样品污染调查 Sample contamination investigation

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样品污染调查是一项系统性的科学和质量管理活动，旨在识别、分析和解决样品在采集、运输、储存、处理或分析过程中被外来物质污染的问题。


污染会严重影响检测结果的准确性、可靠性和有效性，可能导致错误的结论、产品召回、合规失败或科学研究的偏差。



Sample contamination investigation is a systematic scientific and quality management activity aimed at identifying, analyzing, and resolving issues of sample contamination by foreign substances during collection, transportation, storage, processing, or analysis.Pollution can seriously affect the accuracy, reliability, and effectiveness of test results, potentially leading to erroneous conclusions, product recalls, compliance failures, or deviations in scientific research.

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样品污染调查的触发场景

当出现以下情况时，应启动污染调查：

• 检测结果异常：
  • 结果超出预期范围或历史趋势。
  • 出现不应存在的成分或杂质（如在阴性对照中检出目标物）。
  • 空白样品（如溶剂、培养基）显示阳性或高背景值。
    
• 客户投诉：客户质疑检测结果的准确性。
• 内部质量控制失败：
  • 质控样品（QC）结果失控。
  • 重复测试结果差异过大。
    
• 观察到可疑现象：
  
  • 样品外观异常（变色、浑浊、沉淀）。
  • 采样或处理过程中发现操作失误（如手套未更换、工具未清洁）。
    

Trigger scenarios for sample contamination investigation
When the following situations occur, a pollution investigation should be initiated:

Abnormal detection results:
The result exceeds the expected range or historical trend.
The appearance of components or impurities that should not exist (such as the detection of the target substance in the negative control).
Blank samples (such as solvents, culture media) show positive or high background values.
Customer complaint: The customer questions the accuracy of the test results.
Internal quality control failure:
The quality control sample (QC) results are out of control.
The difference in repeated test results is too large.
Observed suspicious phenomena:
Abnormal appearance of the sample (discoloration, turbidity, precipitation).
During the sampling or processing process, operational errors were found (such as gloves not being replaced or tools not being cleaned).

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样品污染调查的核心步骤
🔹 第一步：立即响应与初步评估
暂停相关操作：立即停止使用可能受污染的样品、批次或设备。
隔离证据：安全保存受质疑的样品、空白样品、对照样品、相关试剂、耗材和设备。
初步信息收集：
记录异常现象的具体细节（时间、地点、人员、设备、样品编号）。
调取相关记录（采样记录、实验记录、设备日志、环境监测数据）。
.
The core steps of sample contamination investigation
🔹  Step 1: Immediate response and preliminary assessment
Suspend related operations: Immediately stop using samples, batches, or equipment that may be contaminated.
Isolation evidence: Safely store questioned samples, blank samples, control samples, related reagents, consumables, and equipment.
Preliminary information collection:
Record the specific details of abnormal phenomena (time, location, personnel, equipment, sample number).
Retrieve relevant records (sampling records, experimental records, equipment logs, environmental monitoring data).

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第二步：组建调查团队

• 成员：应包括质量保证（QA）、实验室主管、相关技术人员、生产/采样人员（如适用）、设备维护人员。
• 负责人：指定一名调查负责人，确保调查的独立性和客观性。
  

Step 2: Form an investigation team
Members: should include Quality Assurance (QA), laboratory supervisors, relevant technical personnel, production/sampling personnel (if applicable), and equipment maintenance personnel.
Responsible person: Designate an investigation leader to ensure the independence and objectivity of the investigation.

