FDA 警示函：設備設計對生物薄膜（Biofilm）形成之影響與風險評估
Austin Chuang • April 11, 2026
探討製藥用水系統因忽視性能驗證（PQ）失效及系統性死角（Dead Legs），最終引發 FDA 警告信之始末。
設備設計缺陷引發 FDA 警告信
執行摘要
在近期對一家法國製藥商美國廠區的稽核中，FDA 發現該廠用於製造指示用藥（OTC）之製程系統（經確認為製藥用水系統）存在嚴重的結構性與營運缺陷。該系統具有關鍵設計瑕疵，包含盲管（Dead legs）與死水區，導致生物膜（Biofilm）滋生並引發重複性的微生物檢驗失效。由於該製造商在性能驗證（PQ）期間及結束後，即便系統長期偏離 USP 規格，仍持續將其用於生產，故美國藥監當局對此採取進一步的處分行動。
FDA 強調管路中存在「盲管」與死水區。這些結構性區域會阻礙適當的流體流速與消毒作業，本質上造成了有害生物膜形成的溫床。
即便性能驗證（PQ）期間的大量取樣結果顯示多數樣本未符合 USP 規格，該確認報告仍遭不當核准。
為期兩年的持續監測顯示存在革蘭氏陰性菌，包含 綠膿桿菌 (Pseudomonas aeruginosa) 與 黏質沙雷氏菌 (Serratia marcescens) ，此為系統性生物膜增殖的明確指標。
公司對長期存在的偏差僅作記錄而未採取適當應對。FDA 要求進行全面的技術評估，涵蓋溫度、材質、坡度、配件及流速。
與 梁山工程顧問 (PE) 共同確保衛生系統符合稽核規範
梁山工程顧問有限公司 (Persimmon Engineering) 專精於製藥用水與製程系統的架構設計、評估及合規確認。我們能在 FDA 介入前，協助您識別盲管、排除生物負荷風險並建立完善的再確認策略。
申請技術評估服務Original Source Content
25.03.2026
Deficiencies in Equipment Design lead to Warning Letter
[中譯] 設備設計缺陷導致收受警告信
During the inspection of a US site belonging to a French pharmaceutical manufacturer, the FDA identified serious deficiencies, including in a process system for the manufacture of OTC drugs.
[中譯] 在對一家法國製藥商美國廠區的稽核過程中，FDA 發現了嚴重的缺陷，包括用於製造指示用藥（OTC）的製程系統。
The deficiencies relate to both the equipment design and its qualification.
[中譯] 該缺陷涉及設備設計及其確認（Qualification）作業。
Although the FDA only refers to a system for supplying a medium used in production in its warning letter, it can be assumed from context that this very likely refers to the manufacturer's water system.
[中譯] 儘管 FDA 在警告信中僅提到一個用於供應生產介質的系統，但從上下文可以推斷，這極大機率是指製造商的用水系統。
In the FDA's opinion, the system is neither structurally nor operationally capable of reliably maintaining the required chemical and microbiological quality parameters.
[中譯] FDA 認為，該系統無論在結構或營運上，皆無法可靠地維持所需的化學與微生物品質參數。
Extensive sampling was already carried out during performance qualification (PQ), with the majority of samples failing to meet the relevant USP specifications.
[中譯] 在性能驗證（PQ）階段已進行了大量取樣，但多數樣本未能符合相關的 USP 規格。
Despite these repeated negative results, the qualification report was approved.
[中譯] 儘管重複出現不合格結果，該確認報告仍獲得核准。
In the following two years, the monitoring data continued to show almost continuous deviations from the USP requirements.
[中譯] 在接下來的兩年中，監測數據持續顯示幾乎未曾間斷的 USP 規格偏差。
Nevertheless the system continued to be used in the manufacture of drugs.
[中譯] 儘管如此，該系統仍持續用於藥品製造。
The FDA is particularly critical of the equipment's inadequate design.
