近日，FDA发布了对中国药科大学仪器分析中心的警告信，警告信中披露该单位作为一个合同检测实验室，业务中包含对药物API和中间体的USP样品进行检测，FDA对其进行延伸检查并发现以下缺陷：

 

未能建立实验室控制记录

 

样品测试记录仅包含两行数字，没有标题或抬头。在检查期间，该单位解释说，这些数字代表样品的检测日期、批号和处理数据。

 

检测记录未记录样品制备、检测程序和系统适用性

 

在检测结果发送给与客户之前，未对所有测试记录进行第二人审核

 

未能确保在检查期间随时提供实验室记录。

 

该单位告知检查人员，2023 年 11 月之前的测试数据都存储在外部硬盘驱动器上。但是，当检查人员要求查看此数据时，他们表示可能很难找到数据，因为有许多归档的硬盘驱动器，并且只有归档人员才能检索数据。

 

计算机化系统没有足够的控制措施来防止未经授权的访问或更改数据。其中，检验仪器还用于学术教学和研究，不同用户共享同一个具有完全管理访问权限的登录 ID。

 

在检查期间被问及是否跟踪任何偏差和实验室错误时，该单位回答说他们只提供测试结果。

 

该单位的实验室主管表示，该单位不参与CGMP 活动，但是，FDA表示：他们的客户将数据用于 CGMP 目的。

 

FDA在警告信中表示：该单位作为合同检测实验室，必须了解自己有责任完全按照 CGMP 进行作，并将这些药物测试过程中遇到的任何不合格结果或重大问题告知所有客户。

 

警告信翻译如下：

 

Dear Mr. Shen:

 

The U.S. Food and Drug Administration (FDA) inspected your contract testing laboratory, Center for Instrumental Analysis of China Pharmaceutical University, FEI 3005037448, at Zhongyang Road, No. 24 Tongjiaxing Road, Nanjing, Jiangsu, from September 18 to 20, 2024.

 

This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).

 

FDA 于2024 年 9 月 18 日至20 日检查了位于江苏省南京市通嘉兴路 24 号中阳路的中国药科大学仪器分析中心（FEI 3005037448）。 本警告信总结了活性药物成分 （API） 与CGMP的重大违规。

 

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, the APIs you tested are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).

 

由于你们的制造、加工、包装或保存方法、设施或控制不符合CGMP，你们所测试的 API 按照FD&C 法案501（a）（2）（B）、21 U.S.C. 351（a）（2）（B）被认定为掺假。

 

We reviewed your September 23, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.

 

我们详细审阅了你们于 2024 年 9 月 23 日对FDA 483的回复，并确认收到你们的后续信件。

 

During our inspection, our investigators observed specific deviations including, but not limited to, the following.

 

在我们的检查过程中，我们的检查人员观察到了具体的缺陷，包括但不限于以下：

 

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

 

未能建立实验室控制记录，其中包括从所有实验室测试中获得的完整数据，以确保API 和中间体符合既定规范和标准。

 

Your firm is a contract testing laboratory that analyzes APIs and intermediates, including samples of crude(b)(4), (b)(4), and (b)(4) USP, for the presence of (b)(4) using 1H Nuclear Magnetic Resonance spectroscopy (NMR).

 

贵单位是一家合同检测实验室，使用 1H 核磁共振波谱 （NMR） 分析 API和中间体，包括粗品 （b）（4）、（b）（4） 和 （b）（4） USP 样品中是否存在（b）（4）。

 

Your firm failed to ensure that laboratory testing records were complete. For example, your test record of samples, “(b)(4)(USP) Experiment Records” for Lot (b)(4) contained only two lines of numbers with no explanation headers or titles. During the inspection, you explained that these numbers represented the testing date, lot number, and processing data for (b)(4) samples you analyzed for your customers. Further, the testing records did not document sample preparation, the test procedure(s), and system suitability. Additionally, not all the testing records were reviewed by a second person prior to the results being shared with your customers.

