主体名称浙江仁康医药用品有限公司处罚决定书文号兰市监处罚﹝2025﹞22号处罚类别罚款;没收违法所得处罚决定时间2025-01-23处罚内容有下列情形之一的,由负责药品监督管理的部门责令改正,处1万元以上5万元以下罚款;拒不改正的,处5万元以上10万元以下罚款;情节严重的,责令停产停业,直至由原发证部门吊销医疗器械生产许可证、医疗器械经营许可证,对违法单位的法定代表人、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30%以上2倍以下罚款,5年内禁止其从事医疗器械生产经营活动:……(二)生产、经营说明书、标签不符合本条例规定的医疗器械;;罚款金额（万元）1.100000没收违法所得0.020000暂扣或吊销证照名称及编号-违法行为类型浙江仁康医药用品有限公司生产标签、说明书不符合规定的医疗器械案处罚依据《医疗器械监督管理条例》第八十八条第(二)项;违法事实主要违法事实:生产无中文标签的医疗器械行政处罚种类、依据、内容:根据《中华人民共和国行政处罚法》第二十八条第二款、《医疗器械监督管理条例》第八十八条第二项的规定,决定对当事人处理如下:一、责令改正;二、处罚款11000元;三、没收违法所得200元;以上罚没款共计11200元。行政处罚履行方式和期限:当事人自收到行政处罚决定书之日起十五日内,按照行政处罚决定书载明的履行方式履行。处罚机关兰溪市市场监督管理局处罚机关统一社会信用代码113307810931049759数据来源单位省市场监管局数据来源单位统一社会信用代码11330000MB19062420相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

主体名称宁波市海曙区一佰分大药房有限公司处罚决定书文号甬海市监处罚﹝2025﹞46号处罚类别警告;罚款;没收违法所得处罚决定时间2025-01-23处罚内容当事人超出许可的经营方式从事中药饮片配方经营活动的行为,违反了《药品经营和使用质量监督管理办法》第二十三条第一款之规定,属于药品经营企业未经批准擅自变更许可事项的违法行为。根据《药品经营和使用质量监督管理办法》第六十八条、《中华人民共和国药品管理法》第一百一十五条、《中华人民共和国行政处罚法》第三十三条第一款之规定,决定不予行政处罚。当事人未按规定凭处方销售处方药的行为,违反了《药品经营和使用质量监督管理办法》第四十二条第一款之规定,属于药品零售企业未按规定凭处方销售处方药的行为。执法人员已于2024年2月8日向当事人发放责令改正通知书,当事人已于当月完成整改。当事人将炒理枣仁冒充炒酸枣仁进行配方销售的行为,违反了《中华人民共和国药品管理法》第九十八条第一款、第二款第二项之规定,属于销售以非药品冒充药品或者以他种药品冒充此种药品的假药的违法行为。根据《中华人民共和国药品管理法》第一百一十六条、《中华人民共和国行政处罚法》第五条第二款和第二十八条第一款之规定,决定责令当事人改正违法行为,并减轻处罚如下:一、没收炒理枣仁112.24克;二、没收违法所得14519.03元;三、罚款73838.75元。罚没款合计88357.78元。罚款金额（万元）7.383875没收违法所得1.451903暂扣或吊销证照名称及编号-违法行为类型宁波市海曙区一佰分大药房有限公司销售假药案处罚依据《药品经营和使用质量监督管理办法》第七十二条第一款“药品零售企业有以下情形之一的,由药品监督管理部门责令限期改正;逾期不改正的,处五千元以上五万元以下罚款;造成危害后果的,处五万元以上二十万元以下罚款:(一)未按规定凭处方销售处方药的;”;《中华人民共和国药品管理法》第一百一十六条生产、销售假药的,没收违法生产、销售的药品和违法所得,责令停产停业整顿,吊销药品批准证明文件,并处违法生产、销售的药品货值金额十五倍以上三十倍以下的罚款;货值金额不足十万元的,按十万元计算;情节严重的,吊销药品生产许可证、药品经营许可证或者医疗机构制剂许可证,十年内不受理其相应申请;药品上市许可持有人为境外企业的,十年内禁止其药品进口。第一百一十八条对法定代表人、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三十以上三倍以下的罚款,终身禁止从事药品生产经营活动,并可以由公安机关处五日以上十五日以下的拘留。对生产者专门用于生产假药、劣药的原料、辅料、包装材料、生产设备予以没收。;违法事实主要违法事实:自2022年3月起,由于中药饮片炒酸枣仁的价格不断升高,为获取非法利润,当事人从“药师帮”网站上先后购入10批炒理枣仁,并在其使用的供应链管理系统“流通之星”中以“中药443酸枣仁(炒)”的名义进行入库,同时将炒理枣仁装入“炒酸枣仁”的包装袋,并放置于“炒酸枣仁”药斗中冒充炒酸枣仁对外进行销售。2024年2月1日,当事人在未取得中药饮片配方经营许可的情况下,擅自根据投诉举报人出具的(急)诊病历进行配药,共15副配方药,销售价格为820元。案发后,当事人于2024年3月停止中药饮片配方经营的行为。行政处罚种类、依据、内容:当事人超出许可的经营方式从事中药饮片配方经营活动的行为,违反了《药品经营和使用质量监督管理办法》第二十三条第一款之规定,属于药品经营企业未经批准擅自变更许可事项的违法行为。根据《药品经营和使用质量监督管理办法》第六十八条、《中华人民共和国药品管理法》第一百一十五条、《中华人民共和国行政处罚法》第三十三条第一款之规定,决定不予行政处罚。当事人未按规定凭处方销售处方药的行为,违反了《药品经营和使用质量监督管理办法》第四十二条第一款之规定,属于药品零售企业未按规定凭处方销售处方药的行为。执法人员已于2024年2月8日向当事人发放责令改正通知书,当事人已于当月完成整改。当事人将炒理枣仁冒充炒酸枣仁进行配方销售的行为,违反了《中华人民共和国药品管理法》第九十八条第一款、第二款第二项之规定,属于销售以非药品冒充药品或者以他种药品冒充此种药品的假药的违法行为。根据《中华人民共和国药品管理法》第一百一十六条、《中华人民共和国行政处罚法》第五条第二款和第二十八条第一款之规定,决定责令当事人改正违法行为,并减轻处罚如下:一、没收炒理枣仁112.24克;二、没收违法所得14519.03元;三、罚款73838.75元。罚没款合计88357.78元。行政处罚履行方式和期限:当事人自收到行政处罚决定书之日起十五日内,按照行政处罚决定书载明的履行方式履行。处罚机关宁波市海曙区市场监督管理局处罚机关统一社会信用代码11330203309059836N数据来源单位省市场监管局数据来源单位统一社会信用代码11330000MB19062420相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

