Dihydrocodeine Tartrate

来源：青海药监局     整理：wangxinglai2004近日，青海药监局发布了两则行政处罚通知，两药企在有因检查、专项检查过程中被发现生产质量管理体系严重偏离GMP，检查结论为不符合要求、被处罚。1、青海制药有限公司青海制药有限公司其前身青海制药厂始建于1958年5月，于2000年更名为青海制药有限公司，是国家麻醉药品生产基地、生产范围包括麻醉药品和精神药品，拥有化学原料药及制剂相关生产线，本次在国家局组织的有因检查过程中，发现生产质量管理体系严重偏离GMP要求，不符合要求，被处罚。行政处罚文书号：青药监罚〔2023〕3号案件名称：青海制药有限公司严重违反药品生产质量管理规范案违法企业名称:青海制药有限公司主要违法事实：国家药监局组织的有因检查中，认为其生产质量管理体系严重偏离GMP要求，综合评定结论为不符合要求。违反了《中华人民共和国药品管理法》（2019年修订）第四十三条规定。行政处罚的种类和依据：依据《中华人民共和国药品管理法》（2019年修订）第一百二十六条规定，处以罚款。编语第一百二十六条 除本法另有规定的情形外，药品上市许可持有人、药品生产企业、药品经营企业、药物非临床安全性评价研究机构、药物临床试验机构等未遵守药品生产质量管理规范、药品经营质量管理规范、药物非临床研究质量管理规范、药物临床试验质量管理规范等的，责令限期改正，给予警告；逾期不改正的，处十万元以上五十万元以下的罚款；情节严重的，处五十万元以上二百万元以下的罚款，责令停产停业整顿直至吊销药品批准证明文件、药品生产许可证、药品经营许可证等，药物非临床安全性评价研究机构、药物临床试验机构等五年内不得开展药物非临床安全性评价研究、药物临床试验，对法定代表人、主要负责人、直接负责的主管人员和其他责任人员，没收违法行为发生期间自本单位所获收入，并处所获收入百分之十以上百分之五十以下的罚款，十年直至终身禁止从事药品生产经营等活动。对照法条，因为说的是严重偏离所以一定是情节严重的情况，到底本次检查发现有多严重偏离GMP，恐怕只能自行脑补了；虽然处罚只说了罚款，但是小编猜测停产整顿是在所难免的，尤其是生产麻醉和精神药品的企业，至于相关从业人员是否有罚金不得而知，但是对比过往企业处罚案例，恐怕该企业主要负责人也是难逃法网；对于药企的同仁们只能说从业风险警钟长鸣与君共勉，过往案例整理如下：1、辽宁省2022年9月5日辽宁省药监局发布1则行政处罚通知，辽宁可济药业有限公司未遵守药品生产质量管理规范，被处于125万元罚款，责令停产停业整顿1个月，同时该公司生产、质量负责人也被处罚。没收企业生产负责人张某3918.22元，并处罚款1175.47元，罚没款合计5093.69元；没收企业质量负责人兼质量受权人任某波3556.4元，并处罚款1066.92元，罚没款合计4623.32元。2、四川药监局2022年08月12日，四川药监局发布了1则行政处罚通知，成都芝芝药业有限公司及该司生产负责人李贵权因严重违反《药品生产质量管理规范》分别受到处罚，其中生产负责人被处以10禁业及罚金。没收李贵权违法行为发生期间自本公司所获收入195823元，并处所获收入22%的罚款43081元；禁止李贵权10年内从事药品生产经营活动。3、云南药监局2021年06月25日，云南药监局发布了1则行政处罚通知，云南龙发制药股份有限公司违反GMP改变生产工艺、编造生产记录生产被罚款2017.57567万元；停产停业整顿；主要负责人禁止十年内从事药品生产经营等活动。公司负责人、生产负责人罚款、禁止十年内从事药品生产经营等活动。没收个人违法所得、罚款企业生产地址和生产范围（正本）：青海省西宁市城北区祁连路469号：小容量注射剂，口服溶液剂，原料药，片剂，糖浆剂，麻醉药品，精神药品***生产地址和生产范围（副本）：青海省西宁市城北区祁连路469号：小容量注射剂，口服溶液剂，原料药(盐酸丁丙诺啡、硫酸吗啡、那可丁、盐酸可卡因、盐酸吗啡、阿片粉、盐酸乙基吗啡、盐酸罂粟碱、盐酸哌替啶、盐酸阿扑吗啡、磷酸可待因、氢溴酸烯丙吗啡、乳酸依沙吖啶、酒石酸双氢可待因、盐酸纳洛酮、盐酸美沙酮、盐酸甲氧那明(仅限注册文号申报))，片剂，糖浆剂，麻醉药品，精神药品***2、青海瑞成药业（集团）有限公司青海瑞成药业（集团）有限公司是一家中药制剂生产企业，在本次青海省药监局组织的专项检查过程中，发现生产质量管理体系严重偏离GMP要求，不符合要求，被处罚。行政处罚文书号：青药监罚〔2023〕4号案件名称：青海瑞成药业（集团）有限公司严重违反药品生产质量管理规范案违法企业名称:青海瑞成药业（集团）有限公司主要违法事实：青海省药监局在专项检查中，认为其生产质量管理体系严重偏离GMP要求，综合评定为不符合要求。违反了《中华人民共和国药品管理法》（2019年修订）第四十三条规定。行政处罚的种类和依据：依据《中华人民共和国药品管理法》（2019年修订）第一百二十六条规定，处以罚款。编语第一百二十六条 除本法另有规定的情形外，药品上市许可持有人、药品生产企业、药品经营企业、药物非临床安全性评价研究机构、药物临床试验机构等未遵守药品生产质量管理规范、药品经营质量管理规范、药物非临床研究质量管理规范、药物临床试验质量管理规范等的，责令限期改正，给予警告；逾期不改正的，处十万元以上五十万元以下的罚款；情节严重的，处五十万元以上二百万元以下的罚款，责令停产停业整顿直至吊销药品批准证明文件、药品生产许可证、药品经营许可证等，药物非临床安全性评价研究机构、药物临床试验机构等五年内不得开展药物非临床安全性评价研究、药物临床试验，对法定代表人、主要负责人、直接负责的主管人员和其他责任人员，没收违法行为发生期间自本单位所获收入，并处所获收入百分之十以上百分之五十以下的罚款，十年直至终身禁止从事药品生产经营等活动。对照法条，因为说的是严重偏离所以一定是情节严重的情况，虽然说GMP是否适用于中药行业业界一直存在争议、中药企业的GMP管理在制药行业中属于最底层也是普遍现象，但这并不是违法违规的理由；尤其是出现了严重偏离，这只能说明企业主观存在违法违规的强烈意愿，对也中药行业从业人员来说还是要警醒灰色边缘和底线的区别，以免引火烧身出现从业人员被处罚案例。企业生产地址和生产范围（正本）：西宁市经济技术开发区东新路18号：硬胶囊剂，洗剂***生产地址和生产范围（副本）：西宁市经济技术开发区东新路18号：硬胶囊剂，洗剂(灌肠液)***

CINCINNATI, Ohio, June 14, 2023 (GLOBE NEWSWIRE) -- Blue Water Biotech, Inc. (Nasdaq: BWV), a biotechnology company spanning multiple sectors, today announced the signing of an Asset Purchase Agreement (the “Agreement”) with WraSer, LLC and Xspire Pharma, LLC (together, “WraSer”) for the purchase of six FDA-approved assets across multiple indications, including cardiology, otic infections, and pain management (the “WraSer Assets”). Under the terms of the Agreement, Blue Water Biotech, Inc. (“Blue Water” or the “Company”) will purchase the WraSer Assets for a total of $8.5 million cash consideration payable in three tranches: at signing, upon closing and within one year of