序号1企业名称国药控股丹东有限公司企业类型药品批发企业检查时间2026年3月24日-2026年3月26日所在地市丹东市检查依据《药品管理法》《麻醉药品和精神药品管理条例》《药品经营和使用质量监督管理办法》《药品经营质量管理规范》等法律法规、规范性文件检查事项药品经营检查检查方式常规检查检查内容贯彻执行《药品管理法》《麻醉药品和精神药品管理条例》《药品经营和使用质量监督管理办法》《药品经营质量管理规范》等法律法规、规范性文件情况。存在问题无处理措施无整改情况无序号2企业名称东港鸿庆大药房连锁有限公司企业类型药品零售连锁总部检查时间2026年3月31日-2026年4月3日所在地市丹东市检查依据《药品管理法》《药品经营和使用质量监督管理办法》《药品经营质量管理规范》等法律法规、规范性文件检查事项药品经营检查检查方式常规检查检查内容贯彻执行《药品管理法》《药品经营和使用质量监督管理办法》《药品经营质量管理规范》等法律法规、规范性文件情况。存在问题在培训方面，存在部分内容未纳入培训计划的问题；在储存方面，存在药品储存作业区内暂存生活用品的问题。 处理措施责令限期改正。 整改情况已按要求完成整改。

序号检查时间企业名称生产地址检查范围检查依据检查结论处理措施备注12026年4月30日宿州亿帆药业有限公司安徽省宿州经济开发区金江路北侧一般液态单元；膏霜乳液单元《化妆品监督管理条例》《化妆品生产质量管理规范》《化妆品生产质量管理规范检查要点及判定原则》《化妆品检查管理办法》等。基本符合限期整改无

序号检查时间企业名称生产地址检查依据检查范围检查结论处理措施备注12026.4.23-24奥丽雅日用化妆品（马鞍山）有限公司安徽省马鞍山市经济技术开发区《化妆品监督管理条例》《化妆品生产质量管理规范》《化妆品生产质量管理规范检查要点及判定原则》《化妆品检查管理办法》等。一般液态单元、膏霜乳液单元基本符合限期整改无

序号检查时间企业名称生产地址检查范围检查依据检查结论处理措施备注12026年4月1日安徽露凡西生物科技有限公司安徽省六安市高新技术产业开发区西片区平桥大道246号4#厂房气雾剂及有机溶剂单元《化妆品生产经营监督管理办法》《化妆品生产质量管理规范》《化妆品生产质量管理规范检查要点及判定原则》符合无无22026年3月30日至3月31日安徽德正堂药业集团有限公司安徽省六安市裕安区平桥高新工业集中区平桥大道（105国道）与长景路交叉口一般液态单元、膏霜乳液单元、蜡基单元（具备儿童护肤类、眼部护肤类化妆品生产条件）《化妆品生产经营监督管理办法》《化妆品生产质量管理规范》《化妆品生产质量管理规范检查要点及判定原则》符合无无

序号企业名称经营地址/ 仓库地址企业类型检查时间检查人员检查结果1安徽丽高医药有限公司经营地址:六安市叶集区皖西中路9号2栋1层、2层、3层仓库地址:六安市叶集区皖西中路9号1层、2层批发企业2026年4月14日罗梦婷、马丽、蔡启文基本符合要求2淮南仲德医药有限公司经营地址：安徽省淮南市经济技术开发区朝阳东路与建设路交叉口向北200米安徽永和药业有限公司院内办公楼三层仓库地址：安徽省淮南市经济技术开发区朝阳东路与建设路交叉口向北200米安徽永和药业有限公司院内仓库一层批发企业2026年3月31日-4月1日吴旭娟、高燕基本符合要求3安徽华源大众医药有限公司经营地址：安徽省淮南市寿县经济开发区(北区)东津大道与定湖大道交叉口西北侧1号办公楼2层、3层仓库地址：安徽省淮南市寿县经济开发区（北区）东津大道与定湖大道交叉口西北侧安徽华源中药科技股份有限公司院内1栋1层、2层批发企业2026年4月13日-4月14日李多福、吴旭娟、王秋立基本符合要求检查结果：1.符合要求；2.基本符合要求；3.不符合要求。

序号企业名称经营地址/仓库地址企业类型检查时间检查人员检查结果1安徽长生医药有限公司宿州市循环经济园区龙兴路/宿州市循环经济园区龙兴路507号院内西仓库药品批发企业2026.4.1-2刘丽、许婉如待整改后评定2宿州市亚泰医药有限公司安徽省宿州市纺织东路12号/安徽省宿州市埇桥区纺织东路12号院内仓库一层、二层、三层药品批发企业2026.4.14-15刘丽、许婉如待整改后评定3安徽恒邦医药销售有限公司安徽省宿州市砀山县经济开发区梨都东路682号（安徽微谷电子商务产业园内）2 号仓库二层/安徽省宿州市砀山县经济开发区梨都东路682号2号仓库一层西药品批发企业2026.4.14-15闫培、许珊珊待整改后评定4宿州市田丰医药有限公司宿州市开发区金海南路东侧办公楼1、2层/宿州市开发区金海南路东侧1号仓库1层药品批发企业2026.4.22刘丽、许婉如待整改后评定

