{"id":7759,"date":"2018-06-14T01:00:00","date_gmt":"2018-07-27T09:27:23","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/07\/27\/fda%e8%ad%a6%e5%91%8a%e4%bf%a1%ef%bc%9a%e5%8f%b0%e6%b9%be%e4%bf%a1%e4%b8%9c%e7%94%9f%e6%8a%80\/"},"modified":"2018-07-27T17:27:24","modified_gmt":"2018-07-27T09:27:24","slug":"fda%e8%ad%a6%e5%91%8a%e4%bf%a1%ef%bc%9a%e5%8f%b0%e6%b9%be%e4%bf%a1%e4%b8%9c%e7%94%9f%e6%8a%80","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/7759\/","title":{"rendered":"FDA\u8b66\u544a\u4fe1\uff1a\u53f0\u6e7e\u4fe1\u4e1c\u751f\u6280"},"content":{"rendered":"
\n

\u7ffb\u8bd1\uff1a JULIA  \u6765\u6e90\uff1a <\/span>Julia\u6cd5\u89c4\u7ffb\u8bd1<\/span> <\/span><\/p>\n

Warning Letter 320-18-56 <\/span><\/strong>                 <\/span><\/strong>May 31, 2018<\/span><\/span><\/p>\n

Dr. George Ko<\/span><\/p>\n

Chairman, Taiwan Biotech Company, Ltd.<\/span><\/p>\n

22, Chieh-Shou Road, Taoyuan District, Taoyuan City,Taiwan R.O.C.<\/span><\/p>\n

 <\/span><\/p>\n

Dear Dr. Ko:<\/span><\/p>\n

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Taiwan Biotech Company, Ltd at 22, Chieh-Shou Road, Taoyuan District, Taoyuan City, from September 1 to 11, 2017.<\/span><\/p>\n

\u7f8e\u56fdFDA\u4e8e2017\u5e749\u67081-11\u68c0\u67e5\u4e86\u4f60\u4eec\u4f4d\u4e8e\u53f0\u6e7e\u6843\u56ed\u5e02\u6843\u56ed\u533a\u4ecb\u5bff\u8def22\u53f7\u7684\u4fe1\u4e1c\u751f\u6280\u80a1\u4efd\u6709\u9650\u516c\u53f8\u751f\u4ea7\u573a\u6240\u3002<\/span><\/p>\n

This warning letter summarizes significant violations of current good manufacturing practice (CGMP) regulations for finished pharmaceuticals. See 21 CFR, parts 210 and 211.<\/span><\/p>\n

 <\/span>\u672c\u8b66\u544a\u4fe1\u603b\u7ed3\u4e86\u5236\u5242\u751f\u4ea7\u4e25\u91cd\u8fdd\u53cd<\/span>CGMP<\/span>\u8981\u6c42\u3002\u53c2\u89c1<\/span>21CFR<\/span>\u7b2c<\/span>210<\/span>\u548c<\/span>211<\/span>\u90e8\u5206\u3002<\/span><\/span><\/p>\n

Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products 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\u836f\u54c1\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\u836f\u54c1\u6839\u636e<\/span>FDCA<\/span>\u7684<\/span>501(a)(2)(B)<\/span>\u4ee5\u53ca<\/span>21 U.S.C. 351(a)(2)(B)<\/span>\u88ab\u8ba4\u4e3a\u662f\u63ba\u5047\u836f\u54c1\u3002<\/span><\/span><\/p>\n

We reviewed your November 2, 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>11<\/span>\u6708<\/span>2<\/span>\u65e5\u7684\u56de\u590d\u3002<\/span><\/span><\/p>\n

During our inspection, our investigator observed specific violations 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><\/span><\/p>\n

1.      Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).<\/span><\/strong>\u4f60\u516c\u53f8\u672a\u80fd\u5efa\u7acb\u5145\u5206\u7684\u7cfb\u7edf\u4ee5\u76d1\u6d4b\u65e0\u83cc\u52a0\u5de5\u533a\u57df\u7684\u73af\u5883\u6761\u4ef6\uff08<\/span><\/strong>21 CFR 211.42(c)(10)(iv)<\/span><\/strong>\uff09\u3002<\/span><\/strong><\/span><\/p>\n

During the inspection, our investigator found the following issues related to your sterile over-the-counter (b)(4)<\/strong>: (b)(4)<\/strong> and (b)(4)<\/strong>.<\/span><\/p>\n

