{"id":59923,"date":"2018-10-30T01:00:00","date_gmt":"2018-12-07T02:51:37","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/12\/07\/d99a1ed8a3\/"},"modified":"2018-12-07T10:51:38","modified_gmt":"2018-12-07T02:51:38","slug":"d99a1ed8a3","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/59923\/","title":{"rendered":"\u624b\u52a8\u79ef\u5206\u7684\u5229\u548c\u5f0a"},"content":{"rendered":"
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\"\u624b\u52a8\u79ef\u5206\u7684\u5229\u548c\u5f0a\"<\/p>\n

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\u5b9e\u9a8c\u5ba4\u6570\u636e\u5b8c\u6574\u6027\u5df2\u6210FDA\u68c0\u67e5\u5236\u836f\u4f01\u4e1a\u7684\u4e00\u628a\u5229\u5668\uff0c\u5176\u4e2d\u4e00\u6761\u5173\u4e8e\u968f\u610f\u624b\u52a8\u79ef\u5206\u6216\u8005\u65e0\u4e66\u9762\u7a0b\u5e8f\u89c4\u5b9a\u624b\u52a8\u79ef\u5206\uff0c\u8bf4\u660e\u4e86FDA\u672c\u8eab\u5e76\u4e0d\u662f\u4e0d\u8ba4\u53ef\u624b\u52a8\u79ef\u5206\uff0c\u800c\u662f\u8981\u6c42\u6709\u64cd\u4f5c\u89c4\u7a0b\u89c4\u5b9a\u4ec0\u4e48\u60c5\u51b5\u53ef\u4ee5\u624b\u52a8\u79ef\u5206\uff0c\u5982\u4f55\u79ef\u5206\uff0c\u5e76\u4e14\u5e94\u4fdd\u5b58\u5e76\u8bb0\u5f55\u79ef\u5206\u53c2\u6570\u3002<\/p>\n


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CFDA\u7d27\u8ddfFDA\u7684\u6b65\u4f10\uff0c\u57282016\u5e74\u5ea6\u591a\u6b21\u98de\u68c0\u4e2d\uff0c\u5f00\u5177\u591a\u6761\u6570\u636e\u5b8c\u6574\u6027\u65b9\u9762\u7684\u7f3a\u9677\uff0c\u6536\u56de\u591a\u5f20GMP\u8bc1\u4e66\u3002\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u5e76\u6ca1\u6709\u5f00\u5177\u7f3a\u9677\uff0c\u5236\u836f\u4f01\u4e1a\u5e94\u9632\u60a3\u4e8e\u672a\u7136\uff0c\u63d0\u524d\u628a\u624b\u52a8\u79ef\u5206\u7ba1\u7406\u597d\u3002<\/p>\n


<\/p>\n

\u4e00\u3001\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u6307\u5357<\/strong><\/span><\/p>\n


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\u5173\u4e8e\u624b\u52a8\u79ef\u5206\uff0c\u5e76\u6ca1\u6709\u6307\u5357\u7ed9\u51fa\u660e\u786e\u7684\u5b9a\u4e49\u3002\u7b14\u8005\u53ea\u67e5\u5230\u6709\u4e24\u7bc7\u751f\u7269\u6837\u672c\u5206\u6790\u7684\u65b9\u6cd5\u9a8c\u8bc1\u6307\u5357\u89c4\u5b9a\u4e86\u518d\u79ef\u5206\uff08Reintegration\uff09\u7684\u6ce8\u610f\u4e8b\u9879\u3002<\/p>\n


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FDA\u76842001\u5e74\u5b9a\u7a3f\u6307\u5357 Bioanalytical Method Validation\uff0c\u53ca\u76f8\u5e94\u76842013\u5e74\u8349\u6848\u6307\u5357\u4e5f\u6709\u7c7b\u4f3c\u7684\u8981\u6c42\u3002 \u751f\u7269\u6837\u672c\u5206\u6790\u7684\u65b9\u6cd5\u9a8c\u8bc12013\u8349\u6848\u6307\u5357\uff0c\u7b2cIII.C\u8282\u201c\u6837\u672c\u6570\u636e\u518d\u79ef\u5206\u201d\u89c4\u5b9a\uff1aSOP\u5e94\u8be5\u786e\u5b9a\u518d\u79ef\u5206\u7684\u6807\u51c6\uff0c\u548c\u600e\u6837\u8fdb\u884c\u518d\u79ef\u5206\uff1b\u5e94\u6e05\u695a\u63cf\u8ff0\u3001\u5e76\u8bb0\u5f55\u518d\u79ef\u5206\u7684\u7406\u7531\uff1b\u5e94\u62a5\u544a\u539f\u59cb\u548c\u518d\u79ef\u5206\u6570\u636e\u3002\u7b2cVII.D\u8282\u8fd8\u89c4\u5b9a\uff1a\u518d\u79ef\u5206\u6570\u636e\u5e94\u6709\u7ba1\u7406\u4eba\u5458\u6388\u6743\u518d\u79ef\u5206\u3002<\/p>\n


<\/p>\n

EMA\u76842011\u5e74\u6307\u5357 Guideline on bioanalytical method validation\uff0c\u7b2c5.5\u8282\u89c4\u5b9a\uff1a\u5e94\u8be5\u6709SOP\u63cf\u8ff0\u8272\u8c31\u7684\u79ef\u5206\u548c\u518d\u79ef\u5206\u3002\u5e94\u5728\u5206\u6790\u62a5\u544a\u4e2d\u8ba8\u8bba\u504f\u79bb\u8fd9\u4e2aSOP\u7684\u4efb\u4f55\u504f\u5dee\u3002\u5e94\u8be5\u8bb0\u5f55\u8272\u8c31\u79ef\u5206\u3001\u518d\u79ef\u5206\u7684\u79ef\u5206\u53c2\u6570\u3001\u521d\u59cb\u79ef\u5206\u6570\u636e\u3001\u6700\u7ec8\u79ef\u5206\u6570\u636e\uff0c\u5e76\u5728\u8981\u6c42\u65f6\u7acb\u5373\u53ef\u5f97\u3002<\/p>\n


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\u4e8c\u3001\u4ec0\u4e48\u60c5\u51b5\u4e0b\u53ef\u4ee5\u8fdb\u884c\u624b\u52a8\u79ef\u5206\uff1f<\/span><\/strong><\/p>\n


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1\uff09\u4f4e\u5206\u79bb\u5ea6\u6216\u4f4e\u54cd\u5e94\uff1b<\/p>\n

2\uff09\u6d41\u52a8\u76f8\u4e0d\u7a33\u5b9a\uff0c\u57fa\u7ebf\u7d0a\u4e71\uff0c\u4fdd\u7559\u65f6\u95f4\u53d8\u5316\u5c0f\uff1b <\/p>\n

3\uff09\u8fd0\u884c\u8fc7\u7a0b\u4e2d\uff0c\u51fa\u73b0\u5f02\u5e38\u5cf0\uff1b <\/p>\n

4\uff09\u8f6f\u4ef6\u79ef\u5206\u7684\u5c40\u9650\u6027\uff0c\u5982\u7531\u4e8e\u8f6f\u4ef6\u53c2\u6570\u9608\u503c\u7684\u8bbe\u7f6e\u5bfc\u81f4\u5cf0\u672a\u79ef\u5206\uff0c\u5cf0\u8d77\u70b9\u548c\u7ec8\u70b9\u95f4\u51fa\u73b0\u80a9\u5cf0\u548c\u5f02\u5e38\u7684\u57fa\u7ebf\u6f02\u79fb\uff0c\u8f6f\u4ef6\u9519\u8bef\uff08\u5cf0\u672a\u79ef\u5206\u548c\u9519\u8bef\u8bc6\u522b\u5cf0\uff09\uff1b<\/p>\n

5\uff09\u7531\u4e8e\u6837\u54c1\u6bcd\u4f53\u7684\u5e72\u6270\u5bfc\u81f4\u7684\u590d\u6742\u8272\u8c31\u56fe\uff1a\u88c2\u5cf0\u3001\u76ee\u6807\u6742\u8d28\u7684\u540c\u65f6\u6d17\u8131\/\u80a9\u5cf0\u3001\u57fa\u7ebf\u566a\u97f3\u3001\u8d1f\u5cf0\u3001\u57fa\u7ebf\u4e0a\u5347\u6216\u4e0b\u964d\uff08\u7531\u4e8e\u67d0\u4e9b\u68af\u5ea6\u7a0b\u5e8f\uff09\u3001\u5cf0\u7684\u4e25\u91cd\u62d6\u5c3e\u3001\u70c3\u7c7b\u7684\u5b58\u5728\u5bfc\u81f4\u81ea\u52a8\u79ef\u5206\u4e0d\u6b63\u786e\u3002<\/p>\n


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\u4e09\u3001\u624b\u52a8\u79ef\u5206\u7684\u6743\u9650\u53ca\u64cd\u4f5c<\/span><\/strong><\/p>\n


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\u64cd\u4f5c\u5458\u5728\u6570\u636e\u7cfb\u7edf\u81ea\u52a8\u79ef\u5206\u4e0d\u6b63\u786e\u65f6\uff0c\u9886\u53d6\u624b\u52a8\u79ef\u5206\u5904\u7406\u62a5\u544a\u8868\u5e76\u586b\u5199\uff0c\u624b\u52a8\u79ef\u5206\u7533\u8bf7\u88abQC\u7ecf\u7406\u6279\u51c6\u540e\u7531QC\u7ecf\u7406\u6216QC\u7ec4\u957f\uff08\u82e5\u6709\uff09\u6216\u5176\u6307\u5b9a\u4eba\u5458\uff08\u4e00\u822c\u662f\u6307\u7ecf\u9a8c\u4e30\u5bcc\u7684\u8d44\u6df1QC\uff09\u65b9\u53ef\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u3002<\/p>\n


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\u56db\u3001\u624b\u52a8\u79ef\u5206\u6ce8\u610f\u4e8b\u9879<\/strong><\/span><\/p>\n


