{"id":87120,"date":"2019-04-19T00:00:50","date_gmt":"2019-04-23T03:48:04","guid":{"rendered":"http:\/\/www.05921.net\/index.php\/87120\/"},"modified":"2019-04-23T11:48:09","modified_gmt":"2019-04-23T03:48:09","slug":"8f4fac64e7","status":"publish","type":"post","link":"https:\/\/www.05921.net\/index.php\/87120\/","title":{"rendered":"FDA\u8b66\u544a\u4fe1\uff1a\u9a6c\u6765\u897f\u4e9a Luen Fook Medicine Sdn.,Bhd"},"content":{"rendered":"
\n

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

Warning Letter <\/span><\/strong>320-19-18      April 4, 2019<\/span><\/span><\/p>\n

Mr. Tham Chew Thor<\/span><\/p>\n

Director, Luen Fook Medicine Sdn., Bhd.<\/span><\/p>\n

203 Henderson Road #05-08\/09 (Wing B), HendersonIndustrial Park 159546, Singapore<\/span><\/p>\n

 <\/span><\/p>\n

Dear Mr. Tham Chew Thor:<\/span><\/p>\n

The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Luen Fook Medicine Sdn., Bhd., at Taman Perindustrian Sri Plentong, No 6, Jalan Sri Plentong 5, Masai, Johor,81750 Malaysia, from December 10 to 14, 2018.<\/span><\/p>\n

\u7f8e\u56fd<\/span>FDA<\/span>\u4e8e<\/span>2018<\/span>\u5e74<\/span>12<\/span>\u6708<\/span>10<\/span>\u65e5\u81f3<\/span>14<\/span>\u65e5\u68c0\u67e5\u4e86\u4f60\u4eec\u4f4d\u4e8e\u9a6c\u6765\u897f\u4e9a\u7684<\/span>Luen Fook Medicine Sdn.,Bhd.<\/span>\u751f\u4ea7\u573a\u6240\u3002<\/span><\/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

\u672c\u8b66\u544a\u4fe1\u603b\u7ed3\u4e86\u5236\u5242\u751f\u4ea7\u4e25\u91cd\u8fdd\u53cd<\/span>CGMP<\/span>\u7684\u884c\u4e3a\u3002\u53c2\u89c1<\/span>21CFR<\/span>\u7b2c<\/span>210<\/span>\u4e0e<\/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 is 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\u5236\u5242\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

In addition, as formulated and labeled, African\u201cSEA-COCONUT\u201d Sore Throat Syrup is an unapproved new drug in violation of section 505(a) of the FD&C Act, 21 U.S.C. 355(a). Introduction of such aproduct into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. 331(d). This violation is described in more detailbelow. <\/span><\/p>\n

\u53e6\u5916\uff0c\u6839\u636e\u5176\u914d\u65b9\u548c\u6807\u8bc6\uff0c\u975e\u6d32\u201c\u6d77\u5e95\u6930\u201d\u6da6\u5589\u7cd6\u6d46\u662f\u4e00\u79cd\u672a\u7ecf\u6279\u51c6\u7684\u65b0\u836f\uff0c\u8fdd\u53cd\u4e86<\/span>FDCA<\/span>\u7b2c<\/span>505(a)<\/span>\u6761\u6b3e<\/span>21 U.S.C. 355(a)<\/span>\u3002\u5c06\u8be5\u4ea7\u54c1\u5f15\u5165\u5dde\u9645\u8d38\u6613\u662f<\/span>FDCA<\/span>\u7b2c<\/span>301(d)<\/span>\u6761\u6b3e<\/span>21 U.S.C. 331(d)<\/span>\u6240\u7981\u6b62\u7684\uff0c\u8be5\u8fdd\u89c4\u60c5\u51b5\u5c06\u5728\u4ee5\u4e0b\u5177\u4f53\u8bf4\u660e\u3002<\/span><\/span><\/p>\n

We reviewed your January 7, 2019, response indetail. Your response was inadequate because it did not provide sufficientdetail or evidence of corrective actions to bring your operations into compliance with CGMP.<\/span><\/p>\n

\u6211\u4eec\u5df2\u8be6\u7ec6\u5ba1\u6838\u4e86\u4f60\u516c\u53f8<\/span>2019<\/span>\u5e74<\/span>1<\/span>\u6708<\/span>7<\/span>\u65e5\u7684\u56de\u590d\u3002\u4f60\u4eec\u7684\u56de\u590d\u662f\u4e0d\u5145\u5206\u7684\uff0c\u56e0\u4e3a\u5176\u4e2d\u672a\u63d0\u4ea4\u8be6\u7ec6\u7684\u7ea0\u6b63\u63aa\u65bd\u4fe1\u606f\u6216\u8bc1\u636e\u4f7f\u5f97\u4f60\u4eec\u7684\u64cd\u4f5c\u7b26\u5408<\/span>CGMP<\/span>\u8981\u6c42\u3002<\/span><\/span><\/p>\n

