根据省委统一部署，2024年3月29日至5月30日，省委第一巡视组对省药品监督管理局党组开展了巡视。9月21日，省委巡视组向省药品监督管理局党组反馈了巡视意见。按照巡视工作有关要求，现将巡视整改进展情况予以公布。一、巡视整改组织领导情况巡视反馈以来，省药监局党组坚决扛起巡视整改的政治责任，把巡视整改作为重大政治任务，诚恳照单全收巡视组反馈的8个方面26个问题和上一轮巡视整改还需进一步完善的3个问题，着力从思想认识、组织领导、部署推进、督查落实等方面加大力度，蹄疾步稳抓好巡视意见整改落实。（一）提高政治站位，统一思想行动。省药监局党组充分认识到巡视是党章赋予的重要职责，是加强党的建设的重要举措，是从严治党、维护党纪的重要手段，坚持把巡视整改作为坚定拥护“两个确立”、坚决做到“两个维护”的重大政治任务和全面提升全省药品监管工作水平的重要契机，始终以高度的政治自觉、思想自觉、行动自觉抓实整改。深学笃用习近平总书记关于巡视工作的重要论述，专题学习新修订的《中国共产党巡视工作条例》，高质量召开巡视整改专题民主生活会，带动全局上下以高度的思想自觉正视问题，以坚决的态度、严格的标准、有力的措施，推动巡视整改各项任务落地见效。（二）强化组织领导，压实整改责任。省药监局党组切实担负起整改主体责任，第一时间成立巡视整改工作领导小组，党组主要负责同志任组长、其他班子成员任副组长、分管领导兼任办公室主任，领导小组 下设办公室及专项整改工作组，建立起党组统一领导、班子成员分工协作的巡视整改机制，形成上下协同、点面结合、统筹推动的整改工作格局。省药监局党组主要负责同志认真履行巡视整改“第一责任人”职责，始终站在整改工作第一线，5次主持召开党组会议，专题听取巡视整改进展汇报，同时直接挂帅党组建设、选人用人、信息化建设等16条重点巡视整改措施，既统筹推进总体工作，又带头整改重难点问题，以自身的担当作为带动整体工作。其他班子成员自觉履行“一岗双责”，全力推动分管领域内的巡视整改任务落到实处。（三）突出问题导向，坚持统筹推进。针对省委巡视组提出的问题，逐一对账梳理，逐条分析反思，详细制定工作方案，建立3个整改工作台账，逐项明确责任领导、牵头及参与单位、整改时限和目标要求，实施台账管理，严格“对账”销号，确保整改任务件件有着落、事事见成效。牢固树立系统观念，强化对巡视整改过程的管控，统筹协调整改工作中存在的突出问题，实行“简单问题率先改、复杂问题协作改、重点问题挂牌改”的工作机制，巡视整改工作领导小组定期调度进展，各专项整改工作组和牵头单位按照分工，推动相关责任单位主动抓整改，确保不断取得丰硕成果。（四）完善督查评估，推动标本兼治。突出举一反三、系统施治，把解决巡视反馈突出问题与提升药品监管治理能力相互融合，把解决本轮巡视反馈问题与持续推进上轮巡视反馈问题整改一体贯通，坚持从政治上查找根源、从制度上分析原因、从机制上堵塞漏洞，在巡视整改程序规范、审评审批流程优化、质量安全监管、廉政建设等方面形成一批制度性安排，促进了全省药品监管和医药产业高质量发展。建立跟踪督办、评估通报、严肃问责的工作机制，督促各单位对照巡视反馈问题自查自纠，并将巡视整改情况纳入调研督查和政治巡察重要内容，确保所有问题全面改、改彻底、改到位。在省委的正确领导和省纪委监委机关、省委巡视办的大力指导下，经过集中整改，省药监局的巡视整改工作取得了明显成效。二、整改进展情况及成效（一）关于“上轮巡视整改责任落实方面”问题的整改情况一是落实党组主体责任。成立巡视整改工作领导小组，每月研究推动巡视整改工作，加强对整改事项的研究会办和跟进督促，将巡视整改完成情况“回头看”纳入2025年度省药监局工作要点。制修订各类规章制度12个，在分支机构建设、审评审批流程优化、质量安全监管等方面形成一批制度性安排。二是健全信息化建设统筹机制。省药监局主要负责同志主持召开信息化建设推进会，进一步强化“五个一”统筹协调体系。已完成药品智慧监管综合平台一期，搭建了整体平台架构，有序开展存量系统的整合集成和数据共享工作。三是加强巡视整改过程跟踪问效。派驻省市场监管局纪检监察组严格审核把关巡视整改方案，推动建立巡视整改台账制度，通过约谈提醒等方式定期督促巡视整改进展。建立巡视整改联络员机制，每月梳理汇总整改进展情况，有针对性开展督办。（二）关于“推动医药新质生产力发展支撑不足”问题的整改情况一是加强检验检测能力。省医疗器械检验所完成新版GB9706系列标准扩项宣贯、人员培训与考核以及扩项所需设备采购，已具备新版GB9706系列标准75项检验能力。人工晶体等已通过CMA认定和CNAS认可，具备检测能力。省药品监督检验研究院提升疫苗批签发能力储备，目前正开展相关检验。二是大力支持企业创新。出台《江苏省药品上市后生产场地变更优先受理审评实施细则（试行）》，上线“创新型药械咨询服务交互平台”，制定《创新型医疗器械指导服务工作指南（试行）》，建立工作专班，实行“一品一专班”工作机制，全程跟踪服务。联系全省11个重点医疗器械园区，主动摸排我省创新药械产品研发及申报进展，在线服务243个医疗器械创新产品。三是强化科研技术攻关。2024年以来，省药品监督检验研究院开展面向企业提供支持创新药研制阶段质量标准的制订服务127项，比2023年增加52.7%，开展生物技术药研究24项。省医疗器械检验所利用可用性测试平台开展专题培训2次，签订3项可用性总结测试合同，完成2项科研成果转化。（三）关于“服务高质量发展还有差距”问题的整改情况一是建立常态化对接机制。建立与长三角分中心定期会商工作机制，动态调整长三角区域药品重点项目清单44个，梳理17个优先服务品种。联合长三角分中心开展5场创新药注册相关专题培训及江苏医药产业发展专题服务活动，指导帮助重点药品和创新药品种申报10个。2024年，江苏省获批1类创新药13个，位居全国第一。二是加强助企服务指导。建立我省268个创新产品信息库，定期收集第三类创新型医疗器械在研产品信息，及时做好上门服务工作。利用“创新药械咨询服务交互平台”，服务指导当地园区企业，2024年9月以来解决企业注册申报问题67个，满意度100%。2024年培训分中心人员250人次，建立办件抽查制度，强化审评核查办件质量管理。三是提高审评审批效率。修订《审评核查分中心医疗器械注册技术审评质量审核与评估控制程序》《境内第二类医疗器械审评审批质效评估检查内容》，推进分中心对二类医疗器械低风险产品独立审评能力建设。制定《审评核查分中心医疗器械注册技术审评质量审核与评估控制程序》，每季度组织开展分中心注册审评质量审核。（四）关于“推进高水平监管存在短板”问题的整改情况一是加强制度保障。修订《江苏省药品监督管理条例》已被省政府、省人大常委会列入2025年立法工作计划预备项目。印发《江苏省中药材标准和中药饮片炮制规范制修订工作细则》，制订江苏省中药饮片炮制规范制修订指导原则。优化中药配方颗粒标准制定模式，出台省外已发布的中药配方颗粒质量标准转化为江苏省试行标准工作程序，发布省级中药配方颗粒标准49个、省级试行标准6个。配合省卫生健康委相关部门加强全省医疗机构中药饮片代煎服务管理，配合出台《江苏省中药饮片代煎服务质量管理规范》。发布开展江苏省药品经营批发零售一体化许可工作的通告，全面推行药品经营批零一体化许可改革。二是完善协同机制。印发《江苏省药品监督管理局关于加强跨部门跨区域跨层级药品监管协同的实施意见》。落实稽查执法的职责分工和衔接机制，利用稽查执法信息化系统，了解掌握省内案件查办情况，组织专人协调案件协查及对接省内疑难案件，实现执法联动、业务协同。三是规范行政执法。加大重大复杂案件、跨区域案件的牵头指导力度，加强“黑窝点”案件的挂牌督办，2024年对省内7件案件进行挂牌督办。印发《江苏省药品监督管理局政府信息公开内部办理流程》，对依申请公开办件进行合法性审查。开展稽查执法和投举业务能力培训，进一步规范完善投诉举报内部办理程序。四是提升智慧监管实效。与国家药监局、省大数据中心加强沟通对接，进一步实现数据资源的共享。完成13个地市数据的对接汇集，编制完成智慧监管平台二期项目方案，梳理全部需整合系统，向省数据局上报系统整合计划。正式上线智慧监管化妆品生产子系统。（五）关于“把稳守牢安全底线还有弱项”问题的整改情况一是加强安全监管。出台《江苏省药品监督管理局推动企业落实质量安全主体责任的激励和约束措施管理规定（试行）》。开展药品网络销售环节集中治理行动，全省共检查药品网络交易第三方平台、药品网络销售企业1.4万余家，检查零售药店委托的药品零售配送企业160家。加强对药械网售监测线索的分办、调度、反馈等工作，2024年处置监测线索252条。印发《市县药品监管能力标准化建设评价指标体系》，开展2024年度能力标准化建设评估。二是加强风险防范。出台《江苏省药品领域涉嫌犯罪案件检验认定工作细则》，开展稽查执法能力培训，发布稽查执法典型案例，加强对基层药品案件查办的指导。印发《关于落实企业主体责任进一步加强对药品批发企业和零售连锁总部监管的通知》，指导各地切实加强药品购销渠道、运输储存、药品追溯等重点环节监管。2024年开展药品经营和使用专项检查，全省共检查药品经营和使用单位4.7万家次、疫苗配送使用单位2800余家次。强化省市县能力体系建设，省药品不良反应监测中心开展医疗机构宣贯培训、季度风险信号讨论。组织开展全省药品不良反应个例报告质量评估。加强与省网信办的涉药品安全舆情信息沟通协调，发布风险预警和监管提示，组织药品安全应急演练桌面推演，提高应对处置不良舆情和开展舆论引导的能力。三是严防安全事件。分片区组织召开全省药品生产经营监管风险会商会，明确进一步加强监管、防控风险的措施。对药品批发企业和零售连锁总部开展协同检查，加强对医疗美容医疗器械、青少年近视防治相关医疗器械等重点产品的监督检查。印发《2024年江苏省化妆品安全风险监测工作方案》《江苏省化妆品网络经营平台监管工作方案》，加强化妆品网络销售安全监管。指导全省市县市场监管部门开展2024年度化妆品经营“双随机、一公开”检查，共完成1600余家化妆品经营企业检查。（六）关于“廉政风险防控不够有力”问题的整改情况一是完善内控机制。建立医疗器械审评审批协调联席会议制度，省药监局审评中心修订《外请专家管理制度》，完善专家管理流程，进一步增加“双主审”模式运用比例。加强检查员党风廉政教育，严格落实“一检查两报告”制度，组织开展电话回访及现场廉政回访。持续推动“廉洁药监”建设，健全“全周期管理”机制，分层分类开展各类廉政教育。开展药品行政审批质效抽查，重点围绕审批环节工作人员的工作作风、服务态度、廉洁情况进行监督检查。结合医药领域腐败问题集中整治、行风建设三年攻坚行动，开展整治群众身边不正之风和腐败问题专项行动，紧盯“五个聚焦”重点整治任务，扎实深入推进集中整治工作。二是严守财经纪律。组织开展规划财务与信息化综合培训，督促各单位进一步规范政府采购工作，结合内部审计对部分单位执行情况进行督查。严格落实“零基预算”要求，按照《江苏省药品监督管理局政府采购管理暂行办法（试行）》，加强对政府购买服务项目立项审核、服务合同票据把关，2025年度宣传服务经费预算大幅压减。出台《江苏省药品监督管理局评审工作专家劳务费实施细则（试行）》，修订《江苏省药品监督管理局审核查验中心检查费用报销规定》，进一步加强专家劳务费管理。会同省财政厅修订出台《江苏省药品安全监管专项资金管理办法》，进一步规范管理专项资金的分配与使用，对专项资金使用情况开展审计监督。三是严格监督执纪。派驻省市场监管局纪检监察组建立与省药监局工作联系制度，协作开展信访举报核查，严格监督执纪问责，加强对党员干部的警示教育，对新提拔处级干部开展集体廉政谈话。畅通信访渠道，公布监督举报电话和举报通信地址，及时受理群众来信来访，加强对信访线索的调查研判。出台《江苏省药品监督管理局行风监督员管理暂行办法》，聘请首批行风监督员，强化社会监督和群众监督。2024年组织开展全系统廉政风险排查，全面排查廉政风险点，制定务实管用的防控措施。开展违规吃喝、酒驾醉驾专项整治，组织签署杜绝违规吃喝、酒驾醉驾承诺书，深化医药领域腐败问题集中整治、行风建设三年攻坚行动。制定《江苏省药品监督管理局利益冲突与回避制度》，组织监管人员签订《防范利益冲突及廉政承诺书》、外聘专家签订《无利益冲突声明》，进一步健全内部规章制度。加强检查分局分中心作风建设，组织分中心开展廉政风险排查，对检查分局、分中心企业来访公开接待情况进行督查。（七）关于“干部队伍作风建设不够扎实”问题的整改情况一是强化整治形式主义为基层减负。严格发文审核，管控发文数量，2024年局机关面向基层发文数较2023年有所减少。统筹制定省药监局年度会议计划，合并精简主题相似、时间接近、参会人员相同的会议。实行全局性调研活动备案制，统筹各处室、单位开展调研活动。对同处室同类型政务、事务服务事项工作群进行整合，对于临时性、阶段性的工作群或长期未使用、使用频率过低的及时解散、注销。二是树牢以人民为中心的发展思想。印发《关于做好我省短缺药品保供工作的通知》，做好相关工作。发布“说明书适老化备案”问答，提高企业改造质量和备案效率，加速新版说明书上市流通使用，已完成82个品种适老化说明书备案。省药监局官网、公众号开设适老化说明书专栏，增加适老化说明书查询功能，供社会公众查询。发布《关于印发部分药品上市后备案事项审查要点（试行）》，对于改变不涉及技术审评的载明事项、说明书适老化、变更药品包装规格、增加一致性评价标识等4个事项，五日内审查办结。指导省医药商业协会、省执业药师协会开展“江苏省家庭过期药品回收公益活动”，全省共有137家药品零售连锁企业、719家门店参与活动。三是加强干部队伍作风建设。加强干部队伍建设统筹谋划，进一步贯彻落实《江苏省药品监督管理局关于进一步强化干部选培使用锻造“两争一前列”先锋队的实施意见》，制定出台省药监局容错纠错机制实施意见，激励干部担当作为。印发《江苏省药品监督管理局关于进一步加强公务员考核工作的实施方案》，以考促干，提升干部精气神。推动“能上能下”，2024年下半年组织开展处级领导干部选拔任用和处级职级晋升工作，对不适宜担任现职的副处职领导干部进行调整。结合年度工作考核、组织生活会，开展谈心谈话，从工作、生活等多角度了解掌握干部思想动态，鼓励其积极履职尽责。（八）关于“专业人才队伍建设滞后”问题的整改情况一是加强人才培养。成立省药监局人才工作领导小组，制定出台《江苏省药品监督管理局干部队伍建设规划（2024-2028年）》。积极开展药学专业（药品）职称评审，成功申报生物医药工程序列职称评审。加快推进省药监局干部教育培训工作科学化、制度化、规范化，制定印发《江苏省药品监督管理局干部教育培训管理办法》。2024年以来省药监局共举办监管专业、综合素质等培训40次，不断强化药品监管干部人才队伍整体素质。二是引育高层次人才。指导省药监局所属事业单位开展高层次人才招聘工作、申报专业技术二级岗人才，组织省药监局所属事业单位向国家药监局申报推荐药品审评专家及国家级检查员。省药品监督检验研究院引进一名博士后进站。三是补充专业技术人才。积极对上争取增加专业技术人才编制。分三批共完成269名省级药品检查员评聘工作，进一步优化检查员人才梯队结构，提升检查员能力素质。加大检查员培训培养力度，2024年组织各类检查员培训29次，同时按照PIC/S的要求，对药品生产检查员开展分级培训。拟定《检查员年度考核方案》，加强检查员管理和考核。加强国家级检查员推荐力度，新增国家级检查员9名、境外检查员2名，13个地市目前均已有国家级检查员。对标PIC/S要求不断提升检查员能力水平，顺利通过PIC/S模拟评估。（九）关于“选人用人工作不够规范”问题的整改情况一是严格执行制度。优化干部选拔任用工作方案，在民主推荐环节规范谈话推荐、会议推荐先后顺序。清理规范省药监局所属事业单位在机关长期工作人员。省药监局党组每次讨论决定干部任免事项后，及时形成专题会议纪要。二是加强干部配备。结合2024年度省药监局所属事业单位领导班子考核工作继续开展事业单位优秀年轻干部调研。省药监局党组会专题传达学习省委有关会议精神，对省药监局处级班子建设提出部署要求，制定出台《江苏省药品监督管理局干部队伍建设规划（2024-2028）》。强化省药监局所属事业单位领导班子建设，加强干部轮岗交流，提任交流公务员到省药监局所属事业单位任班子成员，进一步拓宽公务员和事业单位之间的交流渠道。三是优化干部队伍结构。加强优秀年轻干部选培使用力度，结合2024年度考核工作继续开展优秀年轻干部调研工作，选派90后优秀年轻干部参加年轻干部交流锻炼。2024年下半年，组织开展处级领导干部提拔使用工作，已配备40岁左右处长、85后副处职干部共3名。四是化解突出矛盾。积极贯彻落实公务员职务与职级并行政策，开展检查分局科级干部晋升工作。积极向上级部门争取，核定13个检查分局副局长职数。2024年下半年，继续开展检查分局副局长选拔任用工作，打通检查分局之间横向交流渠道，拓宽检查分局干部职务职级晋升通道。三、下一步工作打算经过集中整改，巡视整改工作取得了明显阶段性成效，但仍需进一步深化落实，持续巩固拓展整改成效，切实把巡视整改成果转化为全面从严治党和推动药品监管事业高质量发展的实际成效。一是强化理论武装，夯实持续整改的思想根基。自觉把巡视反馈问题的持续整改，作为捍卫“两个确立”、践行“两个维护”的具体行动，作为全面从严治党的重要抓手，作为推动药监事业发展的现实需要，以高度的政治责任感做好巡视“后半篇文章”，确保整改工作的常态化、长效化。二是突出建章立制，巩固提升巡视整改质效。对已经整改问题坚持举一反三、标本兼治，适时组织开展“回头看”，进一步健全完善制度机制，构建经常性检视和整改问题的制度体系，巩固和提升整改成效，确保整改工作零死角、无盲区。三是用好巡视成果，推进药品监管事业发展。坚持把巡视整改成果贯穿到践行新发展理念和药监事业高质量发展的全过程、各方面，提振精神、提升能力，脚踏实地、真抓实干，把整改成效转化为干事创业的强大动力，以巡视整改推动药品监管各项工作走在前、作示范。欢迎广大干部群众对巡视整改落实情况进行监督。如有意见建议，请及时向我们反映。联系方式：电话025-83273505；邮政信箱：南京市鼓楼街5号；电子邮箱：jigjw@da.js.gov.cn。中共江苏省药品监督管理局党组2025年5月20日

行政相对人名称广东xxx有限公司行政相对人类别法人及非法人组织行政相对人代码_1(统一社会信用代码)XXX法定代表人XXX行政处罚决定书文号粤药监妆罚〔2024〕6009号违法行为类型生产未经注册的特殊化妆品、未按照化妆品生产质量管理规范的要求组织生产。违法事实当事人生产的***染发膏经检验“检出产品标签及注册资料载明的技术要求未标示的染发剂：对氨基苯酚等”，当事人生产的***黑发露经检验“检出注册资料载明的技术要求未标示的染发剂：苯基甲基吡唑啉酮。未检出注册资料载明的技术要求标示的染发剂：间氨基苯酚”，当事人生产的该2批次化妆品属于染发类化妆品，改变了批准文号的配方。当事人在生产***染发膏/黑发露/染发露/炫彩露等16个批次产品过程中未形成生产记录、销售记录，未进行留样。处罚依据《化妆品监督管理条例》第五十九条第二项、第六十条第三项处罚类别1.没收违法所得；2.没收非法财物；3.罚款；4.吊销许可证件；5.责令停产停业。处罚内容1、没收违法所得33422.6元；2、没收违法生产的化妆品2989盒；3、处罚款632942.4元；4、责令停止化妆品经营30日；5、吊销化妆品生产许可证（编号：粤妆20210101）；6、10年内不予办理其提出的化妆品备案或者受理其提出的化妆品行政许可申请；7、对当事人的法定代表人***处罚款102000元； 8、对当事人直接负责的主管人员***处罚款10000元。处罚有效期3年处罚决定日期2025年5月9日处罚机关广东省药品监督管理局处罚机关统一社会信用代码11440000MB2D034421数据来源单位广东省药品监督管理局数据来源单位统一社会信用代码11440000MB2D034421

化妆品抽样检验是化妆品上市后监管的重要手段，对及时发现化妆品安全风险、依法打击化妆品违法行为、规范化妆品生产经营行为等具有重要作用。2024年，国家药监局以习近平新时代中国特色社会主义思想为指导，认真落实“四个最严”的要求，依据《化妆品监督管理条例》等法律法规，组织在全国范围内开展国家化妆品抽样检验工作，旨在推动化妆品产业高质量发展，保障公众用妆安全。　　一、总体情况　　全国药品监督管理部门坚持问题导向、聚焦监管关切，重点关注风险程度较高的化妆品品种和企业，持续强化对重点领域、重点场所的抽检力度，组织对宣称祛痘类、牙膏、普通护肤类、彩妆类、祛斑美白类、儿童类等12类化妆品开展抽检工作，共抽检21362批次产品。经33家化妆品检验机构依据《化妆品安全技术规范》（2015年版）等检验，其中20889批次产品符合规定，占比97.79%。对抽检不符合规定产品涉及的化妆品生产经营者，各省（区、市）药品监督管理部门依法组织调查，发现违法行为的，严肃查处；涉嫌犯罪的，依法移送公安机关。　　二、 抽样情况　　各省（区、市）化妆品抽样批次数量分布情况见图1。抽样主要采用现场抽样和网络抽样两种方式进行，抽样的地域分布情况见图2。样品的产地分布情况见图3。图1 各省（区、市）化妆品抽样分布图图2 各地域类型抽样数量分布图图3 样品产地分布图（按化妆品生产企业所在地划分）注：国内其余省份包括：湖北、陕西、湖南等18个省（区、市）。　　三、检验情况　　在抽检的12类化妆品中，宣称祛痘类、牙膏、普通护肤类、彩妆类、祛斑美白类、儿童类产品等6类化妆品抽检符合规定批次占比均达到99%以上，见图4。图4 12类化妆品抽检符合规定批次占比图　　国家药监局将深入贯彻党的二十大和二十届二中、三中全会精神，继续坚持“全国一盘棋”理念，持续提升国家化妆品抽样检验工作能力和水平，筑牢安全底线，保障人民群众用妆安全，为推进化妆品产业高质量发展贡献力量。