序号企业名称经营地址/仓库地址企业类型检查时间检查结果1芜湖九州通医药销售有限公司芜湖市经济技术开发区万春路27号分拣车间药品批发企业2026年4月8日基本符合要求2芜湖上药医药有限公司芜湖经济技术开发区万春路37号生命健康城内（医药制造项目三号厂房）药品批发企业2026年4月21日基本符合要求3安徽明锐医疗器械销售有限公司芜湖市鸠江区南翔万商商贸物流城一区2#楼H1006、H1007、H1008药品批发企业2026年4月24日基本符合要求4安徽桂龙医药经营有限公司安徽省马鞍山市当涂县经济开发区红旗南路与明珠路交叉口药品批发企业2026年4月17日基本符合要求

经核查，张诗雷等13名执业药师注册单位与实际工作单位不一致，存在“挂证”行为。根据《执业药师职业资格制度规定》（国药监人2019〕 12号）第二十八条和《执业药师注册管理办法》（国药监〔2021〕36号）第三十四条之规定， 海南省药品监督管理局依法撤销张诗雷等13人的《执业药师注册证》， 三年内不予注册并将其个人不良信息记入全国执业药师注册管理信息系统。 特此通告。序号姓名执业药师资格证号执业药师注册证号执业单位备注1张诗雷02620251046000000042461226900070乐东华荣凤泉药行2刘丹20231002615000001292461226900264乐东振德堂保济大药房3徐双02620251043000000764461226900276乐东华健华荣永世大药房（个人独资）4韩慧萍02620251046000000013 2017026460262014460121001657462226900457乐东黎族自治县医药总公司尖峰医药经营部华荣连锁店5邢月丽ZY00261146461226900461乐东华健华荣健民大药房（个人独资）6吉洁20211002646000000427462225901609乐东华荣众欣大药房7陈金林02620251046000000589461226900603乐东大参林抱伦大药房（个人独资）8李佳洁02620251043000004274461226900301文昌博仁东兴药店9彭秀娥20231002643000001708461226900365文昌博仁新健利药店10陈丹20221102631000000737462226900352海南广安大药堂连锁经营有限公司文昌第二药品超市11冯红果2017026460262016460122001309461225901525临高县和舍镇振德堂益仁堂大药房12王海鸾02620241046000000541461226900089海南华建华荣大药房连锁有限公司琼中和平广和堂分店13郭晖虹2017026430262014430311003973462226040054海南菁华药品连锁经营有限公司那大维康分店

