雅培医疗用品（上海）有限公司报告，由于涉及植入式脉冲发生器在接触任何电外科设备时的注意事项等问题，Abbott Medical 雅培医疗器械对其生产的植入式脊髓神经刺激器（注册证号：国械注进20213120264）主动召回。召回级别为二级。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2026年04月22日

行政相对人名称 江苏澳洋医药物流有限公司 行政相对人类别 法人及非法人组织 统一社会信用代码 913205827605209819 工商注册号 组织机构代码 税务登记号 事业单位证书号 社会组织登记证号 法定代表人 朱志皓 法定代表人证件类型 身份证 法定代表人证件号码 320************10 证件类型 证件号码 行政处罚决定书文号 苏药监苏药处罚〔2025〕16号 违法行为类型 违反了《中华人民共和国药品管理法》第九十八条第一款的规定，你公司的行为系销售劣药 违法事实 违反了《中华人民共和国药品管理法》第九十八条第一款的规定，你公司的行为系销售劣药 处罚依据 《中华人民共和国药品管理法》第一百一十七条第一款和《中华人民共和国药品管理法实施条例》第七十五条的规定 处罚类别 没收违法所得 处罚内容 没收违法所得69.89元。 罚款金额（万元） 没收违法所得没收非法财物的金额（万元） 0.006989 暂扣或吊销证照名称及编号 处罚决定日期 2026/04/20 处罚有效期 2026/05/06 公示截止期 2026/07/19 处罚机关 江苏省药品监督管理局 处罚机关统一社会信用代码 11320000014000394R 数据来源单位 江苏省药品监督管理局 数据来源单位统一社会信用代码 11320000014000394R 备注 公示截止期依据文件：关于进一步规范“双公示”信息归集有关工作的通知

Delivery Method:VIA UPSReference #:320-26-68Product:DrugsRecipient:Mr. John CaldwellVP Manufacturing OperationsPar Health USA, LLC & Endo USA, Inc.870 Parkdale RoadRochester,MI48307-1740United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-68April 15, 2026Dear Mr. Caldwell:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, ENDO USA, Inc., FEI 1818977, at 870 Parkdale Road, Rochester, from October 6 to 20, 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 10, 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 perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.42(c)(10)).Inadequate Design of Facility and EquipmentYour firm is a contract manufacturer of sterile injectable drug products produced primarily through aseptic processing including, but not limited to, products for(b)(4)use.(b)(4)of your aseptic processing lines are described as “(b)(4)restricted access barrier systems.” However,(b)(4)of these processing lines(b)(4)are not restricted access barrier systems (RABS). They lacked fundamental RABS design elements, such as(b)(4), that are essential for reducing or eliminating direct gowned personnel intervention into the critical (ISO 5) area during batch manufacturing.(b)(4)are(b)(4)foundational elements of RABS design and control, minimizing contamination risk from the surrounding cleanroom environment. Without these basic features, your processing lines(b)(4)cannot be categorized as RABS.Additionally, your processing lines(b)(4)were designed as traditional aseptic filling lines surrounded by barrier(b)(4)under(b)(4)high efficiency particulate air (HEPA) systems. These processing lines required manually intensive operations during equipment setup and throughout routine production, and did not provide appropriate separation and protection of the ISO 5 areas. For example, we observed the following regarding these aseptic processing lines:Excessive and high-risk manual interventions required during operations on your aseptic processing lines created unacceptable hazards to product sterility. For instance, barrier(b)(4)lines(b)(4)required hundreds of interventions, including numerous lubrications of(b)(4)and conveyor belts with(b)(4), during the production of a batch.Product contact equipment on multiple lines was poorly protected or otherwise exposed to contamination hazards. For example:o Barrier(b)(4)on opposite sides of processing line(b)(4)remained(b)(4)to the surrounding environment for almost(b)(4)during installation of the stopper bowl assembly.o(b)(4)manifold set up on line(b)(4)required personnel to break first pass air to the critical areas of the production line with their arms, head, and upper body, and lasted nearly(b)(4).o The design of the stopper bowl component required personnel to break first pass air with(b)(4)and forearms during installation on production lines(b)(4).o Product tubing extended above and over open vials and filling operations of line(b)(4).Your aseptic processing cleanroom layout, filling equipment design, protection of ISO 5 areas, and the number and complexity of personnel interventions during setup and filling operations are deficient. These basic design deficiencies and manually intensive interventions affect multiple processing lines and compromise your ability to maintain aseptic conditions.Inadequate Environmental MonitoringYou also failed to ensure adequate environmental monitoring (EM) of classified areas used for aseptic production of sterile injectable drug products. For example:EM of critical filling equipment(b)(4)did not ensure each of the(b)(4)were periodically assessed for microbiological quality.Your EM program for ISO 5 non-viable particulate monitoring was deficient. You failed to demonstrate that your sample collection apparatus (using tubing(b)(4)long with(b)(4)bends) provides meaningful and representative samples.Inadequate Unidirectional AirflowThe qualification of airflow in critical areas demonstrated further inadequacies in the suitability and design of aseptic processing lines(b)(4). Dynamic airflow studies demonstrated that airflow patterns failed to adequately protect the aseptic processing line, including exposed sterile product and product contact equipment, from significant contamination hazards.Your dynamic smoke studies did not demonstrate unidirectional airflow protection of the production line while barrier(b)(4)were(b)(4). The study showed air moving at a sharp angle toward(b)(4)vents, leaving critical areas of your aseptic processing line potentially unprotected.Furthermore, design flaws in production equipment led to poor aseptic practices and ergonomics that compromised unidirectional airflow. For example:The(b)(4)assembly design required personnel to grip the(b)(4)with(b)(4), touching the critical portions of the(b)(4)through which the(b)(4)during assembly.Personnel blocked first pass air to(b)(4)with their forearms and(b)(4)during installation of the(b)(4)assembly.Your response emphasizes aseptic processing controls measured by environmental and personnel monitoring recovery rates, numbers of media filled units produced, and sterility tests performed. Furthermore, in your response you also commit to reconfiguring line(b)(4), tightening EM specifications for ISO 5 non-viable particulate monitoring to account for tubing length, eliminating the need for(b)(4)lubrication, and ensuring all(b)(4)are monitored. You also acknowledge the high-risk aseptic line setup activities and have implemented improvements including maintaining(b)(4)protection of equipment for a longer period, changing sequence of setup activities, and improving operator ergonomics.Your response is inadequate as the retrospective review does not overcome fundamental design flaws. Rather than implementing more extensive changes to the aseptic processing operation, you are attempting to partially mitigate significant aseptic processing line hazards. Overall, your response fails to address how you will ensure adequate aseptic processing operations and collect meaningful data to support your aseptic processes.We acknowledge that you also have temporarily suspended manufacture and release of aseptically filled product from all(b)(4)production lines pending a third-party consultant review.Your aseptic manufacturing processes should be designed, and operations executed, to prevent contamination hazards to your sterile product. Flaws in the design of cleanrooms and aseptic processing lines, or improper execution of aseptic operations, can promote influx of contamination into the critical processing area.Your firm’s response also includes evaluation of retrospective sterility testing data. It should be noted that a sterility test, while a critical quality control for aseptically processed products that purport to be sterile, cannot be solely relied upon as justification to release drug product batches. The test is only the last in a series of design provisions and controls intended to protect the consumer from distribution of an unsafe batch.In response to this letter, provide:Comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to:o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of manual interventions wherever possible)o Equipment suitability (e.g., reliability, capability, placement, ergonomics)o Air quality in