ECA新闻：欧盟GMP不合规报告将来可能导致FDA进口停止

ECA新闻：欧盟GMP不合规报告将来可能导致FDA进口停止

EU GMPNon-Compliance Report might lead to FDA Import Stop in future

欧盟GMP不合规报告将来可能导致FDA进口停止

The new MRA Agreement between the EU and the USA on the mutualrecognition of GMP inspections is being discussed in depth. One shouldn'tconclude though that the inspection pressure would decrease now because of therecognition of EU inspections. There is a series of exceptions to look out for.The FDA will first ask the competent authority of the EU when the last GMPinspection was performed at a site in question and which GMP deficiencies werefound. If no recent inspection report is available (e.g. the inspection hasn'tbeen performed recently), the FDA can either request a further inspection(Article 10) or perform an inspection itself. In the MRA Agreement, Article 11states: "Within 15 calendar days of receipt of the request, the recognizedauthority shall acknowledge receipt and confirm whether it will conduct theinspection in accordance with the requested timelines"... further, it isstated that: "For greater certainty, if the recognized authority indicatesthat it will not conduct the inspection, the requesting authority has the rightto conduct its own inspection of the manufacturing facility and the requestedauthority has the right to join the inspection."

欧盟和美国之间关于GMP检查相互认可的新MRA协议正在深入讨论。不应该认为现在由于认可欧盟的检查而使检查压力降低。有一系列例外情况要注意。 FDA会首先询问欧盟主管当局某个场所最近一次GMP检查是在何时？发现了哪些GMP缺陷？如果没有最近的检查报告（例如最近没有进行检查），FDA可以要求进一步检查（第10条）或者FDA亲自进行检查。在“MRA协定”中，第11条指出：“在收到请求后的15个日历日内，认可的当局应确认收到并确认是否按照要求的时间表进行检查”......还进一步指出：“为了更加确定，如果认可当局表示不进行检查，提出请求的当局有权亲自对生产设施进行检查，被要求的当局有权参加检查。”

Beside the fact that the FDA will perform its own inspections in the casesmentioned above, the future consequences of an EU GMP inspection for the USmarket should also be considered. Article 8 "Recognition ofinspections" states: "For purposes of this Annex, to accept anofficial GMPs document means to rely on the factual findings in such document."A GMP Non-Compliance Report is also an official GMP document. If an EUauthority declares a GMP Non-Compliance status - among other things in theEudraGMDP - the FDA will use this assessment and take measures against thefacility in question. In some cases, those measures might lead to an importalert, in other words to an import stop for the US market.

除了FDA将在上述情况下亲自进行检查以外，还应考虑欧盟GMP检查对美国市场今后的影响。第8条“检查的承认”指出：“就本附件而言，接受官方GMPs的文件意味着信赖该文件中的事实检查结果。” GMP不合规报告也是官方GMP文件。此外，如果欧盟当局在EudraGMDP中发布了GMP不合规状态 - FDA将会使用此评估并对有关设施采取措施。在某些情况下，这些措施可能导致进口警示，换句话说就是美国市场停止从该设施进口产品。

There are still substantial questions with regard to which EU GMPinspectorates will be recognised as of the 1st of November, for there is nolist with the recognised authorities yet. According to Article 19: "If, by1 November 2017, the FDA has not completed assessments under this Annex of atleast eight Member State authorities for human pharmaceuticals listed inAppendix 2, despite having received complete capability assessment packagesfrom those authorities as specified in paragraph II.A.1 of Appendix 4 inaccordance with the schedule set out in Appendix 5, application of the Articlesreferred to in paragraph 2 shall be postponed to the date on which the FDA hascompleted assessments of at least eight such authorities."

至于从11月1起，哪个欧盟GMP检查机构将得到承认，仍然存在重大问题，因为目前还没有认可机构的名单。根据第19条：“如果在2017年11月1日之前，FDA尚未完成对附件2所列出的至少八个成员国人用药品当局的评估，尽管依照附录5中列出的时间表，已经从这些当局获得了附录4中第II.A.1段所规定的完整的能力评估资料，也要等到FDA至少完成八个此类机构的评估之后，第2段所述的条款才适用。

Regarding Germany, the Annex has a surprise too. Indeed, the German FederalStates are responsible for GMP supervision. Although a coordinating body (ZLG)exists, the responsibility for GMP monitoring lies solely with the FederalStates. Nevertheless, the Agreement provides that not the Federal inspectorates butthe following authorities be assessed by the FDA:

关于德国，附件也是一个惊喜。事实上，德国联邦国家负责GMP监督。虽然存在协调机构（ZLG），但GMP监督完全由联邦国家负责。然而，协议规定，FDA不是评估联邦检查机构，而是要评估以下机构：

• Bundesinstitut     für Arzneimittel und Medizinprodukte (BfArM) - Federal Institute for Drugs     and Medical Devices联邦药物和医疗器械研究所
• Paul-Ehrlich-Institut     (PEI) - Federal Institute for Vaccines and Biomedicines联邦疫苗和生物医药研究所
• Bundesministerium     für Gesundheit (BMG) - Federal Ministry of Health / Central Authority of     the German Länder for Health Protection Regarding  Medicinal Products联邦卫生部/德国中医药管理局关于医药产品的健康保护
• Bundesamt     für Verbraucherschutz und Lebensmittelsicherheit (BVL) -  Federal     Office of Consumer Protection and Food Safety联邦消费者保护和食品安全办公室
• Federal     Ministry of Food and Agriculture联邦食品和农业部
  9 ]/ t4 L) M% r; c: }; A8 B! Y