主体名称常山县百信药店有限公司处罚决定书文号常市监处罚﹝2025﹞14号处罚类别罚款;没收违法所得处罚决定时间2025-01-23处罚内容没收药品、生产专用设备及原料和违法所得,并处罚款;情节严重的,责令停产停业整顿直至吊销药品批准证明文件、许可证。生产、销售的中药饮片不符合药品标准,尚不影响安全性、有效性的,责令限期改正,警告;可以处罚款。生产、销售劣药且情节严重的,对相关责任人员,没收违法行为发生期间自本单位所获收入,并处罚款,终身禁止从事药品生产经营活动,并可以由公安机关处拘留。;罚款金额（万元）1.000000没收违法所得0.120000暂扣或吊销证照名称及编号-违法行为类型常山县百信药店有限公司销售劣药案处罚依据《中华人民共和国药品管理法》第一百一十七条生产、销售劣药的,没收违法生产、销售的药品和违法所得,并处违法生产、销售的药品货值金额十倍以上二十倍以下的罚款;违法生产、批发的药品货值金额不足十万元的,按十万元计算,违法零售的药品货值金额不足一万元的,按一万元计算;情节严重的,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、药品经营许可证或者医疗机构制剂许可证。生产、销售的中药饮片不符合药品标准,尚不影响安全性、有效性的,责令限期改正,给予警告;可以处十万元以上五十万元以下的罚款。第一百一十八条生产、销售劣药且情节严重的,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三十以上三倍以下的罚款,终身禁止从事药品生产经营活动,并可以由公安机关处五日以上十五日以下的拘留。对生产者专门用于生产假药、劣药的原料、辅料、包装材料、生产设备予以没收。;违法事实主要违法事实:2024年9月4日,被处罚人常山县百信药店有限公司在浙江省衢州市常山县天马街道文峰西路16号销售劣药。行政处罚种类、依据、内容:当事人销售劣药的行为违反了《中华人民共和国药品管理法》第九十八条第三款第三项、第四项之规定,依据《中华人民共和国药品管理法》第一百一十七条第一款之规定,本局决定对当事人处罚如下:一.没收炮山甲55克;二.没收违法所得壹仟贰佰圆整(¥1200.00);三.罚款人民币壹万圆整(¥10000.00)。以上二、三两项,合计人民币壹万壹仟贰佰圆整(¥11200.00),上缴国库。行政处罚履行方式和期限:当事人自收到行政处罚决定书之日起十五日内,按照行政处罚决定书载明的履行方式履行。处罚机关常山县市场监督管理局处罚机关统一社会信用代码11330822313526820F数据来源单位省市场监管局数据来源单位统一社会信用代码11330000MB19062420相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

内容提要英国发布贝组替凡患者警示信息以降低缺氧相关不良反应的风险欧洲经评估认为目前可用的证据不支持多西环素与自杀风险的相关性加拿大评估达沙替尼致儿童发育迟缓的潜在风险丹麦药品管理局就司美格鲁肽导致罕见眼部疾病的疑似风险提交欧洲药品管理局审议　　国家药品不良反应监测中心　　国家药品监督管理局药品评价中心　　http://www.cdr-adr.org.cn　　　　　英国发布贝组替凡患者警示信息以降低缺氧相关不良反应的风险　　2024年11月，英国默沙东药厂（Merck Sharp & Dohme (UK) Limited (MSD)）发布贝组替凡（belzutifan，商品名Welireg）直接与医务人员沟通的患者警示信息卡，提供风险最小化资料以尽量减少缺氧相关不良反应的风险。主要包括以下几个方面内容：　　贝组替凡适用于治疗不适合或不希望进行局部手术的患有von Hippel-Lindau(VHL)综合征相关肾细胞癌(RCC)、中枢神经系统(CNS)血管母细胞瘤或胰腺神经内分泌肿瘤(pNET)的成年患者。　　作为与英国药品和健康产品管理局（MHRA）达成风险管理计划协议的一部分，应向所有处方贝组替凡的患者提供患者警示卡，专门用来提供与治疗相关缺氧风险的指导。　　●贝组替凡可引起严重缺氧，可能需要停药、氧气治疗（氧疗）或住院治疗。　　●在开始使用贝组替凡治疗前和治疗过程中，应定期使用脉搏血氧仪监测患者的血氧饱和度，在治疗的最初6个月监测频率要更高些。　　●如果出现2级缺氧，应考虑氧气治疗并考虑继续或停止使用贝组替凡治疗。如果缺氧消退，应以减少的剂量重新开始使用贝组替凡。　　●对于3级缺氧患者，应暂停使用贝组替凡，治疗缺氧，并考虑降低贝组替凡使用剂量。如果3级缺氧持续复发，应停用贝组替凡。　　●对于4级缺氧，应永久停止使用贝组替凡治疗。　　持有人要求开处方的临床医生确保在治疗开始后为所有患者提供如钱包大小的患者警示卡，并建议他们始终随身携带。　　（英国MHRA网站）　　原文链接：https://assets.publishing.service.gov.uk/media/6759c3a64cbda57cacd34717/1_Welireg_Final.pdf　　欧洲经评估认为目前可用的证据不支持多西环素与自杀风险的相关性　　2024年11月29日，欧洲药品管理局（EMA）网站发布消息，药物警戒风险评估委员会（PRAC）得出结论认为，目前可用的证据不足以确定抗生素多西环素的使用与自杀风险之间存在因果关系。　　多西环素是一种广谱抗生素，广泛用于治疗由细菌引起的各种感染，如痤疮、尿路和下呼吸道感染、牙科感染和皮肤感染，还用于预防某些感染的发展，如疟疾。　　根据向芬兰国家主管当局报告的病例，以及向欧洲可疑不良反应报告数据库（EudraVigilance）报告的其他病例和医学文献，提出了关于多西环素自杀风险、自杀念头或行为的安全性信号。　　PRAC于2023年11月开始审查，并要求多西环素上市许可持有人对所有相关来源的数据进行累积审查。　　PRAC还要求通过“欧盟数据分析和真实世界查询网络项目”（Data Analysis and Real-World Interrogation Network，DARWIN）（DARWIN EU）进行一项基于真实世界证据的研究，其中包括来自电子健康记录和疾病登记处的数据，以促进对信号的评估。在审查了自发报告、文献、关于可能机制的讨论以及通过DARWIN EU进行的研究的所有可用证据后，PRAC认为证据不足以建立因果关系，因此没有必要更新多西环素的产品信息。　　将密切监测与多西环素相关的自杀事件，并在定期安全更新报告（PSUR）中讨论任何新证据。　　（欧洲药监局EMA网站）　　原文链接：　　https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-25-28-november-2024　　加拿大评估达沙替尼致儿童发育迟缓的潜在风险　　2024年12月，加拿大卫生部发布达沙替尼的安全性评估摘要，认为达沙替尼与18 岁以下儿童发育迟缓的风险之间可能存在因果关联性。　　达沙替尼为处方药，属于BCR-ABL酪氨酸激酶抑制剂类药物，在加拿大获批用于治疗患有某些类型白血病（血液和骨髓中的肿瘤）的成人，未批准用于儿科患者。达沙替尼自2007 年以来在加拿大以口服片剂（商品名Sprycel）上市销售，同时有仿制药上市。自2018年以来，加拿大已开具约93,000份达沙替尼处方，其中约600份用于儿童，数据表明已对儿科患者超说明书开具处方。BCR-ABL酪氨酸激酶抑制剂类药物中的另外两种药物，伊马替尼和尼洛替尼在加拿大获批用于治疗儿童某些类型的白血病，其加拿大产品专论（CPM）包括发育迟缓的风险。Sprycel在美国和欧洲获批用于儿科患者。　　加拿大卫生部开展以上评估，是因为欧洲药品管理局更新了Sprycel标签。　　加拿大卫生部评估了持有人提供的信息、加拿大警戒数据库、国际数据库以及科学文献。加拿大卫生部评价了19例（1例加拿大和18 例国际病例）服用达沙替尼的儿科患者发育迟缓报告，其中6例（1例为加拿大）为文献报告；尽管存在混杂因素（可能导致发育迟缓发生的其他因素），但评估证据表明达沙替尼治疗可能会导致发育迟缓。加拿大卫生部还评估了持有人提交的2份临床研究报告和4 篇科学文献，这些研究结果表明达沙替尼治疗可能会导致儿科患者的发育迟缓；以上研究同样存在局限性：包括存在混杂因素，以及在一些研究中样本量小。虽然所评价的病例报告和研究存在许多不足，但总体而言，所评估的证据足以支持使用达沙替尼与儿童发育迟缓的风险之间存在可能的关联性。　　加拿大卫生部经评估认为，达沙替尼与儿童发育迟缓的风险之间存在可能关联性，其将与持有人共同将包括儿童发育迟缓风险等安全性信息纳入到达沙替尼的药品专论（CPM）中。　　