{"id":38167,"date":"2018-08-13T01:00:00","date_gmt":"2018-09-17T06:18:21","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/09\/17\/fda-483%e8%a1%a8%ef%bc%9a%e6%b5%99%e6%b1%9f%e5%8d%8e%e6%b5%b7-3\/"},"modified":"2018-09-17T14:18:22","modified_gmt":"2018-09-17T06:18:22","slug":"fda-483%e8%a1%a8%ef%bc%9a%e6%b5%99%e6%b1%9f%e5%8d%8e%e6%b5%b7-3","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/38167\/","title":{"rendered":"FDA 483\u8868\uff1a\u6d59\u6c5f\u534e\u6d77"},"content":{"rendered":"
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\u5916\u8d44\u5927\u578b\u5236\u836f\u516c\u53f8\u6280\u672f\u3001\u7814\u53d1\u3001\u8d28\u91cf\u603b\u76d1\uff0c\u9a8c\u8bc1\u7ba1\u7406\u8d44\u6df1\u4e13\u5bb6\uff0c\u591a\u5bb6\u5236\u836f\u516c\u53f8\u987e\u95ee\uff0c\u836f\u5b66\u7855\u58eb\u3002\u56fd\u5bb6\u5de5\u827a\u6838\u5bf9\u672a\u96e8\u7ef8\u7f2a\u4e4b\u9645\uff0c\u6210\u529f\u89e3\u51b3\u4e86\u591a\u5bb6\u5728\u4ea7\u4ea7\u54c1\u5904\u65b9\u3001\u5de5\u827a\u95ee\u9898\u3002\u5904\u65b9\u5de5\u827a\u7684\u4e8c\u6b21\u5f00\u53d1\uff0c\u514d\u8d39\u54a8\u8be2\uff0c\u5168\u7a0b\u4fdd\u5bc6\u3002\u90ae\u7bb1\uff1a1193686015@qq.com\u3002<\/span><\/span><\/span><\/p>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n<\/section>\n

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\u53d7\u68c0\u516c\u53f8\uff1a<\/span>Zhejiang Huahai Pharmaceutical Co., Ltd. <\/span><\/span>\u6d59\u6c5f\u534e\u6d77\u836f\u4e1a<\/span><\/p>\n

\u53d7\u68c0\u5730\u5740\uff1a<\/span>Xunqiao, Linhai, Zhejiang 317024, China <\/span><\/span>\u4e2d\u56fd\u6d59\u6c5f\u4e34\u6d77\u6c5b\u6865<\/span><\/p>\n

\u53d7\u68c0\u8eab\u4efd\uff1a\u5236\u5242\u548c\u539f\u6599\u836f\u751f\u4ea7\u5546<\/span><\/p>\n

FEI<\/span>\u53f7\uff1a<\/span>3003999190<\/span><\/p>\n

\u68c0\u67e5\u5458\uff1a<\/span>Justin A, Boyd, Investigator       \/ Peter E.Baker, Investigator<\/span><\/p>\n

\u68c0\u67e5\u65e5\u671f\uff1a<\/span>2016-011-14<\/span> <\/span>\u81f3 <\/span><\/span>2016-11-18<\/span><\/p>\n

\u7b7e\u53d1\u65e5\u671f\uff1a<\/span>2016-11-18<\/span><\/p>\n


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\u53d1\u5e03\u65e5\u671f\uff1a<\/span>2018-08-09<\/span><\/p>\n


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This document lists observations made by the FDA representative(s) during the inspection of your facility. They are inspectional observations. And do not represent a final agency determination regarding your compliance if you have an objection regarding an observation, or have implemented, or plan to implement corrective action in response to an observation, you may discuss the objection or action with the FDA representative(s) during the inspection or submit this information to FDA to address above. If you have any questions, please contact FDA at the phone number and address above.<\/span><\/p>\n

\u672c\u6587\u4ef6\u5217\u51fa\u4e86<\/span>FDA<\/span>\u4ee3\u8868\u5728\u5bf9\u4f60\u5de5\u5382\u68c0\u67e5\u671f\u95f4\u6240\u53d1\u73b0\u7684\u95ee\u9898\u3002\u8fd9\u4e9b\u53ea\u662f\u68c0\u67e5\u53d1\u73b0\uff0c\u5e76\u4e0d\u4ee3\u8868<\/span>FDA<\/span>\u5bf9\u4f60\u516c\u53f8\u5408\u89c4\u6027\u7684\u6700\u7ec8\u7ed3\u8bba\u3002\u5982\u4f60\u4eec\u5bf9\u67d0\u4e00\u7f3a\u9677\u6709\u5f02\u8bae\uff0c\u6216\u5df2\u5b9e\u65bd\u6216\u8ba1\u5212\u5b9e\u65bd\u7ea0\u6b63\u63aa\u65bd\u6765\u7ea0\u6b63\u67d0\u4e2a\u7f3a\u9677\uff0c\u4f60\u4eec\u5728\u68c0\u67e5\u671f\u95f4\u4e0e<\/span>FDA<\/span>\u4ee3\u8868\u8ba8\u8bba\u4f60\u4eec\u7684\u5f02\u8bae\u4e0e\u63aa\u65bd\uff0c\u6216\u901a\u8fc7\u4e0a\u8ff0\u5730\u5740\u5411<\/span>FDA<\/span>\u63d0\u4ea4\u8d44\u6599\u3002\u5982\u6709\u95ee\u9898\uff0c\u8bf7\u901a\u8fc7\u4e0a\u8ff0\u5730\u5740\u7535\u8bdd\u4e0e<\/span>FDA<\/span>\u53d6\u5f97\u8054\u7cfb\u3002<\/span><\/p>\n

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DURING AN INSPECTION OF YOUR FIRM WEOBSERVED: <\/span><\/span>\u68c0\u67e5\u4f60\u516c\u53f8\u671f\u95f4\u6211\u4eec\u53d1\u73b0<\/span><\/p>\n

OBSERVATION 1<\/span><\/span><\/strong> <\/span>\u7f3a\u9677<\/span><\/span><\/strong>1<\/span><\/span><\/strong><\/p>\n

Written procedures designed to prevent contamination of drug products purporting to be sterile are not followed.  <\/span><\/span><\/span>\u672a\u9075\u5b88\u8bbe\u8ba1\u7528\u4ee5\u9632\u6b62\u7406\u5e94\u65e0\u83cc\u7684\u836f\u54c1\u4ea4\u53c9\u6c61\u67d3\u7684\u4e66\u9762\u7a0b\u5e8f\u3002<\/span><\/span><\/p>\n

