主要观点总结
FDA对无锡某医疗器械厂的药物生产质量检查进行了通报，指出了多项违反现行药品生产质量管理规范（CGMP）的问题，包括无菌保障失效、物料检验不足、稳定性研究不充分等。要求企业整改并寻求专业顾问的帮助，否则可能影响产品进口到美国。同时，提出了对违规情况的纠正措施和未来的监管要求。
关键观点总结
关键观点1: 警告信中列出的主要违规情况
包括无菌保障失效、物料检验不足、稳定性研究不充分等，涉及到药品的质量、安全性和有效性。
关键观点2: 对回复的要求
要求企业在收到信件后的15个工作日内回复，说明为解决违规情况和防止其再次发生所采取的措施，提供额外的信息供FDA考虑。
关键观点3: 对纠正措施的要求
如果企业不能在15个工作日内完成纠正措施，需要说明延误原因和完成时间表。
关键观点4: 可能的后果
如果企业不解决任何违规情况，可能会导致FDA继续拒绝接受该设施生产的产品进入美国市场。
正文
Insanitary Conditions | 不卫生条件
Your drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, or held under insanitary conditions whereby drugs may become contaminated with filth or rendered injurious to health. FDA investigators observed your facility to be in a state of disrepair, poorly cleaned, and maintained as evidenced by:
根据FD&C法案第501(a)(2)(A)条款，你们的药品被认定为掺假药品，因为药品的制备、包装或储存条件不卫生，可能导致药品被污物污染或对健康造成危害。FDA调查员发现，你们的设施处于失修、清洁和维护不良的状态，具体表现如下：
• Numerous dead insects were inside the tubing used to transfer the active pharmaceutical ingredient (API), (b)(4), from storage drums to (b)(4) tanks, as well as a (b)(4) used for storing API transfer hoses and (b)(4).
用于将原料药（API）(b)(4)从储罐转移至(b)(4)罐的管道内部、用于贮存API转移软管的(b)(4)装置及(b)(4)内，发现大量死亡昆虫。
• Multiple pieces of unknown debris in an (b)(4) solution that was being (b)(4) to a filling machine and transferred (b)(4) that were packaged and labelled as sterile.
在通过(b)(4)输送至灌装机的(b)(4)溶液中，发现多块不明异物，这些溶液经灌装后作为无菌产品包装并贴标。
• Multiple pieces of tubing used to transfer (b)(4) solution from holding containers to filling machines were cracked, leaking, discolored, or contained unidentified residues.
用于将(b)(4)溶液从储存容器转移至灌装机的多根管道存在开裂、泄漏、变色或含有不明残留物。
• Bulk (b)(4) of (b)(4) used to make (b)(4) had hair, unknown particulates, or insects on them.
用于制备(b)(4)的(b)(4)半成品中发现毛发、不明颗粒物或昆虫。
• The ceiling areas above uncovered filling and packaging machines used to manufacture (b)(4) labelled as sterile were visibly dirty and damaged.
在用于生产标识为无菌的(b)(4)产品的敞开式灌装和包装设备上方天花板区域，存在明显污垢和破损。
CGMP Violations CGMP | 违规项
无菌工艺
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Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all sterilization processes (21 CFR 211.113(b)).
你们未能建立并遵循适当的书面程序，包括验证所有无菌和灭菌工艺的程序，以防止声称无菌的药品受到微生物污染（21 CFR 211.113(b)）。
In addition to the insanitary conditions described above, FDA investigators observed during the inspection that since the previous inspection, your firm discontinued sterilization via (b)(4) without implementing a new sterilization procedure. Furthermore, your firm lacked a procedure for conducting environmental monitoring during manufacturing operations and failed to ensure operators adhered to proper gowning requirements, thereby compromising the sterility assurance of (b)(4) labeled as sterile.
除上述不卫生条件外，调查员发现你们公司自上次检查后已停止使用(b)(4)灭菌工艺，但未实施新的灭菌程序。此外，你们公司缺乏生产操作过程中的环境监测程序，且未确保操作人员遵守更衣规范，导致标识为无菌的(b)(4)产品无菌保证水平受损。
See FDA’s guidance document, Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice, to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing, at https://www.fda.gov/downloads/Drugs/Guidances/ucm070342.pdf.
请参阅 FDA 的指南《通过无菌工艺生产的无菌药品 - 现行药品生产质量管理规范》，以帮助你们在使用无菌工艺生产无菌药品时满足 CGMP 要求，网址（略，见上）。
In response to this letter, provide:
在回复本函时，请提供：
• Comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, that includes, but is not limited to:
• 针对无菌工艺、设备及设施污染风险的全面独立风险评估，包括但不限于：
o All human interactions within the ISO 5 area
ISO 5级区域内所有人员干预
o Equipment placement and ergonomics
设备布局与人机工程学
o Air quality in the ISO 5 area and surrounding room
