{"id":47233,"date":"2018-09-21T01:00:00","date_gmt":"2018-09-26T01:37:49","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/2018\/09\/26\/fda-483%e8%a1%a8%ef%bc%9acook-pharmica-%e7%be%8e%e5%9b%bd\/"},"modified":"2018-09-26T09:37:49","modified_gmt":"2018-09-26T01:37:49","slug":"fda-483%e8%a1%a8%ef%bc%9acook-pharmica-%e7%be%8e%e5%9b%bd","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/47233\/","title":{"rendered":"FDA 483\u8868\uff1aCook Pharmica \u7f8e\u56fd"},"content":{"rendered":"
\n

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


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

\u53d7\u68c0\u516c\u53f8\uff1a<\/span>Cook Pharmica LLC<\/span><\/span><\/p>\n

\u53d7\u68c0\u5730\u5740\uff1a<\/span>1300 S. Patterson Drive Bloomington, IN 47403<\/span><\/span><\/p>\n

\u53d7\u68c0\u8eab\u4efd\uff1a\u539f\u6599\u836f\u751f\u4ea7\u573a\u6240<\/span><\/p>\n

FEI<\/span>\u53f7\uff1a<\/span>3005949964<\/span><\/span><\/p>\n

\u68c0\u67e5\u5458\uff1a<\/span><\/p>\n\n\n\n\n\n\n\n
\n

EMPLOYEE(S)  NAME<\/span><\/p>\n<\/td>\n

\n

TITLE<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Scott  R. Nichols, PhD.<\/span><\/p>\n<\/td>\n

\n

Microbiologist<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Nicholas  L. Paulin<\/span><\/p>\n<\/td>\n

\n

Consumer  Safety Officer<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Critina  Ausin-Moreno, PhD.<\/span><\/p>\n<\/td>\n

\n

Senior  Staff Fellow<\/span><\/p>\n<\/td>\n<\/tr>\n

\n

Yanming  An, PhD.<\/span><\/p>\n<\/td>\n

\n

Chemist<\/span><\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

\u68c0\u67e5\u65e5\u671f\uff1a<\/span>2018-04-23<\/span>\u81f3<\/span> 2018-04-27<\/span>\uff0c<\/span>2018-04-30 <\/span>\u81f3<\/span>2018-05-01<\/span><\/span><\/p>\n

\u7b7e\u53d1\u65e5\u671f\uff1a<\/span>2018-05-01<\/span><\/span><\/p>\n

\u53d1\u5e03\u65e5\u671f\uff1a<\/span>2018-09-10<\/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 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><\/span><\/p>\n

 <\/span><\/p>\n

DURING AN INSPECTIONOF YOUR FIRM WE OBSERVED: <\/span><\/span><\/p>\n

\u68c0\u67e5\u4f60\u516c\u53f8\u671f\u95f4\u6211\u4eec\u53d1\u73b0<\/span><\/span><\/p>\n

Observation1. There is an unacceptably high number of mold recoveries in the classified rooms used for manufacture of (b)(4) bulk drug substance. Specifically, mold recoveries in ISO-8 classified rooms ranged from 6 to 46 during 2017, and one mold was recovered in the ISO-7 manufacturing area during 2017. The mold recoveries have been trending upward since 2015.<\/span><\/p>\n

\u7f3a\u9677<\/span>1<\/span>\uff1a\u7528\u4e8e\u751f\u4ea7<\/span>XX<\/span>\u6563\u88c5\u539f\u6599\u836f\u7684\u6d01\u51c0\u533a\u5185\u9709\u83cc\u56de\u6536\u6570\u5b57\u9ad8\u5f97\u4e0d\u53ef\u63a5\u53d7\u3002\u5177\u4f53\u6765\u8bf4\uff0c<\/span>ISO-8<\/span>\u6d01\u51c0\u7ea7\u522b\u623f\u95f4\u5728<\/span>2017<\/span>\u5e74\u9709\u83cc\u56de\u6536\u5728<\/span>6-46<\/span>\uff0c<\/span>2017<\/span>\u5e74\u5728<\/span>ISO-7<\/span>\u7ea7\u751f\u4ea7\u533a\u56de\u6536\u5230\u4e00\u4e2a\u9709\u83cc\u3002\u81ea<\/span>2015<\/span>\u5e74\u4ee5\u6765\u9709\u83cc\u56de\u6536\u6301\u7eed\u8d8b\u9ad8\u3002<\/span><\/span><\/p>\n

Observation 2. Written procedures to prevent contamination of <\/span>(b)(4) drug substance are not followed. Specifically, deviation PR 104369 was opened due to a bioburden excursion of the (b)(4) of (b)(4)lot (b)(4) on 12 July 2014. 190 CFU\/mL were recovered (action limit: <\/span>\u2264<\/span>(b)(4)CFU\/mL).The root cause investigation showed that equipment ((b)(4)-160-01) was improperly setup: the (b)(4) connector was incorrectly (b)(4) during (b)(4) resulting in an ineffective cleaning cycle.<\/span><\/span><\/p>\n