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1\uff09\u624b\u52a8\u79ef\u5206\u4e0d\u80fd\u8bd5\u56fe\u901a\u8fc7\u4ee5\u4e0b\u52a8\u4f5c\u6765\u4f7f\u6570\u636e\u7b26\u5408\u6807\u51c6\u8981\u6c42\uff1a\u51cf\u5c11\u5cf0\uff08\u51cf\u5c11\u5cf0\u9762\u79ef\uff09\uff1b\u589e\u52a0\u5cf0\uff08\u589e\u52a0\u5cf0\u9762\u79ef\uff09\uff1b\u6539\u53d8\u5cf0\u9ad8\uff1b<\/p>\n


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2\uff09\u540c\u4e00\u6b21\u68c0\u9a8c\u7684\u6240\u6709\u6807\u51c6\u54c1\u3001\u5de5\u4f5c\u5bf9\u7167\u54c1\u3001\u6837\u54c1\u7b49\u5fc5\u987b\u4f7f\u7528\u540c\u4e00\u65b9\u6cd5\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u3002<\/p>\n


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3\uff09\u624b\u52a8\u79ef\u5206\u7ed3\u675f\u540e\uff0c\u5e94\u6253\u5370\u81ea\u52a8\u79ef\u5206\u56fe\u8c31\u548c\u624b\u52a8\u79ef\u5206\u56fe\u8c31\u9644\u4e8e\u624b\u52a8\u79ef\u5206\u7533\u8bf7\u8868\u4e4b\u540e\uff0c\u63d0\u4ea4QC\u7ecf\u7406\u5ba1\u6838\uff1bQC\u7ecf\u7406\u5e94\u590d\u6838\u5b8c\u6574\u7684\u6570\u636e\u627e\u51fa\u6839\u56e0\uff0c\u57fa\u4e8e\u6839\u56e0\u5236\u5b9a\u76f8\u5e94\u7684CAPA\u63aa\u65bd\u6765\u907f\u514d\u7c7b\u4f3c\u4e8b\u4ef6\u3002<\/p>\n


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4\uff09\u81ea\u52a8\u79ef\u5206\u7684\u56fe\u8c31\u4e0d\u5f97\u5220\u9664\u6216\u88ab\u8986\u76d6\uff0c\u5e94\u4e0e\u624b\u52a8\u79ef\u5206\u56fe\u8c31\u4fdd\u5b58\u4e8e\u8ba1\u7b97\u673a\u4e2d\uff1b\u6253\u5370\u7684\u81ea\u52a8\u79ef\u5206\u56fe\u8c31\u548c\u624b\u52a8\u79ef\u5206\u56fe\u8c31\u5e94\u6807\u8bc6\u6e05\u695a\u7b7e\u540d\uff0c\u968f\u540c\u624b\u52a8\u79ef\u5206\u7533\u8bf7\u8868\u9644\u4e8e\u68c0\u9a8c\u539f\u59cb\u8bb0\u5f55\u540e\u9762\u4e00\u8d77\u4ea4\u8d28\u91cf\u7ba1\u7406\u90e8\u7ecf\u7406\u3001QP\u5ba1\u6838\u65e0\u95ee\u9898\u540e\u5f52\u6863\u3002<\/p>\n


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\u4e94\u3001\u8272\u8c31\u8f6f\u4ef6\u9009\u578b\u3001\u6743\u9650\u8bbe\u7f6e\u548c\u7ed3\u679c\u663e\u793a<\/span><\/strong><\/p>\n


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\u6ee1\u8db3\u5408\u89c4\u8981\u6c42\u7684\u8272\u8c31\u8f6f\u4ef6\uff08\u4f8b\u5982Waters\u548cAngilent\u7684\u8f6f\u4ef6\uff09\uff0c\u80fd\u591f\u5206\u522b\u8bbe\u7f6e\u4e0d\u540c\u6743\u9650\uff0c\u4f8b\u5982\u666e\u901a\u5316\u9a8c\u5458\u4e0d\u5177\u5907\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u7684\u6743\u9650\uff0c\u9700\u8981\u4e3b\u7ba1\u8fdb\u884c\u64cd\u4f5c\uff0c\u6709\u4e9b\u8f6f\u4ef6\u5219\u4e0d\u5177\u5907\u8fd9\u4e9b\u529f\u80fd\uff1b\u5373\u4f7f\u662f\u540c\u4e00\u4e2a\u54c1\u724c\u7684\u8f6f\u4ef6\uff0c\u4e5f\u6709\u4e0d\u540c\u7248\u672c\uff1b\u5373\u4f7f\u8f6f\u4ef6\u6709\u8fd9\u4e2a\u529f\u80fd\uff0c\u4f01\u4e1a\u4e5f\u4e0d\u4e00\u5b9a\u542f\u7528\u3002<\/p>\n


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\u6709\u4e24\u4e2a\u4fe1\u606f\u662f\u5426\u663e\u793a\uff0c\u5bf9\u8272\u8c31\u6570\u636e\u900f\u660e\u5ea6\u975e\u5e38\u91cd\u8981\uff1a\u65b9\u6cd5\u540d\u79f0\u548c\u6570\u636e\u7248\u672c\u3002\u5982\u679c\u4f01\u4e1a\u4e0d\u4f7f\u7528\u624b\u52a8\u79ef\u5206\uff08\u91cd\u753b\u57fa\u7ebf\uff09\uff0c\u800c\u91c7\u7528\u4fee\u6539\u53c2\u6570\u7684\u65b9\u5f0f\uff0c\u5219\u6bcf\u4fee\u6539\u4e00\u6b21\uff0c\u662f\u4e0d\u540c\u7684\u65b9\u6cd5\uff08\u89c4\u8303\u7684\u7ba1\u7406\u7a0b\u5e8f\u4f1a\u8981\u6c42\u66f4\u6539\u65b9\u6cd5\u540d\u79f0\u4fdd\u5b58\uff0c\u5426\u5219\u5c31\u53ea\u80fd\u5230\u5ba1\u8ba1\u8ffd\u8e2a\u624d\u80fd\u67e5\u51fa\u6765\u8fd9\u4e2a\u65b9\u6cd5\u5df2\u7ecf\u88ab\u4fee\u6539\u4e86\uff09\uff0c\u800c\u6253\u5370\u7684\u8272\u8c31\u56fe\u53ef\u4ee5\u9009\u62e9\u662f\u5426\u663e\u793a\u65b9\u6cd5\uff1b \u6bcf\u5904\u7406\u4e00\u6b21\u6570\u636e\uff0c\u4f1a\u5f62\u6210\u4e00\u4e2a\u6570\u636e\u7248\u672c\uff0c\u540c\u6837\u7684\uff0c\u6253\u5370\u7684\u8272\u8c31\u56fe\u53ef\u4ee5\u9009\u62e9\u662f\u5426\u663e\u793a\u6570\u636e\u7248\u672c\u3002\u4e00\u4e2a\u5b8c\u5168\u900f\u660e\u7684\u7ed3\u679c\u663e\u793a\uff0c\u4f1a\u5728\u6253\u5370\u7684\u8272\u8c31\u56fe\u4e0a\u663e\u793a\u201c\u65b9\u6cd5\u540d\u79f0+\u6570\u636e\u7248\u672c\u201d\uff08\u540c\u65f6\u8981\u6c42\u4fee\u6539\u53c2\u6570\u5219\u6539\u53d8\u65b9\u6cd5\u540d\u79f0\uff0c\u4e0d\u9700\u8981QA\u6216\u68c0\u67e5\u5458\u4ed4\u7ec6\u68c0\u67e5\u5ba1\u8ba1\u8ffd\u8e2a\u624d\u80fd\u53d1\u73b0\u4fee\u6539\u75d5\u8ff9\uff09\u3002<\/p>\n


<\/p>\n


<\/p>\n

What is Manual Integration?<\/p>\n

\u4ec0\u4e48\u662f\u624b\u52a8\u79ef\u5206\uff1f<\/section>\n

So far we have discussed the regulatory issues around peak integration, the main integration parameters, and the three rules of integration so that you have a fighting chance for automatically integrating your peaks and there is no need to intercede manually. However, we now need to turn our attention to manual integration. As we can see from the regulatory citations and the bioanalytical guidance documents, what is needed is an SOP to control, manage, and authorize integration \u2014 both automatic and manual.<\/section>\n
\u6211\u4eec\u5df2\u7ecf\u8ba8\u8bba\u4e86\u5173\u4e8e\u5cf0\u79ef\u5206\u53d1\u5e03\u7684\u76f8\u5173\u6cd5\u89c4\uff0c\u4e3b\u8981\u7684\u79ef\u5206\u53c2\u6570\uff0c\u548c\u91cd\u65b0\u79ef\u5206\u7684\u4e09\u4e2a\u539f\u5219\uff0c\u6ee1\u8db3\u8fd9\u4e9b\u6211\u4eec\u80fd\u5bf9\u5cf0\u8fdb\u884c\u81ea\u52a8\u79ef\u5206\u800c\u6ca1\u5fc5\u8981\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u3002\u4f46\u662f\uff0c\u73b0\u5728\u6211\u4eec\u9700\u8981\u628a\u6ce8\u610f\u529b\u8f6c\u5411\u624b\u52a8\u79ef\u5206\u3002\u6b63\u5982\u6211\u4eec\u4ece\u6cd5\u89c4\u5f15\u6587\u548c\u751f\u7269\u5206\u6790\u6307\u5357\u6587\u4ef6\u770b\u5230\u7684\uff0c\u6211\u4eec\u9700\u8981\u7684\u662f\u63a7\u5236\u3001\u7ba1\u7406\u6279\u51c6\u81ea\u52a8\/\u624b\u52a8\u79ef\u5206\u7684SOP\u3002<\/section>\n
 <\/section>\n
In an ideal world there would be a definition of manual integration. However, there is not a definition available for manual integration that I could find. Neither in Dyson, nor on any regulatory website. This was the point made by Hill et al. (7), who discussed the scope and terminology of manual reintegration and they concluded that it is essential to develop a consensus with respect to definitions. The problem, they noted, is that that a consensus does not exist.<\/section>\n
\u624b\u52a8\u79ef\u5206\u7684\u5b9a\u4e49\u5e94\u8be5\u786e\u5b9a\u3002\u4f46\u662f\u6211\u6ca1\u6709\u627e\u5230\u4e00\u4e2a\u53ef\u4ee5\u4f7f\u7528\u7684\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u5b9a\u4e49\u3002\u65e0\u8bba\u662fDyson\u8fd8\u662f\u5728\u6240\u6709\u6cd5\u89c4\u7f51\u7ad9\u4e2d\u90fd\u6ca1\u6709\u3002Hill et al. (7) \u4e2d\u63d0\u5230\u8fc7\uff0c\u4ed6\u8ba8\u8bba\u4e86\u624b\u52a8\u79ef\u5206\u7684\u8303\u56f4\u548c\u4e13\u4e1a\u672f\u8bed\uff0c\u4ed6\u4eec\u90fd\u8bf4\u6709\u5fc5\u8981\u5bf9\u5176\u5b9a\u4e49\u8fdb\u884c\u7edf\u4e00\u3002\u95ee\u9898\u662f\uff0c\u6ca1\u6709\u7edf\u4e00\u3002<\/section>\n
 <\/section>\n
This raises an important question: if we can\u2019t define manual integration how can we write an SOP on integration as a whole?<\/section>\n
\u8fd9\u5c31\u51fa\u73b0\u4e86\u4e00\u4e2a\u91cd\u8981\u95ee\u9898\uff1a\u5982\u679c\u6211\u4eec\u4e0d\u80fd\u5b9a\u4e49\u624b\u52a8\u79ef\u5206\uff0c\u600e\u6837\u5728\u6574\u4f53\u4e0a\u7f16\u5199\u4e00\u4e2a\u5173\u4e8e\u79ef\u5206\u7684SOP\uff1f<\/section>\n
 <\/section>\n
Scope of an Integration SOP <\/section>\n
\u79ef\u5206SOP\u7684\u8303\u56f4\uff1f<\/section>\n

