根据《中华人民共和国行政许可法》第七十条、《药品经营和使用质量监督管理办法》第二十七条第一项规定，经企业申请，本机关拟注销乐山衡乐医药连锁有限公司《药品经营许可证》[证书编号：川BA833000001；经营方式：药品零售（连锁总部）；经营地址：四川省乐山市五通桥区牛华镇云华街171号4幢2层1号2号；法定代表人：李海；主要负责人：李海；经营范围：处方药、甲类非处方药、乙类非处方药;中药饮片、中成药、化学药、生物制品(不含细胞治疗类生物制品)(含冷藏药品)、血液制品(含冷藏药品)]。自本公示发布之日起10个工作日内，如无单位、个人提出异议，本机关将依法注销该企业《药品经营许可证》。特此公示。联系电话：028-86912503                                                                                    四川省药品监督管理局                        2026年6月2日

2026年5月18日至2026年5月22日，重庆市药品监督管理局共批准第二类医疗器械产品注册及产品变更备案共35个。

济南海洲大药房有限公司违反《药品经营质量管理规范》的规定，存在质量安全隐患。为防控药品质量风险，依据《中华人民共和国药品管理法》第九十九条的规定，决定对该企业采取暂停销售药品的风险控制措施。特此通告。附件：济南海洲大药房有限公司《药品经营许可证》有关信息山东省药品监督管理局2026年6月2日附件：企业名称许可证编号法定代表人质量负责人注册地址经营范围有效期至备注济南海洲大药房有限公司鲁BA531d00056张海周丽娟山东省济南市天桥区无影山西路708号处方药，甲类非处方药，乙类非处方药：中药饮片,中成药,化学药，生物制品（含血液制品，不含细胞治疗类生物制品）,以上含冷藏冷冻药品2029年12月09日

山东飞龙医药有限公司违反《药品经营质量管理规范》的规定，存在质量安全隐患。为防控药品质量风险，依据《中华人民共和国药品管理法》第九十九条的规定，决定对该企业采取暂停销售药品的风险控制措施。特此通告。附件：山东飞龙医药有限公司《药品经营许可证》有关信息山东省药品监督管理局2026年6月2日附件：企业名称许可证编号法定代表人质量负责人注册地址经营范围有效期至备注山东飞龙医药有限公司鲁AA531000602沙姿言姚树艳山东省济南市莱芜高新区鹏泉街道办事处长江大街75号1幢中药饮片,中成药,化学药,生物制品（除疫苗）,上述经营范围不含冷藏冷冻药品2028年8月21日

Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:26-HFD-45-05-02Product:DrugsRecipient:Leah R. Hanson, Ph.D.Senior Director, Neuroscience ResearchHealthPartners Neuroscience Center Research and Innovation295 Phalen BoulevardSaint Paul, MN 55130-2455United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERFDA Ref. No.: 26-HFD-45-05-02Dear Dr. Hanson:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at HealthPartners Neuroscience Center Research and Innovation (HPNC) between March 17 and 21, 2025. The investigators representing FDA reviewed the role of HPNC as the testing facility for the following nonclinical laboratory studies of the investigational drug (b)(4), performed for sponsor-investigator (b)(4) (formerly performed for (b)(4)).Protocol (b)(4): “(b)(4)”Protocol (b)(4): “(b)(4)”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 the quality and integrity of study data, in accordance with Title 21 of the Code of Federal Regulations, part 58 (21 CFR 58), Good Laboratory Practice (GLP) for Nonclinical Laboratory Studies.At the conclusion of the inspection, the FDA investigators presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your April 11, 2025, written response to the Form FDA 483, and your subsequent correspondence dated June 13, 2025.From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written responses dated April 11 and June 13, 2025, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in 21 CFR 58 governing the conduct of nonclinical laboratory studies. We wish to emphasize the following:1. Failure of the testing facility management to assure that tests for mixtures of articles with carriers were conducted by appropriate analytical methods to determine the uniformity of the mixture and the concentration of the test or control article in the mixture, as applicable [21 CFR 58.31(d) and 21 CFR 58.113(a)(1)].The testing facility management for each nonclinical laboratory study must ensure that test and control articles or mixtures have been appropriately tested for identity, strength, purity, stability, and uniformity, as applicable. For each test or control article that is mixed with a carrier, tests by appropriate analytical methods must be conducted to determine the uniformity of the mixture and to determine, periodically, the concentration of the test or control article in the mixture. The testing facility management failed to adhere to these requirements.Specifically, the protocol and final study report for Study (b)(4) stated that the test article, (b)(4), was dissolved in sterile water to a final dose concentration of 1%, 10%, or 20% (b)(4) (0.5 mg, 5 mg, and 10 mg, respectively), and for Study (b)(4), to a final dose concentration of 1%, 10%, or 20% (b)(4) (2 mg, 20 mg, and 40 mg, respectively). However, after reconstituting the test article with sterile water to the desired final dose concentration, the testing facility failed to test, by appropriate analytical methods, the resulting mixtures to determine their uniformity and concentration before dosing all animals in studies (b)(4) and (b)(4).In your April 11, 2025, written response to the Form FDA 483, and in your subsequent correspondence dated June 13, 2025, you acknowledged that the characteristics of the test article were not analyzed. As corrective and preventive actions, you stated that the following actions were taken: (1) you created a new SOP titled “Receipt, Identification, Storage, Handling, Mixing, and Method of Sampling Chemicals,” which includes procedures for test article characterization; (2) you provided the certificate of analysis for the (b)(4) lot used in study (b)(4); (3) you performed mass spectrometry testing on April 19, 2025, on stored frozen dosing aliquots representative of formulated test articles administered to animals in both studies; and (4) you amended the final study reports for both studies to include the results of this subsequent testing, noting that the selected test article samples were within the concentration specified in the protocol.While we acknowledge the corrective and preventive actions that your testing facility has taken, your response is inadequate because you did not include sufficient details about your corrective action plan. For example, while you provided the results of the testing performed on the stored aliquots that were representative of the test articles administered to animals, this testing occurred after animal dosing and the studies had been completed. We also note that while you provided the testing results for the concentration of these samples, you did not provide the testing results regarding the uniformity of the samples.In addition, while we acknowledge that you created an SOP that includes test article characterization, your written response does not include details about how you will implement these procedures to ensure that testing to determine the concentration and uniformity of test articles is performed in accordance with FDA regulations. For example, your response does not provide sufficient details regarding any completed or planned training of study personnel on this new SOP, or any training on FDA regulations governing the conduct of nonclinical laboratory studies. Without this information, we are unable to determine whether