（加拿大卫生部网站）　　原文链接：　　https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SSR1731422768944　　　　丹麦药品管理局就司美格鲁肽导致罕见眼部疾病的疑似风险提交欧洲药品管理局审议　　丹麦药品管理局将要求欧洲药品管理局药物警戒风险评估委员会（PRAC）对南丹麦大学（SDU）的两项新的注册登记研究进行评估。这些研究指出接受糖尿病治疗药物Ozempic（商品名称：诺和泰，通用名称：司美格鲁肽注射液）治疗的患者罹患罕见眼部疾病非动脉炎性前部缺血性视神经病变（NAION）的风险可能增加。　　NAION是一种罕见疾病，影响视神经前端的小血管，可能导致突然的视力丧失和视野缺损。SDU在两项新研究中调查了使用糖尿病治疗药物Ozempic的糖尿病患者罹患NAION的风险是否会增加。在其中一项研究中，研究人员调查了总计424152名糖尿病患者的数据，其中四分之一（106454人）接受了Ozempic治疗，其余患者接受了其他类型的糖尿病治疗药物。另一项包含丹麦和挪威登记数据的研究，与挪威国家公共卫生研究院合作完成，研究人员调查了2018年至2024年期间接受Ozempic治疗的44517名丹麦糖尿病患者以及2018年至2022年期间接受Ozempic治疗的16860名挪威糖尿病患者的数据。　　在过去的六个月中，丹麦药品管理局一直将NAION作为司美格鲁肽（Ozempic的活性成分）的潜在不良反应予以关注。截至2024年12月10日，丹麦药品管理局已经收到19份NAION的本土不良反应报告。第一份描述NAION为司美格鲁肽疑似不良反应的报告接收于2024年7月。不良反应报告已定期提交给欧洲药品不良反应数据库。　　到目前为止，不良反应报告和NAION前期研究的数据基础还不足以指向药品与症状之间可能存在联系的信号。但SDU最近的研究结果加强了这一怀疑，并可能含有需要PRAC开展评估的新的重要信息，以确定司美格鲁肽和NAION是否存在关联。　　药物警戒部门主任Line Michan指出，他们在过去六个月中与欧洲同事们合作评估了有关NAION的严重眼部疾病的报告和研究。来自丹麦和挪威的新的注册登记研究提供了可能需要PRAC考虑的完整数据，因此他们将要求PRAC评估这些新研究。Line Michan同时指出，NAION是一种极为罕见的疾病。目前尚未确定是Ozempic导致了上述研究中的NAION发病率上升，还是其他原因导致了相关糖尿病患者的病情。　　　　（丹麦药品管理局）　　原文链接：　　https://laegemiddelstyrelsen.dk/en/news/2024/suspicion-of-rare-eye-condition-from-ozempic-use-to-be-investigated-further/

辽宁荟呈药业有限公司报告，由于产品标签与经备案的产品标签内容不一致，公司决定对生产的牙科用口外研磨材料（备案号：辽鞍械备：20220020、产品批号：20220610、20230716、20231023、20240112、20240525、型号规格：光亮型 110g/支）实施主动召回，进行销毁。召回级别为三级。涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。

为了规范化妆品检查工作，按照国家药监局《化妆品检查管理办法》有关要求，结合我省化妆品监管工作实际，省药品监督管理局组织起草了《青海省化妆品检查实施细则（试行）（征求意见稿）》。现向社会公开征求意见，请于2025年1月28日前将有关意见以电子邮件形式反馈至省药品监督管理局。联系人：安红漫 联系电话：0971-8865676电子邮箱：455840895@qq.com青海省药品监督管理局2025年1月22日相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

行政相对人名称江苏博后智造生物科技有限公司行政相对人类别法人及非法人组织统一社会信用代码91321291MA1YEANY8G工商注册号组织机构代码税务登记号事业单位证书号社会组织登记证号法定代表人殷才法定代表人证件类型身份证法定代表人证件号码3****************6证件类型证件号码行政处罚决定书文号苏药监泰检处字〔2024〕15号违法行为类型生产经营不符合技术规范的化妆品违法事实当事人生产的爱后多肽蓝甘菊舒缓柔肤水（批号：24070201，规格：120ml）在2024年江苏省化妆品监督抽检中，菌落总数项目项目不符合《化妆品安全技术规范》（2015年版）规定。处罚依据《化妆品监督管理条例》第六十条第（二）项，《中华人民共和国行政处罚法》第五条及参照《江苏省药品监督管理行政处罚裁量权适用规则》第七条第二项处罚类别罚款处罚内容罚款10000元。罚款金额（万元）1没收违法所得没收非法财物的金额（万元）暂扣或吊销证照名称及编号处罚决定日期2025/01/22处罚有效期2025/06/22公示截止期2025/04/22处罚机关江苏省药品监督管理局处罚机关统一社会信用代码11320000014000394R数据来源单位江苏省药品监督管理局数据来源单位统一社会信用代码11320000014000394R备注相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

行政相对人名称黑龙江华民泰大药房有限公司行政相对人代码(统一社会信用代码)91230102MA1CADH32W法定代表人陈国卫行政处罚决定书文号道里市监处罚〔2025〕32号违法行为类型违反《药品经营和使用质量监督管理办法》第四十二条 第五款：药品零售企业营业时间内，依法经过资格认定的药师或者其他药学技术人员不在岗时，应当挂牌告知。未经依法经过资格认定的药师或者其他药学技术人员审核，不得销售处方药。违法事实经查，黑龙江华民泰大药房有限公司因执业药师不在岗、无处方销售处方药，已于2024年10月15日被道里区市场监督管理局要求责令立即改正并收到了道里区市场监督管理局当场下达的责令改正通知书（哈里市监药械责改字[2024]64号）。道里区市场局执法人员于2024年11月7日再次对该店进行检查时发现，该药店仍存在执业药师不在岗销售处方药乙酰螺旋霉素片规格0.1g*24片1盒的违法行为。处罚依据《药品经营和使用质量监督管理办法》 / 第七十二条 / 第三项　　　　药品零售企业有以下情形之一的，由药品监督管理部门责令限期改正；逾期不改正的，处五千元以上五万元以下罚款；造成危害后果的，处五万元以上二十万元以下罚款：　　（三）违反本办法第四十二条第五款规定的药师或者药学技术人员管理要求的。处罚类别其他-责令改正;罚款处罚内容黑龙江华民泰大药房有限公司，因执业药师不在岗销售处方药，未按责令改正要求完成整改，违反了《药品经营和使用质量监督管理办法》第四十二条第五款“药品零售企业营业时间内，依法经过资格认定的药师或者其他药学技术人员不在岗时，应当挂牌告知。未经依法经过资格认定的药师或者其他药学技术人员审核，不得销售处方药”之规定。依据《药品经营和使用质量监督管理办法》第七十二条第一款第三项 药品零售企业有以下情形之一的，由药品监督管理部门责令限期改正；逾期不改正的，处五千元以上五万元以下罚款；造成危害后果的，处五万元以上二十万元以下罚款：（三） 违反本办法第四十二条第五款规定的药师或者药学技术人员管理要求之规定，要求立即改正违法行为，拟决定给予黑龙江华民泰大药房有限公司罚款5000元（伍仟圆整。¥5000元）的行政处罚罚款金额（万元）0.5处罚决定日期2025-01-22处罚有效期2099-12-31公示截止期2028-01-22处罚机关哈尔滨市道里区市场监督管理局相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

