（2025年第5期总102期）为加强药品质量监管，保障公众用药安全，根据《中华人民共和国药品管理法》及相关法律法规，我省药品监管部门和检验机构对药品生产、经营和使用单位实施了监督抽检。现将本期药品抽检信息通报如下：一、公告情况经核查确认，牡丹皮等11批产品不符合规定（详见附件1）。不符合规定项目包括：性状、显微鉴别、化学反应、薄层色谱、杂质、总灰分、水分、重量差异、溶出度、含量测定、羟基红花黄色素A等。二、不符合规定药品的查处情况江西省药品监督管理局已责成相关部门对检验不符合规定的药品采取查封、扣押、暂停销售、召回等必要的控制措施，并依据相关法律法规对生产企业和被抽样单位进行查处。附件：1.药品监督抽检不符合规定信息汇总表（2025年第5期）2.不符合规定项目的小知识（2025年第5期） 江西省药品监督管理局 2025年7月11日附件2不符合规定项目的小知识1、性状记载产品的外观、臭、味、溶解度以及物理常数等，在一定程度上反映药品的质量特性。中药饮片性状项不符合规定，可能涉及药材种属偏差、炮制工艺有瑕疵、储存不当等情形。2、显微鉴别是利用显微镜观察植(动)物药材的内部组织构造、细胞形状及其后含物的特征,以供鉴别生药的真品、伪品、类似品或代用品的一种方法。它通常应用于单凭性状不易识别的药材，性状相似不易识别的药材,外形特征不明显的破碎药材和粉末状药材，以及用生药原粉为原料制备成的成方制剂的鉴定。3、化学反应是根据药物与化学试剂在一定条件下发生化学反应所产生的颜色、沉淀气体、荧光等现象,鉴别药物真伪的方法,供试品按质量标准中的鉴别项目的要求进行鉴别试验,若试验现象相同,则认定为同一种药物。4、薄层色谱用于检测药品中特定成分的存在与否，以及含量的多少。通过将供试品溶液与对照品或对照药材溶液在同一薄层板上点样、展开、显色后，对比两者的色谱图，可以辅助鉴别中药材的真伪与质量。‌5、杂质是指药物中存在的无治疗作用或者影响药物的稳定性、疗效，甚至对人体的健康有害的物质。6、总灰分测定的目的是检测中药的纯净程度。一定量的样品经炭化后放入高温炉内灼烧，使有机物质被氧化分解，以二氧化碳、氮的氧化物及水等形式逸出，而无机物质以硫酸盐、磷酸盐、碳酸盐、氯化物等无机盐和金属氧化物的形式残留下来，这些残留物即为总灰分。7、水分是指药品中的含水量。水分偏高通常与工艺、包装不当以及储运环境等因素有关。8、重量差异反映片剂的均匀性，检测的目的在于控制各片重量的一致性，保证用药剂量的准确。9、溶出度是指活性药物从片剂、胶囊剂或颗粒剂等普通制剂在规定条件下溶出的速率和程度，是片剂质量控制的一个重要指标。肠溶片在进行溶出度检查时，考虑为防止原料药物在胃内分解失效、对胃的刺激或控制原料药物在肠道内定位释放，一般考察酸中溶出量和缓冲液中溶出量。10、含量测定是指用规定的试验方法测定原料及制剂中有效成分的含量。11、羟基红花黄色素A为红花的主要活性成分之一，通过测定羟基红花黄色素A的含量，可以反映红花质量的优劣。

柯惠医疗器材国际贸易（上海）有限公司报告，由于产品在使用过程中可能出现设备报警未被识别进而导致患者伤害的情况，生产商柯惠有限责任公司Covidien llc对其生产的脉搏血氧饱和度测量仪Sp02 Patient Monitoring System（国械注进20152072123）主动召回。召回级别为一级召回。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》。　　附件：医疗器械召回事件报告表　　2025年7月10日

西门子医学诊断产品（上海）有限公司报告，由于部分批次产品可能含有错误的冲洗包，生产商美国西门子医学诊断股份有限公司 Siemens Healthcare Diagnostics Inc. 对其生产的清洗液 Wash/Waste Cartridge (4) （国械备20220668）主动召回。召回级别为二级召回。本次召回涉及的产品未进口至中国，具体型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　　　附件：医疗器械召回事件报告表　　2025年7月10日

雅培医疗用品（上海）有限公司报告，由于部分产品移动电源装置的交流电源线在插入时没有完全锁定到位，生产商雅培医疗器械 Abbott Medical对其生产的植入式左心室辅助系统Left Ventricular Assist System（国械注进20243120384）主动召回。召回级别为二级召回。本次召回涉及的产品未进口至中国，具体型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　　　　　附件：医疗器械召回事件报告表　　2025年7月10日

飞利浦（中国）投资有限公司报告，由于产品变速箱连接 C 臂滚动电机安装法兰的螺栓可能没有得到足够的扭矩，生产商飞利浦医疗系统荷兰有限公司Philips Medical Systems Nederland B.V.对其生产的医用血管造影X射线系统Medical Angiography X-ray System（国械注进20193060317）主动召回。召回级别为二级召回。本次召回涉及的产品未进口至中国，具体型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　　　　　附件：医疗器械召回事件报告表　　2025年7月10日

上海健臻医疗科技有限责任公司报告，由于读数显示单位设置错误的原因，生产商安晟信糖尿病保健股份公司Ascensia Diabetes Care Holdings AG对其生产的血糖仪CONTOUR NEXT GEN meter 主动召回。召回级别为二级召回。本次召回涉及的产品未进口至中国，具体型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　　　　　附件：医疗器械召回事件报告表　　2025年7月10日

奥林巴斯贸易（上海）有限公司报告，由于部分批次超声电子上消化道内镜附件包装内错误装入其他产品，生产商奥林巴斯医疗株式会社オリンパスメディカルシステムズ株式会社对其生产的超声电子上消化道内窥镜（国械注进20163063147）主动召回。召回级别为三级召回。本次召回涉及的产品未进口至中国，具体型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　　　　　附件：医疗器械召回事件报告表　　2025年7月10日

今年以来，全国市场监管部门持续加大对违法广告的打击力度，防范经营主体借违法广告加剧“内卷式”竞争，切实维护公平有序的广告市场秩序。截至2025年5月底，全国市场监管部门共查处违法广告案件14315件，罚没款1.01亿元。现选取一批已办结的违法广告典型案例予以公布。一、四川省成都市成华区市场监管局查处成都成华韩后医疗美容医院有限公司违法广告案经查，成都成华韩后医疗美容医院有限公司在以直播电商形式推销“半岛超声炮”“欧洲之星全面部全模式”“星耀超光子”等医疗美容项目过程中，宣称的治疗功效与实际情况不符，并使用“单次我们的续航能力是9—12个月”“能够解决肌肤20多种问题”等宣传用语为功效作保证。今年1月，四川省成都市成华区市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款40.98万元的行政处罚。二、河南省郑州市市场监管局查处市野（郑州）网络科技有限公司违法广告案经查，市野（郑州）网络科技有限公司在互联网发布的“市野医生筋骨疼痛贴”医疗器械广告中，含有“日本引进”“日本国民品牌”等与事实不符的信息，并通过宣称“一盒让你3年的腰腿疼痛、浑身酸痛消失”等内容，对产品功效作保证。今年5月，河南省郑州市市场监管局依据《中华人民共和国广告法》有关规定，对市野（郑州）网络科技有限公司作出罚款20万元的行政处罚。三、安徽省阜阳市颍东区市场监管局查处安徽全康药业有限公司违法广告案经查，安徽全康药业有限公司在互联网推广“永邦牌葛根豆蔻片”等保健食品过程中，通过宣称“日产80万瓶”“20余年实力大厂”等与实际情况不符的信息，对消费者造成误导。今年6月，安徽省阜阳市颍东区市场监管局依据《中华人民共和国广告法》有关规定，对安徽全康药业有限公司作出罚款21万元的行政处罚。四、浙江省杭州市拱墅区市场监管局查处杭州迅犹贸易有限公司违法广告案经查，杭州讯犹贸易有限公司在直播电商活动中对化妆品“薇诺娜极润水乳保湿套组”进行广告宣传，宣称该产品对皮肤出现的红、肿、痒、刺痛以及痘痘等过敏症状具有治疗效果，易使消费者将该产品与药品相混淆。今年3月，浙江省杭州市拱墅区市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款17.55万元的行政处罚。违法广告所涉其他经营主体已另案处理。五、广东省广州市白云区市场监管局查处广州岐黄医道文化传媒有限公司违法广告案经查，广州岐黄医道文化传媒有限公司通过宣传视频和宣传册推广“菌方后生元特殊膳食粉”“阿胶颐神膏”等普通食品，宣称上述产品具有治疗腰间盘突出、关节疼、便秘等功效，易使消费者将该产品与药品相混淆。今年3月，广东省广州市白云区市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款13.5万元的行政处罚。六、上海市杨浦区市场监管局查处上海颐摩健康管理有限公司违法广告案经查，上海颐摩健康管理有限公司在互联网发布的“赛乐瑞pro”等普通食品广告中，含有“血栓快速溶解、心脑血管双重调理改善”“可以对中枢神经、肝脏健康、消化系统、骨骼、抗癌等有预防改善效果”等涉及疾病预防、治疗功能的内容。今年3月，上海市杨浦区市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款10万元的行政处罚。七、山东省青岛市市场监管局查处青岛科曼奇商贸有限公司违法广告案经查，青岛科曼奇商贸有限公司在以直播电商形式推销普通产品“药王秘制膏”过程中，通过虚构消费者在使用产品后治愈“湿寒”“经络不通”等疾病的案例，对产品使用效果进行宣传，与实际情况不符。今年3月，山东省青岛市市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款10万元的行政处罚。违法广告所涉其他经营主体已另案处理。八、海南省海口市市场监管局查处海口华夏通物流服务有限公司违法广告案经查，海口华夏通物流服务有限公司在互联网发布新能源汽车轮渡业务宣传广告，通过宣称“新能源车彻底进不了海南了”“新能源车过海车票半个月内基本没有”等内容，捏造与事实不符的信息，制造新能源汽车过海焦虑，妨碍社会公共秩序。今年3月，海南省海口市市场监管局依据《中华人民共和国广告法》有关规定，对当事人作出罚款20万元的行政处罚。九、江西省吉安市安福县市场监管局查处江西同创新睿营销策划有限公司违法广告案经查，江西同创新睿营销策划有限公司在互联网发布的“安福华弘凌云府”房地产广告中，以抵达“城南国际、国光”等商场、超市的时间表示项目位置，并宣称“15年菁英教育入读安福平都四小”，但该小学尚在建设中，并未实际招生。今年1月，江西省吉安市安福县市场监管局依据《中华人民共和国广告法》有关规定，对江西同创新睿营销策划有限公司作出罚款10万元的行政处罚。十、北京市昌平区市场监管局查处中智无线（北京）科技有限公司发布违法广告案经查，中智无线（北京）科技有限公司在互联网发布手机流量卡广告，宣称“超大流量9元/月”，与实际情况不符。今年4月，北京市昌平区市场监管局依据《中华人民共和国广告法》有关规定，对中智无线（北京）科技有限公司作出罚款10万元的行政处罚。

