来源：GMP办公室 （ 翻译组）
2017年03月14日，FDA官网挂出对湖北武汉简德明康药业有限公司的警告信，根据该警告信，简德明康药业有限公司涉嫌冒牌销售、复制粘贴其他公司的分析结果作为自己的检验报告书、销售被列入FDA进口警报的供应商的药品等缺陷。具体如下：
The U.S. Food and Drug Administration (FDA)inspected your drug manufacturing facility, Lumis Global Pharmaceuticals Co.Ltd. at Unit 305 Huishang Mansion Building A, 2 Wudayuan Road Donghu New Technology Development Zone, Wuhan, from September 26 to 28, 2016.
美国FDA于2016于9月26-28日检查了贵公司位于武汉市东湖新技术开发区武大园路2号徽商大厦A-305的药品生产场所简德明康药业（武汉）有限公司。
This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).
本警告信概述了不符合原料药（API）CGMP要求的严重违规情况。
Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your API 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).
由于你们生产、加工、包装和存贮药品的方法、设施和控制不符合CGMP，根据FDAC501(a)(2)(B)和21U.S.C. 351(a)(2)(B) ，你们的药品被认为是掺假药。
In addition, your gabapentin API is misbranded undersections 502(a) and 502(b)(1) of the FD&C Act, 21 U.S.C. 352(a) and352(b)(1).
另外，你们的加巴喷丁原料药根据FDCA的502(a)和 502(b)(1) 部分和 21 U.S.C. 352(a)和352(b)(1)部分认定为冒牌药。
We reviewed your November 9, 2016, response in detail. We note your response addressed some FDA observations, but did not address the issues noted below.
我们详细审核了你们于2016年11月9日所发的回复。我们注意到你们回复中解决了一些FDA发现的缺陷，但并没有解决以下问题：
During our inspection, our investigator observed specific deviations including, but not limited to, the following.
在我们检查期间，我们的调查人员发现具体违规情况包括但不仅限于以下：
CGMP Deviations
CGMP问题
1. Failure to transfer all quality or regulatory information received from the API manufacturer to your customers.
未能将所有从API生产商处收到的法规信息和质量信息转达给你们客户。
You omitted the name and address of the original API manufacturers on the certificates of analysis (COA) you issued to your customers, and did not include copies of the original batch certificate.
你们在你们签发给客户的检验报告书（COA）上没有写上原始API生产商的名称和地址，也没有附上原始的批检验报告副本。
For multiple API, you generated COA by copying and pasting analytical results from the original API manufacturers, replacing the manufacturers’ information with your letterhead, then issuing these COA to your customers. You omitted critical information, including the original manufacturers’ names and addresses and the names, addresses, and telephone numbers of laboratories that performed the testing.
你们通过复制粘贴原始API生产商分析结果的方式制作了多个API的COA，用你们的信笺抬头替换掉了生产商的信息，然后将这些COA签发给你们的客户。你们没有写上关键信息，包括原始生产商的名称和地址、实施该检验的化验室的名称、地址和电话号码。
Customers and regulators rely on COA for information about the quality and sourcing of drugs and their components. Omitting information from COA compromises supply-chain accountability and traceability, and may put consumers at risk.
客户和法规人员依赖于COA来获取药品及其成分的质量和来源信息。在COA上不提供这些信息使得供应链可靠信和可追溯性受到损害，可能会将客户置于风险之下。
2. Failure to control the API repackaging, relabeling, and holding operations in order to avoid mix ups and loss of API identity.
未能控制API重新包装、重新标签和存贮操作以避免混淆和API识别性缺失。
Our FDA investigator documented unlabeled material in your “released for shipping” area. You told the investigator that this material was not to be released to customers, but was in fact intended for destruction.
我们的FDA检查人员记录下了在你们“发货放行”区的无标签的物料。你们告诉检查人员说该物料并不是要放行给客户，而是要进行销毁的。
To avoid mix-ups between materials that can and cannot be released, or between different API, you must repackage, relabel, and hold API under appropriate CGMP controls.
为了避免混淆可以放行和不可以放行的物料，避免混淆不同API，你们必须在恰当的CGMP控制下重新包装、重新标签以及存贮API。
Misbranding Violations
冒牌行为
The gabapentin API labels bear the statement “Manufactured under cGMP conditions by: Lumis Global Pharmaceuticals Co., Ltd.” This statement is misleading because it indicates that the manufacturer of the API is Lumis Global Pharmaceuticals Co., Ltd. instead of (b)(4). Therefore, the gabapentin APIs is misbranded under section 502(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) in that the API labeling is misleading.