1.    <\/span><\/span>During set-up and interventions using the RABS (b)(4) operators were observed to use the (b)(4) directly above sterile surfaces and components. For example, (b)(4) the stopper bowl and stoppers, and open vials at the (b)(4). <\/span><\/span>\u5728\u4f7f\u7528<\/span>RABS XX<\/span>\u88c5\u914d\u548c\u5e72\u9884\u671f\u95f4\uff0c\u53d1\u73b0\u64cd\u4f5c\u4eba\u5458\u5728\u65e0\u83cc\u8868\u9762\u548c\u6210\u5206\u6b63\u4e0a\u65b9\u4f7f\u7528<\/span>XX<\/span>\u3002\u4f8b\u5982\uff0c<\/span>XX<\/span>\u52a0\u585e\u76d8\u548c\u585e\u5b50\uff0c\u4ee5\u53ca\u5728<\/span>XX<\/span>\u6253\u5f00\u897f\u6797\u74f6\u3002<\/span><\/p>\n

2.    <\/span><\/span>Intervention during filling operations have not been defined in procedures and were not documented in the (b)(4) submission batch records. <\/span><\/span>\u7a0b\u5e8f\u4e2d\u672a\u5b9a\u4e49\u5728\u704c\u88c5\u64cd\u4f5c\u671f\u95f4\u7684\u5e72\u9884\uff0c\u4ea6\u672a\u8bb0\u5f55\u5728<\/span>XX<\/span>\u7533\u62a5\u6279\u8bb0\u5f55\u4e2d\u3002<\/span><\/p>\n

3.    <\/span><\/span>There is no preventive change frequency forthe clean room RABS (b)(4). <\/span><\/span>\u672a\u89c4\u5b9a\u6d01\u51c0\u95f4<\/span>RABS XX<\/span>\u7684\u9884\u9632\u6027\u66f4\u6362\u9891\u6b21\u3002<\/span><\/p>\n

4.    <\/span><\/span>No defect set of vials is maintained for training and qualification of the visual inspection process. <\/span><\/span>\u672a\u5236\u4f5c\u76ee\u68c0\u64cd\u4f5c\u57f9\u8bad\u548c\u786e\u8ba4\u7528\u7f3a\u9677\u897f\u6797\u74f6\u7cfb\u5217\u3002<\/span><\/p>\n

OBSERVATION 2<\/span><\/span><\/strong> <\/span>\u7f3a\u9677<\/span><\/span><\/strong>2<\/span><\/span><\/strong><\/p>\n

Failure to establish laboratory controls that include scientifically sound and appropriate specifications, standard sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality and purity..  <\/span><\/span><\/span>\u672a\u5efa\u7acb\u5316\u9a8c\u5ba4\u63a7\u5236\u4f7f\u5176\u5305\u62ec\u79d1\u5b66\u5408\u7406\u9002\u5f53\u7684\u8d28\u91cf\u6807\u51c6\u3001\u6807\u51c6\u53d6\u6837\u8ba1\u5212\u548c\u68c0\u6d4b\u65b9\u6cd5\u7528\u4ee5\u786e\u4fdd\u836f\u54c1\u7b26\u5408\u9002\u5f53\u7684\u9274\u522b\u3001\u5242\u91cf\u3001\u8d28\u91cf\u548c\u7eaf\u5ea6\u6807\u51c6\u3002<\/span><\/span><\/p>\n

1.    <\/span><\/span>Assessments to establish environmental monitoring sampling points were not comprehensive. For example, they did not evaluate expanded sampling points or thoroughly evaluate common activities occurring in the clean room. Further, the environmental monitoring procedures did not define sampling locations with description diagrams to ensurere producible sampling. <\/span><\/span>\u8bbe\u7f6e\u73af\u5883\u76d1\u6d4b\u53d6\u6837\u70b9\u7684\u8bc4\u4f30\u4e0d\u5168\u9762\u3002\u4f8b\u5982\uff0c\u5176\u4e2d\u672a\u8bc4\u4f30\u589e\u52a0\u53d6\u6837\u70b9\u6216\u5f7b\u5e95\u8bc4\u4f30\u5728\u6d01\u51c0\u95f4\u901a\u5e38\u6240\u53d1\u751f\u7684\u6d3b\u52a8\u3002\u53e6\u5916\uff0c\u73af\u5883\u76d1\u6d4b\u7a0b\u5e8f\u5e76\u672a\u91c7\u7528\u63cf\u8ff0\u6027\u56fe\u5f62\u6765\u5b9a\u4e49\u53d6\u6837\u4f4d\u7f6e\u4ee5\u786e\u4fdd\u53d6\u6837\u5177\u6709\u91cd\u590d\u6027\u3002<\/span><\/p>\n

2.    <\/span><\/span>Environmental monitoring media for air, surface, and personnel monitoring does not contain any neutralizer for the disinfectants used in the clean room. <\/span><\/span>\u73af\u5883\u76d1\u6d4b\u4e2d\u7a7a\u6c14\u3001\u8868\u9762\u548c\u4eba\u5458\u76d1\u6d4b\u7528\u57f9\u517b\u57fa\u5e76\u4e0d\u542b\u6709\u4efb\u4f55\u6d01\u51c0\u95f4\u6240\u7528\u6d88\u6bd2\u5242\u7684\u4e2d\u548c\u5242\u3002<\/span><\/p>\n

3.    <\/span><\/span>During open door interventions, environmental monitoring is not performed. For example, non-viable particle counts, active air monitoring, or settle plates is discontinued during open door interventions. <\/span><\/span>\u5728\u5f00\u95e8\u5e72\u9884\u671f\u95f4\u672a\u6267\u884c\u73af\u5883\u76d1\u6d4b\u3002\u4f8b\u5982\uff0c\u5c18\u57c3\u7c92\u5b50\u8ba1\u6570\u3001\u4e3b\u52a8\u53d6\u6837\u76d1\u6d4b\uff0c\u6216\u6c89\u964d\u83cc\u5728\u5f00\u95e8\u5e72\u9884\u671f\u95f4\u88ab\u4e2d\u6b62\u4e86\u3002<\/span><\/p>\n

