海南省药监局启动药品追溯宣贯 推进零售使用环节全覆盖
为全面落实海南自贸港封关运作安全保障要求，进一步提升药品追溯系统应用覆盖率与实操水平，筑牢药品安全与医保基金监管防线，海南省药品监督管理局于3月23日在海口启动药品追溯宣贯培训，将用9天时间在全省开展药品追溯系统宣贯推广活动。本次活动由省药监局组建2个宣贯组，分东西两条线路，覆盖全省各市县药品监管单位、药品经营企业及医疗机构，集中开展政策宣讲、系统教学与实地指导，推动药品追溯全链条落地见效。为解决部分偏远地区小微企业信息化基础薄弱、操作人员年龄偏大等实际困难，打通政策落地“最后一公里”，省药监局专门组建药品追溯系统应用技术帮扶工作组，深入基层开展“手把手”培训指导，制作简易操作手册，提供“保姆式”精准服务，全力帮助小微企业和偏远地区经营主体破解技术瓶颈，确保药品追溯有关政策要求落到实处。宣贯期间，将围绕药品追溯政策法规、系统操作规范、数据采集标准、业务流程嵌入等核心内容，重点对乡村卫生室、私人诊所、偏远地区单体零售药店、未配备信息化设备的零售药店等工作人员进行宣贯教学，并深入一线开展现场指导，帮助基层监管部门、药店与医疗机构人员熟练掌握追溯系统应用，确保扫码采集、数据上传、信息关联等关键环节规范运行。此次宣贯既是提升药品监管效能的务实举措，更是药监系统将正确政绩观转化为保障群众用药安全、服务自贸港建设的实际行动。近年来，海南省药监局在国家药监局指导下，联合省卫健委、省医保局，依托三医联动一张网持续创新突破，不断完善全链条智慧监管体系。2024年，创新建成海南省药品追溯节点平台，有效破解药品零售与使用环节追溯难题，是国家药监局首批全国药品智慧监管5个创新示范项目之一。2025年，在节点平台基础上迭代升级药品追溯管理系统。截至2025年底，全省所有二级公立医院、医保定点药店及70%非医保药店已上线使用药品追溯系统，为医保基金专项治理、药品“清源”行动提供坚实技术支撑。2026年是海南自贸港封关运作的关键之年。海南省药监局持续加大药品追溯体系建设力度，确保6月底前实现全省零售药店药品追溯覆盖率100%，12月底前实现全省医疗机构等使用环节药品追溯覆盖率100%。通过全域覆盖、全程可溯、全员应用，进一步提升药品智慧监管效能，构建与自贸港封关相适应的药品安全风险防控体系，保障人民群众用药安全，服务海南自贸港药品安全治理现代化，以实实在在的工作业绩践行初心使命、彰显责任担当。供稿:综合处、药品流通处
辽宁省药品监督管理局关于同意锦州九洋药业有限责任公司恢复对乙酰氨基酚片生产的通告（辽药监告〔2026〕27号）
2026年3月19日，我局对锦州九洋药业有限责任公司违反《药品生产质量管理规范》（2010版）开展药品生产活动的整改情况进行了现场检查。根据现场检查结果，经综合评定，决定同意锦州九洋药业有限责任公司恢复对乙酰氨基酚片的生产。 特此通告。 辽宁省药品监督管理局2026年3月24日
天津市关于开展挂网药品价格联动调整工作的通知
各相关企业：现就开展挂网药品价格联动调整工作通知如下：一、调整范围及要求（一）调整范围天津市医药采购应用平台挂网价格高于其他地区最低挂网价格的部分药品。（二）调整要求1.相关企业应按照平台展示的全国最低挂网价主动接受价格调整。2.我市已挂网药品，在其他省（市、区）产生更低的挂网价格时，企业应于价格调整后的30天内向平台申请调整。二、调整时间及方式（一）调整时间时间安排：2026年3月25日—3月27日17时。（二）调整方式企业登录天津市医药采购应用平台，在“药品集中采购系统”选择“药品挂网价格调整”栏目查看并确认全国最低挂网价。如对全国最低挂网价有异议，请点击异议上传相关证明材料并写明实际全国挂网最低价，未写明实际全国挂网最低价的按照无效异议处理。三、其他要求未及时确认全国最低挂网价或提出异议的，予以暂停挂网。暂停挂网后，申请恢复挂网的应明确挂网价格，符合规定的予以恢复挂网。本次价格调整结束后，将统一对挂网价格进行调整，具体执行时间请关注通知。四、联系方式办公地址：天津陈塘科技商务区服务中心四楼（天津市河西区洞庭路20号）联系电话：022-24538156电子邮箱：tjmpc@tjmpc.cn天津市医药采购中心2026年3月25日
山东省海氏海诺健康科技股份有限公司对促黄体生成素（LH）测定试纸（胶体金法）主动召回
海氏海诺健康科技股份有限公司报告，由于公司生产的批号为 240202 的促黄体生成素（LH）测定试纸（胶体金法）（规格、型号：条型10人份/盒）监督抽查检验不合格，海氏海诺健康科技股份有限公司对其生产的促黄体生成素（LH）测定试纸（胶体金法）（医疗器械注册证号：鲁械注准 20162400570）主动召回。召回级别为三级召回。涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。2026年3月24日医疗器械召回事件报告表.pdf
浙江省药品监督管理局关于撤销汤可群等6人执业药师注册证的公告（2026年第3号）
根据温州市市场监督管理局《关于对温州市执业药师汤可群等二十八人资格证违规挂靠处理建议的函》，我局依据《执业药师注册管理办法》第三十四条、第三十六条第二项规定，撤销汤可群等6人的《执业药师注册证》（详见附件），并作为不良信息记入全国执业药师注册管理信息系统。特此公告。附件：撤销《执业药师注册证》名单撤销《执业药师注册证》名单序号姓名执业药师注册证号执业药师证注册单位1汤可群3322240360763温州巨兴药房有限公司2程贤花3332230348073温州市和生仁大药房有限公司3杜赛丹3332240351332温州新广源大药房有限公司4胡燕双3312240371648温州市一嘉一大药房有限公司5林高3322240351310文成县林玄堂医药有限公司6朱春燕3312240371316温州康佰家大药房连锁有限公司平阳联东路店
浙江省医疗器械审评中心圆满完成《心磁信号采集设备注册审查指导原则》制定工作
近日，省医疗器械审评中心在杭州组织召开《心磁信号采集设备注册审查指导原则》（以下简称《指导原则》）定稿会，标志着该项指导原则的制定工作圆满完成。 心磁信号采集设备作为极弱磁技术在临床诊断领域的最新应用，是一种非接触、无创、无辐射的新型高端医疗装备，通过采集人体心脏磁信号并进行成像分析，是目前高端医疗器械领域的前沿发展方向之一。作为国家重点培育的创新产业增长点，极弱磁测量技术已成为浙江省重点布局的未来产业方向。目前，浙江已形成了以杭州高新区（滨江）为核心的“零磁科学谷”和以湖州德清为重点的“地磁产业谷”双轮驱动格局。 在《指导原则》制定过程中，省医疗器械审评中心课题组始终坚持科学引领、问题导向。前期，课题组深入开展了国内外相关标准、技术文献及产品临床研究进展的调研工作，并专程赴北京、上海、山东等地，对多家具有代表性的研发生产企业以及医疗机构进行了调研，面对面听取企业在产品设计、性能验证及注册申报过程中的难点与诉求，广泛吸纳各方智慧。 本次定稿会上，课题组详细汇报了项目的研究历程、关键技术点的考量、初稿及中期研讨后的修改情况，以及面向全社会公开征求意见的汇总分析与处理结果。与会专家和代表围绕《指导原则》送审稿进行了严谨细致的审议，重点针对产品名称、性能指标、适用范围等核心内容进行了深入研讨，并最终达成共识。 医疗器械注册审查指导原则是保障上市医疗器械安全有效的重要技术支撑，也是连接科学监管与产业创新的桥梁。此次《指导原则》制定工作的圆满完成，不仅为国家层面统一该类产品的审评尺度贡献了“浙江智慧”，也为我省抢占高端医疗器械新赛道、推动相关产业集群高质量发展提供了坚实的技术支持。
医疗器械优先审批申请审核结果公示（2026年第8号）
依据原国家食品药品监督管理总局《医疗器械优先审批程序》（总局公告2016年168号），对申请优先审批的医疗器械注册申请进行审核，现将符合优先审批情形的项目予以公示，公示时间为2026年3月25日4月1日。序号受理号产品名称申请人同意理由1CQZ2600515血液透析器苏州卓壹医疗器械有限公司该产品属于“列入国家重点研发计划的医疗器械” 公示期内，任何单位和个人如有异议，可填写医疗器械优先审批项目异议表，提交至我中心电子邮箱：gcdivision@cmde.org.cn。国家药品监督管理局医疗器械技术审评中心2026年3月25日
辽宁省药品监督管理局关于第二类创新医疗器械确认结果的公告（辽药监告〔2026〕25号）
经审评，捷镜医疗技术（沈阳）有限公司申请的“一次性使用电子上消化道成像导管”“一次性使用电子下消化道成像导管”符合《辽宁省第二类创新医疗器械注册工作程序》（辽药监告〔2025〕73号）第四条规定的情形，确认为辽宁省第二类创新医疗器械。 上述产品自本公告之日起5年内申报注册的，将按照创新医疗器械注册工作程序实施审评审批。 特此公告。 辽宁省药品监督管理局2026年3月20日
Yangzhou H&R Plastic Daily Chemical Co., Ltd.(320-26-54)
Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-54Product:DrugsRecipient:Mr. Jingcheng GaoGeneral ManagerYangzhou H&R Plastic Daily Chemical Co., Ltd.188 Xingyuan RoadHangjiGuangling QuYangzhou ShiJiangsu Sheng,225111ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-54March 18, 2026Dear Mr. Gao:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou H&R Plastic Daily Chemical Co., Ltd., FEI 3014543859, at 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, from October 21 to 24, 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 your actions to address the deficiencies identified during the inspection and cited on our Form FDA 483. We note that you continue to ship drug products to the United States.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. 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 (21 CFR 211.165(a)).Your firm contract manufactures an over-the-counter(b)(4)drug product. You failed to adequately test batches of your finished drug product for the identity and strength of your active ingredient (e.g.(b)(4)) before release and distribution. Your specification procedures only discuss appearance, color, and weight checks prior to batch release.Full release testing, which includes strength and identity testing of the active ingredient, must be performed before drug product batch release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure that drug product batches conform to appropriate specifications before release.In response to this letter, provide:A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm failed to conduct adequate identity testing on incoming components, including active pharmaceutical ingredients, used in the manufacturing of your drug products. Additionally, you relied on your suppliers’ certificates of analyses (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.Without adequate testing and confirmation of reliability of supplier test results, you lack scientific evidence that the components conform to appropriate specifications prior to use in the drugs products you manufacture.In response to this letter, provide:A comprehensive, independent review of your material system, including but not limited to:o evaluating all suppliers of materials (components, containers, and closures) to determine if they are reliable and appropriately qualified;o an assessment of all materials to determine whether they are consistently of acceptable quality;o a review to ensure assigned expiration or retest dates are appropriate (supported by data);o adequacy of the supplier qualification program, and its selection, qualification, and disqualification provisions.Based on a thorough review, provide a summary of your systems corrective actions and preventive actions to remediate the vendor qualification program and 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 summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.3. Your firm failed to establish adequate 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)).Your firm failed to adequately qualify the equipment and validate the processes used to manufacture your(b)(4)drug product. You have not performed process performance qualification (PPQ) studies, nor do you have a meaningful ongoing program for monitoring process control, to ensure stable manufacturing operations and consistent drug quality.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 to ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality are necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.See FDA’s guidance document for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program forprocess performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing appropriate PPQ for each of your marketed drug products. Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.4. 