Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Mr. Lukas BluecherChief Executive OfficerMAST Biosurgery USA, Inc.11 HughesIrvine,CA92618United Stateslbluecher@mastbio.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS #720661December 17, 2025Dear Mr. Bluecher:During an inspection of your firm located in Irvine, CA from August 18, 2025 through August 21, 2025, an investigator (or investigators) from the United States Food and Drug Administration (FDA) determined that your firm manufactures surgical polymeric mesh devices, marketed as SurgiWrap FROST. 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, 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 Jayson C. Alaba, Quality Manager, dated September 12, 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 to prevent contamination or product by substances that may have an adverse effect on product quality, as required by 21 CFR 820.70(e). Specifically,CAPA 2404, dated 08/09/2024, was opened in response to a BSI finding identifying that your firm does not perform LAL endotoxin testing for your SurgiWrap devices. Your firm stated in pre-market correspondence to the FDA on 11/21/2020 that you would test SurgiWrap FROST for endotoxins to ensure that it is produced with endotoxin levels at or below FDA accepted limits of ≤ 20 EU/device. Additionally, your firm also stated to the FDA that you included a product lot-release endotoxin specification of ≤(b)(4)(≤(b)(4)) for the SurgiWrap FROST. However, your firm never implemented the testing of these specifications prior to distributing SurgiWrap FROST to customers in 2021.We reviewed your firm’s response and conclude that it is not adequate. Your firm confirms that it did not establish a specification or requirement for endotoxin testing for lot release prior to August 2024. Also, your response states you have established a ≤(b)(4)acceptance criteria specification for endotoxin testing of your SurgiWrap FROST; however, your firm did not provide a valid rationale for the acceptability of the specification. Prior to the clearance of your firm’s SurgiWrap FROST device (K200918), your firm committed to testing your SurgiWrap FROST devices for endotoxins to ensure that it is produced with endotoxin levels at or below FDA accepted limits of ≤ 20 EU/device and establishing a ≤(b)(4)(≤(b)(4)) lot-release specification. Your firm also provided a September 21, 2020 Certificate of Analysis premarket demonstrating that your firm was able to meet this lot release specification; endotoxin levels were below(b)(4). However, the August 19, 2024 Certificate of Analysis shows data from(b)(4)lots with endotoxin levels ranging up to(b)(4).Additionally, your response states that the SurgiWrap FROST is an implantable device but does not contact circulating blood or cerebrospinal fluid, therefore, a higher limit than the 20 EU/device typically applied to blood contacting implants is scientifically justified. The recommended 20 EU/device applies to both blood contacting and/or implanted devices. As your device is an implanted device, 20 EU/device is most appropriate.Your firm should evaluate your manufacturing process to identify why there is a large uptick in endotoxin between the(b)(4)test presented in(b)(4)and(b)(4)in your current process. Your firm should take appropriate measures to enhance endotoxin monitoring to ensure your mitigation measures result in acceptable endotoxin levels. Your firm should not reduce monitoring (e.g., reducing sample size to(b)(4)or raising the acceptance criteria to(b)(4)or(b)(4)).2. Failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, as required by 21 CFR 820.198 (a). Specifically,Your firm’s procedure, Complaint Process, Rev. T (effective date: 09/2022), Rev. U (effective date: 05/2023), Rev. V (effective date: 10/05/2023), Rev. W (effective date: 04/30/2025), is inadequate, in that, your firm has not adequately defined and documented complaint handling requirements. Specifically, your firm has categorized complaints as feedback, resulting in the events not being documented and handled as complaints.For example, Complaint C23004, dated 05/15/2023 alleges 8 out of 10 patients developed abdominal swelling after undergoing procedures involving SurgiWrap. Your firm asked your customer if they wanted to classify this complaint as feedback or a complaint. When they decided to classify these events as feedback, your firm closed the complaint by stating that the complaint was reported based on feedback, so there is no need to further delve into the reported case. Your CEO stated that some of the investigational steps were taken in response to this complaint, but they were not documented in your quality management system. There is no record of the nature and details or investigation of each of the 8 events.We reviewed your firm’s response and conclude that it is not adequate. Your response states your firm’s plans to(b)(4). However, it is not clear if your firm’s(b)(4)includes an evaluation of your Customer Feedback forms, Return Material Authorizations (RMAs) or other sources outside of your complaint handling system, to determine if they constitute as a complaint.Medical Device Reporting (MDR) Violation(s)Our inspection also revealed that your firm’s surgical meshes 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 803 - Medical Device Reporting. Significant violations include, but are not limited to, the following:Failure to report to us the information required by § 803.52 in accordance with the requirements of § 803.12(a), no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that your firm markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1). For example,1. The information included for the complaint C23002 reasonably suggests that a patient experienced injuries (e.g., postoperative ileus) following the use of your firm’s SurgiWrap device. As such, medical and surgical interventions such as nasogastric (NG) tube insertion, antibiotic therapy, and total parenteral nutrition (TPN) were administered and deemed necessary to prevent permanent impairment of a body function or permanent damage to a body structure. Your firm became aware of the event on February 1, 2023. Although your firm referenced MDR 3004661493-2023-00001 in its records, FDA has not yet received the refenced report, which is beyond the required 30 calendar day timeframe.2. The information included for complaint C24002 reasonably suggests that a patient experienced an injury (i.e. small intestinal stenosis) following the use of your firm’s SurgiWrap device. As a result, a surgical intervention (i.e. intestinal resection) was performed, which was deemed necessary to prevent permanent impairment of a body function or permanent damage to a body structure. Your firm became aware of the event on(b)(6), (b)(7)(C). Although your firm referenced MDR 3004661493-2023-00002, in its records, FDA has not yet received the referenced report, which is beyond the required 30 calendar day timeframe.We reviewed your firm’s response dated September 13, 2025, and conclude that it is not adequate. The response notes that your firm initiated CAPA-2511 to address the issue, including performing a retrospective risk assessment of the referenced events, which concluded that the events were not MDR reportable based on your firm’s internal risk assessment criteria requiring intervention. The physicians’ assessments indicated a causal relationship between your firm’s device and the referenced events, and that associated medical or surgical interventions were administered. As such, each referenced event meets the criteria of a reportable serious injury under 21 CFR 803.3.A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.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 CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 720661” 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 MarsdenActing DirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCC: Jayson C. Alaba, Quality Manager, jalaba@mastbio.com

Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:26-HFD-45-01-02Product:DrugsRecipient:Bruce S. Gillis, M.D., MPHCEOCenter For Immunology Science, LLC2109 Granville AvenueLos Angeles,CA90025-6105United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERFDA Ref. No.: 26-HFD-45-01-02Dear Dr. Gillis:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted between October 7 and November 20, 2024. The investigator representing FDA reviewed the role of the Center for Immunology Science, LLC (Center for Immunology Science) as the sponsor of a clinical investigation (Protocol CISMX-001/CISMX-001B,1“Use of Heat-KilledMycobacteria smegmatisas a nutritional supplement/biotic to boost immune system and microbiome health”) of the investigational drug, heat-killedMycobacteria smegmatis.This inspection was conducted as a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.At the conclusion of the inspection, the FDA Investigator presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your November 27, 2024, written response to the Form FDA 483.From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated November 27, 2024, it appears that the Center for Immunology Science did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, part 312 (21 CFR 312), governing the conduct of clinical investigations and the protection of human subjects. We wish to emphasize the following:You failed to submit an Investigational New Drug application (IND) for the conduct of a clinical investigation with an investigational new drug that is subject to 21 CFR 312.2(a) [21 CFR 312.20(a), 312.20(b), and 312.40(a)].FDA regulations require a sponsor to submit, and to have in effect, an IND before initiating a clinical investigation of a drug that is subject to 21 CFR 312.2(a) [see 21 CFR 312.20 and 312.40(a)] in human subjects, unless the clinical investigation qualifies for an IND exemption under 21 CFR 312.2.2The Center for Immunology Science failed to comply with these requirements. Specifically, the Center for Immunology Science initiated and conducted Protocol CISMX-001, a clinical investigation of the investigational drug, heat-killedMycobacteria smegmatis, subject to section 505 of the FD&C Act [21 U.S.C. 355], without submitting and having in effect an IND.In the Center for Immunology Science’s November 27, 2024, written response to the Form FDA 483, you stated that an IND is only required for a drug product. You further stated that under the Dietary Supplement Health and Education Act of 1994 (DSHEA), a dietary supplement is not considered a drug and is not subject to the premarket approval requirements for drugs if the intended use for which it is marketed is only to affect the structure or any function of the body. You also stated that whether an IND is needed for a clinical investigation evaluating a dietary supplement is determined by the intent of the clinical investigation, noting that if the clinical investigation is intended only to evaluate a dietary supplement’s effect on the structure or function of the body, an IND is not required. You stated that since the protocol describes heat-killedMycobacteria smegmatisas a nutritional supplement/biotic intended to boost immune system and microbiome health, an IND was not required.For the reasons described below, we conclude that the evidence collected during the inspection shows that heat-killedMycobacteria smegmatiswas intended for use as a drug, not as a dietary supplement, for the clinical investigation conducted under Protocol CISMX-001. Therefore, the Center for Immunology Science was required to submit an IND before initiating and conducting the clinical investigation.Section 201(g)(1) of the FD&C Act [21 U.S.C. 321(g)(1)] defines drug, in part, as “articles intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease….” The Center for Immunology Science studied the efficacy of heat-killedMycobacteria smegmatisto treat or mitigate immune-deficiency diseases. As described in the protocol, the purpose of Protocol CISMX-001 was to determine if subjects with an immune-deficiency disease can benefit from taking heat-killedMycobacteria smegmatis. The protocol stated thatMycobacteria smegmatishas immune-modulating effects that can stimulate or suppress the immune system and may help the body fight cancer, infection, or other diseases. Protocol CISMX-001 also states that information from the study may be used to produce an over-the counter product to boost immune system and microbiome health that may help reduce symptoms associated with an immune-deficiency medical disease. Additionally, outcome assessments for the study, performed after the administration of heat-killedMycobacteria smegmatis, included weekly health questionnaires to evaluate changes in, or the frequency and severity of, subject-reported symptoms, including but not limited to fatigue, pain or tenderness, depression, anxiety, insomnia, headaches, abdominal pain, and respiratory problems. Therefore, Protocol CISMX-001 collected study data to assess the efficacy of heat-killedMycobacteria smegmatisin treating or mitigating the symptoms associated with immune-deficiency diseases.Whether an investigational article is a drug depends on the intent of the investigation. Based on the study design of Protocol CISMX-001, the investigational product, heat-killedMycobacteria smegmatis, as used in the clinical investigation, was a drug as defined in section 201(g)(1) of the FD&C Act, because heat-killedMycobacteria smegmatiswas studied for use in the treatment of immune-deficiency diseases.Thus, before initiating the clinical investigation of heat-killedMycobacteria smegmatisconducted under Protocol CISMX-001, under 21 CFR 312.40, the Center for Immunology Science was required to submit an IND to FDA and to have an IND in effect. FDA’s records indicate that the Center for Immunology Science failed to submit an IND before conducting Protocol CISMX-001, in which 200 human subjects received investigational drug.In your November 27, 2024, written response, you stated that the Center for Immunology Science is prepared to comply with all future obligations. However, your written response does not provide sufficient details about the Center for Immunology Science’s corrective and preventive action plan for developing and implementing procedures to comply with IND regulations, if the Center for Immunology Science should decide in the future to initiate another clinical investigation for which an IND is required. As a result, your response is inadequate. Without this information, we are unable to determine whether the Center for Immunology Science will comply with IND regulations in the future.As a sponsor, you are responsible for complying with IND requirements, which include submitting and having in effect an IND before initiating a clinical investigation. It is also your responsibility, as a sponsor, to be aware of and to follow all applicable FDA regulations. The Center for Immunology Science’s failure to submit, and to have in effect, an IND before initiating Protocol CISMX-001 with an investigational drug raises significant concerns about the safety and welfare of enrolled subjects, and raises concerns about the validity and integrity of data collected during the conduct of this clinical investigation.This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational drug. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address this matter adequately may lead to regulatory action. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.Should you have any questions or concerns regarding this letter or the inspection, please email FDA at CDER-OSI-Communications@fda.hhs.gov. Your written response and any pertinent documentation should be addressed to:Brittany L. Garr, MPHBranch ChiefCompliance Enforcement BranchDivision of Enforcement and Postmarketing SafetyOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug AdministrationBuilding 51, Room 535210903 New Hampshire AvenueSilver Spring, MD 20993Sincerely yours,/S/David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration___________________1Protocol CISMX-001B was conducted in healthy human subjects.2Protocol CISMX-001 does not qualify for any of the exemptions listed at 21 CFR 312.2 from the application of 21 CFR 312. To be IND-exempt under 21 CFR 312.2, the investigational product must, among other things, be lawfully marketed in the United States as a drug product. As stated in your November 27, 2024, written response, heat-killedMycobacteria smegmatisis marketed as a dietary supplement, not as a drug product.

行政相对人名称宁安市杨氏膏药有限公司中医诊所分公司行政相对人代码(统一社会信用代码)91231084MAE40LTG94法定代表人杨金勇行政处罚决定书文号宁市监处罚〔2026〕11号违法行为类型违反《中华人民共和国药品管理法》第七十四条第一款违法事实2026年1月5日我局接到12345政务服务便民热线工单回执单，称市民在宁安市杨氏膏药有限公司中医诊所分公司购买了配制膏药及用于加工膏药的中药粉，花费1200元。违反药品管理法。 2026年1月7日执法人员到该诊所核查，诊所未能提供张先生的当日医师处方，现场发现处置室白色塑料盒内放有事先加工而成的制品深色中药粉，含有多种中药成分，现场称重75.7g，无包装，无中文标识，且不能提供医疗机构制剂许可证。属未取得《医疗机构制剂许可证》生产销售药品。处罚依据依据《药品监督管理行政处罚裁量适用规则》第十一条第（二）项、第（四）项《中华人民共和国药品管理法》第一百一十五条处罚类别罚款处罚内容1.没收违法所得一千二百元（1200.00元）； 2.没收违法使用的药品; 3.罚款一万元（10，000.00元）；罚没款合计一万一千二百元（11200.00元）。罚款金额（万元）1没收违法所得没收非法财物的金额（万元）0.12处罚决定日期2026-01-27处罚有效期2028-01-26公示截止期2026-04-26处罚机关宁安市市场监督管理局