4.    <\/span><\/span>Monitoring of the unfiltered bulk compounded batch does not include evaluation for endotoxin and the samples are collectedat least (b)(4) prior to the start of (b)(4). <\/span><\/span>\u5bf9\u8fc7\u6ee4\u524d\u914d\u5236\u836f\u6db2\u7684\u76d1\u6d4b\u6ca1\u6709\u5185\u6bd2\u7d20\u9879\u76ee\uff0c\u5728<\/span>XX<\/span>\u5f00\u59cb\u4e4b\u524d\u81f3\u5c11\u53d6\u6837<\/span>XX<\/span>\u3002<\/span><\/p>\n

5.    <\/span><\/span>There is a lack of scientific rationale for the establishment of the parameters for the RABS (b)(4) integrity test of(b)(4) pressure hold time between  (b)(4) Pa and greater than (b)(4) Pa drop in pressure. <\/span><\/span>\u5bf9<\/span>RABS XX <\/span><\/span>\u5b8c\u6574\u6027\u6d4b\u8bd5\u4e2d<\/span>XX<\/span>\u5e15\u548c\u5927\u4e8e<\/span>XX<\/span>\u5e15\u538b\u964d\u4fdd\u538b\u65f6\u957f\u53c2\u6570\u8bbe\u5b9a\u7f3a\u4e4f\u79d1\u5b66\u5408\u7406\u6027\u3002<\/span><\/p>\n

6.    <\/span><\/span>Limits on reject type are not established inthe visual inspection procedures. <\/span><\/span>\u76ee\u68c0\u7a0b\u5e8f\u4e2d\u672a\u8bbe\u5b9a\u62d2\u6536\u7c7b\u578b\u7684\u9650\u5ea6\u3002<\/span><\/p>\n

OBSERVATION 3<\/span><\/span><\/strong> <\/span>\u7f3a\u9677<\/span><\/span><\/strong>3<\/span><\/span><\/strong><\/p>\n

Processing areas are deficient regarding the system for cleaning and disinfecting the equipment. <\/span><\/span><\/span>\u5de5\u827a\u533a\u57df\u7684\u8bbe\u5907\u6e05\u6d01\u548c\u6d88\u6bd2\u7cfb\u7edf\u6709\u7f3a\u9677\u3002<\/span><\/span><\/p>\n

1.    <\/span><\/span>The (b)(4) ducts of the (b)(4) are not periodically inspected and cleaned. On 18 November 2016, the (b)(4) duct for (b)(4) GJC008 was observed to have unidentified white dust on the innersurfaces of the (b)(4) duct. <\/span><\/span>XX<\/span>\u7684<\/span>XX<\/span>\u98ce\u7ba1\u672a\u5b9a\u671f\u68c0\u67e5\u548c\u6e05\u6d01\u3002<\/span>2016<\/span>\u5e74<\/span>11<\/span>\u6708<\/span>18<\/span>\u65e5\uff0c\u53d1\u73b0<\/span>XX GJC008<\/span>\u7684<\/span>XX<\/span>\u98ce\u7ba1\u4e2d\u5185\u8868\u9762\u6709\u4e0d\u660e\u767d\u8272\u7c89\u5c18\u3002<\/span><\/p>\n

2.    <\/span><\/span>(b)(4) of the filling room is done (b)(4) to control spores with a (b)(4) solution. The validation of the (b)(4) process didnot include placement of biological indicators in hard to reach areas, such asin RABS (b)(4) areas that may be clocked by equipment, high areas or low areas.<\/span>\u704c\u88c5\u95f4\u7684<\/span>XX<\/span>\u5df2\u5b8c\u6210\u7528\u4ee5\u4f7f\u7528<\/span>XX<\/span>\u6eb6\u6db2\u63a7\u5236\u5b62\u5b50\u3002<\/span>XX<\/span>\u5de5\u827a\u7684\u9a8c\u8bc1\u672a\u5305\u62ec\u5728\u96be\u63a5\u8fd1\u533a\u57df\u653e\u7f6e\u751f\u7269\u6307\u793a\u5242\uff0c\u4f8b\u5982\u5728\u53ef\u80fd\u88ab\u8bbe\u5907\u963b\u788d\u7684<\/span>RABS<\/span>\u7684<\/span>XX<\/span>\u533a\u57df\u3001\u8f83\u9ad8\u533a\u57df\u6216\u8f83\u4f4e\u533a\u57df\u3002<\/span><\/p>\n

3.    <\/span><\/span>Disinfectant efficacy studies did not evaluate the effectiveness on (b)(4) used for the RABS (b)(4) or (b)(4) used as (b)(4) parts for the filling line. During execution of the studies the challenged surfaces were physically wiped preventing evaluation of the effectiveness of the disinfectant that is sprayed. <\/span><\/span>\u6d88\u6bd2\u5242\u6709\u6548\u6027\u7814\u7a76\u5e76\u672a\u8bc4\u4f30\u7528\u4e8e<\/span>RABS<\/span>\u7684<\/span>XX<\/span>\u7684\u6709\u6548\u6027\uff0c\u548c\u704c\u88c5\u7ebf\u4e2d\u7528\u4f5c<\/span>XX<\/span>\u90e8\u5206\u7684<\/span>XX<\/span>\u7684\u6709\u6548\u6027\u3002\u5728\u7814\u7a76\u6267\u884c\u671f\u95f4\uff0c\u6311\u6218\u8868\u9762\u8fdb\u884c\u4e86\u7269\u7406\u64e6\u62ed\u56e0\u6b64\u65e0\u6cd5\u5bf9\u6240\u55b7\u6d88\u6bd2\u5242\u8fdb\u884c\u6709\u6548\u6027\u8bc4\u4f30\u3002<\/span><\/p>\n

4.    <\/span><\/span>Transfer of the filling machine (b)(4) parts from their storage in unclassified areas to the Grade A areas was not evaluated in the validation \u201cEfficiency Qualification of Material Transferring by Non-Sterilization Method into Grade B\u201d. <\/span><\/span>\u9a8c\u8bc1\u201c\u975e\u706d\u83cc\u65b9\u6cd5\u8f6c\u79fb\u7269\u6599\u81f3<\/span>B<\/span>\u7ea7\u533a\u7684\u6709\u6548\u6027\u786e\u8ba4\u201d\u4e2d\u672a\u8bc4\u4f30\u704c\u88c5\u673a<\/span>XX<\/span>\u90e8\u4ef6\u4ece\u5176\u975e\u6d01\u51c0\u533a\u5b58\u8d2e\u5904\u8f6c\u79fb\u81f3<\/span>B<\/span>\u7ea7\u533a\u7684\u64cd\u4f5c\u3002<\/span><\/p>\n