[中譯] FDA 特別對該設備設計不當提出嚴厲批評。
The process system has numerous design flaws, including several so-called dead legs and stagnant locations.
[中譯] 此製程系統存有多處設計瑕疵，包括數個所謂的盲管（Dead legs）與死水區。
According to the FDA, such areas are critical because they can lead to the development of biofilm.
[中譯] 根據 FDA 的說法，此類區域極為關鍵，因為它們會導致生物膜的增殖。
Furthermore, the company was already aware of the existence of these design flaws.
[中譯] 此外，該公司先前已察覺這些設計缺陷的存在。
Microbiological testing confirmed this problem. Gram-negative bacteria, including Pseudomonas aeruginosa and Serratia marcescens, which are considered typical waterborne germs and indicate the presence of biofilms, were repeatedly detected in samples.
[中譯] 微生物檢驗證實了此問題。樣本中反覆檢出革蘭氏陰性菌，包括綠膿桿菌與黏質沙雷氏菌，這些被視為典型的水生菌，顯示系統中存有生物膜。
In its statement, the company announced that it would fundamentally overhaul the process system.
[中譯] 該公司在聲明中宣布將對製程系統進行根本性的翻修。
Among other things, it planned to remove dead legs, install additional system components, and requalify the system.
[中譯] 其中的計劃包括移除盲管、安裝額外的系統組件，並對系統進行再確認（Requalification）。
However, the FDA considers this response to be inadequate, as the company had repeatedly documented deviations over a long period of time without responding appropriately.
[中譯] 然而，FDA 認為此回應不足，因為該公司長期以來反覆記錄偏差，卻未作出適當回應。
The manufacturer also stated that it would temporarily stop using the medium from this system for drug manufacturing and instead use externally sourced material until the system has been completely refurbished.
[中譯] 製造商亦表示，在系統徹底翻新完成前，將暫時停止使用該系統提供的介質進行生產，轉而採用外購原料。
The FDA is requesting a comprehensive technical assessment of the system design and operational controls.
[中譯] FDA 要求對系統設計與營運管制進行全面的技術評估。
This assessment should identify all design and operational weaknesses. In particular, fundamental system parameters that are critical to hygienic design and safe operation should be reviewed.
[中譯] 此項評估應識別所有設計與營運上的弱點。特別是針對衛生設計與安全運行至關重要的基礎系統參數進行審查。
These include, among other things, the temperature in the system, the materials used, the slope of the piping, identified dead legs and other stagnant locations, unsanitary fittings or connections, and the flow velocity within the system.
[中譯] 這些內容包括系統溫度、使用材質、管路坡度、已識別之盲管與其他死水位置、不符合衛生規範的接頭或連接件，以及系統內的流速。
In addition, maintenance and monitoring procedures are to be revised and the system re-qualified.
[中譯] 此外，必須修訂維護與監測程序，並對系統重新進行確認。
Furthermore, the agency has requested a detailed risk assessment regarding the possible impact on drug batches that have already been manufactured and are currently available on the US market.
[中譯] 再者，當局要求針對已生產且目前在美國市場銷售的藥品批次之潛在影響，提交一份詳細的風險評估報告。
The detailed warning letter can be found on the FDA website.
[中譯] 詳細的警告信內容可於 FDA 網站查閱。
出處：https://www.gmp-compliance.org/gmp-news/deficiencies-in-equipment-design-lead-to-warning-letter
Primary Keywords (Short-Tail): FDA Warning Letter, Hygienic Design, Water Systems, Biofilm, Equipment Qualification.
Targeted Phrases (Long-Tail): Dead legs in pharmaceutical water systems, Performance Qualification (PQ) failures, FDA cGMP equipment design compliance, Resolving stagnant piping locations, Waterborne microbiological contamination.
Hashtags: #PharmaCompliance #FDAWarningLetter #HygienicDesign #Validation #PersimmonEngineering.