\u5728\u68c0\u67e5\u671f\u95f4\uff0c\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u4ee5\u4e0b\u4e0e\u4f60\u4eec\u7684\u65e0\u83cc<\/span>OTCXX<\/span>\uff1a<\/span>XX<\/span>\u4e0e<\/span>XX<\/span>\u7684\u95ee\u9898\u3002<\/span><\/span><\/p>\n

Environmental and Personnel Monitoring Alert Investigations<\/span><\/em>\u73af\u5883\u4e0e\u4eba\u5458\u76d1\u6d4b\u8b66\u62a5\u8c03\u67e5<\/span><\/span><\/p>\n

Our investigator identified several environmental monitoring plates from the ISO 5 (Class A) and the surrounding ISO 8 (Class C) clean areas which exceeded action limits and for which investigations were not initiated.<\/span><\/p>\n

 <\/span>\u6211\u4eec\u7684\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u51e0\u4e2a<\/span>ISO5<\/span>\uff08<\/span>A<\/span>\u7ea7\u533a\uff09\u4e0e\u5468\u56f4<\/span>ISO8<\/span>\uff08<\/span>C<\/span>\u7ea7\u533a\uff09\u7ea7\u6d01\u51c0\u533a\u7684\u73af\u5883\u76d1\u6d4b\u789f\uff0c\u8d85\u51fa\u4e86\u884c\u52a8\u9650\uff0c\u4f46\u672a\u542f\u52a8\u8c03\u67e5\u3002<\/span><\/span><\/p>\n

On September 6, 2017, our investigator found containers storing environmental and personnel monitoring microbiological samples, dated August 30 and 31, 2017. Numerous samples lacked basic documentation, including missing colony-forming unit (CFU) counts and the identity of the person who collected the sample. At the request of our investigator, your firm enumerated CFU for these plates. While several plates exhibited counts outside of actionlimits, your firm had not initiated investigations. As an example, a sampletaken for (b)(4)<\/strong> lot (b)(4)<\/strong> yielded an extremely high count of140 CFUs in your ISO 5 area. The action limit for this critical area is < (b)(4)<\/strong>CFU.<\/span><\/p>\n

2017<\/span>\u5e74<\/span>9<\/span>\u6708<\/span>6<\/span>\u65e5\uff0c\u6211\u4eec\u7684\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u5bb9\u5668\u5b58\u8d2e\u73af\u5883\u548c\u4eba\u5458\u76d1\u6d4b\u5fae\u751f\u7269\u6837\u54c1\uff0c\u6807\u793a\u65e5\u671f\u4e3a<\/span>2017<\/span>\u5e74<\/span>8<\/span>\u6708<\/span>30<\/span>\u548c<\/span>31<\/span>\u65e5\u3002\u5927\u91cf\u6837\u54c1\u7f3a\u4e4f\u57fa\u672c\u6587\u4ef6\u8bb0\u5f55\uff0c\u5305\u62ec\u7f3a\u5931\u8fd9\u4e9b\u789f\u7684\u83cc\u843d\u5355\u4f4d\u8ba1\u6570\uff08<\/span>CFU<\/span>\uff09\u4ee5\u53ca\u53d6\u6837\u4eba\u4fe1\u606f\u3002\u5728\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u8981\u6c42\u4e4b\u4e0b\uff0c\u4f60\u516c\u53f8\u5bf9\u8fd9\u4e9b\u789f\u8fdb\u884c\u4e86CFU\u8ba1\u6570\u3002\u6709\u51e0\u4e2a\u789f\u8ba1\u6570\u7ed3\u679c\u8d85\u51fa\u4e86\u884c\u52a8\u9650\uff0c\u4f60\u4eec\u516c\u53f8\u672a\u542f\u52a8\u8c03\u67e5\u3002\u4e3e\u4f8b\u6765\u8bf4\uff0c\u4ece<\/span>ISO5<\/span>\u7ea7\u533a<\/span>XX<\/span>\u6279\u6b21<\/span>XX<\/span>\u6240\u53d6\u6837\u54c1\u7684\u8ba1\u6570\u7ed3\u679c\u9ad8\u8fbe<\/span>140CFU<\/span>\u3002\u8be5\u5173\u952e\u533a\u57df\u7684\u884c\u52a8\u9650<\/span><XXCFU<\/span>\u3002<\/span><\/span><\/p>\n