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-25-59Product:DrugsRecipient:Mr. Jimmy DuivenvoordenSite ManagerNWL Netherlands Services B.V.Amperestraat 12 Hillegom2181 HBZuid-HollandNetherlandsJimmy.duivenvoorden@newellco.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-59April 1, 2025Dear Mr. Duivenvoorden:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, NWL Netherlands Services B.V., FEI 3003696942, at Amperestraat 12, Hillegom, Zuid-Holland, Netherlands, from October 14 to 18, 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).We reviewed your November 8, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your investigations lacked sufficient root cause determinations, corrective actions and preventive actions (CAPAs), and assessment of all potentially affected batches. For example, you did not adequately investigate repeated out-of-limit (OOL) results for microbial content in your(b)(4)system. You used(b)(4)generated from your(b)(4)system as a major component of drug products. In 2024, you obtained seven OOL events, at least two with results as high as 10,000 colony-forming units (CFU)/mL. After the first OOL event, your firm’s response to subsequent OOL events was limited to reviewing(b)(4)system test results from the day before and after, along with relying on finished product test results.You have not shown that you can consistently produce(b)(4)suitable for the manufacture of pharmaceutical products. At a minimum, your(b)(4)must meet the United States Pharmacopoeia (USP) monograph for(b)(4)with appropriate microbial limits. It is essential that you effectively control, maintain, and monitor the system to ensure it consistently produces(b)(4)suitable for pharmaceutical use.In your response, you indicate that individual investigations with impact assessments will be created when you obtain OOL results. You also indicate that your quality lead will review and document(b)(4)results on a(b)(4)basis. Furthermore, you commit to training your quality team on when to report and escalate an OOL result.Your response is inadequate. It fails to provide a comprehensive retrospective risk assessment into the microbial content of(b)(4)used for production of drug products and evaluate the full scope and impact of OOL results. Furthermore, you do not provide any supporting documentation about the CAPAs that were described, such as updated procedures and training records.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification 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 assurance oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.o Include your updated investigation procedures and a clear description of how investigations are initiated, documented, and completed.A detailed risk assessment addressing the potential effects of the observed(b)(4)system failures on the quality of all drug product batches currently in U.S. distribution or within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recall.2. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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 failed to perform identity testing of each component lot used in the production of your over-the-counter drug products, including(b)(4), your active pharmaceutical ingredient. You also relied on the certificates of analysis (COAs) from your suppliers and failed to establish the reliability of each of your component suppliers’ test analyses at appropriate intervals.In your response, you acknowledge the need to update your procedure to require testing of incoming materials, such as(b)(4), for impurities (e.g.,(b)(4)).Your firm’s response is inadequate. You fail to provide a specification for impurities, such as(b)(4), in your incoming materials. Without appropriate testing of components and ingredients, you cannot ensure the quality and safety of your drug products.(b)(4)You manufacture multiple drugs that contain(b)(4). The use of(b)(4)contaminated with(b)(4)has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document(b)(4).In response to this letter, provide: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.The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.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 re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.A comprehensive assessment of the risk to drug product quality for the batches manufactured using(b)(4)that did not undergo incoming identity testing that remain within shelf-life in the U.S. market.(b)(4)testing for all(b)(4)drug product batches released and distributed in the United States within expiry.3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).Your laboratory equipment used to generate analytical data for finished drug product release lacked restricted access and sufficient controls. There was no assurance that your systems had the appropriate controls to prevent data deletion and record modifications. For example, you did not establish unique usernames and passwords, and laboratory staff had administrator rights allowing uncontrolled access to delete or modify high performance liquid chromatography (HPLC), gas chromatography (GC), and fourier transform infrared spectroscopy (FTIR) files. Furthermore, your firm did not adequately maintain backups of data generated by your laboratory equipment.It is important to maintain strict control over CGMP electronic data to ensure that all additions, deletions, or modifications of information in your electronic records are authorized and appropriately documented. Without complete and accurate records, you cannot ensure your firm makes appropriate batch release, stability, and other decisions that are fundamental to ongoing assurance of drug product quality.In your response, you state that your firm’s quality lead will perform a(b)(4)review of software systems and data to confirm there have been no unauthorized editing or deletion of files. You also indicate that you will create a procedure to identify the required access rights for each job function.Your response is inadequate. Your response fails to provide a comprehensive review of your system for identifying deleted or modified data.In response to this letter, provide: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.A comprehensive, independent assessment of computer system performance and security. Provide a report that identifies vulnerabilities in the design and controls, and a thorough CAPA plan for each of your laboratory computer systems, which addresses the following elements:o A list of all hardware (both standalone and networked) and software used by your laboratory.o Identify and evaluate vulnerabilities in performance and security of all of these computer systems, including but not limited to, their configurations, administrative rights, password controls, audit trails capabilities, and state of implementation for each system, qualification/validation status, deviation history, backup capabilities, network requirements, completeness of data records, suitability of current hardware/software for its intended use(s), change management, and management oversight.o Detail the associated user privileges for each system.o Specify user roles and associated user privileges for all staff levels who have access to the laboratory computer system, and provide organizational affiliations, responsibilities, and titles. Clearly specify all staff who have administrator privileges.o Fully describe how you will ensure segregation of firm personnel involved with laboratory testing from those with administrator rights. For all staff roles that are permitted to have administrative rights, specify the scope and type of privileges.o Assess each system to determine if unique usernames and passwords are used.o Evaluate policies and procedures regarding computers and data governance, with special emphasis on audit trails, prohibiting data deletion, and appropriate modifications of results. Specify how your firm prevents data deletion and undocumented/inappropriate modifications of data. Also describe how you ensure original data and information is always preserved. Provide your procedures for audit trail review.o Provide requirements for data retention and backup for all laboratory systems.Summarize your interim controls to assure reliable performance and security while your CAPA plan is being implemented.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. 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.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. 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 any violations.Failure to address any violations may also result in the FDA refusing admission of articles manufactured at NWL Netherlands Services B.V. Zuid-Holland, Netherlands, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).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 3003696942 and ATTN: Yasamin AmeriSincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Product:Biologics、Medical DevicesRecipient:Brian ThomCEOUnited Health Products, Inc.520 Fellowship Road, Suite #D-406Mt. Laurel,NJ08054United States(b)(6)@uhpcorp.