FDA警新加坡欧芳

一片红云

昨夜，FDA官网发出对全球眼药水、隐形眼镜巨头新加坡欧芳有限公司的警告信，缺陷包括：

生产过程中发现容器密封缺陷但是放行了产品导致客户投诉。并且在培养基灌装过程中也发现容器密封缺陷。
重复使用容器成型材料
工艺未验证
未对供应商检验的可靠性进行确认而直接使用供应商的检验结果。
部分产品没有开展稳定性试验，检查时未能提供稳定性试验原始数据。
新药未经批准

具体如下：

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Opto-Pharm Pte Ltd. at 13, Tuas Avenue 12, Singapore, from March 14 to 22, 2016.
FDA于2016年3月14~22日检查了你们的药品生产工厂，新加坡欧芳独资有限公司，位于新加坡大士12道。

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.
本警告信概况了成品CGMP条款的重大违规。见21CFR 210部分和211部分。

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).
因为你们的方法、设施，或者生产、加工、包装或贮存的控制不符合CGMP，你们的药品被认为掺假。

We reviewed your April 7, 2016, response in detail. You have not provided sufficient details or supporting evidence to demonstrate that you have taken adequate corrective actions.
我们审核了你们于2016年4月7日的回复，你们还未能提供充分的细节或支持性证据来证明你们已经采取了充分的纠正措施。

During our inspection, our investigators observed specific violations including, but not limited to, the following.
检查期间，我们的检查员发现的具体违规包括但不限于如下：

1.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 aseptic and sterilization processes (21 CFR 211.113(b)).
未能建立和遵循适当的书面规程以防止无菌药品的微生物污染，包括所有无菌和灭菌工艺的验证。

During aseptic manufacturing of your sterile ophthalmic products(b)(4)(lot(b)(4)) and(b)(4)(lot(b)(4)), you documented numerous leaking containers and other bottle formation defects. To address these defects, you routinely adjusted your(b)(4)((b)(4)) equipment and resumed production. You subsequently released these lots. Following distribution, you received customer complaints of leaking containers.
在无菌眼科产品XX（批号：XX和XX）的无菌生产过程中，你们记录了很多漏液的容器以及其他瓶子结构性缺陷。为了解决这些问题，你们调整了你们的XX设备，并继续生产。你们后来放行了这些批次。再后来销售的时候，你们收到了容器漏液的客户投诉。

In addition, you found numerous critical container-closure defects, including leaking products, during media fills studies. Container integrity is imperative to ensure sterility of ophthalmic drug products. The lack of assurance that your(b)(4)equipment consistently manufactures an integral container-closure system diminishes confidence in the sterility of your marketed products.
另外，你们在培养基灌装试验过程中发现很多容器密封缺陷，包括漏液。容器完整性对眼科药品保持无菌性至关重要。你们的XX设备缺乏始终如一生产出完整的容器密封系统的保证，这减少了对你们的市售产品无菌性的信心。

Additionally, our inspection found that your firm re-uses(b)(4)as many as(b)(4)times before discarding them.(b)(4)should normally be used once, then discarded after manufacturing a single product lot. Repeated use and re-sterilization can compromise(b)(4)efficacy and physical/chemical stability (e.g., particles, leachables, extractables).
另外，我们的检查发现贵公司重复使用XX多达XX次才将它们丢弃。XX通常只能用一次，然后在生产完一个单独批次之后丢弃。重复使用和重复灭菌可能影响XX有效性和物理/化学稳定性（如微粒、滤出物、可提取物）

During our inspection, you acknowledged your failure to validate your process prior to distributing drugs. In your response, you committed to develop and execute protocols for process performance qualification and equipment qualification.
在我们检查期间，你们承认你们未能在药品上市之前验证你们的工艺。在你们的回复中，你们承诺开展和执行方案进行工艺性能确认和设备确认。

2.Your firm failed to establish the reliability of the container-closure supplier’s analyses through appropriate validation of the supplier’s test results at appropriate intervals (21 CFR 211.84(d)(3)).
未能通过在适当的间隔对供应商的测试结果进行适当的验证来建立容器密封部件供应商的分析结果的可靠性。

Your firm uses(b)(4)supplied by(b)(4)in your(b)(4)equipment to manufacture the container-closures for your ophthalmic products. You accepted values reported on the supplier’s certificate of analysis for density and(b)(4)for each incoming lot but did not verify the reliability of the supplier’s results.
贵公司在你们的XX设备使用由XX供应的XX来生产眼科产品的容器密封部件。对于每批入库物料，你们接受了供应商COA所报告的密度和XX的数值而没有确认供应商的结果的可靠性。

Using(b)(4)that does not meet its quality attributes, such as density and(b)(4), may result in container-closure integrity defects that could compromise the sterility of your ophthalmic drug products.
使用XX不符合其质量属性，如密度和XX，的XX，可能导致容器密封完整性缺陷，影响你们的眼科药品的无菌性。

3.Your firm failed to ensure that your drug products bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).
未能确保有适当的稳定性试验支持你们的药品的失效期。

Your firm failed to conduct stability studies for Buffered Saline and(b)(4)ophthalmic solutions produced in 2014 and 2015. Furthermore, at the time of the inspection, you could not provide raw data to support test results from stability studies you conducted for other products.
贵公司未对2014年和2015年生产的生理缓冲液和XX眼药水进行稳定性试验。更有甚者，在检查的时候，你们未能对其他产品提供支持其稳定性试验结果的原始数据。

Your failure to conduct stability studies and lack of data supporting expiration dates compromises your ability to detect quality problems with marketed ophthalmic products. Without stability data, you cannot assure the quality of your products throughout their labeled shelf lives. In addition, you have received multiple customer complaints of leaking ophthalmic containers, which also calls into question your ability to maintain sterility of your ophthalmic products throughout their labeled expiration dates.
你们未能进行稳定性试验并且缺乏数据支持失效期，这使你们发现市售眼科药品质量问题的能力大打折扣。

茶语人生

这些缺陷放在中国，肯定是收证、召回，甚至立案（掺假）。

syhorchid

了解一下

rulai

不要以为国外的企业就一定做得很好。

紫幻剑雨888

天下的乌鸦一般黑啊……

蓝雨~

容器漏液，这在外观检查的时候发现不了吗？应该也是要灯检的吧滴眼剂

scslk0045

新加坡也这样干？美国也制裁自己的小跟班？

xqliu

借鉴，学习一下啦，谢谢提供分享。

一片红云

就是，这种企业越知名，欺骗性越强，患者信赖

小金库

受益匪浅