your testing facility will be able to prevent similar violations in the future.Your testing facility management failed to ensure that tests by an appropriate analytical method were conducted to determine the uniformity and concentration of the mixtures of articles with carriers at the beginning and throughout the study period, to verify the protocol-specified dose concentrations. Because of this failure, FDA is concerned about the uniformity of the mixtures and about the concentration of the test articles in the mixtures used in the nonclinical laboratory studies conducted at your testing facility.2. Failure of the Quality Assurance unit (QAU) to review the final study report to assure that the reported results accurately reflect the raw data of the nonclinical laboratory study [21 CFR 58.35(b)(6)].The QAU must review the final study report to ensure that the reported results accurately reflect the raw data of the nonclinical laboratory study. The QAU at your testing facility did not adhere to these requirements. Specifically, for Protocol (b)(4), the following observations were not accurately documented in the final study report:a. The deaths of two male rats (Rats #41 and #42 in the 10% (b)(4) dosing group) during the conduct of the study were not reflected in the final study report.b. A Day 13 clinical observation of abnormal nose was observed in Female Rat #53 in the 10% (b)(4) dosing group, and a Day 13 clinical observation of abnormal porphyrin was observed in Female Rat #51 in the 1% (b)(4) dosing group. However, the final study report inaccurately documents that abnormal nose was observed on Day 13 in the 1% (b)(4) dosing group, and that abnormal porphyrin was observed on Day 13 in the 10% (b)(4) dosing group.c. Female Rat #84 in the 20% (b)(4) dosing group died on Day 3 of dosing. However, the final study report inaccurately documents that Rat #84 died on Day 1 of dosing.In your April 11, 2025, written response to the Form FDA 483, you acknowledged the observation and stated that you amended the final study reports to make the necessary corrections. You stated that to address the root cause of the violation, you developed a new SOP titled “QAU Review of Final Report” and a checklist to be used in the QAU review of final study reports.While we acknowledge the corrective and preventive actions that your testing facility has taken, your response is inadequate because you did not include sufficient details about your corrective action plan, including how procedures will be implemented at your site to ensure compliance with FDA regulations. For example, your corrective action plan does not include QAU training on the new SOP or the new checklist, or QAU training on FDA regulations governing the conduct of nonclinical laboratory studies, including the QAU’s role and responsibilities. Additionally, your corrective action plan does not include a description of any planned audits to check for compliance with new QAU procedures. Without these details, we are unable to determine whether your corrective actions are adequate to prevent similar violations in the future.Because your testing facility’s QAU failed to ensure that the reported results in the final study report accurately reflect the raw data of the nonclinical laboratory studies, FDA has concerns about the integrity of the data generated and reported from the nonclinical studies conducted at your testing facility.3. Failure of the testing facility management to assure the availability of equipment as scheduled and that the equipment used in the generation, measurement, or assessment of data shall be of appropriate design and adequate capacity to function according to the study protocol [21 CFR 58.31(e) and 21 CFR 58.61].Testing facility management must ensure that equipment is available as scheduled. Additionally, equipment used in the generation, measurement, or assessment of data in a nonclinical laboratory study must be of appropriate design and adequate capacity to function according to the study protocol. The testing facility management failed to adhere to these requirements.Specifically, during the conduct of nonclinical laboratory studies (b)(4) and (b)(4), the testing facility management failed to ensure that equipment of appropriate design and adequate capacity was available to analyze the blood of rat and rabbit species for the protocol-required hematology and serum chemistry laboratory parameters. As a result, the testing facility failed to generate the following Day 15 data:Hematology test results for male and female rats for Protocol (b)(4)Serum chemistry test results for male rats for Protocol (b)(4)Hematology test results for male and female rabbits for Protocol (b)(4)Additionally, the testing facility management did not cross-validate the equipment used to analyze blood samples, to demonstrate their ability to accurately analyze rat blood in Protocol (b)(4) or rabbit blood in Protocol (b)(4).We acknowledge that the finding described above was not included on the Form FDA 483 you received, and that the observation on the Form FDA 483 was limited to the unreported hematology laboratory results for Day 15 female rats in the final study report for Protocol (b)(4). Therefore, your written responses to the Form FDA 483 do not directly address the extent of this finding as discussed in this letter.In your April 11, 2025, written response to the Form FDA 483, regarding the unreported hematology results, you stated that you amended the final study reports to make the necessary corrections. The amended final study reports gave details of the equipment that your testing facility used for hematology laboratory parameters testing in the study animals, and they explained that the hematology results obtained using the equipment were below or above the range of the machine, and therefore no results were displayed on the equipment.While we acknowledge the corrective actions that your testing facility has taken regarding the unreported hematology results, your response is inadequate because we are unable to determine whether your testing facility will be able to ensure the availability of equipment of appropriate design and adequate capacity to evaluate protocol-required laboratory parameters in the animal species included in future nonclinical studies conducted at your testing facility. Because the testing