closing. In addition, WraSer shall receive 1.0 million restricted shares of Blue Water’s common stock on the closing date. The closing of the transaction is subject to certain customary closing conditions, as well as WraSer’s delivery of 2022 audited financial statements for WraSer’s parent company, Legacy-Xspire Holdings, LLC, to Blue Water. Blue Water will assume management of the WraSer Assets during the audit period. The audited financial statements will be publicly filed promptly after completion of the audit. The assets under the Agreement include the patents related to ZONTIVITY®, a medication for the reduction of thrombotic cardiovascular events in patients with a history of myocardial infarction (“MI”) or with peripheral arterial disease (“PAD”), as well as additional products for the treatment of hypertension, otitis media, and pain management. ZONTIVITY®, a once daily pill approved in 2014, is a first-in-class protease activated receptor-1 inhibitor which mediates the cellular effects of thrombin to reduce the risk of major adverse cardiovascular events and major adverse limb events when used in addition to aspirin and/or clopidogrel in patients with PAD. In a pivotal Phase 3 clinical trial, ZONTIVITY® was shown to reduce the rate of a combined endpoint of cardiovascular death, MI, stroke, and urgent coronary revascularization, with 13,186 patients evaluated for safety and 2,187 patients treated with ZONTIVITY® for more than three years. This Agreement also includes the purchase of licenses to market and distribute two antibiotic otic products, OTOVEL® and CETRAXAL®, and their authorized generics currently marketed and distributed by WraSer. OTOVEL®, ciprofloxacin and fluocinolone acetonide, is used to treat acute otitis media (“AOM”) in children 6 months of age and older who have a tiny cylinder tube, known as a tympanostomy tube, inserted in their eardrum that prevents excess fluid in the middle ear. While tympanostomy tubes are typically placed as a result of multiple ear infections within a short timeframe, they do not prevent AOM, and one study found that over 80% of children had an episode of AOM within 18 months of tympanostomy tube placement. OTOVEL®, which contains an antibiotic to treat the infection and an anti-inflammatory to reduce pain and swelling, is the first and only antibiotic and steroid ear drop available in single use vials. In two clinical studies of pediatric patients with AOM with tympanostomy tubes, children who took OTOVEL® were clear of otorrhea in a median of 3.75 and 4.94 days, whereas those on antibiotic alone were not clear until a median of 7.69 and 6.83 days. The clinical studies also showed that the combination of medicines in OTOVEL® had similar side effects as the separate medicines. Blue Water is currently developing a vaccine to prevent acute otitis media regardless of tympanostomy tube insertion, and the Company intends to leverage this experience and expertise in the future commercialization and marketing for OTOVEL®. The second otic product included in the Agreement, CETRAXAL®, ciprofloxacin otic solution available in individual unit dosing vials, is used to treat otitis externa, more commonly called swimmer’s ear, in children with an intact tympanic membrane. Swimmer’s ear is characterized by redness or swelling, irritation, or infection of the outer ear canal and can be very painful