Inspectional Guidance-Sample Data Review – All Negative Results
What to review when all the firm’s Sterility and/or Microbial Limits test results indicate no microbial growth and you need to know whether this is true:
当所有企业的无菌检查/微生物限度检查结果表明没有微生物生长，你需要知道这是否是真的：
1. Medium- Growth Promotion; pH; Low agar or broth volume in container, Incubator temp not set correctly; improper medium storage after QC (crystals from freezing, inadequate mixing prior to dispensing, agar plates dried out during incubation, etc.)
促进生长的方法; pH值;容器中有少量的琼脂或肉汤，培养箱温度设置不正确; QC后不适当的储存介质（琼脂冻结、混合前混合不均匀、培养过程中的琼脂板干燥等）
2. Method Suitability testing- Validation for Sterility; Preparatory testing (BET). May need added neutralizers, product dilution, filtration; water chemical contaminant with toxin effects in buffers, Not following method (excess of product added to broth during test but not during suitability testing, etc)
方法适用性测试 – 无菌检查的验证;预备测试（BET）。可能需要添加中和剂，产品稀释，过滤; 水中的化学污染物，在缓冲液中有毒素作用，不遵循以下方法（在测试期间添加到肉汤中的产品过多，但在适用性测试期间没有，等）
3. Improper tube or agar plate examination- check filter surface on submerged filter membrane (mold budding); surface film, light hazy growth in Thio broth, microbes settle to bottom of tube, pinpoint colonies (microaerophilic); medium not inoculated. Disinfection process adds antimicrobial residue onto/into product during sample preparation; Gas used for Isolator sterilization with medium inside chamber may penetrate into liquid broth and/or test product packaging
不正确的管或琼脂平板检查 – 检查浸没过滤膜上的滤膜表面（霉菌萌芽）; 表面膜、硫肉汤中的轻度模糊生长、微生物沉降到试管底部、精确定位菌落（微嗜温）；未接种培养基。在样品制备过程中，消毒过程会在产品上/中添加抗菌残留物；用于隔离灭菌的气体（室内介质）可能会渗透到液体肉汤和/或测试产品包装中。
4. Fastidious microorganisms found in the product bioburden may require special additives to the medium- Halophilic contaminants in bicarbonate, or high salt products need medium supplements with essential salts for survival
产品生物负载中发现的苛刻微生物可能需要特殊的添加剂来处理碳酸氢盐中的嗜盐污染物，或者高盐产品需要中等补充剂和生存必需盐
5. Water test method- membrane filter with a 0.45 micron pore size may miss quantities of water-borne organisms. Suitability testing necessary. Note: USP <71> only requires “pore size not greater than 0.45µm”.
水测试方法 – 孔径为0.45微米的膜过滤器可能无法截留大量的水生生物。因此有进行必要的适用性测试。注意：USP <71>仅要求“孔径不大于0.45μm”。
6. Inadequate incubation time (14 days)/temp (USP required temps)
培养时间不足（14天）/ 温度（USP要求的温度）
7. Possible falsification or incorrect entry onto worksheets or Laboratory LIM system. Compare LIMs database entries to the analyst’s laboratory notebook; Phrase the question “When you get a positive test result….” not “If you get a positive test result…” Inspect the laboratory refrigerator or freezer for evidence of stored sample isolates. If they lyophilize sample isolates ask to review the spread sheet data storage directly from the computer screen; hard copies could be obtained later.Review the Vitek or Micro Id isolate log book for all microorganisms identified and work backwards to the product lot number, filling rooms, equipment used, components or raw material used for that lot. This may allow you to find other lots associated with the contaminated lot.
可能存在伪造或错误输入工作表或实验室LIM系统的情况。将LIMs数据库条目与分析人员的实验室笔记本进行比较;问题表述“当你得到阳性测试结果……”而不是“如果你得到阳性测试结果……”检查实验室冰箱或冷冻室是否有存储样品隔离物的证据。如果他们冻干样品分离物，请直接在计算机屏幕上查看电子表格数据存储;随后可以获得硬拷贝。查看Vitek或Micro Id的隔离日志中所有已鉴定的微生物，并追溯到产品批号，罐装室，所有设备，该批次的所有组件或原材料。这可以让您找到与受污染批次相关的其他批次。
8. Personnel- review training records and personnel qualifications and experience Observe analysts during sample collection, preparation, etc., to look for errors which may inhibit microbial recovery.
人员-审查培训记录和人员资格和经验，在样品收集、制备等过程中观察分析人员，寻找可能影响微生物回收的错误操作。
9. Visit the microbiology laboratory and look into the refrigerators, incubators, discarded plates from that day’s work or request speciation log book and determine if microbial recovery has occurred, but not recorded on official worksheets or entered into LIMs.
观察微生物实验室，查看冰箱、培养箱、当天工作中丢弃的培养皿或申请物品登记簿，确定是否有微生物回收，但没有记录在正式工作表上或进入LIMS。
本文来自harmaceutical Microbiology Manual2014
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原文始发于微信公众号（药品微生物检测）：Inspectional Guidance 3-审查样本数据- 所有阴性结果
