Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:25-HFD-45-12-01Product:DrugsRecipient:Devalingam Mahalingam, M.D., Ph.D.676 North Saint Clair Street, Suite 1200Chicago,IL60611-3068United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StateWARNING LETTERFDA Ref.No.: 25-HFD-45-12-01Dear Dr. Mahalingam:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at your clinical site between October 7 and October 18, 2024. The investigators representing FDA reviewed your conduct of the following clinical investigations:Protocol(b)(4), “(b)(4),” of the investigational drug(b)(4), performed for(b)(4)Protocol(b)(4), “(b)(4),” of the investigational drugs(b)(4)and(b)(4), performed for(b)(4)This inspection was conducted as a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.At the conclusion of the inspection, the FDA investigators presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your November 6, 2024, written response to the Form FDA 483.From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated November 6, 2024, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, part 312 (21 CFR 312) governing the conduct of clinical investigations and the protection of human subjects. We wish to emphasize the following:You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].As a clinical investigator, you are required to ensure that your clinical investigations are conducted in accordance with the investigational plan. The investigational plan for Protocol(b)(4)required the investigational drug,(b)(4), to be administered to subjects in accordance with the dose-level cohort to which subjects were assigned. The protocol also required that(b)(4)be prepared and administered in accordance with the(b)(4)Pharmacy Manual, which included specific dilution procedures to be followed during dose preparation.You failed to adhere to these requirements. Specifically, Subject(b)(6)was assigned to the Part 1: Group C dose cohort, and was to receive 0.18 mcg/kg of the investigational drug on Cycle 1 Day 1. Based on the subject’s assigned dose-level (0.18 mcg/kg) and body weight (59.3 kg), Subject(b)(6)should have received a total intravenous (IV) infusion dose of 10.674 mcg of(b)(4)from a final drug concentration of 2 mcg/mL. However, during dose preparation, the dilution procedures specified in the pharmacy manual were not correctly followed, resulting in the subject’s(b)(4)IV infusion containing a final drug concentration of 200 mcg/mL, instead of the intended 2 mcg/mL. On April 22, 2024 (Cycle 1 Day 1), Subject(b)(6)was administered an IV infusion dose of approximately 1060 mcg, instead of 10.674 mcg, of the investigational drug. As a result, the subject was administered an IV infusion containing approximately 100 times the protocol-required dose of(b)(4). Subsequently, Subject(b)(6)was hospitalized and experienced multiple serious adverse events, including cardiac arrest, and death on(b)(6).In your November 6, 2024, written response to the Form FDA 483, you stated that because of a compounding error, Subject(b)(6)received a larger than intended dose of study drug, which resulted in a prepared total dose of 1067 mcg of(b)(4)that was added to the IV bag for infusion. You stated that once the dosing error was confirmed, site personnel immediately contacted the subject’s nurse and the pharmacist in the clinic to stop the drug infusion.In addition, in your written response, you stated that the following corrective and preventive actions have been implemented, including but not limited to: (1) study-specific training, attended by you and all oncology Investigational Drug Services (IDS) pharmacists and compounding technicians; (2) the updating of several IDS standard operating procedures (SOPs) and training on these procedures, which included updated observation and verification dose preparation procedures for certain investigational medications, and protocol training for compounding technicians and pharmacists for studies that include certain investigational medications; and (3) sponsor updates to the pharmacy manual, to include additional clarification for dilution steps, with illustrations, and pharmacist verification dosing requirements.While we acknowledge the corrective and preventive actions that your site has taken, your written response is inadequate because you did not provide sufficient details about how you, as the clinical investigator, will ensure adequate oversight of study procedures. For example, while your written response notes that you attended training on Protocol(b)(4), the written response states that only site pharmacists and technicians attended or will attend trainings on revised SOPs, pharmacy manual updates, and future protocols that include certain investigational medications. Therefore, your written response does not provide sufficient details concerning how you, as the clinical investigator, will prevent similar violations from occurring in the future. Without this information, we are unable to determine whether your corrective actions appear adequate to prevent similar violations in future clinical investigations.We emphasize that as the clinical investigator, it is your responsibility to ensure that studies are conducted in accordance with the investigational plan, both to protect the rights, safety, and welfare of subjects and to ensure the integrity of study data. Your failure to conduct the clinical study in accordance with the protocol resulted in an overdose of investigational drug to a subject, who subsequently experienced several serious adverse events, including death. This conduct raises significant concerns about your protection of the study subjects enrolled at your site, and raises concerns about the validity and integrity of the data collected at your site.This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational drug. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address this matter adequately may lead to regulatory action. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.Should you have any questions or concerns regarding this letter or the inspection, please email FDA at CDER-OSI-Communications@fda.hhs.gov. Your written response and any pertinent documentation should be addressed to:Brittany L. Garr, MPHBranch ChiefCompliance Enforcement BranchDivision of Enforcement and Postmarketing SafetyOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug AdministrationBuilding 51, Room 535210903 New Hampshire AvenueSilver Spring, MD 20993Sincerely yours,{See appended electronic signature page}David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration--------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.--------------------------------------------------------------------------------------------/s/------------------------------------------------------------DAVID C BURROW12/11/2025 01:04:21 PM

各有关医药企业：根据《国家医疗保障局办公室关于进一步完善医药价格和招采信用评价制度的通知》（医保办发〔2025〕10号）等文件规定，以法院判决为线索，部分医药企业在我省存在失信行为，涉嫌违背公平、合理和诚实信用、质价相符原则。现将部分医药企业失信行为评级结果予以公示，公示期自2025年12月30日至2026年1月3日。各相关医药企业如对公示内容有异议，请在公示期内反馈。联系电话：0791-88102300附件：价格招采信用评价评级结果江西省医药价格和采购服务中心2025年12月30日

