2025年8月审结转出注册项目审评用时情况Review time of submissions for registration completed and transferred in August 2025备注：1.本表涉及时间均为工作日。The time in this table is working days.2.补正资料平均用时=补正资料总用时/相关项目审结转出总数量average time of deficiency response = total time of deficiency response /total number of completed and transferred submissions with deficiencies.3.第二和第三类产品平均用时=第二类和第三类产品用时/第二类和第三类产品总数量Average time for Class II and III products = total review time of class II and III products/the total number of class II and III product submissions.

相关附件下载：2025年版《中国药典》官方实施公告及各省药监局78个常见问题解答汇总

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDProduct:DrugsRecipient:FWD Care, Inc. dba FWDUnited Stateshttps://fwd.carecontact@fwd.careIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesUnited StatesWARNING LETTERSeptember 9, 2025FWD:This letter is to advise you that the United States Food and Drug Administration (FDA) reviewed your website content at the internet address https://fwd.care in August 2025 and has observed that your website offers various compounded drug products, including semaglutide and tirzepatide.1As described below, your claims concerning compounded semaglutide and tirzepatide products are false or misleading under sections 502(a) and 502(bb) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 352(a) and 352(bb)], resulting in products being introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)].Under section 502(a) of the FDCA [21 U.S.C. § 352(a)] a drug is misbranded if its labeling is false or misleading in any particular. Furthermore, under section 502(bb) of the FDCA [21 U.S.C. § 352(bb)], a compounded drug is misbranded if its advertising or promotion is false or misleading in any particular.The following claims concerning compounded semaglutide and tirzepatide products appear on your website:• “Manage weight affordably with compounded GLP-1, the same active ingredients as Wegovy, Ozempic, Zepbound & Mounjaro”• “Same active ingredient in Mounjaro and Zepbound”• “Same active ingredient as Ozempic and Wegovy”Compounded drug products are not FDA-approved. Your claims imply that your products are the same as an FDA-approved product when they are not. As a result, these claims are false or misleading and your products are therefore misbranded under sections 502(a) and 502(bb) of the FDCA [21 U.S.C. §§ 352(a) and (bb)].The introduction or delivery for introduction into interstate commerce of these misbranded products is a prohibited act under section 301(a) of the FDCA [21 U.S.C. § 331(a)]. The claims identified in this letter put you on notice of our concerns but do not represent an exhaustive list of misbranding violations.2For the reasons discussed above, your compounded semaglutide and tirzepatide products are misbranded drugs under sections 502(a) and 502(bb) of the FDCA [21 U.S.C. §§ 352(a) and 352(bb)], introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FDCA [21 U.S.C. § 331(a)]. Please be advised, the receipt in interstate commerce of misbranded drugs, and the delivery or proffered delivery thereof, is also a violation of section 301(c) of the FDCA [21 U.S.C. § 331(c)].As previously stated, the violations cited in this letter are not intended to be an all-inclusive statement of violations that may exist 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. It is your responsibility to ensure that your operations comply with all requirements of federal law, including FDA regulations.You should take immediate action to address any violations (including, for example, ceasing and desisting from using the language cited above that misbrands the product). Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please provide a written response to the Office of Compounding Quality and Compliance (OCQC) within the Center for Drug Evaluation and Research (CDER)’s Office of Compliance describing the specific steps you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.If you are not located in the U.S., please note that products that appear to be misbranded may be detained or refused admission. We may advise the appropriate regulatory officials in the country from which you operate that your products referenced above appear to be misbranded drugs that cannot be legally sold to consumers in the U.S.All correspondence should include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.Sincerely,/S/George Tidmarsh, M.D., Ph.D.DirectorCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration1The semaglutide and tirzepatide products offered on your website are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.2Overstatements of efficacy or minimization of risk are of particular concern and may constitute misbranding.

