缺陷关键词：数据可靠性，EXCEL表格不受控

企业名称：印度Alkem Laboratories

缺陷项描述：

A During the inspection, we observed two (2) different QC lab analyst demonstrate the ability to change calculation function in the excel spreadsheet used for finished product testing for the following:

在检查期间，我们发现2个不同的QC分析员可以修改成品检测所用EXCEL表格中的计算功能如下：

(1) On 22 March 2018, we observed your QC Analyst use an uncontrolled excel spreadsheet to calculate the Average, Standard Deviation, and %RSD values for (b)(4) Tablets, Batch #(b)(4) product release testing. The use of this spreadsheet is not mentioned in any written procedure when conducting (b)(4) Product Release Testing. In addition, this excel spreadsheet is not saved or printed. Therefore, the QC Reviewer is unable to verify these calculations are correct and the correct formula was used.

2018-03-22，我们发现你们QC分析员使用了一个未受控的EXCEL表格来计算XX片剂XX批号产品放行测试中的平均值、标准偏差和%RSD值。在所有书面程序中均未提及实施XX产品放行测试中使用此表格。另外，该EXCEL表格并未保存或打印。因此，QC复核人员无法确认这些计算是否正确，所用公式是否正确。

(2) On 23 March 2018, we observed the QC Reviewer use an uncontrolled excel spreadsheet to verify the potency of (b)(4) working standard during the Analytical Worksheet review for (b)(4) Tablets, Batch #(b)(4). The use of this spreadsheet is not mentioned in any written procedure when conducting Analytical Report reviews.

2018-03-23，我们发现该QC审核人员在审核XX片剂XX批号的分析工作表过程中使用了未受控的EXCEL表格来核实XX工作标准的效价。在所有书面程序中均未提及在执行分析报告审核时使用此表格。

B. On 19 March 2018, we observed your QC Manager’s use an excel spreadsheet to track quality functions, such as stability samples. This document is not maintained through document control and there is no protection from dat manipulation, overwriting, erasing of data, or audit trails.

2018-03-19，我们发现你们QC经理使用了一份EXCEL表格追踪质量函数，例如稳定性样品。此表格并未按照文件受控的原则进行维护，亦无防止数据篡改、改写、数据擦除或审计追踪的手段来进行保护。

C. On 19 March 2018, during the inspection, we observed two (2) (b)(4) employees use an uncontrolled spreadsheet to calculate due dates used during the manufacturing and packaging of drug products.

2018-03-19，在检查期间，我们发现2个XX员工使用了未受控表格来计算药品生产和包装中所用的有效期。

(1) For example, but not limited to, the (b)(4) stage is to be completed within (b)(4) initiating the compressed tablet stage. However, the dates used to calculate these timeframes has not been validated. In addition, this spreadsheet was no password protected.

例子包括但不限于，XX步骤是在压片开始之后XX时间内完成。但是用于计算这些时间的日期并未经过验证。此外这些表格亦无密码保护。

缺陷关键词：数据可靠性，记录保存

企业名称：印度Alkem Laboratories

缺陷项描述：

In addition, your firm failed to maintain and retain logbooks that are not obsolete or outdated. For example, once completed your firm destroys logbooks from the following areas: (b)(4) block warehouse, Housekeeping (b)(4)-Block QC, (b)(4)-Block QA,(b)(4)-Block Manufacturing, (b)(4)-Block, QC, Warehouse, and Production-(b)(4)Block.

另外，你公司未维护和保存过期的台账记录。例如，一旦完成，你公司即把以下区域的台账记录销毁：XX车间仓库、库管XX车间QC、XX车间QA、XX车间生产、XX车间、QC、仓库和生产-XX车间。

As recent as 2018, the destruction of logbook examples include, but are not limited to: Notification Record for Invalid Data, Line Clearance Checklist, Preventive Maintenance, Instrument Logbooks, training records, cleaning check lists.

近至2018年，台账记录的销毁例子包括但不仅限于：无效数据通知记录、清场记录、预防性维护记录、仪器日志、培训记录、清洁检查清单。

缺陷关键词：数据可靠性，批记录

企业名称：中国湖南新合新

缺陷项描述：

Failure to prepare and use production and control records for each intermediate and API batch.