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 firm failed to establish an adequate quality unit (QU) with the responsibilities and authority to oversee the manufacture of drug products. For example, you failed to ensure:Adherence to an adequate stability program (21 CFR 211.166(a)).Consistent and complete batch records (21 CFR 211.188).Appropriate examination of labeling and packaging materials for correctness, including but not limited to sufficiently accounting for all ingredients used in manufacturing, prior to packaging operations (21 CFR 211.130(d)).There was a fundamental failure of production management to effectively oversee the procedures, practices, and suitability of the manufacturing operations. In addition, even when a QU consists of one or only a few, those persons are still accountable for overseeing ongoing effectiveness of all systems and procedures, and review of the results of manufacture to ensure state of control and adherence to all quality standards.In response to this letter, provide:A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.Quality SystemsYour firm’s quality systems are inadequate. See FDA’s guidance documentICH Q10 Pharmaceutical Quality System, as well asQuality Systems Approach to Pharmaceutical CGMP Regulations, for 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/71553/download and https://www.fda.gov/media/71023/download, respectively.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 corrective actions and preventive actions 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. 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 all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on February 13, 2026.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 188 Xingyuan Road, Hangji, Guangling, Yangzhou, Jiangsu, 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 3014543859 and ATTN: Philip Kreiter.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research
IsoTis OrthoBiologics, Inc.(CMS #723370)
Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Peter P. NalbachVice President and General Manager of Spine OperationsIsoTis OrthoBiologics, Inc.2 Goodyear, Ste A,Irvine,CA92618United States(b)(4)Issuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS #723370February 24, 2026Dear Mr. Nalbach:During an inspection of your firm located in Irvine, CA from October 6, 2025, through October 17, 2025, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures resorbable calcium salt bone void filler devices, branded under the Accell Family of products, to include the Accell Evo3c. 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.Quality System Regulation Violation(s)This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, your 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 your Director Quality Systems, dated November 7, 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 adequately establish procedures for corrective and preventive action, as required by 21 CFR 820.100(a). For example:Your firm failed to adequately take action to correct the cause of nonconformities in order to prevent recurrence. Your firm's corrective and preventative action procedure, Corrective and Preventive Actions CP-1001 Rev. J Effective: 8/22/2022, requires your firm to perform an investigation, determine the need for containment, and assess the risk associated with the issue.Your firm opened CAPA 157738 on 7/27/23 to address potential(b)(4)particulate contamination occurring during the demineralization process of bone tissue, due to the propeller blade contacting the bottom of the demineralization vessel. The issue was discovered by a manufacturing engineer and documented in emails dating back to 06/22/2023.As part of CAPA 157738, your firm conducted a risk assessment for the demineralization process. In your risk analysis document, PFMEA-011 Rev. 12, effective October 23, 2023, your firm identified(b)(4)as a risk for particulate contamination. This risk was assigned a severity rating of Moderate and a probability of Improbable, resulting in an overall Acceptable risk rating. Despite discovering that the propeller blade was potentially