在2025年国家化妆品抽样检验工作中，经浙江省食品药品检验研究院等单位检验，产品标签标示名称为诗朗生姜去屑修护洗发露等37批次化妆品不符合规定（见附件）。　　根据《化妆品监督管理条例》《化妆品生产经营监督管理办法》《化妆品抽样检验管理办法》，国家药品监督管理局已要求上海、山东、广东等省（市）药品监督管理部门对上述不符合规定化妆品涉及的注册人、备案人、受托生产企业等依法立案调查，责令相关企业依法采取风险控制措施并开展自查整改。各省（区、市）药品监督管理部门要依法责令相关化妆品经营者停止经营上述化妆品，并依法调查其进货查验记录等情况，对违法产品进行追根溯源，发现违法行为的，依法严肃查处；涉嫌犯罪的，依法移送公安机关。　　特此通告。　　　　　　附件：37批次不符合规定化妆品信息　　国家药监局　　2025年12月9日

根据《2025年广西化妆品生产企业监督检查实施方案》(桂药监办〔2025〕28号)，我局组织对相关企业进行了监督检查，现将检查结果予以公布（详见附件）。附件：2025年化妆品生产企业监督检查结果汇总表广西壮族自治区药品监督管理局 2025年12月8日                                                            附件2025年化妆品生产企业监督检查结果汇总表序号企业名称检查结果备注1 广西名欧药业有限公司符合要求2 广西壮美生物科技有限公司符合要求3 南宁大旭美化妆品有限公司符合要求4 广西和桂集团有限公司符合要求5 柳州市中兴日用化工有限责任公司符合要求6 南宁名露医疗保健品有限公司符合要求7 广西花之丽人化妆品有限公司符合要求8 广西庆翠堂生物科技有限责任公司符合要求9 广西云康健健康管理有限公司符合要求10 广西露仙娜生物科技发展有限公司符合要求11 广西英和药业有限公司符合要求12 广西茶氏家族山茶籽有限公司符合要求13 广西锦秀堂生物科技有限公司符合要求14 广西国风生物科技有限公司符合要求15 广西肤可迪赛再生医学工程有限公司符合要求16 广西正为生物科技有限公司符合要求17 广西福莱明生物制药有限公司符合要求18 广西鹤兰墨广泽生物科技有限公司符合要求19 广西医大协同医疗技术有限公司符合要求20 广西康嘉化妆品有限公司符合要求21 广西锦生堂生物科技有限公司符合要求22 南宁利仁堂生物技术有限责任公司生产部符合要求23 柳州两面针股份有限公司符合要求24 桂林云汉日用化工有限责任公司符合要求25 桂林市高乐医药保健品有限公司符合要求26 桂林长圣药业有限责任公司符合要求27 广西龙广滑石开发股份有限公司符合要求28 桂林华诺威生物技术有限公司符合要求29 桂林长发小寨生物科技有限公司符合要求30 广西梧州市藤县亮友医药卫生用品有限公司符合要求31 瑞福祥药业（广西）有限公司符合要求32 北海市海真珠化妆品有限公司符合要求33 北海市海珠韵化妆品有限公司符合要求34 北海黑珍珠海洋生物科技有限公司符合要求35 广西百琪药业有限公司符合要求36 广西源盛堂生物科技有限公司符合要求37 广西蓝港生物科技有限公司符合要求38 桂平华宝健康科技有限公司符合要求39 广西博生生物科技有限公司停 产40 广西玉林吉诺生物科技有限公司停 产41 广西法莱澳生物科技有限公司停 产42 广西源林中药制品有限公司符合要求43 广西协成日用化工有限公司符合要求44 广西九香族生物科技有限公司符合要求45 广西妍叶生物科技有限责任公司符合要求46 广西凤山绿贞科技发展有限公司整改后符合要求47 南丹县茂晨农业科技发展有限责任公司停 产48 金秀瑶族自治县瑶山源养生堂有限公司符合要求49 广西象州县丝丝情缘生物科技有限公司符合要求50 广西象州县一丹生物技术有限公司符合要求51 广西瑶之御品贸易有限公司符合要求52 广西同和药业有限公司符合要求53 广西宏瑶生物科技股份有限公司符合要求

　　按照《中华人民共和国药品管理法》《中华人民共和国行政许可法》和《药品经营和使用质量监督管理办法》等相关规定，根据企业申请，现注销郸城县阳光医药超市连锁有限公司的《药品经营许可证》（证书编号：豫BA3946135）。　　特此公告。　　附件：郸城县阳光医药超市连锁有限公司《药品经营许可证》有关信息表　　2025年12月9日附 件郸城县阳光医药超市连锁有限公司《药品经营许可证》有关信息表企业名称企业法人（负责人）质量负责人经营方式经营范围注册地址仓库地址证书编号郸城县阳光医药超市连锁有限公司李明(周双双)周桂荣零售连锁总部中药饮片，中成药，化学药制剂，抗生素制剂，生化药品，生物制品（除疫苗）等等郸城县广场南路碧水湾小区41号一楼商铺郸城县广场南路碧水湾小区41号一楼商铺豫BA3946135

　　按照《中华人民共和国药品管理法》《中华人民共和国行政许可法》和《药品经营和使用质量监督管理办法》等相关规定，根据企业申请，现注销义马市济仁堂医药连锁有限公司的《药品经营许可证》（证书编号：豫BA398000069）。　　特此公告。　　附件：义马市济仁堂医药连锁有限公司《药品经营许可证》有关信息表。　　2025年12月9日附 件郸城县阳光医药超市连锁有限公司《药品经营许可证》有关信息表企业名称企业法人（负责人）质量负责人经营方式经营范围注册地址仓库地址证书编号义马市济仁堂医药连锁有限公司付花丽(付花丽)李阳零售连锁总部处方药、甲类非处方药、乙类非处方药：中药饮片（含冷藏药品）、中成药（含冷藏药品）、化学药（含冷藏药品）、血液制品（含冷藏药品）、其他生物制品（含冷藏药品）河南省三门峡市义马市千秋路西段27号河南省三门峡市义马市千秋路西段27号豫BA398000069

Delivery Method:VIA UPSReference #:320-26-21Product:Drugs、Over-the-Counter DrugsRecipient:Mr. Luis F SalazarPresident/CEOCDL Services, Inc. DBA Technichem3800 E Miraloma AvenueAnaheim,CA92806United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-21November 24, 2025Dear Mr. Salazar:The U.S. Food and Drug Administration (FDA) conducted an inspection at CDL Services, Inc. DBA Technichem, FEI 3012112742, located at 3080 E La Jolla Street, Anaheim, CA, from April 7 to 28, 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 reviewed your May 15, 2025, response to our Form FDA 483 in detail.During our inspection, our investigators 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 manufactures over-the-counter (OTC) drug products including hand sanitizers and(b)(4)hand soap. Your firm failed to adequately test batches of your drug products for the identity and strength of your active ingredients (e.g., ethanol and chloroxylenol) before release and distribution. For example, you stated that finished product testing data provided during the inspection was generated using simulated results and that no testing had been performed on finished drug products in over a year. As a result, your firm released drug product to the market without appropriate testing, review, and approval to ensure satisfactory conformance to final specifications for strength and identity.In your response, you commit to testing products prior to distribution and testing the “most recently distributed” batches. Your response is inadequate in that it does not provide sufficient documentation for finished product testing (e.g., proposed test methodology or specifications). Moreover, your response fails to provide a timeline for when this testing will be completed or to perform any risk assessment.Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished product specifications and are suitable for release to consumers.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 lot disposition decision.An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug products that are within expiry as of the date of this letter.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 test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm failed to ensure that components were suitable for use in manufacturing your OTC drug products. For example, you did not perform identity testing on each shipment of each lot of incoming components, such as glycerin, ethanol and chloroxylenol. Additionally, you relied on your suppliers’ certificates of analysis without verifying your supplier’s test results at appropriate intervals. Furthermore, you have not ensured that water used as a component is suitable for its intended use (e.g.,(b)(4)Water, United States Pharmacopeia (USP) monograph).Products Containing EthanolYou failed to adequately test your incoming component ethyl alcohol (ethanol) at risk of methanol contamination for identity before using it as an active pharmaceutical ingredient (API) in manufacturing your OTC topical drug products. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentPolicy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanolto help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/media/173005/download.Products Containing Ingredients at Risk for Diethylene Glycol or Ethylene Glycol (DEG or EG) ContaminationYou also failed to adequately test your incoming components at high risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination for identity before using them to manufacture your drug products. This includes, but is not limited to, testing of glycerin and propylene glycol to determine its appropriate identity, prior to use in manufacturing your OTC topical drug products.Identity testing for glycerin, propylene glycol and certain other high-risk drug components includes a limit test in the USP to ensure the component meets the relevant safety limits for DEG or EG levels. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in the manufacture of your drug products.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.Water Used as a Component in Drug ProductsMoreover, your firm uses water as a component in the manufacture of your drug products. Your firm has not demonstrated that the water is suitable for its intended use in pharmaceutical manufacturing. At a minimum, such water must meet the(b)(4)Water, USP monograph and appropriate microbial limits.In your response, you commit to performing identity testing of components, testing for methanol and DEG/EG in high-risk components, and testing of your water used as a component. Your response is inadequate in that you did not provide a detailed plan for how your components will be assessed against compendial requirements. Furthermore, it did not include sufficient information regarding test methods or a timeline for implementing the proposed corrective actions.Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.In response to this letter, provide:A summary of results obtained from testing all components to evaluate the reliability of the certificate of analysis (COA) from each component manufacturer. Include your standard operating procedure (SOP) that describes this COA validation program.A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.The chemical and microbiological quality control specifications you use to test each incoming lot of components, including high-risk drug components, to determine acceptability for use in manufacturing.A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.A commitment to provide methanol test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of components within expiry of manufactured drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of methanol.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your water system consistently produces water that meets(b)(4)Water, USP monograph specifications and appropriate microbial limits.3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) lacked adequate control over your OTC drug product manufacturing operations and failed to ensure that you had adequate procedures. For example, your quality unit (QU) failed to ensure the following:Establishment of adequate procedures describing the roles and responsibilities of the QU, including review of complaints, supplier qualification, change control and periodic product quality review (21 CFR 211.22(a) and 211.22(d)).Establishment of appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records or other records (21 CFR 211.68(b)).Establishment of adequate production procedures and process control to assure your drug products have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Drug products bear expiration dates that are supported by appropriate stability testing (21 CFR 211.137(a)).Establishment of adequate batch production and control records that contain the accomplishment of each significant step in the manufacture, processing, packing, or holding of the batch, for each batch of drug product (21 CFR 211.188(b)).In your response, you commit to establishing a dedicated QU with associated procedures. Your response is inadequate in that it lacks detail on systemic remediations for your QU and improvements to your quality system. Your response also fails to provide details on how your QU will have the responsibility and authority to perform its functions.See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.In response to this letter, provide:A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriateo Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decisiono Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productsA complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control. Also, include your program for qualification of your equipment and facility.A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methodso Stability studies for each drug product in its marketed container-closure system before distribution is permittedo 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 valido Detailed definition of the specific attributes to be tested at each station (timepoint)Access to Information During InspectionDuring the inspection, the gas chromatograph and the associated CGMP computer system were not available to the inspection team. This limited FDA’s access to records for inspection to evaluate the CGMP compliance status of your facility.When an owner, operator, or agent delays, denies, limits, or refuses an inspection, the drugs may be deemed adulterated under section 501(j) of the FD&C Act. See FDA’s guidance documentCircumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspectionat https://www.fda.gov/media/86328/download.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical Current Good Manufacturing Practice Regulationsfor guidance on implementing modern quality systems and risk management approaches to meet the requirements of the Agency's CGMP regulations at https://www.fda.gov/media/71023/download.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.Cosmetics Manufactured for Distribution in the United StatesIn addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations 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 man-ufacturer 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 3012112742 and ATTN: Andrew Haack, Compliance Officer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Brent T. LucasCEO & DirectorEnvoy Medical Inc.4875 White Bear ParkwaySaint Paul,MN55110-3325United Statesblucas@envoymedical.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 718762November 11, 2025Dear Mr. Lucas:During an inspection of your firm located in Saint Paul, MN from June 24, 2025, through July 2, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufacturers the Esteem II Implantable Hearing System. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), this product is a device because it is intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.Quality System Regulation Violation(s)This inspection revealed that this device is 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, its manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820. We received your response dated July 22, 2025, from Maksim Trofimovich, Quality Manager, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to you. 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 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 has not adequately implemented your Complaint Handling, Medical Device Reporting and Vigilance Reporting, Document Number 000978, Revision 26, Dated 20-May-2024, to ensure complaints are processed in a uniform and timely manner. For example:a) On November 25, 2024, your firm received Complaint CR-03201 documenting explantation of an Esteem II System due to patient infection. The physical device was received on December 5, 2024, and the incident was reported as a serious injury Medical Device Report (MDR) on December 18, 2024. As of the inspection's conclusion on July 2, 2025, approximately seven months after initial complaint receipt, the investigation remained incomplete. Your firm's complaint procedure (Document 000978) does not include specific requirements for uniform and timely complaint processing. In addition, your firm maintains a procedure for returned product analysis (Document 001005, Revision 12, dated May 20, 2024) that outlines specific failure mode analysis requirements and analytical methods. However, your firm did not conduct and document an investigation for Complaint CR-03201 in accordance with these established protocols as of the conclusion of the July 2025 inspection.b) Your firm received Complaint CR-03042 on September 28, 2023, involving sudden battery depletion of the Esteem II System. Your firm determined this complaint to be a significant high-risk event and reported it as a serious injury on April 12, 2024, or approximately seven months after the initial complaint receipt. The device was received for investigation on June 26, 2024. Documentation for Complaint CR-03042 shows that Complaint File Review (CFR) meetings in September 2024 and October 2024 did not determine which engineering team member would be assigned to conduct the required engineering investigation, with the decision deferred further to the November 2024 CFR meeting. At the time of the inspection ending July 2, 2025, this complaint remained pending an engineering review as required by your firm's complaint procedures. No progress updates beyond October 2024 are documented in the complaint record.c) Your firm received Complaint CR-03165 on August 22, 2024, involving an Esteem II Transducer that was causing feedback and difficulty programming the Esteem II System, which led to revision surgery to replace the sensor. The device was received for investigation on February 4, 2025, and the incident was reported as a serious injury Medical Device Report (MDR) on February 14, 2025. Your Quality Engineer indicated the device investigation is incomplete pending calibration of inspection equipment required for returned product analysis, however, similar calibrated equipment used in production could potentially be utilized for the returned product analysis but was not employed. At the time of the inspection ending July 2, 2025, this complaint remained open and pending testing as required by the firm's complaint procedures. No progress updates beyond January 2025 are documented in the complaint record.The response dated July 22, 2025, is not adequate. Your firm’s response includes a revised SOP 000978 "Complaint Handling, Medical Device Reporting and Vigilance Reporting" (Attachment D - redlined version) which represents a proposed changes rather than an approved, implemented procedure. Concerning timeliness requirements outlined in the procedure, that complaint investigations be completed within 6 months of the first aware date, this may be considered lengthy for addressing regulatory compliance issues. Your firm’s response also includes documentation to demonstrate closure of CR-03201 and CR-03165, but only a progress report for CR-03042 was provided rather than the complete updated complaint record. This suggests CR-03042 remains open pending completion of the ongoing engineering investigation. Your firm’s response indicates your firm’s intent to complete all open complaints by September 2025. However, we have received no updated response(s) from your firm for September/October 2025 to demonstrate the investigation completion of CR-03042 and its closure. In addition, your response acknowledges resource diversion to other work priorities but doesn't provide specific safeguards to ensure adequate resources for complaint investigations going forward.2. Failure to adequately establish and maintain procedures for corrective and preventive action, as required by 21 CFR 820.100(a).Specifically, your firm's CAPA procedures, Corrective and Preventive Actions, Document Number 000422, Revision 17, Dated September 20, 2024; Quality Event Risk Assessment & CAPA Escalation, Document Number 006411, Revision 03, Dated May 15, 2024; and CAPA Work Instruction, Document Number 006342, Revision 08, Dated September 20, 2024, have not been adequately implemented concerning two critical CAPAs involving high particulate counts in your firm’s ISO Class 8 Cleanrooms. For example:a) Your firm opened CAPA-00684 on March 2, 2022, following the discovery of high(b)(4)particulate counts during(b)(4)cleanroom monitoring conducted on February 16, 2022. The monitoring, performed by a third-party service identified particulate counts of(b)(4)at location(b)(4)in your large cleanroom, which exceeded the ISO Class 8 requirement of below 3,520,000 particulates/m³. No Health Hazard Evaluation (HHE), Document 006330, was conducted to assess the potential adverse impact to user safety, including assessment of any impact to products manufactured between February 16, 2022, and May 19, 2022, for the extended period of non-conforming cleanroom conditions.b) Your firm opened CAPA-00708 on July 10, 2024, for high(b)(4)particulate counts discovered during(b)(4)cleanroom monitoring conducted on May 8, 2024. The third-party monitoring service found particulate counts of(b)(4)at location(b)(4)and(b)(4)at location(b)(4)in your large cleanroom, both exceeding ISO Class 8 specifications. No HHE was conducted and no further assessment of any impact to products manufactured between February 27, 2024, and October 14, 2024, for the extended period of non-conforming manufacturing conditions.The response dated July 22, 2025, is not adequate. Your response includes CAPA CA-00712 that addresses the immediate product impact issues both CA-00684 and CA-00708 failed to evaluate. However, CAPA CA-00712 does not provide for an investigation to correct the underlying CAPA system deficiencies that allowed a fundamental failure in risk assessment to occur. Specifically, why qualified personnel conducting CA-00684, and the subsequent CAPA CA-00708, failed to recognize nonconforming conditions, assess the competency or decision-making factors that led to inadequate risk assessment, or updates to underlying CAPA procedures (Documents 000422, 006411, 006342) that allowed the inadequate evaluation to occur. Our concern remains that there appears to be ongoing systemic issues in your CAPA process that CA-00712 does not specifically address.3. Failure to adequately establish and maintain design validation procedures to ensure proper risk analysis is completed, as required by 21 CFR 820.30(g).Specifically, your firm's implementation of your primary risk assessment procedure "Risk Management Process", Document Number 001000, Revision 11, dated April 17, 2025, did not ensure routine updating of hazard evaluation documentation and the consistent assessment of infection-related risks. For example:a) CAPA CA-00701 identified that(b)(4)of(b)(4)used in assembly processes may have incomplete(b)(4)due to(b)(4)excursions in your firm’s large ISO Class 8 cleanroom. However, the risk documentation for the Esteem II Sound Processors which includes Esteem II System HA, Document Number 003682, Revision 12, dated April 20, 2017, and Esteem II FMECA, Document Number 006411, Revision 12, dated April 20, 2017, do not include the hazard identified from CA-00701, to evaluate the risk and its potential effects on the Esteem II System.b) Your firm's risk assessment does not consistently evaluate infection risks for the Esteem II System. Your risk analysis document establishes three contamination events that lead to the same outcome of patient infection but are assigned different severity ratings. "Insufficient flow of filtered air" and "Contaminated(b)(4)water system" resulting in "Excessive contamination or bioburden on parts" are rated as severity(b)(4), while the "Contamination not removed from assembly" with "Infection or reaction" is rated as severity(b)(4). According to your firm’s Risk Management Process procedure, severity(b)(4)indicates temporary health problems requiring routine medical care, while severity(b)(4)indicates life-threatening consequences. It is unclear why these three contamination sources that could all lead to patient infection were given different severity ratings when the potential patient harm would be the same.c) Your firm's Risk Management Process procedure does not specifically identify endotoxins as a hazard to be considered in the risk management process, and you only perform in-process endotoxin testing of your(b)(4)water system while omitting testing of the finished device, Esteem II System. Your firm maintains no documentation demonstrating that the(b)(4)water system testing is representative of endotoxin risk for the finished device or provides for consideration of other possible sources of endotoxin contamination in your manufacturing process for the device.The response dated July 22, 2025, is not adequate. Your response includes CAPA CA-00716 and identified training deficiencies and procedural gaps as root causes. However, your response does not adequately address why your risk analysis system failed to identify and incorporate critical hazards such as(b)(4)effects on(b)(4)for nearly a(b)(4), or why your risk assessment methodology allowed inconsistent severity ratings for infection-related failure modes that could result in similar patient harm. Your immediate corrections including updating FMECA 003799, to add(b)(4)risks and align infection severity ratings, along with hazard analysis training completed in July 2025. This may address the immediate technical issues but does not demonstrate a comprehensive evaluation of your risk analysis process to ensure all relevant hazards have been identified and properly assessed for your sterile implantable device. Your response also includes CAPA CA-00714 indicating a commitment to implement endotoxin testing for finished devices by September 2025 and update procedure 000500 by August 2025. However, your response does not include any retrospective risk assessment of previously released products that were distributed without endotoxin testing. While your corrective actions focus on procedural documentation improvements including updating procedure 000500 to include endotoxin testing requirements, you do not address updates to procedures including your Risk Management Process (Document 001000), Hazard Analysis (Document 003682), and FMECA (Document 003799), to include endotoxin contamination as an identified critical hazard requiring control for your sterile implantable device.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 to: Melissa Michurski, Assistant Director, at CDRHEnforcement@fda.hhs.gov. Refer to CMS # 718762 when replying. If you have any questions about the contents of this letter, please contact Salvatore Randazzo, Compliance Officer, at 407-475-4712 or salvatore.randazzo@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

Delivery Method:VIA UPS、Return Receipt RequestedProduct:Drugs、Over-the-Counter DrugsRecipient:Venkata R. Gogineni, Ph.D.CEOSeaway Pharma Inc.5 County Route 42Massena,NY13662United StatesIssuing Office:Office of Manufacturing QualityUnited StatesWarning Letter320-26-22December 1, 2025Dear Dr. Gogineni and Mr. Lingam:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Seaway Pharma Inc., FEI 3012275336, at 5 County Route 42, Massena, from May 19 to June 18, 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 reviewed your July 30, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to establish adequate written responsibilities and procedures applicable to the quality control unit and to follow such written procedures (21 CFR 211.22(d)).You manufacture over-the-counter (OTC) oral liquid drug products including, but not limited to, analgesics and cough and cold products marketed for infants and children.You failed to ensure adequate quality unit (QU) oversight for release of your OTC drug products. For example, your QU failed to follow your procedure Batch Record Review and Release for Distribution, SOP No. QA-009, Revision 01, and between April 2024 and May 2025, released numerous batches of drug products for distribution prior to reviewing all test results to ensure they met specifications. Furthermore, your QU also failed to ensure that:• each batch of drug products was tested for the strength of active ingredients prior to release (21 CFR 211.165(a))• laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a))In your response, you state you anticipated passing results based on historical data and process validation and “only two batches left [y]our facility without receiving passing microbial results.” Your response is inadequate because you do not address how you plan to ensure your quality unit has sufficient resources to carry out its responsibilities and consistently ensure drug quality. Your response also lacks sound scientific justification with respect to routine batch manufacturing requirements for finished product testing. You also do not address the potential impact to drug products distributed within the United States that are within expiry. An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help in implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR parts 210 and 211 at https://www.fda.gov/media/71023/download.In response to this letter, provide:• A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriateo Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decisiono Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productso An assessment of whether there are an adequate number of qualified personnel to perform and supervise the manufacture, processing, packing, or holding of each drug product.