基于我区医疗器械产业发展现状，针对注册申请人在注册、核查过程中遇到的问题，宁夏药品审评查验和不良反应监测中心进一步优化服务模式，结合第二类医疗器械审评查验工作重点，推出《宁夏第二类医疗器械审评查验常见咨询问答》，帮助企业提高对法规、标准、指南的认知和申报资料质量，进而加快申报产品上市速度。（注：相关答复是基于我们目前的科学认知，对现行的政策法规、指导原则等的认识和理解，仅供参考，不作为政策法规、指导原则最终解读。）1.申报产品是否可以免临床评价？根据《免于进行临床评价医疗器械目录》（2025年第19号）(以下简称《目录》)，查看此类产品是否属于免于进行临床评价的产品，应对《目录》中的“分类编码”、“产品名称”和“产品描述”等内容进行仔细核对。当申报产品的相关内容与《目录》一致时，申报产品即可按免临床评价的方式进行申报；反之，应根据《医疗器械临床评价技术指导原则》（2021年第73号）进行临床评价或开展临床试验。2.免临床评价产品如何提交评价资料？依据《列入免于临床评价医疗器械目录产品对比说明技术指导原则》，对于列入《免于临床评价医疗器械目录》(以下简称《目录》)产品，注册申请人需提交申报产品相关信息与《目录》所述内容的对比资料和申报产品与已获准境内注册的《目录》中医疗器械的对比说明。具体需提交的资料要求如下：(一)提交申报产品相关信息与《目录》所述内容的对比资料；(二)提交申报产品与《目录》中已获准境内注册医疗器械的对比说明，对比说明应当包括《申报产品与目录中已获准境内注册医疗器械对比表》和相应支持性资料。若经对比，申报产品与对比产品存在差异，还应提交差异部分对安全有效性影响的分析研究资料。二者的差异不应引起不同的安全有效性问题，即申报产品未出现对比产品不存在的且可能引发重大风险和/或引起显著影响有效性的问题。提交的上述资料应能证明申报产品与《目录》所述的产品具有等同性。若无法证明申报产品与《目录》所述的产品具有基本等同性，则应开展临床评价。3.未列入《免于临床评价医疗器械目录》的产品采取什么路径进行临床评价？要不要做临床试验？申请人可进入国家药品监督管理局医疗器械技术审评中心官方网站，在“审评科学”栏目下点击“临床评价路径推荐”，四个通告内容包含了医疗器械分类目录中产品的临床评价推荐路径，申请人可参考上述文件确定产品的临床评价路径。产品是否开展临床试验，应参照《决策是否开展医疗器械临床试验技术指导原则》进行判定。4.申报产品是否可以与结构组成、材料成分相同，但分类编码不同、预期用途不同的已上市产品进行对比？对比产品需要与拟申报产品为同一分类编码。例如：申报产品为磁疗贴，需要与同为分类编码09-05-02的磁疗器具进行对比，与20-03-09穴位磁疗器具预期用途不同，不建议作为比对产品。5.第二类医疗器械进行注册检验时，能否委托具有资质的两家第三方机构检验，并分别出具检验报告？可以，同时应提交检验产品的一致性声明。6.第二类医疗器械产品技术要求中引用强制性标准更新，应该申请注册变更还是可以和延续注册合并办理？医疗器械注册许可事项变更中规范产品名称、产品技术要求、适用范围等不涉及实质性内容变化的，可与延续注册合并办理；若引用的强制性标准有实质变化，应申请变更注册。例如：（1）技术要求引用2020版《中国药典》，在2025版《中国药典》中未发生实质性变化，无需单独办理变更注册，可以与延续注册合并办理。（2）2025年12月1日后申请延续注册的医用一次性防护服应针对GB19082-2023变化部分进行检验，并申请变更注册。7.变更注册或延续注册时，如不涉及产品材质及包装材质变化，是否需要按照GB/T 16886.1-2022《医疗器械生物学评价 第1部分：风险管理过程中的评价与试验》对生物学检测项目进行重新评价？延续注册对推荐性标准无强制要求。变更注册应根据具体变更内容，结合结构组成、生产工艺以及既往不良事件监测情况综合评价是否对生物学特性产生影响。8.第二类医疗器械注册证中的新增型号、规格，是否需要补充检验？如涉及检验，需要检验哪些内容？申请变更注册增加产品型号，首先应确认所申请增加的型号规格与原有型号规格是否可作为同一注册单元，属于的才可以申请变更增加。原注册检验报告无法覆盖变更后的技术要求，则需要补充检验，检验项目需要根据产品的技术要求进行判断，需通过变更对比分析明确影响范围，针对性选择与变更内容直接相关的检验项目。9.产品的结构及组成中是否能够体现非医疗器械部件？对于不作为医疗器械管理的产品部件，不能单独申报注册，但可以作为医疗器械的组成部分体现。如果申请人将该部件作为医疗器械的组成部分申报，应将其视为整体的一部分进行评价，因此该部件应随整机一同进行相应的验证、确认（包括检测），如符合要求可以体现在产品注册证书的结构及组成中。10.产品结构组成中的耗材，是否可以单独获证？若耗材属于医疗器械的配套部件（如监护仪的血压袖带），且无独立医疗器械功能，则需要与主机一起注册；若耗材可独立使用或具备医疗器械功能，也可独立申请注册证。依据《医疗器械注册与备案管理办法》第一百一十三条规定，医疗器械注册证中“结构及组成”栏内所载明的组合部件，以更换耗材、售后服务、维修等为目的，用于原注册产品的，可以单独销售。11.热原同细菌内毒素是否等同？热原泛指能引起机体发热的物质，热原包含了材料致热及细菌内毒素致热两方面信息，属于生物学评价项目。细菌内毒素是革兰氏阴性菌死亡、自溶后，释放出的细胞壁中脂多糖成分，通常来源于生产中引入的生物污染，不属于生物学评价项目。一般来说，细菌内毒素是热原,但热原不全是细菌内毒素。12.产品规格型号较多，是否需要做全型号的注册检验？可以选取典型型号进行注册检验。同一注册单元内，典型产品是指能够涵盖本注册单元内全部产品工艺的一个或多个产品。按照“同一注册单元内，所检测的产品应当是能够代表本注册单元内其他产品安全性和有效性的典型产品”的原则，抽取样品应能涵盖该注册单元全部产品的技术要求。13.申报首次注册时在综述资料中如何描述注册产品与同类和/或前代产品的参考和比较？注册人应阐述注册产品与同类和/或前代产品的差异性，可以以列表的形式对以下内容进行比较并说明其差异性：产品命名、工作原理/作用机理、规格型号、结构组成、制造材料、制造工艺/加工助剂使用、性能指标、作用方式(如植入/介入)、适用范围、禁忌症、注意事项、提供形式(如无菌提供/非无菌提供/微生物限度控制要求)、产品有效期、产品包装、产品使用次数(如一次性使用/可重复使用)等。14.申报首次注册时在综述资料中如何描述产品包装？应关注是否已清晰阐述了所有产品组成部分的包装信息，如所有组件为一个整体包装还是分为多个独立包装，产品由内到外共有几层包装，产品每层包装的材质/材质标准、数量、放置物品，每层包装上标识的信息，确保最终使用者可清晰辨识包装完整性的说明等。对于无菌提供/具有微生物限度要求的医疗器械，除上条要求外，是否还清晰阐述了无菌屏障系统的信息、质控要求及包装的材质/性能检测报告等，包装检测报告是否结合产品特点考虑了包装的理化性能、包装的灭菌适应性能、包装的有效期研究、包装的生物相容性评价等内容。15.申报首次注册时应如何描述化学和物理性能研究？应明确指标制定的依据（标准/指导原则/同类产品/临床文献等）；应从材料、工艺、成品三个层面考虑，充分阐述所开展的研究工作，以证实产品在物理性能、化学性能、使用性能等方面能满足预期使用目的。16.申报首次注册时原材料部分应提供哪些信息？