山东章丘-金达药化被FDA和欧盟双杀

风云舍2018-06-12 16:25:38

【FDA警告信】(320-17-25)济南金达(山东章丘)


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相关链接:EU GMP不合格报告:济南金达药化

警告信编号

320-17-25

检查公司

济南金达药化(山东章丘)

检查时间

20165月30-6月1

缺陷项

1.    Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP, and meet established specifications for quality and purity.

 你们质量部没有履行其确保在你们工厂生产的API符合CGMP并符合为质量和纯度建立的既定标准的职责。

 Your quality control laboratory disregarded multiple out-of-specification (OOS) impurity results without justification. For example, on September 22, 2015, you encountered an OOS unknown impurity peak during high performance liquid chromatography (HPLC) testing of (b)(4) 36-month stability batch (b)(4). You terminated the analysis. Testing of a new sample also showed the OOS impurity peak. The chromatogram was then manually rescaled, which hid the presence of this peak. Your laboratory set the integration parameters to omit this peak from integration. Because the peak was omitted, the quality unit was not provided with full information to evaluate whether the stability batch, and potentially other marketed batches, continued to meet quality standards.

你们的质量控制实验室在任何合理理由的情况下删除多个杂质OOS结果。例如,在2015年9月22日,你们在用HPLC进行某产品某批次第36个月稳定性样品分析时观察到一个超过限度的(OOS)的未知杂质峰。但是你们中止了分析。检测了一个新样品仍然显示含有该超过限度的杂质峰。之后该色谱图被手动调整,隐藏了这个杂质峰的存在。你们的实验室设置了积分参数以从积分中删除该杂质峰。因为该杂质峰已被删除,质量部没有得到全部信息来评价该稳定性批次,和潜在的其他市售批次,是否仍符合质量标准。

 In addition, your audit trail showed that from July 1 to 2, 2015, you performed seven sample injections of (b)(4) 60-month stability batch (b)(4) to test for impurities using HPLC. You permanently deleted the first five sample injections. You then renamed the last two injections and reported that they met specifications. Your quality unit failed to identify and address these serious data manipulations.

另外,你们的审计追踪显示在2015年7月1日至2日间,你们用HPLC进了7针样品检验某产品某批的第60个月稳定性样品的杂质。你们永久性地删除了前5针的分析结果。然后重新命名后2针,并报告它们符合质量标准。你们的质量部没有发现和处置这类数据篡改。

2.    Failure to adequately investigate out-of-specification results.

没有充分调查超标(OOS)结果。 

 Your firm did not initiate investigations into failing results as required by your standard operating procedure (SOP) ZL/SOP/ZK/00405. On October 5, 2015, when you encountered an OOS value for an unknown impurity peak through HPLC testing of (b)(4) API 12-month stability batch (b)(4), you prepared and tested new aliquots. You did not investigate the failing result.

贵公司没有按照你们编号为ZL/SOP/ZK/00405的SOP 要求对不合格结果发起调查。2015年10月5日,当你们用HPLC分析某API 某批次第12个月稳定性样品时发现一个未知杂质峰超过限度时,你们制备并分析了新的样品你们没有调查该不合格结果。

We acknowledge your commitment to hire a third-party consultant to identify and evaluate all batches compromised by data integrity lapses. However, you failed to perform a comprehensive retrospective evaluation to determine whether appropriate corrective actions and preventive actions were identified and implemented for each OOS result obtained. Also, your retrospective review does not appear to address whether data integrity breaches occurred when using laboratory methods and systems that do not generate electronic data.

 我们承认你们承诺将雇佣第三方顾问来识别并评估所有受数据完整性影响的批次。然而,你们没有执行一个全面的回顾性评估来确定是否为每一个出现的OOS结果确定并实施了适当的纠正措施和预防措施。你们的回顾性审核也没有体现当使用没有声称电子数据的实验室方法和系统时数据完整性违规是否发生。

For more information about handling OOS results and documentation of your investigations, please refer to the FDA guidance for industry publication Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production available online athttp://www.fda.gov/downloads/Drugs/.../Guidances/ucm070287.pdf.

更多处理OOS结果和调查文件,请参考FDA为行业制定的指南文件:制药生产中的OOS分析结果的调查。

 3.    Failure to prevent unauthorized access or changes to data, and failure to provide adequate controls to prevent omission of data.

未能防止非授权的访问或对数据进行修改,未能为防止数据北删除提供足够的控制措施。 

 Our investigator observed that your laboratory systems lacked controls to prevent your staff from altering or deleting electronic data. Analysts manipulated and deleted audit trails. You lacked adequate controls for all HPLC, gas chromatography, and ultra-violet systems.

我们的检查员发现你们的实验室系统缺乏防止你们的员工修改或删除电子数据的控制措施。分析人员篡改并删除了审计追踪。你们对所有HPLC、气相和紫外光谱缺乏足够的控制措施。 

 For example, an analyst deleted audit trails in your gas chromatography equipment #YQ-07-10 from September 15, 2015, through April 24, 2016, and permanently deleted audit trails from November 6 to 13, 2015. In addition, our investigator observed that your quality control manager and quality control deputy manager had full administrative rights on all of your computerized systems, which allows them to manipulate data and turn off audit trails.

例如,一个分析员在你们的气相色谱仪#YQ-07-10中删除了2015年11月6~13日的审计追踪。另外,我们的检查员发现你们的QC经理和QC副经理对你们的所有计算机化系统都有完整管理权限,这无疑为他们篡改数据和关闭审计追踪开了后门。

 We acknowledge that you commit to upgrading your analytical systems to be compliant with CGMP requirements. However, procuring new instruments, installing new and upgraded data acquisition software, and enabling various software features are insufficient to achieve CGMP compliance. These steps will be effective only if you implement appropriate procedures and systems to ensure that your quality unit reviews all production and control data and associated audit trails as part of the batch release process.

我们承认你们承诺了要升级你们的分析系统以符合CGMP要求。然而,购买新仪器,安装新的升级的数据采集软件,和启用各种软件端口并不足以达到CGMP要求。这些步骤仅在当你们实施了适当的程序和体系来确保你们的质量部门审核所有生产和检验数据,以及相应的审计追踪作为批放行程序的一部分时才会有效。 

 Your response states that your SOP for electronic data management specifies that only information technology staff will have full administrator rights. However, you did not specify which information technology personnel will have these administrator rights. In addition, this SOP became effective on May 9, 2016, prior to the FDA inspection. However, your quality control management still had full administrative rights to all computerized systems during our inspection from May 30 to June 1, 2016.

你们的回复说你们的电子数据管理SOP规定了只有IT人员才能有最高管理权限。然而,你们没有指定哪个IT人员才有这种管理权限。另外,该SOP在FDA检查之前,2016年5月9日就生效了。然而你们的QC经理在2016年5月30到6月1日我们检查期间仍然对所有计算机化系统拥有最高管理权限 。


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