［求教］如何得出磷脂产品不在范围内？

仲夏秋夜云

［求教］如何得出磷脂产品不在范围内？
本来这是件小事，FDA发了一封警告信，然后各大自媒体就发布了原文或者发言稿。警告信的警告内容非常吸引眼球，包括：QC经理阻挠检查实验室、拒绝提供相关记录、QA经理限制检查人员拍照。举报内容包括产品中发现玻璃、毛发、黑蜘蛛等。
本来这件事已经过去了，可是近期，根据网友爆料，这家公司的代理商，向相关的国内制药企业发了一份说明信。这封说明信中称，FDA警告信中所涉及的产品并不包括他们代理的磷脂类产品。
而且他们说，FDA对当天检查很满意！很满意啊！然后咔嚓，警告信就出来了！晴天霹雳啊！
据说有律师，正在沟通中。从核查到发警告信之间确实隔了很长的时间，难道不是给你们时间整改，而你们的CAPA不到位，最后决定发警告信的嘛？（一般来说这是正常程序。）你们的意思是，FDA故意整你们？！（FDA如果真违规，可以告的。）律师要用在刀刃上啊！
对了，说到“律师”，我顺便请教一下，这份加盖公章的公函开头说还有很多企业曾经收到了FDA的警告信，列举得那么清楚……您的意思是说，比你们问题严重、死得难看的企业多了去了，你们的状况就是可以被原谅的？你们不怕被这些企业告吗？这典型的属于，死的时候还需要有个更难看的垫底。可死了就是死了。妈，你别打我，虽然我没及格，但隔壁老王才三十分！一个意思？



我和这位网友都想知道，怎么能够体现出不包括磷脂产品呢？原文中，仅仅用了drug这个词，而且警告信中说到的“阻挠检查”、“不提供相关文件”等等，似乎并不分产品，而是整个企业的质量体系出现问题。所以我也想知道，这家企业是如何证明，磷脂类产品不在警告信范围内的。另外据称，这个生产企业（site）的生产内容包括磷脂产品，并不存在磷脂类产品另有生产基地的说法。



回到正题，我请教一下，如何知道磷脂类产品不在警告性范围内？如果是举报信的内容不包括磷脂产品，那么他们是怎么知道举报信内容的？如果是客户投诉，有时候FDA在检查的时候会告知被检查人投诉内容以便被检查人整改或者配合检查。那么你们公开投诉内容不就好了？大家就能很清楚的知道投诉内容是否涉及到该品种。不过看缺陷条款，似乎是不是涉及到这个产品，已经不重要了，质量系统出了问题。在小妖看来，唯一的可能性……是日本人英文不好 完全没有闹清情况……这就是一场乌龙闹剧！他们是如何得出当天检查员对检查情况很满意的？！
也许一切只是一个误会，在进一步沟通当中，我们也静待结果。



FDA原文，请英语好的蒲友找找其中的理由。http://www.fda.gov/iceci/enforcementactions/warningletters/2016/ucm522801.htm?from=singlemessage&isappinstalled=0
Nippon Fine Chemical Co., LTD 9/26/16
Public Health Service
Food and Drug Administration
  10903 New Hampshire Avenue
Silver Spring, MD 20993  

Warning Letter 320-16-35
Via UPS                                                                                 
Return Receipt Requested

September 26, 2016

Mr. Hiromichi Kaneko
General Manager
Nippon Fine Chemical Co., Ltd
1-1, 5-Chome, Umei
Takasago City, Hyogo 676-0074
Japan

Dear Mr. Kaneko:

On December 14, 2015, the U.S. Food and Drug Administration (FDA) arrived at your drug manufacturing facility, Nippon Fine Chemical Co., Ltd, located at 1-1, 5-Chome, Umei, Takasago City, Hyogo, to conduct an inspection. The FDA investigator documented that your firm limited and/or refused an FDA inspection. Under the Federal Food, Drug, and Cosmetic Act (the FD&C Act), as amended by the Food and Drug Administration Safety and Innovation Act (FDASIA), section 707, 21 U.S.C. 351(j), your drugs are adulterated in that they have been manufactured, processed, packed, or held in an establishment where the owner or operator has limited inspection and refused inspection. We reviewed your responses dated January 5, 2016, April 25, 2016, the two letters from August 18, 2016, and correspondence from counsel dated September 14, 2016, in detail.

Your firm limited an inspection and/or refused to permit the FDA inspection as follows:

1.    Barring access to areas
During the inspection, your firm limited the investigator’s access to the quality control laboratory. The quality control manager directed employees to stand shoulder-to-shoulder, barring our investigator from accessing portions of the laboratory and the equipment used to analyze drugs for U.S. distribution.

2.    Refusal to provide copies of documents
Your firm manufactures certain drugs for the Japanese and U.S. markets using the same equipment and processes, and divides lots for distribution between the two markets. During the inspection, our investigator reviewed complaints you received about your drugs from your customers, including complaints that your drugs contained glass, hair, cardboard, metal, product discoloration, and a black spider. Your firm limited the inspection by refusing to provide FDA copies of these records.

3.    Limiting photography
During the inspection, our investigator attempted to take pictures of the (b)(4) apparatus used to manufacture drugs for U.S. distribution. Your quality assurance manager impeded the inspection by preventing our investigator from photographing this piece of equipment.

Your firm was placed on Import Alert 99-32 on August 8, 2016.

The violations cited in this letter are not intended to be an all-inclusive list. You are responsible for investigating and determining the causes, for preventing their recurrence, and for preventing the occurrence of other violations.

Until FDA is permitted to inspect your facility and confirms compliance with CGMP, this office may recommend withholding approval of any new applications or supplements listing your firm as a drug manufacturer. In addition, shipments of articles manufactured at Nippon Fine Chemical Co, Ltd, Takasago City, into the United States are subject to refusal of admission pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3).

After you receive this letter, respond to this office in writing within 15 working days.

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:

LaKeesha M. Foster, Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Ave
Silver Spring, MD 20993
USA

Please identify your response with FEI 3001722961.

julia朱玉姣

这个声明有点意思哈：
1. 举例别人被发警告信-----这种措词是不恰当的，可能引发其它公司律师函，不知道NFC公司的律师怎么会是这样水平。受到一个国家政府机构的负面行政措施，与人无尤，自求多福是正道。说明自己仅有三项，没有任何意义。就好像说一个人死了，不管怎么死的，反正他就是死了。这个死是有一个客观的医学标准。

2. 某产品不在警告信之列-----的确，在警告信中会有提到根据相关法律法规“药品”被认为是掺假药品。但要知道FDA警告信一般否定的是一个厂区一个GMP质量体系，如果把这理解为同一个厂区依赖同一体系的其它非“面向美国药品”就是符合相关GMP要求，恐怕有点牵强。

3. 审计日期2015-12，警告信日期2016-9，这很正常啊，因为给机会改正，对CAPA不满意才会发警告信。大家都是这个流程，而且这个流程是FDA公开的流程，难道NFC是要质疑FDA有暗箱？讲FDA夸大其词，这个得和FDA去说道，跟客户真扯不上。

根本不让FDA检查员进QC，居然还说人家很满意，我们作为吃瓜的中国群众，实在不懂这个罗生门。

非常好奇，有中国客户曾经被荣幸地赐予机会去这个工厂做过供应商审计吗？

最后，选择采购与否，权利肯定在客户手里，出具一封疑似拉低围观群众智商的说明，只能呵呵了。