if left untreated, primarily impacting children that spend a lot of time in the water. In addition to ZONTIVITY® and otic products, Blue Water will purchase the licensed rights to market and distribute CONJUPRI®, a calcium channel blocker that can be used alone or in combination with other antihypertensive agents for the treatment of hypertension to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and MIs. Additionally, Blue Water will purchase two pain medications, TREZIX™ (acetaminophen, caffeine, and dihydrocodeine bitartrate), for the treatment of moderate to moderately severe pain for which non-opioids are inadequate, and NALFON® (fenoprofen calcium), for relief of mild to moderate pain in adults, as well as relief of the signs and symptoms related to rheumatoid arthritis and osteoarthritis. “The team at WraSer has developed a strong pipeline across cardiology, otic products, as well as pain management, and we are thrilled to add these assets to our portfolio at Blue Water,” said Joseph Hernandez, Chairman and Chief Executive Officer of Blue Water. “In recent months, we have invested significant efforts to build our corporate infrastructure to support our transition into a commercial-stage company, including key hires with extensive experience in commercial operations. We are confident that bringing these assets into our portfolio will strengthen Blue Water’s financial position, allow us to advance our robust vaccine pipeline, and help millions of patients around the world receive proper access to critical treatments.” “Our products have been developed to provide patients with life changing, and potentially lifesaving, treatments, and we are happy to partner with Blue Water to continue this mission,” said Greg Stokes, Chief Executive Officer of WraSer. “Their management team has extensive experience with commercial products across a wide range of treatment areas, and we look forward to supporting them through this transition, as well as seeing the continued success of these products for patients in need.” Blue Water, with its recent purchase of ENTADFI® and through this acquisition, has established itself as a commercial-stage biopharmaceutical company. The Company intends to leverage its robust management and commercial team curated to maximize sales and success of all products acquired from the Agreement, as well as ENTADFI®, to further develop corporate infrastructure and to support and its extensive vaccine pipeline. About Blue Water Biotech Blue Water Biotech, Inc. is a biological and pharmaceutical technology company focused on developing and providing transformational therapies to address significant health challenges globally. Headquartered in Cincinnati, OH, the Company owns ENTADFI®, an FDA-approved, once daily pill that combines finasteride and tadalafil for the treatment of benign prostatic hyperplasia. This combination allows men to receive treatment for their symptoms of benign prostatic hyperplasia without the negative sexual side effects typically seen in patients on finasteride alone. The Company also has a robust vaccine pipeline. Blue Water holds the rights to proprietary technology developed at the University of Oxford, Cincinnati Children’s Hospital Medical Center, St. Jude Children’s Hospital, and The University of Texas Health Science Center at San Antonio. Blue Water is developing a Streptococcus