Delivery Method:Via Electronic Mail - Return Receipt Requested Reference #:320-26-72 Product:DrugsRecipient:Mr. Thomas E. Polen, Jr.Chairman, CEO and PresidentCareFusion 213, LLC1 Becton DriveFranklin Lakes,NJ07417-1880United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-72April 30, 2026Dear Mr. Polen:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, CareFusion 213, LLC (a wholly-owned subsidiary of Becton, Dickinson and Company (BD)), FEI 3004932373, at 1550 Northwestern Drive, El Paso, Texas, from October 15 to 24, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your November 17, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm manufactures sterile drug products for(b)(4), including(b)(4), which are used(b)(4).(b)(4)is also specifically labeled for use in(b)(4). Your manufacturing process includes sterilizing the drug solution in sealed(b)(4)ampoules. Some(b)(4)undergo(b)(4).Inadequate Complaint InvestigationsSince September 2023, your firm has received more than 2,500 customer complaints about your drug products including reports of foreign matter (e.g.,(b)(4)particles and suspected mold), missing components, empty(b)(4), and compromised package seals. Your investigations into these complaints were inadequate, as you repeatedly failed to conduct thorough investigations, adequately identify root causes, provide scientific rationale for your conclusions, and extend investigations to other potentially affected batches. As a result, your corrective actions and preventive actions (CAPAs) were ineffective.For example, your investigation into a complaint of black specks and possible mold on sterile(b)(4)was deficient. You concluded the most likely root cause was the unintentional introduction of particulate matter from the manufacturing environment, yet you failed to extend the investigation to other lots that were manufactured under the same conditions or on the same equipment. Additionally, your investigation did not sufficiently examine potential contributing factors such as facility and equipment cleaning and maintenance, and personnel practices. Your investigation concluded that “a project has been opened to further investigate the reported issue,” but you lacked evidence that the follow-up project was actually initiated.Furthermore, your investigation into a complaint identifying(b)(4)pieces, missing(b)(4), and illegible printing on your(b)(4)was also inadequate. You indicated that the probable root cause of(b)(4)pieces and missing(b)(4)was equipment vibrations during manufacturing, but you did not extend the investigation to other batches processed on the same equipment. Your investigation also did not address the illegible printing on the(b)(4)identified in the complaint.FDA investigators observed numerous other examples in which your firm failed to conduct thorough investigations related to complaints, including failing to follow investigation procedures, failing to extend investigations to other potentially impacted batches, and failing to conduct appropriate market action assessments.Inadequate Out-of-Specification (OOS) Investigations and CAPAYour OOS investigations and CAPA were deficient. For example,(b)(4)Lot(b)(4)failed a sterility test during stability testing. You initiated a recall and concluded that(b)(4)in the(b)(4)used to seal the(b)(4)caused the sterility failure. The(b)(4)created(b)(4)that compromised the sterile barrier. Your(b)(4)supplier informed you that(b)(4)are inherent and cannot be entirely eliminated, and you determined that you had no in-process inspection criteria for(b)(4)defects.Although your investigation examined other batches manufactured with the same lot of(b)(4)and identified(b)(4)in multiple batches, you failed to properly extend your investigation to batches manufactured with other lots of(b)(4)from the same supplier. Notably, the investigation failed to address the scope and severity of a container-closure integrity issue that led to non-sterility and a product recall. Your quality system did not ensure that systemic problems with both the(b)(4)material and your inspection process were addressed by a comprehensive CAPA.In your response, you state that you have engaged a consultant to perform a comprehensive review of your quality system, revised your standard operating procedures for complaint handling, implemented an enhanced training program for complaint investigators and quality personnel, and are conducting a retrospective review of past complaints. Regarding the(b)(4)sterility failure, you state that you extended your investigation to all(b)(4)lots, inspected retain samples, found additional(b)(4)but no sterility failures, and concluded the failure was isolated to the recalled lot.Your response is inadequate. You have not adequately explained how your quality unit failed in its oversight of numerous investigations associated with repeated and systemic product quality deficiencies that led to customer complaints. Your conclusion that the sterility failure was isolated to one incoming(b)(4)lot is contradicted by the supplier’s statements that(b)(4)are inherent to their process and cannot be eliminated. You do not sufficiently address how you will detect when this inherent material attribute causes breaches in container-closure integrity to ensure that defective units are not distributed.Regarding the recall, you performed your extended investigation only after FDA identified significant gaps in the original investigation. You do not discuss why you did not initially extend your investigation when you identified systemic issues with the packaging material.We note that your firm has a history of sterility-related quality issues including multiple recalls and Field Alert Reports. It is essential that you assure sterility of your(b)(4)products.To ensure proper root cause analysis and appropriate CAPA implementation, investigations must be thorough, well-documented, scientifically sound, and timely. Procedural updates and training alone do not address the systemic failures that allowed deficient investigations to persist undetected by quality unit oversight.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final quality unit decisions, and is fully supported by executive management.A comprehensive, independent retrospective review of all complaint investigations for the last three years from the initial date of inspection. In particular, this review should prioritize critical complaints relating to foreign contamination, container-closure integrity, non-integral products (e.g., missing(b)(4)), functionality problems, and potential sterility issues. Include the following independent assessment for each investigation:o Determine whether the scientific justification and evidence relating to the identified root cause(s) were adequately documented. Where a complaint was attributed to factors outside of the firm’s control (e.g., user error), assess the strength of this determination and whether it was based on conclusive or inconclusive information.o Determine whether relevant complaint samples were available and the extent of efforts to obtain the complaint sample from the complainant. If insufficient attempts were made, identify the root cause(s) for not adequately pursuing their return.o For all complaint investigations found by the retrospective review to be deficient, to have an inconclusive