\u7f3a\u9677<\/span>2<\/span>\uff1a\u672a\u9075\u5b88\u9632\u6b62<\/span>XX<\/span>\u539f\u6599\u836f\u6c61\u67d3\u7684\u4e66\u9762\u7a0b\u5e8f\u3002\u5177\u4f53\u6765\u8bf4\uff0c<\/span>2014<\/span>\u5e74<\/span>7<\/span>\u6708<\/span>12<\/span>\u65e5<\/span>XX<\/span>\u6279\u53f7<\/span>XX<\/span>\u4ea7\u54c1\u7684\u751f\u7269\u8d1f\u8f7d\u8d85\u6807\uff0c\u504f\u5dee<\/span>PR104369<\/span>\u542f\u52a8\uff0c\u5176\u4e2d\u53d1\u73b0\u56de\u6536\u503c\u9ad8\u8fbe<\/span>190CFU\/ML<\/span>\uff08\u884c\u52a8\u9650\u2264<\/span>XXCFU\/mL<\/span>\uff09\u3002\u6839\u672c\u539f\u56e0\u8c03\u67e5\u663e\u793a\u8bbe\u5907\uff08<\/span>XX-160-01<\/span>\uff09\u5b89\u88c5\u4e0d\u5f53\uff1a<\/span>XX<\/span>\u8fde\u63a5\u5668\u5728<\/span>XX<\/span>\u671f\u95f4<\/span>XX<\/span>\u4e0d\u6b63\u786e\uff0c\u5bfc\u81f4\u6e05\u6d01\u5faa\u73af\u65e0\u6548\u3002<\/span><\/span><\/p>\n

Observation3. There is a lack of quality oversight in the review of records and proceduresfollowed in drug substance manufacture. Specifically, after deviation PR 176620(due to a bioburden excursion of the (b)(4) on 2 March 2017) was opened, an unacceptably high level of bioburden ((b)(4) CFU\/100mL) was (b)(4) detected on1 May 2017 (LIMS sample #974194) , on the same process equipment (X-165-01) used to manufacture (b)(4) drug substance. The result (LIMS sample #974194) did not automatically trigger a root cause investigation because the associated bioburden limit was \u201creport result\u201d.<\/span><\/p>\n

\u7f3a\u9677<\/span>3<\/span>\uff1a\u5bf9\u8bb0\u5f55\u548c\u539f\u6599\u836f\u751f\u4ea7\u6240\u9075\u5b88\u7a0b\u5e8f\u7684\u5ba1\u6838\u4e2d\u8d28\u91cf\u76d1\u7ba1\u7f3a\u4e4f\u3002\u5177\u4f53\u6765\u8bf4\uff0c\u5728\u504f\u5dee<\/span>PR176620<\/span>\uff08\u7531\u4e8e<\/span>20170302<\/span>\u751f\u7269\u8d1f\u8f7d\u8d85\u6807\uff09\u542f\u52a8\u4e4b\u540e\uff0c<\/span>20170501<\/span>\u53d1\u73b0\u7528\u4e8e\u751f\u4ea7<\/span>XX<\/span>\u539f\u6599\u836f\u7684\u540c\u4e00\u5de5\u827a\u8bbe\u5907\uff08<\/span>X-165-01<\/span>\uff09\u7684\u751f\u7269\u8d1f\u8f7d\u6c34\u5e73\u9ad8\u81f3\u4e0d\u53ef\u63a5\u53d7\uff08<\/span>XXCFU\/100ML<\/span>\uff09\u3002\u8be5\u7ed3\u679c\uff08<\/span>LIMS<\/span>\u6837\u54c1<\/span>#974194<\/span>\uff09\u672a\u81ea\u52a8\u6fc0\u6d3b\u6839\u672c\u539f\u56e0\u8c03\u67e5\uff0c\u56e0\u4e3a\u76f8\u5173\u7684\u751f\u7269\u8d1f\u8f7d\u9650\u5ea6\u4e3a\u201c\u62a5\u544a\u7ed3\u679c\u201d\u3002<\/span><\/span><\/p>\n

Observation4. Corrective actions do not include implementation of adequate procedures to prevent similar deviations from recurring. Specifically, deviations PR 188727 and PR 189163 were opened because (b)(4) \u03bcm (b)(4) filter, item Master (IM) number 403350 (lot (b)(4)) failed to pass the (b)(4) integrity test. the root cause was determined to be a defect in the filter\u2019s manufacturing process. The filter vendor implemented corrective actions to the filter manufacturing process inAugust 2017. The corrective actions implemented after deviations PR 188727 and PR 189163 did not include establishing appropriate procedures to prevent use of defective filters in the (b)(4) manufacturing process.<\/span><\/p>\n