 

贵单位未能确保实验室检测记录完整。例如，你们的样品测试记录，XX批次的“XX（USP）实验记录”仅包含两行数字，没有说明标题或抬头。在检查期间，你们解释说，这些数字代表你们为客户分析的 （b）（4） 样品的检测日期、批号和处理数据。此外，检测记录未记录样品制备、检测程序和系统适用性。此外，在与客户共享结果之前，并非所有测试记录都由第二人审核。

 

Your firm also failed to ensure that laboratory records were readily available during the inspection. You informed our investigators that your(b)(4) 1H NMR testing data before November 2023 were stored on external hard drives. However, when our investigators requested to review this data, you stated that it might be difficult to locate the data because there were many archived hard drives and only the archiving personnel could retrieve the data. As a result, you did not provide any CGMP data stored on the external hard drives for review during the inspection. We acknowledge that you provided limited data after the inspection.

 

贵单位也未能确保在检查期间随时提供实验室记录。你们告知我们的检查人员，你们在2023 年 11 月之前的 （b）（4） 1H NMR 测试数据都存储在外部硬盘驱动器上。但是，当我们的检查人员要求查看此数据时，你们表示可能很难找到数据，因为有许多归档的硬盘驱动器，并且只有归档人员才能检索数据。因此，在检查期间，你们没有提供存储在外部硬盘驱动器上的任何CGMP 数据以供审计。我们也知道你们在检查之后提供了有限的数据。

 

Additionally, your firm failed to ensure that your computerized systems, such as the computers used to control to the NMR equipment, and to store raw data files or process data, have adequate controls in place to prevent unauthorized access or changes to data. The NMR equipment was also used for academic teaching and research, and it appears that various users shared one login ID with full administrative access.

 

此外，贵单位未能确保你们的计算机化系统（例如用于控制NMR 设备以及存储原始数据文件或过程数据的计算机）具有足够的控制措施来防止未经授权的访问或更改数据。NMR 设备还用于学术教学和研究，似乎不同的用户共享同一个具有完全管理访问权限的登录 ID。

 

In your response, you acknowledge your failure to keep adequate records and have now established procedures outlining requirements for laboratory documentation and sample tracking. You also state that you implemented user management settings on your computerized system and completed the system validation.

 

在你们的回复中，你们承认未能保存足够的记录，并且现在已经建立了概述实验室文件和样品追溯要求的程序。你们还声明在计算机化系统上实施了用户管理设置并完成了系统验证。

 

Your response is inadequate because the procedures appear to lack sufficient detail to be effective. Moreover, you did not consider a retrospective review and risk assessment to evaluate the potential impact of the inadequate documentation and lack of access controls, along with their associated risks, on the validity of your test results.

 

你们是回复是不充分的，因为这些程序似乎缺乏足够的细节来确保有效。此外，你们没有考虑进行回顾性审查和风险评估，以评估文件不充分和缺乏访问控制及其相关风险对测试结果有效性的潜在影响。

 

In response to this letter, provide:

 

回复此函，请提供：

 

A complete assessment of     documentation systems used throughout your laboratory operations to     determine where documentation practices are insufficient. Include a     detailed corrective action and preventive action plan that comprehensively     remediates your firm’s documentation practices to ensure you retain     attributable, legible, complete, original, accurate, contemporaneous     records throughout your operation.

 

对整个实验室操作中使用的文件系统进行全面评估，以确定文件记录实践不足的地方。包括详细的纠正措施和预防措施计划，全面纠正你们的文件记录实践，以确保在整个操作过程中保留可追溯、清晰、完整、原始、准确、同步的记录。

 

A risk assessment     summarizing the potential impact of inadequate documentation on product     quality, and a commitment to notify customers of any deficiencies.

 

一份风险评估总结文件不充分对产品质量的潜在影响，并承诺将任何缺陷通知客户。

 

A risk assessment     summarizing the potential impact of lack of access controls of the     computers and NMR equipment on product quality, and a commitment to notify     customers of any deficiencies.

 

一份风险评估总结计算机和 NMR 设备缺乏访问控制对产品质量的潜在影响，并承诺将任何缺陷通知客户。

 

See FDA’s guidance documentData Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/media/119267/download.