facility management failed to ensure that appropriate equipment was available to conduct protocol-required laboratory assessments, FDA has concerns about the integrity of the data generated and reported from the nonclinical studies conducted at your testing facility.4. Failure of the testing facility to establish standard operating procedures in writing, setting forth nonclinical laboratory study methods that management is satisfied are adequate to insure the quality and integrity of the data generated in the course of the studies [21 CFR 58.81(a) and 58.81(b)].A testing facility must establish and follow written SOPs for nonclinical laboratory studies, to ensure the quality and integrity of the data generated in the studies. Your testing facility did not adhere to these requirements. For example, your testing facility failed to establish SOPs for:a. Receipt, identification, storage, handling, mixing, and method of sampling of the test and control articlesb. Test system observationsc. Laboratory testsd. Handling of animals found to be moribund or dead during a studye. Collection and identification of specimensIn your April 11, 2025, written response to the Form FDA 483, and in your subsequent correspondence dated June 13, 2025, you acknowledged the observation and stated that you created an SOP titled “SOP Creation, Review, and Approval.” Additionally, you created SOPs for the five procedures that were identified as lacking, along with additional SOPs that were not previously established. You also revised existing SOPs to include versioning and dates. We acknowledge your corrective and preventive actions. However, we emphasize that as a testing facility conducting nonclinical laboratory studies under 21 CFR 58, it is your responsibility to establish SOPs before conducting nonclinical laboratory studies. You are also responsible for following your written SOPs to ensure consistency in study conduct and to ensure the quality and integrity of data generated during your studies.As evidenced by FDA’s inspection findings, the deficiencies found in the oversight and conduct of the testing facility management and QAU at your testing facility demonstrate a failure to comply with FDA’s GLP regulations governing the conduct of nonclinical laboratory studies. As a result, FDA is concerned about the validity and integrity of the nonclinical data generated by your testing facility.We emphasize that as a testing facility conducting nonclinical laboratory studies under 21 CFR 58, you are responsible for ensuring that nonclinical laboratory studies submitted to FDA are conducted and reported in accordance with FDA regulations to ensure the quality and integrity of study data. Your failure to conduct and report nonclinical studies in accordance with FDA regulations raises concerns about the validity and integrity of the data collected at your site.This letter is not intended to be an all-inclusive list of deficiencies with the nonclinical laboratory studies of investigational drugs conducted at your testing facility. 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 without further notice to you. 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.Your written response, and any questions or concerns about this letter or the inspection, should be sent via email to the FDA at CDER-OSI-Communications@fda.hhs.gov.Sincerely,{See appended electronic signature page}David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administration--------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.--------------------------------------------------------------------------------------------/s/------------------------------------------------------------DAVID C BURROW05/19/2026 12:58:47 PM

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-79Product:Drugs;Over-the-Counter DrugsRecipient:Mr. Márcio Paranhos MikszaCEOAeroflex Industria de Aerosol Ltda.Rua Paul Garfunkel, 1335Cidade Industrial de Curitiba Curitiba-PR 81460-040BrazilIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-79May 22, 2026Dear Mr. Miksza:Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter drug products.Previous correspondence you sent to the FDA indicated manufacture and importation of multiple drug products. Additionally, your (b)(4) drug product is available for purchase via online marketplaces. On October 27, 2025, the FDA sent an electronic request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 374(a)(4), to the contact e-mail address provided in your registration file. This request went unanswered as did numerous follow-up requests.It is a prohibited act under section 301(e) of the FD&C Act (21 U.S.C. 331(e)) to refuse to permit access to or copying of any record as required by section 704(a). Because your firm failed to respond to the section 704(a)(4) records requests and associated communication attempts, we have no indication of the level of quality assurance for drugs listed as manufactured at your facility.ConclusionRespond to this letter to confirm or update your registration and/or drug listing status and indicate whether you will respond to the request for records and other information. If you are no longer manufacturing drugs, delist all the drugs previously listed with FDA, using the last lot expiration date as the marketing end date of the product, and deregister your facility accordingly.Until FDA is able to confirm compliance with current good manufacturing practices and other applicable requirements, we may withhold approval of any new applications or supplements listing your firm as a drug manufacturer. In addition, shipments of articles manufactured at Aeroflex Industria de Aerosol Ltda., at Rua Paul Garfunkel, 1335, Cidade Industrial de Curitiba, Curitiba – Paraná CEP 81460-040 into the United States that appear to be adulterated are subject to being detained or refused admission pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). After you receive this letter, respond to this office in writing within 15 working days. In response to this letter, you may provide information for our consideration as we continue to assess your activities and practices, and/or submit a request to schedule an FDA inspection.