the ISO 5 area and surrounding roomo Facility layouto Material transferso Personnel and material/process flow throughout all rooms used to conduct and support sterile operationsA detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible, comprehensive improvements to be made to aseptic processing operation design (e.g., separation, automation) and control, and explain how this corrective action and preventive action (CAPA) plan will systematically remediate your aseptic processing operation.2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).Inadequate Process SimulationYour media fills failed to accurately simulate aseptic manufacturing operations.Your data reported maximum aseptic intervention counts per batch of over(b)(4)for line(b)(4)and nearing(b)(4)for line(b)(4). Approximately 30% of these interventions involved lubricating productions lines with(b)(4)due to persistent challenges with the proper functioning and movement of vials during processing. However, the number of worst-case interventions performed during routine batch manufacturing was significantly reduced in your media fill simulations. Additionally, you made the total number of units in your media fill simulations substantially smaller than some of your aseptically produced batch sizes.In your response, you commit to including the maximum number of interventions during a media fill and to addressing the need for lubricating production lines. However, you fail to address media fill batch sizes. Given the manually intensive nature of your processes and fundamental design flaws, your media fills should reflect the worst-case number and type of interventions. When the potential for contamination is higher, as it is with the use of(b)(4)processing lines surrounded by barrier(b)(4), the number of units in a media fill should be the same as, or approach, the maximum production batch size. If a media fill program fails to incorporate contamination risk factors and closely simulate actual drug product exposure, the state of process control and assurance of sterility cannot be accurately assessed. Furthermore, your aseptic processing lines require an inordinate number of interventions and necessitate fundamental design remediations. Notably, media fills cannot justify unsuitable manufacturing lines and processing conditions.Poor Aseptic Technique and Cleanroom BehaviorWe observed poor aseptic practices that were due, in part, to inadequate line design. In addition, our investigators observed operators failing to follow your written procedures during production operations on aseptic processing lines(b)(4). These deviations included, but were not limited to:Reaching over the(b)(4)processing line, open vials, and(b)(4)equipment with(b)(4), sleeves, head, and shoulders to perform line interventions.Inappropriate transfer of(b)(4)stoppers to the production line. For example:o Failure to follow procedures to disinfect the stopper bag during transfer to the production room.o Cutting open the stopper bag and exposing stoppers to the ISO 7 environment prior to emptying the contents into the ISO 5 production line.Your response includes changes to procedures with applicable training for aseptic processing operators. However, your response fails to sufficiently acknowledge design flaws (e.g., equipment ergonomic flaws that affect operator performance), excessive need for manual manipulations, insufficiency of barrier protection to provide adequate separation from surrounding areas, and other fundamental issues.See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practice to help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.In response to this letter, provide:Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures including, not but limited to, an independent assessment of the following with accompanying CAPA:o suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing 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 processing and its support operationso adequacy of written procedureso evaluation of how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.A comprehensive independent review of your process simulation (e.g., media fill) program to ensure appropriate simulations of worst-case conditions in commercial manufacturing.3. 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)).Your visual inspection program was inadequate to ensure your sterile injectable drug products were essentially free of visible particulates. For example,Inadequate Personnel CapabilitiesYour probability of detection of particulates using(b)(4)visual inspection was inadequate. You conducted Knapp studies for(b)(4)-mL and(b)(4)-mL vials and demonstrated that personnel were often not able to achieve a probability of detection of 70% for certain critical particulates larger than 150 microns (e.g., dark fibers, light fibers, glass, and(b)(4)).Inadequate Procedures and Particle CharacterizationYou incorrectly categorized critical defects as major and subsequently approved products that passed acceptable quality limits (AQL) testing. After completion of our inspection, you submitted Field Alert Reports for(b)(4)different products manufactured on(b)(4)different product lines where major particulates were recategorized as critical with subsequent AQL failures.Your written procedures allowed multiple re-inspections for visual particulates, and you acknowledged that up to(b)(4)re-inspections may be performed in support of batch release.Furthermore, since 2023 you failed to conduct thorough investigations of trends in product quality glass defects that adequately remediate your visual inspection program and include adequate support for your product quality impact conclusions.Your response included further details pertaining to a September 2023 deviation for adhered glass defect from a specific vial vendor. Your clarification further acknowledges that your visual inspection program did not adequately assess this defect type.Although you stopped using the glass supplier and determined the defect had no impact on your batches, your investigation failed to assess the full scope, including the number of vials procured and used, and the impact on your entire product portfolio.Additionally, adhered glass defects represent a recurring problem inadequately detected by your visual inspection program and not properly addressed through CAPA. For example, you produced(b)(4)batches of(b)(4)in July and August 2024. Your quality unit approved them for release, but later you identified internal adhered glass defects in these batches.Further, you initiated CAPA 11768 following our inspection to assess 28 AQL failures related to visual inspection. You identified six as needing CAPA improvement.Your response acknowledges serious deficiencies in your visual inspection program, as you have halted all visual inspection activities and hired a third-party consultant to completely remediate your process. You also commit to retrospective evaluation of all deviations for the previous three years, re-inspection of all retained samples for batches associated with adhered glass AQL failures, procedural changes to particle characterization/classification including performing retrospective trending and review, enhanced personnel training, and limiting the number of re-inspections to(b)(4)prior to batch disposition. Your response omits an assessment of products currently in commerce. You continue to lack assurance that distributed products are essentially free of visible particulate matter.Visual detection of particulates is a probabilistic process that depends on, among other things, ensuring that visible particulates can be reproducibly detected by trained personnel with appropriate visual acuity. At a minimum, personnel should reliably be capable of detecting particulates of 150 microns or greater at a 70% probability of detection. Furthermore, written procedures governing 100% inspections for visual particulates should clearly define the number of times re-inspection may be performed. You should limit and justify re-inspections. Generally, FDA