FDA 就微生物检测选择性记录数据向 Eurofins SF Analytical Laboratories 发出警告信

2026年10月13日，FDA公布一封警告信。

检查对象：Eurofins SF Analytical Laboratories, Inc.（欧陆集团旗下美国子公司）

检查日期：2026 年 6 月 1 日至 3 日

483回复提交时间：2026 年 6 月 22 日

FDA 警告信日期：2026 年 10 月 6 日

This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).

本警告信概述了成品药品现行良好生产规范（CGMP）法规存在的重大违规事项。参见《美国联邦法规》第21篇第210和211部分（21 CFR 第210、211部分）。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, the drug products 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).

由于贵公司在生产、加工、包装或存放环节所采用的方法、设施或控制措施不符合CGMP要求，根据《联邦食品、药品和化妆品法案》（FD&C法案）第501(a)(2)(B)条（《美国法典》第21编351(a)(2)(B)）定义，贵公司检测的药品属于掺假药品。

We reviewed your June 22, 2026, response to our Form FDA 483 in detail.

我们已详细审阅贵公司2026年6月22日针对FDA 483表提交的回复材料。

Violations of the Federal Food, Drug, and Cosmetic Act

违反《联邦食品、药品和化妆品法案》事项

The following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.

以下为本次检查与审阅过程发现的违规事项。特此提醒，该清单并未穷尽贵生产场所存在的全部违规问题。

1. 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)).

1. 贵公司未能确保实验室记录包含所有为保证符合既定质量标准与规范所需开展的全部试验产生的完整数据（21 CFR 211.194(a)）。

Your firm conducts microbiological analyses of components and drug products for your customers.

贵公司为客户开展原料及药品的微生物检测。

You perform (b)(4) pour plate methods for microbial enumeration of (b)(4) samples. During the inspection, our investigator observed that your microbiologist failed to record the (b)(4) results when they were assessed as too numerous to count (TNTC), recording only the pour plate counts. The investigator also noted that while the (b)(4) for the pour plate samples was cracked and desiccated, the pour plate counts were recorded as within acceptable limits. When (b)(4) plates are desiccated and cracked, the media can no longer reliably support uniform microbial growth. A result recorded from a compromised plate, even one that falls within specification, cannot be considered valid, as the physical condition of the media may have suppressed or obscured actual microbial recovery.

贵公司采用(b)(4)倾注平板法对(b)(4)样品进行微生物计数。检查期间，我方检查员发现贵公司微生物检验人员在判定(b)(4)结果为菌落过多无法计数（TNTC）时，未记录该(b)(4)结果，仅记录倾注平板计数结果。检查员同时发现，部分倾注平板样品的(b)(4)已经开裂、干燥，但平板计数结果仍被记录为符合可接受限度。当(b)(4)平板干燥开裂时，培养基无法稳定支持微生物均匀生长。在受损平板上得到并记录的结果，即便数值符合标准，也不能视为有效结果，因为培养基物理状态可能抑制或掩盖真实的微生物回收率。

Additionally, your data review procedure is deficient in that it does not require secondary verification when an initial plate count is recorded as 0 colony forming units (CFU), creating a systemic gap where microbial growth can go undetected. During the inspection, the investigator identified a colony on a plate recorded as 0 CFU by your analyst. Further, several samples with desiccated and cracked (b)(4) were recorded as 0 CFU and discarded without secondary analyst review. The practice of non-reporting of TNTC (b)(4) results, and the investigator's direct observation of a colony on a plate recorded as 0 CFU illustrates the unreliability of your data, and further demonstrates that lack of secondary verification is unacceptable.

此外，贵公司的数据复核程序存在缺陷：当初次平板计数记录为0菌落形成单位（CFU）时，程序未要求二次复核，形成系统性漏洞，微生物生长情况有可能无法被检出。检查期间，检查员在检验员记录为0 CFU的平板上发现菌落。另有多个样品的(b)(4)干燥开裂，结果记录为0 CFU，未经第二名检验人员复核就被丢弃。不报告TNTC的(b)(4)结果、以及检查员直接观察到记录为0 CFU平板上存在菌落的事实，证明贵公司数据不可靠，也说明缺少二次复核的做法不可接受。

In your response, you state that analyst interviews and a retrospective review of laboratory data revealed inconsistent reporting practices dating back to February 2025. You acknowledge that some analysts were selectively recording test results, documenting only pour plate results when (b)(4) results were TNTC (out of specification), and only documenting (b)(4) results when they were within specification. You commit to revising your procedures, training analysts, and periodically auditing plate readings.