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Kai W. TrompeterPresident and Chief Executive OfficerInsightra Medical Inc.2543 Madison St. Ste. 105Clarksville,TN37043United Stateskai@tn-mi.comsandi@tn-mi.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS #706921June 3, 2025Dear Mr. Trompeter:During an inspection of your firm located in Clarksville, TN, on January 21, 2025, through January 27, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Double Pump as well as the Ultra Intra Aortic Balloon Pump (IABP) Catheter Kits. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.We received a response from Sandie Hetland, Chief Financial Officer, dated February 14, 2025, concerning our investigator’s observations noted on the FDA 483, List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:Unapproved Device Violation(s)Our inspection revealed that the IABP Catheter Kit is adulterated under section 501(f)(1)(A) of the Act, 21 U.S.C. § 351(f)(1)(A), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(b) of the Act, 21 U.S.C. § 360e(b), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed. This device is also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm introduced or delivered for introduction into interstate commerce for commercial distribution this device with major changes or modifications to the intended use without submitting a new premarket notification to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3)(ii).Specifically, your device was cleared under K082746. In the supplement to your firm’s premarket notification, you recommended the device for use with the Datascope System 97, System 98, System 98XT, CS100 and CS300 devices and the Arrow ACAT, AutoCat, AutoCat 2, AutoCat 2 Wave, and KAAT II devices. However, your firm’s labeling, including promotional materials and information on your website (www.insightra.com), now state that, in addition to the devices mentioned above, your device is compatible with the Cardiosave IABP Hybrid and the AutoCat 3.Specifically, your website (www.insightra.com) contains a certificate of compatibility listing these devices. Additionally, a section of your website also states that there is “safe compatibility of the ULTRA 7FR IABP with the most common pumping consoles on the market,” and lists the Cardiosave IABP Hybrid and the AutoCat 3, in addition to the pump consoles that are within the scope of the current clearance. Finally, there is a document found on the Product Resources page of your website entitled, “Operator Presentation,” Although the presentation includes at the bottom of each slide the language, “THIS PRESENTATION IS STRICTLY CONFIDENTIAL – FOR INTERNAL TRAINING PURPOSES ONLY,” the document is publicly available on your website. The second slide of that presentation includes the statement, “Compatible with all common Datascope and Arrow consoles – kit comes with adaptors.” The pump console device is critical to the safe and effective operation of your device because your device cannot function without it. Pump consoles may have different performance characteristics and differences in performance characteristics between pump consoles may impact the safety and effectiveness of your device.The listing of the Cardiosave IABP Hybrid and the AutoCat 3 in the labeling for your device as compatible pump consoles constitutes a significant change or modification to your device’s intended use that requires a new premarket notification. As explained in Section V.A of FDA’s Guidance Document, Deciding When to Submit a 510(k) for a Change to an Existing Device - Guidance for Industry and Food and Drug Administration Staff, on pages 20 and 21, when making changes concerning the compatibility or interoperability of a device with other devices, components or accessories, manufacturers should consider the criticality of the other device, component or accessory. The more critical the other device, component, or accessory is to overall system function, the more likely a labeling change regarding compatibility or interoperability could significantly affect safety or effectiveness. As we have noted, the pump console is required for the operation of your device and therefore has substantial impact on the safety and effectiveness of your device. A change to a different pump console that may have different performance characteristics could impact the safety and effectiveness of an IABP catheter. The addition of the Cardiosave IABP Hybrid and the Arrow AutoCat 3 required the submission of a new 510(k), per 21 CFR 807.81(a)(3)(ii).We also note that your device’s current indications listed in your operator’s manual are as follows:The Insightra Intra Aortic Balloon Catheter Kit has the following indications for use:A. Refractory Unstable Angina.B. Impending Infarction.C. Post infarction angina.D. Refractory left ventricular failure.E. Complications of Acute MI (i.e. Acute MR or VSD or papillary muscle rupture).F. Cardiogenic shock.G. Support for diagnostic, percutaneous revascularization and interventional procedures.H. Ischemic related intractable ventricular arrythmias.I. Septic shock.J. Intraoperative pulsatile flow generation.K. Weaning from cardiopulmonary bypass.L. Cardiac support for non-cardiac surgery.M. Prophylactic support in preparation for cardiac surgery.N. Post-surgical myocardial dysfunction/low cardiac output syndrome.O. Cardiac contusion.P. Mechanical bridge to other assist devices.Q. Cardiac support following correction of anatomical defects.While we acknowledge that these indications were cleared under K082746, on December 30, 2013, FDA issued a final order to reclassify intra-aortic balloons and control systems (FR 2013-Doc 31218) (78 FR 79300). It states that:“The Food and Drug Administration (FDA) is issuing a final order to reclassify intra-aortic balloon and control system (IABP) devices when indicated for acute coronary syndrome, cardiac and non-cardiac surgery, or complications of heart failure, a preamendments class III device, into class II (special controls), and to require the filing of a premarket approval application (PMA) or a notice of completion of a product development protocol (PDP) for IABPs when indicated for septic shock or pulsatile flow generation.”It further instructs that “[a] PMA or notice of completion of a PDP is required to be filed with the Food and Drug Administration on or before March 31, 2014, for any intra-aortic balloon and control system indicated for septic shock or pulsatile flow generation that was in commercial distribution before May 28, 1976, or that has, on or before March 31, 2014, been found to be substantially equivalent to any intra-aortic balloon and control system indicated for septic shock or pulsatile flow generation that was in commercial distribution before May 28, 1976.”In addition, on March 20, 2014, FDA sent your firm a letter informing you of the final order requirements and clarifying the steps you should take to ensure compliance with the final order. We informed you that you must file a PMA or notice of completion of a PDP within 90 days of the date of issuance of the final order for IABP devices indicated for septic shock or pulsatile flow generation. We noted that if you did not file a PMA or notice of completion of a PDP for an IABP device with these indications within 90 days of the date of issuance of the final order, you must cease commercial distribution of your device for these indications because the device is deemed adulterated under section 501(f)(1)(A). We also noted that you may notify FDA that you wish to revise your indications by submitting an add-to-file to your previously cleared 510(k) on or before March 31, 2014.FDA has not received a notice of completion of a PDP or a PMA from your firm nor did you notify FDA that you wish to revise your indications by submitting an add-to-file to your previously cleared 510(k). Because you continue to market your device with a septic shock and pulsatile flow indication, your device is adulterated under section 501(f)(1)(A) of the Act, 21 U.S.C. § 351(f)(1)(A), because your firm does not have an approved PMA in effect pursuant to section 515(b) of the Act, 21 U.S.C. § 360e(b), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed.Medical Device Reporting (MDR) Violation(s)1. Our inspection revealed that your firm has failed to adequately develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. For example, during the inspection, your firm provided a draft document titled “Adverse Event & Vigilance Reporting,” SOP‐16, Version 2.1, undated, and identified it as your written MDR procedure. After reviewing the procedure, the following deficiencies were noted:a. There is no evidence that the draft document identified as your firm’s written MDR procedure has been implemented, as required by 21 CFR 803.17. For example, there is no effective date.b. The document does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example, the procedure, as written, does not define the term “serious injury” as defined in 21 CFR 803.3.***This is a repeat Observation from Warning Letter# 20-15 issued on May 21, 2015***Your firm’s response dated February 14, 2025, did not address the noted violation, as it was not listed on the FDA 483.Our inspection also revealed that your firm’s IABP Catheter Kit is misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under Section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 803 ‐ Medical Device Reporting. Significant violations include, but are not limited to, the following:2. Failure to submit a report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).For example, the information included in CMP‐36 reasonably suggests that a patient experiencing worsening heart failure underwent a procedure involving your firm’s IABP Catheter Kit, which malfunctioned (i.e., ruptured balloon) during use, potentially causing or contributing to a serious injury requiring the patient to be upgraded on the heart transplant list. There is no information included in the complaint indicating that the device did not cause or contribute to the patient’s serious injury. Your firm became aware of the event in October 2023. Based on our records, FDA has not yet received an MDR for the adverse event referenced in Complaint# CMP-36.Your firm’s response dated February 14, 2025, did not address the noted violation, as it was not listed on the FDA 483.3. Failure to submit a report to FDA no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets has malfunctioned and this device or a similar device that you market would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, as required by 21 CFR 803.50(a)(2).For example, the information included in CMP‐44 reasonably suggests that your firm’s IABP Catheter Kit malfunctioned (i.e., ruptured ballon) during use. In October 2023, your firm became aware through its investigation results for Complaint# CMP‐36, that the referenced malfunction (i.e., ruptured balloon) for the same or similar device, caused or contributed to the patient sustaining a serious injury. This prior incident established a precedent demonstrating that such a malfunction (i.e., balloon rupture leading to IABP failure) was previously linked to a serious injury. It is reasonable to conclude that a recurrence of this malfunction would be likely to cause or contribute to a death or serious injury. As such, the malfunction referenced in CMP‐44 represents an MDR reportable malfunction for which an MDR must be submitted. Your firm became aware of the event on January 22, 2024. Based on our records, FDA has not yet received an MDR for the malfunction event subject of Complaint #CMP‐44.