In the spirit of the early pioneers, this column will present a possible approach to writing an SOP in the form of a flowchart that will consider some, but not all, options for both automatic and manual integration. Of course, there is a little trepidation because one definition of pioneer is finding new and exotic ways to die (!) However, I hope that this column and my views stimulate a debate about what constitutes manual integration and we can get a definition agreed upon.<\/section>\n
\u672c\u7740\u62d3\u8352\u8005\u7684\u7cbe\u795e\uff0c\u8fd9\u4e2a\u4e13\u680f\u5c06\u63d0\u51fa\u4e00\u4e2a\u53ef\u80fd\u7684\u65b9\u6cd5\u6765\u7f16\u5199SOP\uff0c\u4ee5\u6d41\u7a0b\u56fe\u7684\u5f62\u5f0f\u8ba8\u8bba\u4e86\u624b\u52a8\u79ef\u5206\u548c\u81ea\u52a8\u79ef\u5206\u7684\u4e00\u4e9b\u9009\u9879\u3002\u5f53\u7136\uff0c\u8fd9\u6709\u4e00\u4e9b\u62c5\u5fe7\uff0c\u56e0\u4e3a\u62d3\u8352\u5c31\u662f\u4f5c\u6b7b\u7684\u8282\u594f\u554a\u3002\u4f46\u662f\uff0c\u6211\u5e0c\u671b\u8fd9\u4e2a\u4e13\u680f\u548c\u6211\u7684\u89c2\u70b9\u80fd\u591f\u5f15\u53d1\u4e00\u4e2a\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u5927\u8ba8\u8bba\uff0c\u4f7f\u6211\u4eec\u80fd\u591f\u5f97\u5230\u4e00\u4e2a\u7edf\u4e00\u7684\u5b9a\u4e49\u3002<\/section>\n
 <\/section>\n
In this discussion we need to balance sound science with regulatory compliance. Therefore, let me pose a question \u2014 which is worse: not reintegrating when you know the results are wrong or accepting wrong results when you can see an unknown peak in the sample chromatograms? You see the dilemma? We know the outcomes of both situations are undesirable, but as a result of inflexible procedures or fear of the regulations sound scientific judgement cannot be exercised.<\/section>\n
\u5728\u8fd9\u4e2a\u8ba8\u8bba\u4e2d\u6211\u4eec\u9700\u8981\u5e73\u8861\u5404\u79cd\u79d1\u5b66\u5408\u7406\u7684\u6cd5\u89c4\u7b26\u5408\u6027\u3002\u56e0\u6b64\uff0c\u8ba9\u6211\u4eec\u63d0\u51fa\u4e00\u4e2a\u95ee\u9898\u770b\u770b\u4e00\u4e0b\u54ea\u4e00\u4e2a\u66f4\u7cdf\u7cd5\uff1a\u5f53\u4f60\u77e5\u9053\u7ed3\u679c\u9519\u8bef\u7684\u65f6\u5019\u6ca1\u6709\u91cd\u65b0\u79ef\u5206\uff0c\u6216\u8005\u4f60\u770b\u5230\u6837\u54c1\u8272\u8c31\u56fe\u4e2d\u6709\u672a\u77e5\u5cf0\uff0c\u7136\u800c\u4f60\u63a5\u53d7\u4e86\u9519\u8bef\u7684\u7ed3\u679c\uff1f\u4f60\u770b\u5230\u56f0\u5883\u4e86\u5417\uff1f\u6211\u4eec\u77e5\u9053\u8fd9\u4e9b\u60c5\u51b5\u662f\u4e0d\u53ef\u53d6\u7684\uff0c\u4f46\u662f\u6b7b\u677f\u7684\u7a0b\u5e8f\u6216\u8005\u5bf9\u6cd5\u89c4\u7684\u62c5\u5fe7\u4f7f\u5f97\u79d1\u5b66\u5224\u65ad\u4e0d\u80fd\u884c\u9a76\u3002<\/section>\n
 <\/section>\n
First, let us consider a \u201cno manual integration allowed\u201d option. Personally, I think that this is an untenable situation, particularly if a regulated laboratory is using recently developed methods, analyzing impurities where the limits of quantification or detection are close to baseline noise, or investigating stability of products. In these situations, manual reintegration is scientifically sound and defendable provided that it is covered in the integration SOP.<\/section>\n
\u9996\u5148\uff0c\u8ba9\u6211\u601d\u8003\u4e00\u4e2a\u201c\u4e0d\u5141\u8bb8\u624b\u52a8\u79ef\u5206\u201d\u7684\u89c2\u70b9\uff0c\u4e2a\u4eba\u8ba4\u4e3a\u8fd9\u662f\u4e00\u4e2a\u7ad9\u4e0d\u4f4f\u811a\u7684\u89c2\u70b9\uff0c\u7279\u522b\u662f\u53d7\u63a7\u7684\u5b9e\u9a8c\u5ba4\u4f7f\u7528\u8fd1\u671f\u5f00\u53d1\u7684\u65b9\u6cd5\u5206\u6790\u6742\u8d28\uff0c\u4e14\u5b9a\u91cf\u9650\u6216\u68c0\u6d4b\u9650\u63a5\u8fd1\u57fa\u7ebf\u566a\u97f3\uff0c\u6216\u8005\u5728\u7814\u7a76\u4ea7\u54c1\u7684\u7a33\u5b9a\u6027\u65f6\u3002\u8fd9\u4e9b\u60c5\u51b5\u624b\u52a8\u79ef\u5206\u90fd\u662f\u79d1\u5b66\u5408\u7406\u7684\u5e76\u4e14\u5728\u79ef\u5206SOP\u4e2d\u53ef\u4ee5\u6db5\u76d6\u7684\u3002<\/section>\n
 <\/section>\n
A suggested flowchart for consideration of integration is shown in Figure 3. It begins with the completion of the chromatographic run and the automatic integration of peaks by the original processing method. The resulting chromatograms are reviewed by the chromatographer to see if retention times and peak shapes are as expected, the peak(s) have been correctly identified, baseline placement is as required by the analytical procedure, and the sample is integrated consistently with the standard. There may be other criteria that an individual laboratory wishes to apply. We now come to a decision point: is the run acceptable? If yes the individual results and the reportable value are calculated and all is well. All data at this point have been calculated automatically by the CDS, the chromatographer is merely confirming what the software has done conforms to pre-defined expectations.<\/section>\n
\u5728\u56fe3\u662f\u5173\u4e8e\u79ef\u5206\u8003\u8651\u7684\u5efa\u8bae\u6027\u6d41\u7a0b\u56fe\u3002\u5b83\u5728\u8272\u8c31\u8fd0\u884c\u5b8c\u6210\u65f6\u5f00\u59cb\uff0c\u901a\u8fc7\u521d\u59cb\u5904\u7406\u65b9\u6cd5\u8fdb\u884c\u5cf0\u7684\u81ea\u52a8\u79ef\u5206\u3002\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u5bf9\u8272\u8c31\u7ed3\u679c\u8fdb\u884c\u590d\u6838\uff1a\u4fdd\u7559\u65f6\u95f4\u548c\u5cf0\u7684\u6027\u72b6\u90fd\u662f\u5426\u548c\u9884\u671f\u4e00\u81f4\uff1f\u5cf0\u662f\u5426\u80fd\u591f\u88ab\u6b63\u786e\u9274\u522b\uff1f\u57fa\u7ebf\u4f4d\u7f6e\u662f\u5426\u7b26\u5408\u5206\u6790\u7a0b\u5e8f\uff1f\u6837\u54c1\u6309\u7167\u6807\u51c6\u8fdb\u884c\u79ef\u5206\uff1f\u4e2a\u522b\u5b9e\u9a8c\u5ba4\u53ef\u80fd\u6709\u5176\u4ed6\u6807\u51c6\u3002\u73b0\u5728\u6211\u4eec\u9700\u8981\u51b3\u7b56\uff1a\u8fd0\u884c\u662f\u5426\u53ef\u63a5\u53d7\uff1f\u5982\u679c\u662f\uff0c\u5c31\u8ba1\u7b97\u5404\u4e2a\u7684\u7ed3\u679c\u548c\u62a5\u544a\u7684\u6570\u503c\uff0c\u4e00\u5207\u90fd\u597d\u3002\u6240\u6709\u6570\u636e\u90fd\u901a\u8fc7CDS\u8fdb\u884c\u81ea\u52a8\u8ba1\u7b97\uff0c\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u4ec5\u9700\u8981\u786e\u8ba4\u8f6f\u4ef6\u6240\u505a\u7684\u7b26\u5408\u9884\u671f\u671f\u671b\u5c31\u53ef\u4ee5\u4e86\u3002<\/section>\n
 <\/section>\n
However, if the integration is not acceptable we move to a second decision point: is manual integration (whatever that term may cover) permitted for this analytical procedure? If not the next stage is a laboratory investigation. What methods could we consider for inclusion for no manual integration? Perhaps measurement of active pharmaceutical ingredients (APIs) or registered methods for finished product for the active ingredient? If these peaks cannot be integrated correctly are you out of control? We will consider if this is tenable when we have finished discussing the flowchart.<\/section>\n
\u4f46\u662f\uff0c\u5982\u679c\u79ef\u5206\u4e0d\u80fd\u63a5\u53d7\u6211\u4eec\u9700\u8981\u8fdb\u884c\u7b2c\u4e8c\u4e2a\u51b3\u7b56\uff1a\u8be5\u5206\u6790\u7a0b\u5e8f\u662f\u5426\u5141\u8bb8\u624b\u52a8\u79ef\u5206\uff08\u65e0\u8bba\u8be5\u672f\u8bed\u5305\u542b\u54ea\u4e9b\u5185\u5bb9\uff09\uff1f\u5982\u679c\u4e0d\u80fd\uff0c\u4e0b\u4e00\u9636\u6bb5\u5c31\u662f\u5b9e\u9a8c\u5ba4\u8c03\u67e5\u3002\u6211\u4eec\u5e94\u8be5\u8003\u8651\u4f7f\u7528\u54ea\u4e9b\u65b9\u6cd5\u4e0d\u80fd\u624b\u52a8\u79ef\u5206\u5417\uff1f\u5982\u679c\u662fAPIs(active pharmaceutical ingredients)\u7684\u68c0\u6d4b\u6216\u5bf9\u6700\u7ec8\u4ea7\u54c1\u7684\u6d3b\u6027\u6210\u5206\u7684\u6ce8\u518c\u65b9\u6cd5\u5462\uff1f\u5982\u679c\u8fd9\u4e9b\u5cf0\u4e0d\u80fd\u88ab\u6b63\u786e\u79ef\u5206\uff0c\u4f60\u5c31\u6ca1\u8f99\u5417\uff1f\u6211\u4eec\u5c06\u5728\u5b8c\u6210\u8fd9\u4e2a\u6d41\u7a0b\u56fe\u8ba8\u8bba\u7684\u65f6\u5019\u601d\u8003\u8fd9\u662f\u5426\u7ad9\u5f97\u4f4f\u811a\uff1f<\/section>\n
 <\/section>\n
In my view, manual integration must be specifically prohibited in the following circumstances:<\/section>\n
\u6211\u8ba4\u4e3a\uff0c\u5728\u4ee5\u4e0b\u60c5\u51b5\u624b\u52a8\u79ef\u5206\u662f\u7981\u6b62\u4f7f\u7528\u7684\u3002<\/section>\n