未为每个批次中间体和原料药制订并使用生产和检验批记录。

Your Quality Unit failed to retain and locate 20 of (b)(4) of your (b)(4) base batch records, including but not limited to records for batches (b)(4) and (b)(4).In your response, you stated the batch records “are not missing” and are “archived properly.” Your response is inadequate because you did not provide evidence, such as copies of the executed batch records.

你们质量部门未能保存和找到20批你们的XX批产品的记录，包括但不仅限地XX批和XX批记录。在你们的回复中，你们声称批记录“并未丢失”，而是“妥善归档保存”了。你们的回复是不充分的，因为你们未提交证据，如已执行批记录的副本。

Additionally, your Quality Assurance department approved batch record 0220151203 and batch record0220151204 despite the inaccuracy of the weight of raw materials added. In your response, you stated the operator “did not follow the procedure” and did not recognize this as a deviation. You also stated personnel had “inadequate awareness of deviations.” It is your responsibility to ensure the accuracy and completeness of your batch records in order to establish that your manufacturing process was followed and is reproducible.

另外，你们的QA部分已批准了批记录0220151203和批记录0220151204，但所加入的原料重量是不准确的。在你们的回复中，你们声称操作工“未遵守程序”，并且不认为这是一个偏差。你们还声称人员“对偏差的了解不足”。你们有责任确保你们批记录的准确性和完整性，以证明你们遵守你们的生产工艺，并且工艺是可重复的。

缺陷关键词：数据可靠性，捏造COA数据

企业名称：日本Daito Kasei Kogyo Co., LTD., Okayama Factory

缺陷项描述：

Failure to completely report test results on certificates of analysis.

未在COA上完整报告检测结果

During the inspection, were viewed certificates of analysis (COA) for batches of (b)(4) API that you manufactured and released between June 2011 and February 2016. Your quality control unit signed these COA, which indicated that all required tests had been conducted on these batches. However, you told our investigator during the inspection that you signed these COA without having conducted all the tests for which you reported results on these COA. For example, your COA reported the results of identity and impurities tests that you never conducted.

在检查期间，我们审核了你们在2011年至2016年2月期间生产和放行的XX批次API的COA。你们的QC部门签署了这些COA，这表示对这些批次的所有所需检测均已执行。但是，你们在检查期间告诉我们调查人员说你们并未执行所有检测就获得了这些COA上的报告结果，并签署了这些COA。例如，你们的COA报告了鉴别结果和杂质检测，但你们根本未进行检测。

You falsified the COA you issued to your customers. Regulators and customers rely on COA for accurate information about the quality and sourcing of drugs and their components. Falsifying information about the quality of your drugs on COA compromises supply chain accountability and traceability, and may put consumers at risk.

你们捏造了签发给客户的COA。法规监管人员和客户依赖于COA，来确认药品及其成分的质量准确信息和来源。在COA上捏造关于你们药品的质量信息使得供应链可靠性和可追溯性受到破坏，可能会将消费者置于风险下。

缺陷关键词：数据可靠性

企业名称：韩国Cosmecca Korea Co., Ltd.

缺陷项描述：

Your firm’s quality control unit failed to review and approve all drug product production and control records to determine compliance with all established, approved written procedures before a batch is released or distributed (21 CFR 211.192).

你们公司的质量控制部门未能审核和批准所有药品生产和检测记录来确定产品在放行或销售之前是否符合所有既定的已批准的书面程序(21 CFR 211.192)。

Your OTC sunscreen drug product, (b)(4), contains (b)(4) active ingredients: (b)(4).Your batch records for lot (b)(4)of this product included concentration values for these active ingredients that did not match the data found in your instruments. You used the inaccurate data reported in your batch records to calculate potency results that were within specification, and you relied on these inaccurate results to release your product. However, when we used the instrument data instead of the results in your batch records to perform the same calculations, we found that the lot was out-of-specification (OOS)(super potent) for (b)(4) active ingredients. Your quality unit did not identify this discrepancy prior to releasing this lot.

你们的OTC防晒药品XX中含有XX活性成分：XX。你们XX批次的该药品的批记录包括有这些活性成分的浓度值，与在你们仪器中发现的数据并不相符。你们使用了不准确的数据报告在你们的批记录中用以计算得到符合质量标准的含量结果，你们依赖这些不准确的结果来放行你们的产品。但是，当我们使用仪器中的数据替代你们批记录中的数据来进行相同的计算时，我们发现该批次的XX活性成分是OOS(超过效价)。你们的质量部门在放行此批准时并未发现此分歧处。

缺陷关键词：数据可靠性，计算机化系统，权限控制

企业名称：韩国Cosmecca Korea Co., Ltd.