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWarning LetterMarch 24, 2025Dear Mr. Thom:This Warning Letter is to inform you of objectionable conditions observed during the Food and Drug Administration (FDA) inspection conducted at United Health Products, Inc. from September 23, 2024, to October 4, 2024, by an investigator from the FDA’s Office of Bioresearch Monitoring Inspectorate (OBMI). This inspection was conducted to determine whether activities and procedures as sponsor in the significant risk clinical study “Efficacy and Safety of HemoStyp as an Adjunct for Management of Secondary Hemostasis in the Operative Setting,” for CelluSTAT Absorbable HemoStat, Premarket Approval (PMA) Application,(b)(4), complied with applicable federal regulations. The CelluSTAT Absorbable Hemostat is a device as that term is defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)(1), because it is 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 function of the body. This letter also requests prompt corrective action to address the violations cited and discusses your written response, dated October 25, 2024, to the noted violations.The inspection was conducted under the Bioresearch Monitoring (BIMO) Program designed to ensure that data and information contained in requests for Investigational Device Exemptions (IDEs), PMA applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.Our review of the inspection report prepared by OBMI revealed serious violations of Title 21, Code of Federal Regulations (CFR) Part 812 - Investigational Device Exemptions and 21 CFR Part 50 - Protection of Human Subjects, which concern requirements prescribed under section 520(g) of the Act, 21 U.S.C. § 360j(g). At the close of the inspection, the FDA investigator presented an inspectional observations Form FDA-483 for your review and discussed the observations listed on the form with you. The deviations noted on Form FDA-483, your written response, and our subsequent review of the inspection report are discussed below:1. Failure to submit an IDE application to FDA and failure to obtain FDA approval prior to beginning an investigation for which FDA’s approval is required [21 CFR 812.20(a)(1) and (2).Sponsors must submit an IDE application to the FDA if the sponsor intends to use a significant risk device in a clinical investigation. In addition, a sponsor may not begin an investigation for which FDA’s approval of an application is required until FDA has approved the application. You did not submit an IDE application to FDA or obtain FDA approval prior to beginning such an investigation.You conducted your study, UHP001, without submission and approval of an IDE application to FDA. The Western Copernicus Group (WCG) Institutional Review Board (IRB) determined that the procedures in the research posed a potential significant risk to subjects and requested documentation of the FDA’s non-significant risk (NSR) determination in multiple communications. You provided to the IRB FDA written feedback for(b)(4)and FDA meeting minutes for(b)(4), which had been modified from the FDA official correspondence by removal of references to future IDE submission and by addition of language that purported to indicate FDA agreement that the study was non-significant risk (NSR). In particular, you provided the transmittal email from FDA along with these meeting minutes, which imply that the meeting minutes that you submitted to the IRB were those provided by FDA to you as the official record. The IRB used this documentation, which misrepresented the FDA risk determination for this study, to support their determination of the regulatory status of the study, and to review and approve this study without FDA oversight.FDA maintains that the study UHP0001 that you have conducted to support(b)(4)as a Class III device is considered a significant risk device clinical investigation for which you should have submitted an IDE application to FDA and obtained FDA approval prior to initiation. Your device is an absorbable hemostat intended to be used as an adjunct to primary hemostasis in surgical procedures to assist in controlling capillary, venous and small arterial hemorrhage when other conventional methods are ineffective or impractical. Absorbable hemostatic agents are intended to be absorbed into the body and are Class III devices per 21 CFR 878.4490. The agency considers such devices to be significant risk devices because they are absorbed internally and present “a potential for serious risk to the health, safety, or welfare of a subject” per 21 CFR 812.3(m). 21 CFR 812.20(a) requires any sponsor who intends to use a significant risk device in an investigation to submit an application to FDA, and to wait to begin the investigation until FDA has approved the application. FDA approval of an IDE application helps to ensure subject safety and that the risks associated with the device and study procedures are minimized.This was conveyed to you in the Form FDA-483, and your response dated October 25, 2024 is inadequate. Your written response includes a discussion of the interactions with FDA regarding this study and describes your misunderstanding of those interactions and of NSR/significant risk studies. It indicates that the meeting minutes for(b)(4)that you had provided to the IRB were your modifications to the minutes received from FDA and that you had informally emailed them to FDA. However, there is no record of your submission of these revised meeting minutes to FDA either by email or with a Meeting Minutes Disagreement amendment, the procedure outlined in FDA’s transmittal email for handling changes to meeting minutes. Importantly, there is also no agreement by FDA on these meeting minutes that you had revised. Your response also does not speak to the modifications that were made to the official FDA correspondence for(b)(4), where you inserted the word “NSR” in describing the name of the study and removed references to a(b)(4). FDA is greatly concerned about your misrepresentation of the FDA’s stance regarding the risk determination of the study to the IRB, which resulted in you inappropriately conducting this study without submitting and obtaining approval of an IDE application from FDA prior to initiation.2. Failure to ensure proper monitoring of the investigation [21 CFR 812.40].Sponsors are responsible for ensuring that a clinical investigation is properly monitored. However, you failed to properly monitor your clinical investigation. Examples include, but are not limited to, the following:a. Although you had described in the study protocol, UHP001, sections 10 and 14.9, that details regarding monitoring would be provided in the study specific Monitoring Plan and clinical site monitoring would be documented in a Clinical Monitoring Plan (CMP), respectively, you did not have an effective and implemented CMP during study conduct.b. You did not maintain adequate documentation regarding those monitoring activities that did occur:i. You failed to maintain adequate site initiation visit (SIV) documentation for the two clinical investigation sites. There were several discrepancies in documentation of SIV Monitoring Visit Reports, investigator site’s personnel training logs (SIV Training Logs), and Site Visit Logs. For example, the SIV Monitoring Visit Report for site 01 documented the visit was held on-site on December 17, 2018, with the clinical investigator and research coordinator. However, the SIV Training Log for site 01 documented the clinical investigator received SIV training on December 10, 2018, and the research coordinator received SIV training on March 19, 2019. The Site Visit Log for site 01 documented a single SIV date as December 19, 2018.ii. You failed to maintain adequate interim monitoring documentation for the two clinical investigation sites. For example, the Site Visit Log for site 01 documented the interim monitoring visit was held on-site on July 9, 2019, but there was no interim monitoring report for this visit. In addition, the site visit log for site 02 documented the interim monitoring visit was held on-site on September 10, 2019, but there was no interim monitoring report for this visit.Proper monitoring helps ensure that the safety, rights, and well-being of the subjects are protected, and that the data are complete and accurate. Monitoring should be an on-going program performed with the frequency necessary to ensure that the investigation is conducted according to the investigational plan, FDA regulations, and any conditions of approval required by the FDA or the reviewing IRB. Inadequate monitoring can lead to reporting of inaccurate data, missing data, enrollment of subjects that do not meet eligibility criteria, and poor adverse event reporting, among other concerns. In addition, without adequate monitoring there is no assurance that your study conduct is compliant and that any instances of noncompliance are resolved properly.This was conveyed to you in the Form FDA-483, and your written response dated October 25, 2024 is inadequate. Your response includes a retrospectively-created CMP, new Standard Operating Procedures (SOPs) for clinical monitoring, clinical site selection, and site initiation, and revised Site