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

\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

CGMP Violations CGMP<\/span><\/span><\/strong>\u8fdd\u89c4<\/span><\/strong><\/span><\/strong><\/span><\/p>\n

1.     Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)). <\/span><\/strong>\u4f60\u516c\u53f8\u672a\u5728\u653e\u884c\u524d\u5bf9\u6bcf\u6279\u5236\u5242\u8fdb\u884c\u9002\u5f53\u7684\u5b9e\u9a8c\u5ba4\u68c0\u6d4b\uff0c\u786e\u5b9a\u5176\u7b26\u5408\u836f\u54c1\u7684\u6700\u7ec8\u8d28\u91cf\u6807\u51c6\uff0c\u5305\u62ec\u6bcf\u79cd\u6d3b\u6027\u6210\u5206\u7684\u9274\u522b\u548c\u5242\u91cf\uff08<\/span><\/strong>21 CFR 211.165(a)<\/span><\/strong>\uff09\u3002<\/span><\/strong><\/span><\/strong><\/span><\/p>\n

You do not test your finished drug product, African \u201cSEA-COCONUT\u201d Sore Throat Syrup, to determine the identity and strength of the active ingredient prior to release.<\/span><\/p>\n

\u4f60\u4eec\u5728\u653e\u884c\u4e4b\u524d\u672a\u68c0\u6d4b\u4f60\u4eec\u5236\u5242\uff0c\u975e\u6d32\u201c\u6d77\u5e95\u6930\u201d\u6da6\u5589\u7cd6\u6d46\uff0c\u4ee5\u786e\u5b9a\u6d3b\u6027\u6210\u5206\u7684\u6027\u8d28\u548c\u6570\u91cf\u3002<\/span><\/p>\n

In response to this letter, provide a summary of results obtained from testing retain samples of all drug products within expiry that have been distributed in the United States. Include results for identity and strength of active ingredients, including any ingredient in your drug product that may have pharmacological activity, and all other appropriatechemical and microbial quality attributes. Also evaluate your formulation to identify all active ingredients intended to furnish pharmacological activity.<\/span><\/p>\n

\u5728\u56de\u590d\u6b64\u51fd\u65f6\uff0c\u8bf7\u63d0\u4ea4\u4e00\u4efd\u6240\u6709\u9500\u552e\u81f3\u7f8e\u56fd\u4ecd\u5728\u6709\u6548\u671f\u5185\u7684\u5236\u5242\u7559\u6837\u590d\u6d4b\u7ed3\u679c\u7684\u6c47\u603b\uff0c\u5305\u62ec\u6d3b\u6027\u6210\u5206\u9274\u522b\u548c\u5242\u91cf\uff0c\u5305\u62ec\u4f60\u4eec\u5236\u5242\u4e2d\u4efb\u4f55\u53ef\u80fd\u5177\u6709\u836f\u7269\u6d3b\u6027\u7684\u6210\u5206\uff0c\u4ee5\u53ca\u5176\u5b83\u9002\u5f53\u7684\u5316\u5b66\u548c\u5fae\u751f\u7269\u8d28\u91cf\u5c5e\u6027\u3002\u4ea6\u8bf7\u8bc4\u4f30\u4f60\u4eec\u7684\u914d\u65b9\u4ee5\u8bc6\u522b\u51fa\u6240\u6709\u610f\u5728\u63d0\u4f9b\u836f\u5b66\u6d3b\u6027\u7684\u6d3b\u6027\u6210\u5206\u3002<\/span><\/p>\n