针对原材料的相关信息，注册人应阐述与使用者和/或患者直接或间接接触的材料成分；阐述所包含的生物材料或衍生物的物质来源、原材料、预期使用目的、主要作用方式、应符合的材质标准、供方提供的材质证明资料等。17.经环氧乙烷灭菌后无菌提供的医疗器械，在申报首次注册时应提供哪些灭菌验证资料？灭菌验证资料应包括灭菌方案及灭菌报告，报告中至少应包含灭菌的主要信息(如灭菌批号，生产批号) 及灭菌结果、灭菌结论。灭菌结果应以列表的方式阐述灭菌过程中的数据汇总信息(如短周期、半周期及全周期的实验结果，菌片、IPCD、EPCD及产品的检测结果)；灭菌结论应包含灭菌参数和装载图，装载图应至少能体现灭菌验证中菌片、温度传感器的放置情况。灭菌验证的原始记录，应提交各个周期的灭菌批记录单(包含灭菌批号、生产批号和委托灭菌企业公章)和灭菌服务协议(应包含产品清单)，其他原始记录依据灭菌验证资料的完整性选择提供或不提供。18.申报首次注册时，生产制造信息至少应阐述哪些信息？首次注册资料中生产制造信息至少应阐述总体生产工艺的简要说明、生产工艺流程图、关键工序控制说明、特殊过程控制参数、外协工序说明(含供应商名称和地址)、生产检验设备清单、生产场地介绍、研发场地介绍、场地平面图等。19.非无菌创面敷料产品是否需进行使用稳定性研究？非无菌的创面敷料开封后如在注册人规定的使用期限/使用次数内使用，为确认产品开封后在实际使用环境下，经过一段时期仍然能够满足使用要求的最长存放时间，建议按照有效期验证检测项目（除装量、尺寸等），对其开封后的使用稳定性进行研究。20.定制式活动义齿中同种材质同种工艺的全口义齿是否能作为局部义齿的典型型号进行检测？不能，全口义齿与局部义齿性能指标存在明显差异，如局部义齿金属部分内部质量，卡环体与卡环臂连接处、舌杆下缘、前腭杆、后腭杆、腭板厚度为局部义齿性能指标，但全口义齿不能覆盖上述性能指标。21.首次申报含3D打印义齿型号的义齿产品是否按增加规格型号申报？产品名称及型号如何命名？可以按增加规格型号申报，也可以按照单独的注册单元进行首次申报。产品名称应符合《医疗器械通用名称命名规则》的要求，定制式义齿可命名为定制式固定义齿或定制式活动义齿。具体型号的命名应能反映制作产品的主要材料、工艺和结构，并适当考虑临床的习惯称谓，一般采用“主要材料+工艺+结构功能”的命名方法。应注意，规格型号中工艺特征词建议使用“激光选区熔化”或“激光熔融”等描述，不使用“3D打印”。22.如何确定有源类医疗器械货架有效期？医疗器械货架有效期是指保证医疗器械终产品正常发挥预期功能的期限，产品设计开发阶段需完成产品货架有效期研究。可以对该产品进行使用状态列举，完整分析出临床使用的情况，直接进行产品的老化试验研究；也可以将产品（系统）分解为不同子系统/部件进行评价，应详细分析分解关系，在此基础上通过不同的分解方式（如将产品分为关键部件及非关键部件等）确定产品的使用期限。23.对有源产品进行使用期限评价时，能否仅对其核心部件的使用期限进行评价，代替产品的使用期限评价？有源产品的使用期限评价应为整机评价，产品所含全部部件均需纳入整机评价。经分析，某些部件若不对整机的使用期限产生影响需说明理由。核心部件的使用期限评价不能替代整机评价，但可作为整机评价的支持性证据。24.GB/T 25000.51-2016 《系统与软件工程 系统与软件质量要求和评价（SQuaRE） 第51部分：就绪可用软件产品（RUSP）的质量要求和测试细则》检测报告是否可以提交自检报告？可以是自检报告，自检报告应按照要求，提供测试计划、测试说明、测试结果等文件。根据GB/T 25000.51-2016 《系统与软件工程 系统与软件质量要求和评价（SQuaRE） 第51部分：就绪可用软件产品（RUSP）的质量要求和测试细则》第7章的要求，符合性评价组织可以是根据某种认证模式工作的测试实验室，或是独立于RUSP供方的内部测试实验室。如是内部实验室，建议参考《医疗器械注册自检管理规定》。25.医疗器械产品注册，应在什么时间阶段建立完善的质量管理体系？申请人在产品研发和样品生产前，应当结合产品特点，建立健全与所生产医疗器械相适应的质量管理体系，并保证其有效运行，确保样品在符合《医疗器械生产质量管理规范》及相关附录的要求下生产。26.《医疗器械注册质量管理体系核查指南》的重点核查内容都有哪些？主要包括机构与人员；厂房、设施、设备；文件管理；设计和开发；采购；生产和质量控制等内容，应当符合《医疗器械生产质量管理规范》及其附录的规定。此外，还要重点关注样品真实性核查内容，涉及研制生产样品、产品检验样品、临床试验样品、留样产品、设计开发全过程的时间逻辑等相关可以证明其真实性的记录。27.医疗器械首次注册，设计开发阶段需重点留样哪些批次，留样数量有什么规定？依据《医疗器械注册质量管理体系核查指南》的要求，申请人应当结合产品特点，制订留样管理规定，留存一定数量的注册检验产品、临床试验产品。生产产品或者留样产品数量和规格型号应当能满足产品检验和临床评价（含临床试验）的需要。留样产品去向应当可追溯，保留留样产品台账、留样观察记录。28.洁净车间布局改变是指车间的功能、传递窗、门、通风口等发生改变吗？如增加生产设备，属于车间布局改变吗？需要对洁净车间重新进行第三方的环境检测吗？洁净室相关设备的布局发生变化，属于车间布局变化，需要进行环境检测与验证。企业可自行检测，也可委托有资质的第三方检测机构进行检测。29.有源医疗器械的出厂检验，不检验GB 9706.1-2020《医用电气设备 第1部分：基本安全和基本性能的通用要求》，除安规三项以外的部分和YY 9706.102-2021《医用电气设备 第1-2部分：基本安全和基本性能的通用要求 并列标准：电磁兼容 要求和试验》电磁兼容部分，是否需要制定周期检验规程？依据医疗器械生产质量管理规范的要求，产品检验规程应当覆盖产品技术要求的全部项目，其中包括对原材料质量进行控制的进货检验规程、对中间品等生产过程中半成品质量控制的过程检验规程、对成品质量进行控制的成品检验规程；对于其他项目应当明确在一定周期内进行质量控制的方式和频次，制订周期性的检验规程并有效运行。30.终端灭菌的第二类医疗器械产品，洁净服灭菌前清洗应使用什么工艺用水？医疗器械生产企业应当严格按照YY/T 0033-2000《无菌医疗器具生产管理规范》标准及其他标准和文件规定做好工艺用水的辅助使用工作。洁净服（无菌服）末道清洗至少使用纯化水。企业可以直接使用纯化水对洁净服（无菌服）进行清洗，也可先使用饮用水对洁净服（无菌服）进行漂洗，再使用纯化水进行清洗。同时，企业应当结合自身实际情况制订洁净服（无菌服）清洗作业指导书。

　　为进一步完善北京市医疗器械不良事件监测体系建设，强化进口医疗器械代理人的不良事件监测意识，全面保障公众用械安全，市药品不良反应监测中心积极开展医疗器械不良事件监测工作现场检查，检查工作有序推进，目前进度已过半。　　此次检查覆盖了集采中选、无菌植入、医用防护、医疗美容等重点领域的20家进口医疗器械代理人。针对进口医疗器械代理人的特点，检查围绕机构人员、制度流程、收集上报、调查评价等重点内容，坚持“以查促建”，通过现场法规宣贯和座谈，对产品风险防控能力建设、主动报告发现挖掘和风险分析评价等方面问题给予解答和个性化建议。　　下一步，中心将持续跟踪整改落实情况，继续以推进医疗器械不良事件监测专项检查为抓手，持续加强法规宣传和培训，进一步推动注册人、备案人、进口代理人履行主体责任，切实保障人民群众用械安全，支持产业高质量发展。