Visit Logs for both clinical investigation sites. Your response indicates that the retrospectively-created CMP reflects the monitoring practices that were followed during the study conduct and indicates that the updated Site Visit Log added visits that occurred for SIV training for both clinical investigation sites, but were not present on the initial Site Visit Log. You did not provide SIV Monitoring Visit Reports for the additional SIV training conducted for both clinical investigation sites that were added to the Site Visit Logs. You also did not provide the interim monitoring reports for both clinical investigation sites that document the activities that occurred during the interim monitoring visits, nor did you provide the follow-up communication to the investigator/study personnel that discusses visit findings, outstanding action items, and requests for additional information. These items are needed to assess the adequacy of the monitoring conducted for this study.3. Failure to secure clinical investigator’s compliance with the signed agreement, the investigational plan, applicable FDA regulations, and any other conditions of approval imposed by the reviewing IRB or FDA, or if compliance could not be obtained, failure to discontinue shipments of the device to the investigator and terminate the investigator’s participation in the investigation [21 CFR 812.46(a)].As part of monitoring responsibilities, a sponsor is responsible for securing the investigator’s compliance with the investigational plan to ensure adherence with the study protocol and other regulatory requirements. You failed to obtain and secure the clinical investigator’s compliance with the investigational plan and applicable FDA regulations. Examples include, but are not limited to, the following:a. Forty (40) subjects had baseline laboratory results indicating thrombocytopenia or no baseline platelet laboratory results. As a result, these subjects met exclusion criterion # 9, which lists subjects with a coagulation disorder, thrombocytopenia, liver disease and anti-thrombin therapy as not eligible for study. You did not ensure that investigators properly enrolled subjects according to the investigational plan.b. According to your Protocol Deviation Log, there were three (3) subjects whose informed consent forms were not signed by the subject, which violates inclusion criterion # 4, as well as 21 CFR 812.100, which requires that investigators obtain informed consent in accordance with 21 CFR Part 50. You did not ensure that investigators obtained informed consent according to the investigational plan and applicable FDA regulations.Securing clinical investigator compliance is a critical component of monitoring and is critical for ensuring the safety and welfare of study subjects. Failure to secure compliance impacts the reliability and quality of the data resulting from the study and in turn adversely impacts FDA’s ability to assess the overall safety and effectiveness of the device. As you failed to conduct proper monitoring, you did not identify that enrollment criteria were violated or that informed consent was not properly obtained, and also did not take steps to secure compliance with these requirements. Having failed to secure the investigator’s compliance, you also did not discontinue shipments of the device to the investigator and terminate the investigator’s participation in the investigation.This was conveyed to you in the Form FDA-483, and your written response dated October 25, 2024 is inadequate. While your response acknowledged the issue of enrolling subjects that did not meet the eligibility criteria related to thrombocytopenia and provided a comprehensive corrective action and preventative action plan, you have not addressed the issue of failing to obtain informed consent. Specifically, you did not provide any root cause analysis regarding the informed consent protocol deviations. You also did not identify any corrective or preventative actions taken to ensure that informed consent is properly obtained by investigators such that human subjects are adequately protected.4. Failure to immediately conduct an evaluation of any unanticipated adverse device effects and failure to report results of such an evaluation to FDA and to all reviewing IRB’s and participating investigators within 10 working days [21 CFR 812.46(b)(1) and 21 CFR 812.150(b)(1)].As a sponsor, you are responsible for conducting an evaluation of any adverse device effects that are reported as serious and unanticipated to ensure adverse events are adequately recorded and reported, and that appropriate follow-up occurs. You failed to conduct these evaluations. Examples include, but are not limited to, the following:a. You failed to evaluate the unanticipated adverse device effect (UADE) for subject 02-0074 that occurred on April 30, 2019. Information for this UADE was recorded in an Adverse Event (AE) Form; however, there is no documentation to show that the UADE was evaluated as required by 21 CFR 812.46(b)(1) and study protocol, UHP001, section, 9.8.2.b. You failed to evaluate the UADE for subject 02-0074 that occurred on May 12, 2019. Information for this UADE was recorded in an AE Form; however, there is no documentation to show that the UADE was evaluated as required by 21 CFR 812.46(b)(1) and study protocol, UHP001, section, 9.8.2.Proper evaluation of UADEs, as required by 812.46(b)(1), is a critical step in ensuring the safety and welfare of study subjects. Appropriate review and evaluation of UADEs and their resolution allows for any necessary changes to be made to the investigational plan to protect study participants. Furthermore, the regulations under 812.150(b)(1) require that a sponsor who conducts an evaluation of an unanticipated adverse device effect under 812.46(b) report the results of such evaluation to FDA. Proper evaluation and timely reporting to FDA of the result of any evaluation of a UADE is important for FDA’s assessment of the overall safety profile of the device.This was conveyed to you in the Form FDA-483, and your written response dated October 25, 2024 is inadequate. Your response includes a description that the clinical site did not report these AEs to the sponsor as UADEs, and that they therefore were not handled as UADEs. In addition, you provided an updated SOP (CLN-06 Adverse Event Monitoring) to include UADE reporting requirements. However, these documents do not describe how an AE designated as a UADE by an investigator on the AE paper form is reported to the sponsor. It appears that the designation of an AE as a UADE is not captured in the electronic case report form (eCRF) and therefore these two AEs were not reported to the sponsor as UADEs, despite being identified by the investigator as such. As a result, these two AEs were not properly evaluated to determine whether they met the definition of a UADE, as required by the study protocol, UHP001, sections 9.1 and 9.8. Neither the updated SOP nor the protocol provide adequate detail to prevent a recurrence of this scenario in future studies. In addition, you did not provide source documentation for subject 02-0074 that was obtained according to Section 9.4 of the study protocol, UHP001, to assess the causal relationship between the AE and the investigational device. This documentation is needed to ensure that you have adequately conducted an evaluation of reported AEs as expected in the UHP001 study protocol. Although in this case, these two AEs were ultimately determined not to be UADEs through your postinspection activities, timely investigation of UADEs identified by study investigators while the study is ongoing is required by 21 CFR 812.46(b)(1) and a critical element of good clinical practices and does not appear to be assured by your corrective actions.Finally, section 7.6.1 of your updated SOP provides UADE reporting requirements and suggests that the requirement only applies to IDE studies. The evaluation requirement under 812.46 and reporting requirement under 812.150(b)(1) for UADEs also apply to non-significant risk studies subject to abbreviated requirements per 812.2(b), not just studies being conducted under an IDE. The regulatory requirements should be clarified and corrected in the SOP.5. Failure to maintain accurate, complete, and current device shipment and disposition records [21 CFR 812.140(b)(2)].As a sponsor, you are responsible for maintaining accurate, complete, and current records relating to an investigation. Specifically, records of shipment must include the name and address of the consignee, type and quantity of device, date of shipment, and batch number or code mark, and records of disposition must describe the batch number or code marks of any devices returned to the sponsor, repaired, or disposed of in other ways by the investigator or another person, and the reasons for and method of disposal. You failed to maintain the necessary records. Examples include, but are not limited to, the following:a. You failed to maintain records of investigational devices received by a sponsor employee, investigational devices returned to the sponsor, or unused investigational devices disposed