Due to our investigator\u2019s findings, you initiated investigations during the inspection regarding the undocumented microbial growth. On September 7, 2017, you provided a copy of these initial investigations.<\/span><\/p>\n

\u7531\u4e8e\u6211\u4eec\u7684\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u4e86\u6b64\u4e8b\uff0c\u4f60\u4eec\u5728\u68c0\u67e5\u671f\u95f4\u542f\u52a8\u4e86\u9488\u5bf9\u672a\u8bb0\u5f55\u7684\u5fae\u751f\u7269\u751f\u957f\u60c5\u51b5\u7684\u8c03\u67e5\u3002<\/span>2017<\/span>\u5e74<\/span>9<\/span>\u6708<\/span>7<\/span>\u65e5\uff0c\u4f60\u4eec\u63d0\u4ea4\u4e86\u4e00\u4efd\u8fd9\u4e9b\u521d\u59cb\u8c03\u67e5\u7684\u526f\u672c\u3002<\/span><\/span><\/p>\n

Notably, when asked by the investigator to provide all deviations from environmental monitoring limits, your firm had reported noresults outside limits for over a year prior to the inspection date. This reported level of environmental control is dubious, in that during the current FDA inspection, several environmental monitoring samples were found to have significant growth, and these results had not been enumerated and recorded.<\/span><\/p>\n

\u663e\u7136\uff0c\u5f53\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u8981\u6c42\u63d0\u4f9b\u6240\u6709\u73af\u5883\u76d1\u6d4b\u9650\u5ea6\u504f\u5dee\u65f6\uff0c\u4f60\u4eec\u516c\u53f8\u62a5\u544a\u8bf4\u622a\u6b62\u68c0\u67e5\u65e5\u671f\u5728\u8fc7\u53bb\u4e00\u5e74\u6ca1\u6709\u8fc7\u8d85\u9650\u7ed3\u679c\u3002\u6b64\u73af\u5883\u63a7\u5236\u7684\u62a5\u544a\u6c34\u5e73\u592a\u53ef\u7591\u4e86\uff0c\u5728\u5f53\u65f6<\/span>FDA<\/span>\u68c0\u67e5\u671f\u95f4\uff0c\u51e0\u4e2a\u73af\u5883\u76d1\u6d4b\u6837\u54c1\u5747\u53d1\u73b0\u6709\u663e\u8457\u7684\u751f\u957f\uff0c\u8fd9\u4e9b\u7ed3\u679c\u5747\u672a\u88ab\u8ba1\u6570\u4ea6\u672a\u8bb0\u5f55\u3002<\/span><\/span><\/p>\n

Your failure to accurately account for numerous environmental monitoring plates, enumerate the results, and fully investigate the systemic flaws that led to the unreported data raises questions regardingthe integrity of data generated by your firm.<\/span><\/p>\n

\u4f60\u4eec\u672a\u80fd\u51c6\u786e\u8ba1\u7b97\u5927\u91cf\u73af\u5883\u76d1\u6d4b\u789f\u3001\u8ba1\u6570\u7ed3\u679c\uff0c\u4ea6\u672a\u5168\u9762\u8c03\u67e5\u7cfb\u7edf\u6027\u7455\u75b5\uff0c\u5bfc\u81f4\u672a\u62a5\u544a\u7684\u6570\u636e\u5f15\u53d1\u4f60\u516c\u53f8\u6240\u751f\u6210\u6570\u636e\u7684\u5b8c\u6574\u6027\u95ee\u9898\u3002<\/span><\/p>\n

Insufficient surface monitoring <\/span><\/em> <\/span><\/em>\u8868\u9762\u5fae\u751f\u7269\u76d1\u6d4b\u4e0d\u5145\u5206<\/span><\/em> <\/span><\/span><\/p>\n

On September 6, 2017, our investigator determined that your microbiology technician had not collected required surface samples since September 1, 2017. Further, our inspection revealed that your firm lacked environmental sampling during your (b)(4)<\/strong> and (b)(4)<\/strong>. Your management acknowledged that deficient environmental monitoring on these production (b)(4)<\/strong> had been occurring for approximately 1\u20132 years.<\/span><\/p>\n