加巴喷丁原料药标签带有这样的声明：“由简德明康药业(武汉)有限公司在CGMP条件下生产”。该声明是误导性的，因为它标示生产商是简德明康药业(武汉)有限公司而不是XX。 因此，该加巴喷丁原料药根据《联邦食品、药品和化妆品法案（FD&CA）》第502（a）章节规定，因其标签带有误导性，是冒牌的。
In addition, section 502(b)(1) of the FD&C Act requires a drug to contain the name and place of business of the manufacturer, packer, or distributor of the drug. The label of Lumis’ API product is misbranded under section 502(b)(1) because it misidentifies Lumis, which is a distributor or packer, as the manufacturer. As evidenced by the certificates of analysis, (b)(4) is the manufacturer of the gabapentin API, not Lumis Global Pharmaceuticals Co. Ltd.
另外， FD&CA第502（b）（1）章节要求药品包含有生产商、分包商和分销商的名字、地址。简德明康的原料药根据章节502（b）（1）是冒牌的，因为它把分销商或者分包商，简德明康，标成生产商。由检验报告书可以证明，XX才是加巴喷丁的生产商，而不是简德明康药业（武汉）有限公司。
Shipping drugs from a manufacturer on FDA Import Alert 66-66
销售被列入FDA进口警报66-66的生产商的药品
(b)(4), one of your suppliers, has been on Import Alert 66-66 since (b)(4), specifically for their (b)(4) USP API. However, you shipped (b)(4) USP API manufactured by this firm to the United States in February 2015 and declared that you were the manufacturer on importation documents.
你们的一个供应商，XX，从XX开始已经被列入进口警报66-66，特别是他们的XX USP原料药。然而，你们于2015年2月份销售该公司生产的XX USP原料药到美国，并在进口文件中声称你们就是生产商。
2017年03月21日，FDA官网挂出对济南金达药化有限公司的警告信。该检查为欧美联合检查。FDA提出的缺陷包括：删除HPLC数据或结果，重复进样，删除审计追踪，QC经理拥有系统最高权限而不能有效防止数据删除和篡改等。具体如下：
公司名称：Jinan Jinda Pharmaceutical Chemistry Co., Ltd.
济南金达药化有限公司
受检地址：No. 6121 Longquan Road, Zhangqiu City (Jinan), Shandong Province
山东省济南市章丘市龙泉路6121号
检查日期：2016-05-30~2016-06-01
1. Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP, and meet established specifications for quality and purity.
质量部门未能履行其职责确保贵公司生产的API符合CGMP并确保其质量和纯度符合既定标准。
Your quality control laboratory disregarded multiple out-of-specification (OOS) impurity results without justification. For example, on September 22, 2015, you encountered an OOS unknown impurity peak during high performance liquid chromatography (HPLC) testing of (b)(4) 36-month stability batch (b)(4). You terminated the analysis. Testing of a new sample also showed the OOS impurity peak. The chromatogram was then manually rescaled, which hid the presence of this peak. Your laboratory set the integration parameters to omit this peak from integration. Because the peak was omitted, the quality unit was not provided with full information to evaluate whether the stability batch, and potentially other marketed batches, continued to meet quality standards.
你们的QC实验室在没有论证的情况下删除多个超标的杂质分析结果。例如，在2015年9月22日，你们在用高效液相（HPLC）进行XX产品XX批次第36个月的稳定性检验的时候发现一个未知杂质峰OOS。你们中止了分析。对新样品的检验仍然显示含有该杂质峰OOS。之后该色谱图被手动调整，隐藏了这个杂质峰的存在。你们的实验室设置了积分参数以从积分中删除该杂质峰。由于该杂质峰已被删除，质量部门未能得到全部信息来评价该稳定性批次，甚至是其他市售批次，是否仍符合质量标准。
In addition, your audit trail showed that from July 1 to 2, 2015, you performed seven sample injections of (b)(4) 60-month stability batch (b)(4) to test for impurities using HPLC. You permanently deleted the first five sample injections. You then renamed the last two injections and reported that they met specifications. Your quality unit failed to identify and address these serious data manipulations.
另外，你们的审计追踪显示在2015年7月1日~2日期间，你们用HPLC进了7针样品检验XX产品XX稳定性 批次第60个月的杂质。你们永久性地删除了前5针的分析结果。然后重新命名后2针，并报告他们符合标准。你们的质量部门未能发现和处理这类数据篡改。
2. Failure to adequately investigate out-of-specification results.
未能充分调查超标结果。
Your firm did not initiate investigations into failing results as required by your standard operating procedure (SOP) ZL/SOP/ZK/00405. On October 5, 2015, when you encountered an OOS value for an unknown impurity peak through HPLC testing of (b)(4) API 12-month stability batch (b)(4), you prepared and tested new aliquots. You did not investigate the failing result.
贵公司没有按照你们的标准操作规程ZL/SOP/ZK/00405要求对不合格结果开展调查。2015年10月5日，当你们通过HPLC对XX API 第12个月稳定性批次XX进行检验发现未知杂质OOS数值的时候 ，你们没有调查该不合格结果，而是准备并检验了新的样品。
3. Failure to prevent unauthorized access or changes to data, and failure to provide adequate controls to prevent omission of data.