does not recommend more than one re-inspection in an attempt to release a batch with atypical defect levels1.In response to this letter, provide:A comprehensive assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The remediation plan should incorporate:o Implementing enhancements to your 100% visible inspection programo Ensuring adequate methods and personnel qualifications to reproducibly detect visible particulates including particulates which historically have been identified in your operation.o For drug products that are difficult to inspect (e.g.,(b)(4), suspension products,(b)(4)containers), implementing destructive testing or other advanced technologies (e.g.,(b)(4)) as appropriate, with statistically significant sample sizes to test for critical defects.o Incorporating product-specific knowledge, process experience, deviation investigation analysis, recall/complaint data, and quality risk management to improve the visual inspection program.Your associated remediations to your visual inspection program including any newly established written procedures and methods. Include a summary of the review and recommendations made by your independent consultant.Provide an assessment of changes implemented to your component supplier qualification program, visual inspection qualification practices, and CAPA to prevent visible particulates (e.g., glass) from contaminating your injectable drug products.A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, action level results (out of limits), 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.Visible Particulate ContaminationWe encourage the use of suitable automated visual inspection for particulates to augment the(b)(4)visual inspection program. Automated methods should be rigorously studied, and qualified, to assess their capability and robustness under various conditions, machine settings, container-closure sizes, defect types, product characteristic, and other variables. In addition, any use of automated particulate inspection as an adjunct method does not supplant the need for(b)(4)visual inspection for various other attributes (e.g., cracks; myriad defects of container or closure;(b)(4)issues, volume, atypical(b)(4)or other appearance defects).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 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.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.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.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 days2. 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 1818977 and ATTN: Matthew R. Dionne, Pharm.D., Compliance Officer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research___________________________1See FDA’s draft guidance document Inspection of Injectable Products for Visible Particulates to help you meet the CGMP requirements pertaining to visible particulate inspections of sterile injectable drug products at https://www.fda.gov/media/154868/download.2Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.

近期，我局在对江西烁之康医药物流有限公司开展日常监督检查过程中，发现该公司存在严重违反《药品经营质量管理规范》（GSP）的行为，经综合研判，认定其药品经营活动已存在重大质量安全隐患。依据《中华人民共和国药品管理法》第九十九条第三款、《药品经营和使用质量监督管理办法》第六十三条以及《药品检查管理办法（试行）》第六十二条等相关规定，现决定自本公告发布之日起，对江西烁之康医药物流有限公司采取暂停药品销售的风险控制措施。在暂停销售期间，该公司不得以任何形式擅自从事药品采购、储存、销售、配送等经营活动。如需恢复经营，须在完成全面整改并通过我局组织的复查验收后，方可依法依规恢复相关业务。特此公告。                                                      江西省药品监督管理局                                                       2026年4月20日 附：江西烁之康医药物流有限公司基本情况序号企业名称许可证编号经营地址仓库地址经营范围1江西烁之康医药物流有限公司赣AA7900667江西省新余市渝水区下村工业平台大一路12号5栋101江西省新余市渝水区下村工业平台大一路12号新余市嘉晟工贸有限公司厂区-5#厂房中药饮片,中成药,化学原料药,化学药制剂,抗生素原料药,抗生素制剂,生化药品（冷藏冷冻药品除外）,生物制品（血液制品、冷藏冷冻药品除外）

为全面反映2025年湖北省医疗器械不良事件监测情况，省药监局组织省药品（医疗器械）不良反应监测中心（以下简称省中心）编撰了《湖北省医疗器械不良事件监测年度报告（2025年）》。一、 全省医疗器械不良事件报告总体情况（一） 报告数量总体情况2025年，省中心通过国家医疗器械不良事件监测信息系统收到医疗器械不良事件报告55028份，其中省内报告42831份，较2024年增加18.69%。2015年至2025年，全省累计上报医疗器械不良事件报告247770份（图1-1）图1-1 2015-2025年全省上报医疗器械不良事件报告数量（二）每百万人口平均报告数量2025年，全省每百万人口平均医疗器械不良事件报告数为734份，较2024年增加18.81%。（三）注册基层用户数量截至2025年12月31日，全省医疗器械不良事件监测在线使用基层用户13703家。其中医疗器械注册人、备案人1672家，较2024年增加2.70%，占基层用户总数的12.20%；经营企业7945家，较2024年增加1.78%，占基层用户总数的57.98%；使用单位4086家，较2024年增加2.15%，占基层用户总数的29.82%（图1-2）。图1-2 2025年全省医疗器械不良事件监测系统注册基层用户情况二、 医疗器械不良事件报告统计分析（一） 按报告来源统计分析2025年，全省上报的医疗器械不良事件报告中，使用单位报告40456份，占报告总数的94.45%；经营企业报告2158份，占报告总数的5.04%；注册人、备案人报告212份，占报告总数的0.49%；其他5份，占报告总数约0.01%（图2-1）。图2-1 2025年全省医疗器械不良事件报告来源情况（二）按不良事件伤害程度统计分析2025年，全省上报的医疗器械不良事件报告中，伤害程度为严重伤害的4972份，占报告总数的11.61%；死亡报告1份；其他报告37858份，报告总数的88.39%（图2-2）。图2-2 2025年全省医疗器械不良事件伤害程度情况    （三）按医疗器械管理类别统计分析2025年，全省上报的医疗器械不良事件报告中，涉及III类医疗器械的报告17175份，占报告总数的40.10%；涉及II类医疗器械的报告22719份，占报告总数的53.04%；涉及I类医疗器械的报告2570份，占报告总数的6.00%；未填写医疗器械管理类别的报告367份，占报告总数的0.86%。（图2-3）。图2-3 2025年全省医疗器械不良事件涉及医疗器械管理类别情况（四）按医疗器械管理类别统计分析按《医疗器械分类目录》一级分类排序，报告数量排名前五位的分别为140000_注输、护理和防护器械，070000_医用诊察和监护器械，090000_物理治疗器械，220000_临床检验器械和080000_呼吸、麻醉和急救器械（表2-1）。表2-1 按分类目录一级分类排名前十位排名产品分类报告数百分比（%）1140000_注输、护理和防护器械1966846.502070000_医用诊察和监护器械464010.973090000_物理治疗器械32467.674220000_临床检验器械24755.855080000_呼吸、麻醉和急救器械22135.236060000_医用成像器械17304.097100000_输血、透析和体外循环器械15043.568180000_妇产科、辅助生殖和避孕器械12282.909200000_中医器械9902.3410020000_无源手术器械9062.14按《医疗器械分类目录》二级分类排序，报告数量排名前五位的分别为140200_血管内输液器械，140100_注射、穿刺器械，070400_监护设备，070300_生理参数分析测量设备，141000_创面敷料（表2-2）。表2-2 按分类目录二级分类排名前十位排名产品分类报告数百分比（%）1140200_血管内输液器械950522.472140100_注射、穿刺器械29206.903070400_监护设备21905.184070300_生理参数分析测量设备18764.435141000_创面敷料16343.866090200_温热（冷）治疗设备/器具15703.717140500_非血管内导（插）管13703.248221100_采样设备和器具13343.159080600_呼吸、麻醉用管路、面罩8972.1210100300_血液净化及腹膜透析设备8371.98按《医疗器械分类目录》三级分类排序，报告数量排名前五位的分别为140205_输液器，070401_病人监护设备，140102_无菌注射器，140212_药液用转移、配药器具，141001_创面敷贴（表2-3）。表2-3 按分类目录三级分类排名前十位排名产品分类报告数百分比（%）1140205_输液器543212.842070401_病人监护设备21665.123140102_无菌注射器19264.554140212_药液用转移、配药器具17774.205141001_创面敷贴13173.116140207_血管内留置针12953.067140503_导尿管10722.538070303_无创血压测量设备8932.119140101_注射泵8271.9610100301_血液透析设备7831.85    （五）按涉及使用场所统计分析产品使用场所为医疗机构的报告40086份，占报告总数的93.59%；使用场所为家庭的报告2017份，占报告总数的4.71%；使用场所为其他的报告728份，占报告总数的1.70%（图2-4）。图2-4 2025年全省医疗器械不良事件涉及使用场所情况三、全省医疗器械不良事件监测工作进展情况（一）夯实监测基础，持续提升报告数量质量。2025年共收到医疗器械不良事件报告42831份，每百万人口平均报告数734份。强化质量管理，组织对13家医疗机构报告进行现场核查，指导基层提升监测能力。对标《湖北省医疗器械不良事件报告表质量评分标准》，组织开展报告质量评估，建立质量评分系统，推动医疗器械不良事件监测报告信息的真实性、准确性、规范性持续提升。（二）精准风险识别，充分发挥技术支撑作用。强化风险分析评价，及时审核定期风险评价报告，及时发现并处置风险信号；指导督促持有人开展产品风险评价，深入分析查找原因，制定风险控制措施，为助力全省医药产业高质量发展，保障群众用械安全提供了有力技术支撑。（三）强化专业指导，助力企业落实主体责任。坚持问题导向，组织开展医疗器械注册人备案人不良事件监测现场指导，同步对未纳入国家药品不良反应监测系统的企业进行清理，督促其在监测系统内完成产品注册，落实医疗器械不良事件监测主体责任。（四）主动担当作为，服务药品监管科研大局。深度参与国家中心监测项目，圆满完成完成“十四五”期间高电位治疗设备等重点监测工作。积极开展法规制度与课题研究，有效提升我省医疗器械不良事件监测综合能力。（五）拓展宣传培训，构建共治共享新格局。举办2025年湖北省医疗器械不良事件监测哨点医院培训班，促进监测哨点和医护人员能力监测提升。积极开展“安全用械进社区”等安全科普宣传活动，有效提升群众用械安全意识。四、有关情况说明（一）与大多数国家一样，我国医疗器械不良事件报告通过自发报告系统收集并录入到数据库中，当怀疑某种事件可能与医疗器械有关时，就可以报告。受报告者主观意识、经验水平、认知程度、甚至所持立场等影响，医疗器械不良事件的报告可能存在片面性和局限性，如伤害程度判读不准确、报告填写不规范、信息不完善等，甚至将与医疗器械无关的事件也按照不良事件报告，因此统计结果可能与实际发生的医疗器械不良事件情况存在偏差。（二）不同医疗器械的不良事件报告数量受使用数量、风险程度、报告意识等诸多因素影响，因此报告数量的多少不直接代表医疗器械不良事件发生率的高低或者风险严重程度。（三）上述统计数据来源于国家医疗器械不良事件监测信息系统中2025年1月1日至2025年12月31日接收的数据，统计中由于四舍五入进位规则，可能会出现百分比加和不等于100%的情况。（四）本年度报告完成时，部分死亡及严重伤害医疗器械不良事件报告尚处在调查和评价过程中，因此统计结果为统计时数据收集情况的真实反映，不代表医疗器械安全性评价最终结论。小贴士1.医疗器械：是指直接或者间接用于人体的仪器、设备、器具、体外诊断试剂及校准物、材料以及其他类似或者相关的物品，包括所需要的计算机软件；其效用主要通过物理等方式获得，不是通过药理学、免疫学或者代谢的方式获得，或者虽然有这些方式参与但是只起辅助作用；其目的是：（1）疾病的诊断、预防、监护、治疗或者缓解；（2）损伤的诊断、监护、治疗、缓解或者功能补偿；（3）生理结构或者生理过程的检验、替代、调节或者支持；（4）生命的支持或者维持；（5）妊娠控制；（6）通过对来自人体的样本进行检查，为医疗或者诊断目的提供信息。2.无源医疗器械：不依靠电能或者其他能源，但是可以通过由人体或者重力产生的能量，发挥其功能的医疗器械。3.有源医疗器械：任何依靠电能或者其他能源，而不是直接由人体或者重力产生的能量，发挥其功能的医疗器械。4.体外诊断试剂：是指按医疗器械管理的体外诊断试剂，包括在疾病的预测、预防、诊断、治疗监测、预后观察和健康状态评价的过程中，用于人体样本体外检测的试剂、试剂盒、校准品、质控品等产品。可以单独使用，也可以与仪器、器具、设备或者系统组合使用。按照药品管理的用于血源筛查的体外诊断试剂和采用放射性核素标记的体外诊断试剂，不属于本报告范围。5.国家对医疗器械按照风险程度实行分类管理：第一类是风险程度低，实行常规管理可以保证其安全、有效的医疗器械。第二类是具有中度风险，需要严格控制管理以保证其安全、有效的医疗器械。第三类是具有较高风险，需要采取特别措施严格控制管理以保证其安全、有效的医疗器械。6.医疗器械不良事件监测：是指对医疗器械不良事件的收集、报告、调查、分析、评价和控制的过程。7.医疗器械不良事件：是指已上市的医疗器械，在正常使用情况下发生的、导致或者可能导致人体伤害的各种有害事件。8.死亡医疗器械不良事件报告：指患者最终结果为死亡的医疗器械不良事件报告。不表示患者的死亡与使用医疗器械有明确的关联性。9.正确认识医疗器械不良事件报告数量增加：经过各方努力，注册人、经营企业、医疗机构报告医疗器械不良事件的积极性已经逐步提高，我省医疗器械不良事件报告数量稳步增长，与全国及欧盟、美国等国家和地区医疗器械不良事件报告数量发展趋势相同。医疗器械不良事件报告数量增多，并非说明医疗器械安全水平下降，而是意味着监管部门掌握的信息越来越全面，对医疗器械的风险更了解，风险更可控，对医疗器械的评价更加有依据，监管决策更加准确。在医疗实践中，能及时了解医疗器械不良事件发生的表现、程度，并最大限度地加以避免，也是保证患者用械安全的重要措施。