　　为进一步提升服务企业效能，近日，市药品审查中心充分发挥专业技术优势，对某外资医药企业品种变更生产场地申请开展技术审评与联合检查，通过优化审评流程、深化联合检查机制等精准举措，为其提供全流程技术支持，推动该品种高效落地。　　在前期审评环节，为强化审评与项目推进的衔接性，中心专门指派资深审评员深度参与申报前本品场地转移项目定期沟通协调会，提前介入掌握项目核心需求与难点。申报后，中心凭借前期积累的项目认知，快速衔接审评工作，精准把握项目审评要点。通过靶向性技术评估与全流程衔接机制，坚持“质量与效率并重”原则，中心既严格守住药品质量安全底线，又实现审评时限“应减尽减”，在保障科学性的同时，为企业压缩了宝贵的时间成本，让优质药品加速进入市场通道。　　同时，中心深化联合检查模式，为品种落地按下“加速键”。中心组建联合检查组，将品种场地转移行政许可检查与GMP 符合性检查同步实施，实现“一次检查、双重确认”。检查组提前与企业深度对接，结合产品工艺特性定制个性化检查方案，在检查中重点核查生产条件匹配性与质量体系连续性。检查组通过现场指导、问题即时反馈等方式，确保场地变更过程中产品质量稳定可控，从技术层面为品种转移保驾护航。　　中心始终以专业服务精神践行 “行业技术管家” 职责，通过一系列的务实举措，在满足群众用药需求的同时，让外资医药企业切实感受到北京营商环境的温度与效率，为外资医药企业在京扩大产能、深耕市场提供了有力支撑，为推动首都医药产业能级提升贡献专业力量。

Delivery Method:VIA Electronic MailReference #:320-25-84Product:DrugsRecipient:Ms. Lori A. PetersonChief Information Officer Quality Assurance/OwnerNature’s Fusions LLC57 North 1380 WestOrem,UT84057United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-84June 25, 2025Dear Ms. Peterson:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Nature’s Fusions LLC, FEI 3012853845, at 57 North 1380 West, Orem, Utah, from January 15 to 21, 2025.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 have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. Your firm failed to establish a written testing program designed to assess the stability characteristics of drug products and determine appropriate storage conditions and expiration dates. Your firm also failed to have buildings used in the manufacture, processing, packing, or holding of drug products with adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination (21 CFR 211.166(a) and 21 CFR 211.42(b)).Your facility repackages and manufactures over-the-counter (OTC) drug products, such as hand sanitizers. You failed to establish an adequate stability program that includes adequate chemical and microbial testing and lacked adequate controls for material storage.Lack of Stability StudiesYou used expired bulk ethanol hand sanitizer gel for repackaging into smaller units and assigned a two-year expiry date without conducting stability studies. In addition, you did not conduct stability studies for isopropyl alcohol (IPA) spray hand sanitizers manufactured onsite to demonstrate that your OTC drug products will remain acceptable throughout their assigned two-year expiry period.Inadequate Material StorageBulk totes of ethanol hand sanitizer gel were stored outdoors, and you informed our investigator that these totes had been stored outdoors since April 2020. Labeling for the bulk ethanol hand sanitizer gel lists a temperature storage range of(b)(4)F. The totes are exposed to temperature excursions that often exceed the specified temperature storage range, which could compromise the quality of the drug product therein.