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your written response with FEI 3018057637 and ATTN: Bryce Hammer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-78Product:Drugs;Over-the-Counter DrugsRecipient:Mr. Jaime LabastidaManaging DirectorLaboratorios Jaloma S.A. de C.V.Calle Emiliano Zapata, No. 422Oblatos 44380 Guadalajara, Jal.MexicoIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-78May 22, 2026Dear Mr. Labastida:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Laboratorios Jaloma S.A. de C.V., FEI 3002600322, located at Calle Aquiles Serdan No. 438, Colonia Oblatos, Guadalajara, Jalisco, from December 15 to 19, 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 January 12, 2026, 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 ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).You failed to accurately document microbiology sampling and testing results for components used in your over-the-counter (OTC) drug products.Your laboratory records did not accurately reflect activities performed. For example, your microbiologist documented the collection of routine (b)(4) samples, but after questioning, your microbiologist admitted that the samples were never actually taken. Furthermore, the microbiologist admitted to routinely performing colony counts after only (b)(4) of incubation, rather than following the required (b)(4) period specified in your procedure. Your firm affirmed this unacceptable practice to our investigators. Your firm’s actions represent a critical breakdown in your laboratory controls and undermine the integrity of your data.In your response, you state that you have updated incubator logbooks to include entry fields for incubation start and end times, provided formal training to personnel, and will perform (b)(4) internal audits to assess effectiveness.Your response is inadequate because it lacks a retrospective assessment to determine the validity of all data generated in your laboratory. Furthermore, your response does not include a gap analysis of your data integrity controls to identify systemic vulnerabilities that allow unauthorized modification or deletion of CGMP data. You also do not provide an evaluation of whether your management is appropriately qualified to provide adequate oversight of CGMP laboratory operations and data integrity.The failure to record and maintain complete and accurate records of all test results and their associated parameters fundamentally compromises data reliability. Consequently, this lack of reliable data prevents the quality unit (QU) from effectively fulfilling its responsibility to ensure compliance with applicable standards.Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP: Questions and Answers for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers.We strongly recommend that you retain an independent third-party qualified consultant to assist in your remediation. In response to this letter, provide:A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.o A comprehensive retrospective evaluation of the nature of the testing and manufacturing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan are commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating corrective and preventive action (CAPA) effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated by independent quality assurance function, along with expertise from outside entities whenever needed.o A status report for any of the above activities already underway or completed.2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).You failed to adequately validate your alternative microbial methods used to test drug products to assure the methods were equivalent to or better than United States Pharmacopeia (USP) methods.Specifically, the (b)(4) methods your firm uses for microbial analysis of (b)(4) were deficient. Their scope was limited to testing for (b)(4), while failing to include testing for anaerobic bacteria, total yeasts and molds, or (b)(4). Additionally, the incubation times specified in your procedure were not aligned with the specifications provided in USP for microbial enumeration. Further, during the inspection, your firm stated that your microbial methods had not been validated.In your response, you state that you discontinued use of the (b)(4) method for analysis of (b)(4) samples and updated your procedures. You also provided updated microbial methods for analysis of (b)(4) samples and training records for personnel.Your response is inadequate because it does not provide evidence that you validated your revised methods or demonstrate they are equivalent to or better than the methods in USP chapters (b)(4). Additionally, it lacks a broader evaluation of all the microbial methods to ensure they are appropriately validated or verified and suitable for use. Further, your response does not provide a comprehensive assessment of the drug products that you manufactured using components analyzed with substandard testing methods.Test methods must be validated to demonstrate they are suitable for their intended use, reproducible, equivalent or superior to applicable USP compendial methods, and capable of detecting the presence of objectionable microorganisms in each component or finished drug product.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 components before you release to manufacturing. Provide a comparative analysis demonstrating that the methods you use have been appropriately verified (USP) or validated and are equivalent to or better than USP monograph methods (non-USP).Validation of your microbiological test methods, including growth promotion testing, demonstrating they are equivalent to, or better than USP compendial methods, and suitable for their intended use.3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).Your firm lacked sufficient controls over your gas chromatography (GC) instrument used to test components in your finished drug products. Your GC laboratory instrument was not adequately qualified because you failed to validate the control software or enable audit trails, and the GC data file creation and modification dates were not accurate.Additionally, you did not have proper controls in place to prevent the deletion or manipulation of your laboratory’s electronic raw data. During the inspection, our investigators documented several chromatograph data files that could not be located in the storage folders on your GC computer. Your firm confirmed that you did not back up the electronic data located on the GC computer.In your