pneumoniae vaccine candidate, designed to specifically prevent highly infectious middle ear infections, known as AOM, in children, and prevention of pneumonia in the elderly. The Company is also developing a universal flu vaccine that will provide protection from all virulent strains in addition to licensing a novel norovirus S&P nanoparticle versatile virus-like particle vaccine platform from Cincinnati Children’s to develop vaccines for multiple infectious diseases, including Marburg and monkeypox, among others. Additionally, the Company is developing a Chlamydia vaccine candidate with UT Health Science Center San Antonio to prevent infection and reduce the need for antibiotic treatment associated with contracting Chlamydia disease. For more information about Blue Water, visit www.bwbioinc.com. Forward-Looking Statements Certain statements in this press release are forward-looking within the meaning of the Private Securities Litigation Reform Act of 1995. These statements may be identified by the use of forward-looking words such as “anticipate,” “believe,” “forecast,” “estimate,” “expect,” and “intend,” among others. These forward-looking statements are based on Blue Water’s current expectations and actual results could differ materially. There are a number of factors that could cause actual events to differ materially from those indicated by such forward-looking statements. These factors include, but are not limited to, risks related to Blue Water’s ability to realize the benefits of its acquisitions of ENTADFI®, ZONTIVITY®, OTOVEL®, CETRAXAL®, CONJUPRI®, TREZIX™ and NALFON®, risks related to Blue Water’s ability to expand its business scope, commercialize ENTADFI® and integrate the assets and commercial operations acquired from WraSer into Blue Water’s business, risks related to the development of Blue Water’s vaccine candidates; the failure to obtain FDA clearances or approvals and noncompliance with FDA regulations; delays and uncertainties caused by the global COVID-19 pandemic; risks related to the timing and progress of clinical development of our product candidates; our need for additional financing; uncertainties of patent protection and litigation; uncertainties of government or third party payor reimbursement; limited research and development efforts and dependence upon third parties; and substantial competition. As with any vaccine under development, there are significant risks in the development, regulatory approval and commercialization of new products. Blue Water does not undertake an obligation to update or revise any forward-looking statement. Investors should read the risk factors set forth in Blue Water’s Annual Report on Form 10-K, filed with the Securities and Exchange Commission (the “SEC”) on March 9, 2023 and periodic reports filed with the SEC on or after the date thereof. All of Blue Water’s forward-looking statements are expressly qualified by all such risk factors and other cautionary statements. The information set forth herein speaks only as of the date thereof. Media Contact Information:Blue Water Media RelationsTelephone: (646) 942-5591 Email: Nic.Johnson@russopartnersllc.com Investor Contact Information:Blue Water Investor RelationsEmail: investors@bwbioinc.com A photo accompanying this announcement is available at https://www.globenewswire.com/NewsRoom/AttachmentNg/d66c95d4-fd36-4f08-9971-f362edf2a98a