<\/section>\n
    \n
  • \n
    Symmetrical peaks that have acceptable baseline to baseline fitting following automatic integration.<\/section>\n
    \u6709\u53ef\u4ee5\u63a5\u53d7\u57fa\u7ebf\u7684\u5bf9\u79f0\u5cf0\uff0c\u57fa\u7ebf\u62df\u5408\u540e\u53ef\u4ee5\u81ea\u52a8\u79ef\u5206\u3002<\/section>\n<\/li>\n
  • \n
    Enhancing or shaving peak areas to meet SST acceptance criteria or allowing a run to meet the test specification.<\/section>\n
    \u589e\u52a0\u6216\u6d88\u51cf\u5cf0\u9762\u79ef\u4ee5\u7b26\u5408SST\uff08\u9002\u7528\u6027\u8bd5\u9a8c\uff09\u63a5\u53d7\u6807\u51c6\u6216\u8005\u5141\u8bb8\u8fd0\u884c\u7b26\u5408\u6d4b\u8bd5\u6807\u51c6\u3002<\/section>\n<\/li>\n<\/ul>\n

    <\/section>\n
    Now we come to what constitutes \u201cmanual integration\u201d. Figure 3 presents three options that I have selected for discussion, your laboratory SOP may have more areas depending on the work performed. The outcome you require is consistent and appropriate manual integration that is scientifically defensible. Therefore, you need to avoid situations where you have inconsistent or inappropriate integration.<\/section>\n
    \u73b0\u5728\u6211\u4eec\u6765\u8c08\u8c08\u4ec0\u4e48\u662f\u624b\u52a8\u79ef\u5206\uff0c\u56fe3 \u63d0\u51fa\u4e863\u4e2a\u89c2\u70b9\u8fdb\u884c\u8ba8\u8bba\uff0c\u4f60\u7684\u5b9e\u9a8c\u5ba4SOP\u6839\u636e\u6240\u8fdb\u884c\u7684\u5de5\u4f5c\u53ef\u80fd\u5305\u542b\u66f4\u591a\u5185\u5bb9\u3002\u4f60\u6240\u9700\u8981\u7684\u7ed3\u679c\u662f\u4e00\u81f4\u7684\uff0c\u5e76\u9002\u5f53\u7684\u624b\u52a8\u79ef\u5206\u662f\u79d1\u5b66\u5408\u7406\u7684\u3002\u56e0\u6b64\u6211\u4eec\u9700\u8981\u907f\u514d\u4e00\u4e9b\u4e0d\u4e00\u81f4\u548c\u4e0d\u9002\u5f53\u7684\u79ef\u5206\u3002<\/section>\n
     <\/section>\n
    Manual Intervention Versus Manual Integration<\/section>\n
    \u624b\u52a8\u5e72\u9884VS\u624b\u52a8\u79ef\u5206

    <\/section>\n
    In Figure 3 options 1 and 2 are shown as manual intervention and option 3 as manual integration. Let me clarify my reasoning.<\/section>\n
    \u56fe3\u4e2d\u60c5\u51b51\u548c2\u8868\u660e\u624b\u52a8\u5e72\u9884\uff0c\u60c5\u51b53\u662f\u624b\u52a8\u79ef\u5206\u3002\u8ba9\u6211\u6765\u8bf4\u660e\u4ee5\u4e0b\u6211\u7684\u7406\u7531<\/section>\n

    <\/section>\n

      <\/p>\n
    • \n
      Option 1: Peaks have slipped out of a window and they are not correctly identified. The automatic integration is acceptable and all that is required is to change the peak windows in the integration method and reprocess. Peak areas are not changed by this approach.<\/section>\n
      \u60c5\u51b51\uff1a\u5cf0\u8d85\u51fa\u4e86\u754c\u9762\uff0c\u4ed6\u4eec\u4e0d\u80fd\u88ab\u6b63\u786e\u8bc6\u522b\u3002\u81ea\u52a8\u79ef\u5206\u662f\u53ef\u4ee5\u63a5\u53d7\u7684\uff0c\u6240\u9700\u8981\u7684\u662f\u6539\u53d8\u79ef\u5206\u65b9\u6cd5\u7684\u5cf0\u754c\u9762\u5e76\u91cd\u65b0\u5904\u7406\u3002\u901a\u8fc7\u8fd9\u4e2a\u65b9\u6cd5\u5cf0\u9762\u79ef\u5e76\u6ca1\u6709\u6539\u53d8\u3002<\/section>\n

      <\/section>\n<\/li>\n
    • \n
      Option 2: Parameters in the integration or processing method need to be adjusted and then applied to all injections in the run. An example could be change of the peak threshold or minimum area to reduce the impact of baseline noise. Peak areas may or may not be changed under this option but there is no manual placement of the baselines by an analyst.<\/section>\n
      \u60c5\u51b52\uff1a\u79ef\u5206\u53c2\u6570\u6216\u5904\u7406\u65b9\u6cd5\u9700\u8981\u8c03\u6574\uff0c\u7136\u540e\u9002\u7528\u4e8e\u8fd0\u884c\u4e2d\u7684\u6240\u6709\u8fdb\u9488\u3002\u4e00\u4e2a\u4f8b\u5b50\u53ef\u80fd\u6539\u53d8\u8d85\u8fc7\u9608\u503c\u89d2\u6216\u6700\u5c0f\u9762\u79ef\u6765\u51cf\u5c11\u5bf9\u57fa\u7ebf\u566a\u97f3\u7684\u5f71\u54cd\u3002\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\u5cf0\u9762\u79ef\u53ef\u80fd\u6539\u53d8\u4e5f\u53ef\u80fd\u4e0d\u53d8\uff0c\u4f46\u662f\u57fa\u7ebf\u5e76\u6ca1\u6709\u88ab\u5206\u6790\u5e08\u624b\u5de5\u5904\u7406\u3002<\/section>\n<\/li>\n
    • \n
      Option 3: Manual placement of baselines by the chromatographer is required because of a late running peak or noise if undertaking an impurity analysis. Peaks areas will be changed by the reintegration.<\/section>\n
      \u60c5\u51b53\uff1a\u5728\u8fdb\u884c\u6742\u8d28\u5206\u6790\u65f6\uff0c\u56e0\u4e3a\u540e\u671f\u51fa\u73b0\u7684\u5cf0\uff08late running peak\uff1a\u62d6\u5c3e\u5cf0\uff1f\uff09\u6216\u566a\u97f3\uff0c\u53ef\u80fd\u9700\u8981\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u624b\u52a8\u5904\u7406\u57fa\u7ebf\u3002\u901a\u8fc7\u91cd\u65b0\u79ef\u5206\u5cf0\u9762\u79ef\u5c06\u4f1a\u6539\u53d8\u3002<\/section>\n<\/li>\n<\/ul>\n<\/section>\n<\/section>\n<\/section>\n
      \n
      \"\u624b\u52a8\u79ef\u5206\u7684\u5229\u548c\u5f0a\"<\/section>\n<\/section>\n
      \n
      \n
      \n
      Figure 3: A suggested flow chart for manual intervention and manual integration.<\/section>\n