***This is a repeat Observation from the 2015 FDA Inspection***Your firm’s response dated February 14, 2025, did not address the noted violation, as it was not listed on the FDA 483.Quality System Regulation Violation(s)This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.4. Failure to adequately document corrective and preventive action activities and results, as required by 21 CFR 820.100(b). For example:a. SOP-15, Corrective and Preventive Action, effective 10/26/2022 indicates that CAPAs are generated and documented in the Qualio system, an electronic record system used by your firm to manage quality documents. The following CAPAs were not adequately documented:i. CAPA-10 (closure date: 3/6/2023) related to batch release not being performed per the firm’s procedure was closed without completion of all the CAPA sections on the form.ii. CAPA-12 (closure date: 7/19/2023) related to the complaint reporting the Double Pump had an unspecified failure was closed without completion of all the CAPA sections on the form.iii. CAPA-11 which lists CASE-2023-00163655 on the top of the form did not contain any filled-out information on the form.iv. CAPA-22 was related to internal audit findings noting supplier evaluations and reevaluations were not being performed as per schedule. The verification of effectiveness activities performed on 11/11/2024 for this CAPA which was to “Verify and Check supplier evaluation for all critical suppliers,” failed to address the overdue evaluations for at least 3 suppliers.v. CAPA-24 was opened to address relevant information of identified quality problems not being captured in records. The verification of effectiveness, “Training has been imparted to new staff” was listed as being completed on 07/13/2023, despite the CAPA being opened on 11/11/2024.b. Your firm failed to initiate a CAPA to document the investigations, the actions to correct and prevent the recurrence of quality problems, and the verifications that actions were effective for known quality issues. For example:i. Between July 2023 and May 2024, at least 35 complaints were received from your US customers related to a device malfunction that causes leaking of the Double Pumps used for diagnostic and operative arthroscopic procedures. No CAPA was opened to investigate this known and ongoing issue to identify actions needed to correct and prevent the recurrence of nonconforming product or other quality issues.ii. CMP-27, dated 8/8/2023, was related to a complainant reporting the inner lumen of the IABP Catheter device being broken during patient use. Your firm failed to open a CAPA to document your investigation activities and corrective actions. Furthermore, a corrective action implemented for this quality issue was to update the distributor training to recommend the insertion technique of pushing the catheter at a 45-degree angle to prevent kinking which may lead the central lumen of the catheter to break. There was no assessment of the verification and/or validation activities needed for this corrective action or an identification of the required changes in methods and procedures needed to correct and prevent the identified quality problem.***This is a repeat Observation from the 2018 FDA Inspection***We reviewed your firm’s response and conclude that it is not adequate. The response failed to comprehensively address the systemic deficiencies identified within your CAPA process. Your firm only addressed the examples listed as opposed to addressing how your firm will correct the CAPA issues systemically to prevent the recurrence of the issues identified. For example, your firm fails to include as a corrective action the need to update the CAPA procedure to ensure that CAPAs that are voided have a documented rationale and to ensure that the CAPA void process does not impact product quality. Furthermore, in regard to CAPA-22, your firm failed to address why the supplier you no longer are doing business with was still listed on your firm’s approved supplier list and how your firm was planning on making corrections to prevent this issue from recurring.Regarding the ongoing leaking Double Pump issue discussed in part b of this observation, your firm’s response does not address whether your firm will open a CAPA to address the ongoing known quality issue. Your contract manufacturer proposed a potential correction to the known leaking issue in a February 2024 complaint report. According to your contract manufacturer, they had already proposed the potential correction to your firm before February 2024, as well, including in August 2021; however, your firm failed to make corrections or to assess this proposed solution. It is a requirement of 21 CFR 820.100 that you as a manufacturer investigate the cause of nonconformities relating to product, processes, and the quality system. Furthermore, you are required to identify actions needed to correct and prevent the recurrence of nonconforming product and other quality problems.Your firm is planning to have personnel involved in the CAPA documentation be retrained with an emphasis on proper record-keeping and compliance with SOP-15; however, it is important to make the proper corrections to your CAPA procedure to ensure it includes all requirements of 21 CFR 820.100 such as verifying or validating