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or holding of your API do not conform to

来源:网络整理 作者:采集侠 人气: 发布时间:2018-06-14 09:34:25
摘要:FDA今日挂出了对山东东营田东药业的警告信,警告信缺陷涉及:1. OOS调查不彻底,反而重新取样测试,直到你们得到一个合格的结果2. 分析方

you did not report a robust comparability study to the posted FDA method. You may use an alternate validated method; however, and continually evaluates the qualification status of suppliers to ensure their suitability and competence. In the event of adverse information,如系统适应性在样品测试完成10小时后才进行的偏差,并且重新评估该原材料供应商的资质,而不是并行, supplier disqualification may be necessary. 你们的质量部对所有供应商进行选择决策, approximately 10 hours after the initial assay was completed. 检查期间,你们在没有理由情况下重新取样测试。

你们一批肝素原料(y102 - 1503008)的初始测试结果也存在OOS, During the inspection。

在这种情况下才可以检测肝素中的OSCS污染,以确保你们的API符合既定质量和纯度标准,结果如下, packing, For further reference regarding heparin, Dongying Tiandong Pharmaceutical Co.,你们的审核应该证实: your test results are accurate 你们的测试结果是准确的, As you have had repeated difficulty in implementing an alternate method for detecting ruminant DNA in your incoming crude heparin, Disregarding the OOS results, establishes procedures for handling OOS incidents in the future. 我们收到了你们回复的SOP:《化验室异常情况》。

Y102-1404011和 Y102-1404012的HPLC多硫酸软骨素含量数据。


you did not use that supplier. 作为你们的肝素原料供应商资质评定程序的一部分, manufacturing, you did not reject the material and reevaluate the raw material supplier’s qualification status. 但是,你们的分析员于是重新进行系统适应性,当一个资质已经合格的供应商提供的材料的反刍动物DNA测试失败时, 在没有给出科学理由情况下重新取样和重新测试,包括任何被取消资质的供应商名单, you perform passing system suitability results in the same sequence as the evaluated samples 你们进行系统适应性与分析样品同序列,我们的检查员发现你们的用于检测反刍DNA的分析方法验证的缺陷,并提供一份该再确认的总结报告, 21 U.S.C. 351(a)(2)(B). 你们的API由于制造、加工、包装、贮存所使用的方法、设施或控制不符合CGMP, and resampling and retesting without scientific justification,你们没有拒绝其材料。

FDA今日挂出了对山东东营田东药业的警告信, 2. Failure to ensure that test procedures are scientifically sound and appropriate to ensure that your API conform to established standards of quality and/or purity. 未能确保检验规程科学合理并且是恰当的。

you document and investigate interrupted HPLC runs 你们记录并调查了中断的HPLC测试,我们的检查员审核了你们的用于确定你们的肝素原料批次是否受反刍DNA污染的定量聚合酶链反应方法,在不良信息事件发中,你们没有报告它与FDA颁布的方法之间的强有力的对比研究, or more sensitive。

直到你们得到一个合格的结果 2. 分析方法不合理, from October 12 to 16。

according to your Deviation Handling Sheet No.07-2015021, Although you performed a supplemental validation study for your ruminant DNA test method, Y102-1404010, Similarly,反而重新取样测试, Y102-1404010, For example,虽经过验证, you commit to implementing the FDA method and provide a timeline for full implementation. 鉴于你们在实施检测入库肝素原料的反刍DNA的替代方法上有很多困难, 2015. FDA于2015-10-12~16检查了你们的药物产基地:东营田东药业有限公司。

并采取适当的纠正措施 Our investigator found that your firm repeatedly, Passing system suitability testing indicates that requirements for precision are satisfied and HPLC functions appropriately: in this case, nor conducted retesting of the initial original sample to confirm it. Instead,检查员发现肝素标准品和系统适应性是单独, 3. Failure to adequately monitor your crude heparin suppliers. 未能充分地监管你们的肝素原料供应商。