      <\/section>\n<\/section>\n<\/section>\n<\/section>\n
      \n
      <\/section>\n<\/section>\n
      \n
      \n
      \n
      \u56fe3\uff1a\u624b\u52a8\u5e72\u9884\u548c\u624b\u52a8\u79ef\u5206\u7684\u5efa\u8bae\u6d41\u7a0b\u56fe<\/section>\n

      <\/section>\n
      Options 1 and 2 are manual intervention but the baseline placement is performed by the CDS and is not altered by a chromatographer. These are the preferred options and easier to justify scientifically. Option 3 is where everything else has failed and a chromatographer goes through individual chromatograms and repositions the baselines where appropriate. This latter point is important, it is an exercise of scientific judgement that needs to be backed up by the procedures within the integration SOP.<\/section>\n
      \u60c5\u51b51\u548c2\u662f\u624b\u52a8\u5e72\u9884\uff0c\u5176\u57fa\u7ebf\u4f4d\u7f6e\u7531 CDS\u672c\u8eab\u786e\u5b9a\uff0c\u6ca1\u6709\u88ab\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u6539\u53d8\u3002\u8fd9\u662f\u4e00\u4e2a\u4f18\u9009\u7684\u60c5\u51b5\uff0c\u53ef\u4ee5\u6bd4\u8f83\u5bb9\u6613\u7684\u8fdb\u884c\u79d1\u5b66\u8bf4\u660e\u3002\u60c5\u51b53\u5728\u6240\u6709\u5176\u4ed6\u7684\u90fd\u8bd5\u8fc7\u4e0d\u884c\uff0c\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u5728\u9002\u5f53\u7684\u60c5\u51b5\u4e0b\uff0c\u5bf9\u8272\u8c31\u8fdb\u884c\u57fa\u7ebf\u8c03\u6574\u3002\u540e\u9762\u8fd9\u70b9\u5f88\u91cd\u8981\uff0c\u5b83\u662f\u4e00\u4e2a\u79d1\u5b66\u5224\u65ad\u7684\u8fc7\u7a0b\uff0c\u79ef\u5206SOP\u4e2d\u9700\u8981\u6709\u7a0b\u5e8f\u5bf9\u5b83\u8fdb\u884c\u5907\u4efd\u3002<\/section>\n

      It\u2019s All Plain Sailing Now?<\/section>\n
      \u8fd9\u6837\u5c31\u597d\u4e86\u5417\uff1f

      <\/section>\n
      Let us return to the scenario we discussed earlier at the top of the flowchart in Figure 3. If the automatic integration has failed because the peaks have slipped out of the retention windows (option 1 in the manual intervention section) do you want to trigger a laboratory investigation? Especially when the peak windows are readjusted and, after reintegration, the run now passes. The peaks are now correctly labelled and the peak areas are unchanged after the manual intervention. Although the FDA classifies this situation under \u201cmanual integration\u201d, there is no change to the actual measurement of the peaks of interest. Should this situation be classified as manual integration? In my opinion no \u2013 this is a manual intervention but not reintegration. This is not intended to be word play but a means of trying to define exactly what the regulators want in light of zero guidance and multiple citations on the subject. Furthermore, because there is no agreed definition of the term we have a problem \u2013 would this be permitted? Would you take the Clint Eastwood approach to risk management by feeling lucky or could you justify that this is an acceptable practice?<\/section>\n
      \u8ba9\u6211\u4eec\u56de\u5230\u8ba8\u8bba\u56fe3\u4e4b\u524d\u7684\u60c5\u5f62\uff0c\u5982\u679c\u5cf0\u8d85\u51fa\u754c\u9762\u4ee5\u5916\u5bfc\u81f4\u81ea\u52a8\u79ef\u5206\u5931\u8d25\uff08\u60c5\u51b51\u624b\u52a8\u5e72\u9884\u7ae0\u8282\uff09\u4f60\u662f\u5426\u613f\u610f\u53d1\u8d77\u5b9e\u9a8c\u5ba4\u8c03\u67e5\uff1f\u7279\u522b\u662f\u5f53\u5cf0\u754c\u9762\u88ab\u91cd\u65b0\u8c03\u6574\u5e76\u91cd\u65b0\u79ef\u5206\u540e\uff0c\u8fd0\u884c\u662f\u901a\u8fc7\u7684\u3002\u624b\u52a8\u5e72\u9884\u540e\u73b0\u5728\u8fd9\u4e9b\u5cf0\u88ab\u6b63\u786e\u6807\u5b9a\u5e76\u4e14\u5cf0\u9762\u79ef\u6ca1\u6709\u6539\u53d8\u3002\u867d\u7136FDA\u5b9a\u4e49\u8fd9\u79cd\u60c5\u51b5\u4e3a\u201c\u624b\u52a8\u79ef\u5206\u201d\uff0c\u6ca1\u6709\u6539\u53d8\u76f8\u5173\u5cf0\u7684\u5b9e\u9645\u6d4b\u91cf\u3002\u8fd9\u79cd\u60c5\u51b5\u662f\u5426\u5e94\u8be5\u88ab\u5b9a\u4e49\u4e3a\u624b\u52a8\u79ef\u5206\uff1f\u6309\u7167\u6211\u7684\u89c2\u70b9-\u8fd9\u662f\u624b\u52a8\u5e72\u9884\u5e76\u4e0d\u662f\u624b\u52a8\u79ef\u5206\u3002\u8fd9\u4e0d\u662f\u6587\u5b57\u6e38\u620f\u800c\u662f\u5728\u6ca1\u6709\u76f8\u5173\u6307\u5357\u5e76\u591a\u6b21\u5f15\u7528\u7684\u60c5\u51b5\u4e0b\uff0c\u8bd5\u56fe\u66f4\u52a0\u7cbe\u786e\u7684\u5b9a\u4e49\u76d1\u7ba1\u8005\u9700\u8981\u7684\u662f\u4ec0\u4e48\u3002\u6b64\u5916\uff0c\u56e0\u4e3a\u8be5\u95ee\u9898\u6ca1\u6709\u7edf\u4e00\u7684\u5b9a\u4e49\uff0c\u6211\u4eec\u6709\u4e00\u4e2a\u95ee\u9898-\u8fd9\u662f\u5141\u8bb8\u7684\u5417\uff1f\u4f60\u53ef\u4ee5\u91c7\u7528Clint Eastwood\u65b9\u6cd5\u611f\u89c9\u5e78\u8fd0\u7684\u8fdb\u884c\u98ce\u9669\u8bc4\u4f30\u6216\u8005\u4f60\u80fd\u8bc1\u660e\u8fd9\u662f\u4e00\u4e2a\u53ef\u4ee5\u63a5\u53d7\u7684\u505a\u6cd5\u5417\uff1f<\/section>\n
       <\/section>\n
      Ideally the SST, standards, and QC samples should be integrated the same way consistently throughout the run; however, this may not be the case, particularly near limits of quantification or detection. Let us look at a different situation that can arise when operational efficiency is considered and different material types are analyzed in a single run. Although the method is validated for these different sample types, there can be differences in the chromatography that require different integration parameters. So how can you apply the same integration parameters across the run? The classic example is mixing APIs and stability samples where the methods have different aims; for example, determination of purity versus degradation. Perhaps the case of data integrity should win over operational efficiency and it would be better to separate different types of analytical procedure?<\/section>\n
      \u7406\u60f3\u60c5\u51b5\u4e0b\uff0cSST\uff08\u7cfb\u7edf\u9002\u7528\u6027\u8bd5\u9a8c\uff09\uff0c\u6807\u51c6\u54c1\u548cQC\u6837\u54c1\u5e94\u8be5\u6309\u7167\u7edf\u4e00\u7684\u65b9\u6cd5\u8fd0\u884c\u8fdb\u884c\u79ef\u5206\uff1b\u7136\u800c\uff0c\u8fd9\u53ef\u80fd\u5e76\u975e\u5982\u6b64\uff0c\u7279\u522b\u662f\u63a5\u8fd1\u5b9a\u91cf\u9650\u6216\u68c0\u6d4b\u9650\u65f6\u3002\u8ba9\u6211\u4eec\u6765\u770b\u770b\u5728\u8003\u8651\u5de5\u4f5c\u6548\u7387\u5e76\u4e14\u5206\u6790\u4e0d\u540c\u7c7b\u578b\u7269\u6599\u65f6\uff0c\u80fd\u591f\u51fa\u73b0\u7684\u4e0d\u540c\u60c5\u51b5\u3002\u867d\u7136\u65b9\u6cd5\u5bf9\u4e0d\u540c\u7c7b\u578b\u7684\u6837\u54c1\u90fd\u7ecf\u8fc7\u4e86\u9a8c\u8bc1\uff0c\u4e0d\u540c\u7c7b\u578b\u7684\u6837\u54c1\u5176\u8272\u8c31\u56fe\u8fd8\u662f\u6709\u6240\u4e0d\u540c\u7684\uff0c\u9700\u8981\u4e0d\u540c\u7684\u79ef\u5206\u53c2\u6570\u3002\u6240\u4ee5\u4f60\u600e\u4e48\u80fd\u5e94\u7528\u76f8\u540c\u7684\u79ef\u5206\u53c2\u6570\u6765\u8fd0\u884c\u6d4b\u8bd5\uff1f\u4e00\u4e2a\u7ecf\u5178\u7684\u4f8b\u5b50\u662fAPIs\u548c\u7a33\u5b9a\u6027\u6837\u54c1\uff0c\u8fd9\u4e9b\u6837\u54c1\u7684\u5206\u6790\u65b9\u6cd5\u6709\u4e0d\u540c\u7684\u76ee\u7684\uff1b\u4f8b\u5982\uff0c\u6d4b\u5b9a\u7eaf\u5ea6VS\u964d\u89e3\u7269\u3002\u53ef\u80fd\u6570\u636e\u5b8c\u6574\u6027\u91cd\u8981\u8fc7\u5de5\u4f5c\u6548\u7387\uff0c\u6545\u6700\u597d\u5206\u6210\u4e0d\u540c\u7684\u5206\u6790\u7a0b\u5e8f\uff1f<\/section>\n
       <\/section>\n
      Regardless of the content of the final SOP, chromatographers must be trained to perform manual integration using a scientifically sound, justifiable, and transparent process. We are looking at consistency of an integration technique among all trainees to ensure a consistent approach, which can be provided via a CDS by copying methods and chromatograms to a training project or directory and allowing chromatographers to integrate the same files. One outcome of the training is that trained chromatographers will think about where they place a baseline when manually integrating a peak so that it is scientifically justified and complies with the laboratory procedure.<\/section>\n
      \u4e0d\u7ba1\u6700\u7ec8SOP\u7684\u5185\u5bb9\uff0c\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u5e94\u8be5\u53d7\u5230\u57f9\u8bad\u4f7f\u5176\u4ee5\u79d1\u5b66\u5408\u7406\u5e76\u4e14\u900f\u660e\u7684\u65b9\u5f0f\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u3002\u6211\u4eec\u9700\u8981\u5173\u6ce8\u7684\u662f\u79ef\u5206\u6280\u672f\u5728\u6240\u6709\u53d7\u8bad\u4eba\u5458\u4e2d\u4f7f\u7528\u540c\u4e00\u65b9\u6cd5\u7684\u4e00\u81f4\u6027\uff0c\u5b83\u53ef\u4ee5\u901a\u8fc7\u5728CDS\u4e2d\u590d\u5236\u65b9\u6cd5\u548c\u8272\u8c31\u56fe\u6765\u8fdb\u884c\u57f9\u8bad\uff0c\u5e76\u4e14\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u5bf9\u540c\u4e00\u4e2a\u6587\u4ef6\u8fdb\u884c\u79ef\u5206\u3002\u57f9\u8bad\u7684\u5176\u4e2d\u4e00\u4e2a\u76ee\u7684\u662f\u53d7\u8bad\u7684\u8272\u8c31\u5de5\u4f5c\u4eba\u5458\u5c06\u80fd\u591f\u601d\u8003\u624b\u52a8\u79ef\u5206\u65f6\u57fa\u7ebf\u5e94\u8be5\u753b\u5728\u54ea\u91cc\u624d\u662f\u79d1\u5b66\u5408\u7406\u5e76\u7b26\u5408\u5b9e\u9a8c\u5ba4\u89c4\u7a0b\u7684\u3002<\/section>\n
       <\/section>\n
      Another outcome of the training is that all trainees must understand that unauthorized manual integration outside of the scope of the SOP is considered as data falsification. The more times that a run is reprocessed either via manual intervention or manual integration the more quality assurance and regulatory scrutiny it will attract, that is, the larger the size of the red rag. Unfortunately large red rags are not very effective at stopping regulatory bulls.<\/section>\n
      \u57f9\u8bad\u7684\u53e6\u5916\u4e00\u4e2a\u76ee\u7684\u662f\u6240\u6709\u53d7\u8bad\u4eba\u5458\u5fc5\u987b\u7406\u89e3\u5728SOP\u8303\u56f4\u4e4b\u5916\u7684\u975e\u6cd5\u7684\u624b\u52a8\u79ef\u5206\u662f\u88ab\u8ba4\u4e3a\u662f\u6570\u636e\u9020\u5047\u7684\u3002\u4e00\u4e2a\u6d4b\u8bd5\u901a\u8fc7\u4eba\u5de5\u5e72\u9884\u6216\u8005\u624b\u52a8\u79ef\u5206\u8fdb\u884c\u91cd\u590d\u5904\u7406\u7684\u6b21\u6570\u8d8a\u591a\uff0c\u7531\u6b64\u5f15\u8d77\u7684\u8d28\u91cf\u4fdd\u8bc1\u548c\u76d1\u7ba1\u5ba1\u67e5\u7684\u95ee\u9898\u8d8a\u591a\uff0c\u4e5f\u5c31\u662f\u8bf4\uff0c\u7ea2\u8272\u8b66\u544a\u7684\u7a0b\u5ea6\u8d8a\u5927\u3002\u4e0d\u5e78\u7684\u662f\u5927\u91cf\u7684\u7ea2\u8272\u8b66\u544a\u5e76\u6ca1\u6709\u6709\u6548\u9632\u6b62\u76d1\u7ba1\u6212\u6761\u3002<\/section>\n
       <\/section>\n
      As a final comment, chromatographic integration should be included in the data integrity self-inspections to ensure that the training and procedure are being complied with in operational use.<\/section>\n
      \u6700\u7ec8\u8bc4\u8bba\uff0c\u6570\u636e\u5b8c\u6574\u6027\u81ea\u68c0\u5e94\u8be5\u5305\u62ec\u8272\u8c31\u79ef\u5206\u4ee5\u786e\u4fdd\u5728\u65e5\u5e38\u4f7f\u7528\u4e2d\uff0c\u57f9\u8bad\u548c\u89c4\u7a0b\u5f97\u5230\u9075\u5faa\u3002<\/section>\n

