近日，FDA 发布了 Shailendra Jha的483缺陷报告，其中提及A级环境物品管理和消毒剂使用、气流流型测试以及可见异物检查相关的缺陷：

SOP未声明禁止在A级环境设备安装过程中使用非无菌工具。

SOP未明确规定A级环境清洁所使用的消毒剂为无菌级。

烟雾试验（气流流型测试）发烟量不足，无法清晰观察是否存在单向流

产品可见异物检查和过程未将瓶子旋转 360°，以确保充分发现产品存在的任何颗粒或缺陷。

可见异物检查过程中，样品是在检验人员戴手套的手中滚动的，无法提供足够的对比度，以确保能够充分发现可见异物。 

有关烟雾试验（气流流型测试），示例如下：

缺陷翻译如下：

OBSERVATION 1

缺陷 1

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

未制定用以防止无菌药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.

贵司的文件SOP-FT111-PR-0018《××，以及西林瓶分装、加塞和密封机、轧盖机、××系统 ×× RABS的清洁程序》（版本 8.0，2025 年 4 月 29 日生效），允许在批次结束时使用非无菌 ×× 清洁 ××表面。该 SOP 中未声明禁止在设备安装活动期间引入或使用非无菌 ××。此外，该 SOP 未明确说明在清洁 A 级 ×× 表面时，日常使用的 ××消毒剂是否无菌。而你们的全球质量/药物警戒负责人表示，不存在风险，因为在无菌生产前，A级××的表面将使用××进行去污染处理。

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.

用以防止无菌药品微生物污染的程序，未包含对无菌工艺的充分验证。

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，我们观察了贵司的静态和动态烟雾研究（气流流型测试）。由于产生的烟雾不足，无法清晰观察是否存在单向流，以保护暴露的无菌××胶塞和瓶子，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.

未在放行前通过适当的实验室检测来确定其是否符合最终质量标准。

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，我们观察了贵司对 ××药品的目视检查过程，发现目视检查人员手持、倾斜xx药品容器，在XX灯检机背景前前后移动，但未将瓶子旋转 360°，以确保瓶内存在的任何颗粒或缺陷都能被看到。此外，目视检查的样品在检验人员戴手套的手中滚动，无法提供足够的对比度，以确保能发现类似 ××(12) 的颗粒。