主体名称宁波鄞州平飞大药房有限责任公司处罚决定书文号甬鄞市监处罚﹝2025﹞129号处罚类别罚款处罚决定时间2025-01-22处罚内容责令限期改正;逾期不改正的,处五千元以上五万元以下罚款;造成危害后果的,处五万元以上二十万元以下罚款。;罚款金额（万元）0.500000没收违法所得0.000000暂扣或吊销证照名称及编号-违法行为类型宁波鄞州平飞大药房有限责任公司其它违法行为案处罚依据《药品经营和使用质量监督管理办法》第七十二条第一款“药品零售企业有以下情形之一的,由药品监督管理部门责令限期改正;逾期不改正的,处五千元以上五万元以下罚款;造成危害后果的,处五万元以上二十万元以下罚款:(一)未按规定凭处方销售处方药的;”;违法事实主要违法事实:经查明,当事人在2024年05月05日、2024年05月16日、2024年07月22日、2024年08月26日分别在线下销售处方药阿奇霉素分散片1盒,但4张处方笺均没有执业药师审核签名。另查明,当事人2024年06月17日在美团网络销售1盒处方药双氯芬酸钠缓释胶囊,处方笺未经执业药师审核签名。当事人2024年08月31日在美团网络销售1盒处方药复方酮康唑发用洗剂,处方笺未经执业药师审核签名。行政处罚种类、依据、内容:当事人未遵守药品销售相关管理规定进行处方药的销售,其行为违反了《药品经营和使用质量监督管理办法》第四十二条第五款之规定,属未经执业药师审核销售处方药的违法行为。依据《药品经营和使用质量监督管理办法》第七十二条第一款第一项之规定,对当事人责令限期15天之内改正。当事人未遵守药品销售相关管理规定进行网络处方药的销售,其行为违反了《药品网络销售监督管理办法》第九条第二款之规定,属未经执业药师审核网络销售处方药的违法行为。依据《药品网络销售监督管理办法》第三十四条第一款之规定予以处罚。对当事人责令限期15天之内改正并处罚如下:罚款5000元。行政处罚履行方式和期限:当事人自收到行政处罚决定书之日起十五日内,按照行政处罚决定书载明的履行方式履行。处罚机关宁波市鄞州区市场监督管理局处罚机关统一社会信用代码11330227309031876A数据来源单位省市场监管局数据来源单位统一社会信用代码11330000MB19062420相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

Delivery Method:Via EmailReference #:320-25-22Product:DrugsRecipient:Mr. Paul HudsonChief Executive OfficerSanofi54, Rue La Boétie75008ParisFranceIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-22January 15, 2025AMENDED(This letter replaces Warning Letter No. 320-25-22 dated December 16, 2024.)Dear Mr. Hudson:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Genzyme Corporation (a Sanofi subsidiary), FEI 1220423, at 8, 31, 45, 49, 51, 55, 68, 74, 76, 80 New York Ave., Framingham, MA, from June 12 to July 9, 2024.This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs are 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).We reviewed your July 29, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific deviations including, but not limited to, the following.1. Failure to investigate all critical deviations.FDA documented that approximately 20 percent of bioreactor runs attempted between January 2022 and July 2024 were rejected for contamination or other quality failures. This rate is excessive and calls into question the state of control of your process. You failed to conduct adequate investigations into critical deviations, including multiple microbiological contamination events recorded in this timeframe. For example:A. Two lots of(b)(4)and three lots of(b)(4)were out-of-specification (OOS) for appearance due to the presence of(b)(4)particles and were not adequately investigated.B. Three in-process high-pressure events associated with product leakage during the transfer of bulk(b)(4)through a(b)(4)to(b)(4)L shipping bags were not adequately investigated.Your investigations failed to identify all potential contributing causes, did not consider the conclusions of an engineering study that contradicted your assigned root cause for the OOS appearance events, and did not document all investigational activities, including the collection of at least one sample found in a storage room by FDA investigators.In your response, you reference numerous corrective actions and preventive actions (CAPAs) initiated to address the inadequate investigations into the microbiological contamination and the in-process high-pressure events including:• “… additional quality