response, you state that you purchased a GC software package and will validate the GC system. You also commit to strengthening data controls for computer systems and software, enabling audit trails, and routinely backing up electronic data.Your response is inadequate because it fails to include a comprehensive impact assessment of the chromatography data that was discarded or lost from your GC computer. Your response does not explain how you ensure traceability of your CGMP electronic data files that have inaccurate time stamps and lack audit trail data. Furthermore, it does not provide a timeline for completion of your GC validation and qualification activities.In response to this letter, provide:A comprehensive, independent assessment and CAPA plan for computer system security and integrity. Include a report that identifies design and control vulnerabilities, provides appropriate remediations for each of your laboratory and manufacturing computer systems, and addresses the following elements:o A list of all hardware that includes all equipment, both stand-alone and network, in your laboratory.o A list of all software configurations (both equipment software and laboratory information management system) and versions, details concerning all user privileges, and oversight responsibilities for your computerized systems. Regarding user privileges, specify user roles and associated user privileges (including the specific permissions allowed for anyone who has administrative rights) for all staff who have access to the laboratory and manufacturing computer systems, with their organizational affiliation and title. Also describe how you will ensure that staff are not given administrative rights or other permissions that may compromise data retention or reliability.o System security provisions including, but not limited to, whether unique usernames/passwords are always used and their confidentiality is safeguarded.o Detailed procedures for robust use and review of audit trail data, and the current status of audit trail implementation for each of your systems.o Technological improvements to increase the integration of data generated through electronic systems from stand-alone equipment (for example, balances, pH meters, (b)(4) content testing equipment).o A detailed summary of your procedural updates and associated training including, but not limited to, system security control to prevent unauthorized access and to ensure appropriate user role assignments, secondary review of all analyses, and other system controls.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 QU lacked adequate oversight and control over your OTC drug product manufacturing operations to ensure state of control and adherence to all quality standards.Significant 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 QU 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.Your firm’s quality systems are inadequate. See FDA’s guidance documents ICH Q10 Pharmaceutical Quality System, and Quality 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.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 Also describe how top management supports quality assurance and reliable operations, including, but not limited to, timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.A comprehensive independent assessment of documentation practices used throughout your laboratory operations to determine where documentation is insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.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 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.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.FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on April 23, 2026. FDA had previously placed your firm on Import Alert 66-78 on August 3, 2020, due to violative sampling results in your (b)(4) OTC drug product.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 Laboratorios Jaloma S.A. de C.V., Calle Aquiles Serdan No. 438, Colonia Oblatos, Guadalajara, Jalisco, Mexico, 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.After you receive this letter, respond to this office in writing within 15 working days. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices, and/or submit a request to schedule an FDA inspection.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3002600322 and ATTN: Christopher Keating.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via UPS and EMAILReference #:CBER 26-728085Product:BiologicsRecipient:Dr. Brian MehlingChief Medical Officer and FounderBlue Horizon International, LLC214 State Street Suite 101Hackensack, NJ 07601United Statesbmehling@bluehorizoninternational.comIssuing Office:Center for Biologics Evaluation and Research (CBER)United StatesWARNING LETTERMay 26, 2026CBER 26-728085Dear Dr. Mehling:The United States Food and Drug Administration (FDA) reviewed your company’s website at https://bluehorizonstemcells.com (last visited May 2026), through which your company markets “Stem Cell Therapy” derived from umbilical cord blood and “Exosome Therapy”1 derived from Wharton’s Jelly Mesenchymal Stem Cells (“WJ-MSC[s]”) for allogeneic use (hereafter, “your products”). This letter is to advise you that your misbranding of your products while held for sale after shipment in interstate commerce violates section 301(k) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. § 331(k).Unapproved New Drug and Unlicensed Biological Product ViolationsBased on information and records reviewed by FDA, including your website, https://bluehorizonstemcells.com, (last visited May 2026), your products are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease or conditions in humans and/or are intended to affect the structure or function of the body. For example,After identifying your products, and under the heading “What Can We Treat,” your homepage lists various diseases and conditions, including:o Digestive System Diseases, including Hepatic steatosis and Chronic pancreatitiso Respiratory Diseases, including Allergic rhinitis, Rhinitis, and Sinusitiso Rheumatic Diseases, including Lupuso Endocrine Diseases, including Hashimoto’s thyroiditis and Hypothyroidismo Musculoskeletal Diseases, including Myositis, and Sports-related injury complicationso Cardiovascular Diseases, including Coronary artery diseaseYour home page states, “Our stem cell treatments