      <\/section>\n
      Summary<\/section>\n
      \u603b\u7ed3<\/section>\n

      We have discussed manual integration in the context of a regulated laboratory and have found a number of problems. Regulations and guidance are lacking in GMP and the only guidance on the subject is for regulated bioanalytical laboratories, which can result in an overly bureaucratic approach. However, we lack an agreed definition of what constitutes manual integration. Not withstanding this minor problem, a suggested workflow for determining how manual intervention and manual integration can be combined in an overarching SOP on chromatographic integration to meet regulatory concerns. I hope this will stimulate a debate to define what constitutes manual integration and that regulatory agencies will provide guidance on the subject \u2014 eventually.<\/section>\n
      \u6211\u4eec\u5df2\u7ecf\u8ba8\u8bba\u4e86\u53d7\u63a7\u8bd5\u9a8c\u5ba4\u7684\u624b\u52a8\u79ef\u5206\u548c\u53d1\u73b0\u7684\u4e00\u4e9b\u95ee\u9898\u3002\u5728GMP\u4e2d\u7f3a\u4e4f\u6cd5\u89c4\u548c\u6307\u5357\uff0c\u8fd9\u4e2a\u8bfe\u9898\u4e0a\u4ec5\u6709\u7684\u6307\u5357\u662f\u751f\u7269\u5206\u6790\u5ba4\u6cd5\u89c4\uff0c\u5e76\u4e14\u6211\u4eec\u6ca1\u6709\u624b\u52a8\u79ef\u5206\u7684\u7edf\u4e00\u5b9a\u4e49\u3002\u907f\u5f00\u8fd9\u4e9b\u5c0f\u95ee\u9898\uff0c\u901a\u8fc7\u4e00\u4e2a\u5efa\u8bae\u6027\u5de5\u4f5c\u6d41\u6765\u786e\u5b9a\u5982\u4f55\u628a\u624b\u52a8\u5e72\u9884\u548c\u624b\u52a8\u79ef\u5206\u7ed3\u5408\u5728\u4e00\u4e2a\u8272\u8c31\u79ef\u5206SOP\u4e2d\u6765\u6ee1\u8db3\u76d1\u7ba1\u7684\u8981\u6c42\u3002\u6211\u5e0c\u671b\u8fd9\u80fd\u6fc0\u52b1\u51fa\u4e00\u6b21\u4ec0\u4e48\u662f\u624b\u52a8\u79ef\u5206\u7684\u8ba8\u8bba\u5e76\u4e14\u76d1\u7ba1\u673a\u6784\u53ef\u4ee5\u63d0\u4f9b\u5173\u4e8e\u8fd9\u4e00\u8bfe\u9898\u7684\u6307\u5357\u3002<\/section>\n<\/section>\n<\/section>\n<\/section>\n


      <\/p>\n

      1.\u4ec0\u4e48\u60c5\u51b5\u4e0b\u53ef\u4ee5\u8fdb\u884c\u624b\u52a8\u79ef\u5206\uff1f <\/span><\/strong><\/p>\n

      1\uff09\u4f4e\u5206\u79bb\u5ea6\u6216\u4f4e\u54cd\u5e94\uff1b<\/span><\/p>\n

      2\uff09\u6d41\u52a8\u76f8\u4e0d\u7a33\u5b9a\uff0c\u57fa\u7ebf\u7d0a\u4e71\uff0c\u4fdd\u7559\u65f6\u95f4\u53d8\u5316\u5c0f\uff1b<\/span><\/p>\n

      3\uff09\u8272\u8c31\u67f1\u6027\u80fd\uff1a\u8fd0\u884c\u8fc7\u7a0b\u4e2d\uff0c\u51fa\u73b0\u5f02\u5e38\u5cf0\uff1b<\/span><\/p>\n

      4\uff09\u8f6f\u4ef6\u79ef\u5206\u7684\u5c40\u9650\u6027\uff0c\u5982\u7531\u4e8e\u8f6f\u4ef6\u53c2\u6570\u9608\u503c\u7684\u8bbe\u7f6e\u5bfc\u81f4\u5cf0\u672a\u79ef\u5206\uff0c\u5cf0\u8d77\u70b9\u548c\u7ec8\u70b9\u95f4\u51fa\u73b0\u80a9\u5cf0\u548c\u5f02\u5e38\u7684\u57fa\u7ebf\u6f02\u79fb\uff0c\u8f6f\u4ef6\u9519\u8bef\uff08\u5cf0\u672a\u79ef\u5206\u548c\u9519\u8bef\u8bc6\u522b\u5cf0\uff09\uff1b<\/span><\/p>\n

