序没有被遵循
?- Laboratory records did not always include a description and identification of the sample received for testing, the date the sample
was taken, the date the sample was received for testing and the data
derived from testing.
实验室测试记录里没有样品的鉴别和形状测试、样品的来源、样品的接受时间、测试的原始数据。
?- Laboratory did not enter the date on which the results are read into the logbook.
实验室在日志中没有加入结果被读取的时间。
?- There were not always the initials or signature of second person showing that the original records have been adequately reviewed by a
second person
在另一个人已经回顾的原始记录里有初始者和复核者漏签名。
?
?- The investigations did not always extend to other batches of the drug or other drug products that may have been associated with specific
failure or discrepancy
?调查没有延伸到其他批次的药，其他批次的药品很可能存在不合格和不符项。
W-168
Keywords: supplier evaluation, process validation, complaints, computer validation, training, quality system
关键词：供应商评估，过程验证，投诉，计算机验证，培训，质量体系?Primary deviations: No or inadequate procedures for design control, no documentation that products have been developed in accordance with
design control, inadequate review of complaints, no procedures for
evaluation of suppliers, contractors, and consultants, no notification of
changes by the supplier, effective and complete procedures for
implementing corrective and preventative action operations, no
validation of the manufacturing processes, no or inadequate validation
of computer systems, insufficient controlling the storage of product in
order to prevent mix-ups, no or insufficient training, quality system not
fully implemented
?主要偏差：投诉回顾不充分，没有供应商、承包人、咨询者评估程序，生产步骤没有确认，计算机系统没有确认或确认不充分，在产品存贮中防止混淆的控制不够，没有培训或培训不足，质量体系没有得到完全的执行。
?Examples:
?举例：
-written procedures for controlling the design of the Hemoglobin Alc
Reagent and formulation changes to the Liquid Glucose Hexokinase
Reagents were not adequately established during the implementation of these design projects
在这些设计法案执行中控制血色素反应物和阐明改变液体葡萄糖酶反应
物的书面程序制定不充分。
?- design history files do not demonstrate that these devices were developed in accordance with the design control requirements
没有证明这些设备能达到设计文件的要求。
?- Your firm failed to ensure complaints involving possible failures are adequately reviewed and evaluated to determine if investigations are
necessary你们公司没有保证投诉所包含的可能发生的问题进行足够的
回顾或评估然后再决定调查是否必须进行。
?- Your firm failed to establish procedures for the evaluation of suppliers, contractors, and consultants
你们公司没有建立供应商，承包人，咨询者的评估程序。
?- For example, there is no documentation to demonstrate that your firm has evaluated the importer or is aware of the manufacturer from Asia
supplying the reagents used to produce the Hemoglobin Alc Reagent
例如，这里没有文件证明你们公司评价进口商或者知道从亚洲供给试剂的厂商
?- In addition there are no clear agreements from the suppliers to notify you of changes
?另外同供应商没有一个清楚的协议去通报你
?- Your firm failed to validate computer software used to control automated production and quality system operations, as required by 21 CFR 820.70(i). For example, your firm has not validated the software
used to produce labels and manage your complaints
根据21C FR 820.70(i)规定你们公司缺乏用于生产和质量体系控制的计
算机软件的验证，例如，你们公司没有验证你们标签打印及投诉管理软件。
?- Your firm failed to follow procedures for controlling the storage of product in order to prevent mix-ups, damages, or other adverse effects ?你们公司没有遵循程序去存储产品
W-167
Keywords: Part 11, electronic records, integrity, stability testing, documentation, storage conditions, people resources
关键词：11部分，电子记录，完整性，稳定性测试，文件，储存条件，人员资源
Primary deviations: Electronic raw data not saved, laboratory records incomplete, inadequate documentation of storage conditions of samples, insufficient personnel and equipment in the quality control unit for testing
主要偏差：原始电子数据没有保存，实验室记录不完善，关于样品储存条件的文件不充分，质量控制部门没有为配备足够的人员和测试设备。
?Examples:
?举例：
- Operating parameters were maintained with the relevant xxx. However, electronic raw data was not saved.
?操作参数根据相应的xxx被修改，可是原始电子数据没有被保存。
According to the Director of Quality Assurance, xxx began saving
electronic raw data just recently at the beginning of February 2006.
However, that was not observed during the inspection
?根据质量保证部主管所说，他从2006年2月开始保存电子原始数据，可是在检查期间没有看到。
?- The SOP allows "discarding" data due to variation in the xxx area or any other reason
由于在XXX范围内变更或其他的任何原因SOP充许丢弃数据?- Your firm failed to establish and follow an adequate written stability testing program design to assess the stability characteristics of drug
products.