 <\/span><\/p>\n

OBSERVATION 4<\/span><\/span><\/strong> <\/span>\u7f3a\u9677<\/span><\/span><\/strong>4<\/span><\/span><\/strong><\/p>\n

Data is not recorded contemporaneously. <\/span><\/span><\/span>\u6570\u636e\u8bb0\u5f55\u4e0d\u540c\u6b65\u3002<\/span><\/span><\/p>\n

1.    <\/span><\/span>The \u201cchecked by\u201d entries for batch (b)(4) of(b)(4) Tablets were not documented at the time of batch production. <\/span><\/span>XX<\/span>\u7247\u5242<\/span>XX<\/span>\u6279\u6b21\u6279\u8bb0\u5f55\u4e2d\u590d\u6838\u9879\u672a\u5728\u6279\u751f\u4ea7\u65f6\u8bb0\u5f55\u3002<\/span><\/p>\n

2.    <\/span><\/span>The QC analyst responsible for environmental monitoring does not document sampling at the time it occurs. It was reported the analyst remembers the times and documents all at once after finishing. <\/span><\/span>\u8d1f\u8d23\u73af\u5883\u76d1\u6d4b\u7684<\/span>QC<\/span>\u5316\u9a8c\u5458\u672a\u5728\u53d6\u6837\u65f6\u5373\u884c\u8bb0\u5f55\u3002\u62a5\u544a\u8bf4\u5316\u9a8c\u5458\u51ed\u8bb0\u5fc6\u8bb0\u4e0b\u65f6\u95f4\u7136\u540e\u5728\u5b8c\u6210\u4e4b\u540e\u5168\u90e8\u5199\u4e0b\u6765\u3002<\/span><\/p>\n

<\/mpcps><\/section>\n
<\/mpcps><\/section>\n

FDA\u8b66\u544a\u4fe1\uff1a\u65e5\u672cYuki Gosei Kogyo<\/span><\/h2>\n


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

Warning Letter <\/span><\/span><\/strong>320-18-63 <\/span> <\/span>          <\/span>July 17, 2018<\/span><\/p>\n


<\/p>\n

Mr. Masaru Matsui<\/span><\/p>\n

President and CEO<\/span>, <\/span><\/span>Yuki Gosei Kogyo Co., Ltd.<\/span><\/p>\n

10-4, Nihonbashi-Ningyocho 3-Chome<\/span>, <\/span><\/span>Chuo-Ku, Tokyo 103-0013<\/span>, <\/span><\/span>Japan<\/span><\/p>\n

 <\/span><\/p>\n

Dear Mr. Matsui:<\/span><\/p>\n

The U.S. Food and Drug Administration (FDA) inspected yourdrug manufacturing facility, Yuki Gosei Kogyo Co., Ltd. at Ochiai 788, Joban Nishigo-machi, Jobannishigo-Machi Iwaki, Fukushima, from November 13 to 17, 2017.<\/span><\/p>\n

\u7f8e\u56fd<\/span>FDA<\/span>\u4e8e<\/span>2017<\/span>\u5e74<\/span>1<\/span>1<\/span>\u6708<\/span>1<\/span>3-17 <\/span><\/span>\u65e5\u68c0\u67e5\u4e86\u4f60\u4eec\u4f4d\u4e8e\u65e5\u672c\u798f\u5c9b\u7684<\/span>YukiGosei Kogyo Co., Ltd.<\/span>\u751f\u4ea7<\/span>\u573a\u6240\u3002<\/span><\/p>\n

This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).<\/span><\/p>\n

 <\/span>\u672c\u8b66\u544a\u4fe1\u603b\u7ed3\u4e86\u539f\u6599\u836f\uff08<\/span>API<\/span>\uff09\u751f\u4ea7\u4e25\u91cd\u8fdd\u53cd<\/span>CGMP<\/span>\u8981\u6c42\u3002<\/span><\/p>\n

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).<\/span><\/p>\n

\u7531\u4e8e\u4f60\u4eec\u7684\u751f\u4ea7\u3001\u52a0\u5de5\u3001\u5305\u88c5\u6216\u4fdd\u5b58\u7684\u65b9\u6cd5\u3001\u573a\u6240\u6216\u63a7\u5236\u4e0d\u7b26\u5408<\/span>CGMP<\/span>\u8981\u6c42\uff0c\u4f60\u4eec\u7684\u539f\u6599\u836f\u6839\u636e<\/span>FDCA<\/span>\u7684<\/span>501(a)(2)(B)<\/span>\u4ee5\u53ca<\/span>21U.S.C. 351(a)(2)(B)<\/span>\u88ab\u8ba4\u4e3a\u662f\u63ba\u5047\u836f\u54c1\u3002<\/span><\/p>\n

We reviewed your December 8, 2017, response in detail and acknowledge receipt of your subsequent correspondence.<\/span><\/p>\n

 <\/span>\u6211\u4eec\u5df2\u8be6\u7ec6\u5ba1\u6838\u4e86\u4f60\u516c\u53f8<\/span>2017<\/span>\u5e74<\/span>12<\/span>\u6708<\/span>8<\/span>\u65e5\u7684\u56de\u590d\uff0c\u5e76\u6b64\u544a\u77e5\u6536\u5230\u540e\u7eed\u901a\u4fe1\u3002<\/span><\/p>\n

During our inspection, our investigator observed specific deviations including, but not limited to, the following.<\/span><\/p>\n

 <\/span>\u68c0\u67e5\u671f\u95f4\uff0c\u6211\u4eec\u7684\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u7684\u5177\u4f53\u95ee\u9898\u5305\u62ec\u4f46\u4e0d\u4ec5\u9650\u4e8e\u4ee5\u4e0b\uff1a<\/span><\/p>\n

1.      <\/span>Failure to maintain complete data derived from all laboratory tests conducted to ensure your API complies with established specifications and standards.<\/strong><\/span>\u672a\u80fd\u7ef4\u62a4\u4e3a\u786e\u4fdd\u4f60\u4eec<\/span><\/strong>API<\/span><\/strong>\u7b26\u5408\u65e2\u5b9a\u8d28\u91cf\u6807\u51c6\u6240\u6267\u884c\u7684\u6240\u6709\u5316\u9a8c\u5ba4\u68c0\u6d4b\u6240\u751f\u6210\u7684\u5b8c\u6574\u6570\u636e\u3002<\/span><\/strong><\/p>\n

