近日，FDA在發給Adept Medical Ltd.的警告信中提及滅菌用生物指示劑相關的缺陷：

未建立生物指示劑（BI） 進貨檢驗和驗收程序

丟棄BI 的出廠合格證

未對收到的 BI 批次執行 BI 含菌量確認檢測，以確保菌落數在運輸或存儲過程中沒有變化，FDA認為這是一個關鍵步驟

該公司辯解稱：他們使用的 BI 符合 ISO 11138-1：2017 和ISO 11138-2：2017， 并且它們在使用前一直處于無菌包裝中。FDA則表示：該公司沒有進行任何檢測來確認所購買的BI 在使用時是否確實存活。

滅菌后 BI測試報告中未記錄無菌裝載中使用的BI 的批號和有效期等關鍵信息

翻譯如下：

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.

貴公司當前的生物指示劑（b）（4）（BI） 進貨檢驗和驗收程序尚未充分建立。這種不足可能會影響滅菌過程，從而可能影響產品的安全性和有效性。貴公司丟棄了（b）（4）為每個 BI 批次提供的合格證書，這是檢查期間FDA 檢查人員需要的。貴公司似乎未能保留關鍵文件，例如臺賬、生產批記錄或（b）（4）合格證明，這些是你們自己的文件：WI22《生產 QC 和放行產品登記冊》，特別是第 2.3 節所要求的用以證明產品已成功滅菌的文件。檢查顯示，貴公司未對收到的 BI 批次執行 BI 含菌量確認檢測，以確保菌落數在運輸或存儲過程中沒有變化。這是一個關鍵步驟，對于 BI 能夠支持確認成品通過XX滅菌程序成功滅菌提供保障是必要的。此外，檢查還發現，滅菌后 BI測試報告中未記錄無菌裝載中使用的BI 的批號和有效期等關鍵信息，這些報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） 貴公司的答復指出，貴工廠生產的 stenle 產品沒有風險，因為他們使用的 BI 符合 ISO 11138-1：2017 和ISO 11138-2：2017， 并且它們一直處于無菌包裝中一直到使用前。但是，檢查表明，貴公司沒有進行任何檢測來確認所購買的用以證明已實現最終滅菌的BI 在使用時是否確實存活。此外，檢查顯示，沒有記錄 BI 批號和有效期等關鍵數據，因此，如果 BI 錯誤地表示滅菌成功，貴公司就沒有機制可以將無菌產品的批次追溯到失敗的 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，貴公司沒能提供糾正措施的文件或證據，因為它們正在進行中且尚未完成。此外，鑒于上述觀察結果，貴公司尚未承諾對所有已使用該生物指示劑進行滅菌確認的成品進行回顧性評估，以確定無菌性是否受到影響。

我國GMP指南（2023版）

“生物指示劑的常規性能測試一般包括含菌量復核、純度確認、形態鑒定。如果認為有必要，可以用表型法或基因法進行菌種鑒別(如在異常情況調查時)。外購的生物指示劑，當完全按照廠家的用途、使用說明使用時，無需進行D值測定，將供應商提供的D值數據作為該批指示劑的D值。《中國藥典》指導原則9208 生物指示劑耐受性檢查法指導原則 中，有詳細的生物指示劑菌含量復核及D值測定的方法。”

“典型的微生物進廠質控(復核測試)報告包含以下內容。生產商、菌名、批號、標示含菌量、D值、效期、稀釋過程、稀釋倍數、計數結果、每個生物指示劑含菌量、是否合格等。可以將生物指示劑的廠家質檢報告或其復印件與上述文件一起存放。檢驗合格的生物指示劑要經過批準和發放后才可以使用。領用時要登記領用人日期、數量等。”