oversight of significant deviations…,”• implementation of “… an investigation job aid” for(b)(4)technology items that help determine product impact,• and revising your procedure governing appearance testing of APIs to ensure the observation of particles will result in an investigation that includes particle characterization.Your response is inadequate. You did not provide the completed investigations alluded to in your response, identify the root cause(s), justify each CAPA, or explain how the effectiveness of the CAPA will be determined. You also did not address the impact of excessive(b)(4)particles in your drug substances potentially reducing the ability of(b)(4)to successfully remove objectional microbiological contamination.In response to this letter, provide:• An update on your investigation into reducing particle load in your process. Include in this update both an updated control and removal strategy, including an analysis of load,(b)(4)capacity,(b)(4), and parameters to monitor to ensure(b)(4)used to remove microorganisms are not adversely affected by(b)(4)from particulates.• A comprehensive assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit (QU) oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.• A retrospective, independent review of all investigations into unexplained discrepancies or the failure of a batch or any of its components to meet any of its specifications for U.S. products, irrespective of whether the batch was ultimately distributed in the U.S. market, and within expiry as of the date of this letter and a report summarizing the findings of the analysis, including the following for each investigation: o Determine whether each investigation was thorough, described all investigational activities, including sampling and analysis of samples, identified root cause(s), identified scientifically justified CAPA and appropriate means of determining CAPA effectiveness. o Determine whether the scientific justification and evidence relating to an invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error. o For investigations that conclusively establish root cause, provide rationale and ensure that all other methods, procedures, processes, and materials vulnerable to the same or similar root cause are identified for remediation. o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.2. Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes.You repeatedly deviated from your validated manufacturing process for the production of(b)(4). For example:A. You performed(b)(4)of the(b)(4)during(b)(4)of the(b)(4)bioreactor runs while the manufacturing process was validated with(b)(4). You identified the(b)(4)process as increasing the risk of microbiological contamination events in an investigation into a March 2024 in-process contamination event.B. Your manufacturing personnel were observed to use a written work instruction (Pre-Job Briefing) describing itself as “… not a GMP document/process…” to deviate from your validated manufacturing procedure by replacing the(b)(4)with(b)(4)L shipping bag to control the frequency of high-pressure and in-process leaking events. The(b)(4)manufacturing process described in the electronic batch record used by manufacturing personnel was validated using a(b)(4)to