      5\uff09<\/span>\u7531\u4e8e\u6837\u54c1\u6bcd\u4f53\u7684\u5e72\u6270\u5bfc\u81f4\u7684\u590d\u6742\u8272\u8c31\u56fe\uff1a\u88c2\u5cf0\u3001\u76ee\u6807\u6742\u8d28\u7684\u540c\u65f6\u6d17\u8131\/\u80a9\u5cf0\u3001\u57fa\u7ebf\u566a\u97f3\u3001\u8d1f\u5cf0\u3001\u57fa\u7ebf\u4e0a\u5347\u6216\u4e0b\u964d\uff08\u7531\u4e8e\u67d0\u4e9b\u68af\u5ea6\u7a0b\u5e8f\uff09\u3001\u5cf0\u7684\u4e25\u91cd\u62d6\u5c3e\u3001\u70c3\u7c7b\u7684\u5b58\u5728\u5bfc\u81f4\u81ea\u52a8\u79ef\u5206\u4e0d\u6b63\u786e\u3002<\/span><\/p>\n


      <\/span><\/p>\n

      2\u3001\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u68c0\u67e5\u4e0d\u5408\u683c\u9879
      <\/strong>      \u5728 2014\u5e74\uff0cFDA\u5bf9\u6b27\u6d32\u67d0\u5b9e\u9a8c\u5ba4\u7684\u68c0\u67e5\u4e2d\uff0c483\u8868\u683c\u4e2d\u6709\u4e00\u4e2a\u89c2\u5bdf\u9879\u8fd9\u6837\u8868\u8ff0\uff1a\u6ca1\u6709\u63cf\u8ff0\u5982\u4f55\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u7684\u64cd\u4f5c\u89c4\u7a0b\uff08Noprocedure exists describing how to perform manual integration\uff09\u3002\u57282007\u5e748\u6708\uff0cFDA\u7ed9Leiner Health Products\u516c\u53f8\u7684\u8b66\u544a\u4fe1\u4e2d\uff0c\u6709\u4e00\u6761\u7f3a\u9677\u9879\u8fd9\u6837\u8868\u8ff0\uff1a\u68c0\u67e5\u5458\u8bb0\u5f55\u4e86\u5f88\u591a\u201c\u6570\u636e\u634f\u9020(manipulation of data)\uff0c\u5374\u6ca1\u6709\u89e3\u91ca\u634f\u9020\u539f\u56e0\u201d\u3002\u8fd9\u4e2a\u634f\u9020\u5305\u62ec\uff1a\u6539\u53d8\u8272\u8c31\u79ef\u5206\u53c2\u6570\u3001\u91cd\u65b0\u6807\u8bb0\u5cf0\uff0c\u8fd9\u6837\u4e4b\u524d\u672c\u5e94\u8be5\u79ef\u5206\u7684\u5cf0\u5c31\u4e0d\u518d\u79ef\u5206\uff0c\u4e0d\u8ba1\u5165\u6742\u8d28\u7684\u8ba1\u7b97\u3002\u8fd9\u8bf4\u660e\u4e86FDA \u662f\u63a5\u53d7\u624b\u52a8\u79ef\u5206\u7684\uff0c\u4f46\u5e94\u8be5\u6709\u64cd\u4f5c\u89c4\u7a0b\u63a7\u5236\u624b\u52a8\u79ef\u5206\u7684\u6761\u4ef6\u3001\u6743\u9650\u3001\u6ce8\u610f\u4e8b\u9879\u7b49\uff0c\u4e0d\u80fd\u80cc\u79bb\u79d1\u5b66\u5730\u901a\u8fc7\u624b\u52a8\u79ef\u5206\u4f7f\u68c0\u9a8c\u7ed3\u679c\u5408\u683c\u3002
      \u5907\u6ce8\uff1a\u5728FDA\u7684\u73b0\u573a\u68c0\u67e5\u4e2d\uff0c\u4f8b\u5982\u53d1\u73b0\u9884\u8fdb\u6837\u3001\u91cd\u590d\u68c0\u9a8c\u7684\u60c5\u51b5\uff0c\u68c0\u67e5\u5458\u7684\u89c2\u70b9\u662f\uff1a\u5982\u679c\u4f01\u4e1a\u8bc1\u660e\u662f\u79d1\u5b66\u7684\u3001\u5fc5\u8981\u7684\uff0c\u5c31\u5e94\u8be5\u5199\u5165\u64cd\u4f5c\u89c4\u7a0b\u3002\u8fd9\u4e5f\u610f\u5473\u7740\uff0c\u9700\u8981\u7ecf\u8fc7\u5145\u5206\u9a8c\u8bc1\u3001\u79d1\u5b66\u8bc4\u4f30\u3002<\/span><\/em><\/span><\/span><\/p>\n


      <\/span><\/p>\n

      3\u3001<\/span>\u624b\u52a8\u79ef\u5206\u7684\u7528\u5904<\/strong>
            \u7406\u60f3\u6761\u4ef6\u4e0b\uff0c\u5728\u901a\u8fc7\u7cfb\u7edf\u9002\u7528\u6027\u8bd5\u9a8c\u540e\uff0c\u6807\u51c6\u54c1\u3001\u6837\u54c1\u7684\u8272\u8c31\u5e94\u4e00\u76f4\u4ee5\u76f8\u540c\u7684\u65b9\u6cd5\u8fdb\u884c\u79ef\u5206\u3002\u4f46\u662f\u5b9e\u9645\u60c5\u51b5\u5e76\u975e\u5982\u6b64\uff0c\u5c24\u5176\u662f\u63a5\u8fd1\u5b9a\u91cf\u9650\u3001\u68c0\u6d4b\u9650\u7684\u60c5\u51b5\u4e0b\uff0c\u6709\u4e9b\u5cf0\u81ea\u52a8\u79ef\u4e0d\u4e0a\uff0c\u9700\u8981\u624b\u52a8\u79ef\u5206\u3002\u624b\u52a8\u79ef\u5206\u867d\u7136\u4f1a\u53d7\u4e3b\u89c2\u56e0\u7d20\u7684\u5f71\u54cd\uff0c\u5728\u79d1\u5b66\u5206\u6790\u8272\u8c31\u7ed3\u679c\u65f6\u4e5f\u662f\u9700\u8981\u7684\u3002\u4e3e\u4e24\u4e2a\u4f8b\u5b50\u8bf4\u660e\uff1a
      \u4f8b1\uff0c\u5f53\u51fa\u73b0\u5f02\u5e38\u5cf0\uff0c\u5206\u79bb\u5ea6\u4e0d\u597d\u7684\u5cf0\u65f6\uff0c\u53ef\u4ee5\u624b\u52a8\u5f3a\u5236\u5206\u5272\u3002
      \u4f8b2\uff0c\u7814\u53d1\u9636\u6bb5\uff0cAPI\u3001\u7a33\u5b9a\u6027\u6837\u54c1\u7684\u7eaf\u5ea6\u3001\u964d\u89e3\u4ea7\u7269\u7684\u68c0\u9a8c\u65b9\u6cd5\u8272\u8c31\u8fd0\u884c\u6761\u4ef6\u76f8\u540c\uff0c\u4f46\u5e94\u8003\u8651\u5230\u68c0\u6d4b\u5206\u6790\u7684\u91cd\u70b9\u4e0d\u540c\uff0c\u53ef\u80fd\u9700\u8981\u4e0d\u540c\u7684\u79ef\u5206\u53c2\u6570\u3002\u5728\u8fd9\u79cd\u60c5\u51b5\u4e0b\uff0c\u6700\u597d\u5efa\u7acb\u4e0d\u540c\u7684\u5206\u6790\u65b9\u6cd5\u3001\u7a0b\u5e8f\u3002<\/span><\/p>\n

      <\/span><\/p>\n


      4\u3001\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u6307\u5357<\/strong>
             \u5173\u4e8e\u624b\u52a8\u79ef\u5206\uff0c\u5e76\u6ca1\u6709\u6307\u5357\u7ed9\u51fa\u660e\u786e\u7684\u5b9a\u4e49\u3002\u7b14\u8005\u53ea\u67e5\u5230\u6709\u4e24\u7bc7\u751f\u7269\u6837\u672c\u5206\u6790\u7684\u65b9\u6cd5\u9a8c\u8bc1\u6307\u5357\u89c4\u5b9a\u4e86\u518d\u79ef\u5206\uff08Reintegration\uff09\u7684\u6ce8\u610f\u4e8b\u9879\u3002
            FDA \u76842001\u5e74\u5b9a\u7a3f\u6307\u5357 Bioanalytical Method Validation\uff0c\u53ca\u76f8\u5e94\u76842013\u5e74\u8349\u6848\u6307\u5357\u4e5f\u6709\u7c7b\u4f3c\u7684\u8981\u6c42\u3002 \u751f\u7269\u6837\u672c\u5206\u6790\u7684\u65b9\u6cd5\u9a8c\u8bc12013\u8349\u6848\u6307\u5357\uff0c\u7b2cIII.C\u8282\u201c\u6837\u672c\u6570\u636e\u518d\u79ef\u5206\u201d\u89c4\u5b9a\uff1aSOP\u5e94\u8be5\u786e\u5b9a\u518d\u79ef\u5206\u7684\u6807\u51c6\uff0c\u548c\u600e\u6837\u8fdb\u884c\u518d\u79ef\u5206\uff1b\u5e94\u6e05\u695a\u63cf\u8ff0\u3001\u5e76\u8bb0\u5f55\u518d\u79ef\u5206\u7684\u7406\u7531\uff1b\u5e94\u62a5\u544a\u539f\u59cb\u548c\u518d\u79ef\u5206\u6570\u636e\u3002\u7b2cVII.D\u8282\u8fd8\u89c4\u5b9a\uff1a\u518d\u79ef\u5206\u6570\u636e\u5e94\u6709\u7ba1\u7406\u4eba\u5458\u6388\u6743\u518d\u79ef\u5206\u3002
            EMA \u76842011\u5e74\u6307\u5357 Guideline on bioanalytical methodvalidation\uff0c\u7b2c5.5\u8282\u89c4\u5b9a\uff1a\u5e94\u8be5\u6709SOP\u63cf\u8ff0\u8272\u8c31\u7684\u79ef\u5206\u548c\u518d\u79ef\u5206\u3002\u5e94\u5728\u5206\u6790\u62a5\u544a\u4e2d\u8ba8\u8bba\u504f\u79bb\u8fd9\u4e2aSOP\u7684\u4efb\u4f55\u504f\u5dee\u3002\u5e94\u8be5\u8bb0\u5f55\u8272\u8c31\u79ef\u5206\u3001\u518d\u79ef\u5206\u7684 \u79ef\u5206\u53c2\u6570\u3001\u521d\u59cb\u79ef\u5206\u6570\u636e\u3001\u6700\u7ec8\u79ef\u5206\u6570\u636e\uff0c\u5e76\u5728\u8981\u6c42\u65f6\u7acb\u5373\u53ef\u5f97\u3002<\/span><\/p>\n

