FDA给印度生产商Polydrug的警告信(内容很不可思议)

FDA给印度生产商Polydrug的警告信(内容很不可思议)April 14, 2016 Mr. Punit Thakrar, Managing DirectorPolydrug Laboratories Pvt. Ltd. Corporate OfficeA201-202, Navbharat Estates, Zakaria Bonder RoadSewri(W)Mumbai – 400015Maharashtra, India Dear Mr. Thakrar: From March 16-23, 2015, an investigator from the U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Polydrug Laboratories Pvt. Ltd., PlotN-37, Addl. Ambarnath Industrial Area, MIDC, Anand Nagar, Ambarnath (East), Maharashtra, Mumbai.2015年3月16-23日，我们FDA的调查员检查了你们位于上述地址的生产工厂。

We identified significant deviations from current good manufacturing practice (CGMP) for the manufacture of active pharmaceutical ingredients (API).我们发现了严重违反原料药生产CGMP的问题。

These deviations cause your drugs to be 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), in that the methods used in, or the facilities or controls used for, their manufacture, processing, packing, or holding do not conform to, or are not operated or administered in conformity with, CGMP.这些问题导致你们生产的药品根据联邦食品药品化妆品法案501(a)(2)(B) 部分21 U.S.C. 351(a)(2)(B)被认定为掺假药。

We have reviewed your April 9, 2015, response in detail and acknowledge receipt of your subsequent response.我们已经详细审核了你们于2015年4月9日的回复，并且告知已收到之后的回复。

Our investigator observed specific deviations during the inspection, including, but not limited to, the following.我们的调查员在检查期间发现的具体违规情况，包括但不限于以下：1. Failure to record and investigate all quality-related customer complaints according to an established procedure.未能根据既定程序记录和调查所有与质量相关的客户投诉。

During the inspection our investigator found a torn sheet of paper titled “Product Quality Complaints” on the floor of your warehouse. We compared it to your firm’s official complaint log and discovered that only 2 of the 17 customer complaints on the torn sheet were recorded in your firm’s official complaint log. Further, your firm indicated that there may be additional unlogged and/or uninvestigated complaints, but did not provide further explanation. Your firm had not investigated the complaints we found on the torn sheet. These uninvestigated complaints reported API that were either sub-potent or containedfilth, including the following problems:在检查期间，我们的调查员在你们仓库的地面上发现了一张被撕毁的表，标题是“产品质量投诉”。

我们将它与你们公司的正式投诉登记本进行了比较，发现在被撕毁的表上有17个投诉，而在公司正式的客诉登记本上只登记了2条。

还有，你们公司说可能还有其它没有登记和/或没有调查的投诉，但没有做出进一步解释。

你们公司没有对我们在被撕毁的表上发现的那些投诉。

这些未经调查的投诉报告了原料药效价不达标以及受到污染的情况。

low assay value for (b)(4) API某原料药含量低particles and hairs in (b)(4) API某原料药发现颗粒和头发an insect and dirt in (b)(4) API原料药里发现昆虫和脏物safety goggles in (b)(4) API原料药里发现护目镜(b)(4) scoop in (b)(4) API 原料药里发现料勺Your response stated that you will initiate a corrective action and preventive action (CAPA) plan to include your quality unit’s assessment of your current practices.你们的回复说你们会启动CAPA计划，其中会包括你们质量部门对现行做法的评估。

Your response is inadequate because it is silent on any retrospective investigations conducted for the 17 complaints that our investigator found on the sheet of paper on your warehouse floor. Your response also did not specify improvements to yourcomplaint handling procedures and documentation practices or efforts to locate and investigate any other unlogged and/or uninvestigated complaints that your firm acknowledged could exist.你们的回复是不充分的，因为你们对于我们调查员在你们仓库地面上发现的表上列出的17个投诉的回复性调查保持沉默。

你们的回复也没有说明对你们投诉处理程序和记录规范的改进，也没有努力锁定其它未登记和/未调查的投诉，你们公司已知存在的那些投诉。

Although the 17 complaints in the unofficial log were not from U.S. customers, your firm uses shared equipment, personnel, and materials to manufacture products for multiple markets, including the Un ited States. Your firm’s poor complaint handling practices and your inability to prevent and detect product quality defects, such as filth, indicate significant lapses in your firm’s quality system. You are responsible for ensuring that prior to release your API meet quality and safety requirements and for assuring that any subsequent quality defects are thoroughly investigated. You are also responsible for taking appropriate corrective actions and preventive actions.虽然在非正式的登记本上的17个投诉并不是来自美国客户，但你们公司使用了相同的设备、人员和物料来生产药品供给多个市场，其中包括美国市场。

你们公司差劲的客户投诉处理做法，对防止和发现产品质量缺陷如污染的无能为力，显示出你们公司质量体系的严重失策。

你们有责任在放行原料药之前确保其符合质量和安全要求，确保随后的质量缺陷受到彻底调查。

你们还有责任采取适当的CAPA。

In response to this letter, provide the following:在回复此信函时，请提供以下内容：a summary of your investigations of all complaints received since 2012, noting whether each complaint is logged in your official complaint log and including root cause determinations and CAPA你们对所有自2012年以来收到的投诉的调查总结，注意是否每个投诉都登记在你们的正式投诉登记本上，并且包括了对根本原因的确定以及CAPAyour improved complaint handling procedure and details of any further controls implemented to ensure that all complaints are logged, documented, and promptly investigated你们改善过的客户投诉处理程序，你们为了确保所有投诉都会登记、记录和尽快调查所实施的所有进一步控制方法2. Failure to review and investigate all production deviations.未能审核和调查所有生产偏差Our investigator found a torn page from a batch production record for lot (b)(4) of API(b)(4) in the trash. He noted discrepancies between the discarded page and the complete batch production record that your firm represented as the officialrecord for that lot. Your firm did not investigate this deviation or the unacceptable practice of discarding a manufacturing record. You did not determine the root cause or assess its effect on drug quality prior to releasing lot (b)(4).我们的调查员在垃圾中发现某原料药某批号批生产记录上撕下来的一页。