2017<\/span>\u5e74<\/span>9<\/span>\u6708<\/span>6<\/span>\u65e5\uff0c\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u4f60\u4eec\u7684\u5316\u9a8c\u5ba4\u6280\u672f\u5458\u81ea<\/span>2017<\/span>\u5e74<\/span>9<\/span>\u6708<\/span>1<\/span>\u65e5\u8d77\u5373\u672a\u91c7\u96c6\u6240\u9700\u7684\u8868\u9762\u6837\u54c1\u3002\u53e6\u5916\uff0c\u6211\u4eec\u7684\u68c0\u67e5\u63ed\u793a\u4f60\u516c\u53f8\u5728\u4f60\u4eec\u7684<\/span>XX<\/span>\u548c<\/span>XX<\/span>\u671f\u95f4\u7f3a\u5c11\u73af\u5883\u53d6\u6837\u3002\u4f60\u4eec\u7684\u7ba1\u7406\u4eba\u5458\u77e5\u6653\u8fd9\u4e9b\u751f\u4ea7<\/span>XX<\/span>\u73af\u5883\u76d1\u6d4b\u7f3a\u9677\u5df2\u6301\u7eed\u53d1\u751f\u7ea6<\/span>1-2<\/span>\u5e74\u3002<\/span><\/span><\/p>\n

In your response, you stated that you created a standard operating procedure (SOP) to track your environmental monitoring samples, and committed to hiring more personnel to supervise activities. However, your response was inadequate. You did not provide the SOP or indicate plans to fully remediate your environmental monitoring program. You also did not indicate whether all unaccounted samples identified by our investigator were enumerated,and if investigations and risk assessments were initiated in response to anyresults outside established limits. In addition, you did not indicate whether acomprehensive review of all laboratory practices and controls was conducted toensure reliable laboratory operations, including but not limited toaccurate reporting of all laboratory data.<\/span><\/p>\n

\u5728\u4f60\u4eec\u7684\u56de\u590d\u4e2d\uff0c\u4f60\u4eec\u58f0\u79f0\u4f60\u4eec\u5236\u8ba2\u4e86<\/span>SOP<\/span>\u6765\u8ffd\u8e2a\u4f60\u4eec\u7684\u73af\u5883\u76d1\u6d4b\u6837\u54c1\uff0c\u5e76\u627f\u8bfa\u4f1a\u8058\u7528\u66f4\u591a\u4eba\u5458\u6765\u76d1\u7ba1\u6d3b\u52a8\u3002\u4f46\u662f\uff0c\u4f60\u4eec\u7684\u56de\u590d\u662f\u4e0d\u5145\u5206\u7684\u3002\u4f60\u4eec\u5e76\u672a\u63d0\u4f9b<\/span>SOP<\/span>\u4ea6\u672a\u5199\u660e\u5168\u9762\u5f25\u8865\u4f60\u4eec\u73af\u5883\u76d1\u6d4b\u7a0b\u5e8f\u7684\u8ba1\u5212\u3002\u4f60\u4eec\u4ea6\u672a\u8bf4\u660e\u6211\u4eec\u8c03\u67e5\u4eba\u5458\u53d1\u73b0\u7684\u6240\u6709\u672a\u8ba1\u6570\u7684\u6837\u54c1\u662f\u5426\u5747\u5df2\u8ba1\u6570\uff0c\u5e76\u4e14\u9488\u5bf9\u6240\u6709\u8d85\u51fa\u65e2\u5b9a\u9650\u5ea6\u7684\u7ed3\u679c\u5747\u542f\u52a8\u4e86\u8c03\u67e5\u548c\u98ce\u9669\u8bc4\u4f30\u3002\u6b64\u5916\uff0c\u4f60\u4eec\u5e76\u672a\u8bf4\u660e\u662f\u5426\u5bf9\u6240\u6709\u5316\u9a8c\u5ba4\u505a\u6cd5\u548c\u63a7\u5236\u8fdb\u884c\u4e86\u5168\u9762\u5ba1\u6838\u4ee5\u786e\u4fdd\u53ef\u9760\u7684\u5316\u9a8c\u5ba4\u64cd\u4f5c\uff0c\u5305\u62ec\u4f46\u4e0d\u4ec5\u9650\u4e8e\u51c6\u786e\u62a5\u544a\u6240\u6709\u5316\u9a8c\u5ba4\u6570\u636e\u3002<\/span><\/span><\/p>\n

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

\u5728\u56de\u590d\u6b64\u51fd\u65f6\uff0c\u8bf7\u63d0\u4ea4\u4ee5\u4e0b\uff1a<\/span><\/p>\n