use ethically sourced cells from umbilical cord blood and adipose tissue to treat chronic conditions, injuries, and degenerative diseases.” This statement is followed by a link to your stem cell treatment webpage and a list of uses for stem cells: “Tissue regeneration[;] Immune modulation[;] Anti-inflammatory effects[; and] Pain reduction”.Under the heading “Revolutionary Stem Cell Therapy,” your stem cell treatment webpage states, “Explore the power of stem cells in treating various medical conditions[,]” followed by, among other conditions and diseases:o Neurological Marvels …Spinal Cord Regeneration Stroke Recovery Multiple Sclerosis Reliefo Cardiovascular Miracles …Myocardial Rejuvenation …Cardiomyopathy Triumph Reversing Atherosclerosiso Musculoskeletal Wonders …Osteoarthritis Solutions Rheumatoid Arthritis Breakthrougho Lung Restoration … Defying COPDo Liver Regeneration Reviving Liver Function Cirrhosis Reversalo Bowel Revolution Conquering Crohn’s Diseaseo Metabolic Transformation Diabetes RemissionsUnder the heading “Our Results” on your exosome webpage, “These exosomes demonstrate strong regenerative and anti-inflammatory properties…”Under the heading “Our Exosomes” on your homepage: “These next generation therapies enhance tissue regeneration, reduce inflammation, and support natural healing processes through the body.”Under the heading “What Are Exosomes” on your exosome webpage, “Functionally, exosomes are pivotal in regulating immune responses, promoting tissue repair, and facilitating cellular regeneration.”Therefore, 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).Your umbilical cord blood derived stem cell 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, Blue Horizon International does not qualify for any exception in 21 CFR 1271.15, and your umbilical cord blood derived stem cell product fails to meet all criteria in 21 CFR 1271.10(a).Your umbilical cord blood derived stem cell product fails to meet the criterion that the HCT/Ps be “intended for homologous use only.” Homologous use 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) and 1271.10(a)(2)). Your umbilical cord blood derived stem cell product is not intended solely to perform the same basic function or functions of the HCT/P in the recipient as in the donor (e.g., forming and replenishing the lymphohematopoietic system). Rather, your umbilical cord blood derived stem cell product is intended for use in the treatment of several diseases and conditions, including multiple sclerosis, rheumatoid arthritis, cardiovascular and musculoskeletal conditions, which is not a basic function of umbilical cord blood in the donor.Moreover, your umbilical cord blood derived stem cell product fails to meet the criterion in 21 CFR 1271.10(a)(4) because it is manufactured from allogeneic umbilical cord blood, is dependent on the metabolic activity of living cells for their primary function, and is not for autologous use, allogeneic use in a first-degree or second-degree blood relative, or reproductive use.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 See 21 CFR 1271.20. In addition to being regulated under section 361 of the PHS Act and 21 CFR part 1271, your umbilical cord derived 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 a biological product as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i), as stated above.To lawfully market a drug that is also a biological product, a valid biologics license must be in effect. 42 U.S.C. § 262(a). Such licenses are issued only after a demonstration 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 FDA regulations. 21 U.S.C. § 355(i); 42 U.S.C. § 262(a)(3); 21 CFR Part 312. Neither of your products are the subject of an approved biologics license application (BLA) nor is there an IND in effect for either of them.Both your products, the umbilical cord blood derived stem cell product and the WJ-MSC/UC exosome product, are misbranded drugs under section 502(f)(1) of the FD&C Act, 21 U.S.C. § 352(f)(1). A drug is misbranded under section 502(f)(1) if the drug fails to bear adequate directions for its intended use(s). “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended. 21 CFR 201.5. Prescription drugs, as defined in section 503(b)(1)(A) of the FD&C Act, 21 U.S.C. § 353(b)(1)(A), can only be used safely at the direction, and under the supervision, of a licensed practitioner.Your products are intended for use in the treatment of one or more diseases that are not amenable to self-diagnosis or treatment without the supervision of a licensed practitioner. Therefore, it is impossible to write adequate directions for a layperson to use your products safely for their intended purposes. Accordingly, your products fail to bear adequate directions for its intended uses and, therefore, is misbranded under section 502(f)(1) of the FD&C Act, 21 U.S.C. § 352(f)(1). Misbranding your products while they are held for sale after shipment of the drug or one or more of its components in interstate commerce is prohibited under section 301(k) of the FD&C Act, 21 U.S.C. § 331(k).ConclusionThis letter is not intended to be an all-inclusive list of deficiencies that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure full compliance with all applicable requirements in the FD&C Act, PHS Act, and all applicable regulations.This letter notifies you of our concerns and provides you with an opportunity to address them. Failure to adequately address these matters may result in action without further notice including, without limitation, seizure and/or injunction.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 products are 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 CBER’s Office of Compliance and Biologics Quality, Division of Case Management at CBERDCMRecommendations@fda.hhs.gov.Sincerely,/S/Vincent AmatrudoDirector (Acting)Office of Compliance and Biologics QualityCenter for Biologics Evaluation and Research_______________________1 We direct your attention to FDA’s Public Safety Notification on Exosome Products, available at https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-products. FDA issued this public safety notification following multiple reports of serious adverse events experienced by patients who were treated with exosome products.2 Because your products fail 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).

