检查员能有点击回复的吗？药企也可做参考——之一

领松（GMP）

前些日子发的帖子——《想试发一些与认证检查员有关的帖子，不知能否讨论起来？》 heatlevel  ...234。
结果看来还能够讨论起来。于是乎便想继续发帖子，期待大家的回复讨论。

10版GMP在认证检查时各章的检查重点，究竟怎么检查，才不失于GMP的精髓和宗旨？才不流于形式？才能真正起到认证的初衷和效果？

针对第二章：看一个药企是真GMP,还是假GMP，就看他的QA和QC的人数能不能干的过来？也就是说，根据该药企的剂型、品种、用水点、洁净区的数量等等，判断出QA的工作量、QC的工作量，推断出究竟需要多少QA、QC的人数。然后，再看看该药企的QA、QC的用工合同。——因为确有认证时临时借用的现象。
检查员是这样检查的吗？药企的老板都重视QA、QC了吗？

至于质量风险管理的部分，即十三、十四、十五条。检查员重点检查其“系统过程”，看看是否出现了梗阻？还有就是带有“风险评估”的条款，看看是否做到位了，譬如，第一百三十八条。就是说凡是涉及到的验证，必须要进行“风险评估”。对药企的工作量是很大的，对检查员的要求也是很高的！

怀谷

问得好！

yuansoul

怀谷 发表于 2014-6-17 11:30
问得好！

你说哪句？

青城/怒云

借用的只是不是关键人员
检查员好像不能把人家开除吧
也不说不是企业人员吧

yyylggglll

孙悟空都有真假，儿子也有真假。

qdxuanyu

人员是否被重视，检查看不出来吧

冰城

检查应该深入下去，不是看和听，而是多去问一线的人员，如果做好换位思考，会事半功倍。如对于QA人员，看培训记录和合同档案不会有任何问题的，反而去现场对工作细节进行提问、工作职责进行梳理、工作关键点进行观摩，会发现一些真实的问题。

咕咕

人数没见有规定多少，一人身兼数值的现象很多。

领松（GMP）

575231000 发表于 2014-6-17 11:41
检查应该深入下去，不是看和听，而是多去问一线的人员，如果做好换位思考，会事半功倍。如对于QA人员，看培 ...

同意。用工合同还是能够看出来的吧？
认真回复讨论谢了！

pczzq

Dear Mr. Subramanian Kalyanasundaram:



During our November 13 through November 16, 2013, inspection of your pharmaceutical manufacturing facility, Sun Pharmaceutical Industries Limited - Karkhadi located at Plot No. 817/A, Village, Karkhadi, Taluka, Padra District, Vadodara, Gujarat, India, investigators from the U.S. Food and Drug Administration (FDA) identified violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211, and deviations from current good manufacturing practice (CGMP) for the manufacture of active pharmaceutical ingredients (APIs). These violations and deviations cause your drug products and APIs to be adulterated within the meaning of Section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 351(a)(2)(B), in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.

检查日期：2013年11月13-16日



We have conducted a detailed review of your firm’s initial response and note that it lacks sufficient corrective actions.  We also acknowledge receipt of your firm's additional correspondence dated January 28, 2014, and March 11, 2014.   

我们对你们公司的首次回复进行了仔细审阅，发现你们的纠正措施不够充分。我们也收到了你们的补充回复，回复日期分别为2014年1月28日和2014年3月11日。



Our investigators observed specific deviations during the inspection of the API manufacturing facility, including, but not limited to, the following:

我们的调查员在对原料药生产场所的检查中发现了一些偏差，包括但不仅限于以下内容：



1.    Failure to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards.

未在保证化验室记录包括所有检测中产生的完整数据，无法保证与已有质量标准的符合性。



For example,

例如



a.    Your firm is missing the fundamental raw data and information necessary to document your analyses. For example, these analyses lack the following critical data:

公司缺失分析的基本原始数据和资料。例如，以下关键数据缺失：

identification of the samples tested, including name and source, batch number or other distinctive code, and date of the sample
the complete record of all raw data generated during each test, including graphs and electronic files from laboratory instrumentation
test method used
sample preparation as prescribed by the method, preparation and testing of standards, reagents and standard solutions
records of all calculations performed in connection with the test
test results
the signature of the person who performed each test and the date(s) the tests were performed, and the date and signature of a second person showing that the original records have been reviewed for accuracy, completeness, and compliance with prescribed acceptance criteria
所检样品的识别信息，包括品种、来源、批号或其它可区分的代码，取样日期
在所有检测中产生的所有原始数据的完整记录，包括图谱和化验室仪器产生的电子文件
所用的检验方法
按方法进行样品制备的记录、标准品、试剂和标准溶液的制备和检测
所有与检测相关的计算记录
检验结果
各检验的检验员签名和检测日期，以及对原始记录复核其准确性、完整性和与可接受标准的符合性的第二人签名和日期


This basic analytical information allows for documentation, review, authentication, traceability, quality control and quality assurance at your pharmaceutical firm.

这些基本的分析数据是保证你们制药公司进行记录、审核、确认、追踪、质量控制和质量保证所需的原始资料。



In addition, minimum laboratory control also includes documenting and retaining your system suitability data.   

另外，对化验室进行控制的最低要求也应包括文件记录和对系统适用性数据的保留。

郝小琴

咕咕 发表于 2014-6-17 11:45
人数没见有规定多少，一人身兼数值的现象很多。

恩，是的

pczzq

这是前几天坛子里分享的一部分内容，我们的企业怎么干的？检查员是怎样检查的？对比一下就可以了。

pczzq

b.    Your firm frequently performs “unofficial testing” of samples, disregards the results, and reports results from additional tests. For example, during stability testing, your firm tested a batch sample six times and subsequently deleted this data.   

