浠婂ぉ鏄細

瀹為獙瀹よ祫璁綉

FDA璀﹀憡淇★細鍚夋灄鑸掑叞鍚堟垚鑽笟鑲′唤鏈夐檺鍏徃

瀹為獙瀹よ祫璁綉鏃堕棿:2018-07-06 鐐瑰嚮: 娆?/span> 鐧惧害鎼滅储

銆愬璇汇€?/strong>缇庡浗FDA浜?017骞?1鏈?-10鏃ユ鏌ヤ簡浣犱滑浣嶄簬涓浗鍚夋灄鐪佽垝鍏板競浜烘皯澶ц矾2066鍙风殑鍚夋灄鑸掑叞鍚堟垚鍒惰嵂鏈夐檺鍏徃鐢熶骇鍦烘墍銆傛湰璀﹀憡淇℃€荤粨浜嗗師鏂欒嵂鐢熶骇涓ラ噸杩濆弽CGMP鐨勮涓恒€?.....
TAG鏍囩锛?FDA 璀﹀憡淇?/a> 鍚夋灄鑸掑叞鍚堟垚鑽笟 FDA璀﹀憡淇?/a>

缈昏瘧锛?nbsp;JULIA 鏉ユ簮锛?/span>Julia娉曡缈昏瘧

 

Warning Letter 320-18-51

May 14, 2018

Mr. Daqian Li, Genera lManager

Jilin Shulan Synthetic Pharmaceutical Co., Ltd.

No. 2066 People’s Main Road, Shulan City, Jilin Province, 132600 China

 

Dear Mr. Li:

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Jilin Shulan Synthetic Pharmaceutical Co., Ltd., at No. 2066 People’s Main Road,Shulan City, Jilin Province, from November 7 to 10, 2017.

缇庡浗FDA浜?/span>2017骞?/span>11鏈?/span>7-10鏃ユ鏌ヤ簡浣犱滑浣嶄簬涓浗鍚夋灄鐪佽垝鍏板競浜烘皯澶ц矾2066鍙风殑鍚夋灄鑸掑叞鍚堟垚鍒惰嵂鏈夐檺鍏徃鐢熶骇鍦烘墍銆?/span>

This warning letter summarizes significant deviations from current good manufacturing practice (CGMP) for active pharmaceutical ingredients (API).

 鏈鍛婁俊鎬荤粨浜嗗師鏂欒嵂鐢熶骇涓ラ噸杩濆弽CGMP鐨勮涓恒€?/span>

Because your methods,facilities, or controls for manufacturing, processing, packing, or holding donot conform to CGMP, your API are adulterated within the meaning of section501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21U.S.C. 351(a)(2)(B).

鐢变簬浣犱滑鐨勫師鏂欒嵂鐢熶骇銆佸姞宸ャ€佸寘瑁呮垨淇濆瓨鐨勬柟娉曘€佸満鎵€鎴栨帶鍒朵笉绗﹀悎CGMP瑕佹眰锛屼綘浠殑鍘熸枡鑽牴鎹?/span>FDCA鐨?/span>501(a)(2)(B)浠ュ強21U.S.C. 351(a)(2)(B)琚涓烘槸鎺哄亣鑽搧銆?/span>

We reviewed your November 27, 2017, response in detail.

鎴戜滑宸茶缁嗗鏍镐簡浣犲叕鍙?/span>2017骞?/span>11鏈?/span>27鏃ョ殑鍥炲銆?/span>

During our inspection, our investigators observed specific deviations including, but notlimited to, the following.

 妫€鏌ユ湡闂达紝鎴戜滑鐨勮皟鏌ヤ汉鍛樺彂鐜扮殑鍏蜂綋闂鍖呮嫭浣嗕笉浠呴檺浜庝互涓嬶細

1. Failure to document known deviations and out-of-specification results and conduct a thorough investigation. 鏈兘璁板綍宸茬煡鍋忓樊鍜?/span>OOS缁撴灉骞跺疄鏂藉交搴曡皟鏌ャ€?/span>

Undocumented manufacturing deviation

鏈褰曠殑鐢熶骇鍋忓樊

You failed to ensure that manufacturing process deviations are documented, and any critical process deviations are investigated, and resolved. Specifically, the (b)(4). Our investigator found a note in your batch record stating that the (b)(4)(which violated the process) and the operator was to be fined 50 yuan. There was noformal deviation report documented. You failed to investigate the effects ofthis deviation on product quality, nor did you evaluate the criticality of this process parameter.