为全面反映2025年全省化妆品不良反应监测情况，提高公众用妆安全，湖北省药品监督管理局组织湖北省药品（医疗器械）不良反应监测中心（以下简称：省中心）编撰了《湖北省化妆品不良反应监测年度报告（2025）》。一、化妆品不良反应报告整体情况 （一）不良反应报告数图1-1 2017-2025年度不良反应/事件报告总体情况2025年度全省共收集到化妆品不良反应报告15066份，与2024年度相比，增长21.48%（见图1-1）。其中一般报告15052份，严重报告14份。每百万人口平均报告数261份。（二）不良反应报告来源情况2025年报告来源以医疗机构为主，全年医疗机构上报11162份，占报告总数的74.09%，较2024年增加了24.28%，主要为监测哨点医院上报；经营单位上报3095份，占报告总数的20.54%；化妆品注册人/备案人上报122份，占报告总数的0.81%；受托生产企业上报6份，占报告总数0.04%；个人上报585份，占报告总数的3.88%；其他上报95份，占报告总数0.63%（见表1-1）。表1-1 2024—2025年不良反应报告来源情况报告单位类型2025年报告数（份）2024年报告数（份）较2024年增加数量（份）较2024年报告增长（%）医疗卫生机构111628981218224.28经营单位309529581374.63 化妆品注册人/备案人12211932.52 个人58530028595.00 受托生产企业610-4-40.00 其他（监测机构）953461179.41境内责任人101——（三）不良反应报告质量评估得分2025年，全省化妆品报告质量评估平均得分为99.38，较2024年提高3.97%。其中，严重报告平均分为103.63，一般报告平均分为99.37。各市州化妆品报告质量均有较大的提高，评估得分居前六位的市州依次为神农架林区、天门市、十堰市、鄂州市、仙桃市、荆州市。见表1-2。表1-2 2024—2025年各市州化妆品报告质量评估得分表地区2025年报告质量评估得分2024年报告质量评估得分神农架林区105.64 105.40 天门市104.63 96.14 十堰市102.85 99.33 鄂州市102.37 101.32 仙桃市102.00 96.50 荆州市101.74 101.41 潜江市101.34 86.68 恩施州101.30 99.03 黄冈市101.13 95.89 武汉市99.93 100.39 黄石市99.48 89.36 孝感市98.77 93.65 咸宁市98.12 90.52 随州市97.17 92.37 襄阳市96.94 88.45 荆门市96.20 93.42 宜昌市92.57 89.19 平均分99.37 95.58 （四）患者/消费者人口学信息1.性别分布情况2025年全省共收到15066份化妆品不良反应报告，其中涉及男性患者/消费者的报告1443份，占9.58%；涉及女性患者/消费者的报告13623份，占90.42%。女性数量远高于男性，该现象与女性在化妆品使用数量和种类上普遍多于男性有关。（见图1-2）。图1-2 2022-2025不良反应涉及性别分布情况    2.年龄分布情况2025年化妆品不良反应报告信息显示，患者/消费者年龄主要集中在16-44岁、45-64岁，其中16-44岁的患者/消费者10486例，占69.60%；45-64岁的患者/消费者3584例，占23.79%；0-12岁患者/消费者为194例，占1.29%，年龄分布数据显示化妆品重点使用人群为中青年女性（见图1-3）。图1-3 不良反应涉及患者/消费者年龄分布（五）不良反应/事件表现1.初步判断 初步判断是根据不良反应症状选择的初步诊断结果。2025年度化妆品不良反应报告涉及初步判断15397例次，居前5位的依次为化妆品接触性皮炎（13896例次，占90.25%）、化妆品荨麻疹（273例次，占1.77%）、化妆品毛发损害（268例次，占1.74%）、化妆品痤疮（231例次，占1.50%）、化妆品唇炎（198例次，占1.29%）、化妆品光感性皮炎（193例次，占1.25%）（见图1-4）。图1-4 不良反应初步判断情况2.自觉症状自觉症状28184例次（同一患者可能同时出现两种或者两种以上自觉症状），表现为瘙痒11415例次，占比40.50%；灼热感5622例次，占比19.95%；紧绷感4317例次，占比15.32%；干燥4221例次，占比14.98%（见图1-5）。图1-5 化妆品不良反应自觉症状3.皮损形态21711例次（一份不良反应报告中可能含有两种或两种以上皮损形态），皮损形态为红斑有8886例次，占比40.93%；丘疹4669例次，占比21.51%；水肿2062例次，占比9.50%；鳞屑914例次，占比4.21%；斑块845例次，占比3.89%；粉刺820例次，占比3.78%；抓痕505例次，占比2.33%；毛细血管扩张433例次，占比1.99%等。（六）产品信息分析1.化妆品类别情况统计分析2025年，化妆品不良反应报告中涉及特殊化妆品的共有2732例次，占比17.99%；涉及普通化妆品12379例次，占比81.53%；涉及牙膏73例次，占比0.48%。普通化妆品属于日常肌肤护理保养类产品，报告数量多与其在日常生活中使用频繁、使用人群广泛有关。 特殊化妆品主要集中在祛斑美白类、防晒类、染发类。普通化妆品主要为护肤类，包括面霜、乳液、面膜、化妆水、膏、化妆用油和爽身粉等；其次为洁肤类、发用类、美容修饰类（见表1-3）。表1-3 不良反应报告的化妆品类别一级分类二级分类例次占比（%）特殊化妆品祛斑美白类109740.15 防晒类87532.03 染发类48417.72 防脱发类632.31 美乳类562.05 祛斑类471.72 脱毛类270.99 除臭类250.92 烫发类210.77 育发类190.70 宣称新功效类150.55 健美类30.11 合计2732100.00 一级分类二级分类例次占比（%）普通化妆品护肤类886671.62 洁肤类168313.60 发用类8737.05 美容修饰类8366.75 香水类590.48 脱毛类400.32 除臭类220.18 合计12379100.00 一级分类二级分类例次占比（%）牙膏/73100.00 2.产品来源情况统计分析15184例次怀疑化妆品不良反应中，产品主要来源于网购，共9277例次，占比61.10%，比2024年增加了4.45%；其次商场（超市、专柜）4180例次，占比27.53%；美容美发机构806例次，占比5.31%；其他855例次，占比5.63%；未填写产品来源的报告66例次，占比0.43%，较去年有所下降（见表1-4）。表1-4 2024-2025不良反应报告产品来源分布情况产品来源2025年2024年例次占比（%）例次占比（%）网购927761.10 706956.65 商场418027.53 406432.57 美容美发机构8065.31 5584.47 其他8555.63 6565.26 未填写660.43 1311.05 合计15184100.00 12478100.00 二、化妆品不良反应报告监测趋势综合分析（一）报告总数稳步增长，报告质量进一步提升。2025年，各级监管部门和监测机构攻坚克难，扎实开展化妆品不良反应监测工作。化妆品不良反应监测报告总数15066份，同比增长21.48%。全省每百万人口平均报告数达261份。报告质量评估平均分为99.38，同比增长3.97%。（二）监测哨点持续发挥积极示范带动作用。61家省级监测哨点医院共上报化妆品不良反应报告3931份，占上报总数的26.09%，比2024年增长了23.31%；58家市级监测哨点医院共上报化妆品不良反应报告1636份，占上报总数的10.86%，比2024年增加了11.29%。9例严重风险信号来自哨点医院，占严重报告64.29%，为监管部门和监测机构提供了有力的技术支持。 （三）化妆品商标名，类别和生产企业分布变化不明显。市场占有率较高的大品牌、大企业化妆品不良反应报告数量排名靠前。化妆品类别主要为普通化妆品，以护肤类为主，特殊化妆品主要集中在祛斑美白类、防晒类和染发类。化妆品商标名、类别和生产企业整体分布与2024年相比无明显变化。（四）关注网购渠道的化妆品风险。网购化妆品引起不良反应仍占比最高，网购已连续八年成为化妆品不良反应涉及产品来源的主要渠道。对于儿童化妆品，2025年网购来源化妆品引起的不良反应占据首位，达到51.55%；对于染发类化妆品，网购来源引起的不良反应占比为57.97%。疑似激素依赖性皮炎报告所涉及化妆品网购来源达到41.67%。网购渠道的化妆品来源复杂，一些不良商家可能会销售假冒伪劣产品导致不良反应的发生，建议消费者在网购化妆品时，应尽量选择正规、信誉良好的电商平台，仔细查看产品的资质证明、成分表等信息，避免购买假冒伪劣产品。（五）关注儿童化妆品使用风险。儿童消费者的不良反应初步判断以化妆品接触性皮炎为主，占比92.78%，自觉症状主要表现为瘙痒、干燥、灼热感、紧绷感、疼痛，皮损部位主要为面部，皮损形态主要为红斑、丘疹。涉及的化妆品大多数为普通化妆品，以霜为主，其次为清洁类、乳液和洗发。特殊化妆品中的防晒类占比有所提高。鉴于儿童群体的特殊性，建议家长在为儿童选购化妆品时，应选择有小金盾标识，成分简单、无刺激的产品，并且要通过正规渠道购买。同时，要注意儿童使用化妆品的频率和用量，避免过度使用。三、有关说明（一）本年度报告中的数据来源于国家化妆品不良反应监测数据库中2025年1月1日至2025年12月31日湖北省收集上报的数据。（二）湖北省化妆品不良反应报告是通过自发报告系统收集并录入到数据库中的，也存在自发报告系统的局限性，如漏报、报告不规范、信息不完善、无法计算不良反应发生率等。

行政执法案件信息公开表（2026年第3期，总第189期）序号行政处罚决定书文号案件名称违法企业名称或违法自然人名称违法企业组织机构代码证/ 统一社会信用代码法定代表人/负责人姓名主要违法事实行政处罚内容决定机关名称处罚决定日期公示日期备注1渝药监处罚〔2025〕48号重庆悦鹿视光医疗器械有限公司生产销售未取得医疗器械注册证的第二类医疗器械案重庆悦鹿视光医疗器械有限公司91500103MA613KTE9Y        魏素娟当事人生产销售未取得医疗器械注册证的第二类医疗器械视知觉训练治疗软件。当事人的行为违反了《医疗器械监督管理条例》第十三条第一款的规定。依据《医疗器械监督管理条例》第八十一条第一款第一项的规定，责令当事人改正违法行为，并决定给予行政处罚如下：1.没收违法所得15000元；2.罚款42000元。重庆市药品监督管理局2026.04.202026.04.21

Delivery Method:Via Electronic Mail - Delivery and Read Receipt RequestedProduct:DrugsRecipient:Raymond R. CarlsonRPh OwnerRC Outsourcing, LLC102 East Water StreetLowellville,OH44436-1117United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERWL # 722877March 20, 2026Dear Mr. Carlson:You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. § 353b]1on October 7, 2015, and most recently on November 27, 2025. From August 18, 2025 to August 28, 2025, an FDA investigator inspected your facility, RC Outsourcing, LLC located at 102 East Water St., Lowellville, OH 44436. The investigator noted serious deficiencies in your practices for producing drug products, which put patients at risk.FDA issued a Form FDA 483 to your facility on August 28, 2025. We reviewed your September 19, 2025, October 28, 2025, and November 21, 2025, responses to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence on December 31, 2025. FDA also acknowledges that, on September 22, 2025, your firm initiated a voluntary recall of four (4) lots of Bevacizumab 1.75 mg/0.07 mL Syringe, 0.25 mL, within expiry, due to a lack of sterility assurance. Based on this inspection, it appears you produced drugs that violate the FD&C Act.A. Compounded Drug Products under the FD&C ActUnder section 503B(b) of the FD&C Act, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FD&C Act [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FD&C Act [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FD&C Act are met.An outsourcing facility, which is defined in section 503B(d)(4) of the FD&C Act [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that—(i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FD&C Act, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.B. Violations of the FD&C ActAdulterated Drug ProductsThe FDA investigator noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FD&C Act. For example, the investigator observed that:1. You exposed sterile drugs and materials to lower than ISO 5 quality air.Specifically, your handling of container-closure system components for Povidone-Iodine Sterile Ophthalmic Solution may result in contamination. During the repackaging process, dropper bottle caps containing the applicator tips are staged(b)(4)on the surface of your ISO 5 laminar flow hood. This practice exposes critical surfaces—specifically, the interior of the dropper bottle cap and the applicator tip—to the non-sterile surface of the ISO 5 hood. Additionally, this(b)(4)The FDA investigator also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act. The violations include, for example:1. Your firm failed to thoroughly investigate any unexplained discrepancy or the 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).2. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing area (21 CFR 42(c)(10)(iv)).3. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic processes (21 CFR 211.113(b)).4. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).5. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1), 211.84(d)(2)).6. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FD&C Act. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance,Current Good Manufacturing Practice—Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.Under section 301(a) of the FD&C Act [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FD&C Act [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.Unapproved New Drug ProductsYou do not have any FDA-approved applications on file for the drug products that you repackage, such as Povidone-Iodine 5% Ophthalmic Solution.2Under sections 505(a) and 301(d) of the FD&C Act [21 U.S.C. §§ 331(d)], a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FD&C Act is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FD&C Act.3In addition, you do not have any FDA-approved applications on file for certain other products that you manufacture, such as Bevacizumab 1.75 mg/0.07 mL, 0.25 mL Syringe. Products such as Bevacizumab 1.75 mg/0.07 mL, 0.25 mL Syringe are unapproved new drugs under section 505 of the FD&C Act [21 U.S.C. § 355(a)] and also biological products under section 351 of the Public Health Service Act (PHS Act) [42 U.S.C. § 262]. In order to lawfully market a drug that is also a biological product, a valid biologics license application (BLA) must be in effect under the PHS Act. Your biological products, such as Bevacizumab 1.75 mg/0.07 mL, 0.25 mL Syringe, are not the subject of an approved BLA. The introduction or delivery for introduction of these products into interstate commerce is prohibited under section 301(d) of the FD&C Act [21 U.S.C. § 331(d)].4Misbranded Drug ProductsYou repackage drug products, such as Povidone-Iodine 5% Ophthalmic Solution, that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses.You manufacture other products, such as Bevacizumab 1.75 mg/0.07 mL, 0.25 mL Syringe, that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use this product safely for their intended uses.Accordingly, the labeling of these products fails to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FD&C Act.5Additionally, the label of a product you manufacture, Bevacizumab 1.75 mg/0.07 mL, 0.25 mL Syringe, states that the quantity or proportion of bevacizumab is 1.25 mg. However, based on the declared concentration of 25 mg/mL, the accurate quantity or proportion of bevacizumab in your 0.25 mL syringe is 1.75 mg. Under section 502(a) of the FD&C Act [21 U.S.C. § 352(a)], a drug product is misbranded if its labeling is false or misleading in any particular. Because the labeling of this drug product is false or misleading, it is misbranded under section 502(a) of the FD&C Act.The introduction or delivery for introduction of misbranded drugs into interstate commerce is prohibited under section 301(a) of the FD&C Act. It is also a prohibited act under section 301(k) of the FD&C Act to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.C. Corrective ActionsWe have reviewed your facility’s responses to the Form FDA 483. We acknowledge your recall of the following four (4) lots of Bevacizumab 1.75 mg/0.07 mL Syringe, 0.25 mL, within expiry, due to a lack of sterility assurance. We are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:1. Regarding your firm’s failure to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic processes:We acknowledge the actions your firm has taken in response to the failure to ensure that components of your container-closure system, used for sterile ophthalmic drug products, are handled in a manner that maintains their sterility. We note your statement that “All Betadine (povidone-iodine) production has been suspended as of 28-AUG-2025 to allow the quality unit to assess and evaluate a potential new container-closure system and the repackaging process.” While we acknowledge that temporarily suspending production of this drug product mitigates immediate risk, you have not submitted documentation describing your Quality Unit's evaluation of any process modification designed to prevent microbiological contamination. Your response did not include a timeframe for completion of this evaluation or a plan outlining the specific steps your firm will take to resolve this deficiency.2. Regarding your firm’s failure to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that drug products conform to appropriate standards of identity, strength, quality, and purity:We acknowledge the actions your firm has taken in response to the failure to employ appropriately validated analytical methods for assay testing of active pharmaceutical ingredients (API) in the following drug products: Lidocaine 23%-Tetracaine 7% ointment (LT), Lidocaine, USP 20%-Tetracaine, USP 6%-Phenylephrine, HCl 2% ointment (LTP), Benzocaine 20%-Lidocaine 6%-Tetracaine 4% ointment (BLT), and Lidocaine HCl 2% Injection. We noted your commitment to suspend all production of drug products using bulk API powder until strength methods are validated for CGMP release testing, and that you continue working with your contract testing laboratory to develop and validate these methods. While temporarily suspending production mitigates immediate risk, we cannot fully evaluate the adequacy of your long-term corrective action plan without additional documentation. Specifically, we require fully executed analytical method validation protocols demonstrating successful method validation, including appropriately defined system suitability criteria.3. Regarding your firm’s failure to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced:We acknowledge the actions your firm has taken in response to the failure to consistently record the lot numbers of sterile,(b)(4)beakers ((b)(4)Sterile Beakers) and sterile(b)(4)in the batch production records for Lidocaine 2% Injection. We note your commitment to verify the accuracy and completeness of batch production records going forward. However, we cannot fully verify the adequacy of your corrective action plan due to the lack of supporting documentation, such as executed batch production records demonstrating implementation of the corrective actions. We recognize that your firm has suspended production of drug products produced from API, including Lidocaine 2% Injection. Given this production suspension, demonstrating full correction of this violation may not be feasible at this time. Therefore, the effectiveness of your corrective actions will be assessed during the next inspection of your firm.Some of your corrective actions appear deficient:4. Regarding your firm’s failure to thoroughly investigate any unexplained discrepancy or the failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed:a. We acknowledge the actions taken by your firm in response to your failure to adequately investigate the sterility failure of bevacizumab, lot # 20250428-488A81, and to extend the investigation to other potentially affected batches of drug product. Your investigation, documented as Nonconformance Report-2 (NCR-2), identified a medical condition (i.e., eczema) experienced by a sterile drug production operator as the likely cause of the contamination. According to the timeline you provided, the operator in question experienced the skin condition for approximately three months (i.e., from 04/21/2025 to 07/21/2025), yet your firm did not evaluate the potential impact on other drug product batches manufactured during this period. Additionally, despite identifying the operator's medical condition as a potential root cause, you allowed the operator to continue performing aseptic operations while wearing a patch, although you failed to provide evidence supporting the effectiveness of this control measure in reducing contamination risk. In addition, while the revised SOP-28 “Out-of-Specification and Out-of-Trend Investigations” (effective 09/12/2025) now requires evaluation of all lots produced within a particular timeframe and/or by the same operator, the procedure fails to consider other variables that may contribute to such deviations or discrepancies (e.g., drug product contamination). A comprehensive investigation should evaluate common elements such as equipment, components, and personnel in an effort to determine both potential root cause(s) and the full scope of the event.b. We acknowledge the actions taken by your firm in response to your failure to investigate numerous instances of microbial recovery from the sleeves of gowns worn by operators who enter the ISO 5 space during sterile drug production. We note that SOP-57 “Testing of Sterile Environment” (effective 07/16/2025), which was current at the time