shedding(b)(4)particles during demineralization, your firm did not investigate whether this finding affected your risk probability rating. In CAPA 157738, your firm classified the risk as low without providing justification for this conclusion and determined that containment action was not required due to your determined low risk. Your firm's CAPA investigation and actions are inadequate because it did not assess the potential impact to finished devices, including distributed product.Additionally, your firm’s Verification of Effectiveness included reviewing 18 work orders to confirm that visual inspection of the propeller was performed. The verification of effectiveness does not demonstrate that visual inspection of the propeller is sufficient to identify potential(b)(4)particulate in your firm's demineralized bone matrix (DBM). Your firm did not verify if the corrective actions performed were sufficient to correct the potential(b)(4)particulate contamination.Your firm closed CAPA 157738 on 12/17/2024 without evidence that(b)(4)particulate contamination was no longer occurring during your demineralization process.We reviewed your firm’s response and conclude that it is not adequate. While your firm’s response acknowledges procedural deficiencies and proposes process improvements, the CAPA defers critical product risk elements to separate CAPAs without clear indication that all deficiencies identified in CAPA-157738 have been adequately addressed. For example, in HHE-(b)(4), your firm identified(b)(4)complaints determined to be relevant now that(b)(4)contamination has been identified as a potential contributing factor. However, none of the related CAPAs indicate whether an MDR assessment was performed for these complaints.Additionally, it is not clear why the scope of the CAPA retrospective review is from 01/01/2022 to present.2. Failure to revalidate a validated process when changes or process deviations occurred, as required by 21 CFR 820.75(c). For example:Your firm’s procedure, Validation Program QA-035 Effective: 6/11/21, requires revalidation for previously validated process parameters, component changes, and major design changes; however, your firm did not revalidate your demineralization press when a major design change was made.Your firm opened CAPA 157738 on 7/27/23 to address a finding that during the manufacturing process of demineralizing bone tissue, the propeller blade contacts the bottom of the demineralization vessel creating the potential shedding of(b)(4)particulates. Two corrective actions were implemented:(b)(4)(b)(4)Your firm updated TL-0091 for the Demineralization Press in design change order (DCO), DCO 6306 Released: 5/24/24, which changed the equipment design by(b)(4). Your firm determined that qualification or validation is not required, though the DCO describes the change category as Major. Your firm answered No to the question: Is there a change in the manufacturing equipment while maintaining the existing process? on your Form CPF-0302-001 Decision Tree, although your firm changed the equipment design by(b)(4). Your firm’s Director of Quality Systems and Assurance told the investigator that they considered the demineralization press to be a tool and not equipment.Additionally, your firm determined that(b)(4)inspection was sufficient to identify potential(b)(4)contaminants and required training of your demineralization team to(b)(4)inspect the propellers, however your firm has not validated the(b)(4)inspection process for the propeller blades to demonstrate it is sufficient in identifying potential(b)(4)contaminants in your firm’s demineralized bone matrix (DBM). In an email from your firm’s manufacturing engineer, they note that(b)(4)particulates are(b)(4).We reviewed your firm’s response and conclude that it is not adequate. Your firm opened CAPA-100520 to address production and process related deficiencies identified in Observation 2. Actions include validating the(b)(4)inspection method with(b)(4)study, completing Installation Qualification for all(b)(4)demineralization assemblies, and establishing preventative maintenance and calibration programs. However, while your firm validated the inspection method and qualified equipment, there is no objective evidence that:An evaluation of the existing process validation was conducted to determine if the changes to the demineralization assemblies could impact the applicability of the existing Operational and Performance Qualifications.