Your firm does not ensure that complete data from testing of your API are included in the official batch record and reviewed by your quality unit. For example, you reported passing results for related substances testing of <\/span>(b)(4)<\/strong> <\/span>lot #(b)(4)<\/strong> <\/span>analyzed starting at <\/span>(b)(4) <\/span><\/strong>on July 28, 2015. However, our investigator found unreported analyses including out-of-specification (OOS) results for the same lot acquired earlier on the same date, and on the next day as the reported results. You failed to includethis data to be reviewed by your quality unit prior to the release of the lot.Our investigator documented the same pattern with other products not intended for the U.S. market.<\/span><\/p>\n

 <\/span>\u4f60\u516c\u53f8\u672a\u80fd\u786e\u4fdd\u4f60\u4eec<\/span>API<\/span>\u68c0\u6d4b\u6240\u751f\u6210\u7684\u5b8c\u6574\u6570\u636e\u88ab\u653e\u5728\u6b63\u5f0f\u7684\u6279\u8bb0\u5f55\u4e2d\uff0c\u5e76\u7531\u4f60\u4eec\u8d28\u91cf\u90e8\u95e8\u8fdb\u884c\u5ba1\u6838\u3002\u4f8b\u5982\uff0c\u4f60\u4eec<\/span>2015<\/span>\u5e74<\/span>7<\/span>\u6708<\/span>28<\/span>\u65e5\u5728<\/span>XX<\/span>\u68c0\u6d4b\u4e86<\/span>XX<\/span>\u4ea7\u54c1<\/span>XX<\/span>\u6279\u6b21\u6709\u5173\u7269\u8d28\uff0c\u62a5\u544a\u4e86\u5408\u683c\u7ed3\u679c\u3002\u4f46\u662f\uff0c\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u672a\u66fe\u62a5\u544a\u7684\u5206\u6790\u4e2d\u6709\u76f8\u540c\u6279\u6b21\u7684<\/span>OOS<\/span>\u7ed3\u679c\uff0c\u662f\u5728\u540c\u4e00\u5929\u65e9\u4e9b\u65f6\u95f4\u4ee5\u53ca\u5728\u62a5\u544a\u7ed3\u679c\u7684\u6b21\u65e5\u3002\u4f60\u4eec\u672a\u80fd\u5c06\u6b64\u6570\u636e\u653e\u5165\u8bb0\u5f55\u7531\u8d28\u91cf\u90e8\u95e8\u5728\u653e\u884c\u8be5\u6279\u6b21\u4e4b\u524d\u8fdb\u884c\u5ba1\u6838\u3002\u6211\u4eec\u7684\u8c03\u67e5\u4eba\u5458\u8bb0\u5f55\u4e86\u4e0d\u9500\u5f80\u7f8e\u56fd\u7684\u5176\u5b83\u4ea7\u54c1\u4e5f\u5b58\u5728\u6709\u76f8\u540c\u60c5\u51b5\u3002<\/span><\/p>\n

In your response, you explained that this \u201ctrial analysis\u201d was performed on the sample solution for conditioning the high-performance liquid chromatography (HPLC) column. However, your explanation did not address why the \u201ctrial analysis\u201d was performed using a sample solution instead of a standard solution, or why you ran this extra analysis in addition to the system suitability test, which verifies that a chromatographic system is adequate as set forth in USP <621>. <\/span><\/p>\n

 <\/span>\u5728\u4f60\u4eec\u7684\u56de\u590d\u4e2d\uff0c\u4f60\u4eec\u89e3\u91ca\u8bf4\u8fd9\u79cd\u201c\u8bd5\u5206\u6790\u201d\u662f\u7528\u6837\u54c1\u6eb6\u6db2\u8c03\u6574<\/span>HPLC<\/span>\u67f1\u3002\u4f46\u662f\uff0c\u4f60\u4eec\u7684\u89e3\u91ca\u5e76\u672a\u8bf4\u660e\u4e3a\u4f55\u4f1a\u4f7f\u7528\u6837\u54c1\u6eb6\u6db2\u6267\u884c\u201c\u8bd5\u5206\u6790\u201d\u800c\u4e0d\u662f\u7528\u6807\u51c6\u6eb6\u6db2\uff0c\u6216\u8005\u662f\u4e3a\u4f55\u4f60\u4eec\u5728\u7cfb\u7edf\u9002\u7528\u6027\u6d4b\u8bd5\u4ee5\u5916\u8fd8\u8981\u8fd0\u884c\u6b64\u989d\u5916\u5206\u6790\uff0c\u7cfb\u7edf\u9002\u7528\u6027\u6d4b\u8bd5\u662f\u7528\u4ee5\u6838\u67e5\u8272\u8c31\u7cfb\u7edf\u7b26\u5408<\/span>USP<621><\/span>\u8981\u6c42\u7684\u3002<\/span><\/p>\n

You also acknowledged that a retrospective review conducted after the inspection found additional instances of unreported electronic datain original batch records. Your review only assessed laboratory data and did not assess all parts of your facility\u2019s operation where CGMP information is generated and maintained. In addition, you failed to provide details of your review criteria and methodology. <\/span><\/p>\n

 <\/span>\u4f60\u4eec\u4ea6\u544a\u77e5\u8bf4\u5728\u68c0\u67e5\u4e4b\u540e\u8fdb\u884c\u7684\u56de\u987e\u6027\u5ba1\u6838\u53d1\u73b0\u5728\u539f\u59cb\u6279\u8bb0\u5f55\u4e2d\u8fd8\u6709\u672a\u62a5\u544a\u7684\u7535\u5b50\u6570\u636e\u7684\u5176\u5b83\u6848\u4f8b\u3002\u4f60\u4eec\u7684\u5ba1\u6838\u4ec5\u8bc4\u4f30\u4e86\u5316\u9a8c\u5ba4\u6570\u636e\uff0c\u5e76\u672a\u8bf4\u660e\u4f60\u4eec\u5de5\u5382\u751f\u6210\u548c\u4fdd\u5b58<\/span>CGMP<\/span>\u4fe1\u606f\u7684\u6240\u6709\u64cd\u4f5c\u90e8\u5206\u3002\u6b64\u5916\uff0c\u4f60\u4eec\u4ea6\u672a\u63d0\u4ea4\u4f60\u4eec\u5ba1\u6838\u6807\u51c6\u548c\u65b9\u6cd5\u5b66\u8be6\u7ec6\u4fe1\u606f\u3002<\/span><\/p>\n