process the transfilling of all(b)(4)L shipping bags used in a batch.In your response, you commit to executing a protocol intended to identify additional CAPA to increase control of upstream processing and thereby reduce the incidence of microbiological contamination events. In addition, you commit to prohibiting the practice of replacing the(b)(4)with(b)(4)L shipping bag during the manufacture of(b)(4). You also state the Pre-Job Briefing document was used incorrectly to implement the change to the validated manufacturing process and commit to identify and correct any other manufacturing instructions that rely on a Pre-Job Briefing document to deviate from the validated manufacturing process.Your response is inadequate. There is no indication you initiated an investigation into your deviating from the validated manufacturing process by replacing the(b)(4)filling bags on multiple occasions. In addition, there is no retrospective review of batch records for batches within expiry, to identify any other process deviations performed without the appropriate corresponding documentation including risk assessment(s). You did not provide your rationale for ending the practice of replacing the(b)(4)for(b)(4)L shipping bag during the manufacture of(b)(4). Furthermore, you did not identify an alternative control strategy to address the high-pressure events that resulted in the in-process product leakage events. You also did not investigate or describe your CAPA to address your QU’s roles in these deviations from validated manufacturing processes.When significant variability is observed in a drug manufacturing process or in its input materials, it is essential for executive management to support and implement effective actions to promptly address the source(s) of the variation and ensure a continued state of control.See FDA’s guidance documentProcess Validation: General Principles and Practicesfor general principles and approaches that FDA considers appropriate elements of process validation athttps://www.fda.gov/media/71021/download.In response to this letter, provide:• An assessment of each drug production process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes, will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.• A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.• Timelines for completed further process performance qualification studies on remediated processes for marketed drug products for which a state of control has not been adequately/fully established.• Process performance protocol(s), and written procedures for qualification of equipment and facilities.• A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.3. Failure to have equipment of the appropriate design and suitability for their intended use for the manufacture of APIs.Your firm used equipment unsuitable for its intended use in microbiologically controlled manufacturing environments. For example:A. Mobile carts used in the setup of(b)(4)units required operators to get down to the floor and manually lock and unlock the cart brakes despite previously determining equipment proximity to the floor as a contributing root cause in microbiological contamination events.B.