FDA警告信。
模具偏差调查。
美国食品和药物管理局。
FDA（美国食品和药物管理局）向Sun Pharma India发出了警告信，其中包括对霉菌偏差的调查。
部分原文如下。
your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 cfr 211.192).
your investigations into water leaks in your cleanroom were inadequate because they lacked appropriate capa and failed to extend to other potentially affected batches.
for example, water leaked from the service floor through the heating, ventilation, and air conditioning (hvac) duct floor and into the ceiling directly above the iso 5 filling area. your investigation report noted water accumulated on the service floor due to a leak from an old, punctured (b)(4). water then collected over the (b)(4) partition ceiling prior to entering the aseptic filling room where medroxyprogesterone acetate injectable suspension usp, was manufactured. your personnel confirmed there was substantial water accumulation on the service floor.
although you sealed gaps in the ceiling, you did not sufficiently inspect the service floor, (b)(4) laf ceiling, and hvac duct floor for mold growth and water damage after the repairs were made. you also failed to extend the scope of your investigation to potentially impacted batches of medroxyprogesterone acetate injectable suspension usp manufactured in this room since the last preventive maintenance of the (b)(4), approximately two months before the leak was observed.
in your response, you state the leak was isolated to the day it was observed. you acknowledge that your investigation did not evaluate the impact of the leak to other batches. you initiated a recall on may 17, 2022, for all marketed batches of medroxyprogesterone acetate injectable suspension usp, 150 mg/ml, 1 ml vials manufactured on this line, for events unrelated to this investigation.
your response is inadequate. while we acknowledge you initiated actions to address this specific leak, your investigation failed to sufficiently address facility damage and the potential for microbial (i.e., particularly fungal) contamination that could persist in the facility due to water leaks and moisture.
in response to this letter, provide a comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, oos results, and failures. provide a detailed action plan to remediate this system. your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, capa effectiveness, quality assurance unit oversight, and written procedures. address how your firm will ensure all phases of investigations are appropriately conducted.
关键点总结。
在制药厂的注射车间，生产醋酸甲羟孕酮注射液混悬液。 在灌装室的日常监测中发现了霉菌。
发现模具后，开始进行偏差调查，发现灌装室的技术夹层漏水，恰好进入灌装室，导致发霉。
制药厂采取了措施：它密封了天花板上的缝隙。
但FDA认为，仅仅密封天花板上的缝隙是不够的。 例如，对技术夹层的全面检查，对其他房间和夹层造成的漏水的处理一直没有做好。
空调系统是否被霉菌污染尚未查治。 如果空调系统受到污染，就会成为严重的隐患，空调系统的污染难以处理。
FDA 要求：对整个系统进行全面、独立的评估，以调查偏差、差异、投诉、OOS 结果和故障。 提供详细的行动计划来修正系统。 您的行动计划应包括但不限于调查能力、范围确定、根本原因评估、CAPA 有效性、质量保证部门监督和书面程序的重大改进。 解释贵公司将如何确保调查的所有阶段都得到适当进行。
霉菌对于洁净室来说是可怕的。
制药洁净室中最常见的霉菌（青霉菌）。
菌丝通常是无色的，分生孢子是蓝绿色的。
分生孢子是细菌传播的主要方式，但并非所有青霉菌都是蓝绿色的，但也有白色或绿色。
该属喜欢潮湿、阴凉的环境。
青霉菌也是一种常见的环境真菌，可以在室内空气和灰尘中分离出来。
它甚至可以在天花板上生存。
在医药原料乳糖中也很容易检测到。
根据一项研究，洁净室中透明真菌的总检出率为51%。
霉菌在物质、湿度和营养物质的条件下，可在3天内在空调系统的回风管道中检测到。
凡通工程师可以做到。
追踪霉菌发现的来源：利用分子生物技术，确定污染是来自技术夹层还是原材料。
其他房间（包括技术交叉点）用于模具监控、打字。
评估空调系统中的污染。
洁净区包括一个技术夹层，具有全面的消毒过程。