Data Integrity Remediation <\/span><\/span><\/strong>\u6570\u636e\u5b8c\u6574\u6027\u5f25\u8865\u63aa\u65bd<\/span><\/strong><\/p>\n

Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. We strongly recommend that you retain a qualified consultant to assist in your remediation.<\/span><\/p>\n

 <\/span>\u4f60\u4eec\u7684\u8d28\u91cf\u4f53\u7cfb\u4e0d\u80fd\u5145\u5206\u786e\u4fdd\u6570\u636e\u7684\u51c6\u786e\u6027\u548c\u5b8c\u6574\u6027\uff0c\u65e0\u6cd5\u652f\u6301\u4f60\u4eec\u751f\u4ea7\u7684\u836f\u54c1\u7684\u5b89\u5168\u6027\u3001\u6709\u6548\u6027\u548c\u8d28\u91cf\u3002\u6211\u4eec\u5f3a\u70c8\u5efa\u8bae\u4f60\u4eec\u8058\u8bf7\u4e00\u4f4d\u6709\u8d44\u8d28\u7684\u987e\u95ee\u6765\u5e2e\u52a9\u4f60\u4eec\u8fdb\u884c\u5f25\u8865\u3002<\/span><\/p>\n

In response to this letter, provide the following.<\/span><\/p>\n

 <\/span>\u5728\u56de\u590d\u6b64\u51fd\u65f6\u8bf7\u63d0\u4ea4\u4ee5\u4e0b\u8d44\u6599\uff1a<\/span><\/p>\n

A. A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include: <\/span><\/span>\u4e00\u4efd\u5bf9\u6570\u636e\u8bb0\u5f55\u548c\u62a5\u544a\u4e0d\u51c6\u786e\u6027\u7a0b\u5ea6\u7684\u5168\u9762\u8c03\u67e5\u3002\u4f60\u4eec\u7684\u8c03\u67e5\u5e94\u5305\u62ec<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u8be6\u7ec6\u7684\u8c03\u67e5\u65b9\u6848\u548c\u65b9\u6cd5\u5b66\uff1b\u5bf9\u8bc4\u4f30\u6240\u8986\u76d6\u7684\u6240\u6709\u5316\u9a8c\u5ba4\u3001\u751f\u4ea7\u64cd\u4f5c\u548c\u7cfb\u7edf\u7684\u603b\u7ed3\uff0c\u4ee5\u53ca\u5bf9\u4f60\u4eec\u610f\u5728\u6392\u9664\u7684\u64cd\u4f5c\u4e2d\u6240\u6709\u90e8\u5206\u7684\u8bba\u8bc1\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>Interviews of currentand former employees to identify the nature, scope, and root cause of datain accuracies. We recommend that these interviews be conducted by a qualified third party.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u4e0e\u73b0\u6709\u7684\u548c\u5df2\u79bb\u804c\u7684\u5458\u5de5\u8fdb\u884c\u9762\u8c08\uff0c\u627e\u51fa\u6570\u636e\u4e0d\u51c6\u786e\u7684\u8868\u73b0\u3001\u8303\u56f4\u3001\u6839\u672c\u539f\u56e0\u3002\u6211\u4eec\u5efa\u8bae\u8fd9\u4e9b\u9762\u8c08\u7531\u4e00\u4e2a\u6709\u8d44\u8d28\u7684\u7b2c\u4e09\u65b9\u6765\u5b9e\u65bd\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>An assessment of the extent of data integrity deficiencies at your facility. Identify omissions,alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility\u2019s operations in which you discovered data integrity lapses.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u4f60\u4eec\u5de5\u5382\u6570\u636e\u5b8c\u6574\u6027\u7f3a\u9677\u7684\u7a0b\u5ea6\u7684\u8bc4\u4f30\u3002\u8bc6\u522b\u51fa\u7701\u7565\u3001\u4fee\u6539\u3001\u5220\u9664\u3001\u8bb0\u5f55\u9500\u6bc1\u3001\u4e0d\u540c\u6b65\u8bb0\u5f55\u586b\u5199\u548c\u5176\u5b83\u7f3a\u9677\u3002\u63cf\u8ff0\u4f60\u4eec\u5de5\u5382\u64cd\u4f5c\u4e2d\u53d1\u73b0\u6570\u636e\u5b8c\u6574\u6027\u95ee\u9898\u7684\u6240\u6709\u90e8\u5206\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>A comprehensive retrospective evaluation of the nature of the testing, manufacturing and otherdata integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u4e00\u4efd\u5bf9\u6570\u636e\u5b8c\u6574\u6027\u7f3a\u9677\u72b6\u51b5\u7684\u5168\u9762\u56de\u987e\u6027\u8bc4\u4f30\u3002\u6211\u4eec\u5efa\u8bae\u7531\u4e00\u4e2a\u6709\u8d44\u8d28\u7684\u7b2c\u4e09\u65b9\u91cc\u5177\u6709\u8be5\u9886\u57df\u4e13\u4e1a\u6c34\u5e73\u7684\u4e13\u5bb6\u8bc4\u4f30\u6240\u6709\u6570\u636e\u5b8c\u6574\u6027\u95ee\u9898\u3002<\/span><\/p>\n

B. A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity, and risks posed by ongoing operations.<\/span><\/p>\n

\u5bf9\u4f60\u4eec\u836f\u54c1\u8d28\u91cf\u4e2d\u6240\u53d1\u73b0\u7684\u4e0d\u5408\u683c\u60c5\u51b5\u7684\u6f5c\u5728\u5f71\u54cd\u7684\u5f53\u524d\u98ce\u9669\u8bc4\u4f30\u3002\u4f60\u4eec\u7684\u8bc4\u4f30\u5e94\u5305\u62ec\u7531\u4e8e\u53d7\u5230\u6570\u636e\u5b8c\u6574\u6027\u95ee\u9898\u5f71\u54cd\u7684\u836f\u54c1\u653e\u884c\u5bfc\u81f4\u7684\u60a3\u8005\u98ce\u9669\u7684\u5206\u6790\uff0c\u4ee5\u53ca\u6301\u7eed\u8fd0\u8425\u6240\u5177\u6709\u7684\u98ce\u9669\u3002<\/span><\/p>\n