the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, and submitting relevant information on identified quality problems, as well as corrective and preventive actions, for management review.5. Failure to adequately maintain complaint files, as required by 21 CFR 820.198(a). For example:a. Section 5.1.2.2 of your procedure SOP-14 Customer Complaints, versions 1.0 and 2.0 state, “Complaints are evaluated using the MDV, MDR or MPR Decision Trees (found in SOP-16 Adverse Event & Vigilance Reporting) to determine if the complaint is a Reportable Complaint; the Decision Tree is attached to the Complaint Notification.” The following customer complaint notifications involving patients did not have an MDR decision tree attached:i. CMP-30ii. CMP-44iii. CMP-70iv. CMP-27v. CMP-36b. Section 5.1.2.3 of your procedure SOP-14 Customer Complaints, versions 1.0 and 2.0, state, “Quality Assurance promptly initiates investigation and reporting to meet the required report dates.” Review of complaints revealed complaint records were not opened in a timely manner as evidenced by:i. Compliant CMP-44, received on 01/22/2024 and entered into the Qualio database on 2/29/2024. CMP-44 was opened due to a complainant reporting a rupture of the intra-aortic balloon.ii. Complaint CMP-36, received in October 2023 and entered into the Qualio database on 12/04/2023. CMP-36 is associated with a serious injury reported to the FDA as a Medwatch Report by a complainant and brought to your firm’s attention by FDA.c. Section 5.1.1. of your procedure SOP-14 Customer Complaints, versions 1.0 and 2.0 state, “ Quality Assurance follows-up on any incomplete information to proceed with the complaint.” Review of complaints revealed complete and accurate information was not always included within your complaints as evidenced by:i. The complaint description within CMP-36 does not align with what was included within the documented investigation or the MedWatch Report submitted for the event. For example, the investigation documented that the Ultra IABP device was used for a matter of minutes; however, the MedWatch report indicates an implant date of 8/23/23 and explant date on 8/27/23. The complaint record does not explain the contradiction.ii. CMP-52, dated 03/26/2024, was opened due to a complainant reporting four leaking cassettes at the level of the insertion of the tubing into the rigid cassette. This complaint record failed to include that this is a known product issue reported by complainants previously and that there was currently an ongoing investigation by the firm. Furthermore, under the “Investigation Summary” section of the complaint record, it mentions, “There is no complaint product for return to further evaluation.” Your firm failed to document any follow up attempts to obtain information pertinent to conducting a meaningful investigation.iii. CMP-44, dated 02/29/2024, failed to include any follow up attempts for the firm to carry out an adequate investigation. The “Closure Activities” section of the complaint record states, “No complaint product for return to further evaluation.The detailed complaint description was not provided. hence [sic], it is difficult to carry out the investigation.”***This is a repeat Observation from the 2015 FDA Inspection and Warning Letter# 20-15 issued on May 21, 2015***We reviewed your firm’s response and conclude that it is not adequate. The response was not comprehensive to address the systemic deficiencies identified within your complaint handling process. For example, your response mentions that you will retrieve the MDR decision trees for the complaints referenced in the observation; however, your firm did not clearly address how you will ensure that MDR determinations are made within required timeframes. Section 5.1.2.2. of the procedure SOP-14, version 2.0 states, “These trees do not need to be completed for each complaint file IF the complaint does not impact any patient or surgical procedure.” Please note, complaints are to be evaluated to determine whether the complaint represents an event which is required to be reported to FDA under 21 CFR 803, Medical Device Reporting, as required by 21 CFR 820.198(a).Your response also mentions that the Qualio software will be modified to include a provision for closure time justification in cases where a complaint closure exceeds 30 days. It does not mention what corrective actions will be implemented to ensure complaints are processed in a uniform and timely manner once your firm becomes aware of the complaints, as required by 21 CFR 820.198(a). Please note, the delay between awareness of a complaint and the date the complaint is entered into the database has the potential for not allowing for an adequate follow up and prolongs the initiation of the investigation. Lastly, your response mentions that you will reopen CMP-52 and add all necessary details to document a clear understanding of events; however, you do not address making the proper corrections to your complaint procedure to ensure complaints undergo adequate investigation and include all relevant known information.6. Failure to adequately establish and maintain procedures for the identification, documentation, validation or where appropriate verification, review, and approval of design changes before their implementation, as required by 21 CFR 820.30(i). For example, your firm failed to ensure the following design changes were adequately identified, documented, and reviewed prior to implementation:a. Design