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-82Product:DrugsRecipient:Mr. James BoyleChief Executive OfficerMedline Inc3 Lakes DriveNorthfield, IL 60093United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-82May 28, 2026Dear Mr. Boyle:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Medline Industries, LP, FEI 3003983334, at 1710 South Lakeside Drive, Waukegan, Illinois, from October 6 to 14, 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 November 4, 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 thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm manufactures (b)(4) for (b)(4) is also specifically labeled for (b)(4). Your manufacturing process includes (b)(4), and sealed into the respective finished drug product packaging.Between June 2, 2023 and August 27, 2025, your firm isolated objectionable microorganisms (e.g., Bacillus cereus (B. cereus)) from (b)(4) finished drug product samples on approximately nine occasions. You also recovered B. cereus in at least five samples taken from your manufacturing environment since January 2025. You failed to adequately investigate and implement corrective actions and preventive actions (CAPA) to determine root causes and prevent recurrence of these repeated contamination incidents. This issue was cited on the previous Form FDA 483 issued to your firm in January 2025 and subsequently discussed during the most recent regulatory meeting held with your firm in May 2025.Further, your investigations into contaminated drug product samples identified B. cereus in your manufacturing environment, including (b)(4) at your facility, as well as on (b)(4) at another Medline facility (Hartland), which supplies your bulk (b)(4). Multiple investigations since 2023 have determined that (b)(4) are a root cause for the B. cereus contamination in your drug products.In your response, you acknowledge “that the FDA inspection identified gaps in adherence to the corrective actions and cGMP’s.” You suspended (b)(4) drug product production in October 2025. You also committed to verifying corrective actions and their effectiveness before notifying FDA of your intent to resume production. You also refer to several previously initiated CAPA in response to the microbiological contamination incidents, including management controls, deviation investigations, and facility and process improvements.Your response is inadequate because you have not explained why your previous CAPA attempts were not successful. Additionally, your investigations failed to adequately identify the root causes of contamination in your drug products and the source of B. cereus contamination within your manufacturing environment, including from your bulk (b)(4). Your response also states that you have not released any drug product batches with failing microbiological test results. However, finished product microbiological testing cannot be relied upon as sole justification to release drug product batches, as contamination is not uniformly distributed in a system and any given sample may not be representative of the type or level of contamination.Inadequate investigations can lead to unidentified root causes, ineffective CAPA, and recurring problems that may pose a patient safety hazard. Your manufacturing processes and cleanroom environments are inadequately designed to assure an ongoing state of control. It is your responsibility to design and control operations to prevent contamination of your (b)(4).Microbial contamination of (b)(4) drugs used for (b)(4) poses a significant risk of patient harm and adverse (b)(4) outcomes, (b)(4). Thus, the use of manufacturing processes that render these drugs sterile is an integral part of ensuring safety of patients due to the vulnerability to (b)(4) infection.In response to this letter, provide:A comprehensive, independent risk assessment of all contamination hazards with respect to your manufacturing processes, equipment, and facilities, including, but not limited to:o All human interactions within the cleanroom areas (e.g., risk reduction or elimination of manual interventions wherever possible)o Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficient cleanroom spaceo Air quality in the cleanroom area and surrounding room including, but not limited to, air volume and flowo Facility layouto Personnel Flow and Material Flow (movement throughout all rooms used to conduct and support manufacturing operations, and all material transfers).A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe comprehensive improvements to be made to manufacturing operation design and control at your facility and explain how this CAPA plan will robustly remediate your deficient manufacturing operations. Include comprehensive changes to the design of both your manufacturing lines and cleanrooms. Also, describe your plans for qualification and validation of your extensively remediated operations.An independent assessment by qualified experts of the various sterilization options that can be implemented for your (b)(4) products. Based on this assessment, provide a comprehensive plan and timeline to transition your (b)(4) drugs to terminal sterilization, or implement aseptic processing of these products. In the event that you are considering continued use of processes that are inherently vulnerable to contamination issues, provide a detailed rationale justifying your scientific and public health basis, with particular attention to the unacceptable patient risks posed by your historical contamination problems.A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An independent, retrospective review of all critical investigations (including each in-process, release, and stability test specification failure) for the last three years as of the date of this letter. Evaluate the adequacy of each investigation, including, but not limited to:o Determine whether a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history) was conductedo Assess sufficiency of review of past related investigations (deviations, failures) to identify potential associated causes or linkageso Evaluate adequacy of scope, rigor, staff competencies, scientific/analytical foundation, and CAPAo Summary of findings of the assessment for each of the above elements.