浣犱滑鏈兘纭繚璁板綍鐢熶骇宸ヨ壓鍋忓樊锛屽苟璋冩煡鍜岃В鍐虫墍鏈夊叧閿伐鑹哄亸宸€傚叿浣撴潵璇达紝鎴戜滑璋冩煡浜哄憳鍦ㄤ綘浠殑鎵硅褰曚腑鍙戠幇涓€寮犱究鏉″啓鐫€XX锛堣繚鍙嶅伐鑹猴級鍜屾搷浣滀汉鍛樼綒娆?/span>50鍏冦€傛病鏈夋寮忕殑鍋忓樊鎶ュ憡璁板綍銆備綘浠湭瀵规鍋忓樊瀵逛骇鍝佽川閲忕殑褰卞搷杩涜璋冩煡锛屼篃娌℃湁璇勪及姝ゅ伐鑹哄弬鏁扮殑鍏抽敭绋嬪害銆?/span>

In your response, yousaid the operator violated your procedure for (b)(4). Your response was inadequate because you did not explain why the operator did not follow the procedure. Also, you did not explain how you will ensure all deviations are documented and critical deviations are investigated as required.

鍦ㄤ綘浠殑鍥炲涓紝浣犱滑璇存搷浣滀汉鍛樿繚鍙嶄簡浣犱滑鐨?/span>XX绋嬪簭銆備綘浠殑鍥炲鏄笉鍏呭垎鐨勶紝鍥犱负浣犱滑鏈В閲婁负浣曟搷浣滀汉鍛樺苟鏈伒瀹堢▼搴忋€傝繕鏈変綘浠害鏈В閲婁綘浠濡備綍纭繚浼氳褰曟墍鏈夊亸宸紝骞舵寜瑕佹眰瀵瑰叧閿亸宸繘琛岃皟鏌ャ€?/span>

Dual sets of laboratory records and uninvestigated OOS results

2濂楀寲楠屽璁板綍鍜屾湭缁忚皟鏌ョ殑OOS缁撴灉

Our investigator also found that you failed to document, investigate, and resolve out-of-specification (OOS) results in your laboratory. The investigator identified two sets of laboratory testing records for four (b)(4) batches and five (b)(4) batches: one set of records included OOS results; the second set included results within specifications. You could not provide evidence to support the passing results. You also failed to conduct investigations for the OOS results. Your quality department acknowledged this practice during the inspection.

鎴戜滑鐨勮皟鏌ュ憳鍙戠幇浣犱滑鏈褰曘€佽皟鏌ュ拰瑙e喅浣犱滑鍖栭獙瀹や腑鐨?/span>OOS缁撴灉銆傝皟鏌ュ憳鍙戠幇4鎵规XX鍜?/span>5鎵规XX鍧囨湁2濂楀寲楠屽妫€楠岃褰曪細涓€濂楄褰曚腑鏈?/span>OOS缁撴灉锛岀浜屽璁板綍閲岀殑缁撴灉鍒欑鍚堟爣鍑嗐€備綘浠湭鑳芥彁渚涜瘉鎹敮鎸佸悎鏍肩粨鏋溿€備綘浠害鏈OOS缁撴灉杩涜璋冩煡銆備綘浠殑璐ㄩ噺閮ㄩ棬鐭ユ檽浜嗘鏌ヤ腑鍙戠幇鐨勮繖浜涗簨鎯呫€?/span>

In your response, you stated that the failure to investigate these deviations was due to the staff’slack of CGMP knowledge. You provided retest results and your updated “Out-Of-Trend (OOT) Manage Procedure.” Your response was inadequate because you addressed OOT results instead of OOS results; you did not provide your investigations into the original OOT/OOS results. You also failed to identify the root causes of the OOS results.

鍦ㄤ綘浠殑鍥炲涓紝浣犱滑澹扮О鏈皟鏌ヨ繖浜涘亸宸槸鍥犱负鍛樺伐缂轰箯CGMP鐭ヨ瘑銆備綘浠彁渚涗簡澶嶆祴缁撴灉锛屼互鍙婁綘浠洿鏂板悗鐨?ldquo;OOT绠$悊绋嬪簭”銆備綘浠殑鍥炲鏄笉鍏呭垎鐨勶紝鍥犱负浣犱滑澶勭悊浜?/span>OOT缁撴灉鑰屼笉鏄?/span>OOS缁撴灉銆備綘浠害鏈彁渚涗綘浠殑瀵瑰師濮?/span>OOT/OOS缁撴灉鐨勮皟鏌ャ€備綘浠害鏈壘鍒?/span>OOS缁撴灉鐨勬牴鏈師鍥犮€?/span>

For more information about handling failing, OOS, OOT, or other unexpected results and documentationof your investigations, see FDA’s guidance document, Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production, at https://www.fda.gov/downloads/drugs/guidances/ucm070287.pdf.