南京神奇科技开发有限公司报告，由于在江苏省局监督抽检中出现外观不符合要求的原因，南京神奇科技开发有限公司对其生产的长效抗菌材料主动召回。召回级别为三级。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》。

贝克曼库尔特实验系统（苏州）有限公司报告，由于电脑在模式切换过程中，可能出现非预期错误，导致无法开始分析的原因，贝克曼库尔特实验系统（苏州）有限公司对其生产的全自动生化分析仪主动召回。召回级别为三级。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》。

 根据《中华人民共和国药品管理法》《中华人民共和国药品管理法实施条例》《药品生产监督管理办法》等有关规定，海南省药品监督管理局依法注销海南天煌制药有限公司、海南美大制药有限公司的《药品生产许可证》。序号企业名称许可证编号注册地址备注1海南天煌制药有限公司琼20160058海口市美兰区江东新市区机场北路6号药品生产许可证有效期届满2海南美大制药有限公司琼20160081海口市保税区内C03号药品生产许可证有效期届满 特此通告。 海南省药品监督管理局                                  2025年12月30日（此件主动公开）

各药品（耗材、试剂）相关企业：按照《国家医疗保障局关于建立医药价格和招采信用评价制度的通知》（医保发﹝2020﹞34号）、《医药价格和招采信用评级的裁量基准》等相关要求，我中心对2024年第四季度医药商业贿赂案件进行了信用评级处置，请相关药品（耗材、试剂）企业（见附件）至我中心领取《价格招采信用评价预评级函》。领取时需携带授权书，领取时间为本公告发布之日起15日内，逾期视为送达。领取地址：省医药采购中心督查科（614）相关附件：安徽省医药价格和集中采购中心 2026年1月26日

企业名称大连德昌药业有限公司医药批发分公司企业类型药品批发检查时间2025年11月20日-2025年11月21日所在地市大连市检查依据《药品管理法》《药品经营质量管理规范》检查事项药品经营检查检查方式飞行检查合并常规检查检查内容药品经营执行GSP情况存在问题在质量管理体系文件方面存在制订的《质量管理体系内审管理制度》内容表述不准确的问题；在设施与设备方面存在仓库未设置拼箱发货区域的问题；在储存与养护方面存在零货区货架上不同品种、不同批号中药饮片有混摆现象的问题。处理措施责令限期整改整改情况已按要求完成整改

企业名称大连致美义齿有限公司企业类型医疗器械生产企业检查时间2026年1月15日-2026年1月15日所在地市大连市检查依据《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》等法规规章和规范性文件检查事项医疗器械生产检查检查方式常规检查检查内容贯彻落实《医疗器械监督管理条例》《医疗器械生产监督管理办法》及《医疗器械生产质量管理规范》情况存在问题在生产管理方面存在紫外线消毒记录表记录项目不全的情况；在质量控制方面存在比色板自校记录项目不全的情况。处理措施限期整改整改情况已按要求完成整改

近日，国家药监局综合司公布了药品监管系统2025年药品检验能力验证结果为满意的机构名单。其中，贵州省医疗器械检测中心参与的“人血清中葡萄糖含量检测”、“爬电距离和电气间隙试验”及“血清生化指标检测能力验证”三项能力验证均取得“满意”成绩。同时，根据中国食品药品检定研究院、广检集团机构公布的2025年度能力验证计划结果显示，省医疗器械检测中心在2025年度报名参加的“输注器具溶出液中镉含量测定”及“幽门螺杆菌抗原定性检测”“纺织品织物拉伸性能（断裂强力）测定”、“口罩过滤效率测定”及“一次性使用卫生用品微生物指标测定”五项能力验证项目结果均取得“满意”结果。在整个过程中，省医疗器械检测中心实验室严格依据国家标准和技术规范，独立完成样品检测、数据分析与结果报送，所有项目均在规定时间内提交了完整、准确的检测数据和原始记录。最终，八个项目结果均获组织方评定为“满意”，通过率100%，实现了年度外部能力验证“全满意”的优异成绩。充分展现了省医疗器械检测中心在多个专业领域稳定可靠的检验检测技术能力。能力验证是国际公认的评价实验室技术能力的重要手段。此次“全满意”成绩的取得，是中心长期坚持质量管理、夯实技术基础、强化人员培训的集中体现。它不仅是对中心现有质量管理体系有效性和技术能力可靠性的权威佐证，更是对技术人员实操水平与问题解决能力的成功检阅。此次优异成绩将激励全体员工继续秉持诚实守信、方法科学、行为公正、数据可靠的质量方针。未来，省医疗器械检测中心将持续参与更广泛、更高水平的能力验证活动，以评促建，以验促强，不断提升综合技术能力，为保障医疗器械产品质量安全、服务市场监管和产业发展提供更加坚实的技术支撑。