of for the(b)(4)investigational device units packaged.b. You failed to maintain accurate device accountability records for both clinical investigation sites. For example, your Master Device Accountability Log documented that there were 230 subjects who received the investigational device in site # 01 and 4 subjects who received the investigational device in site # 02, with zero returned devices. However, there were only a total of 118 subjects randomized to receive the investigational device and the other subjects were assigned to the control group. In addition, the UHP001 Inventory Log for Site # 02 indicated that only 1 device was used, but the Master Device Accountability Log documented that there were 4 devices used.Proper records of device shipment and disposition are necessary for control of devices and to confirm that the investigational device is used only by qualified investigators on subjects appropriately enrolled in the study. If the devices were used by unqualified individuals on patients not enrolled in the study, there would be an increased risk of harm to both the user and patient.This was conveyed to you in the Form FDA-483, and your written response dated October 25, 2024 is inadequate. Your response provided a SOP for investigational device management and a corrected Master Accountability Log. However, you did not provide source documentation of study subjects’ randomization assignment to verify the changes made to the Master Accountability Log and to demonstrate that device usage was appropriate.The violations described above are not intended to be an all-inclusive list of problems that may exist with your clinical study. It is your responsibility as a study sponsor to ensure compliance with the Act and applicable regulations.Within 15 working days of receiving this letter, please provide documentation of the additional corrective and preventative actions that you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which you are the study sponsor. Any submitted corrective action plan must include projected completion dates for each action to be accomplished as well as a plan for monitoring the effectiveness of your corrective actions. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you.Your response should reference “CTS#(b)(4)” and be sent via email to: Irfan.Khan@fda.hhs.gov.A copy of this letter has been sent to FDA’s OII BIMO Division 1 via email OIIBIMODivision1Correspondence@fda.hhs.gov. Please send a copy of your response to that office.The Division of Clinical Policy and Quality has developed introductory training modules in FDA-regulated device clinical research practices, which are available on the FDA website. The modules are for persons involved in FDA-regulated device clinical research activities. These modules are located at the following website address: http://www.fda.gov/Training/CDRHLearn/.If you have any questions, please contact Alejandra Cambonchi by phone at (301) 796-0552 or email at Alejandra.Cambonchi@fda.hhs.gov.Sincerely yours,/S/Soma Kalb, PhDDirectorDivision of Clinical Policy and QualityOffice of Clinical Evidence & AnalysisOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA UPSReference #:320-25-71Product:DrugsRecipient:Mr. Phillip A.S. MillerCo-CEOProduct Society LLC13056 Saticoy StreetNorth Hollywood,CA91605United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-71May 8, 2025Dear Mr. Miller:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Product Society LLC, FEI 3023272193, at 13056 Saticoy Street, North Hollywood, CA 91605, from November 18 to 27, 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).We reviewed your December 20, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity strength, and quality. Also, your firm 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) drugs both for topical and oral use. You failed to adequately test incoming components, such as glycerin, for identity before using them in the manufacture of your drug products. Additionally, you relied on your supplier’s certificates of analysis without establishing the reliability of each of your suppliers’ analyses at appropriate intervals.Identity testing for glycerin and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of Diethylene Glycol (DEG) and Ethylene Glycol (EG). Because you did not perform adequate identity testing on a representative sample using the USP identification test, which detects these hazardous impurities, you failed to assure the acceptability of these components 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.Furthermore, your firm used water as a component in your finished drug products. Your water system was not adequately monitored to ensure that it can produce water that meets USP(b)(4)water monograph specifications. Water for pharmaceutical purposes must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.In response to this letter, provide: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 batches 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, glycerin). 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 action and preventive action 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.A thorough remediation plan to install and operate a suitable water system to produce water adhering to(b)(4)Water, USP monograph specifications and appropriate microbial limits.2. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products manufactured have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Your firm failed to validate your manufacturing processes for your OTC drug products (e.g.,(b)(4), and(b)(4)). You are responsible for assuring your manufacturing processes will consistently result in drug products meeting predefined quality attributes.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs.Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.See FDA’s guidance document, Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.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) lacked adequate control over your OTC drug product manufacturing operations and failed to ensure that you had adequate procedures. For example, your QU failed to ensure:Establishment of an adequate ongoing stability program (21 CFR 211.166(a)).Performance of periodic (i.e., at least annual) product reviews (21 CFR 211.180(e)).Use of adequate laboratory control mechanisms (e.g., calibrated equipment) (21 CFR 211.160(a)).Your firm’s quality systems are inadequate. 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.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.Drug Production CeasedWe acknowledge your commitment to cease production of all OTC drugs and that you deregistered your facility as a drug manufacturer. In response to this letter, clarify whether you intend to resume manufacturing drugs for the U.S. market at this facility in the future.If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. If your firm intends to resume manufacturing drugs, you should engage a consultant qualified to evaluate your operations to assist your firm in meeting CGMP requirements. 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.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 3023272193 and ATTN: Andrew Haack.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCC:Max J. SteirCo-CEOProduct Society LLC13056 Saticoy StreetNorth Hollywood, CA 91605

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-25-61Product:DrugsRecipient:Mr. Chongjiu LiGeneral ManagerWuxi Medical Instrument Factory Co., Ltd.No.43 Xixin Road, Zhangjing, Xibei TownWuxi ShiJiangsu Sheng,214194ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-61April 4, 2025Dear Mr. Li:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Wuxi Medical Instrument Factory Co., Ltd., FEI 3006851654, located at No. 43 Xixin Road, Zhangjing, Xibei Town, Wuxi, from November 11 to 15, 2024.Because your drug products were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, your drug products are also adulterated within the meaning of section 501(a)(2)(A) of the FD&C Act, 21 U.S.C. 351(a)(2)(A).