 <\/span>2.     Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess, and your firm\u2019s quality control unit did not review and approve those procedures, including any changes (21 CFR 211.100(a)). <\/span><\/strong>\u4f60\u516c\u53f8\u672a\u5236\u8ba2\u4e66\u9762\u751f\u4ea7\u548c\u5de5\u827a\u63a7\u5236\u7a0b\u5e8f\uff0c\u8bbe\u8ba1\u7528\u4ee5\u786e\u4fdd\u4f60\u4eec\u751f\u4ea7\u7684\u836f\u54c1\u5177\u5907\u5176\u7406\u5f53\u5177\u5907\u6216\u58f0\u79f0\u7684\u9274\u522b\u3001\u5242\u91cf\u3001\u8d28\u91cf\u548c\u7eaf\u5ea6\uff0c\u5e76\u4e14\u4f60\u516c\u53f8\u8d28\u91cf\u90e8\u95e8\u5e76\u672a\u5ba1\u6838\u548c\u6279\u51c6\u8fd9\u4e9b\u7a0b\u5e8f\uff0c\u5305\u62ec\u5176\u4e2d\u6240\u6709\u53d8\u66f4\uff08<\/span><\/strong>21 CFR 211.100(a)<\/span><\/strong>\uff09\u3002<\/span><\/strong><\/span><\/strong><\/span><\/span><\/p>\n


<\/p>\n

Your firm failed to validate the manufacturing process for your African \u201cSEA-COCONUT\u201d Sore Throat Syrup. Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drug products. Process qualification studies determine whether an initial state of control has been established.<\/span><\/p>\n

\u4f60\u516c\u53f8\u672a\u80fd\u9a8c\u8bc1\u4f60\u4eec\u975e\u6d32\u201c\u6d77\u5e95\u6930\u201d\u6da6\u5589\u7cd6\u6d46\u7684\u751f\u4ea7\u5de5\u827a\u3002\u5de5\u827a\u9a8c\u8bc1\u662f\u8bc4\u4f30\u6574\u4e2a\u751f\u547d\u8fc7\u7a0b\u4e2d\u5de5\u827a\u7684\u8bbe\u8ba1\u5408\u7406\u6027\u548c\u53d7\u63a7\u72b6\u6001\u3002\u4e00\u4e2a\u751f\u4ea7\u5de5\u827a\u7684\u6bcf\u4e2a\u91cd\u8981\u9636\u6bb5\u5747\u5fc5\u987b\u8fdb\u884c\u6070\u5f53\u8bbe\u8ba1\uff0c\u5e76\u786e\u4fdd\u539f\u6599\u8f93\u5165\u3001\u4e2d\u95f4\u4f53\u548c\u5236\u5242\u6210\u54c1\u7684\u8d28\u91cf\u3002\u5de5\u827a\u786e\u8ba4\u7814\u7a76\u786e\u5b9a\u662f\u5426\u5efa\u7acb\u4e86\u521d\u59cb\u53d7\u63a7\u72b6\u6001\u3002<\/span><\/p>\n

In your response, you provided a validation master plan. However, it lacked adequate detail and only listed pieces of equipment that you intended to qualify as a part of your validation program.<\/span><\/p>\n

\u5728\u4f60\u4eec\u7684\u56de\u590d\u4e2d\uff0c\u4f60\u4eec\u63d0\u4ea4\u4e86\u4e00\u4efd\u9a8c\u8bc1\u4e3b\u8ba1\u5212\u3002\u4f46\u662f\uff0c\u8be5\u8ba1\u5212\u4e0d\u591f\u8be6\u7ec6\uff0c\u53ea\u662f\u5217\u51fa\u4e86\u4f60\u4eec\u51c6\u5907\u4f5c\u4e3a\u4f60\u4eec\u9a8c\u8bc1\u8ba1\u5212\u4e00\u90e8\u5206\u8fdb\u884c\u786e\u8ba4\u7684\u51e0\u53f0\u8bbe\u5907\u3002<\/span><\/p>\n

Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. SeeFDA\u2019s guidance for industry, Process Validation: General Principles andPractices<\/em>, at:https:\/\/www.fda.gov\/downloads\/drugs\/guidances\/ucm070336.pdf<\/span><\/span><\/span><\/p>\n

\u5546\u4e1a\u9500\u552e\u4e4b\u524d\u6709\u5fc5\u8981\u8fdb\u884c\u6210\u529f\u7684\u5de5\u827a\u786e\u8ba4\u7814\u7a76\u3002\u4e4b\u540e\u5219\u5e94\u5bf9\u5de5\u827a\u6027\u80fd\u548c\u4ea7\u54c1\u8d28\u91cf\u8fdb\u884c\u6301\u7eed\u8b66\u89c9\u76d1\u7ba1\uff0c\u4ee5\u786e\u4fdd\u4f60\u4eec\u5728\u4ea7\u54c1\u751f\u547d\u5468\u671f\u4e2d\u5747\u7ef4\u6301\u7a33\u5b9a\u7684\u751f\u4ea7\u64cd\u4f5c\u3002\u53c2\u89c1<\/span>FDA<\/span>\u884c\u4e1a\u6307\u5357\u201c\u5de5\u827a\u9a8c\u8bc1\uff1a\u901a\u5219\u4e0e\u89c4\u8303\u201d\u3002<\/span><\/span><\/p>\n