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第三步：根本原因分析（Root Cause Analysis, RCA）

使用系统性方法追溯污染来源。常见污染源包括：

污染来源调查要点
1. 采样过程污染- 采样工具/容器是否清洁、无菌？<br>- 采样人员是否佩戴手套并规范操作？<br>- 采样环境是否受控（如洁净室、现场环境）？<br>- 不同样品间是否发生交叉污染（如使用同一工具）？
2. 运输与储存污染- 运输条件是否符合要求（温度、避光）？<br>- 样品容器是否密封良好？<br>- 储存环境是否清洁？是否存在挥发性污染物？<br>- 是否与其他样品或化学品混放？
3. 实验室处理污染- 实验台面、移液器、离心机等设备是否清洁？<br>- 试剂、溶剂、水是否纯净且未过期？<br>- 耗材（枪头、离心管）是否为无DNA酶/RNA酶、无热原？<br>- 操作人员是否遵守无菌/无污染操作规范？
4. 分析仪器污染- 进样口、色谱柱、管路、检测器是否残留前一样品？<br>- 是否执行了足够的空白运行或清洗程序？<br>- 仪器维护记录是否完整？
5. 环境污染- 实验室空气洁净度（颗粒物、微生物）是否达标？<br>- 是否存在气溶胶污染（如超声、离心）？<br>- 实验室是否存在高浓度目标物（如PCR实验室的扩增产物）？
6. 人为因素- 操作人员培训是否到位？<br>- 是否存在操作失误或违反SOP？

分析工具：

• 5Why分析法：连续追问“为什么”，直至找到根本原因。
• 鱼骨图（因果图）：从人、机、料、法、环、测六个方面系统分析。
• 流程图分析：绘制样品从采集到分析的全流程，识别潜在污染点。
  

Step 3: Root Cause Analysis (RCA)
Use systematic methods to trace the source of pollution. Common sources of pollution include:

Key points of pollution source investigation
1. Pollution during the sampling process - Are the sampling tools/containers clean and sterile? <br>-Do the sampling personnel wear gloves and operate in a standardized manner? <br>-Is the sampling environment controlled (such as clean rooms, on-site environment)? <br>-Is there cross contamination between different products (such as using the same tool)?
2. Transportation and storage pollution - Do the transportation conditions meet the requirements (temperature, light avoidance)? <br>-Is the sample container well sealed? <br>-Is the storage environment clean? Are there any volatile pollutants present? <br>-Is it mixed with other samples or chemicals?
3. Laboratory pollution treatment - Are laboratory tables, pipettes, centrifuges, and other equipment clean? <br>-Are the reagents, solvents, and water pure and not expired? <br>-Are the consumables (gun head, centrifuge tube) DNase/RNAase free and pyrogen free? <br>-Do operators comply with sterile/non contaminated operating procedures?
4. Are there any residual samples from the previous sample in the injection port, chromatographic column, tubing, and detector due to contamination of the analytical instrument? <br>-Have sufficient blank runs or cleaning programs been executed? <br>-Is the instrument maintenance record complete?
5. Environmental pollution - Does the laboratory air cleanliness (particulate matter, microorganisms) meet the standard? <br>-Is there aerosol pollution (such as ultrasound, centrifugation) present? <br>-Is there a high concentration target substance in the laboratory (such as amplification products from PCR laboratories)?
6. Human factors - Is operator training in place? <br>-Is there any operational error or violation of SOP?
Analysis tools:

5Why analysis method: Continuously ask "why" until the root cause is found.
Fishbone diagram (causal diagram): a systematic analysis from six aspects: human, machine, material, method, environment, and measurement.
Process diagram analysis: Draw the entire process of sample collection and analysis, identify potential pollution points.

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第四步：制定纠正与预防措施（CAPA）
根据根本原因，制定并实施有效的措施：

根本原因        可能的纠正与预防措施（CAPA）
工具/容器污染        - 建立严格的清洁验证程序。<br>- 使用一次性或专用工具。<br>- 引入超声波清洗、高温灭菌等清洁方法。
交叉污染        - 严格执行“先阴性后阳性”、先空白后样品的分析顺序。<br>- 增加空白运行（Blank Run）。<br>- 物理隔离高风险样品区域。
试剂/耗材问题        - 更换供应商或批次。<br>- 加强试剂验收测试。<br>- 使用高质量认证的耗材（如无酶、无核酸）。
仪器残留        - 优化仪器清洗程序（增加清洗次数、更换清洗溶剂）。<br>- 定期维护和更换易污染部件（如进样针、衬管）。
人员操作不当        - 加强培训和考核。<br>- 更新SOP并进行可视化指导。<br>- 实施双人复核制度。
环境控制不足        - 升级空气过滤系统（HEPA）。<br>- 增加环境监测频次。<br>- 设立专用洁净工作台或负压实验室。