(b)(4)particulate contamination is no longer occurring in production and that the(b)(4)" clearance is sufficient to prevent all contact under all operating conditionsTesting has been performed to confirm absence of(b)(4)particles in DBMFurthermore, the verification of effectiveness plan measures compliance to procedures and execution of preventative maintenance but does not include testing for(b)(4)particulates in finished product.Additionally, it is not clear why the scope identified in CAPA-100520 for reviewing tooling changes is January 2022 to present, when the affected timeframe extends back to 2008.3. Failure to establish an adequate risk analysis, as required by 21 CFR 820.30(g). For example:Your firm’s procedure, CP-0305 Risk Management Rev. J1 Effective: 5/27/22, requires in Section 6.26.2 Perform Risk Reassessment (As Necessary), that if new or updated risk information is identified, it will be fed back into the risk management system and documented via update and approval of the appropriate risk management forms (such as the Hazard Analysis or FMEA).Your firm opened CAPA 157738 on 7/27/23 to address a finding, during the manufacturing process of demineralizing bone tissue, the propeller blade contacts the bottom of the demineralization vessel creating potential shedding of(b)(4)particulates. The CAPA identified the risk in PFMEA-001 for OrthoBlast II and PFMEA-002 DynaGraft II as(b)(4)for Supplier error leading to particulate contamination resulting in transient inflammation, which defined a severity of Moderate and a probability occurrence of Improbable, and the Risk Acceptability as Acceptable.Your firm identified the propeller blade was potentially shedding(b)(4)particulates during the demineralization process; however, your firm did not update PFMEA-001 for OrthoBlast II and PFMEA-002 DynaGraft II to identify this new risk factor.(b)(4)only addresses potential contaminants from your supplier resulting in transient inflammation and does not address the risk of contaminants during your firm’s manufacturing processes. Your firm did not identify the risk of(b)(4)contaminants and the potential impact to patient harm. Your firm’s risk management files were not updated after identifying this new risk, including identifying the severity of patient harm, as required by your procedure.Additionally, your firm did not reevaluate the probability of occurrence for potential contaminants.(b)(4)Supplier error leading to particulate contamination resulting in transient inflammation defines a probability occurrence of Improbable. Your firm did not update the occurrence probability after identifying the new risk of potential(b)(4)contaminants.According to your firm’s Senior Manager, New Product Initiatives and Sustaining Engineering, since your firm implemented the demineralized process in 2008,(b)(4)particulates may have been present in your DBM, potentially impacting over(b)(4)devices.We reviewed your firm’s response and conclude that it is not adequate. Your firm opened CAPA-100520 to address risk management deficiencies identified in Observation 3. Although your firm acknowledges that risk assessment associated with CAPA 157738 and related PFMEAs and Hazard Analysis (HA-(b)(4)) required revision and initiated procedural changes, your response is still inadequate. Your firm’s actions included:Updated PMFEAs ((b)(4)) to