      <\/span><\/p>\n


      5\u3001\u6ca1\u6709\u516c\u8ba4\u7684\u624b\u52a8\u79ef\u5206\u5b9a\u4e49<\/strong>
           \u76ee\u524d\u6ca1\u6709\u5173\u4e8e\u624b\u52a8\u79ef\u5206\u7684\u516c\u8ba4\u7684\u5b9a\u4e49\uff0cHill\u7684\u4e00\u7bc7\u6587\u7ae0\uff0c\u8ba8\u8bba\u4e86\u624b\u52a8\u518d\u79ef\u5206\u7684\u8303\u56f4\u548c\u672f\u8bed\uff0c\u5e76\u603b\u7ed3\u8ba4\u4e3a\uff0c\u5efa\u7acb\u4e00\u81f4\u7684\u5b9a\u4e49\u662f\u6709\u5fc5\u8981\u7684\u3002\u5982\u679c\u6ca1\u6709\u624b\u52a8\u79ef\u5206\u7684\u5b9a\u4e49\uff0c\u4f01\u4e1a\u600e\u4e48\u5efa\u7acb\u79ef\u5206\u7684SOP\u5462\uff1f
           \u57282015\u5e7411\u6708\uff0c\u7f8e\u56fd\u8d39\u57ce\u7684ISPE\u5e74\u4f1a\u4e0a\uff0c\u4f01\u4e1a\u4eba\u5458Bob McDowall\u548cMark Newton\u5efa\u8bae\u533a\u5206\u624b\u52a8\u5e72\u9884\uff08Manual Intervention\uff09\uff0c\u548c\u624b\u52a8\u79ef\u5206\uff08Manual Integration\uff09,\u5e76\u63d0\u51fa\uff1a
      \u624b\u52a8\u5e72\u9884 \uff1a\u6ca1\u6709\u624b\u52a8\u6539\u53d8\u57fa\u7ebf\uff0c\u4f8b\u5982\uff1a1\uff09\u5bf9\u5cf0\u91cd\u547d\u540d\uff0c\u6216\u8c03\u6574\u79ef\u5206\u7a97\u53e3\uff1b2\uff09\u6539\u53d8\u79ef\u5206\u53c2\u6570\uff1b
      \u624b\u52a8\u79ef\u5206 \uff1a\u5206\u6790\u5458\u624b\u52a8\u91cd\u65b0\u5212\u57fa\u7ebf\u3002
      \u4e3e\u4e24\u4e2a\u4f8b\u5b50\u8bf4\u660e\uff1a
      \u4f8b1\uff0c\u5728\u8272\u8c31\u5cf0\u7684\u4fdd\u7559\u65f6\u95f4\u4e0d\u5728\u9884\u671f\u7684\u65f6\u95f4\u7a97\u53e3\u5185\uff0c\u9700\u8981\u624b\u52a8\u5e72\u9884\u65f6\u95f4\u7a97\u53e3\uff0c\u800c\u5cf0\u9762\u79ef\u4e0d\u4f1a\u6539\u53d8\uff1b\u9700\u8981\u8c03\u67e5\u4fdd\u7559\u65f6\u95f4\u504f\u79bb\u7684\u539f\u56e0\u3002\u53ef\u80fdFDA\u4f1a\u628a\u8fd9\u4e2a\u5e72\u9884\u4e5f\u5f52\u4e3a\u624b\u52a8\u79ef\u5206\uff1b\u4f46\u662fBob\u8ba4\u4e3a\u4e0d\u5fc5\u5f52\u7c7b\u4e3a\u624b\u52a8\u79ef\u5206\u3002\u6240\u4ee5\u5e0c\u671b\u76d1\u7ba1\u673a\u6784\u7ed9\u51fa\u660e\u786e\u5b9a\u4e49\u7684\u6307\u5357\u3002
      \u4f8b2\uff0c\u6709IPEM\u5b66\u5458\u5355\u4f4d\u63d0\u8bae\uff1a\u624b\u52a8\u5e72\u9884\u3001\u624b\u52a8\u79ef\u5206\u8fd9\u4e24\u79cd\u65b9\u5f0f\u5728\u6709\u4e9b\u60c5\u51b5\u4e0b\u53ef\u66ff\u4ee3\u4f7f\u7528\u7684\u3002\u5cf0\u65e0\u6cd5\u8bc6\u522b\uff08\u6216\u4e0d\u80fd\u6b63\u786e\u8bc6\u522b\uff09\u65f6\u53ef\u80fd\u901a\u8fc7\u624b\u52a8\u79ef\u5206\uff08\u91cd\u753b\u57fa<\/span>\u7ebf\uff09\u6216\u8c03\u6574\u79ef\u5206\u53c2\u6570\u89e3\u51b3\uff1b\u5cf0\u79ef\u5206\u4e0d\u597d\u65f6\u53ef\u901a\u8fc7\u624b\u52a8\u79ef\u5206\uff08\u91cd\u753b\u57fa\u7ebf\uff09\u6216\u8c03\u6574\u79ef\u5206\u53c2\u6570\u89e3\u51b3\u3002<\/span><\/p>\n

      <\/span>
      6\u3001\u624b\u52a8\u79ef\u5206\u4f7f\u7528\u7684\u6ce8\u610f\u4e8b\u9879<\/strong>
             \u901a\u5e38\uff0c\u5728\u5f97\u5230\u81ea\u52a8\u79ef\u5206\u8272\u8c31\u56fe\u540e\uff0c\u5206\u6790\u4fdd\u7559\u65f6\u95f4\u3001\u5cf0\u578b\u662f\u5426\u5982\u9884\u671f\uff0c\u5cf0\u662f\u5426\u88ab\u6b63\u786e\u8bc6\u522b\uff0c\u57fa\u7ebf\u662f\u5426\u6ee1\u8db3\u8981\u6c42\uff0c\u6216\u8005\u5176\u5b83\u6807\u51c6\u3002\u53ea\u6709\u5728\u8272\u8c31\u56fe\u4e0d\u53ef\u63a5\u53d7\u65f6\uff0c\u624d\u53ef\u8003\u8651\u662f\u5426\u53ef\u4ee5\u8fdb\u884c\u624b\u52a8\u79ef\u5206\uff0c\u6216\u8005\u8fdb\u884c\u5b9e\u9a8c\u5ba4\u8c03\u67e5\u3002
      \u6709\u4e24\u79cd\u60c5\u51b5\uff0c\u662f\u7981\u6b62\u8fdb\u884c\u624b\u52a8\u79ef\u5206\u7684\uff1a
      <\/span><\/p>\n

        \n
      • \n

        \u5728\u81ea\u52a8\u79ef\u5206\u540e\uff0c\u5bf9\u79f0\u7684\u5cf0\u6709\u53ef\u63a5\u53d7\u7684\u57fa\u7ebf\uff1b<\/span><\/p>\n<\/li>\n

      • \n

        \u589e\u5f3a\u5cf0\u3001\u6216\u524a\u51cf\u5cf0\u7684\u76ee\u7684\u662f\u4e3a\u4e86\u6ee1\u8db3\u7cfb\u7edf\u9002\u7528\u6027\u63a5\u53d7\u6807\u51c6\uff0c\u6216\u6ee1\u8db3\u653e\u884c\u8d28\u91cf\u6807\u51c6\u3002<\/span><\/p>\n<\/li>\n<\/ul>\n


              \u603b\u4e4b\uff0c\u4f01\u4e1a\u5e94\u5efa\u7acb\u79d1\u5b66\u3001\u5408\u7406\u3001\u900f\u660e\u7684\u81ea\u52a8\u79ef\u5206\u64cd\u4f5c\u89c4\u7a0b\uff0c\u5e76\u6ee1\u8db3\u6570\u636e\u5b8c\u6574\u6027\u7684\u8981\u6c42\u3002\u5728SOP\u4e4b\u5916\u8fdb\u884c\u7684\u624b\u52a8\u79ef\u5206\u53ef\u80fd\u88ab\u89c6\u4e3a\u6570\u636e\u9020\u5047\u3002<\/span><\/p>\n


        <\/p>\n<\/p><\/div>\n","protected":false},"excerpt":{"rendered":"

        \u5b9e\u9a8c\u5ba4\u6570\u636e\u5b8c\u6574\u6027\u5df2\u6210FDA\u68c0\u67e5\u5236\u836f\u4f01\u4e1a\u7684\u4e00\u628a\u5229\u5668\uff0c\u5176\u4e2d\u4e00\u6761\u5173\u4e8e\u968f\u610f\u624b\u52a8\u79ef\u5206\u6216\u8005\u65e0\u4e66\u9762\u7a0b\u5e8f\u89c4\u5b9a\u624b\u52a8\u79ef\u5206\uff0c\u8bf4\u660e\u4e86F […]<\/p>\n","protected":false},"author":1,"featured_media":59924,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[2],"tags":[],"_links":{"self":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/59923"}],"collection":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/comments?post=59923"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/59923\/revisions"}],"predecessor-version":[{"id":59927,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/59923\/revisions\/59927"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/59924"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=59923"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=59923"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=59923"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}