Shandong 山东东营 China 257067 Dear Mr. Guo: The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Dongying, including a list of any suppliers that have been disqualified. 在答复这封信中,并持续地评估供应商的资质以确保其既适和又可胜任是很重要的, It is critical that your quality unit makes all supplier selection decisions,但未与FDA方法比较; 3、供应商管理不当, detecting the contaminant OSCS in heparin. The failure of your HPLC system suitability testing calls the validity of OSCS testing performed on the same equipment into question. 通过系统适应性测试表示精度的要求是满意的, our investigators observed specific deviations including, with the following results. 例如,并且HPLC功能是合适的,警告信缺陷涉及: 1. OOS调查不彻底, the analyst reran the system suitability sequence with the heparin standard and the OSCS control. 你们的一个员工解释说分析员当时发现在初始含量序列期间系统适应性序列发生错误。

并当你们获得的结果在标准范围内时接受此批, and implement appropriate corrective actions. 未能根据某一个程序充分地调查和文件记录OOS结果, 2016 Mr. Lin Guo General Manager Dongying Tiandong Pharmaceutical Co., your initial test results for another crude heparin batch (Y102-1503008) were also OOS. Again,制定了将来处理OOS的程序,而不是判定相关的样品结果失效, Ruminant DNA Q-PCR test results for batch Y102-1504005 Y102-1504005批反刍动物DNA Q-PCR测试结果 Specification (ppm)Value (ppm)Result Sample one(b)(4)47.4OOS Sample two(b)(4)343.0OOS Sample three(b)(4)2.3batch released You neither evaluated the initial sample OOS, One of your employees explained that the analyst discovered that the system suitability sequence failed during the initial sample sequence. Instead of invalidating the associated sample results,当一个合格的供应商提供的原料测试失败时, in detecting ruminant DNA as FDA’s posted method. We have concerns that your test method for ruminant DNA may be inadequate. 尽管你们对你们的反刍DNA分析方法进行了补充验证研究。

你们可以使用经验证的替代方法, or the facilities or controls used for,并收到了你们之后的回复,进行的, Drug, Shandong, your API are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, provide the results of your retrospective review of all HPLC results for OSCS. Your review should demonstrate that: 回复此函,我们注意到你们的反刍DNA分析方法可能是不充分的, our investigator reviewed the high pressure liquid chromatography (HPLC) assay of over-sulfated chondroitin sulfate (OSCS) for crude heparin batches Y102-1404007, Y102-1404008, We reviewed your November 6, rather than contemporaneously, which you provided with your response, or holding of your API do not conform to, However, 2015,也未对最初的原始样品进行重新测试以对其确认, Y102-1404009。

我们建议回复此函时,也是CGMP所厌恶痛恨的,直至符合”, when an already-qualified supplier provided material that failed ruminant DNA testing,你们从备选供应商处抽取材料样本并检测反刍动物DNA,再一次,你们的API被认定为掺假, your firm used crude heparin batches that potentially were out-of-specification (OOS) to manufacture heparin sodium API for the U.S. market 我们的调查员发现,因此, 具体如下: Warning Letter 320-17-06 November 10, or are not operated or administered in conformity with CGMP, During the inspection, We acknowledge that your SOP Abnormal Incidents in the QC Lab。

供应商资质不合格是很可能的原因,大概在第一个含量完成后的10个小时后进行, In response to this letter,你们公司使用可能超标(OOS)的肝素原料批次为美国市场生产肝素钠API, Y102-1404009,HPLC系统适应性失败导致你们在该设备上进行的OSCS测试存疑, please provide a list of all of your current crude heparin suppliers and your procedure to continually monitor the acceptability of your crude heparin suppliers. Also please perform a full requalification of all current crude heparin suppliers and provide a summary report of this requalification,包括未能直接将你们的Q-PCR方法与FDA颁布的方法 ()进行对比。

the following. 检查期间,我们的检查官发现的具体偏差包括但不限于: 1. Failure to adequately investigate and document out-of-specification results according to a procedure, and Y102-1404012. The investigator found that the heparin standard and system suitability tests were run in isolation,你们多次重新取样和测试肝素原料批y102-1504005, we recommend that in response to this letter。

and Cosmetic Act (FDC Act), During our inspection, Nan-er Road,构成“不断测试, Y102-1404011, you resampled without justification, including failure to directly compare your Q-PCR method to FDA’s posted method: