近日，FDA在发给Adept Medical Ltd.的警告信中提及灭菌用生物指示剂相关的缺陷：

未建立生物指示剂（BI） 进货检验和验收程序

丢弃BI 的出厂合格证

未对收到的 BI 批次执行 BI 含菌量确认检测，以确保菌落数在运输或存储过程中没有变化，FDA认为这是一个关键步骤

该公司辩解称：他们使用的 BI 符合 ISO 11138-1：2017 和ISO 11138-2：2017， 并且它们在使用前一直处于无菌包装中。FDA则表示：该公司没有进行任何检测来确认所购买的BI 在使用时是否确实存活。

灭菌后 BI测试报告中未记录无菌装载中使用的BI 的批号和有效期等关键信息

翻译如下：

Your firm's current incoming inspection and acceptance procedure for Biological Indicator(b)(4) (BI) is not adequately established. This inadequacy could compromise the sterilization process, potentially affecting the safety and effectiveness of the NeoZoline V ntilation Tubes. Your firm discards the Certificate of Conformance provided by (b)(4) with each BI batch, which was requested by the FDA investigator during the inspection. It appears that your firm failed to retain critical documents such as the reconciliation sheet, production batch record, or (b)(4) Certification of Conformance, which are required under your own WI22 "Production QC and Release Product Register," specifically section 2.3, to demonstrate that the product was successfully sterilized. The inspection revealed that your firm does not perform BI Population verification tests on the received BI batches to ensure that the population has not changed during shipping or storage. This is a critical step is necessary to provide a high degree of assurance that the BIs are viable to support verification that finished product is successfully sterilized through the (b)(4) Sterilization process. Additionally, the inspection revealed that critical information such as the batch number and expiration date of the BI used in the sterile load is not documented on the post-sterilization B1 Test Reports, which are used as part of the finished device acceptance and release process.

贵公司当前的生物指示剂（b）（4）（BI） 进货检验和验收程序尚未充分建立。这种不足可能会影响灭菌过程，从而可能影响产品的安全性和有效性。贵公司丢弃了（b）（4）为每个 BI 批次提供的合格证书，这是检查期间FDA 检查人员需要的。贵公司似乎未能保留关键文件，例如台账、生产批记录或（b）（4）合格证明，这些是你们自己的文件：WI22《生产 QC 和放行产品登记册》，特别是第 2.3 节所要求的用以证明产品已成功灭菌的文件。检查显示，贵公司未对收到的 BI 批次执行 BI 含菌量确认检测，以确保菌落数在运输或存储过程中没有变化。这是一个关键步骤，对于 BI 能够支持确认成品通过XX灭菌程序成功灭菌提供保障是必要的。此外，检查还发现，灭菌后 BI测试报告中未记录无菌装载中使用的BI 的批号和有效期等关键信息，这些报告用作成品接受和放行流程的一部分。

(b)(4) your firm's response states that there is no risk for the stenle products manufactured at your facility because the BIs that they use conform to ISO 11138-1:2017 and ISO 11138-2:2017, and that they are in their sterile packaging until they are needed. However, the inspection demonstrated that your firm does not do any testing to verify that the BIs purchased for the purpose of demonstrating that terminal sterilization is achieved, are actually viable when they are used. Additionally, the inspection revealed that they do not capture key data such as BI batch number and expiration date, and thus if a BI falsely indicated that a sterilization was successful, there is no mechanism by which your firm can trace the lots of sterile products back to a failed BI.

（b）（4） 贵公司的答复指出，贵工厂生产的 stenle 产品没有风险，因为他们使用的 BI 符合 ISO 11138-1：2017 和ISO 11138-2：2017， 并且它们一直处于无菌包装中一直到使用前。但是，检查表明，贵公司没有进行任何检测来确认所购买的用以证明已实现最终灭菌的BI 在使用时是否确实存活。此外，检查显示，没有记录 BI 批号和有效期等关键数据，因此，如果 BI 错误地表示灭菌成功，贵公司就没有机制可以将无菌产品的批次追溯到失败的 BI。

Additionally, your firm did not include documentation or evidence of the corrections or corrective actions because they are in progress and have not been completed. Additionally, given the observations described above, your firm has not provided a commitment to conduct a retrospective assessment of all finished devices whose sterilization was verified using Biological Indicator(b)(4) to determine whether sterility was compromised.

此外，贵公司没能提供纠正措施的文件或证据，因为它们正在进行中且尚未完成。此外，鉴于上述观察结果，贵公司尚未承诺对所有已使用该生物指示剂进行灭菌确认的成品进行回顾性评估，以确定无菌性是否受到影响。

我国GMP指南（2023版）

“生物指示剂的常规性能测试一般包括含菌量复核、纯度确认、形态鉴定。如果认为有必要，可以用表型法或基因法进行菌种鉴别(如在异常情况调查时)。外购的生物指示剂，当完全按照厂家的用途、使用说明使用时，无需进行D值测定，将供应商提供的D值数据作为该批指示剂的D值。《中国药典》指导原则9208 生物指示剂耐受性检查法指导原则 中，有详细的生物指示剂菌含量复核及D值测定的方法。”

“典型的微生物进厂质控(复核测试)报告包含以下内容。生产商、菌名、批号、标示含菌量、D值、效期、稀释过程、稀释倍数、计数结果、每个生物指示剂含菌量、是否合格等。可以将生物指示剂的厂家质检报告或其复印件与上述文件一起存放。检验合格的生物指示剂要经过批准和发放后才可以使用。领用时要登记领用人日期、数量等。”