{"id":116828,"date":"2019-06-11T12:38:30","date_gmt":"2019-06-11T04:37:40","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/116828\/"},"modified":"2019-06-11T12:37:40","modified_gmt":"2019-06-11T04:37:40","slug":"ece576e1d0","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/116828\/","title":{"rendered":"FDA 483\u8868\uff1a\u5370\u5ea6 Lupin Ltd."},"content":{"rendered":"
\n

\u7ffb\u8bd1\uff1aJULIA     \u6765\u6e90\uff1a<\/span> <\/span>Julia\u6cd5\u89c4\u7ffb\u8bd1<\/span> <\/span><\/p>\n

\u53d7\u68c0\u516c\u53f8\uff1a<\/span>Lupin Ltd.<\/span>
<\/span><\/p>\n

\u53d7\u68c0\u5730\u5740\uff1a<\/span>28-1,Midc Industrial Area, Chikalthana, Aurangabad, Maharaahtra, 431210, India<\/span><\/span><\/p>\n

\u53d7\u68c0\u8eab\u4efd\uff1a<\/span>Manufacturer of Finished Drugs<\/span>\u5236\u5242\u751f\u4ea7\u5546<\/span><\/span><\/p>\n

FEI<\/span>\u53f7\uff1a<\/span>3004995645<\/span><\/span><\/p>\n

\u68c0\u67e5\u5458\uff1a<\/span>RuamcyC Penn\/Investigator<\/span><\/span><\/p>\n

\u68c0\u67e5\u65e5\u671f\uff1a<\/span>2019-05-06 <\/span>\u81f3 <\/span>2019-05-15<\/span><\/span><\/p>\n

\u7b7e\u53d1\u65e5\u671f\uff1a<\/span>2019-05-15<\/span><\/span><\/p>\n

\u53d1\u5e03\u65e5\u671f\uff1a<\/span>2019-05-22<\/span><\/span><\/p>\n

 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 actionwith 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><\/span><\/p>\n

 <\/span><\/p>\n

DURING AN INSPECTIONOF YOUR FIRM WE OBSERVED: <\/span>\u68c0\u67e5\u4f60\u516c\u53f8\u671f\u95f4\u6211\u4eec\u53d1\u73b0<\/span><\/span><\/p>\n

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

Written records of investigationsin to unexplained discrepancies and the failure of a batch or any of its components to meet specifications do not always include the conclusions and follow-up.<\/span>\u672a\u80fd\u89e3\u91ca\u7684\u5dee\u5f02\u4ee5\u53ca\u4ea7\u54c1\u6279\u6b21\u6216\u5176\u7ec4\u4efd\u4e0d\u7b26\u5408\u6807\u51c6\u7684\u4e66\u9762\u8c03\u67e5\u8bb0\u5f55\u6709\u65f6\u65e0\u7ed3\u8bba\u6216\u65e0\u8ddf\u8e2a\u3002<\/span><\/span><\/p>\n

Specifically, <\/span>\u5177\u4f53\u6765\u8bf4\uff0c<\/span><\/span><\/p>\n

Your firm has notdocumented completed investigations for the following:<\/span><\/p>\n

\u4f60\u516c\u53f8\u672a\u5b8c\u6574\u8bb0\u5f55\u4ee5\u4e0b\u8c03\u67e5\uff1a<\/span><\/p>\n

A.   <\/span>From July 2017 until February 2019, there were (b)(4) cases ((b)(4) cases of (b)(4)mg; (b)(4) cases of (b)(4)mg; (b)(4) cases of (b)(4)mg) where the In-Process Control (b)(4) testing of (b)(4) tablets yielded out of specification results. Retesting was conducted but no corrective actions were taken at the time including conclusions of \u201cNo assignable cause\u201d or \u201cManual Error\u201d without documentation of the manual error. The (b)(4) tester and formulation were changed in January and August 2018, but no CAPA was developed and no follow-up action was assigned.<\/span><\/p>\n

