01.04.2026
FDA Warning Letter: Significant Violations of Aseptic Manufacturing Procedures uncovered [中譯] 2026年4月1日 - FDA 警告信：揭發無菌製造程序之重大缺失

In March 2026, the US Food and Drug Administration (FDA) issued a Warning Letter to Simtra BioPharma Solutions. [中譯] 美國食品藥物管理局 (FDA) 於 2026 年 3 月向 Simtra BioPharma Solutions 發出警告信。

This was based on an unannounced inspection of the Simtra Deutschland GmbH (formerly Baxter Oncology GmbH) manufacturing site in Halle/Westphalia, Germany, which took place from 18 to 26 September 2025. During the inspection, the authority identified several serious violations of the requirements of Current Good Manufacturing Practice (CGMP) as set out in 21 CFR Parts 210 and 211. [中譯] 該警告信源於 2025 年 9 月 18 日至 26 日對位於德國 Halle/Westphalia 的 Simtra Deutschland GmbH（原 Baxter Oncology GmbH）廠區進行的突擊檢查。檢查期間，官方發現其嚴重違反 21 CFR Parts 210 及 211 所規範之現行優良製造規範 (CGMP)。

According to the FDA, the methods, facilities and controls used in the manufacture, processing, packaging or storage of the medicinal products do not comply with regulatory requirements. [中譯] 根據 FDA 報告，該廠用於藥品製造、加工、包裝或儲存的方法、設施與管制手段均不符合法規要求。

The products manufactured are therefore considered "adulterated" within the meaning of the Federal Food, Drug, and Cosmetic Act, i.e. they have not been manufactured in accordance with GMP. [中譯] 根據聯邦食品、藥物與化妝品法案，該廠生產之產品被視為「劣藥」，意即未依照 GMP 標準生產。

One of the main points is the controls in the aseptic manufacturing process. [中譯] 核心缺失之一為無菌製造製程的管制。

The FDA found that the facility did not have clearly enough defined or segregated areas to reliably prevent contamination or product mix-ups during aseptic manufacturing. [中譯] FDA 發現該設施未具備足夠明確定義或區隔的作業區域，難以在無菌製造過程中可靠地防止污染或產品混淆。

Several production lines were particularly affected, including facilities with Restricted Access Barrier Systems (RABS) used to manufacture sterile medicinal products for the US market. [中譯] 數條生產線受到特別影響，包括用於生產供應美國市場無菌藥品之限制進入屏障系統 (RABS) 設施。

Further significant deficiencies concerned the cleaning and disinfection systems. According to the inspection report, a cleaning solution was fed to the cleaning points via pipes with very long so-called "dead legs". [中譯] 另一項重大缺失涉及清潔與消毒系統。根據稽核報告，清潔液經由包含極長「盲管 (Dead legs)」的管路輸送至各清潔點。

Such dead legs can lead to stagnation of liquids and thus promote the growth of microorganisms. [中譯] 該類盲管會導致液體停滯，進而促進微生物滋長。

In fact, between June 2023 and September 2025, a total of 47 microbiological detections were identified during routine testing, 14 of which exceeded the specified limits. Internal investigations identified the design of the cleaning system’s pipework as the likely cause of the contamination. [中譯] 事實上，在 2023 年 6 月至 2025 年 9 月間，例行檢驗共發現 47 次微生物檢出，其中 14 次超過規格。內部調查已將清潔系統管路設計列為污染的可能主因。

However, the FDA considered that the corrective and preventive actions (CAPA) implemented were insufficient to resolve the underlying design issues. [中譯] 然而，FDA 認為廠方實施的矯正與預防措施 (CAPA) 不足以解決潛在的設計問題。

In addition, as part of the Environmental Monitoring programme, Gram-negative microorganisms were repeatedly detected in ISO 5 areas of the aseptic production facility. [中譯] 此外，作為環境監測計畫的一環，無菌生產區的 ISO 5 區域反覆檢出革蘭氏陰性菌。

From the FDA’s perspective, this indicates fundamental weaknesses in the hygiene management system and in the control of critical production environments. [中譯] 以 FDA 的觀點來看，這顯示其衛生管理系統以及對關鍵生產環境的控制存在根本性弱點。

The FDA has called on the company to submit detailed measures to address the identified deficiencies in the Warning Letter. [中譯] FDA 已要求該公司針對警告信中指出之缺陷提交詳細的改善措施。

These include, in particular, improvements to the design of the systems, an effective root cause analysis of the microbiological findings, and sustainable corrective actions to ensure aseptic process control. [中譯] 這些措施特別包括系統設計的改良、對微生物檢出進行有效的根本原因分析 (RCA)，以及確保無菌製程管制的持續性矯正行動。

This case once again highlights the high level of regulatory scrutiny that the FDA applies to aseptic manufacturing (also with unannounced inspections). [中譯] 本案再次突顯了 FDA 對於無菌製造極為嚴格的監管審查（包含突擊檢查）。

In particular, the combination of technical design flaws, repeated microbiological findings and inadequate CAPA measures is frequently viewed by inspectors as an indicator of systemic weaknesses in quality management. [中譯] 特別是技術設計缺陷、重複發生微生物檢出與無效 CAPA 的組合，常被稽核員視為品質管理系統性崩潰的指標。

Read the full Warning Letter to Simtra BioPharma Solutions on the FDA website. [中譯] 請至 FDA 官網閱讀發予 Simtra BioPharma Solutions 的完整警告信內容。

Source: https://www.gmp-compliance.org/gmp-news/fda-warning-letter-significant-violations-of-aseptic-manufacturing-procedures-uncovered [中譯] 來源：https://www.gmp-compliance.org/gmp-news/fda-warning-letter-significant-violations-of-aseptic-manufacturing-procedures-uncovered