鍏充簬澶勭悊澶辫触銆?/span>OOS銆?/span>OOT鎴栧叾瀹冮潪棰勬湡缁撴灉浠ュ強璁板綍浣犱滑璋冩煡鎯呭喌鐨勬洿澶氫俊鎭紝鍙傝FDA鎸囧崡鏂囦欢銆?/span>

2. Failure to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data, and failure to have adequate controls to prevent omission of data. 鏈璁$畻鏈哄寲绯荤粺杩涜鍏呭垎鎺у埗浠ラ槻姝㈡湭缁忔巿鏉冭繘鍏ユ垨淇敼鏁版嵁锛屼害鏈繘琛屽厖鍒嗘帶鍒朵互闃叉鏁版嵁閬楁紡銆?/span>

Our investigator found that audit trails in your standalone instruments ((b)(4) high-performance liquid chromatography systems, (b)(4) gas chromatography systems, and (b)(4) infrared radiation system) were not enabled. You also did not have other mechanisms for recording and monitoring any changes to data generated on these instruments. Your firm backed up electronic data from these instruments to a portable drive (b)(4). However, the drive was not password-protected, and itwas stored in an unlocked drawer in an unlocked office.

鎴戜滑璋冩煡鍛樺彂鐜颁綘浠崟鏈轰华鍣紙XX HPLC绯荤粺閲岀殑瀹¤杩借釜锛?/span>XX姘旂浉绯荤粺锛屼互鍙?/span>XX绾㈠绯荤粺锛夋湭婵€娲汇€備綘浠害鏃犲叾瀹冩満鍒惰褰曞拰鐩戞祴瀵规墍杩欎簺浠櫒鎵€鐢熸垚鐨勬暟鎹墍鍋氱殑鍙樻洿銆備綘鍏徃灏嗚繖浜涗华鍣ㄤ腑鐨勭數瀛愭暟鎹浠借嚦绉诲姩纭洏XX銆備絾鏄紝璇ョ‖鐩樺苟鏈湁瀵嗙爜淇濇姢锛屽苟涓旀斁缃湪涓€涓湭涓婇攣鐨勫姙鍏閲屼竴涓湭涓婇攣鐨勬娊灞変腑銆?/span>

Our investigator also found that operators had full system permissions, including the ability tomodify and delete files. For example, our investigator found files related to system suitability tests for (b)(4) in the recycle bin folder on the computer connected to high performance liquid chromatography system.

鎴戜滑鐨勮皟鏌ュ憳杩樺彂鐜版搷浣滀汉鍛樺叿鏈夊叏闈㈢殑绯荤粺鏉冮檺锛屽寘鎷彲浠ヤ慨鏀瑰拰鍒犻櫎鏂囦欢銆備緥濡傦紝鎴戜滑璋冩煡鍛樺湪杩炴帴HPLC绯荤粺鐨勮绠楁満鍥炴敹绔欓噷鍙戠幇浜嗕笌绯荤粺閫傜敤鎬ф湁鍏崇殑鏂囦欢銆?/span>

In your response, you committed to upgrading your chromatography computer systems to a software version with audit trails. Your response was inadequate because you did not provide appropriate procedures or details on your updated computer systems to demonstrate how you will restrict access or changes to your data.

鍦ㄤ綘浠殑鍥炲涓紝浣犱滑鎵胯瑕佸崌绾т綘浠殑鑹茶氨璁$畻鏈虹郴缁熻嚦甯﹀璁¤拷韪殑杞欢鐗堟湰銆備綘浠殑鍥炲鏄笉鍏呭垎鐨勶紝鍥犱负浣犱滑骞舵湭鎻愪緵浣犱滑鏇存柊鍚庤绠楁満绯荤粺鐨勯€傚綋绋嬪簭鎴栬缁嗕俊鎭互璇佹槑浣犱滑瑕佸浣曢檺鍒惰繘鍏ユ垨淇敼浣犱滑鐨勬暟鎹€?/span>

3. Failure to record activities at the time they are performed. 鏈兘鍦ㄥ疄鏂芥椿鍔ㄦ椂鍗宠褰曚箣銆?/span>

Our investigator found numerous examples of your failure to record manufacturing operations contemporaneously with their performance. For example, our investigator discovered blank batch production records that were pre-signed by your operator, partially-completed batch records, and batch records with data changes in pencil without any justification. Our investigator also identified two process batch records for the same operation for (b)(4) batch (b)(4); one record was partially filled out by one operator and the second record was completed by a different operator.