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).Inadequate ResponseWe reviewed your December 5, 2024 response to our Form FDA 483 in detail. Your response is inadequate because you fail to provide adequate evidence of corrective actions taken to bring your operations into compliance with CGMP or confidence that you can manufacture sterile drugs. Your response notes that your “…company does not have the ability to pass FDA factory inspection and was not prepared to produce sterilized(b)(4)in accordance with the requirements of OCT [sic] Drug product so it does not produce sterilized(b)(4), nor carry out the testing of sterility testing.” Drug manufacturers labeling their product as sterile must recognize the serious public health implications of distributing a non-sterile product, as it poses a significant health risk to patients.During our inspection, our investigators observed specific violations including, but not limited to, the following.Insanitary ConditionsYour drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, or held under insanitary conditions whereby drugs may become contaminated with filth or rendered injurious to health. FDA investigators observed your facility to be in a state of disrepair, poorly cleaned, and maintained as evidenced by:Numerous dead insects were inside the tubing used to transfer the active pharmaceutical ingredient (API),(b)(4), from storage drums to(b)(4)tanks, as well as a(b)(4)used for storing API transfer hoses and(b)(4).Multiple pieces of unknown debris in an(b)(4)solution that was being(b)(4)to a filling machine and transferred(b)(4)that were packaged and labelled as sterile.Multiple pieces of tubing used to transfer(b)(4)solution from holding containers to filling machines were cracked, leaking, discolored, or contained unidentified residues.Bulk(b)(4)of(b)(4)used to make(b)(4)had hair, unknown particulates, or insects on them.The ceiling areas above uncovered filling and packaging machines used to manufacture(b)(4)labelled as sterile were visibly dirty and damaged.CGMP Violations1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all sterilization processes (21 CFR 211.113(b)).In addition to the insanitary conditions described above, FDA investigators observed during the inspection that since the previous inspection, your firm discontinued sterilization via(b)(4)without implementing a new sterilization procedure. Furthermore, your firm lacked a procedure for conducting environmental monitoring during manufacturing operations and failed to ensure operators adhered to proper gowning requirements, thereby compromising the sterility assurance of(b)(4)labeled as sterile.See FDA’s guidance document,Sterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practice, to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing, at https://www.fda.gov/downloads/Drugs/Guidances/ucm070342.pdf.In response to this letter, provide:Comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, that includes, but is not limited to:o All human interactions within the ISO 5 areao Equipment placement and ergonomicso Air quality in the ISO 5 area and surrounding roomo Facility layouto Personnel Flows and Material Flows (throughout all rooms used to conduct and support sterile operations)A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made in the design and control of the aseptic processing operation.Your plan to ensure appropriate aseptic practices and cleanroom behavior during production. Include steps to ensure routine and effective supervisory oversight for all production batches. Also describe the frequency of quality unit oversight (e.g., audit) during aseptic processing and its support-operations.A thorough retrospective review and risk assessment that evaluates how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.A robust sterilization method and rigorous validation protocol that assures a sterility assurance level of 10-6 or more is achieved (e.g., provide F-value and Z-value data for any heat sterilization method), and uses an appropriate resistant biological indicator that represents the worst-case resistance of microbes that could be found in your environment and product. Include D-value determinations for each biological indicator lot to demonstrate its resistance to the specific sterilization method proposed for use by your firm.2. Your firm failed to conduct appropriate laboratory testing to determine whether each batch of drug product purporting to be sterile and pyrogen-free conforms to such requirements (21 CFR 211.167(a)).You manufactured and distributed an(b)(4)product labeled as "sterile." However, you failed to perform sterility testing. It is essential that you conduct sterility testing on these and other purportedly sterile drugs prior to batch disposition decisions.In response to this letter, provide a list of chemical and microbial test methods and specifications used to analyze each batch of your drug product before making a batch disposition decision, and the associated written procedures.3. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. 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 relied solely on certificates of analysis (COAs) for incoming lots of(b)(4), instead of conducting identity testing and verification for purity, strength, and quality or qualifying your component supplier. Additionally, your firm failed to test the(b)(4)system for(b)(4)and microbial limits, despite its use in drug production. Without adequate testing, there is no assurance that these critical components meet required specifications before use in manufacturing. The failure to perform appropriate identity and testing raises concerns about product quality and associated potential risks to patients.In response to this letter, provide:The chemical and microbiological quality control specifications you use to test and release each incoming lot of components for use in manufacturing.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 re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.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.4. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).Your firm assigned a(b)(4)expiration date to your sterile(b)(4)despite having only(b)(4)of stability data. Additionally, your firm's procedure did not address ongoing stability testing to monitor your drug’s integrity throughout its shelf life. Without sufficient data, there is no assurance that your drug product maintains its identity, strength, quality, and purity for the full labeled expiration period.In response to this letter, provide:A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.o Detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability program.Drug RecallOn January 21, 2025, the FDA held a teleconference with you recommending you consider removing any batches of sterile(b)(4)currently in distribution from the U.S. market.On February 11, 2025, you issued a voluntary recall of sterile(b)(4)due to a lack of sterility assurance and CGMP violations observed during an inspection.Quality SystemsYour firm’s quality systems are inadequate. 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.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 evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. 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.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed products offered for import into the United States from your firm on Import Alert 66-40 on January 21, 2025.Correct any violations promptly. 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 any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Wuxi Medical Instrument Factory Co., Ltd., Wuxi, China, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).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 3006851654 and ATTN: Joseph Lambert, Pharm.D.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Gary GregoryPresident & CEONeuroSync, Inc.118 Washington St, Ste 14Holliston,MA01746United States(b)(6), (b)(7)(C)Issuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 705489May 9, 2025Dear Mr. Gregory:During an inspection of your firm located in Holliston, MA, on January 6, 2025, through February 5, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures EYE-SYNC, consisting of a virtual reality headset and tablet computer which performs eye assessments. 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.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.We received your response, dated February 27, 2025, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. These violations include, but are not limited to, the following:1. Failure to establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). Specifically:a. You failed to verify your device design to confirm that the design output meets the design input requirements, as required by 21 CFR 820.30(f). You did not implement your Design Controls, Software Design, Development and Maintenance Procedure, Section 6.4, which requires that “(b)(4).” For example:i. Your EYE-SYNC Design Input Requirements, DIR-10101, Rev 007, includes a design requirement related to tracking performance accuracy that states, “(b)(4).” However, your TR-10332 Eye Tracking Performance Test Result –(b)(4), identifies that the average accuracy was(b)(4), and the test report was approved on August 16, 2021, even though this requirement was not met.ii. Your EYE-SYNC Software Requirements Specification, SRS-10102, states, “If the data quality is low the users will be warned. If the data quality is insufficient, the users are alerted, and the analysis result score is not offered to the user for the given assessment.” However, you did not have any testing to verify that low quality data results in a warning to the user, and that insufficient data quality does not present a score.b. You failed to identify, document, validate or where appropriate verify, review, and approve of design changes before their implementation, as required by 21 CFR 820.30(i). You did not implement your Design Controls, Software Design, Development and Maintenance Procedure, Section 6.7.iii, which requires that “Changes are identified, documented, validated or where appropriate verified, reviewed, and approved prior to the implementation of the change.” For example:i. ECO 24-0033 