In response to this letter, provide a validation plan for ensuring a state of control throughout the product lifecycle. Include a timeline for performing appropriate process performance qualification for each of your drug products. Describe your program for monitoring batch-to-batch variation to ensure an ongoing state of control. Also include your process performance protocol(s) and your written procedures for qualification of equipment and facilities.<\/span><\/p>\n

\u5728\u56de\u590d\u672c\u51fd\u65f6\u8bf7\u63d0\u4ea4\u4e00\u4efd\u9a8c\u8bc1\u8ba1\u5212\uff0c\u786e\u4fdd\u5728\u6574\u4e2a\u4ea7\u54c1\u751f\u547d\u5468\u671f\u4e2d\u7684\u53d7\u63a7\u72b6\u6001\u3002\u5305\u62ec\u5bf9\u4f60\u4eec\u6bcf\u4e2a\u836f\u54c1\u5b9e\u65bd\u9002\u5f53\u7684\u5de5\u827a\u6027\u80fd\u786e\u8ba4\u7684\u65f6\u95f4\u8868\uff0c\u5728\u5176\u4e2d\u63cf\u8ff0\u4f60\u4eec\u76d1\u6d4b\u6279\u95f4\u6ce2\u52a8\u4ee5\u786e\u4fdd\u6301\u7eed\u53d7\u63a7\u72b6\u6001\u7684\u8ba1\u5212\u3002\u4ea6\u8bf7\u5305\u62ec\u4f60\u4eec\u7684\u5de5\u827a\u6027\u80fd\u65b9\u6848\u548c\u4e66\u9762\u7684\u8bbe\u5907\u4e0e\u8bbe\u65bd\u786e\u8ba4\u7a0b\u5e8f\u3002<\/span><\/p>\n

3.     Your firm failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and\/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)). <\/span><\/strong>\u4f60\u516c\u53f8\u672a\u80fd\u6309\u6070\u5f53\u7684\u65f6\u95f4\u95f4\u9694\u6e05\u6d01\u3001\u7ef4\u62a4\u548c\u6839\u636e\u836f\u54c1\u5c5e\u6027\u5728\u9002\u5f53\u65f6\u6d88\u6bd2\u548c<\/span><\/strong>\/<\/span><\/strong>\u6216\u706d\u83cc\u8bbe\u5907\u4e0e\u5de5\u5668\u5177\uff0c\u4ece\u800c\u9632\u6b62\u53ef\u80fd\u6539\u53d8\u836f\u54c1\u5b89\u5168\u6027\u3001\u9274\u522b\u3001\u5242\u91cf\u3001\u8d28\u91cf\u6216\u7eaf\u5ea6\u7684\u6545\u969c\u6216\u6c61\u67d3\u8d85\u51fa\u5b98\u65b9\u6216\u5176\u5b83\u65e2\u5b9a\u8981\u6c42\uff08<\/span><\/strong>21 CFR 211.67(a)<\/span><\/strong>\uff09\u3002<\/span><\/strong><\/span><\/strong><\/span><\/p>\n

You failed to perform cleaning validation for the equipment used in the production of your African \u201cSEA-COCONUT\u201d Sore Throat Syrup. In addition, your current cleaning procedures do not include a sanitizer. You clean and rinse only with (b)(4)<\/strong>.<\/span><\/p>\n

\u4f60\u4eec\u672a\u5bf9\u4f60\u4eec\u975e\u6d32\u201c\u6d77\u5e95\u6930\u201d\u6da6\u5589\u7cd6\u6d46\u751f\u4ea7\u6240\u7528\u8bbe\u5907\u8fdb\u884c\u6e05\u6d01\u9a8c\u8bc1\u3002\u53e6\u5916\uff0c\u4f60\u4eec\u5f53\u524d\u7684\u6e05\u6d01\u7a0b\u5e8f\u5e76\u672a\u5305\u62ec\u6d88\u6bd2\u5242\u3002\u4f60\u4eec\u4ec5\u4f7f\u7528\u4e86<\/span>XX<\/span>\u8fdb\u884c\u6e05\u6d01\u548c\u6dcb\u6d17\u3002<\/span><\/span><\/p>\n

In your response, provide the following. <\/span>\u5728\u4f60\u4eec\u7684\u56de\u590d\u4e2d\u8bf7\u63d0\u4ea4\u4ee5\u4e0b<\/span><\/span><\/p>\n