Step 4: Develop Corrective and Preventive Action (CAPA)
Develop and implement effective measures based on the root cause:

Root Cause Possible Corrective and Preventive Actions (CAPA)
Tool/container contamination - Establish strict cleaning validation procedures. <br>-Use disposable or specialized tools. <br>-Introduce cleaning methods such as ultrasonic cleaning and high-temperature sterilization.
Cross contamination - strictly follow the analysis sequence of "negative first, positive second" and blank first, sample second. <br>-Add Blank Run. <br>-Physically isolate high-risk sample areas.
Reagent/consumable issues - change supplier or batch. <br>-Strengthen the acceptance testing of reagents. <br>-Use high-quality certified consumables (such as enzyme free and nucleic acid free).
Instrument residue - Optimize instrument cleaning procedures (increase cleaning frequency, replace cleaning solvents). <br>-Regular maintenance and replacement of easily contaminated components (such as injection needles and liners).
Improper personnel operation - Strengthen training and assessment. <br>-Update SOP and provide visual guidance. <br>-Implement a dual person review system.
Insufficient environmental control - Upgrade air filtration system (HEPA). <br>-Increase the frequency of environmental monitoring. <br>-Establish dedicated clean workbenches or negative pressure laboratories.

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第五步：验证与关闭

• 措施验证：
  • 实施CAPA后，进行测试（如运行空白样品、质控样品、已知阴性样品）。
  • 确认污染问题已消除，检测结果恢复正常。
    
• 文件化：
  • 编写完整的《样品污染调查报告》，内容包括：
    • 问题描述
    • 调查过程与证据
    • 根本原因分析
    • 实施的CAPA
    • 验证结果
    • 责任人与完成日期
      
    
    
• 报告审批与关闭：报告由QA和管理层审批后正式关闭。
• 知识共享：将调查结果和经验教训分享给相关人员，防止类似问题再次发生。
  

Step 5: Verification and Closure
Verification of measures:
After implementing CAPA, conduct testing (such as running blank samples, quality control samples, known negative samples).
Confirm that the pollution issue has been eliminated and the test results have returned to normal.
Documenting:
Write a complete 'Sample Pollution Investigation Report', which includes:
Problem description
Investigation process and evidence
Root Cause Analysis
Implemented CAPA
Verification result
Responsible person and completion date
Report approval and closure: The report is officially closed after being approved by QA and management.
Knowledge sharing: Share survey results and lessons learned with relevant personnel to prevent similar issues from happening again.

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预防样品污染的关键措施

• 制定并遵守SOP：所有操作必须有标准操作程序。
• 人员培训：定期培训员工关于污染风险和防控措施。
• 使用高质量耗材：选择经过认证的无污染耗材。
• 环境控制：维持实验室的洁净度和温湿度。
• 仪器维护：定期清洁和维护分析仪器。
• 设置对照：每次实验都应包含空白对照、阴性对照和阳性对照。
• 记录完整：详细记录所有操作步骤和观察结果.
  

Key measures to prevent sample contamination
Develop and comply with SOP: All operations must have standard operating procedures.
Personnel training: Regularly train employees on pollution risks and prevention and control measures.
Use high-quality consumables: Choose certified non polluting consumables.
Environmental control: Maintain the cleanliness and temperature and humidity of the laboratory.
Instrument maintenance: Regularly clean and maintain analytical instruments.
Set controls: Each experiment should include blank controls, negative controls, and positive controls.
Complete recording: Detailed recording of all operational steps and observation results.

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