鎴戜滑鐨勮皟鏌ュ憳鍙戠幇澶ч噺浣犱滑鏈兘鍦ㄦ搷浣滄椂鍚屾璁板綍鐢熶骇鎿嶄綔鐨勪緥瀛愩€備緥濡傦紝鎴戜滑璋冩煡鍛樺彂鐜板凡缁忕敱浣犱滑鎿嶄綔浜哄憳鎻愬墠绛惧悕濂界殑绌虹櫧鎵硅褰曘€侀儴鍒嗗畬鎴愮殑鎵硅褰曚互鍙婄敤閾呯瑪淇敼鏁版嵁鑰屾病鏈変换浣曡璇佺殑鎵硅褰曘€傛垜浠皟鏌ュ憳杩樺彂鐜?/span>2鏈壒璁板綍閮芥槸XX浜у搧XX鎵规鐨勭浉鍚屾搷浣滐紝涓€浠借褰曠敱涓€涓搷浣滃憳濉啓浜嗕竴鍗婏紝鍙︿竴浠藉垯鐢卞彟涓€涓搷浣滃憳濉啓瀹屾垚浜嗐€?/span>

In your response, you indicated that these deficiencies were due to the lack of oversight by your quality assurance department. Your response was inadequate because you did not explain why your quality unit did not ensure contemporaneous documentation or exercise adequate oversight.

鍦ㄤ綘浠殑鍥炲涓紝浣犱滑璇磋繖浜涚己闄锋槸鍥犱负缂轰箯QA閮ㄩ棬鐩戠銆備綘浠殑鍥炲鏄笉鍏呭垎鐨勶紝鍥犱负浣犱滑鏈兘瑙i噴涓轰綍浣犱滑璐ㄩ噺閮ㄩ棬鏈兘纭繚鍚屾璁板綍鎴栧疄鏂藉厖鍒嗙洃绠°€?/span>

Data Integrity Remediation 鏁版嵁瀹屾暣鎬у讥琛ユ帾鏂?/span>

Significant findingsin this letter indicate that your quality unit is not able to fully exerciseits authority and/or responsibilities. Your firm must provide the quality unitwith the appropriate authority, sufficient resources, and qualified staff to carry out its responsibilities and consistently ensure drug quality. 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.

姝ゅ嚱涓殑涓ラ噸缂洪櫡鏄剧ず浣犱滑鐨勮川閲忛儴闂ㄤ笉鑳藉叏闈㈠饱琛岃亴鏉冦€備綘浠叕鍙稿繀椤讳负璐ㄩ噺閮ㄩ棬鎻愪緵閫傚綋鐨勬潈鍔涖€佸厖鍒嗙殑璧勬簮鍜屾湁璧勮川鐨勪汉鍛樻潵灞ヨ鍏惰亴璐o紝鎸佺画纭繚鑽搧璐ㄩ噺銆備綘浠殑璐ㄩ噺浣撶郴涓嶈兘鍏呭垎纭繚鏁版嵁鐨勫噯纭€у拰瀹屾暣鎬э紝鏃犳硶鏀寔浣犱滑鐢熶骇鐨勮嵂鍝佺殑瀹夊叏鎬с€佹湁鏁堟€у拰璐ㄩ噺銆傛垜浠己鐑堝缓璁綘浠仒璇锋湁璧勮川鐨勯【闂潵鍗忓姪浣犱滑杩涜寮ヨˉ銆?/span>

In response to this letter, provide the following.

鍦ㄥ洖澶嶆鍑芥椂锛屾彁渚涗互涓嬭祫鏂欙細

A. A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include: 涓€浠藉鏁版嵁璁板綍鍜屾姤鍛婁笉鍑嗙‘鎬х▼搴︾殑鍏ㄩ潰璋冩煡銆備綘浠殑璋冩煡搴斿寘鎷?/span>

  A detailed investigation protocol and methodology; a summary of all laboratories,manufacturing operations, and systems to be covered by the assessment; and ajustification for any part of your operation that you propose to exclude.