of these microbial excursions, defined the Action Limit for sleeves as “(b)(4)CFUs.” We acknowledge your intent to “change the CFU action limit to(b)(4)for sleeve monitoring” and recognize your voluntary recall of four (4) lots of drug product, each associated with the recovery of 1 CFU from the sleeve of a production operator involved in producing the respective batch.However, your response fails to address significant elements of the violation. Although you acknowledge the failure to investigate an adverse trend in personnel monitoring results, you have not initiated a retrospective investigation into this discrepancy. Consequently, you have not identified a root cause or implemented corrective and preventive actions to prevent recurrence.We further note that SOP-57 “Testing of Sterile Environment” (effective 07/16/2025), which was current when this violation occurred, defined an “Alert Limit” for “ISO 7 (Sleeves)” at “(b)(4)CFUs.” However, your procedures do not define the implications of meeting or exceeding an Alert Limit. Additionally, your firm has not committed to defining what constitutes an adverse “trend” or how it will analyze such data when identified. Finally, the classification of sleeve samples as “ISO 7” is inappropriate because operators' sleeves routinely enter the ISO 5 space during aseptic operations.5. Regarding your firm’s failure to establish an adequate system for monitoring environmental conditions in aseptic processing area:a. We acknowledge the actions your firm has taken in response to the failure to perform adequate viable air monitoring within the ISO 5 laminar flow hood during sterile drug production activities. We note your plan to(b)(4)“to provide a better representative air sample in ISO 5 conditions.” However, you have not fully implemented and documented this corrective action through batch production records and associated environmental monitoring data. Additionally, the qualification of any such equipment should include airflow visualization studies (i.e., “smoke studies”) to demonstrate that the equipment does not adversely affect laminar airflow within the ISO 5 space and, therefore, does not compromise drug product protection.b. We acknowledge the actions your firm has taken in response to the failure to ensure that settle plates used for passive air monitoring of the ISO 5 laminar flow hood during sterile drug production are appropriately positioned to generate data representative of the ISO 5 environment during aseptic operations. We acknowledge your plan to replace(b)(4)plates with(b)(4)plates, as(b)(4)plates are not appropriate for passive air (i.e., “settle plate”) monitoring. We further note the revisions to section 5.6.2 of SOP-57 “Testing of Sterile Environment” (effective 10/15/2025), which now states, in part, that settle plates should be “placed within the ISO 5 space near the area of highest activity or critical manipulations... without obstructing airflow or work...” However, while your response indicates that plates will now be located in closer proximity to critical operations, it fails to describe the process by which these locations are determined or whether airflow visualization studies will be conducted to verify that the plates do not adversely affect airflow within the ISO 5 space.c. We acknowledge the actions your firm has taken in response to operators' failure to properly perform personnel sampling and monitoring (i.e., gown sleeve) as part of your environmental monitoring program. We note your plans to retrain personnel on the proper technique. However, your response failed to provide evidence that personnel have been adequately retrained and are qualified to conduct personnel sampling (i.e., gown sleeve) appropriately and consistently.6. Regarding your firm’s failure to establish the reliability of your component supplier’s test analyses (i.e., Certificates of Analysis) at appropriate intervals, as well as your failure to conduct at least one test to verify the identity of each shipment of every lot of components:We acknowledge the actions your firm has taken in response to the failure to conduct at least one identity test on each shipment of every lot of components, including APIs. Specifically, we note the implementation of SOP-94 “Active Pharmaceutical Ingredient Identification Testing” (Version 3.0, Effective September 12, 2025). However, your procedure contains a significant gap. Section 5.1.3 states, “If a(b)(4)lot number of an API is received, it will be held in quarantine until sampling can be obtained for identity testing.” This language indicates that your procedure would permit subsequent shipments of a previously received lot to be released to production without identity testing. This approach is inadequate. The regulatory requirement is that each shipment of each lot must be subject to at least one identity test, regardless of whether that lot number has been received previously. Lastly, your response does not include a corrective action plan to address the requirement to establish the reliability of your supplier's analyses at appropriate intervals, such as(b)(4)for APIs.In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products.Seesection 501 of the FD&C Act. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See21 CFR 210.1(b), 21 CFR 200.10(b).]FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.D. ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations 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. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.All correspondence should refer to the Warning Letter Number above (#722877) and include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.Sincerely,/S/Matthew J. LashActing DirectorOffice of Compounding Quality and ComplianceOffice of ComplianceCenter for Drug Evaluation and Research_______________________1See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).2The specific products repackaged by your firm are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FD&C Act [21 U.S.C. 321(p)] because they are not generally recognized as safe and effective for their labeled uses.3Drugs that are repackaged are not eligible for the exemptions for compounded drugs under sections 503A and 503B of the FD&C Act. For additional information, you may wish to review FDA’s 2017 guidance document, “Repackaging of Certain Human Drug Products by Pharmacies and Outsourcing Facilities.” More specifically, the guidance sets forth conditions under which FDA does not intend to take action against drug products repackaged by pharmacies and outsourcing facilities for certain violations of the FD&C Act. Such conditions include, but are not limited to, the label on the immediate container (primary packaging, e.g., the syringe) of repackaged products including the statement “Not for resale.”4Biological products subject to licensure under section 351 of the PHS Act are not eligible for the exemptions for compounded drugs under sections 503A and 503B of the FD&C Act. For additional information, you may wish to review FDA’s 2018 guidance document, “Mixing, Diluting, or Repackaging Biological Products Outside the Scope of an Approved Biologics License Application.” More specifically, the guidance sets forth conditions under which FDA does not intend to take action for certain violations of the FD&C Act when certain biological products are mixed, diluted, or repackaged in a manner not described in their approved labeling. Such conditions include, but are not limited to: (1) the label on the immediate container (primary packaging, e.g., the syringe) of mixed, diluted, or repackaged biological products including the dosage form; and (2) the mixed, diluted, or repackaged biological products are included on a report submitted to FDA each June and December identifying the drug products made by the outsourcing facility during the previous 6-month period.5Your repackaged and manufactured drug products are not exempted from the requirements of section 502(f)(1) of the FD&C Act by regulations issued by the FDA (see, e.g., 21 CFR 201.115).