贵公司在回复中称，通过检验人员访谈与实验室数据回顾，发现自2025年2月起就存在报告操作不一致的问题。贵公司承认部分检验人员选择性记录检测结果：当(b)(4)结果为TNTC（超标）时，仅记录倾注平板结果；只有(b)(4)结果合格时，才记录(b)(4)结果。贵公司承诺修订SOP、培训检验人员，并定期对平板读数开展审计。

Your response is inadequate. You do not address whether the selective omission TNTC (b)(4) results during this period affected the accuracy of certificates of analysis issued to customers, or whether any customers received incomplete or potentially inaccurate microbiological data. Although you updated your reporting procedure to require secondary review, you provided no evidence to verify the completeness and accuracy of the historical data reviewed.

贵公司的回复不充分。贵公司未说明此期间选择性省略TNTC的(b)(4)结果，是否影响向客户出具的分析报告（COA）准确性，也未说明是否有客户收到不完整或潜在不准确的微生物数据。虽然贵公司更新报告程序，增加二次复核要求，但未提供证据证明已复核历史数据的完整性与准确性。

Reliability of data is compromised when there is a failure to maintain complete records of the conditions and data associated with all tests. Furthermore, the lack of complete data compromises the quality unit's (QU) ability to exercise its function of ensuring compliance to applicable standards.

如果无法完整留存所有试验相关条件与试验数据记录，数据可靠性就会受损。此外，不完整的数据会削弱质量部门（QU）履行职责、保证符合适用标准的能力。

In response to this letter, provide:

针对本警告信，请提供下述材料：

A comprehensive independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.
对贵公司实验室操作、规程、检测方法、设备、文件记录以及检验人员能力开展全面独立评估。基于本次评估，提交详细整改方案，并制定方案有效性评估计划。

A comprehensive assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm's documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.
对贵公司生产与实验室全流程的文件体系开展全面评估，识别文件管理存在缺陷的环节。提交详细纠正与预防措施（CAPA）计划，全面整改文件管理工作，确保在全部业务活动中，留存可归属、清晰可读、完整、原始、准确、同步记录的资料。

2. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).

2. 无论批次是否已经放行上市，当批次或其组分出现无法解释的偏差、不符合质量标准时，贵公司未能开展充分调查（21 CFR 211.192）。

Your firm failed to investigate aberrant media conditions (e.g., cracked or desiccated (b)(4) plates) used for testing raw material and drug product samples in your microbiological laboratory.

贵公司微生物实验室用于原料与药品样品检测的培养基出现异常状态（例如开裂、干燥的(b)(4)平板），贵公司未对此开展调查。

In your response, you state that you opened an investigation to determine the scope of affected samples and adequacy of results and transferred microbial samples into an alternative incubator as an interim measure. Based on analyst interviews and a limited records review, you concluded that the results are valid. We acknowledge your plan to retest affected samples as a means of confirming your initial test results.

贵公司在回复中表示，已经启动调查以确定受影响样品范围以及结果有效性，并将微生物样品转移至备用培养箱作为临时措施。贵公司基于检验人员访谈以及有限的记录审阅，判定检测结果有效。我们注意到贵公司计划复测受影响样品，以此验证初始检测结果。

Your response is inadequate. With out photographic evidence of plate conditions at the time of reading, there is no basis to retroactively confirm any result. Your conclusions rely solely on analyst interviews and data records that you acknowledged are unreliable. Furthermore, you did not commit to discontinuing the use of damaged plates for microbiological testing.

贵公司的回复不充分。缺少读数当时平板状态的照片证据，无法回溯验证任何结果。贵公司结论仅依靠检验人员访谈以及贵公司自己承认不可靠的数据记录。此外，贵公司未承诺停止使用受损平板开展微生物检测。

Data integrity depends on complete and accurate documentation of test results and conditions. Failure to maintain such records undermines the reliability of your data. The use of deficient media similarly compromises the validity of microbiological test results and raises questions about the suitability and robustness of your methods.

数据完整性依赖于完整、准确记录试验结果与试验条件。无法留存这类记录会破坏数据可靠性。使用存在缺陷的培养基同样会影响微生物检测结果的有效性，同时让人质疑检测方法的适用性与稳健性。

In response to this letter, provide:

针对本警告信，请提供：

A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.
针对偏差、不符项、投诉、超标结果、超限结果、不合格事项的整体调查体系开展全面独立评估。提交详细整改方案。方案内容包括但不限于：提升调查能力、范围判定、根本原因分析、CAPA有效性评估、质量部门监督以及书面规程。说明贵公司如何保证调查全流程规范开展。

A comprehensive CAPA plan, overseen by a qualified consultant, for handling microbiological sampling media to ensure robust and reliable data. Establish a system that ensures uninterrupted custody and full reconciliation of all microbiological samples, including but not limited to:

在具备资质顾问监督下，制定微生物取样培养基管理的全套CAPA计划，保障数据稳健可靠。建立体系保证所有微生物样品全程保管不间断、样品可完整追溯，要求包含但不限于：

o Unique labeling of each sample o Signatures of all staff who handle the sample o Complete tracking of sample integrity and custody

每个样品唯一标识；所有接触样品人员的签名；样品完整性与保管全流程追踪；

o Date and time of each activity (e.g., sample collection, delivery, incubation, removal from incubator)

每项操作的日期与时间（例如样品采集、递送、培养、从培养箱取出）；

o Digital time-stamped photos of all plates at the time of reading. Ensure full implementation of photographic evidence to support all results obtained.

所有平板在读数时拍摄带时间戳的电子照片，全面落实照片证据，支撑所有检测结果；

o Signatures of personnel performing reading of microbial counts

微生物计数读数人员签名；

o Provisions for verifications and routine quality assurance oversight.

复核机制以及常态化质量保证监督机制。

3. Your firm's quality unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).

3. 贵公司质量部门未能履行职责，无法保证所生产药品符合CGMP要求，满足鉴别、效价、质量与纯度的既定标准（21 CFR 211.22）。

Your QU lacked adequate oversight and control over your laboratory operations to ensure a state of control and adherence to applicable quality standards.

贵公司质量部门对实验室运营缺少充分监督管控，无法维持受控状态，也无法保证遵守适用质量标准。

Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your laboratory operations, we found your QU is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company's global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.

本警告信中重大缺陷表明贵公司没有按照CGMP建立并运行有效的质量体系。除实验室运营缺少有效管理监督外，我们发现贵公司质量部门无法正常行使相应权限，或是未能充分落实职责。高层管理者应立即全面评估公司全球生产运营，确保体系、流程、产品均符合FDA要求。

Your firm's quality systems are inadequate. See FDA's guidance documents ICH Q10 Pharmaceutical Quality System and Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71553/download and https://www.fda.gov/media/71023/download, respectively.

贵公司质量体系存在不足。可参考FDA指南文件《ICH Q10 药品质量体系》与《药品CGMP法规的质量体系方法》，建立质量体系与风险管理思路，满足21 CFR第210、211部分CGMP法规要求，两份文件下载链接分别为：https://www.fda.gov/media/71553/download 和 https://www.fda.gov/media/71023/download。

In response to this letter, provide 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:

针对本警告信，请提交全面评估与整改计划，保证赋予质量部门相应权限与资源，使其有效履职。评估内容包括但不限于：

A determination of whether procedures used by your firm are robust and appropriate
评估贵公司现有规程是否稳健、适用

Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices
建立质量部门全流程监督机制，评估各项操作是否符合规范

A complete and final review of each batch and its related information before the QU disposition decision
质量部门在对批次做出处置决定前，完成对该批次及全部相关资料的最终完整审核

Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products
监督并审批各类调查，履行质量部门全部其他职责，保证所有产品的鉴别、效价、质量、纯度符合要求

Also describe how top management supports quality assurance and reliable operations including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.

同时说明高层管理层如何支持质量保证与可靠运营，包括但不限于：及时提供资源，主动应对新出现的生产/质量问题，确保持续处于受控状态。

CGMP Consultant Recommended

建议聘请CGMP顾问

Based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm's compliance status with FDA.

基于贵公司违规事项的性质，贵公司应当聘请符合21 CFR 211.34资质要求的顾问评估贵公司运营，协助贵公司满足CGMP要求。在贵公司寻求与FDA解决合规状态之前，该具备资质顾问需要对贵公司全业务开展CGMP六大系统全面审计，并评估纠正预防措施的完成情况与有效性。

Your use of a consultant does not relieve your firm's obligation to comply with CGMP. Your firm's executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.

聘请顾问不能免除贵公司遵守CGMP的法定义务。贵公司高层管理层仍需负责解决全部缺陷与系统性问题，确保持续符合CGMP要求。

Conclusion

结论

You are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.

贵公司有义务开展调查，确定所有违规事项的根本原因，落实纠正和预防措施，保证未来持续合规，避免再次发生此类以及其他违规问题。

Unresolved violations may prevent other Federal agencies from awarding contracts. Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.

未能解决的违规事项可能导致其他联邦机构无法授予合同。未能整改违规事项还会导致FDA暂停出具出口证书。在贵公司所有违规事项全部整改完毕、我方确认贵公司满足CGMP之前，FDA可能暂缓批准将贵公司列为药品生产商的新申请或补充申请。FDA可安排再次现场检查，核实贵公司已完成违规事项的整改措施。