未能防止非授权的进入或修改数据，并且未能提供充分的控制以防止数据删除。
Our investigator observed that your laboratory systems lacked controls to prevent your staff from altering or deleting electronic data. Analysts manipulated and deleted audit trails. You lacked adequate controls for all HPLC, gas chromatography, and ultra-violet systems.
我们的检查员发现你们的实验室系统缺乏控制来防止你们的员工修改或删除电子数据。分析人员篡改并删除审计追踪。你们对所有HPLC、气相和紫外光谱缺乏充分的控制。
For example, an analyst deleted audit trails in your gas chromatography equipment #YQ-07-10 from September 15, 2015, through April 24, 2016, and permanently deleted audit trails from November 6 to 13, 2015. In addition, our investigator observed that your quality control manager and quality control deputy manager had full administrative rights on all of your computerized systems, which allows them to manipulate data and turn off audit trails.
例如，一个分析员在你们的气相色谱仪#YQ-07-10中删除了2015年11月6~13日的审计追踪。另外，我们的检查员发现你们的QC经理和QC副经理对你们的所有计算机化系统都有完整管理权限，这无疑为他们篡改数据和关闭审计追踪开了后门。
We acknowledge that you commit to upgrading your analytical systems to be compliant with CGMP requirements. However, procuring new instruments, installing new and upgraded data acquisition software, and enabling various software features are insufficient to achieve CGMP compliance. These steps will be effective only if you implement appropriate procedures and systems to ensure that your quality unit reviews all production and control data and associated audit trails as part of the batch release process.
我们知道你们承诺升级你们的分析系统以符合CGMP要求。然而，购买新仪器，安装新的升级的数据采集软件，和启用各种软件端口并不足以达到CGMP要求。这些步骤仅在当你们实施了适当的程序和体系来确保你们的质量部门审核所有生产和检验数据，以及相应的审计追踪作为批放行程序的一部分时才会有效。
Your response states that your SOP for electronic data management specifies that only information technology staff will have full administrator rights. However, you did not specify which information technology personnel will have these administrator rights. In addition, this SOP became effective on May 9, 2016, prior to the FDA inspection. However, your quality control management still had full administrative rights to all computerized systems during our inspection from May 30 to June 1, 2016.
你们的回复说你们的电子数据管理SOP规定了只有IT人员才能有最高管理权限。然而，你们没有指定哪个IT人员才有这种管理权限。另外，该SOP在FDA检查之前，2016年5月9日就生效了。然而你们的QC经理在2016年5月30到6月1日我们检查期间仍然对所有计算机化系统拥有最高管理权限 。
一同参与检查的机构还有西班牙药品和医疗器械局（欧盟检查不符合后的复查），并于2016-07-29签发了不符合报告。西班牙当局检查提出的缺陷如下：
The site was inspected by EDQM in June 2015 and foundnon-compliant; as a result, the site’s CEP was suspended. Despite the 2015non-compliance, sales to EU customers continued (list available by EDQM onauthorities’ request).
EDQM于2015年06月检查了该企业并检查不合格。所以，该公司的CEP证书就失效了。尽管如此，公司仍继续向EU 客户销售产品（在官方索取下EDQM取得清单）。
The Company has been found to be not GMP compliant; atotal of 30 deficiencies were identified in total, two of them classified ascritical and eight as major.
检查发现公司不符合EU GMP，总共发现30条缺陷，其中2条关键缺陷，8条主要缺陷。
The CAPA for the previous EDQM inspection (June2015, CEP suspension) report were found as not having been implemented in a satisfactoryway.
为之前EDQM检查所做的CAPA（2015年06月，CEP失效）被发现实施不满意。
Critical deficiencies were found on raw data safety, control and OOSreview. Moreover, several major deficiencies were found in training, changecontrol, quality assessment, process and cleaning validations.
关键缺陷为原始数据安全性、控制和OOS审核。此外，还有几个关于培训、变更控制、质量评估、工艺和清洁验证方面的主要缺陷。
Import Alert # 99-32
进口警报#99-32
Published Date: 03/29/2017
发布日期：2017年3月29日
Gauke Healthcare Co., Ltd.
湖北高格医疗用品有限公司
Chengnan Industrial Park , Tuanfang Dadao; Tuanfengxian, Huanggang,Hubei CHINA
中国湖北黄冈市团风县团风大道城南工业园
Import Alert Name:
进口警报名称：
"DETENTION WITHOUT PHYSICAL EXAMINATION OF PRODUCTS FROM FIRMS REFUSING FDA FOREIGN ESTABLISHMENT INSPECTION"
产品无需实物检查即被自动扣押制裁，因企业拒绝FDA国外检查。