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-62Product:DrugsRecipient:Dr. Robin C. CummingDirector, Radiopharmaceutical FacilityUCSF Radiopharmaceutical Facility185 Berry St. Ste. 350San Francisco,CA94107-9107United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-62April 13, 2026Dear Dr. Cumming:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, UCSF Radiopharmaceutical Facility, FEI 3005947301, at 185 Berry St. Ste. 350, San Francisco, from July 21 to 24, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for(b)(4)drugs. See Title 21 Code of Federal Regulations (CFR), part(b)(4)(21 CFR part(b)(4)).Because your methods, facilities, or controls for manufacturing, processing, packaging, or holding do not conform to CGMP, your(b)(4)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 August 14, 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 conduct adequate investigations and take appropriate corrective action when a failure of a production batch or any component of the batch failed to meet any of its specifications. (21 CFR (b)(4)).You manufacture(b)(4)drug products for(b)(4)administration. Your investigations into multiple failing sterility test results were inadequate. From 2022 to 2023, you initiated multiple investigations into sterility test failures for batches of(b)(4)injection and concluded that the probable root cause was contamination by the operator during sampling of the finished product vial. However, your investigations did not adequately support this root cause.For example, you opened a sterility failure investigation on April 3, 2023, after your analyst reported turbidity in the(b)(4)tube during incubation of your sterility sample for a batch of(b)(4)for injection. The recovered microorganism was identified as Bacillus species, a gram-positive spore-forming bacterium. Although no conclusive laboratory testing errors were found, your investigation postulated that the batch of(b)(4)was contaminated with the bacteria during sterility testing. You invalidated the sterility test result based on your flawed assumption that the organism also should have grown in the(b)(4)tube.Your firm failed to thoroughly evaluate whether this and other batch sterility test failures were caused by deficient aseptic manufacturing practices. Notably, your facility has experienced multiple recoveries of spore-forming organisms in sterility samples and production environments.You also investigated deviations from sterility test procedures in which your analyst discarded sterility samples for at least two(b)(4)batches on(b)(4)of incubation instead of day 14 as specified in USP . Your investigation stated that “it is highly unlikely that bacterial growths would occur on the 14th day of incubation. . . it is more likely that growth would appear before(b)(4)of testing.” However, your firm failed to note that slow growing or injured microorganisms may become detectable at the end of the incubation period.In your response, you indicate that the sterility failures were false positives and that root causes were described in reports for each incident. You also state that you updated your sample labeling and identification procedures to prevent discarding of sterility samples before the required incubation period.Your response is inadequate because there remains a lack of compelling evidence that the sterility failures were attributable to laboratory contamination. Your belief that(b)(4)media must both exhibit growth and if they do not, the test should be considered a false positive, fails to recognize that each medium possesses unique sensitivities, limitations, and growth capabilities. It is not appropriate to require growth in both media to establish a positive sterility failure for a sterile drug product batch.Furthermore, you did not sufficiently detail improvements to ensure that any future sterility positive is investigated properly and includes a comprehensive evaluation of potential manufacturing root causes. Your response also lacks adequate provisions for thoroughly reviewing your sterility test method to minimize potential for false positives.(b)(4)drug products have short expiry periods. Consequently,(b)(4)drug products are released and administered before the results of batch specific sterility testing and environmental monitoring (EM) are known. A robust ongoing EM program is essential to detect and respond to potential product contamination hazards in your manufacturing environment in a timely manner. Loss of environmental control in an aseptic manufacturing facility can ultimately pose a serious hazard to patients.In response to this letter, provide the following:A comprehensive assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-limit (OOL) and 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, corrective action and preventive action (CAPA) effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.A retrospective, independent review of all invalidated sterility test results for U.S. products for the last three years from the initial date of inspection and a report summarizing the findings of the analysis, including the following for each sterility test:o Determine whether the scientific justification and evidence relating to the invalidated sterility test result conclusively or inconclusively demonstrates causative laboratory error.o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.o For all sterility test results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include 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). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.o Also, the independent, third-party review and CAPA plan should identify significant improvements to your sterility testing method that will better ensure minimization of false positives.2. Your firm failed to follow written quality assurance procedures. (21 CFR (b)(4)).You lacked investigations or failed to ensure their timely completion.Your quality unit (QU) did not investigate adverse EM trends in your production areas as required by your standard operating procedure (SOP), SOP Q043 “Laminar Flow Hood Environmental Monitoring.” Specifically, in 2025, multiple EM results fell outside your action limit, but you failed to launch investigations to evaluate the adverse trends.Additionally, your procedure required investigations to be completed within(b)(4). However, our review found systemic failures to meet this timeframe. Numerous investigations remained open for more than a year. For example, two investigations remained open for over 1000 days.In your response, you acknowledge that you failed to follow your procedures for conducting environmental trending investigations. You state that you will perform retrospective investigations, create a new procedure for sterility failures and OOL investigations, and hire a Document Control Manager to oversee quality-related activities.Your response is inadequate because it fails to propose a comprehensive CAPA plan to address systemic deficiencies in your investigation program. Furthermore, it lacks an analysis of the quality assurance oversight failures that allowed these deficiencies to occur and persist.In response to this letter, provide the following:All EM data and personnel monitoring data from June 2023 to present (preferably in a spreadsheet tabular format). Include pertinent details such as sample location, date and time of collection, and colony forming unit (CFU) counts. For each recovery, describe the microbial differentiation performed by the laboratory (gram stain result, color, colony morphology description, genus or species-level identification).Your revised EM SOP detailing ISO 5(b)(4)monitoring during production and requiring identification of all isolates recovered during environmental and personnel monitoring. In addition to your current action limits, confirm that you have established an appropriate limit with associated procedures that ensure evaluation and investigation of such recoveries.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 control3. Procedures to ensure that all equipment is clean, suitable for its intended purposes, properly installed, maintained, and capable of repeatedly producing valid results, are not adequately followed. (21 CFR (b)(4)).Your procedures lack sufficient details to ensure that you adequately control and monitor your equipment for aseptic conditions. During our inspection, investigators observed your technician performing contact plating of the ISO 7 area of the(b)(4)immediately after disinfection of surfaces with(b)(4), a practice which is likely to inhibit microbial growth on the sampling media and produce false negative results. Additionally, you lacked EM of the ISO 5 area of the(b)(4)where aseptic manipulations of sterile(b)(4)drug products occur(b)(4). An effective environmental monitoring program, with samples that appropriately represent production conditions, is essential for detecting microbial contamination in critical areas and triggering prompt actions to maintain a state of control.In your response, you explain that contact plating is performed in the ISO 7 area to establish cleaning efficacy prior to production, and that you use air settle plates for EM in the ISO 7 area during production, as there are no opportunities to sample inside the(b)(4)after(b)(4). You commit to updating your disinfection procedures to include allowing disinfectants to fully dry before contact plating. You also commit to performing EM of the ISO 5 area where quality control and sterility samples are withdrawn from the finished product vial within the(b)(4).Your response is inadequate. Although spore-forming microbes were identified in several instances, you did not provide evidence that you comprehensively evaluated efficacy of disinfection procedures (e.g., sufficiency of methods, frequency of use, before handling of material transfers), in response to these events. Furthermore, you did not provide an assessment of how the lack of sufficient EM data within the(b)(4)ISO 5 and ISO 7 areas impacts the ability to meaningfully identify environmental trends as part of your root cause determination of sterility failures. Vigilant and responsive EM programs should be designed to provide meaningful information on the state of control of your aseptic processing environment and ancillary classified areas.In response to this letter, provide the following:Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.An independent assessment of your EM program including, but not limited to, establishing appropriate limits, sampling locations and frequencies (including in ISO 5 environment), investigating deviations, and trend analysis, and a comprehensive CAPA plan.A CAPA plan, based on the retrospective assessment of your cleaning and disinfection program, that includes appropriate remediations to your cleaning and disinfection processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning and disinfection. Describe improvements to your cleaning and disinfection program, including enhancements to cleaning effectiveness, improved ongoing verification of proper cleaning and disinfection execution for all products and equipment, and all other needed remediations.Guidance on (b)(4) DrugsSee FDA’s guidance document(b)(4)to help you meet the CGMP requirements when manufacturing(b)(4)drugs, at(b)(4). This guidance document also references FDA’s guidance documentSterile Drug Products Produced by Aseptic Processing—Current Good Manufacturing Practicewith additional concepts and expectations that may apply to(b)(4)drug manufacturing, at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/sterile-drug-products-produced-aseptic-processing-current-good-manufacturing-practice.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations to assist your firm in meeting CGMP requirements. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.Field Alert ReportingYour firm failed to submit Field Alert Reports to FDA in compliance with 21 C.F.R. 314.81(b)(1)(ii), as required by section 505(k) of the FD&C Act [21 U.S.C. 355(k)] upon discovery of a product quality defect. An applicant is required to submit, within three working days of receipt, information concerning any bacteriological contamination or any significant chemical, physical, or other change or deterioration in the distributed drug product, or any failure of one or more distributed batches of drug product to meet the specifications established for it in the application.The intent of the 21 CFR 314.81(b)(1) regulation is to establish an early warning system so that significant problems are brought to the Agency’s attention by applicant holders to prevent potential safety hazards from drug products already in distribution.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.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356C(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.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.1Specify 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 3005947301 and ATTN: Christopher Keating.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research________________1Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.