  璇︾粏鐨勮皟鏌ユ柟妗堝拰鏂规硶瀛︼紱瀵硅瘎浼版墍瑕嗙洊鐨勬墍鏈夊寲楠屽銆佺敓浜ф搷浣滃拰绯荤粺鐨勬€荤粨锛屼互鍙婂浣犱滑鎰忓湪鎺掗櫎鐨勬搷浣滀腑鎵€鏈夐儴鍒嗙殑璁鸿瘉銆?/span>

  Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.

  涓庣幇鏈夌殑鍜屽凡绂昏亴鐨勫憳宸ヨ繘琛岄潰璋堬紝鎵惧嚭鏁版嵁涓嶅噯纭殑琛ㄧ幇銆佽寖鍥淬€佹牴鏈師鍥犮€傛垜浠缓璁繖浜涢潰璋堢敱涓€涓湁璧勮川鐨勭涓夋柟鏉ュ疄鏂姐€?/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’s operations in which you discovered data integrity lapses.

  浣犱滑宸ュ巶鏁版嵁瀹屾暣鎬х己闄风殑绋嬪害鐨勮瘎浼般€傝瘑鍒嚭鐪佺暐銆佷慨鏀广€佸垹闄ゃ€佽褰曢攢姣併€佷笉鍚屾璁板綍濉啓鍜屽叾瀹冪己闄枫€傛弿杩颁綘浠伐鍘傛搷浣滀腑鍙戠幇鏁版嵁瀹屾暣鎬ч棶棰樼殑鎵€鏈夐儴鍒嗐€?/span>

  A comprehensive retrospective evaluation of the nature of the testing, manufacturing and other data 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.

  涓€浠藉鏁版嵁瀹屾暣鎬х己闄风姸鍐电殑鍏ㄩ潰鍥為【鎬ц瘎浼般€傛垜浠缓璁敱涓€涓湁璧勮川鐨勭涓夋柟閲屽叿鏈夎棰嗗煙涓撲笟姘村钩鐨勪笓瀹惰瘎浼版墍鏈夋暟鎹畬鏁存€ч棶棰樸€?/span>

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.

瀵逛綘浠嵂鍝佽川閲忎腑鎵€鍙戠幇鐨勪笉鍚堟牸鎯呭喌鐨勬綔鍦ㄥ奖鍝嶇殑褰撳墠椋庨櫓璇勪及銆備綘浠殑璇勪及搴斿寘鎷敱浜庡彈鍒版暟鎹畬鏁存€ч棶棰樺奖鍝嶇殑鑽搧鏀捐瀵艰嚧鐨勬偅鑰呴闄╃殑鍒嗘瀽锛屼互鍙婃寔缁繍钀ユ墍鍏锋湁鐨勯闄┿€?/span>

C. A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:

浣犱滑鍏徃鐨勭鐞嗙瓥鐣ワ紝鍖呮嫭浣犱滑鍏ㄧ悆CAPA璁″垝璇︾粏鎯呭喌銆備綘浠殑绛栫暐搴斿寘鎷細

  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.

  璇︾粏鐨?/span>CA璁″垝锛屾弿杩颁綘浠浣曠‘淇濅綘浠敓鎴愮殑鎵€鏈夋暟鎹殑鍙潬鎬у拰瀹屾暣鎬э紝鍖呮嫭鍒嗘瀽鏁版嵁銆佺敓浜ц褰曞拰鎵€鏈夋彁浜ょ粰FDA鐨勬暟鎹€?/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.

  涓€浠藉畬鏁寸殑鎻忚堪浣犱滑鏁版嵁瀹屾暣鎬ч棶棰樼殑鏍规湰鍘熷洜鐨勬弿杩帮紝鍖呮嫭璁ゅ畾褰撳墠琛屽姩璁″垝鐨勮寖鍥村拰娣卞害涓庤皟鏌ュ拰椋庨櫓璇勪及鍙戠幇鐩哥О鐨勮瘉鎹€傝鏄庢槸鍚﹀鏁版嵁瀹屾暣鎬ч棶棰樻壙鎷呰矗浠荤殑涓汉浠嶆湁鑳藉姏瀵逛綘鍏徃瀵?/span>CGMP鐩稿叧鎴栬嵂鐗╁簲鐢ㄦ暟鎹骇鐢熷奖鍝嶃€?/span>

  Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality 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.