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).o All procedures that describe the listed elements of your remediated stability program.A comprehensive, independent assessment of all drug products in the U.S. market to determine if you have data to support that they conform to specifications throughout their shelf-life, including evaluating storage conditions, differences in each formulation, packaging configurations, and all historical stability studies that have been performed. If there are gaps in the data needed to scientifically support that your drug products retain their quality attributes through their labeled shelf-life, provide a CAPA plan which will include an impact assessment for any batches that remain within their shelf-life in the market.A summary of results from testing reserve samples within expiry for all drug product batches not currently in your existing stability program. Testing of each batch should be completed within 60 days of this letter. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients as well as microbiological quality of each batch. If testing yields an out-of-specification result, indicate the corrective actions you will take, including notifying customers and initiating recalls.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)).You failed to test all incoming raw materials, including isopropyl alcohol received from suppliers, used to manufacture your OTC hand sanitizer drug product. You relied on your supplier’s certificate of analysis (COA) for components, such as isopropyl alcohol, in lieu of testing each component for purity, strength, identity, and quality.You manufacture drugs that contain IPA. Methanol substitution in alcohols has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentPolicy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanolat https://www.fda.gov/media/173005/download.Without adequate testing and confirmation of reliability of supplier and external laboratory testing results, you lack scientific evidence that the components or drug products conform to appropriate specifications.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 summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedures that describes this COA validation program.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.Methanol testing for all hand sanitizer batches released and distributed in the United States within expiry.3. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release. Your firm also failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)).You failed to conduct adequate finished product release testing for each batch of your drug product, including but not limited to, testing the identity and strength of the active ingredient, isopropyl alcohol and testing for objectionable microorganisms. For example, your COA for(b)(4)indicates that you calculated the assay value instead of performing testing, and that you only performed organoleptic evaluation for appearance, color, and odor.Drug product batches must be tested for identity, strength, and purity prior to release. Testing is an essential part of ensuring that the drug products you manufacture conform to all predetermined quality attributes and are appropriate for their intended use. Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release.In response to this letter, provide:A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a batch disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of reserve samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing reserve samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.4. Your firm failed to establish written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess. (21 CFR 211.100(a)).You used water as a component to manufacture your OTC drug products. You were unable to provide adequate documentation demonstrating that your water system is validated. You failed to routinely monitor your(b)(4)water system for all required quality attributes to ensure that your water, at a minimum, meets the(b)(4)Water USP monograph and appropriate microbial limits. You lacked conductivity and total organic carbon limits and testing and did not test for specific objectionable microorganisms.Your total microbial specification limit is(b)(4). This is above the appropriate limits for water intended for pharmaceutical manufacturing. Our inspection revealed at least one instance of elevated bioburden in 2024(b)(4). These microorganisms were not further isolated to determine the identification of the bacterial species. Furthermore, your current schedule of quarterly microbiological testing is also insufficient.The lack of data regarding the state of control of your water system poses a potential risk for objectionable microbiological contamination into your drug products. Pharmaceutical water 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 comprehensive, independent remediation plan for the design, control, and maintenance of the water system.o A(b)(4)water system validation report specific for each water system in each building. Also include the summary of any improvements made to system design and to the program for ongoing control and maintenance for each water system.A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug product lots 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 recalls.A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.The current action/alert limits for total counts and objectionable organisms used for your(b)(4)water system.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets(b)(4)Water, USP monograph specifications and appropriate microbial limits.Drug Production CeasedDuring the inspection, you provided a document indicating that you will discontinue manufacturing of various drug products and did not anticipate renewing your registration as an OTC drug manufacturer. We acknowledge your commitment to cease manufacturing of pain relief rubs and various hand sanitizer drugs. In response to this letter, clarify whether you intend to resume manufacturing any 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. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPAs.CGMP Consultant RecommendedIf your firm intends to resume manufacturing drugs for the U.S. market, you should engage a consultant qualified 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. 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 3012853845 and ATTN: Jamie Dion.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