缺陷项描述：

Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).

你公司未能对计算机和相关系统执行适当的控制以确保只有经过授权的人员才可以修改主生产和检测记录以及其它记录(21 CFR211.68(b))。

Laboratory equipment used to generate analytical data for release purposes lacked restricted access. For example, analysts shared usernames and passwords, and all users had administrator rights that permitted them to delete or modify files in high-performance liquid chromatography and gas chromatography equipment. You had no mechanism to facilitate traceability of the individuals who changed, adjusted, or modified data generated by computerized systems.

用于生成放行所需的分析数据的实验室设备缺乏权限控制。例如，实验室共用用户名和密码，所有用户都具有管理员权限，均可以删除或修改HPLC和GC仪器中的文件。你们没有机制来审计跟踪何人修改、调整或改动了计算化系统生成的数据。

缺陷关键词：数据可靠性，伪造实验室数据

企业名称：印度Alchymars ICM SM Private Limited

缺陷项描述：

Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure your API complies with established specifications and standards.

没有实验室检测记录，其中包括为确保你们API符合既定质量标准所实施的所有实验室测试所生成的完整数据。

Our investigator found that your firm was falsifying laboratory data. For example, the number of colony-forming units (CFU) found on (b)(4) plates for (b)(4)water point-of-use tests differed substantially from the number recorded on your (b)(4) water report. For multiple points of use, your analyst reported far fewer CFU than observed on the plate by our investigator. In addition, while you reported absence of growth on a selective media plate used to detect objectionable microorganisms, our investigator observed growth on this plate. This is concerning because you use(b)(4) water to manufacture products, such as (b)(4) API, that are intended for use in sterile injectable dosage forms.

我们的调查人员发现你们公司伪造实验室数据。例如，在XX用水点检测XX碟上发现的菌落形成单位(CFU)数量与你们的XX水报告上所记录的数值有显著差异。有多个使用点，你们分析员所报告的数值都远低于我们调查人员在你们碟上看到的。另外，虽然你们报告说在一个用于检出致病菌的选择性培养基碟上未检出微生物生长，但我们调查人员却在该碟上看到了微生物生长。这种情况令人担忧，因为你们使用XX水用于例如XX原料药的生产，该原料药又将用于无菌注射制剂药品的生产。

缺陷关键词：数据可靠性，检测数据

企业名称：中国浙江绿岛科技

缺陷项描述：

Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to assure compliance with established specifications and standards (21 CFR 211.194(a)).

你们公司未能确保实验室记录包括为确保符合既定质量标准所必须的所有检测项的完整数据(21 CFR211.194(a))。

Your firm lacks basic laboratory controls to prevent changes to paper and electronic records for your over-the-counter (OTC) drug products. You were not able to provide analytical test data for three batches of (b)(4) spray and one batch of (b)(4). We found that you created certificates of analysis (COA) for these four batches before they were manufactured and tested.

你们公司缺乏基本的实验室控制来防止对OTC药品纸质和电子记录进行修改。你们无法提供3批XX喷雾剂和1批XX的分析检测数据。我们发现你们在这4批药品生产和检测之前就编制了它们的COA。

When questioned, your firm acknowledged falsifying the analytical test results on the COA you used to support release and distribution of (b)(4) spray and (b)(4) drug products to the United States.

在问到你们时，你们公司告知我们你们捏造了用以支持放行和销售至美国XX喷雾剂和XX药品的COA上的分析检测结果。

In addition, we found three electronic data files in the electronic recycle bin of the stand-alone HPLC system you used to test finished drug product (b)(4) spray. Because this instrument lacks back-up and audit trail capabilities, we could not determine how frequently test data obtained prior to “official” batch testing was discarded. You were unable to explain why these electronic files were deleted.

此外，我们在你们用以检测成品XX喷雾剂的单机版HPLC系统的电子回收站发现3个电子数据文件。由于此仪器缺乏备份和审计追踪能力，我们无法确定你们在“正式”批检测之前弃除了多少次的检测数据。你们无法解释为什么要删除这些电子文件。

cGMP-related data must be retained by a laboratory to enable appropriate assessments and decisions by the quality unit regarding batch disposition and to demonstrate ongoing control.

实验室必须保存cGMP相关的数据，供质量部门进行适当的评估和批处理决定并保证其持续受控。