\u81ea<\/span>2017<\/span>\u5e74<\/span>7<\/span>\u6708\u81f3<\/span>2019<\/span>\u5e74<\/span>2<\/span>\u6708\uff0c\u5171\u6709<\/span>XX<\/span>\u8d77\u4e2d\u63a7<\/span>XX<\/span>\u68c0\u6d4b\u7ed3\u679c\u8d85\u6807\u3002\u8fdb\u884c\u4e86\u590d\u6d4b\uff0c\u4f46\u5f53\u7ed3\u8bba\u4e3a\u201c\u672a\u627e\u5230\u53ef\u5f52\u7ed3\u539f\u56e0\u201d\u6216\u201c\u4eba\u4e3a\u9519\u8bef\u201d\u65f6\u672a\u91c7\u53d6\u7ea0\u6b63\u63aa\u65bd\uff0c\u672a\u8bb0\u5f55\u4e0b\u4eba\u4e3a\u9519\u8bef\u3002<\/span>XX<\/span>\u68c0\u6d4b\u4eea\u548c\u5904\u65b9\u4e8e<\/span>2018<\/span>\u5e74<\/span>1<\/span>\u6708\u548c<\/span>8<\/span>\u6708\u8fdb\u884c\u4e86\u53d8\u66f4\uff0c\u4f46\u672a\u5236\u8ba2<\/span>CAPA<\/span>\u4ea6\u672a\u6307\u5b9a\u8ddf\u8e2a\u63aa\u65bd\u3002<\/span><\/span><\/p>\n

B.   <\/span>No investigation was initiated for the discrepancy found with the (b)(4) Tablet Compressor showing an out of range compaction force in the end protocol compaction force statistics versus the operating messages in (b)(4)mg batch (b)(4) (finished goods batch (b)(4)).<\/span><\/p>\n

\u53d1\u73b0\u538b\u7247\u673a<\/span>XX<\/span>\u7684\u538b\u529b\u8d85\u8303\u56f4\u65f6\u672a\u542f\u52a8\u8c03\u67e5\u3002<\/span><\/span><\/p>\n

C.   <\/span>Complaint DPC-AU-261-18-0016 consisted of human hair being embedded within an (b)(4) mg tablet. There was no expansion of the investigation to determine microbial contamination and impact.<\/span><\/p>\n

\u6295\u8bc9<\/span>DPC-AU-261-18-0016<\/span>\u8bf4<\/span>XX<\/span>\u7247\u5242\u91cc\u5d4c\u6709\u4eba\u53d1\uff0c\u672a\u5c06\u8c03\u67e5\u6269\u5c55\u81f3\u5fae\u751f\u7269\u6c61\u67d3\u68c0\u6d4b\u548c\u5f71\u54cd\u3002<\/span><\/span><\/p>\n

 <\/span><\/p>\n

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

Laboratory controls do notinclude the establishment of scientifically sound and appropriate specifications, sampling plans and test procedures designed to assure that components, in-process materials and drug products conform to appropriate standards of identity,strength, quality and purity.<\/span>\u5b9e\u9a8c\u5ba4\u63a7\u5236\u672a\u5305\u62ec\u5efa\u7acb\u79d1\u5b66\u5408\u7406\u548c\u6070\u5f53\u7684\u8d28\u91cf\u6807\u51c6\u3001\u53d6\u6837\u8ba1\u5212\u548c\u68c0\u6d4b\u65b9\u6cd5\uff0c\u7528\u4ee5\u786e\u4fdd\u7ec4\u5206\u3001\u4e2d\u95f4\u4f53\u548c\u6210\u54c1\u7b26\u5408\u9002\u5f53\u7684\u5747\u4e00\u6027\u3001\u542b\u91cf\u3001\u8d28\u91cf\u548c\u7eaf\u5ea6\u6807\u51c6\u3002<\/span><\/span><\/p>\n

Specifically, <\/span>\u5177\u4f53\u6765\u8bf4\uff0c<\/span><\/span><\/p>\n

Growth promotion isdeficient in that (b)(4) average colony counts obtained from the certificates of analysis are used to accept new media rather than using actual counts obtained from verified, already accepted media. This process has not been validated to show at least equivalency to USP methods.<\/span><\/p>\n

\u4fc3\u751f\u957f\u8bd5\u9a8c\u6709\u7f3a\u9677\uff0c<\/span>COA<\/span>\u4e0a\u7684<\/span>XX<\/span>\u5e73\u5747\u83cc\u843d\u8ba1\u6570\u88ab\u7528\u4e8e\u63a5\u53d7\u65b0\u7684\u57f9\u517b\u57fa\uff0c\u800c\u672a\u4f7f\u7528\u5df2\u9a8c\u8bc1\u5df2\u63a5\u53d7\u7684\u57f9\u517b\u57fa\u6240\u5f97\u7684\u5b9e\u9645\u8ba1\u6570\u7ed3\u679c\u505a\u5224\u5b9a\u3002\u8be5\u7a0b\u5e8f\u672a\u7ecf\u8fc7\u9a8c\u8bc1\u8bc1\u660e\u5176\u81f3\u5c11\u7b49\u540c\u4e8e<\/span>USP<\/span>\u65b9\u6cd5\u3002<\/span><\/span><\/p>\n

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

Control procedures are not established which monitor the output and validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug product. <\/span>\u672a\u5efa\u7acb\u6536\u7387\u76d1\u6d4b\u63a7\u5236\u7a0b\u5e8f\uff0c\u672a\u9a8c\u8bc1\u53ef\u80fd\u5bfc\u81f4\u4e2d\u95f4\u4f53\u548c\u6210\u54c1\u7279\u6027\u53d8\u5316\u7684\u751f\u4ea7\u5de5\u827a\u6027\u80fd\u3002<\/span><\/span><\/p>\n

Specifically, <\/span>\u5177\u4f53\u6765\u8bf4\uff0c<\/span><\/span><\/p>\n

A.   <\/span>Temperature mapping studies were conducted onthe finished drug product warehouses (b)(4) but did not use the data to scientifically justify the placement of the temperature data loggers. The loggers were not placed in the hot spots derived from the studies. The variability for the movement of the shelves was also not taken into account during the studies.<\/span><\/p>\n

\u5236\u5242\u6210\u54c1\u4ed3\u5e93<\/span>XX<\/span>\u505a\u4e86\u6e29\u5ea6\u5206\u5e03\u7814\u7a76\uff0c\u4f46\u672a\u4f7f\u7528\u8fd9\u4e9b\u6570\u636e\u6765\u79d1\u5b66\u8bba\u8bc1\u6e29\u5ea6\u8bb0\u5f55\u4eea\u7684\u653e\u7f6e\u70b9\u3002\u8bb0\u5f55\u4eea\u672a\u653e\u5728\u7814\u7a76\u6240\u7ed3\u8bba\u7684\u6700\u70ed\u70b9\u3002\u5728\u7814\u7a76\u4e2d\u4ea6\u672a\u8003\u8651\u8d27\u67b6\u79fb\u52a8\u7684\u53d8\u5316\u3002<\/span><\/span><\/p>\n

B.   <\/span>Yield limit specifications have not been established for critical manufacturing steps such as in-process (b)(4) of (b)(4)mg and (b)(4) capsules. The process was stated to have been validated but (b)(4) commercial batches would be needed to validate the yield specification.<\/span><\/p>\n

\u5173\u952e\u751f\u4ea7\u6b65\u9aa4\u5982<\/span>XX<\/span>\u80f6\u56ca\u7684\u4e2d\u95f4\u6b65\u9aa4\u672a\u5236\u5b9a\u6536\u7387\u9650\u5ea6\u6807\u51c6\u3002\u516c\u53f8\u58f0\u79f0\u8be5\u5de5\u827a\u5df2\u7ecf\u8fc7\u9a8c\u8bc1\uff0c\u4f46<\/span>XX<\/span>\u5546\u4e1a\u6279\u6b21\u9700\u8981\u9a8c\u8bc1\u5176\u6536\u7387\u6807\u51c6\u3002<\/span><\/span><\/p>\n

DATES OF INSPECTION <\/span>\u68c0\u67e5\u65e5\u671f<\/span><\/span><\/p>\n

2019-05-06 <\/span>\u81f3<\/span>2019-05-10 <\/span>\uff08\u5468\u4e00\u81f3\u5468\u4e94\uff09<\/span>2019-05-13 <\/span>\u81f3<\/span>2019-05-15<\/span>\uff08\u5468\u4e00\u81f3\u5468\u4e09\uff09<\/span><\/span><\/p>\n

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

\u7ffb\u8bd1\uff1aJULIA     \u6765\u6e90\uff1a Julia\u6cd5\u89c4\u7ffb\u8bd1  \u53d7\u68c0\u516c\u53f8\uff1aLu […]<\/p>\n","protected":false},"author":1,"featured_media":116829,"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\/116828"}],"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=116828"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/116828\/revisions"}],"predecessor-version":[{"id":116831,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/116828\/revisions\/116831"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/116829"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=116828"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=116828"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=116828"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}