各药品上市许可持有人，机关相关处室、各有关直属单位：为深入贯彻落实《中华人民共和国药品管理法》（以下简称《药品管理法》），加快推进药品生产环节信息化追溯体系建设，打造“一物一码、物码同追”的药品全过程信息化追溯链条，持续提升药品生产监管效能，切实保障人民群众用药安全，现就我省药品生产环节追溯体系建设工作有关事项通知如下：一、工作目标贯彻落实《药品管理法》和国务院关于药品追溯的部署要求，积极推动药品生产环节信息化追溯体系建设，提高药品生产监管工作水平和效率，切实保障药品质量安全。药品上市许可持有人（以下简称“企业”）应当落实企业主体责任，建立药品追溯体系，原则上，自 2025 年 7 月 1 日起，对各级销售包装单元赋码，并做好各级销售包装单元药品追溯码之间的关联，保证药品追溯码的准确性、唯一性，于药品正式商业上市时实现赋码销售。二、工作重点（一）建立健全追溯管理制度。企业要结合本企业实际建立药品信息化追溯管理制度，明确追溯系统日常使用管理流程、规范及相关要求，将药品追溯工作纳入企业质量管理体系，指定专门机构和人员，实行有效管理。（二）实施药品赋码追溯管理。企业应根据《药品追溯码编码要求》，对各级销售包装单元赋码，并做好各级销售包装单元药品追溯码之间的关联，于药品正式商业上市时实现赋码销售。（三）督促下游企业开展追溯。企业要采取合同约定等方式督促一级下游经营企业或使用单位配合做好下游追溯数据的录入上传，组织开展对一级下游企业追溯工作的延伸审计，确保追溯信息及时、准确传递。三、工作要求（一）强化人民至上，确保认识到位。建立并实施药品追溯制度，是贯彻落实党中央、国务院决策部署，坚持人民至上、生命至上理念的具体实践，是落实企业药品全生命周期质量安全主体责任的重要体现。要进一步提高认识，建立健全工作机制，采取多种措施协同推进药品追溯工作，实现药品赋码销售，切实保障人民群众用药安全。（二）强化主体责任，确保准确规范。企业要对追溯系统进行定期回顾检查，按照《药品上市许可持有人和生产企业追溯基本数据集》要求，及时维护追溯系统中涉及药品的相关信息，确保追溯系统良性运行。质量受权人应当对放行产品进行查验，确保产品各级销售单元均按规定赋码并做好信息关联和信息采集，及时向追溯系统上传信息。（三）强化监督检查，确保落实到位。相关处室和单位要严格落实监管责任，加强对企业的行政指导和监督检查，督促落实追溯责任，将追溯管理制度建立、各级销售包装单元赋码、信息上传等落实纳入许可检查、日常监督检查项目，并在检查报告专章描述，推动企业主体责任持续有效落实，确保全面完成药品追溯赋码工作。（四）强化沟通协调，确保对接到位。相关处室和单位要结合药品智慧监管一体化平台建设，加强与企业沟通交流，制定追溯数据接口方案，通过对接采集生产环节追溯数据，服务监管业务需要。企业应配合提供追溯数据，采用第三方追溯技术服务的企业应及时授权并督促服务商向省药监局药品追溯监管系统推送追溯数据，自建系统的企业应在系统建设完成后及时与省药监局联系，做好数据对接工作。联系人：崇岚（药品生产处） 电话：0791-88158468李虞鸿浩（一体化专班） 电话：13907030286江西省药品监督管理局2025 年 5 月 9 日

各有关单位：　　我中心结合医疗器械注册法规、境内外注册申报产品的特点及申报现状，在总结技术审评实际情况，参考相关文献资料的基础上，新制定了《透析用留置针注册审查指导原则（公开征求意见稿）》。　　为了使该指导原则更具有科学性及合理性，即日起在网站公开征求意见。衷心希望相关领域的专家、学者、管理者及从业人员积极参与，提出建设性的意见和建议，推动指导原则的丰富和完善，促进医疗器械研发及技术审评质量和效率的提高。　　请将反馈意见以电子邮件的形式于2025年6月27日前反馈我中心。　　联系人：骆庆峰 肖 丽　　电话：010-86452840、86452844　　电子邮箱： luoqf@cmde.org.cn 　　通信地址：北京市大兴区经济技术开发区广德大街22号院一区6号楼 国家药品监督管理局医疗器械技术审评中心 　　邮编：100076　　附件：1.《透析用留置针注册审查指导原则（公开征求意见稿）》　　　　　2.《透析用留置针注册审查指导原则（公开征求意见稿）》修订反馈意见表国家药品监督管理局医疗器械技术审评中心2025年5月16日

各市（州）市场监管局：《贵州省第二类创新医疗器械特别审查程序》已经省药品监管局党组会审议通过，现印发给你们，请遵照执行。贵州省药品监督管理局2025年5月14日贵州省第二类创新医疗器械特别审查程序第一条 为鼓励我省医疗器械研究与创新，促进医疗器械新技术推广和应用，推动医疗器械产业高质量发展，根据《医疗器械监督管理条例》《医疗器械注册与备案管理办法》《体外诊断试剂注册与备案管理办法》《创新医疗器械特别审查程序》等法规、规章和文件，结合我省实际，制定本程序。第二条 本程序适用于省内第二类创新医疗器械特别审查申请的审查认定工作。外省市已获得国家药监局审查认定的第二类创新医疗器械，迁至我省申报第二类创新医疗器械首次注册的，直接按已获得本程序认定的第二类创新医疗器械情形执行。第三条 省药品监管局医药产业发展靠前服务工作专班（以下简称靠前服务专班）各成员单位，根据各自职责和本程序规定，按照提前介入、专人负责、科学审查的原则，在标准不降低、程序不减少的前提下，对创新医疗器械予以优先办理，并加强与申请人的沟通交流。第四条 省局医疗器械注册管理处（以下简称省局器械处）负责第二类创新医疗器械特别审查认定工作的组织和统筹协调，特别审查申请的接收、决定、异议处理。省局检查中心，承担创新医疗器械申请的技术审查、体系核查并出具审查意见、核查报告，加强与国家药品监局器审中心的沟通对接。第五条 符合以下条件的，申请人可以向省局申请第二类创新医疗器械特别审查：（一）产品已明确界定为第二类医疗器械；（二）产品具有技术创新和领先优势；（三）申请人已完成申报产品的前期研究并具有基本定型产品，研究过程真实和受控，研究数据完整和可溯源；（四）产品具有显著的临床应用价值。第六条 有下列情形之一的，可认为该产品具有技术创新和领先优势：（一）申请人通过其主导的技术创新活动，在中国依法拥有产品核心技术发明专利权，创新医疗器械特别审查申请时间距专利授权公告日不超过5年；（二）依法通过受让取得在中国发明专利权或其使用权，创新医疗器械特别审查申请时间距专利授权公告日不超过5年；（三）核心技术发明专利的申请已由国务院专利行政部门公开，并由国家知识产权局专利检索咨询中心出具检索报告，报告载明产品核心技术方案具备新颖性和创造性；（四）申请人通过其主导的技术创新活动，在中国依法拥有产品实用新型专利，或者依法通过受让取得在中国实用新型专利权或其使用权，实用新型专利的技术领域应与临床应用相关，并取得专利权评价报告，创新医疗器械审查申请时间距实用新型专利权生效之日起不超过5年；（五）申报产品主要工作原理或作用机理为国内首创，产品性能或者安全性与同类产品比较有根本性改进，技术上处于为国内领先水平或可取代同类进口产品。第七条 拟申请创新医疗器械特别审查的，申请人应当在第二类医疗器械注册申请前，向省局器械处提交《贵州省第二类创新医疗器械特别审查申请表》（见附件1），并提交支持拟申请产品符合本程序第五条、第六条要求的资料。申报资料应当使用中文，原文为外文的，应当有中文译本。资料应当包括：（一）企业营业执照副本或事业单位法人证书的复印件；（二）产品知识产权情况及证明文件；（三）产品研发过程及结果的综述资料；（四）产品作为第二类医疗器械管理的分类依据；（五）产品技术文件，至少应当包括：1.