 

请参阅 FDA指南《药物 CGMP 的数据完整性和合规性》，了解有关在建立和遵循 CGMP 合规数据可靠性实践的指南。

 

2. Failure of your quality unit to ensure that drugs are appropriately tested and the results are reported.

 

质量部门未能确保药物得到适当的测试并报告结果。

 

You failed to establish a quality unit (QU), including defining responsibilities and procedures applicable to a QU. Additionally, when asked during the inspection whether you track any deviations and laboratory errors, you responded that you only provide testing results. Your laboratory director stated that the firm is not involved in CGMP activities, however, your customers used your data for CGMP purposes.

 

你们未能建立质量部门（QU），包括制定适用于 QU 的责任和程序。此外，在检查期间被问及你们是否跟踪任何偏差和实验室错误时，你们回答说你们只提供测试结果。你们的实验室主管表示，贵单位不参与CGMP 活动，但是，你们的客户将你们的数据用于 CGMP 目的。

 

Without an adequate QU and quality system in place, there is inadequate assurance that controls are implemented to ensure that your CGMP testing operations are performing in a state of control.

 

如果没有足够的 QU 和质量体系，就无法充分保证实施控制措施来确保你们的 CGMP 测试操作在受控状态下执行。

 

In your response, you state that you established a quality department and provided supporting documentation, including standard operating procedures. Your response is inadequate as your procedures appear to lack sufficient detail and comprehensive coverage of all the systems supporting your CGMP testing operations.

 

在回复中，你们声明建立了质量部门并提供了支持文件，包括标准操作程序。你们的回复是不充分的，因为你们的程序似乎缺乏足够的细节并全面覆盖支持 CGMP 测试操作的所有系统。

 

In response to this letter, provide:

 

回复此函，请提供：

 

A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:

 

全面的评估和补救计划，以确保你们的 QU 获得有效运行的权限和资源。评估还应包括但不限于：

 

A determination of whether procedures used by your firm are robust and appropriate.

 

确定贵单位所使用的程序是否稳健和适当。

Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.

 

在整个操作过程中进行QU 监督的规定，以评估对适当做法的遵守情况。

A complete and final review of the laboratory record for each sample and its related information before the QU disposition decision.

 

在 QU 处置决定之前，对每个样本的实验室记录及其相关信息进行完整和最终的审查。

Oversight and approval of investigations and discharging of all other QU duties to ensure validity of the laboratory test results without having negative impact on identity, strength, quality, and purity of your customers’ drug products.

 

监督和批准调查并履行所有其他 QU 职责，以确保实验室检测结果的有效性，而不会对客户药品的特性、强度、质量和纯度产生负面影响。

 

A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedures to ensure changes, such as changes to or deviations from a validated test method, are justified, reviewed, investigated, and approved by your QU. Your change management program should also include provisions for determining change effectiveness.

 

对变更管理系统进行全面、独立的评估。此评估应包括，但不限于，你们的程序，以确保变更，例如对已验证的分析方法的变更或偏差，由你们的QU论证、审查、调查和批准。你们的变更管理程序还应包括确定变更有效性的规定。

 

An adequate QU overseeing all elements of CGMP is necessary to consistently ensure drug product quality. Your firm’s quality systems are inadequate. See FDA’s current thinking on quality systems in the FDA guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download for help in implementing quality systems and risk management approaches.

 

一个适当的 QU监督 CGMP 的所有要素对于始终如一地确保药品质量是必要的。贵单位的质量体系不足。请参阅 FDA 指南《药品 CGMP 法规的质量体系方法》中 FDA 对质量体系的当前考量，以帮助实施质量体系和风险管理方法。

 

Responsibilities of a Contract Testing Lab

 

合同测试实验室的职责

 

FDA considers contractors as extensions of the manufacturer’s own facility. Your failure to comply with CGMP may affect the quality, safety, and efficacy of the drugs you test for your customers. It is essential that you understand your responsibility to operate in full compliance with CGMP, and that you inform all your customers of any out-of-specification results or significant problems encountered during the testing of these drugs.

 

FDA 将承包商视为制造商自身设施的延伸。你们不符合CGMP 可能会影响你们为客户检测的药物的质量、安全性和有效性。你们必须了解自己有责任完全按照 CGMP 进行操作，并将这些药物测试过程中遇到的任何不合格结果或重大问题告知所有客户。

来源：Internet

关键词： 仪器分析