C. A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:<\/span><\/p>\n

\u4f60\u4eec\u516c\u53f8\u7684\u7ba1\u7406\u7b56\u7565\uff0c\u5305\u62ec\u4f60\u4eec\u5168\u7403<\/span>CAPA<\/span>\u8ba1\u5212\u8be6\u7ec6\u60c5\u51b5\u3002\u4f60\u4eec\u7684\u7b56\u7565\u5e94\u5305\u62ec\uff1a<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate, including analytical data,manufacturing records, and all data submitted to FDA.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u8be6\u7ec6\u7684<\/span>CA<\/span>\u8ba1\u5212\uff0c\u63cf\u8ff0\u4f60\u4eec\u5982\u4f55\u786e\u4fdd\u4f60\u4eec\u751f\u6210\u7684\u6240\u6709\u6570\u636e\u7684\u53ef\u9760\u6027\u548c\u5b8c\u6574\u6027\uff0c\u5305\u62ec\u5206\u6790\u6570\u636e\u3001\u751f\u4ea7\u8bb0\u5f55\u548c\u6240\u6709\u63d0\u4ea4\u7ed9<\/span>FDA<\/span>\u7684\u6570\u636e\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>A comprehensive description of the root causes of your data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u4e00\u4efd\u5b8c\u6574\u7684\u63cf\u8ff0\u4f60\u4eec\u6570\u636e\u5b8c\u6574\u6027\u95ee\u9898\u7684\u6839\u672c\u539f\u56e0\u7684\u63cf\u8ff0\uff0c\u5305\u62ec\u8ba4\u5b9a\u5f53\u524d\u884c\u52a8\u8ba1\u5212\u7684\u8303\u56f4\u548c\u6df1\u5ea6\u4e0e\u8c03\u67e5\u548c\u98ce\u9669\u8bc4\u4f30\u53d1\u73b0\u76f8\u79f0\u7684\u8bc1\u636e\u3002\u8bf4\u660e\u662f\u5426\u5bf9\u6570\u636e\u5b8c\u6574\u6027\u95ee\u9898\u627f\u62c5\u8d23\u4efb\u7684\u4e2a\u4eba\u4ecd\u6709\u80fd\u529b\u5bf9\u4f60\u516c\u53f8\u5bf9<\/span>CGMP<\/span>\u76f8\u5173\u6216\u836f\u7269\u5e94\u7528\u6570\u636e\u4ea7\u751f\u5f71\u54cd\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>Interim measures describing the actions you have taken or will take to protect patients and to ensure thequality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u4e34\u65f6\u63aa\u65bd\uff0c\u63cf\u8ff0\u4f60\u4eec\u5df2\u91c7\u53d6\u7684\u884c\u52a8\uff0c\u6216\u5373\u5c06\u91c7\u53d6\u7528\u4ee5\u4fdd\u62a4\u60a3\u8005\u786e\u4fdd\u4f60\u4eec\u836f\u54c1\u8d28\u91cf\u7684\u52aa\u529b\uff0c\u4f8b\u5982\u901a\u77e5\u4f60\u4eec\u7684\u5ba2\u6237\u3001\u53ec\u56de\u4ea7\u54c1\u3001\u5b9e\u65bd\u989d\u5916\u6d4b\u8bd5\u3001\u5411\u7a33\u5b9a\u6027\u8bd5\u9a8c\u8ba1\u5212\u4e2d\u589e\u52a0\u6279\u6b21\u4ee5\u786e\u4fdd\u7a33\u5b9a\u6027\u3001\u836f\u54c1\u7533\u62a5\u884c\u52a8\u4ee5\u53ca\u52a0\u5f3a\u6295\u8bc9\u76d1\u6d4b\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>Long-term measures describing any remediation efforts and enhancements to procedures, processes,methods, controls, systems, management oversight, and human resources (e.g.,training, staffing improvements) designed to ensure the integrity of your company\u2019s data.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u957f\u671f\u63aa\u65bd\uff0c\u5176\u4e2d\u63cf\u8ff0\u6240\u6709\u5bf9\u7528\u4ee5\u786e\u4fdd\u4f60\u4eec\u516c\u53f8\u6570\u636e\u5b8c\u6574\u6027\u7684\u7a0b\u5e8f\u3001\u6d41\u7a0b\u3001\u65b9\u6cd5\u3001\u63a7\u5236\u3001\u7cfb\u7edf\u3001\u7ba1\u7406\u76d1\u7ba1\u548c\u4eba\u529b\u8d44\u6e90\uff08\u4f8b\u5982\u57f9\u8bad\u3001\u5458\u5de5\u63d0\u9ad8\uff09\u7684\u5f25\u8865\u548c\u63d0\u5347\u3002<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>A status report forany of the above activities already underway or completed.<\/span><\/p>\n

\u009f  <\/span><\/span><\/span>\u5bf9\u4e0a\u8ff0\u6d3b\u52a8\u5df2\u5f00\u5c55\u6216\u5df2\u7ecf\u5b8c\u6210\u7684\u72b6\u6001\u62a5\u544a\u3002<\/span><\/p>\n

Conclusion<\/span><\/strong> <\/span>\u7ed3\u8bba<\/span><\/strong><\/p>\n

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

 <\/span>\u6b64\u51fd\u4e2d\u6240\u5f15\u7528\u7684\u8fdd\u89c4\u5e76\u4e0d\u662f\u5168\u90e8\u3002\u4f60\u4eec\u6709\u8d23\u4efb\u5bf9\u8fd9\u4e9b\u504f\u5dee\u8fdb\u884c\u8c03\u67e5\uff0c\u786e\u5b9a\u539f\u56e0\uff0c\u9632\u6b62\u5176\u518d\u6b21\u53d1\u751f\uff0c\u9632\u6b62\u4f60\u4eec\u8bbe\u65bd\u5185\u5176\u5b83\u504f\u5dee\u7684\u53d1\u751f\u3002<\/span><\/p>\n

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\u2019s 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 dependon your products.<\/span><\/p>\n

