近日，FDA发布了对LCC Ltd.的警告信，其中包含多个实验室数据完整性问题：

在中控实验室垃圾桶中看到丢弃的原始数据（例如pH 测试记录）。审查发现测试日期、pH 校准数据与最终测试报告之间存在差异。

在该垃圾桶中还发现了一份带有测试数据（例如 pH 值、比重）的废弃实验记录，与所报告的试验记录相比，测试日期不同。

在现场检查过程中，QC实验室的高效液相色谱（HPLC）/气相色谱 （GC）房间中看到垃圾桶装满了。后来回到该房间后，检查人员发现垃圾桶空了，然后跟随 QC 人员来到外面的垃圾箱，在那里员工取回了装有丢弃测试数据的垃圾袋。

丢弃的测试数据包括不合格的 HPLC 分析计算，但所报告的结果是合格的。也未执行OOS调查。

在该垃圾桶中还发现了熔点的原始数据，与所记录的数据不完全匹配。

FDA要求查看检验结果的电子原始数据时，工厂经理表示数据已丢失。

无法提供用于成品药 COA 报告的微生物检测数据。

FDA在警告信中要求对现任和前任员工进行访谈，以确定数据不准确的性质、范围和根本原因。并建议这些访谈由有资质的第三方进行。

FDA还要求聘请有资质的顾问进行广泛的年度审计，至少 2 年，以协助在执行数据完整性补救协议后评估 CAPA 的有效性

FDA要求其告知是否聘请一名首席诚信官，该首席诚信官完全有权接收员工报告数据完整性问题的匿名投诉，并有权确保及时调查任何潜在的违规行为（通过独立的质量保证职能部门，以及在需要时来自外部实体的专业知识）。

翻译如下：

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

Your laboratory records lacked complete and trustworthy data to support the analyses performed.

你们的实验室记录缺乏完整且值得信赖的数据来支持所进行的检测。

For example:

例如：

Our investigators observed original data (e.g., pH test     records) discarded in the trash located in your in-process laboratory. A     review of the discarded pH test records found discrepancies between the     test dates, pH calibration data, and the final test report. Additionally,     a discarded worksheet with test data (e.g., pH, specific gravity) was also     found in the trash with different dates for testing compared to the     reported worksheet.

我们的检查人员看到丢弃在中控实验室垃圾桶中的原始数据（例如 pH 测试记录）。对丢弃的 pH 测试记录的审查发现，测试日期、pH 校准数据与最终测试报告之间存在差异。此外，在垃圾桶中还发现了一份带有测试数据（例如 pH 值、比重）的废弃实验记录，与所报告的试验记录相比，测试日期不同。

During a walkthrough by the investigator, a full trash bin was     observed in the high-performance liquid chromatography (HPLC)/gas     chromatography (GC) equipment room of the quality control (QC) laboratory.     Upon later returning to the room, the investigator observed that the trash     bin was then empty, and then followed QC personnel to the outside dumpster     where the employee retrieved the trash bag with discarded test data. The     discarded test data included an HPLC assay calculation that failed     acceptance criteria, but the reported result was found within     specification. No out-of-specification (OOS) investigation was performed.     Additionally, raw data for melting point were also found in the trash and     did not completely match the data recorded.

在现场检查过程中，质量控制（QC）实验室的高效液相色谱（HPLC）/气相色谱 （GC）设备房间中看到垃圾桶装满了。后来回到该房间后，检查人员发现垃圾桶空了，然后跟随 QC 人员来到外面的垃圾箱，在那里员工取回了装有丢弃测试数据的垃圾袋。丢弃的测试数据包括未达到接受标准的 HPLC 分析计算，但所报告的结果是符合标准的。也未执行OOS调查。此外，在垃圾桶中也发现了熔点的原始数据，与所记录的数据不完全匹配。

Upon request to review the electronic raw data for your assay     test results generated for drug products distributed to the U.S. market,     your plant manager indicated the data was lost. In addition, you could not     provide the microbiological test data for testing reported on your     finished drug product COA upon request.

在要求查看美国市场药品的检验结果的电子原始数据时，你们的工厂经理表示数据已丢失。此外，你们无法根据要求提供用于成品药 COA 报告的微生物检测数据。

In your response, you acknowledge that your laboratory system lacks appropriate procedures and controls to ensure the integrity of your data. While we acknowledge your commitment to remediate your laboratory system, your response fails to fully consider the gaps and uncertainties in a retrospective review when there is a significant adverse pattern of data that is discarded, lost, or recorded non-contemporaneously. Additionally, your response did not consider plans to assess your manufacturing operation’s documentation system to determine where they are insufficient.