  涓存椂鎺柦锛屾弿杩颁綘浠凡閲囧彇鐨勮鍔紝鎴栧嵆灏嗛噰鍙栫敤浠ヤ繚鎶ゆ偅鑰呯‘淇濅綘浠嵂鍝佽川閲忕殑鍔姏锛屼緥濡傞€氱煡浣犱滑鐨勫鎴枫€佸彫鍥炰骇鍝併€佸疄鏂介澶栨祴璇曘€佸悜绋冲畾鎬ц瘯楠岃鍒掍腑澧炲姞鎵规浠ョ‘淇濈ǔ瀹氭€с€佽嵂鍝佺敵鎶ヨ鍔ㄤ互鍙婂姞寮烘姇璇夌洃娴嬨€?/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’s data.

  闀挎湡鎺柦锛屽叾涓弿杩版墍鏈夊鐢ㄤ互纭繚浣犱滑鍏徃鏁版嵁瀹屾暣鎬х殑绋嬪簭銆佹祦绋嬨€佹柟娉曘€佹帶鍒躲€佺郴缁熴€佺鐞嗙洃绠″拰浜哄姏璧勬簮锛堜緥濡傚煿璁€佸憳宸ユ彁楂橈級鐨勫讥琛ュ拰鎻愬崌銆?/span>

  A status report forany of the above activities already underway or completed.

  瀵逛笂杩版椿鍔ㄥ凡寮€灞曟垨宸茬粡瀹屾垚鐨勭姸鎬佹姤鍛娿€?/span>

Conclusion 缁撹

Deviations cited inthis 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.

姝ゅ嚱涓墍寮曠敤鐨勮繚瑙勫苟涓嶆槸鍏ㄩ儴銆備綘浠湁璐d换瀵硅繖浜涘亸宸繘琛岃皟鏌ワ紝纭畾鍘熷洜锛岄槻姝㈠叾鍐嶆鍙戠敓锛岄槻姝㈠叾瀹冨亸宸殑鍙戠敓銆?/span>

FDA placed your firm on Import Alert 66-40 on March 1, 2018.

FDA宸蹭簬2018骞?/span>3鏈?/span>1鏃ュ皢浣犲叕鍙告斁鍦ㄤ簡杩涘彛绂佷护66-40娓呭崟涓€?/span>

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.

鍦ㄨ吹鍏徃鏈兘瀹屾垚鎵€鏈夊亸宸籂姝e苟涓旂敱鎴戜滑纭浣犱滑绗﹀悎CGMP涔嬪墠锛?/span>FDA鍙兘浼氭悂缃墍鏈夊皢浣犲叕鍙稿垪涓鸿嵂鍝佺敓浜х殑鏂扮敵鎶ュ拰澧炶ˉ鐢虫姤鐨勬壒鍑嗐€?/span>

Failure to correctthese deviations may also result in FDA refusing admission of articles manufactured at Jilin Shulan Synthetic Pharmaceutical Co., Ltd., at No. 2066 People’s Main Road, Shulan City, Jilin Province, into the United States undersection 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, in that the methodsand controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C.351(a)(2)(B).

鏈兘绾犳杩欎簺鍋忓樊鍙兘杩樹細瀵艰嚧FDA渚濇嵁FDCA绗?/span>801(a)(3)鏉″拰21 U.S.C. 381(a)(3)鎷掔粷鎺ュ彈鍦ㄤ笂杩板湴鍧€鐢熶骇鐨勪骇鍝佽繘鍏ョ編鍥姐€?/span>

After you receivethis 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 cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.

鍦ㄦ敹鍒版鍑藉悗锛岃鍦?/span>15涓伐浣滄棩鍐呭洖澶嶈嚦鏈姙鍏銆傚湪鍥炲涓鏄庤嚜浠庢鏌ュ悗锛屼綘浠仛浜嗗摢浜涘伐浣滄潵绾犳浣犱滑鐨勫亸宸紝闃叉鍏跺啀娆″彂鐢熴€傚鏋滀笉鑳藉湪15涓伐浣滄棩鍐呭畬鎴愮籂姝f帾鏂斤紝璇存槑寤惰繜鐨勫師鍥犱互鍙婂畬鎴愯鍒掋€?/span>

Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov or mail your reply to:

 

Mr. Lixin (Leo) Xu

Compliance Officer, U.S.Food and Drug Administration

White Oak Building51, Room 4212, 10903 New Hampshire Avenue

Silver Spring, MD20993, USA

 

Please identify yourresponse with FEI 3003091092.

 

Sincerely,

/s/

Francis Godwin, ActingDirector

Office ofManufacturing Quality, Office of Compliance, Center for Drug Evaluation andResearch

锛堟湰鏂囨潵婧愶細钂插叕鑻?锛?

(璐d换缂栬緫锛氬瓙璞?

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