你们公司没有建立和遵循一个书面的稳定性测试计划去评估药品的特性。
?- Storage condition for samples retained for stability testing are not adequately documented
没有充分的文件去说明稳定性测试样品的留样储存条件。
?- The Quality Control Unit lacks adequate laboratory resources (personnel equipment) for conducting stability testing of drug products ?质量控制部门缺发足够的资源（人员设备）去实施药品稳定性测试。
W-166
Keywords: Part 11, electronic records, raw data, method validation, USP methods, SOP, paper notebooks
关键词：11段，电子记录，原始数据，方法确认，USP方法，SOP，文件本?Primary deviations: No FDA-483, Inspectional Observations, issued to the firm. Several items have been discussed verbally with
management:
?主要偏差：没有FDA-483，检查资料，论述公司发布管理方面的几个条款
?Examples:
?举例：
- I explained that computerized records that the firm keeps to make it
easier to sort or find certain information would not necessarily have to
comply with Part 11 regulations. As an example, I explained that if the
firm has a database for complaints, but still records everything on
paper (and the paper copy is the official record), the database would
not have to comply with Part 11. However, if the database was their
only record, the database would have to comply with Part 11
特别说明：如果公司使用电子记录仅仅是为了更加方便的去分类或查找
所需的信息，则该电子记录没有必要遵守（ICH有关电子记录管理的）
11部分规则。例如公司建立了一个用于管理投诉信息的数据库，但同
时仍然使用纸式文件来记录跟（投诉相关的）所有信息（复制的记录也
属于正式记录），则该电子数据库就没有必要遵循11部分规则了。总
而言之，如果电子数据库是唯一的记录（没有相关的纸式记录），就必
须要符合11部分规则。
?- if not using the methods listed in the USP, firm's methods have to be validated and/or shown to be as good as or better than the USP
methods.
如果使用的方法不在USP方法清单中，公司的方法必须被验证及说明
跟USP方法一样可靠或者更好。
?- firm needs to have a system for accountability for raw data. Raw data was recorded onto a loose leaf piece of paper. The firm must
have a a system of accountability in place to assure that raw data is
being lost. I further explained that the firm could use bound laboratory
notebooks or pre-numbered laboratory worksheets to fulfill this
requirement. 公司必须有个原始数据管理制度。原始数据被记录在任意
的一张纸上，公司必须规定有一个适当的制度去保证原始数据，更深解
释是为了满足要求实验室可以使用装订的本或者预先编码的工作表。
?- firm needs to either update SOPs so that they reflect what is actually being done at the firm or follow SOPs as written.
?公司需要更新SOP以至使它能反映现在的行为或者书写SOP
W-165
Keywords: Part 11, electronic records, integrity, API, calibration
Includes 483 - Establishment Inspection report (EIR) - Company's response letter - FDA's answer
关键词：11部分，电子记录，完整性，API，校正包括483－制定检查报告（EIR）公司的反馈信，FDA的回答
?Primary deviations: Failing integrity of QC results, no testing of bulk solvents prior to receipt, failure to retain and review alarm history printout and equipment cleaning:
?主要偏差：实验室结果的不完整性，大多数试剂在接受前没有测试，没有保留和回顾过去警告及设备的清洗。
?Examples:
?举例：
- There is no system for assuring the integrity of blank sheets used in the recording of results in the paper documentation system
在纸式文件管理系统中，没有制度保证用于记录结果的空白记录的完整性。
（空白原始纪录管理没受控）
?- The computerized system is not secure in that it is possible for data entered to be changed. This was observed following a request during
inspection for a challenge to be performed during which it was
determined that previously recorded input including sample gross and net weights and the final result could be changed..
?计算机系统安全性不符合要求。在检查过程中，可以发现在执行（一个设定的工作）时。之前输入的数据：如样品的毛重、净重及最后的结果，都有可能被更改。
- There is no written procedure regarding the documentation and review of deviations which occur during sterility testing
?在中性测试出现时没有关于偏差回顾的书面程序
?- Testing which is performed on incoming lots of solvent to the tank farm is limited to identity testing
?在大量溶剂放入罐里时仅作了鉴别测试。
- The xxx used in the manufacturing in-process laboratory and the QC
laboratory was calibrated .
?xxx在生产过程控制实验室和QC实验室被校正。
W-164
Keywords: Equipment qualification, IQ/OQ/PQ, procedures, cleaning validation, failure investigation, washing facilities, testing, preventive maintenance
关键词：设备确认，IQ/OQ/PQ，程序，清洗验证，故障调查，清洗设备，测试，预防维护
?Primary deviations: Equipment not performing, procedures not followed, inadequate equipment qualification, PQ protocol missing, validation
protocol not followed, inadequate cleaning validation procedures,
missing failure investigation, master production and control records not
signed, inadequate washing facilities, insufficient testing, missing
preventive maintenance, forms inadequate to record complete IQ
information, IQ/OQ not performed
?主要偏差：设备没有执行（IQ、OQ等），没有遵循程序操作，设备确认不完整，缺少PQ草案，没有履行确认文件，清洗确认程序不充分，缺少故障调查，主要备件和控制记录没有签名，清洗设备不充分，测试不完整，缺少预防维护，IQ的信息没有足够的表格记录。没有履行IQ/OQ。
?Examples:
?举例：
- Failure to ensure that automatic, mechanical, or electrical equipment
or other types of equipment will perform a function satisfactorily. For
example.....
没有（任何证据）确保自动化机械、电设备或其它类型的设备的主要功能是达到预期要求。
?- Failure to follow your standard operating procedure
?- For example, , Inspection and Testing of Manufacturing Equipment, which applies to all activities for testing and inspection of equipment at
Cody Labs, and the Installation Qualification Manufacturing Equipment