\u5982\u679c\u4f60\u4eec\u5728\u8003\u8651\u8981\u91c7\u53d6\u7684\u63aa\u65bd\u53ef\u80fd\u4f1a\u5bfc\u81f4\u4f60\u4eec\u5de5\u5382\u6240\u751f\u4ea7\u7684\u836f\u54c1\u4f9b\u5e94\u4e2d\u65ad\uff0c<\/span>FDA<\/span>\u8981\u6c42\u4f60\u7acb\u5373\u8054\u7cfb<\/span>CDER<\/span>\u836f\u54c1\u77ed\u7f3a\u8d1f\u8d23\u4eba\u5458\uff0c\u8fd9\u6837<\/span>FDA<\/span>\u53ef\u4ee5\u4e0e\u4f60\u4eec\u4e00\u8d77\u91c7\u7528\u6700\u4e3a\u9ad8\u6548\u7684\u65b9\u5f0f\u5f15\u5bfc\u4f60\u4eec\u7684\u64cd\u4f5c\u7b26\u5408\u6cd5\u89c4\u8981\u6c42\u3002\u8054\u7cfb\u836f\u54c1\u77ed\u7f3a\u8d1f\u8d23\u4eba\u5458\u8fd8\u80fd\u8ba9\u4f60\u6ee1\u8db3\u4f9d\u636e<\/span>21 U.S.C. 356C(b)<\/span>\u4f60\u53ef\u80fd\u5fc5\u987b\u62a5\u544a\u4f60\u4eec\u836f\u54c1\u4e2d\u6b62\u6216\u4e2d\u65ad\u7684\u4e49\u52a1\uff0c\u8ba9<\/span>FDA<\/span>\u5c3d\u5feb\u8003\u8651\u662f\u5426\u9700\u8981\u91c7\u53d6\u4f55\u79cd\u63aa\u65bd\u6765\u907f\u514d\u77ed\u7f3a\uff0c\u4fdd\u62a4\u4f9d\u8d56\u4e8e\u4f60\u4eec\u836f\u54c1\u7684\u60a3\u8005\u5065\u5eb7\u3002<\/span><\/p>\n

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

\u5728\u8d35\u516c\u53f8\u672a\u80fd\u5b8c\u6210\u6240\u6709\u504f\u5dee\u7ea0\u6b63\u5e76\u4e14\u7531\u6211\u4eec\u786e\u8ba4\u4f60\u4eec\u7b26\u5408<\/span>CGMP<\/span>\u4e4b\u524d\uff0c<\/span>FDA<\/span>\u53ef\u80fd\u4f1a\u6401\u7f6e\u6240\u6709\u5c06\u4f60\u516c\u53f8\u5217\u4e3a\u836f\u54c1\u751f\u4ea7\u7684\u65b0\u7533\u62a5\u548c\u589e\u8865\u7533\u62a5\u7684\u6279\u51c6\u3002<\/span><\/p>\n

Failure to correct these deviations may also result in FDA refusing admission of articles manufactured at Yuki Gosei Kogyo Co. Ltd., atOchiai 788, Joban Nishigo-machi, Jobannishigo-Machi Iwaki, Fukushima into theUnited 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, inthat the methods and controls used in their manufacture do not appear toconform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act,21 U.S.C. 351(a)(2)(B).<\/span><\/p>\n

 <\/span>\u672a\u80fd\u7ea0\u6b63\u8fd9\u4e9b\u504f\u5dee\u53ef\u80fd\u8fd8\u4f1a\u5bfc\u81f4<\/span>FDA<\/span>\u4f9d\u636e<\/span>FDCA<\/span>\u7b2c<\/span>801(a)(3)<\/span>\u6761\u548c<\/span>21U.S.C. 381(a)(3)<\/span>\u62d2\u7edd\u63a5\u53d7\u5728\u4e0a\u8ff0\u5730\u5740\u751f\u4ea7\u7684\u4ea7\u54c1\u8fdb\u5165\u7f8e\u56fd\u3002<\/span><\/p>\n

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 cannotcomplete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.<\/span><\/p>\n

\u6536\u5230\u6b64\u51fd\u540e\uff0c\u8bf7\u5728<\/span>15<\/span>\u4e2a\u5de5\u4f5c\u65e5\u5185\u56de\u590d\u81f3\u672c\u529e\u516c\u5ba4\u3002\u5728\u56de\u590d\u4e2d\u8bf4\u660e\u81ea\u4ece\u68c0\u67e5\u540e\uff0c\u4f60\u4eec\u505a\u4e86\u54ea\u4e9b\u5de5\u4f5c\u6765\u7ea0\u6b63\u4f60\u4eec\u7684\u504f\u5dee\uff0c\u9632\u6b62\u5176\u518d\u6b21\u53d1\u751f\u3002\u5982\u679c\u4e0d\u80fd\u5728<\/span>15<\/span>\u4e2a\u5de5\u4f5c\u65e5\u5185\u5b8c\u6210\u7ea0\u6b63\u63aa\u65bd\uff0c\u8bf4\u660e\u5ef6\u8fdf\u7684\u539f\u56e0\u4ee5\u53ca\u5b8c\u6210\u8ba1\u5212\u3002<\/span><\/p>\n

Send your electronic reply to <\/span><\/span>CDER-OC-OMQ-Communications@fda.hhs.gov<\/span> <\/span>or mail your reply to:<\/span><\/p>\n

 <\/span><\/p>\n

Rebecca Parrilla<\/span><\/p>\n

Compliance Officer<\/span><\/p>\n

U.S. Food and Drug Administration<\/span><\/p>\n

White Oak Building 51, Room 4359<\/span><\/p>\n

10903 New Hampshire Avenue<\/span><\/p>\n

 Silver Spring, MD 20993<\/span><\/p>\n

 USA<\/span><\/p>\n

 <\/span><\/p>\n

Please identify your response with FEI 3002808534.<\/span><\/p>\n

 <\/span><\/p>\n

Sincerely,<\/span><\/p>\n

\/S\/ <\/span><\/p>\n

Francis Godwin<\/span><\/p>\n

Acting Director<\/span><\/p>\n

Office of Manufacturing Quality<\/span><\/p>\n

Office of Compliance<\/span><\/p>\n

Center for Drug Evaluation and Research <\/span><\/p>\n

 <\/span><\/p>\n

cc:
Mr. Nobuyoshi Miyata, General Manager Joban Factory<\/span><\/p>\n

Yuki Gosei Kogyo Co., Ltd.<\/span><\/p>\n

788, Ochiai, Joban Nishigo-machi<\/span><\/p>\n

Iwaki-shi, Fukushima, 972-8316 Japan<\/span><\/p>\n

<\/mpcps><\/section>\n
<\/mpcps><\/section>\n


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

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