Delivery Method:Via Electronic Mail - Delivery and Read Receipt RequestedProduct:DrugsRecipient:James KrogmanPresident and CEOApollo Care, LLC3801 Mojave Court, Suite 101Columbia,MO65202-4042United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERWL # 715955February 2, 2026Dear Mr. Krogman:You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]1on September 14, 2017, and most recently on December 24, 2025. From March 10, 2025, to March 27, 2025, an FDA investigator inspected your facility, Apollo Care, LLC, located at 3801 Mojave Court, Suite 101, Columbia, MO 65202. During the inspection, the investigator noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.FDA issued a Form FDA 483 to your facility on March 27, 2025. FDA acknowledges that on April 15, 2025, your firm initiated a voluntary recall of Lot AC-016878 of Fentanyl 500mcg (2mcg/mL) and Ropivacaine HCl 250mg (0.1%) added to 250 mL, 0.9% Sodium Chloride Injection (For Epidural Use Only), within expiry, due to lack of sterility assurance. FDA also acknowledges receipt of your facility’s responses, dated April 17, 2025, June 10, 2025, and September 8, 2025. Based on this inspection, it appears you produced drugs that violate the FDCA.A. Compounded Drug Products under the FDCAUnder section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.B. Violations of the FDCAAdulterated Drug ProductsThe FDA investigator noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigator observed:1. You used sanitizing and sporicidal agents without providing adequate segregation in preventing contamination of in-process bulk drug solution. Specifically, your operator repeatedly sprayed a microfiber mop head with cleaning agents near the beaker containing non-sterile bulk drug solution that was loosely covered with aluminum foil in the ISO(b)(4)classified Hallway/Anteroom(b)(4)during area cleaning.2. You did not perform adequate product evaluation and take appropriate corrective action after microbial contamination was recovered within the ISO(b)(4)aseptic processing area. Instead, your firm approved and distributed drug products that were produced with 1 CFU recoveries found on ISO(b)(4)operator gowning gloves or sleeves.3. Your firm had foreign matter in the production area. Specifically, white fiber-like particles and debris were observed on the floor of the ISO(b)(4)Lab, where ISO(b)(4)laminar air flow hoods (LAFHs) are located, and the ISO(b)(4)Hallway/Anteroom(b)(4)following area cleaning that included equipment, ceilings, walls, and floors.4. Your firm had production areas or equipment that are difficult to clean or contain porous, particle-generating, or visibly dirty (e.g., rusty) equipment or surfaces (e.g., shelving, floors, walls, doors, ceilings). Specifically, wall panels overlaid on top of your ISO(b)(4)Hallway/Anteroom(b)(4)walls are not smooth. The textured surface is difficult to clean and may harbor contamination and generate particles when other materials come into contact with it.The FDA investigator also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:1. You failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).2. You failed to clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).3. Your firm’s aseptic processing areas are deficient regarding systems for maintaining any equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance,Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.It is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.C. Corrective ActionsWe have reviewed your facility’s responses to the Form FDA 483. We acknowledge your voluntary recall of Lot AC-016878 of Fentanyl 500mcg (2mcg/mL) and Ropivacaine HCl 250mg (0.1%) added to 250mL, 0.9% Sodium Chloride Injection (For Epidural Use Only), within expiry, due to lack of sterility assurance on April 15, 2025. We also acknowledge that you have contracted with third party consultants.Some of your corrective actions appear adequate. However, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:1. Regarding your smoke studies, we acknowledge you have initiated a revision of SOP CQI025Air Flow Pattern Visualizationand intended to conduct “formal static and dynamic smoke studies,” as stated in your June 10, 2025, response. Your September 8, 2025, response provided the protocol and report in Attachment 2 for the May 30, 2025, static smoke studies of the(b)(4)hoods, as part of CAPA C-25-013. However, the protocol and report did not specify what production equipment was included during testing. Without accompanying videos, we lack evidence to evaluate or verify whether you have resolved the issue of turbulence around production equipment such as the repeater pump. This turbulence will persist given that the repeater pump represents a substantial piece of equipment within a(b)(4)laminar flow hood. The report only provided a general statement indicating that “[t]hese static conditions were tested using an LFH [laminar flow hood] with all production materials inside but without any operational tasks being conducted.” Given that these hoods are located in(b)(4)separate rooms and serve distinct functions, each would require different equipment/materials that should have been specifically documented and evaluated.2. Regarding the bulk drug solution exposed to(b)(4)during(b)(4)cycles, we acknowledge you will no longer store the bulk solution in(b)(4)Lab(b)(4)during any(b)(4)cycle until you “can demonstrate there is no opportunity for(b)(4)ingress for the exposure concentration and hold duration.” You also engaged(b)(4), a(b)(4)equipment manufacturer, to assist in developing a(b)(4)penetration study protocol specific to the(b)(4)bag material and provided the results of the(b)(4)penetration study in your September 8, 2025, response. You stated this study utilized the(b)(4)exposure time, the(b)(4)exposure, and the(b)(4)bag to demonstrate compatibility. However, this study appeared to test empty bags and bags filled with(b)(4). It is not clear why you did not test bags filled with any bulk drug product, such as bulk Vancomycin solution, or whether you have conducted other container closure compatibility studies as part of the process validation of the drug products. Therefore, we lack data to fully evaluate whether the storage bags filled with your bulk drug solution are suitable for their intended use, including exposure to the(b)(4)used in your facility.Some of your corrective actions appear deficient:1. Regarding your firm’s cleaning of the ISO(b)(4)Hallway/Anteroom(b)(4)while non-sterile in-process bulk drug solution was stored there, your firm lacked assurance that the non-sterile in-process bulk drug solutions exposed to cleaning agents during this cleaning process do not alter the quality and purity of sterile compounded finished drug product produced from the exposed bulk drug solution.We acknowledge you will no longer store the bulk drug solution in the area while the cleaning or(b)(4)cycles are ongoing, and that SOP PRC004(b)(4)Processrequires disinfection and cleaning of any supplies that must be transferred from an unclassified space to an ISO environment. However, the effectiveness of using a(b)(4)lid to replace foil covering on the bulk drug solution beaker has not been demonstrated or validated through appropriate methods such as media fills. Additionally, your SOP and related batch record forms do not require or specify how to clean and/or disinfect the large beaker, including the new(b)(4)lid, containing non-sterile bulk drug solution formulated in ISO(b)(4)Storage/Anteroom(b)(4)when transferring from one area to another, particularly from Anteroom(b)(4)(ISO(b)(4)) to(b)(4)Lab (ISO(b)(4)).2. Regarding your firm’s use of the Hallway/Anteroom(b)(4)as both ISO(b)(4)and ISO(b)(4)space depending on whether you are conducting non-sterile or sterile activities, your response is inadequate because you provided contradictory and incomplete information on how the ISO(b)(4)Lab will be accessed. You continue using the Hallway/Anteroom(b)(4)as an entry to reach both non-sterile and sterile activities. In your June 10, 2025, follow-up response, you reiterated that “this hallway is used as an entry to both an ISO(b)(4)and an ISO(b)(4)space” and acknowledged the risk of using Hallway/Anteroom(b)(4)for an entry to both ISO(b)(4)and ISO(b)(4)rooms.The following responses appear to be contradictory:In your April 17, 2025, response to Observation 2A, you stated, “Per Change Control 25-CM-016, the non-sterile bulk drug solution is now moved from the ISO(b)(4)Anteroom into the ISO(b)(4)room after the technician completes full sterile gowning with sterile gloves and completes a thorough wipe down of the beaker with(b)(4). The ISO(b)(4)Anteroom is then subjected to a full cleaning.”In your June 10, 2025, response to Observation 2B, you stated, “Apollo Care requires that Anteroom(b)(4), or what was referred to as the hallway, to undergo a full clean prior to gowning and entry into the ISO(b)(4)environment. This requirement is in place when ISO(b)(4)activities have occurred immediately prior to the need for ISO(b)(4)entry.”In your response to Observation 2A, non-sterile bulk solution is moved into the ISO(b)(4)room before a full clean of Hallway/Anteroom(b)(4), while in your response to Observation 2B, you state that ISO(b)(4)access first requires sterile garbing and full cleaning of Hallway/Anteroom(b)(4).3. Regarding the EM (environmental monitoring) Alert and Action limits for personnel who access the ISO(b)(4)environment, we acknowledge you have defined(b)(4)and(b)(4)support compounding personnel in SOP EMP001(b)(4)Support Compounding Personnel Job Descriptionand SOP EMP002(b)(4)Support Compounding Personnel Job Description. You also updated SOP CQI003Clean Room Monitoringto define respective Alert and Action Limits for(b)(4)and(b)(4)support compounding personnel and require labeling “(b)(4)” for(b)(4)support compounding, and “(b)(4)” for(b)(4)support compounding on the Personnel Monitoring plates.However, you have not designated fields to document(b)(4)Support Compounding Personnel in related forms used in batch records, such as EM/PM form F002. For example, in the newest version of form F002, you still list “(b)(4)” and “(b)(4)” under each category of Direct Compounding Personnel and(b)(4)Support Compounding Personnel Contact Plates. Furthermore, the scope of the(b)(4)’s role during compounding operations has not been specified in batch record instructions, or in any updated written procedure.IMAGE (b)(4)4. Regarding white fiber-like particles and debris observed on the floor of the ISO(b)(4)Lab and the ISO(b)(4)Hallway/Anteroom(b)(4)following area cleaning, we acknowledge you rejected and destroyed the three affected lots. However, you have not provided any preventive actions regarding particles observed in the anteroom and in the cleanroom space where ISO(b)(4)LAFH used for production are located. In your June 10, 2025 response, the specification sheet from(b)(4). (refer to pages 95-96 of the Response Attachment 3) appeared to be a specification sheet for(b)(4)Mop, which is a different product line, with part numbers such as(b)(4), none of which appeared to match the mops being used at your firm.5. Regarding documentation of incomplete(b)(4)cycles, your SOP PRC002Facility Cleaning Procedureonly mandates documentation of “all executed facility cleanings.” However, the SOP fails to address the documentation requirements for incomplete(b)(4)cycles within individual rooms or incomplete “full clean” of the cleanroom suite (all(b)(4)rooms). CGMP regulations require comprehensive documentation of all CGMP activities, including those that are incomplete or terminated early. The SOP should be revised to include:Documentation requirements for all(b)(4)cycle attempts, whether completed or incomplete; andExplanation for partial or terminated cycles.6. Regarding the textured panels in your cleanroom suite, the manufacturer’s Technical Data sheet indicates the panels with textured or smooth surface have fire, mold and mildew resistance. However, there is no statement in the Technical Data sheet supporting the panel’s suitability for cleanroom applications, especially for pharmaceutical manufacturing facilities producing products intended to be sterile. Your response is inadequate because you have not evaluated the risk associated with using walls with textured surface in the cleanroom suite, nor have you developed a strategy to mitigate this risk. The photograph below depicts a section of the reconstructed area and wall in the ISO(b)(4)Hallway/Anteroom(b)(4)after the sink removal. The image shows difficult to clean areas such as textured wall surface and the gap in the molding.IMAGE (b)(4)In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b).]FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.D. ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations 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. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.All correspondence should refer to the Warning Letter Number above (# 715955) and include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.Sincerely,/S/Matthew J. LashActing DirectorOffice of Compounding Quality and ComplianceOffice of ComplianceCenter for Drug Evaluation and Research______________________1See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).