• A commitment that your quality unit will review all test results for finished products prior to their release.• A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedure(s) to ensure changes are justified, reviewed, and approved by your quality unit. Your change management program should also include provisions for determining change effectiveness.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).You failed to adequately test your incoming components at high risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination prior to use in manufacturing. For example, glycerin and sorbitol solution were used to manufacture your OTC oral drug products marketed for infants and children prior to obtaining results for identity testing of the components. Furthermore, you distributed finished products containing these high-risk components (e.g., glycerin, sorbitol 70%) before performing, reviewing, and approving adequate identity testing of the components.In your response, you state, “Currently, there are no enforceable provisions in either the United States Code or the Code of Federal Regulations (CFR) regarding: 1) Defined acceptance criteria for DEG and/or EG.” We acknowledge your commitment to perform identity testing of high-risk components, including the required DEG and/or EG analysis. However, regarding your assertion that there are no enforceable provisions, identity testing is required under 21 CFR 211.84(d)(1) and specifically the limits for DEG and EG tests are specified in the United States Pharmacopeia (USP) which is enforceable under section 501(b) of the FD&C Act, 21 U.S.C. 351(b).The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. Of particular concern, lethal contamination events have taken place in drug products similar to those manufactured by Seaway Pharma Inc. See FDA’s guidance document Testing of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.In response to this letter, provide: • 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 certificates of analysis (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 your program for qualifying and overseeing contract facilities that test the drug products you manufacture.• A commitment that your quality unit will review all test results for components prior to their release for use in manufacturing.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)).You failed to ensure adequate process validation for the OTC drug products you manufacture, including those indicated for infants and children. For example, you have not performed adequate process validation for the manufacture of your(b)(4)drug product to ensure control over batch-to-batch variability. For example:• You failed to ensure that validation records included adequately pre-defined critical steps, such as(b)(4)of bulk suspension during filling.• Your validation batch record documentation was incomplete and missing information, such as component lot and equipment identification.In your response, you state you will fulfill all process validation requirements prior to manufacturing any batch. Your response is inadequate because you do not evaluate the potential effects of your failure to adequately validate your manufacturing processes on the quality and safety of all products that you released for distribution in the United States remaining within expiry.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to 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 is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance documentProcess Validation: General Principles and Practicesfor 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 for process 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 process performance qualification (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.· 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.· Provide time frames for all corrective action and preventive action (CAPA) and whether the CAPA are resolved or in progress and the percent complete.Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.Change of Ownership at FacilityIn a previous warning letter, dated May 14, 2019 (CMS #572904), FDA cited similar CGMP violations pertaining to Kingston Pharma, LLC, for the lack of quality oversight and failure to adequately validate manufacturing processes. While there was a subsequent transfer of ownership of the company, the manufacturing facility and multiple responsible officials remained the same. Repeated failures demonstrated during subsequent inspections conducted in September 2021, September 2023, and June 2025 indicate that executive management oversight and control over the manufacture of drugs are inadequate. Your firm was notified of persistent CGMP violations during the two subsequent regulatory meetings held with you on May 3, 2022, and May 13, 2024. While current and past owners have been notified of these violations, you continue to fail to implement quality commitments within a timely manner as demonstrated during our most recent inspection. Ineffective Quality SystemSignificant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.CGMP Consultant RecommendedWe note that you are using consultants to assist you in meeting FDA requirements. Because you failed to correct repeat violations, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA 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.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 3012275336 and ATTN: Lynnsey Renn.Sincerely,/s/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA EMAIL AND UNITED PARCEL SERVICE、Signature RequiredProduct:BiologicsRecipient:Robert J. Hariri, M.D., Ph.DFounder, Chairman & CEOCelularity, Inc170 Park AvenueFlorham Park,NJ07932United Statesrobert.hariri@celularity.comIssuing Office:Office of Compliance and Biologics QualityUnited StatesWARNING LETTERDecember 1, 2025CBER 25-681480 Dear Dr. Hariri:This is to advise you that the United States Food and Drug Administration (FDA) has reviewed information related to a product that you manufacture, Interfyl®, which is a decellularized human placental connective tissue matrix product derived from the chorionic plate for allogeneic use. FDA has reviewed your website (celularity.com) and your distributor’s website and marketing materials (available at www.arthrex.com, https://www.arthrex.com/orthobiologics/interfyl-connective-tissue-matrix and http://cdn.arthrex.io/image/upload/525a2674-c770-484a-945b-f6037d73b4ac.pdf). In addition, FDA inspected your facility, located at the above address, between August 14, 2023 and August 22, 2023. During the inspection, FDA documented that your company manufactures Interfyl®.This letter is to advise you that your product is an unapproved new drug in violation of section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 355(a). Your product is also an unlicensed biological product in violation of section 351(a)(1) of the Public Health Service Act (PHS Act), 42 U.S.C. § 262(a)(1). A biological product for which a biologics license application (BLA) has been approved under section 351(a) of the PHS Act is not required to have an approved application under section 505 of the FD&C Act, 21 U.S.C. § 355; 42 U.S.C. § 262(j). Otherwise, with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act. Your introduction or delivery for introduction of your product into interstate commerce, or the causing thereof, is prohibited under sections 301(d) of the FD&C Act, 21 U.S.C. § 331(d).Unapproved New Drug and Unlicensed Biological Product ViolationsBased on information and records reviewed by FDA, including your website, https://celularity.com (last visited November 2025), and the website and promotional materials of your distributor Arthrex, Inc. (www.arthrex.com),1 your product is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease or conditions in humans and/or is intended to affect the structure or function of the body. For example, your product is intended for use in the treatment of certain conditions involving the musculoskeletal system and promoting a healing response, treatment of inflammation and wound healing as well as use in treatment of soft tissue voids, and soft tissue augmentation during repair of surgical defects. Specifically, videos on the Arthrex website promote uses of Interfyl® in treatment of peroneal tendinopathy and tears, achilles tendon tears, non-insertional achilles tendinosis, first metatarsophalangeal joint hallux, stenosing peroneal tenosynovitis, and insertional calcific tendinosis. In addition, the patient’s guide readily made available to healthcare professionals titled “Interfyl® Human Connective Tissue Matrix – A Patient’s Guide,” available at https://www.arthrex.com/resources/pLB1-000333-en-US/interfyl-human-connective-tissue-matrix-a-patients-guide?referringteam=orthobiologics, indicates that the Interfyl® product works through its chemically active composition, which “contains proteins and biochemicals that support healing.” The guide further indicates that Interfyl® works by “replacing and supplementing the damaged tissue,” describes soft tissue injuries in this context as injuries that “occur to the muscles, tendons, and ligaments,” and includes images depicting various joints in the body. In addition, promotional material and videos on the Arthrex website further promote uses of Interfyl® for wound healing and treatment of inflammation. Therefore, your product is a drug as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and biological product as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i).Your Interfyl® product is also a human cell, tissue, or cellular or tissue-based product (HCT/P) as defined in 21 CFR § 1271.3(d) and is subject to regulation under 21 CFR part 1271, issued under the authority of section 361 of the PHS Act, 42 U.S.C. § 264. HCT/Ps that do not meet all the criteria in 21 CFR § 1271.10(a) are not regulated solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271. Unless an exception in 21 CFR § 1271.15 applies, such products are regulated as drugs, devices, and/or biological products under the FD&C Act and/or the PHS Act and are subject to additional regulation, including applicable premarket review. Based on a review of relevant materials, your company does not qualify for any exception in 21 CFR § 1271.15, and your product fails to meet all criteria in 21 CFR §1271.10(a).Specifically, your Interfyl® product fails to meet the criterion that the HCT/Ps be “intended for homologous use only,” which means that the “labeling, advertising, or other indications of the manufacturer’s objective intent” demonstrate that the HCT/P is intended to perform “the same basic function or functions in the recipient as in the donor.” 21 CFR §§ 1271.3(c) & 1271.10(a)(2). Your product is not intended solely to perform the same basic function or functions of the HCT/P in the recipient as in the donor, and the intended uses are not limited to the uses described in the 2004 Request For Designation Letter to Celgene Cellular Therapeutics for the decellularized particulate human placental connective tissue matrix product (replacement or supplementation of damaged or inadequate integumental tissue) that FDA determined qualified for regulation solely under section 361 of the PHS Act. Rather, your product is also intended for use in the treatment of certain orthopedic conditions, such as healing and repair of soft tissue injuries involving the musculoskeletal system, which involves serving as a connection between muscle and bone and is not a basic function of the chorionic plate in the donor and involves a different organ system from the integumentary system that has distinct functions and components. In addition, stimulation of wound healing and treatment of inflammation are not homologous uses.Therefore, this HCT/P is not regulated solely under section 361 of the PHS Act, 42 U.S.C. § 264, and the regulations in 21 CFR part 1271.2 In addition to being regulated under section 361 of the PHS Act and 21 CFR part 1271, your product is regulated as a drug as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and as a biological product as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i).Subject to certain exceptions not applicable here, to lawfully market a new drug that is a biological product, a valid biologics license application (BLA) must be in effect under section 351(a) of the PHS Act, 42 U.S.C. § 262(a). Such licenses are issued only after showing that the product is safe, pure, and potent. While in the development stage, such products may be distributed for clinical use in humans only if the sponsor has an investigational new drug application (IND) in effect as specified by section 505(i) of the FD&C Act, 21 U.S.C. § 355(i), section 351(a)(3) of the PHS Act, 42 U.S.C. § 262(a)(3), and 21 CFR part 312. Your product is not the subject of an approved BLA, nor is there an IND in effect.Responses to the Form FDA-483We acknowledge receipt of your responses, dated September 12, 2023, October 31, 2023, and December 22, 2023, to FDA’s Form FDA-483. We have reviewed your responses and concluded that they are not adequate. For example, your responses contain no corrective actions to the concerns detailed in the FDA-483. You assert that your products are HCT/Ps that should be regulated solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271. As stated above, your products are drugs as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and biological products as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i) that are not regulated solely under section 361 of the PHS Act, 42 U.S.C. § 264, and 21 CFR part 1271.ConclusionThis letter is not intended to be an all-inclusive list of deficiencies. It is your responsibility to ensure full compliance with all applicable requirements in the FD&C Act, PHS Act, and their implementing regulations.Please submit your response in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to address any violations and prevent their recurrence. Include any documentation necessary to show that the matters have been addressed. If you cannot address these matters within fifteen (15) working days, please explain the reason for your delay and the timeframe for completion. If you do not believe your product is in violation of the FD&C Act, PHS Act, or applicable regulations, include your reasoning and any supporting information for our consideration.Send your electronic response and any questions regarding this letter to CBERDCMRecommendations@fda.hhs.gov.Sincerely,/s/Melissa J. MendozaDirectorOffice of Compliance and Biologics QualityCenter for Biologics Evaluation and Research1Per your Supply and Distribution Agreement with Arthrex, all of Arthrex’s marketing and promotional materials for your placental-derived products are subject to Celularity’s review and approval prior to use. Furthermore, your annual report, FORM 10-K, for the fiscal year ending on December 31, 2023, states that you entered into a six-year supply and distribution agreement with Arthrex, Inc. on May 7, 2021, which includes an exclusive license for the distribution and commercialization of Interfyl® within the United States in the field of orthopedic surgery.2Because your product fails to meet at least one criterion in 21 CFR § 1271.10(a), this letter does not evaluate all other criteria in 21 CFR § 1271.10(a).

为贯彻落实国家药监局年度医疗器械监督管理工作要求，持续推进重点医疗器械企业和产品的监督管理，督促注册人、备案人切实履行产品质量安全主体责任，提升本市医疗器械经营企业主体责任意识，严厉打击违法违规行为，切实保障医疗器械产品的质量安全，我局结合本市实际，按照年度工作计划，依据医疗器械生产经营质量管理规范及其现场检查指导原则等，组织对本市部分医疗器械生产经营企业开展了飞行检查，相关情况通报如下：  （一）生产企业检查情况。共检查27家医疗器械生产企业、注册人。其中，23家企业经综合评审认为存在一般缺陷，均已督促其针对生产质量管理体系存在的不符合项完成整改；2家企业经综合评审认为存在严重缺陷，经停产整改后目前已复产；1家企业存在严重缺陷且涉嫌违法违规，予以进一步调查处置；1家企业今年以来处于主动停产状态。（详见附件1）  （二）经营企业检查情况。共检查36家医疗器械经营企业。其中，32家企业存在不符合项，均已督促其针对经营质量管理体系存在的缺陷项完成整改；4家企业涉嫌违法行为（不涉及产品安全有效），经进一步调查对企业实施行政处罚，并已督促企业完成整改。（详见附件2）  附件：  1.2025年医疗器械生产企业、注册人飞行检查情况  2.2025年医疗器械经营企业飞行检查情况  上海市药品监督管理局  2025年12月4日

行政处罚信息摘要序号行政处罚决定书文号当事人名称法定代表人名称违法事实行政处罚内容和法律依据作出行政处罚决定的行政机关名称和日期1新药监药处罚〔2025〕19号新疆颐仁堂医药连锁有限公司吴子宣新疆颐仁堂医药连锁有限公司在第三方平台违规展示药品信息。依据《药品网络销售监督管理办法》第三十六条的规定,责令当事人立即改正违法行为，并给予罚款的行政处罚。新疆维吾尔自治区药品监督管理局2025年10月24日