change related to changing the shelf life of the IABP Catheter Kit from 1 year to 5 years. This design change was not properly identified and reviewed. Although real time aging studies to support a 5-year shelf life were conducted on October 20, 2015, the studies did not include any evaluation that the sterility for the device can be maintained over the labeled shelf-life. Furthermore, in 2022, the contract sterilizer for the Ultra IABP Catheter Kit was changed from(b)(4)to(b)(4), and there is no evidence to demonstrate that you evaluated the impact of this change on the shelf-life for your product.b. Design change related to implementing the use of a(b)(4)with the IABP Catheter Kit. This design change was not properly identified and reviewed. For example, you failed to ensure that the change included a proper update of the instructions for use and that the syringe maintains sterility when performing(b)(4)filling of the intra-aortic balloon. Furthermore, the design history file was not updated to reflect the addition of using the(b)(4)or the removal of this instruction to use a(b)(4)on or about 11/07/2024.***This is a repeat Observation from the 2018 FDA Inspection***We reviewed your firm’s response and conclude that it is not adequate. It fails to address the need to update your design control procedures to ensure they include the requirements of 21 CFR 820.30(i).Corrections and Removals Violation(s)Our inspection also revealed that your firm’s IABP Catheter Kit devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 806 Medical Devices; Reports of Corrections and Removals. Violations include, but are not limited to, the following:7. Failure to submit any report required by 21 CFR 806.10(a) within 10 working days of initiating a correction or removal, as required by 21 CFR 806.10(b). For example, you updated your IABP distributor training materials to add instructions to use an angle of insertion of 45 degrees or less to reduce the incidence of kinking. Kinking may lead to a break of the central lumen of the catheter, cause poor gas filling, or contribute to balloon leak or rupture. Your Failure Modes and Effects Analysis document states that balloon rupture or leak has gas emboli as a potential effect to the failure mode. Gas embolism occurs when gas bubbles enter the bloodstream and obstruct blood flow, potentially leading to serious complications or death. This update to your training materials meets the definition of a medical device correction or removal initiated to reduce a risk to health posed by the device or remedy a violation of the Act caused by the device which may present a risk to health, for which you are required by 21 CFR 806.10 to report the correction or removal to FDA. As of 4/15/2025, you did not submit a Medical Device Report of Correction or Removal to FDA for this action.Your firm’s response, dated February 14, 2025, did not address the noted violation, as it was not listed on the FDA 483.Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.Your firm’s response should be sent via email to Melissa Michurski, Establishment Assessment Team 2, Assistant Director, at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, CMS Case #706921 when replying. If you have any questions about the contents of this letter, please contact: Ashley Mutawakkil at Ashley.Mutawakkil@fda.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.Sincerely,/S/Matthew G. HillebrennerDeputy DirectorOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA Electronic MailReference #:320-25-83Product:DrugsRecipient:Mr. Gavin Victor CollierCEODynamic Blending Specialists, Inc.523 East 1750 N., Suite 100Vineyard,UT84059-8109United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-83June 18, 2025Dear Mr. Collier:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Dynamic Blending Specialists, Inc., FEI 3013719300, at 523 East 1750 N. Suite 100, Vineyard, Utah 84059-8109, from December 3 to 6, 2024.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products 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).In addition, “(b)(4)” is an unapproved new drug introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d). Additionally, this product is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of a misbranded product into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.We reviewed your December 24, 2024 response to our Form FDA 483 in detail.During our inspection, our investigators observed specific violations including, but not limited to, the following.CGMP Violations1. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm manufactures over-the-counter (OTC) topical analgesic and oral care drug products. You failed to perform adequate identity testing of each component lot used in the manufacture of your OTC drug products, including for glycerin and active ingredients such as stannous fluoride, menthol, and camphor. Additionally, you relied on your suppliers’ certificates of analyses (COAs) without establishing the reliability of each of your suppliers’ test analyses at appropriate intervals.GlycerinYou failed to adequately test each shipment of each lot of glycerin for identity, a component at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. Identity testing for glycerin and certain other high-risk drug components1includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform adequate identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of this component for use in manufacture of your drug products.