released EYE-SYNC tablet software version 1.2.9_25_1234 to correct an issue which allowed the device to continue collecting data in the event the headset is removed, potentially resulting in the incorrect color of the data quality indicator. However, associated software testing in TR-10139, Rev 34 did not verify that version 1.2.9_25_1234 corrected this issue.c. You failed to establish design inputs to ensure that the design requirements relating to a device are appropriate and address the intended use of the device, including the needs of the user and patient, as required by 21 CFR 820.30(c). You did not implement your Design Controls, Software Design, Development and Maintenance Procedure, Section 6.2 Requirements, which explain that design inputs “…(b)(4).”For example:i. EYE-SYNC Design Input Requirements, DIR-10101, Rev 007, lists requirements that are not related to the current device. For example, requirement C2.3, Latch Fit, states “(b)(4),” and requirement C4.2 states “Device shall have USB(b)(4)of similar form factor to Eye Tracker Unit (ETU).” Both of these requirements are outdated and refer to Model X02 of EYE-SYNC, which was replaced by model X03 in April 2021.d. You failed to validate your device design to ensure that devices conform to defined user needs and intended uses, as required by 21 CFR 820.30(g). For example,i. Your Risk Management Procedure, SOP-10011, Rev 002, states that the level of risk is determined by Risk Priority Numbers (RPN) and that the design(b)(4)will use the severity and occurrence rating scales described in the procedure. However, your software(b)(4), RA-10110, Rev 006, does not use RPNs, and the impact and probability scale used to calculate inherent and residual risk are not adequately defined within SOP-10011.We reviewed your firm response dated February 27, 2025, and concluded that it is not adequate. We understand that you opened several CAPAs to identify necessary updates to your design control processes; however, your response does not provide sufficient detail to ensure that these failures will not recur and that your current devices meet all your design control requirements. For example, your CAPA 202502053 for design change indicates that Test Reports and ECOs issued from February 4-19, 2025, will be reviewed but does not explain why older reports are not being reviewed.Our review also noted that the EYE-SYNC system, as released to users beginning April 2021, uses either the(b)(4)or(b)(4)as the eye tracking unit of the EYE-SYNC. We encourage you to perform a thorough review of your current design to ensure any changes made to the EYE-SYNC after FDA clearances have been reviewed properly. For example, for the above hardware design change, we would expect your firm to have documentation of the appropriate verification, review, and approval of design changes before their implementation. In response to this Warning Letter, please provide a timeline of when all proposed corrective actions to your design control processes will be completed, including when you will complete a review of your current device to ensure all specified design requirements are met.2. Failure to establish and maintain procedures for implementing corrective and preventive action, including implementing and recording changes in methods and procedures needed to correct and prevent identified quality problems, as required by 21 CFR 820.100(a)(5). For example, CAPA 202110081 was opened on October 8, 2021, to address higher than expected assessment scores. The CAPA included a corrective action that stated, “To correct the core non-conformity, the raw data capture implementation of the eye tracker software must be updated to appropriately capture head and eye position data to accurately reflect scores within the typical range.” During the inspection, your firm indicated that a software correction to the eye tracker software had not been made.We reviewed your firm response dated February 27, 2025, and concluded that it is not adequate. You have not provided documentation to demonstrate that you have completed a corrective action for the above CAPA.3. Failure to establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. You have not implemented your Supplier Management Procedure, SOP-10025, Rev 004. Specifically:a. Your vendor who manufactures the EYE-SYNC’s Eye Tracker, p/n P-10114, has not been evaluated since March 15, 2022, despite your Supplier Management Procedure and Supplier Status Form, F-10093, identifying that the supplier requires(b)(4)performance evaluations.b. Your software vendor who supplies the sensor which is placed in the Eye Tracker is not listed on your firm's Approved Supplier List and has not been approved or evaluated as per your procedure.We reviewed your firm response dated February 27, 2025, and concluded that it is not adequate. You have not provided documentation that the above vendors have successfully completed evaluations as per your procedures.4. Failure to establish and maintain procedures for acceptance activities. Acceptance activities include inspections, tests, or other verification activities, as required by 21 CFR 820.80(a). For example, your firm’s Release for Shipment Procedure, SOP-10029, Rev 003, describes the activities needed to release a finished device, which include "visual inspection of product to ascertain that all specified operations are completed and to detect any visible quality problems.” During the inspection, you confirmed the employee tasked with finished device inspection works(b)(4)and does not review test reports or perform a visual inspection as required by your procedure.We reviewed your firm response dated February 27, 2025, and concluded that it is not adequate. You have not provided documentation to show that your corrective actions have been implemented to ensure visual inspection requirements are currently being performed as required by your procedure.Our inspection also revealed that your firm’s EYE‐SYNC Eye Tracker 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:Failure to submit any report required within 10 working days of initiating a correction or removal, as required by 21 CFR 806.10. For example, on or about September 19, 2023, your firm replaced/removed Pico 2 components of EYE‐SYNC devices. The devices would stall or freeze, resulting in a delay of diagnostic procedure or inability to assess a patient. CDRH’s risk assessment concluded the devices failing to perform as intended may cause temporary or medically reversible adverse health consequences or a remote probability of serious adverse health consequences. This action meets the definition of a medical device correction or removal initiated to reduce a risk to health posed by the device, for which you are required to submit a Report of Correction or Removal to FDA. You did not submit a Medical Device Report of Correction or Removal to FDA for this action.Your firm’s response to Observation 12 of the FDA‐483, dated February 27, 2025, is not adequate. You have not submitted Reports of Correction or Removal to FDA as of this date.Our inspection revealed that your devices are also misbranded within the meaning of section 502(c) of the Act, 21 U.S.C. § 352(c), because a word, statement, or other information required by or under authority of section 519 of the Act, 21 U.S.C. § 360i, to appear on the label or labeling of the devices was not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use. In particular, 21 CFR 801.20(a) – which was promulgated under authority of section 519 of the Act, among other provisions – requires, with exceptions not relevant here, that the label and device package of every medical device bear a unique device identifier (UDI) that meets the requirements of 21 CFR Part 801, subpart B, and 21 CFR Part 830. The labels of the EYE-SYNC Model X03 devices do not bear such a UDI.Specifically, the labels for EYE-SYNC Model X03 do not include a device identifier within the meaning of 21 CFR 801.3 or 830.3, and there is no UDI presented in easily readable plain-text on the label of EYE-SYNC Model X03 (see 21 CFR 801.40(a)(1)), and there is no UDI presented in machine-readable form that uses(b)(4)technology on the label of EYE-SYNC X03 (see 21 CFR 801.40(a)(2)).Your response dated February 27, 2025, is not adequate. Your firm promised to obtain mock-ups of revised labeling for review by March 27, 2025, and to obtain UDIs for issuing agency(b)(4), update procedures to include them, and submit GUDID entries. However, you have not provided revised labels as evidence that your labels will include valid UDIs as of this date.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 Gina Brackett, Establishment Assessment Team 1 (EAT-1) Assistant Director at CDRHEnforcement@fda.hhs.gov. Refer toCMS case #705489when replying. If you have any questions about the contents of this letter, please contact: Karen Archdeacon, Compliance Officer, at karen.archdeacon@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 MailProduct:Medical DevicesRecipient:Gaston S. LevesquePresident and CEOMicrospecialties, LLC430 Smith StreetMiddletown,CT06457United Statessteven.levesque@microspecialties.