产品的适用范围或者预期用途；2.产品工作原理或者作用机理；3.产品主要技术指标及确定依据，主要原材料、关键元器件的指标要求，主要生产工艺过程及流程图，主要技术指标的检验方法；4.产品性能研究，提交产品已开展的非临床研究、临床研究及结果（如有）。（六）产品创新的证明性文件，至少应当包括：1.核心刊物公开发表的能够充分说明产品临床应用价值的学术论文、专著及文件综述；2.国内外已上市同类产品应用情况的分析及对比（如有）；3.产品的创新内容及在临床应用的显著价值。（七）产品风险分析资料；（八）产品说明书和标签样稿；（九）所提交资料真实性的自我保证声明。第八条 申请人向省局提出第二类创新医疗器械特别审查申请，省局应在收到申请之日起2个工作日内，完成对申请资料完整性和规范性的形式审查，符合要求的予以接收并转省局检查中心；不符合要求的一次性告知申请人需要补正的内容。省局检查中心根据需要提出创新医疗器械特别审批程序初审专家论证会方案，在5个工作日内组织靠前服务专班有关专家对拟作为创新医疗器械审批的产品是否符合本程序第五条、第六条要求进行审查，并根据专家意见提出初审建议结论。必要时，可组织系统外专家通过会审或函审等方式进行审查，所需时间不计算在审查时限内。专家组织管理由省局检查中心负责。对于已接收的第二类创新医疗器械特别审查申请，申请人在省局作出审查决定前，可书面提出撤回申请。第九条 存在以下情形之一的申请资料，直接按审查不予通过处理：（一）申请资料虚假的；（二）申请资料内容混乱、矛盾的；（三）申请资料的内容与申报项目明显不符的；（四）申请资料中产品知识产权证明文件不完整、专利权不清晰的；（五）前次审查意见已明确指出产品主要工作原理或者作用机理非国内首创，且再次申请时产品设计未发生改变或无法提供相关证明资料的。第十条 省局应及时通知申请人初审结论，审查未通过的应一并告知理由，创新审查结果不影响申请人按照法定程序申请第二类医疗器械注册。符合创新医疗器械特别审批条件的，在2个工作日将申报资料和初审意见一并报送国家药监局行政受理服务中心。第十一条 对于经国家药监局创新医疗器械审查办公室审查同意按创新医疗器械审批的，省局检查中心应当指定专人，在产品注册申请受理前以及技术审评过程中，与申请人及时沟通、提供指导。在标准不降低、程序不减少的前提下，省局对于纳入创新产品注册程序的医疗器械，在产品检验、现场核查、技术审评、行政审批等环节，开通绿色通道，予以优先办理。省医疗器械检测中心为创新医疗器械提供技术服务和指导，对其检验申请单独排序、优先检验、优先出具检验报告，在满足必需检验时间的前提下，检验时限缩减20%。省局可协调省内具有资质的第三方检验检测机构参照执行。省局检查中心对纳入创新产品注册程序的医疗器械，在注册申请受理前以及技术审评过程中，建立沟通机制，对企业申报注册工作给予专项辅导，进一步压缩现场核查、技术审评的工作时限。省局对纳入创新产品注册程序的医疗器械进一步压缩行政审批时限，按照《关于优化贵州省第二类医疗器械审评审批的若干措施》规定，对生产许可事项开展并联审批。第十二条 省局对创新医疗器械的临床试验的备案，提交材料齐全的，当场备案，并依法对临床试验进行监督检查和指导。第十三条 申请人在产品注册申请受理前以及技术审评过程中，可就下列问题填写《贵州省第二类创新医疗器械沟通交流申请表》（附件2）并向省局提出沟通交流申请：（一）重大技术问题；（二）重大安全性问题；（三）临床试验方案；（四）阶段性临床试验结果的总结与评价；（五）其他需要沟通交流的重要问题。第十四条 省局收到申请人提出的沟通交流申请后，应当对申请人提交的沟通交流申请及相关资料及时进行审核，同意进行沟通交流的，在2个工作日内主动与创新医疗器械注册申请人联系，并明确告知申请人拟讨论的问题，与申请人商定沟通交流的形式、时间、地点、参加人员等，安排与申请人沟通交流。沟通交流应形成记录，记录需经双方签字确认，供该产品的后续研究及审评工作参考。第十五条 注册资料准备完成后，申请人可向省局提交首次注册申请。省局收到第二类创新医疗器械首次注册申请，在2个工作日内做出是否受理的决定，受理的注册申请项目标记为“创新医疗器械”，并及时转省局检查中心进行技术审评。同时，优先安排注册质量管理体系核查现场核查，在5个工作日内出具核查结果（企业整改时间不计算在内）。第十六条 省局检查中心对创新医疗器械优先进行技术审评，在30个工作日内出具审评意见（申请人补正材料时间和专家审评时间不计算在内）。省局收到省局检查中心出具的审评意见后对创新医疗器械优先进行行政审批，并在2个工作日内做出审批决定。第十七条 医疗器械需要进行重大设计变更的，如临床试验方案修订，结构组成、使用方法、规格型号、预期用途、适用范围或人群的调整等，申请人应当评估变更对医疗器械安全性、有效性和质量可控性的影响。产品主要工作原理或作用机理发生变化的创新医疗器械，应当按照本程序重新申请。第十八条 纳入创新产品注册程序的医疗器械，在5年内未申报注册，不再按照本程序实施审批。第十九条  属于下列情形之一的，省局可终止本程序并告知申请人：（一）申请人主动要求终止的；（二）申请人未按规定的时间及要求履行相应义务的；（三）申请人提供虚假资料或采取其他欺骗手段的；（四）全部核心技术发明专利申请被驳回或视为撤回的；（五）失去产品全部核心技术发明专利专利权或者使用权的；（六）申请产品不再作为第二类医疗器械管理的；（七）经专家审查会议讨论确定不宜再按照本程序管理的。第二十条 经审查纳入创新注册程序并获准上市的第二类医疗器械，在产品注册证有效期内，申请变更注册的，省局予以优先办理。第二十一条 第二类创新医疗器械按省发展改革委、省财政厅的有关规定，免收产品注册费。第二十二条 本程序自发布之日起实施，原《贵州省创新医疗器械特别审批工作程序》（试行）同时废止。附件：1.贵州省第二类创新医疗器械特别审查申请表2.贵州省第二类创新医疗器械沟通交流申请表附件1贵州省第二类创新医疗器械特别审查申请表产品名称申请人名称申请人住所生产地址型号、规格性能结构及组成/主要成分主要工作原理/作用机理适用范围/预期用途联系人：             联系电话：               传真：                联系地址：           e-mail：                 手机：                 申请资料目录：（可附页）资料真实性保证声明我公司保证，本次递交的贵州省第二类创新医疗器械特别审查申请的材料均真实有效，如有虚假，本公司愿承担相应的法律责任。（公司盖章）法定代表人（签名）：   日期：附件2创新医疗器械沟通交流申请表申请人名称产品名称目前工作进展的阶段拟沟通交流的方式拟沟通交流的议题沟通交流的相关资料：（可附页）申请参加人员（可附页）姓名工作单位职称专业研究中负责的工作备注申请单位（盖章）                             申请日期               联系人：             联系电话：               传真：                联系地址：           e-mail：                 手机：          注：申请人提出沟通交流时，对拟讨论问题应有完整的解决方案或合理的解释依据。