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.In your response, you commit to updating your standard operating procedure (SOP) to require testing of incoming materials for identification, microbiology, and other required tests. You state that you will send your component retains for testing before use in new drug product batches. Additionally, you commit to sampling the first lot received from a supplier and periodically sampling subsequent lots for comparison testing against the COA. Your response is inadequate. You failed to provide a detailed plan for how your components will be tested, including test methods and review of compendial requirements, or a timeline for implementing the corrective actions proposed. Further, you did not consider a retrospective review of previously distributed OTC drug products.Without adequate testing, you do not have appropriate assurance that components conform to appropriate specifications prior to use in the drug products you manufacture.In response to this letter, provide:A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product lots for the presence of DEG and EG.A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, propylene glycol). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective actions and preventive actions (CAPAs) that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.The chemical and microbiology quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).Your sampling plans prior to the release of your drug products are not sufficient to assure their quality. Specifically, your sampling and testing plan for SmileSense Fluoride Toothpaste and KT Tape Pain Relief Gel is not adequately justified to represent the quality attributes of the entire drug product batch. For example, for a(b)(4)batch of your SmileSense Flouride Toothpaste, a suspension drug product, single(b)(4)samples were collected from the(b)(4)and from the(b)(4)of the bulk tank.(b)(4)was used to evaluate microbiological attributes and the other for assay, without adequate justification, such as development uniformity studies or supportive process qualification data, that the collected samples are representative of the entire batch.In addition, you were unable to provide documentation to demonstrate that your(b)(4)water system is adequately monitored and tested for conductivity or microbiology.(b)(4)water from this system was used as a component in the drug products you manufacture and distribute. In your response, you state that the justification for product sampling is being evaluated. You also state that the SOP governing the frequency, methods, and responsibility for performing water sampling would be reviewed. Your response is inadequate. You did not provide or commit to provide any justification for your drug product sampling plans. Additionally, you did not provide or describe a specific plan or timeline for monitoring to ensure the suitability of your(b)(4)water. Further you did not consider testing retains or a retrospective review of distributed batches where there was incomplete or inadequate water testing.Without appropriate sampling plans, you do not have scientific evidence to support whether your drug products meet their established finished product chemical and microbiological specifications. Product released without adequate determination of homogeneity or microbiological evaluation poses a risk to patients.In response to this letter, provide:A comprehensive, independent assessment of your in-process monitoring and sampling operations, focusing on each upstream process step that can introduce variability. Provide your remediation plan to improve: (1) in-process detection of variation; (2) upstream controls; and (3) sampling plans.A list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a batch disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.The current action/alert limits for total counts and objectionable organisms used for your(b)(4)Water system. Ensure that the total count limits for your(b)(4)water are appropriately stringent in view of the intended use of each of the products produced by your firm.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets(b)(4)Water,(b)(4)monograph specifications and appropriate microbial limits.3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not provide adequate oversight and control over your drug manufacturing operations. Specifically, your QU did not implement adequate controls to ensure the complete documentation of the accomplishment of each significant step in the manufacture of your drug products. For example:Your scale calibration logs consisted of loose pages printed without unique identifiers.You could not provide a non-conformance (NC) report referenced in(b)(4)executed batch records because your previous NC data system was no longer maintained.Shred bins containing what appeared to be CGMP records were located in your manufacturing and warehouse areas.Water monitoring records stored on an employee’s personal computer could not be provided.You could not provide data to support the labeled expiration date of drug products manufactured by your facility.In your response, you commit to updating your SOPs to ensure adequate control of your original CGMP documents, evaluating other options to track non-conformances, and removing the shred bins. Your response is inadequate as it did not provide sufficient detail or evidence of corrective actions to bring your operations into compliance with CGMP.An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.In response to this letter, provide:A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources 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. 