\u7f3a\u9677<\/span>4<\/span>\uff1a\u7ea0\u6b63\u63aa\u65bd\u672a\u5305\u62ec\u5b9e\u65bd\u8db3\u591f\u7684\u7a0b\u5e8f\u6765\u9632\u6b62\u7c7b\u4f3c\u504f\u5dee\u7684\u91cd\u590d\u53d1\u751f\u3002\u5177\u4f53\u6765\u8bf4\uff0c\u504f\u5dee<\/span>PR188727<\/span>\u548c\u504f\u5dee<\/span>PR189163<\/span>\u7531\u4e8e<\/span>XX\u03bcmXX<\/span>\u8fc7\u6ee4\u5668\uff0c\u6750\u6599\u7f16\u53f7<\/span>403350<\/span>\uff08\u6279\u53f7<\/span>XX<\/span>\uff09\u672a\u901a\u8fc7<\/span>XX<\/span>\u5b8c\u6574\u6027\u6d4b\u8bd5\u800c\u542f\u52a8\u3002\u6839\u672c\u539f\u56e0\u786e\u5b9a\u4e3a\u8fc7\u6ee4\u5668\u751f\u4ea7\u5de5\u827a\u6709\u7f3a\u9677\u3002\u8be5\u8fc7\u6ee4\u5668\u4f9b\u5e94\u5546\u4e8e<\/span>2017<\/span>\u5e74<\/span>8<\/span>\u6708\u5bf9\u8fc7\u6ee4\u5668\u7684\u751f\u4ea7\u5de5\u827a\u5b9e\u65bd\u4e86\u7ea0\u6b63\u63aa\u65bd\u3002\u5728\u504f\u5dee<\/span>PR188727<\/span>\u548c<\/span>PR189163<\/span>\u4e4b\u540e\u5b9e\u65bd\u7684\u7ea0\u6b63\u63aa\u65bd\u4e0d\u5305\u62ec\u5efa\u7acb\u9002\u5f53\u7684\u7a0b\u5e8f\u9632\u6b62\u5728<\/span>XX<\/span>\u751f\u4ea7\u5de5\u827a\u4e2d\u4f7f\u7528\u6709\u7f3a\u9677\u7684\u8fc7\u6ee4\u5668\u3002<\/span><\/span><\/p>\n

Observation 5. Sufficient controls to prevent unauthorized changes to data stored on your firm\u2019s HPLC and GC computer systems are inadequate. Specifically, on 25 April 2018, a Senior Scientist demonstrated that the time zone setting could be changed and saved on the HPLC and GCsystems. No requirement of administrative privileges was required to change the time zone of your firm\u2019s <\/span>(b)(4) HPLCs and (b)(4) GC system, thereby allowing for the alteration of real-time records and data collection.<\/span><\/span><\/p>\n

\u7f3a\u9677<\/span>5<\/span>\uff1a\u9632\u6b62\u672a\u7ecf\u6388\u6743\u4fee\u6539\u4f60\u4eec\u516c\u53f8\u7684<\/span>HPLC<\/span>\u548c<\/span>GC<\/span>\u8ba1\u7b97\u673a\u7cfb\u7edf\u4e0a\u6240\u5b58\u8d2e\u7684\u6570\u636e\u7684\u63a7\u5236\u662f\u4e0d\u5145\u5206\u7684\u3002\u5177\u4f53\u6765\u8bf4\uff0c<\/span>20180425<\/span>\uff0c\u4e00\u4f4d\u9ad8\u7ea7\u5b9e\u9a8c\u5458\u6f14\u793a\u4e86\u53ef\u4fee\u6539\u65f6\u533a\u5e76\u4fdd\u5b58\u5728<\/span>HPLC<\/span>\u548c<\/span>GC<\/span>\u7cfb\u7edf\u4e0a\u3002\u4fee\u6539\u4f60\u4eec\u516c\u53f8\u7684<\/span>XXHPLC<\/span>\u548c<\/span>XXGC<\/span>\u7cfb\u7edf\u7684\u65f6\u533a\u4e0d\u9700\u8981\u6709\u7ba1\u7406\u5458\u6743\u9650\uff0c\u4ece\u800c\u53ef\u4ee5\u4fee\u6539\u5b9e\u65f6\u8bb0\u5f55\u548c\u6570\u636e\u96c6\u3002<\/span><\/span><\/p>\n


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

\u7ffb\u8bd1\uff1aJULIA \u6765\u6e90\uff1aJulia\u6cd5\u89c4\u7ffb\u8bd1 \u53d7\u68c0\u516c\u53f8\uff1aCook Pharmica LLC \u53d7\u68c0\u5730\u5740\uff1a […]<\/p>\n","protected":false},"author":1,"featured_media":47234,"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\/47233"}],"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=47233"}],"version-history":[{"count":1,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/47233\/revisions"}],"predecessor-version":[{"id":47235,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/posts\/47233\/revisions\/47235"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media\/47234"}],"wp:attachment":[{"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/media?parent=47233"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/categories?post=47233"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.05921.net\/index.php\/wp-json\/wp\/v2\/tags?post=47233"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}