依据《中华人民共和国行政许可法》第七十条、《医疗器械生产监督管理办法》第二十一条的规定，因行政许可有效期届满未延续，我局依法注销内蒙古好大夫医疗技术有限公司等5家企业《医疗器械生产许可证》。附件：注销的许可证内容内蒙古自治区药品监督管理局2025年12月30日附件注销的许可证内容序号企业名称许可证名称许可证编号1内蒙古好大夫医疗技术有限公司医疗器械生产许可证内食药监械生产许20200003号2内蒙古科日沁蒙医器械有限公司医疗器械生产许可证内食药监械生产许20200004号3呼伦贝尔松鹿制药有限公司医疗器械生产许可证内食药监械生产许20200007号4内蒙古孟和制药股份有限公司医疗器械生产许可证内食药监械生产许20200009号5内蒙古泰领海创生物科技有限公司医疗器械生产许可证内食药监械生产许20200010号

根据《宁夏回族自治区药品经营企业长期停业和恢复经营监督管理规定》（宁药监规发〔2025〕2号）相关要求，宁夏永丰医药有限公司向宁夏回族自治区药品监督管理局提交停业申请，企业承诺停业期间停止一切药品经营活动。企业在《药品经营许可证》有效期内恢复药品经营活动，需向宁夏回族自治区药品监督管理局提交书面报告，并经检查符合要求后方可恢复药品经营活动。现将企业信息予以通告。 附件：长期停业药品经营企业信息 宁夏回族自治区药品监督管理局2025年12月29日（此件公开发布）

根据《中华人民共和国行政许可法》第七十条和《医疗器械监督管理条例》第六十六条的相关规定，按照《浙江省食品药品监督管理局办公室关于发布第二类医疗器械注册证书补办程序等5个相关工作程序的通知》（浙食药监规[2016]3号）的具体要求，依企业申请，现注销以下2家企业共3个产品的医疗器械注册证： 一、绍兴守仁医疗健康科技有限公司的1个产品：一次性使用医用口罩，注册证编号：浙械注准20202141434。 二、温州市邦盾智能安防有限公司的2个产品：一次性手术衣，注册证编号：浙械注准20222140397；医用防护服，注册证编号：浙械注准20222140312 特此通告。联系电话：0571-88903347联系地址：杭州市莫干山路文北巷27号 邮编：3100122025年12月30日

相关附件：新疆维吾尔自治区2025年药品抽检不符合规定药品名单

企业名称天津天士力（辽宁）制药有限责任公司企业类型药品生产企业检查时间2025年10月13日-2025年10月16日所在地市阜新市检查依据《药品管理法》《药品生产监督管理办法》《药品生产质量管理规范》检查事项药品生产检查检查方式常规检查；有因检查检查内容1.执行GMP情况 2.集采品种核查存在问题在机构与人员方面存在丸剂生产区设置的办公室内含计算机、打印机等易产尘物品；在厂房与设施方面存在企业饮片库中储存成品；在质量控制与质量保证方面存在2024年度产品质量回顾报告对个别品种的回顾不全面。处理措施责令限期整改整改情况已按要求完成整改

依据《中华人民共和国药品管理法》第九十九条、《药品检查管理办法（试行》第六十三条之规定，重庆市药品监督管理局依法对重庆广聚汇医药有限公司（药品经营许可证号：渝AA023000672）开展现场检查，企业已完成问题整改，现决定对该企业解除暂停销售药品风险控制措施。　　特此通告。　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　重庆市药品监督管理局                                　　　　　　　　　　　　　　　　　　　　　　 　2025年12月30日

行政相对人名称合肥君乐美医疗器械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91340121MA8L85XD4K法定代表人储转华行政处罚决定书文号皖药监械处罚﹝2025﹞1-34号处罚类别罚款;没收违法所得处罚决定日期2025-12-26处罚内容1.没收违法所得1564元；2.罚款50000元。罚款金额（万元）5.000000没收违法所得、没收非法财物的金额（万元）0.156400暂扣或吊销证照名称及编号违法行为类型《医疗器械监督管理条例》第三十二条第一款、《医疗器械生产监督管理办法》第十五条第一款违法事实当事人在未经许可的生产场地生产第二类医疗器械定制式义齿处罚依据《医疗器械监督管理条例》第八十一条第一款第（二）项、《医疗器械生产监督管理办法》第七十四条第一款第（二）项处罚机关安徽省药品监督管理局处罚机关统一社会信用代码11340000MB19570665数据来源单位安徽省药品监督管理局数据来源单位统一社会信用代码11340000MB19570665状态

沪药监通告〔2025〕37号  按照《医疗器械监督管理条例》的规定，根据企业申请，上海市药品监督管理局注销以下3家企业共3个产品的医疗器械注册证：  一、上海圣为医疗科技有限公司的1个产品：眼科影像管理与通讯系统软件，注册证编号：沪械注准20222210133。  二、上海沪雅科技有限公司的1个产品：一次性使用医用口罩，注册证编号：沪械注准20212140466。  三、上海维固医疗器械有限公司的1个产品：组合式外固定支架，注册证编号：沪械注准20212040527。  特此通告。  上海市药品监督管理局  2025年12月27日  （公开范围：主动公开）