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.A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.Unapproved New Drug and Misbranded Drug Violations“(b)(4)” is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because it is intended to affect the structure or any function of the body.Examples of claims from the “(b)(4)” product labeling, including the product website,(b)(4), that provide evidence of the intended use (as defined in 21 CFR 201.128) of the product as a drug include, but may not be limited to, the following:“(b)(4)”“(b)(4).” [from the product label]“(b)(4)” [from the product label]“(b)(4).” [from the product label]“(b)(4)…” [from the product website]Unapproved New Drug ViolationsBased on the above labeling evidence, “(b)(4)” is intended for use as an oral antiseptic drug product. As described below, this product is an unapproved new drug marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for this drug product identified above.OTC oral antiseptic products have been the subject of rulemakings under the Agency’s OTC Drug Review. In particular, oral antiseptics were addressed in a TFM entitled “Oral Health Care Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Oral Antiseptic Drug Products; Proposed Rule,” 59 FR 6084 (February 9, 1994) (hereinafter “Oral Antiseptics Proposed Rule”). The Oral Antiseptics Proposed Rule classified a number of active ingredients as Category III for use by consumers in antiseptic-containing drug products applied topically to the oral cavity to help prevent infection in minor cuts, scrapes or oral irritation caused by dental procedures, dentures, orthodontic appliances, or accidental injury, because additional effectiveness data are needed to support a determination that a drug product containing one of these active ingredients would be GRASE for use as an OTC oral antiseptic.Section 505G of the FD&C Act, 21 U.S.C. 355h governs nonprescription drugs marketed without an approved application. Under section 505G(a)(3) of the FD&C Act, drugs that were classified as Category III for safety or effectiveness in a tentative final monograph (TFM) that is the most recently applicable proposal or determination for such drugs issued under 21 CFR Part 330 – and that were not classified as Category II for safety or effectiveness – are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM and comply with all other applicable requirements.However, “(b)(4)” does not conform to the Oral Antiseptics Proposed Rule, nor any other TFM, proposed rule, or final rule, and does not meet the conditions under sections 505G(a)(1) or 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505. Specifically, the product label lists the following ingredients: “(b)(4)” None of these ingredients are permitted in combination or as sole active ingredients in the Oral Antiseptics Proposed Rule or any other TFM, proposed rule, or final rule.In addition, the product label includes claims, such as to “(b)(4),” that go beyond merely describing the general intended uses for an oral antiseptic drug product as set forth in the Oral Antiseptics Proposed Rule.Thus, as formulated and labeled, “(b)(4)” does not comply with the applicable conditions set forth in the Oral Antiseptics Proposed Rule.2Moreover, there is no evident basis under the FD&C Act under which this product would be legally marketed without an approved application. Thus, this product is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p). Accordingly, this product is an unapproved new drug marketed in violation of section 505(a) of the FD&C Act, 21 U.S.C 355(a).Introduction or delivery for introduction of such a product into interstate commerce is prohibited under section 301(d) of the FD&C Act, 21 U.S.C 331(d).Misbranded Drug ViolationsAdditionally, “(b)(4)” is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because this product is a nonprescription drug subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but does not comply with the requirements for marketing under that section and is not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355. The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.Cosmetics Manufactured for Distribution in the United StatesIn addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations 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 violations may also prevent other Federal agencies from awarding contracts.Failure to address violations 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 violations 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 violations.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 violations 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 3013719300 and ATTN: Christina Capacci-Daniel.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research/S/Tina SmithCaptain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceCenter for Drug Evaluation and Research_______________________1Components with higher risk of DEG or EG contamination compared to other drug components.2FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that “(b)(4)” product is GRASE for use under the conditions prescribed, recommended, or suggested in its labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).