[FDA]关于HPLC警告信.docx

2009－2011年FDA警告信涉及HPLC的内容欧盟符合性研究院（ECA）GünterBrendelberger博士昨天（2012年2月28日）发布了：2009－2011年FDA警告信中涉及高效液相色谱法的主要问题内容非常好，我快速进行了翻译在使用高效液相色谱（HPLC）存在的关键问题包括以下4个方面：1.电子记录的原始数据/保护2.校准/确认3.方法验证4.系统的适用性/序列原文链接： Go here to access the complete list of FDAfindings regarding HPLC.全部译文如下：           2009–2011年FDA警告信涉及HPLC的内容1.Raw Data / Protection of Electronic Records 电子记录的原始数据/保护Yourfirm lacks systems to ensure that all electronic data generated in your QualityControl laboratory is secure and remains unaltered. All analysts have systemadministrator privileges that allow them to modify, overwrite, and deleteoriginal raw data files … in the High Performance Liquid Chromatography (HPLC)units.贵公司缺乏系统以确保所有的在质量控制实验室产生的电子数据是安全的并保持不变。

你们HPLC岗位所有的分析员都具有系统管理员的权限去修改，覆盖并删除原始数据Thereare no procedures that address the security measures in place for generationand modification of electronic data files for these instruments used for rawmaterial, in-process,finished product and stability testing. In addition, yourfirm's review of laboratory data does not include a review of an audit trail orrevision history to determine if unapproved changes have been made. 没有建立一个程序规定如何对原材料、中间控制、成品和稳定性测试的电子文件进行安全保存和修改贵公司的实验室数据审查并不包括审计跟踪或未经批准修改数据的历史记录审查Forexample,your firm has failed to periodically conduct back-up procedures Thisserver was used to store, back-up, and/or archive raw test data from computersystems (Software:…controlling and monitoring… High-performance liquidchromatography (HPLC) systems in accordance to SOP …”.例如贵公司未能按SOP的要求对服务器上存贮的原始数据进行定期备份。

Yourresponse, however, is inadequate because you fail to adequately address whetheryou were able to recover the critical data not backed-up between August 2010and when you first implemented the daily backup process. Your firm has yet toindicate whether HPLC raw data records could be retrieved for the duration oftime that the … server was not backing-up the HPLC system data.你们的回复是不适当的，因为你们不能充分叙述2010年8月是否对关键数据进行了备份，2010年8月是你们第一次执行备份程序贵公司还不能表明能否找到那段时间的HPLC原始数据，…服务器不支持备份HPLC系统数据Your firm's laboratory analysts have theability to access and delete raw chromatographic data located on the … of …used to conduct HPLC testing. Due to this unrestrictive access, there is noassurance that laboratory records and raw data are accurate and valid.贵公司实验室分析员个具有访问和删除原始色谱数据的权力，你们这种不受限制的访问无法保证实验记录和原始数据的准确性和有效性。

2.Calibration / Qualification 校准/确认Youreplaced the … HPLC systems operating on … software with … new qualified HPLCunits from … software. This validation information will be reviewed at the nextinspection. In addition, your response is inadequate because it lacks aretrospective evaluation of the data from the former HPLC units.你们回复说更换了高效液相色谱系统的操作软件......我们将会在下次检查中确认你们进行的验证相关文件此外，你们的回复是不充足的，因为缺乏对过去PHLC岗位数据的回顾性评价For the testing of incoming components,your firm failed to conduct HPLC system qualification using certified standardsand validated procedures … . Your laboratory failed to certify … against aprimary standard from an ccredited institution and/or to fully characterize thematerial as a standard.对进厂组份检验，贵公司不能使用权威部门的标准品对HPLC系统进行确认与验证。

你们实验室未能证明你们使用的标准品是合法性，或从认可机构购置和/或从用基准标准品标定工作标准品Yourfirm failed to conduct injector and detector performance testing for the … HPLCsystem. For example, no HPLC injector and detector testing for linearity, accuracy,and precision were conducted, such as: 1) various injection volumes andstandard concentration testing; 2) evaluation of detector for noise/drift; and3) carryover testing to evaluate response at low levels to determine thedetection of possible interferences that may affect peaks of interest.贵公司没有对HPLC的注样器和检测器进行性能测试。

例如，没有对HPLC注样器和检测器进行线性，准确度，精度度确认例如：1）不同注射量和标准液的测试；2）对检测器的噪音/漂移评估；3）残留试验，来评估低峰响应时，确定可检测出可能干扰主峰的残留YourHPLC calibration lacks a carry over test (sample injection residual test),sample energy (intensity of light source), and lamp use hours determination.你们的HPLC校准缺少进样残留试验，能源（光源强度），灯泡使用时间的测定内容Your firm also fails to maintain raw dataassociated with the re-qualification and calibration of your laboratoryinstruments. During the inspection the investigators were informed that theannual re-qualification and calibration of your laboratory equipment (e.g.,HPLC, GC, polarimeter, and analytical balance) is performed by the … . However,you were unable to provide raw data or documentation regarding thequalification and calibration of your instruments and data to demonstrate thatyour quality unit reviewed and approved the work performed by your contractor. 贵公司不能对实验室仪器进行重新确认和校准来维护原始数据。

在考察期间调查员要求你们要对实验室设备进行年度重新确认和校准（例如，高效液相色谱仪，气相色谱，旋光仪，分析天平），然而你们无法提供重新确认和校准的原始数据或文件和质量部门审核文件，和承包商审查的批准文件3.Method Validation 方法验证Yourfirm failed to generate and document chromatographic data to support thevalidation of the analytical method .. used for the determination of Urea inUrea Cream 40%. In addition, your firm failed to generate a and documentchromatographic data to support stress studies …to demonstrate that the methodis suitable for determin。