翻译：JULIA 来源：Julia法规翻译
ViaUPS
Warning Letter 320-17-39
June 22, 2017
Mr. Liu Jian Hua
Professor and Director
Shandong Analysis and Test Center
19 Keyuan Road
Jinan, Shandong, China 250014
Dear Mr. Liu Jian Hua:
The U.S. Food and Drug Administration (FDA) inspectedyour drug manufacturing facility, Shandong Analysis and Test Center at 19Keyuan Road, Jinan, Shandong, from January 16–18, 2017.
美国FDA于2017年1月16-18日检查了你们位于山东省济南市历下区科院路19号的药品生产场所---山东省分析检测中心。
This warning letter summarizes significant deviationsfrom current good manufacturing practice (CGMP) for active pharmaceuticalingredients (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 formanufacturing, processing, packing, or holding do not conform to CGMP, your APIare 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 February 20, 2017 response indetail.
我们详细审核了你们公司2017年2月20日的回复。
During our inspection, our investigators observedspecific 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 ensure thattest procedures are scientifically sound and appropriate to ensure that yourAPI conform to established standards of quality and/or purity.
未能确保检测程序科学合理适当，无法确保你们的API符合既定的质量和/或纯度标准。
Your site is a contract testing lab that analyzessamples of heparin and heparin-related drugs for the presence of over-sulfatedchondroitin sulfate (OSCS) using Nuclear Magnetic Resonance (NMR)spectroscopy.
你们的场所是肝素和肝素相关药品样品分析的委托化验室，提供多硫酸软骨素（OSCS）项目核磁共振（NMR）检测服务。
You failed to routinely establish system suitabilitywhen testing samples for OSCS.
你们在检测样品的OSCS项目时，日常检测未运行系统适用性。
Furthermore, on December 26, 2014, you conducted asystem suitability test that failed. You did not investigate why your equipmentfailed system suitability for detection of OSCS, or determine the reliabilityof other OSCS tests conducted prior to the date of the system suitabilityfailure.
另外，2014年12月26日，你们运行了系统适用性，但系统适用性失败。你们未调查为什么仪器的OSCS检测用系统适用性会失败，也没有确定该系统适用性失败之前其它OSCS检测结果是否可靠。
In your response, you acknowledge that your laboratoryperformed system suitability infrequently, noting that “the heparin standards(USP) and OSCS were detected at least (b)(4).” You committed toroutinely establish system suitability before analyzing batch samples in thefuture.
在你们的回复中，你们说你们化验室很少运行系统适用性，因为你们看到“肝素标准品（USP）和OSCS至少在XX中检出”。你们承诺会在将来进行样品分析之前常规运行系统系统性。
Your response is inadequate because you did notinvestigate the validity of all test results for OSCS in heparin orheparin-related drugs during the period in which you failed to conduct systemsuitability in coordination with sample analyses.
你们的回复是不充分的，因为你们没有调查你们未运行系统适用性期间样品分析中肝素或肝素相关药物中OSCS所有检测结果的有效性。
System suitability testing determines whetherrequirements for precision are satisfied and ensures the NMR spectrometer isfit for the intended testing before analyzing samples. It is critical that yoursystem be demonstrated as suitable for detecting OSCS contamination in heparinto avoid the possibility of samples erroneously passing when an instrument isnot working properly.
系统适用性检测决定了精密度是否满足要求，在开始样品分析之前确保NMR仪器适合既定检测。证明系统适合于检出肝素中的OSCS污染，避免仪器不正常工作时使得样品错误地通过检测是非常重要的。
For further reference regarding heparin, see theguidance for industry Heparin for Drug and Medical Device Use: MonitoringCrude Heparin for Quality athttp://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM291390.pdf.
关于肝素的更多参考资料，参见行业指南：药用和医疗器械用肝素：监测肝素粗品的质量。
2. Failure to prevent unauthorizedaccess or changes to data, and to provide adequate controls to preventmanipulation and omission of data.
未能防止未经授权进入和修改数据，未能提供足够的控制以防止数据修改和删除。
Your quality control unit did not have basic controlsto prevent changes to your electronically-stored laboratory data. During ourinspection, we requested that you display original electronic data for analysisof heparin and heparin-related drug samples. Your analyst was unable to retrieverequested data, and explained that he deletes older data to make space fornewly acquired data.
你们质量控制部门没有基本的控制用以防止对你们电子存贮实验室数据的修改。在我们的检查期间，我们要求你们显示肝素和肝素相关药物样品分析的原始电子数据。你们的化验员未能恢复所要求展示的数据，还解释说他删除了旧数据，给新产生的数据腾出空间。
In your response, you committed to revise proceduresregarding analyst computer permission levels, but did not address the data thatwas deleted.
在你们的回复中，你们承诺说要修订化验室计算机许可水平的程序，但没有说明数据删除的问题。
Access to information during inspection检查期间信息获取
During the inspection, you provided a document listingthe names of (b)(4) customers for which you performed testing. However,you only provided additional requested information, such as sample informationand test results, regarding (b)(4) of these customers. You stated thatyou would not provide data related to testing performed for other customersuntil you obtained their prior consent.
在检查期间，你们提供了一份文件，其中列出了你们受委托进行检测的客户名称。但是，你们只是提供了我们要求查看的与这些客户的XX有关的其它信息，如样品信息和检测结果。你们说你们不能提供为其它客户所检测的样品数据，除非获得其许可。
For example, you failed to provide informationpertaining to samples analyzed for (b)(4), a firm that produces heparinand heparin-related drugs for the U.S. supply chain.
例如，你们未能提供包含有为XX客户所检测的样品的信息。该公司为美国供应链生产肝素和肝素有关药品。
When an owner, operator, or agent delays, denies,limits, or refuses an inspection, the drugs manufactured, processed, packed, orheld in the facility may be deemed adulterated under section 501(j) of theFD&C Act. See FDA’s guidance document, Circumstances thatConstitute Delaying, Denying, Limiting, or Refusing a Drug Inspection, athttps://www.fda.gov/downloads/regulatoryinformation/guidances/ucm360484.pdf.
当一个场所的所有人、操作员或代理延误、否决、限制和拒绝检查时，在该场所生产、加工、包装和存贮的药品根据FDCA的501（j）会被作为掺假药。参见上述指南。
Conclusion结论
The deviations cited in this letter are not intendedas an all-inclusive list. You are responsible for investigating the deviations,for determining the causes, for preventing their recurrence, and for preventingother deviations.
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。
Until you correct all deviations completely and weconfirm your compliance with CGMP, FDA may withhold approval of any newapplications 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 inFDA refusing admission of articles manufactured at Shandong Analysis and TestCenter at 19 Keyuan Road, Jinan, Shandong, into the United States under section801(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 andcontrols used in their manufacture do not appear to conform to CGMP within themeaning 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 officein writing within 15 working days. Specify what you have done since ourinspection to correct your deviations and to prevent their recurrence. If youcannot complete corrective actions within 15 working days, state your reasonsfor 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 [email protected]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地址：
Rokhsana Safaai-Jazi
Compliance Officer
U.S. Food and Drug Administration
White Oak Building 51, Room 4359
10903 New Hampshire Avenue
Silver Spring, MD 20993
USA
Please identify your response with FEI 3011060456.
Sincerely,
/S/
Thomas J. Cosgrove, J.D.
Director
Office of Manufacturing Quality
Office of Compliance
Center for Drug Evaluation and Research