(b)(4)used to establish temporary sterile boundaries for tubing continue to be used despite being identified in a June 2023 microbial contamination event investigation as possessing a “design flaw” that may allow microbial ingress.In your response, you commit to removing all brakes from the(b)(4)carts, assessing potential design improvements to the carts, and you note supplemental contamination control training to manufacturing personnel. You explain the previous documented description of a design flaw in the(b)(4)was incorrect, and the problem is a “design limitation” that requires specific instruction to fully mitigate the risk of microbiological contamination. You also commit to verification of the(b)(4)usage by a second operator.Your response is inadequate. You disregarded your previous conclusion that equipment and personnel proximity to the floor is a contributing root cause in microbiological contamination events and state the design of the mobile carts is “… fit for purpose when used per the SOP and in a manner consistent with manufacturing training.” You do not commit to reassess manufacturing equipment to ensure it is of appropriate design to minimize the risk of microbial contamination. You do not describe the(b)(4)“design limitation” or explain why this “design limitation” was not previously mitigated. You also do not discuss how the revised instructions for usage and verification will mitigate the risk associated with their use.In response to this letter provide, your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, ensuring suitability for use, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.4. Failure of your quality unit to exercise its responsibility to ensure the API manufactured at your facility are in compliance with CGMP.Our inspection documented approximately 84 open and past due deviation investigations existed as of June 21, 2024. For example:A. QE-000270 (187 days past due)B. QE-004069 (179 days past due)C. QE-004896 (129 days past due)D. QE-023790 (45 days past due)Multiple past due investigations also lacked procedurally required extensions to the due date.The procedure governing deviation handling requires non-significant deviations be closed within(b)(4)and significant deviations be closed within(b)(4). The procedure further requires a documented and approved request for extension in the event a deviation investigation cannot be closed within the specified timeframe.In your response, you identify four contributing root causes: excessive personnel attrition of trained investigators, process knowledge gaps amongst newer investigators, prioritization of investigations associated with lots pending release, and inconsistent communication of “deviation performance metrics.”Your response is inadequate. Although you identified CAPA, for each contributing root cause, you did not provide sufficient detail for their implementation. You commit to adding resources to your “Compliance Engineer and QA team to sustain the deviation quality system…” and assess this action “… against adherence to performance metrics and the(b)(4)planning exercises for resource allocation.” You also commit to reassigning existing personnel and to bring in subject matter experts to assist with addressing the investigation backlog but do not explain how this will impact other operations, how