你们公司频繁地对样品进行“非正式的检测”，而不管结果如何，也不对额外的检测所得的结果进行报告。例如，在稳定性试验期，你们公司对一个批号的样品检测了6次，随后删除了数据。



Our investigators found your practice of performing initial “trial” sample high performance liquid chromatography (HPLC) analyses prior to acquiring the “official” analyses. The “trial” sample results were subsequently discarded. “Trial” HPLC analyses for (b)(4) USP ((b)(4)) were apparently run as part of the 12-month long-term stability studies on batch #(b)(4) for related substances. The inspection revealed that on August 26, 2011, your employee ran an HPLC analysis sequence with the sample names (b)(4) and subsequently deleted the raw data files.  It was noted that the assigned names for the sequence injections indicates that your quality control staff named the samples using the last three digits of the batch numbers to link the "trial" injections for the batches with the official assay analyses. Your Senior Quality Control (QC) Officer confirmed that these were analyses of batch samples. Furthermore, we found that on August 27, 2011, this batch was analyzed for unknown impurities and the results were reported to be within specifications.  However, the chromatographic data showed that the "trial" injection data for this batch failed the unknown impurities specification of (b)(4)% in multiple cases.  

我们的调查员发现你们在对一个样品进行HPLC“正式”分析前，进行了“试验性”检测。该“试验性”样品结果随后被丢弃。对XXX批的“试验性”HPLC分析显然是XXX批有关物质12个月长稳试验的一部分。检查发现，在2011年8月26日，你们的员工运行了一个HPLC分析序列，样品名为XXX，随后删除了原始数据文件夹。还有，你们的QC人员采用了样品批号的最后三位数字对进样序列进行命名，以便将“试验性”进样与正式含量分析进行链接。你们的资深QC主管确认了这些批号样品的分析。另外，我们发现在2011年8月27日，对该批次进行了未知杂质的检测，结果报告符合质量标准。但是，图谱数据显示该批次“试验性”进样数据在多个结果中均不符合未知杂质的质量标准YYY。



Your Senior QC Officer confirmed that QC laboratory employees had frequently practiced the use of “trial” injections at your facility.   Significantly, in addition to the example above, our inspection found 5,301 deleted chromatograms on a computer used to operate two HLPC instruments in your QC laboratory. Many of these files were “trial” injections of batches.   

你们的资深QC主管确认了QC化验室员工经常在你们的仪器上进行“试验性”进样。除上述例子外，我们检查发现了你们QC实验室的1台控制2台HPLC仪器的电脑上，有多达5301个被删除的色谱图。这些文件多是“试验性”批次进样。

pczzq

Your response is inadequate in that you did not conduct an adequate investigation into the pervasive practice of deleting files. In the reports provided in your response, you did not identify what criteria you used to designate each type of HPLC and GC data files (e.g. blanks, standards, samples, and system suitability runs). The response does not identify any impurity standards used in your procedures and does not provide the procedures that your firm was using to conduct the “trial” and “unofficial” runs. In addition, your investigation found 47 instances of apparent trial injections of samples for which the results were out-of–specification (OOS), and some of these batches were distributed to the U.S. market. The investigation failed to adequately examine why your analysts hid or deleted these runs. Your response only explains that your firm chose to retest samples from the implicated lots, but does not address the causes of the original OOS results, or justify the basis of your decision to invalidate the original failing result and accept the passing retest result. Such an investigation is necessary for any OOS event. Refer to the FDA’s guidance on OOS investigations Guidance for Industry, Investigating Out-of-Specification (OOS), Test Results for Pharmaceutical Production.

你们的回复不充分。在回复中，你们没有对删除文件这种普遍的作法进行充分的调查。在你们回复所提供的报告中，你们没有识别出准备用什么标准来给每类HPLC和GC数据文件命名（例如，空白、标准、样品和系统适用性运行）。回复中没有识别出用于你们检测程序的所有杂质标准品，没有提供你们公司准备用于实施“试验性”和“非正式”测试的程序。另外，你们的调查发现有47例明显的试验性样品进样，其结果为OOS，其中一些批次已销往美国市场。调查未能充分检查为什么你们的化验员隐藏或删除这些测试。你们的回复只是解释了你们公司选择对相关批次样品进行复测，但没有说明原始OOS结果的原因，或论述你们决定将原始不合格数据认定无效，而接受复测的合格结果的原因。对所有的OOS事件，均需要进行这样的调查。请参见FDA对OOS调查的指南。

依雪轻寒

一般药企还真不重视QA，QC的人数，老板不给招人，那咋整！

pczzq

这是FDA的检查，我们的企业恐怕会被毙掉的占多少，你懂的{:soso_e100:}

冰城

领松（GMP） 发表于 2014-6-17 11:46
同意。用工合同还是能够看出来的吧？
认真回复讨论谢了！

真的，头一次听说检查员还会看这个，不过应该看不出来，顶多看出来是短期来的，甚至这个都看不出来，除非调取你的保险上交清单，不过如果遇到企业不给上交的也不好查。

yuansoul

qdxuanyu 发表于 2014-6-17 11:41
人员是否被重视，检查看不出来吧

美女少，恐龙多，说明重视人员

幻影

现在检查官想查肯定都能查到问题，但查出来怎么办，能怎么办？大环境不好，只能随大流了。

厚德载物008

根据车间多少，剂型不同，需要多少QA和QC及相关人员还是能大概估算出来的