在你们回复中，你们承认实验室系统缺乏适当的程序和控制措施来确保数据完整性。虽然我们知道你们致力于修复实验室系统，但当存在重大的不合格数据被丢弃、丢失或非同期记录时，你们的回复未能充分考虑回顾性审查中的差距和不确定性。此外，你们的回复没有考虑评估你们的文件系统以确定它们不足的地方。

Reliability of data is fundamentally compromised when there is a failure to record or maintain complete and accurate records of test results, or conditions associated with all tests. Furthermore, the lack of reliable data compromises the QU’s ability to exercise its function of ensuring compliance to applicable standards.

当未能记录或维护测试结果或与所有测试相关的条件的完整和准确记录时，数据的可靠性会受到根本影响。此外，缺乏可靠的数据损害了质量部门行使其确保符合适用标准的职能的能力。

Data Integrity Remediation

数据完整性修复

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. 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.

你们的质量体系无法充分确保数据的准确性和完整性，以支持所生产的药物的安全性、有效性和质量。请参阅 FDA 指南《药物 CGMP 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。

We acknowledge that you are using an independent third-party consultant to perform data integrity (DI) training. However, we strongly recommend that you retain an independent third-party qualified consultant to audit your operation and assist in your DI remediation in meeting FDA requirements. In response to this letter, provide:

我们知道你们正在使用独立的第三方顾问来执行数据完整性（DI）培训。但是，我们强烈建议你们聘请独立的第三方合格顾问来审核你们的操作，并协助你们的DI 补救以满足 FDA 要求。回复此函请提供：

A comprehensive investigation into the extent of the     inaccuracies in data records and reporting. Your investigation should     include:

对数据记录和报告中不准确程度的全面调查。你们的调查应包括：

A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.

详细的调查方案和方法;评估涵盖的所有实验室、生产操作和系统的摘要;以及你们提议排除的任何部分的理由。

Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.

对现任和前任员工进行访谈，以确定数据不准确的性质、范围和根本原因。我们建议这些访谈由有资质的第三方进行。

An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.

评估你们工厂的数据完整性缺陷程度。识别遗漏、更改、删除、记录销毁、非同步记录和其他缺陷。描述发现数据完整性缺失的工厂操作的所有部分。

A comprehensive retrospective evaluation of the nature of the testing/manufacturing/other data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.

对检验/生产/其他数据完整性缺陷的性质进行全面的回顾性评估。我们建议在发现潜在违规行为的领域具有特定专业知识的有资质的第三方评估所有数据完整性问题。

A current risk assessment of the potential effects of the     observed failures on the quality of your drugs. Your assessment should     include analyses of the risks to patients caused by the release of drugs     affected by a lapse of data integrity and analyses of the risks posed by     ongoing operations.

对所发现的失败对药物质量的潜在影响的当前风险评估。你们的评估应包括分析因数据完整性失效而影响的药物放行对患者造成的风险，以及分析持续操作带来的风险。

A management strategy for your firm that includes the details     of your global CAPA plan. Your strategy should include:

贵公司的管理策略，包括CAPA 计划的详细信息。你们的策略应包括：

A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.

一份详细的纠正行动计划，描述你们打算如何确保所生成的所有数据的可靠性和完整性，包括检验数据、生产记录和提交给FDA 的所有数据。

A comprehensive description of the root causes of your data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.

对数据完整性失效的根本原因的全面描述，包括证明当前行动计划的范围和深度与调查和风险评估的结果相称的证据。说明对数据完整性失误负责的个人是否仍然能够影响贵公司的CGMP 相关数据或药物应用数据。

Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.

描述你们为保护患者和确保药物质量而采取或将要采取的措施的临时措施，例如通知用户、召回商品、进行额外检测、在稳定性计划中增加批次以确保稳定性、药物应用活动和加强投诉监控。

Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.

长期措施，描述旨在确保公司数据完整性的程序、流程、方法、控制、系统、管理监督和人力资源（例如，培训、人员配备改进）的任何补救工作和改进。

A commitment to have a qualified consultant conduct extensive annual audits, for at least 2 years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.

承诺聘请有资质的顾问进行广泛的年度审计，至少 2 年，以协助在执行数据完整性补救协议后评估 CAPA 的有效性。

Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).

告知FDA你们是否聘请一名首席诚信官，该首席诚信官完全有权接收员工报告数据完整性问题的匿名投诉，并有权确保及时调查任何潜在的违规行为（通过独立的质量保证职能部门，以及在需要时来自外部实体的专业知识）。

A status report for any of the above activities already underway or completed.

上述任何已进行或已完成的活动的状态报告。