近日，FDA 發布了 Shailendra Jha的483缺陷報告，其中提及A級環境物品管理和消毒劑使用、氣流流型測試以及可見異物檢查相關的缺陷：

SOP未聲明禁止在A級環境設備安裝過程中使用非無菌工具。

SOP未明確規定A級環境清潔所使用的消毒劑為無菌級。

煙霧試驗（氣流流型測試）發煙量不足，無法清晰觀察是否存在單向流

產品可見異物檢查和過程未將瓶子旋轉 360°，以確保充分發現產品存在的任何顆粒或缺陷。

可見異物檢查過程中，樣品是在檢驗人員戴手套的手中滾動的，無法提供足夠的對比度，以確保能夠充分發現可見異物。 

有關煙霧試驗（氣流流型測試），示例如下：

缺陷翻譯如下：

OBSERVATION 1

缺陷 1

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile are not written.

未制定用以防止無菌藥品微生物污染的程序。

Your SOP entitled, “Procedure for cleaning of ×× along with vial filling, stoppering and sealing machine, capping machine, ×× system ×× RABS”. SOP-FT111-PR-0018, Version 8.0, Effective 29-Apr-2025 allows the use of non-sterile ×× to clean the surfaces of the ×× during the end of the batch. There is no statement in the SOP to prohibit the introduction or use of non-sterile ×× during set up activities. Furthermore, the SOP does not specify if the ×× sanitization agents that are routinely used during cleaning the surfaces of the Grade A ×× are sterile. According to the Global Head Quality/Pharmacovigilance, there is no risk because the surfaces of the Grade A ×× will be decontaminated with ×× prior to aseptic production.

貴司的文件SOP-FT111-PR-0018《××，以及西林瓶分裝、加塞和密封機、軋蓋機、××系統 ×× RABS的清潔程序》（版本 8.0，2025 年 4 月 29 日生效），允許在批次結束時使用非無菌 ×× 清潔 ××表面。該 SOP 中未聲明禁止在設備安裝活動期間引入或使用非無菌 ××。此外，該 SOP 未明確說明在清潔 A 級 ×× 表面時，日常使用的 ××消毒劑是否無菌。而你們的全球質量/藥物警戒負責人表示，不存在風險，因為在無菌生產前，A級××的表面將使用××進行去污染處理。

OBSERVATION 2

缺陷2

Procedures designed to prevent microbiological contamination of drug products purporting to be sterile did not include adequate validation of the aseptic process.

用以防止無菌藥品微生物污染的程序，未包含對無菌工藝的充分驗證。

On July 17,2025, we watched your most recent static and dynamic smoke studies performed in ××(01) for your ××(02) which are used to manufacture sterile drug products that are distributed in the United States. Poor visualization was seen due to inadequate generation of smoke to ensure the sweeping unidirectional airflow is present to protect exposed sterile ××(03) stoppers under the sensor, protect vials that are loaded ××(04) and unloaded ××(05) (stopped but not sealed) from ××(06)

2025 年 7 月 17 日，我們觀察了貴司的靜態和動態煙霧研究（氣流流型測試）。由于產生的煙霧不足，無法清晰觀察是否存在單向流，以保護暴露的無菌××膠塞和瓶子，包括已加塞但未密封的瓶子。

OBSERVATION 3

缺陷 3

Testing and release of drug product for distribution do not include appropriate laboratory determination of satisfactory conformance to the final specifications prior to release.

未在放行前通過適當的實驗室檢測來確定其是否符合最終質量標準。

On 7/11/2025, we watched the firm’s visual inspection process of ××(01) drug products for presence of particulate matter of ××(02) for ××(03) Injection, ××(04) mg/vial, Batch # ××(05) and observed the visual inspector hold, tilt ××(06) drug product containers forward and back ××(07) against the ××(08) background of the visual inspection booth but fail to rotate the vials 360° against the ××(09) background to ensure that any particles or defects present in the vials will be visible to the eye. Furthermore, the ××(10) vials of ××(11) are rolled in the gloved hands of the visual inspector which does not provide adequate contrast required to ensure that particles similar to ××(12)

2025 年 7 月 11 日，我們觀察了貴司對 ××藥品的目視檢查過程，發現目視檢查人員手持、傾斜xx藥品容器，在XX燈檢機背景前前后移動，但未將瓶子旋轉 360°，以確保瓶內存在的任何顆粒或缺陷都能被看到。此外，目視檢查的樣品在檢驗人員戴手套的手中滾動，無法提供足夠的對比度，以確保能發現類似 ××(12) 的顆粒。