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program whenever needed, ensures final quality unit decisions, and is fully supported by executive management.2. Your firm failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups; failed to perform operations within specifically defined areas of adequate size; and failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.42(c) and 21 CFR 211.67(b)).Your firm isolated significant opportunistic pathogens, including B. cereus, in numerous samples of your (b)(4) finished drug products and the manufacturing environment.You failed to establish appropriate design and control of your manufacturing operation to assure your (b)(4) drug products (b)(4) were suitable for their intended use. This issue was cited on the previous Form FDA 483 issued to your firm in January 2025 and subsequently discussed during the most recent regulatory meeting conducted with your firm in May 2025.Deficient Manufacturing PracticesYour manufacturing operators engaged in practices that pose significant contamination risk to (b)(4) drug products, such as using cleaning tools without suitable gloves and then repeatedly touching the (b)(4). Investigations by your firm identified objectionable aseptic behaviors as a root cause of B. cereus contamination in your products.Your manufacturing process involves (b)(4) manipulations including the (b)(4) drug components, equipment, and scrap materials. These activities are particularly worrisome if your operations are not conducted and maintained in an aseptic manner (e.g., donning sterile gowning), or the drug product is not sterilized in its final packaging. It is essential that manufacturers establish robust manufacturing design and process control measures to prevent contamination throughout production operations. In addition to appropriate manufacturing facilities and processes, raw materials (e.g., components, containers, and closures) must also be suitable for their intended use.In your response, you acknowledge “that the FDA inspection identified gaps in adherence to the corrective actions and cGMP’s.” As noted above, you also state that you suspended production of the (b)(4) drug product in October 2025. You commit to verifying your corrective actions as effective prior to notifying FDA of your intent to resume production. You also refer to several previously initiated CAPA in response to the microbiological contamination incidents, including corrections to cleanroom behaviors, cleaning and maintenance procedures, contamination controls, and retraining.Inadequate Cleaning and DisinfectionYour manufacturing operators have routinely deviated from procedures for cleaning and disinfection of your drug manufacturing equipment, including (b)(4) for (b)(4) drug products. For example, numerous deviation investigations have noted operator failures to properly clean and disinfect your (b)(4) and valves with (b)(4). Notably, (b)(4) have been identified as a root cause for B. cereus contamination in your drug products since 2023.Establishing and following appropriate procedures for cleaning, disinfection, and whenever appropriate, sterilization is essential to ensuring product safety.Your response is inadequate. Your proposed corrections are insufficient to remediate flawed facility and process design. You have unsuccessfully attempted similar corrective actions in the past.In response to this letter, provide:An independent assessment and associated CAPA plan, following a thorough retrospective review of your cleaning, disinfection, and sterilization program, that includes appropriate remediations and timelines for completion. Provide a detailed summary of vulnerabilities in your processes and procedures relating to equipment cleaning, disinfection, and sterilization. Describe improvements to your program, including enhancements to cleaning and disinfection types and practices; addition or improvement of sterilization methods; and all other needed remediations.Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to a thorough independent assessment of the following with accompanying CAPA:o Suitability of actual practices based on a retrospective review and prospective observation of cleanroom operationso Deficiencies in production management oversight, and identification of specific improvements to ensure effective and routine supervisory oversight for all batcheso Frequency and depth of quality unit oversight (e.g., audit, ad hoc, daily interactions) of aseptic behaviors and its support operationso Adequacy of written procedureso The risk assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality of your drugs.Repeat Observations at Multiple SitesFDA cited similar CGMP observations at other facilities in your company’s network, including inadequate investigations into OOS results at your Hartland, Wisconsin site. These repeated failures at multiple sites demonstrate that management oversight and control over the manufacture of drugs is inadequate.Your executive management remains responsible for fully resolving all deficiencies and ensuring ongoing CGMP compliance. You should immediately and comprehensively assess your company’s global manufacturing operations to ensure that systems, processes, and the products manufactured conform to FDA requirements.For more information about handling failing, out-of-specification, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/media/158416/download.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 3003983334 and ATTN: Philip Kreiter.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

江西康恒医疗器械有限公司报告，由于包装问题等原因，江西康恒医疗器械有限公司对其生产的医用微网雾化器(注册备案号:赣械注准20242080061)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》。附件：医疗器械召回事件报告表.pdf2026年6月2日