include(b)(4)Updated Hazard Analysis HA-(b)(4)to(b)(4)Conducted a retrospective Health Hazard Evaluation (HHE-(b)(4))HHE-(b)(4)concluded that no correction, removal, or recall recommended, as the risk level assessed as Low and Acceptable. Your firm acknowledges that(b)(4)contamination occurred from 2008-2024, with over(b)(4)devices potentially affected, however no actual testing was performed to confirm the absence of(b)(4)in distributed product. The HHE is deficient in that:Your firm reviewed(b)(4)complaints and deemed(b)(4)clinically relevant for your probability calculation. There was no clear indication on which were not deemed clinically relevant and why. Your firm concluded that(b)(4)complaints related to(b)(4)contamination without adequately documenting an investigation showing how they ruled out(b)(4)contamination as a contributing factor.Your firm’s Probability Assessment disregards potential inflammation or foreign body reaction due to(b)(4)particles as typical post-surgical inflammationSeverity Assessment deemed Moderate, which firm has defined in your firm’s procedure, Risk Management Rev. J1 Effective: 5/27/22 and identified in the Severity Ratings Table in HHE-(b)(4)as a minor intervention (i.e. Medical intervention that may result in procedural delay, requiring removal and re-insertion of device resulting in additional patient discomfort or increased anesthesia requirements; Minor, transient, or self-limiting injury not requiring medical intervention; Cancellation of an elective medical procedure / surgery). While complaint data included in HHE includes revision surgery, hospitalization, IV antibiotics, osteolysis consistent with a higher severity rating as noted in your procedure.Biocompatibility has not been adequately evaluated. Your firm states that(b)(4)is used in permanently implanted devices (stents, pledgets, endoprostheses), therefore,(b)(4)exposure is not expected to cause adverse effects. However, the cited devices use intact(b)(4)structures, not particulate contamination. Your firm provides no data demonstrating that they have:o Characterized potential particle generation during normal use and wear.o Conducted biocompatibility testing per ISO 10993 standards if particle release is expected.o Assessed the clinical significance of any particle elution through risk analysis.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.On February 2, 2024, the FDA issued afinal ruleamending the device current good manufacturing practice (CGMP) requirements of the Quality System (QS) Regulation under 21 CFR 820 to align more closely with the international consensus standard for Quality Management Systems for medical devices used by many other regulatory authorities around the world. The revised part 820, referred to as the Quality Management System Regulation (QMSR), became effective on February 2, 2026. Your most recent inspection on October 6, 2025 through October 17, 2025 was conducted pursuant to the QS Regulation, which was in effect at the time of the inspection. However, any corrective actions you propose, or implement must be pursuant to the QMSR requirements in effect as of February 2, 2026. For more information on the QMSR please refer to our frequently asked questions webpage: https://www.fda.gov/medical-devices/quality-system-qs-regulationmedical-device-current-good-manufacturing-practices-cgmp/quality-management-system-regulation-final-rule-amending-quality-system-regulation-frequently-asked.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 CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 723370” when replying. If you have any questions about the contents of this letter, please contact: Shaquenta Perkins at shaquenta.perkins@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/Barbara C. MarsdenActing DirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health
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