these personnel will be trained to conduct specific aspects of the investigations, and how their performance will be monitored and assessed.In response to this letter, provide:• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources, including adequate training, to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.o Also describe how top management supports quality assurance and reliable operations, including but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.5. Failure to ensure all production deviations are reported and evaluated, and that critical deviations are investigated, and the conclusions are recorded.Multiple production deviations went unaddressed until our investigators informed facility personnel of the issues. For example:A. An(b)(4)line used for aseptic processing was observed to be touching the floor during(b)(4)setup activities. The batch record specifically includes an instruction for personnel to ensure production lines do not contact the floor.B. An operator was observed to touch their gown and hairnet with their hands and then handle sterile manufacturing equipment without sanitizing their hands.C. The(b)(4)located between the(b)(4)L(b)(4)and a(b)(4)L shipping bag was observed to be oriented(b)(4)during processing of(b)(4)lot(b)(4). The batch record specifically instructs personnel to orient the(b)(4).In your response, you commit to conducting additional training for all facility personnel and to revise your(b)(4)contamination control training to include additional instructions on when to use(b)(4)and when gowning changes are appropriate. You also commit to making procedural changes associated with equipment management and using additional resources for operational coaching and oversight.Your response is inadequate. You do not provide your investigation(s) into the objectionable behaviors, assess your training program, or assess your oversight of setup and manufacturing operations.In response to this letter, provide:• Your investigation(s) into the objectionable behaviors.• Your revision(s) to personnel training and written procedures that instruct personnel on proper aseptic practices including situations requiring sanitization of gloves.• An assessment of training program effectiveness for all training given to personnel performing activities in, and in support of, production activities. Your assessment should include identification of specific CAPA, date(s) of implementation, and the means of determining CAPA effectiveness.Quality Unit AuthoritySignificant findings in this letter indicate that your QU is not able to fully exercise its authority and/or responsibilities. Your firm must provide the QU with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.ConclusionThe deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.Correct any deviations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved deviations may also prevent other Federal agencies from awarding contracts.Failure to address deviations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any deviations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any deviations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 1220423 and ATTN: Jason F. Chancey.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research