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 707614May 8, 2025Dear Gaston S. Levesque:During an inspection of your firm located in Middletown, CT, from January 14, 2025, through February 18, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm contract manufactures Class I and II ophthalmic surgical devices such as sterile I-PACK injection kits, punctum plugs, and microkeratome blades. 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.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.We received a response from Rick Brinsmade, Quality Assurance and Regulatory Affairs (QA/RA) Manager, dated March 4, 2025 concerning our investigator’s observations noted on the Form FDA 483 (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:1. Failure to establish and maintain procedures for finished device acceptance to ensure that each production run, lot, or batch of finished devices meets acceptance criteria, as required by 21 CFR 820.80(d).Specifically, you failed to implement section 6.13 of your “Sterilization Process Control” procedure (QA-0041; Rev 3; Effective: 1/27/23) which requires release of sterile products to inventory via Form 0070 once accompanying dosimetry records and certificates of processing (COPs) are received back from the contract sterilizer. For example, you stated that Form 0070 was never utilized to release(b)(4)boxes of I-PACK injection kits (Lot #: P62764979R, P63044983R, P62764965R and P62764970R) into inventory because you fabricated the(b)(4)sterilization COPs ((b)(4)and(b)(4)) as if they originated from the customer-approved contract sterilizer. Subsequently, on 03/21/24, your Director of Quality Assurance released the above nonconforming lots of I-PACK injection kits, which are intended for administration of intravitreal injections during eye surgery, as sterile to your customer on 3/12/24 despite never shipping these products to the customer-approved contract sterilizer (or elsewhere) for sterilization. This event resulted in a Class II recall RES 94794 initiated by your firm on 6/5/24 followed up by a Class I recall by your customer on(b)(4)under RES(b)(4).The adequacy of the response dated 3/4/25 cannot be determined at this time. Under CAR # 1288 (2/20/25) opened to address the failure to follow QA-0041, you reference CAR # 1261 (5/31/24) for the root cause which pointed to limited resources, lack of effectiveness of training, storage of product in a non-routine location, and lack of(b)(4)sterilization labels. Corrective actions included notification of the nonconforming lots to your customer upon discovery of the error; replacement of your Director of Quality Assurance with a new Quality Assurance and Regulatory Affairs Manager; addition of(b)(4)exposure indication dots to shipping cartons; update of Form 0070 to include verification of(b)(4)indicator dot color changes; update of QA-0041 to restrict product release to QA, President, or Administrative Assistant; update the training procedure (QA-0019) to include effectiveness tests, including a test for sterilization processes; and retrospective review of sterilization and release documentations to verify accuracy. Under CAR # 1289 (2/20/25) opened to address release of nonconforming product, you also reference the root cause(s) and several of the corrective actions above under CAR # 1261 and note additional completed actions which included the requirement for(b)(4)irradiation exposure dots on shipping cartons and process specifications for your new contract sterilizer in QA-0041; addition of integrity requirements to the document, part number, and data control procedure (QA-0020); and a new code of conduct and ethics procedure (QA-0099) for which all employees completed training. By 6/1/25, you plan to also add irradiation exposure dots to each individual carton of trays and microkeratome blades. Please provide updates on the progress of these corrective actions and corrections, including any supporting evidence.2. Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a).Specifically:a. You failed to implement sections 5.1.2 and 5.2.1 of your “Process Validation” procedure (QA-0063; Effective: 11/8/23) which requires that Operations (with input from Quality) determine “***if re-validation is needed for changes to validation manufacturing processes***” and that Quality “***Reviews and approves the assessments of validation needs and revalidation determinations***,” respectively. For example, you authorized the release of lots(b)(4)on 9/4/24;(b)(4)on 10/14/24; and(b)(4)on 11/19/24, containing medical devices, such as punctum plugs, customized injection trays, microkeratome blades, microkeratome tubing, and ophthalmic convenience kits, for distribution without documented justification for why a revalidation was not required, prior to switching to a new contract sterilizer for(b)(4)sterilization of such devices on 3/19/24.b. You failed to implement sections 1.0 and 2.0 of your “Process Validation” procedure (QA-0063; Effective: 11/8/23) which require validations of processes related to inventory items such as “***a component, material, assembly, packaging, and labeling that is part or will become part of the finished medical device including the finished medical device***.” For example, you did not conduct a validation of the(b)(4)inspection method outlined in section 6.1.2 of the “Seal Inspection” procedure (QA-0042; Effective: 6/30/24) for testing the seal integrity of sterile pouches containing Microkeratome Blades, to ensure that manufacturing employees are able to repeatably and reproducibly able to detect conforming and nonconforming seal pouches with a high degree of assurance as a part of finished device acceptance. These devices are indicated for use during LASIK surgery to shave tissue from sections of the cornea for a lamellar (partial thickness) transplant.The response dated 3/4/25 is not adequate. Under CAR # 1290 (2/20/25) initiated to address release of sterile products prior to conducting a revalidation for the new contract sterilizer, you state that management did not believe that a revalidation was required because the new contract(b)(4)sterilizer was able to sterilize the product with the specified dose mapping and dose audits and bioburden testing continued. In addition, you point out that your newly hired QA/RA manager determined that a retrospective validation was required such that a comprehensive validation was conducted and formally approved on 12/16/24. However, there were no corrective actions identified to address the primary issue which is that you did not follow your procedure to review and approve your decision not to revalidate the sterilization process at the time these products were released for distribution.With regards to the lack of test method validation for the seal integrity inspection, you state that you will write a formal process adoption by analyzing the data outputs from the seal validations by 5/1/25. However, there were no corrective actions identified to review whether any other test methods require process validations to demonstrate that that you are able to consistently detect conforming and nonconforming product with a high degree of assurance. Therefore, please provide a response on how you plan to address the above deficiencies.3. Failure to ensure that sampling plans are written and based on a valid statistical rationale when used, as required by 820.250(b).Specifically, you acknowledged there was no statistical rationale documented for the sampling plan in section 6.1.2 of the “Seal Inspection” procedure (QA-0042; Effective: 6/30/24) to inspect the first(b)(4)pouches for seal integrity.The response dated 3/4/25 is not adequate. Under CAR # 1290 (2/20/25) initiated to address the lack of test method validation for the seal integrity inspection as well as failure to provide statistically supported evidence when sampling, you state that you will write a formal process adoption by analyzing the data outputs from the seal validations by 5/1/25. However, there were no corrective actions identified to address the concerns relating to lack of valid statistical rationale for the sampling plan employed during sealing inspections of sterile pouches. Therefore, please provide a response on how you plan to address the above deficiencies.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 Gina Brackett, Establishment Assessment Team 1 (EAT-1) Assistant Director at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case # 707614” when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, Compliance Officer at sargum.morgan@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 HealthCC: Rick Brinsmade, QA/RA Manager, rick@pro-paks.com

案件名称辽宁国康医药物流有限公司未遵守药品经营质量管理规范案处罚决定文书号辽药监(稽十二)罚〔2025〕1号被处罚企业名称辽宁国康医药物流有限公司统一社会信用代码91211303MA7MGB2BXW法定代表人李伟华主要违法事实当事人未遵守药品经营质量管理规范，向不具备血液制品经营范围的零售药店销售血液制品人血白蛋白。 行政处罚种类和依据对当事人罚款、对当事人相关责任人没收违法行为发生期间自本单位所获收入并罚款。依据《中华人民共和国药品管理法》第一百二十六条和《药品经营和使用质量监督管理办法》第六十九条的规定。处罚结果1、对当事人罚款50000元；2、没收当事人法定代表人（主要负责人）李伟华违法行为发生期间（2025年1月）自本单位所获收入4570.6元，并处所获收入百分之十五罚款685.59元，罚没款合计5256.19元；没收当事人开票员范影违法行为发生期间（2025年1月）自本单位所获收入4381.6元，并处所获收入百分之十五罚款657.24元，罚没款合计5038.84元。行政处罚履行方式和期限主动履行；当事人已于2025年5月16日履行完毕。作出处罚的日期2025-05-13