FDA警告信：常州市金坛前药制药原料厂

Via UPS                                                                                 Warning Letter 320-17-38

May 11, 2017

Mr. Zheng Goubin

General Manager

Changzhou Jintan Qianyao Pharmaceutical Raw Material Factory

No. 678 Zhuangcheng, Baita Town,

Jintan District, Changzhou City,

China 213200

Dear Mr. Goubin:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Changzhou Jintan Qianyao Pharmaceutical Raw Materials at No. 678 Zhuangcheng, Changzhou, Jintan, from February 13–17, 2017.

美国FDA于2017年2月13-17日检查了你们位于江苏省常州市金坛区白塔庄城678号的常州市金坛前药制药原料厂生产场所。

This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).

本警告信总结了原料药生产严重违反CGMP的行为。

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).

由于你们的原料药生产、加工、包装或保存的方法、场所或控制不符合CGMP要求，你们的原料药根据FDCA的501(a)(2)(B)以及21 U.S.C. 351(a)(2)(B)被认为是掺假药品。

We reviewed your March 2017 response in detail.

我们详细审核了你们公司2017年3月的回复。

During our inspection, our investigator observed specific deviations including, but not limited to, the following.

检查期间，我们的调查人员发现的具体问题包括但不仅限于以下：

1.    Failure to implement a system for managing quality encompassing the organizational structure, procedures, processes and resources, as well as activities to ensure confidence that the API will meet its intended specifications for quality and purity. Failure to define and document all quality-related activities.

未能实施质量管理体系，指导公司结构、程序、工艺和资源，以及确保原料药符合其既定质量和纯度标准的活动。未能界定和记录所有质量相关活动。

Before August 2016, your firm did not have any quality-related procedures in place even though you were manufacturing and shipping drugs to the United States. Although you had drafted some procedures by the time of our February 2017 inspection, you had not yet implemented any such procedures as of the date of our inspection.

在2016年8月之前，你们公司虽然在生产和发运药品至美国，但你们并没有任何质量相关程序。尽管到2017年2月，你们已经起草了一些程序，但截至我们检查时，你们还没有实施任何程序。

2.    Failure to have adequate written procedures for the receipt, identification, quarantine, storage, sampling, testing, handling, and approval or rejection of raw materials.

没有充分的原料接收、鉴别、隔离、存贮、取样、检测、处理和批准及拒收书面程序。

For example, when our investigator asked for a list of your critical raw materials and your sampling requirements, you told our investigator that you had no written procedures for testing and sampling incoming materials. Instead, you explained, your warehouse employees accounted for incoming raw material handling, sampling, and testing “in their heads.”

例如，当我们调查人员询问你们关键原料药清单以及你们的取样要求时，你们告诉我们调查人员你们没有进厂物料检测和取样的书面程序。你们解释说，你们的仓库员工“脑子里知道”如何对进厂原料进行处理、取样和检测。

3.    Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure compliance with established specifications and standards.

没有化验室控制记录，包括化验室里实施的所有用于确保符合既定质量标准的测试所产生的完整数据。

For example, our investigator reviewed the audit trail from your assay testing for (b)(4) lot (b)(4), and found that you tested the same sample set three times over several days without documentation or investigation. You reported only the result of the third and final test for purposes of completing your certificate of analysis and releasing this batch of API.

例如，我们的调查人员审核了你们XX物料XX批准的含量检测的审计追踪，发现你们在几天之内检测了同一个样品序列三次，而没有文件记录或调查。你们只报告了第三次最终的检测结果，为的是完成你们的检验报告以及放行该批原料药。

4.    Failure to prepare adequate batch production records and record the activities at the time they are performed.

未制订充分的批生产记录，未在生产实施时记录生产活动。

For example, our investigator found that your operator used process parameter values from previous batches of (b)(4) to complete new batch records when she was too tired to immediately record the data and had forgotten the values.         

例如，我们调查人员发现你们的操作人员使用了来自之前批次的生产工艺值来填写新的批记录，因为当时她太累，没有立即记录数据，所以忘记了实际值。

API CGMP Guidance 原料药CGMP指南

FDA considers the expectations outlined in ICH Q7 in determining whether API are manufactured in conformance with CGMP. See FDA’s guidance document, Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients, for guidance regarding CGMP for the manufacture of API, athttps://www.fda.gov/iceci/compliancemanuals/compliancepolicyguidancemanual/ucm200364.htm.

FDA在确定原料药生产是否符合CGMP要求时考虑的是ICH 17里列出的要求。参见FDA指南文件Q7 原料药GMP指南。

CGMP consultant recommended 建议聘请CGMP顾问

Based upon the nature of the deviations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations, and to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance.

根据我们在你们工厂发同的违规情况，我们强烈建议你们聘请一位有能力评估你们操作的顾问，协助你们符合CGMP要求。你们聘用顾问并不能免除你们公司符合CGMP的义务。你们公司的执行管理人员仍保有全面解决所有缺陷，确保持续符合CGMP要求的职责。

Conclusion 结论

Deviations cited in this letter are not intended as an all-inclusive list. You are responsible for investigating these deviations, for determining the causes, for preventing their recurrence, and for preventing other deviations in your facility.

在此函中所引用的偏差并不是全部。你们有责任对这些偏差进行调查，确定原因，防止其再次发生，防止其它偏差的发生。

If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b) and allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.

如果你们正在考虑可能会导致你们工厂所生产的药品供应中断的措施，FDA要求你们立即通过上述邮箱联系CDER药物短缺办公室，使得FDA可以与你们一起，以最高效的方式将你们的运行带回符合的轨道。与药物短缺办公室联系还能让你们完成所你们所承担的报告你们药品生产中断的义务，使得FDA尽可能快地考虑是否需要采取何种措施来避免短缺，保护依赖于你们药品的患者健康。

FDA placed your firm on Import Alert 66-40 on May 4, 2017.

FDA已于2017年5月4日将你们公司放在进口禁令66-40清单中。

Until you correct all deviations completely and we confirm your compliance with CGMP, FDA may withhold approval of any new applications or supplements listing your firm as a drug manufacturer.

在贵公司未能完成所有偏差纠正并且由我们确认你们符合CGMP之前，FDA可能会搁置所有将你公司列为药品生产的新申报和增补申报的批准。

Failure to correct these deviations may also result in FDA continuing to refuse admission of articles manufactured at Changzhou Jintan Qianyao Pharmaceutical Raw Materials at No. 678 Zhuangcheng, Changzhou, Jintan into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Under the same authority, articles may be subject to refusal of admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).

未能纠正这些偏差可能还会导致FDA依据FDCA第801(a)(3)条和21 U.S.C. 381(a)(3)拒绝接受在上述地址生产的产品进入美国。

After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done since our inspection to correct your deviations and to prevent their recurrence. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

在收到此函后，请在15个工作日内回复至本办公室。在回复中说明自从检查后，你们做了哪些工作来纠正你们的偏差，防止其再次发生。如果不能在15个工作日内完成纠正措施，说明延迟的原因以及完成计划。

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

请将你们的电子回复发送至上述邮箱或者以下邮箱。

Chhaya Shetty

Compliance Officer

U.S. Food and Drug Administration

White Oak Building 51, Room 4355

10903 New Hampshire Avenue

Silver Spring, MD 20993

USA

Please identify your response with FEI 3005587213.

Sincerely,

/S/

Thomas J. Cosgrove, J.D.

Director

Office of Manufacturing Quality

Office of Compliance

Center for Drug Evaluation and Research