root cause, or to have no root cause identified, 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, OOS history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation and any identified CAPA (e.g., manufacturing operation improvements).o Identify any patterns or trends across complaints that may indicate systemic manufacturing, quality control, supplier qualification, or design issues requiring corrective action.o Based upon this independent review, provide a comprehensive assessment of your overall complaint handling program that identifies any deficiencies and corresponding CAPA.A comprehensive review and remediation plan for your OOS-result investigation systems. The CAPA should include but not be limited to addressing the following:o Quality unit oversight of laboratory investigationso Identification of adverse laboratory control trendso Resolution of causes of laboratory variationo Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequate scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediationsProvide a comprehensive, independent review of your process capability and quality performance, including:o Comprehensive identification of all defects encountered at each manufacturing process stage.o Classification of each identified defect by type, frequency (i.e., average, range), severity, and root cause(s).o Analysis of multi-year, longitudinal batch-to-batch trending data for each defect.o Actual in-process and finished product yield data for each batch.o Process capability index calculations for all critical manufacturing steps.o A thorough independent assessment of both sporadic (i.e., unexpected spikes) and average variability observed based upon detailed review of above items. Provide analytical findings, associated operational weaknesses and root causes, and potential remediation options.Your commitment to implement CAPA based on the above process performance analysis and to begin conducting annual capability analysis with quality oversight across all product lines.2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).Your firm lacked appropriate spore population verification on in-house prepared biological indicators (BIs) used in your(b)(4)sterilization(b)(4)process. You used these BIs for verifying sterilization effectiveness and as a batch release specification for(b)(4)drug products.You validated your method for preparing BIs for your(b)(4)process in 2015 and included a target specification for(b)(4)spores of(b)(4)colony forming units (CFU). However, you have failed to perform quantitative verification of the spore population for these BIs since the initial validation. Instead, your firm has relied on a combination of vendor certificates for the initial spore count, theoretical calculations, and qualitative (growth/no growth) testing after(b)(4)with the final prepared BIs to evaluate sterilization effectiveness. Your procedure for preparing BIs states that population verification is not required because the preparation method was validated. However, validation of a preparation method does not eliminate the need for ongoing verification.In your response, you state that you have subsequently performed verification studies on recent BI preparations, and you commit to implementing ongoing verification. You also state that there is no impact to finished products because your(b)(4)parameters are set to ensure the reproducibility of the(b)(4)process.Your response is inadequate because you did not assess the impact of the lack of quantitative verification of your BIs. Your assertion of(b)(4)process reproducibility assumes the BIs consistently contained adequate spore populations, which you have not demonstrated.Without quantitative verification, you cannot determine whether “no growth” results after(b)(4)are due to an effective sterilization cycle or are because the BIs are lacking sufficient viable spore population.In response to this letter, provide:A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.For any(b)(4)products that are not terminally sterilized by your company (or its contract facilities), explain whether you distribute these unsterilized products with the expectation that your customers will ultimately perform terminal sterilization of these batches.A comprehensive plan and timeline to transition all(b)(4)drug products to terminal sterilization. If your firm does not intend to transition all(b)(4)drug products to terminal sterilization, provide a detailed rationale justifying your scientific and public health basis. Also include a risk assessment that addresses your history of sterility-related quality issues.A comprehensive process description for all(b)(4)products your firm distributes. When describing each of the process options that your firm can use, detail whether the(b)(4)finished product is sterilized. For any process option that does not involve(b)(4)(including(b)(4)) prior to sterilization, comprehensively describe the(b)(4)steps that occur following the interim sterilization step. Also explain whether(b)(4)are sterilized, and if not, what your microbial bioburden specifications are for these parts and under what cleanroom conditions(b)(4)occurs.3. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment; and failed to perform operations within specifically defined areas of adequate size; and failed to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups (21 CFR 211.67(b) and 21 CFR 211.42(c)).During our inspection, we observed inadequate cleaning and inadequate contamination control throughout your manufacturing facility where sterile drug products are assembled and packaged.For example, our investigators found(b)(4)and(b)(4)inside your(b)(4)chambers which sterilize your drug product ampoules. During the inspection, your firm confirmed that the chamber cleaning procedure involved(b)(4)the(b)(4)chambers(b)(4)to remove(b)(4). However, we noted multiple instances of your operators’ failure to appropriately document(b)(4)during a period when multiple U.S. batches were being sterilized. Additionally, you did not test the(b)(4)used in your(b)(4)process for chemical or microbiological specifications. Unsuitable(b)(4)quality could introduce(b)(4),(b)(4), and bioburden – further compromising chamber cleanliness and sterilization efficacy.FDA investigators observed(b)(4)residue on air vents, walls, and equipment surfaces in your main production area, packaging lines, ampoule rinsing room, and equipment washroom, despite cleaning logs documenting these areas had been cleaned. FDA investigators also observed broken(b)(4)on(b)(4)with sterilized ampoules next to assembly lines where these ampoules are(b)(4).Your contamination control practices were also inadequate. FDA investigators observed personnel wearing face masks improperly in violation of your gowning procedures. Your quality notification QN 201162939 documented a bioburden excursion in non-sterile(b)(4)product showing(b)(4)CFU withStreptococcus pneumoniaeidentified, a significant opportunistic pathogen commonly found in the nose and throat.Multiple environmental monitoring (EM) excursions also occurred in your filling areas. These contamination control failures are particularly worrisome if your(b)(4)do not ultimately undergo terminal sterilization on the(b)(4), including the(b)(4). When terminal sterilization is not applied to the finished product, robust aseptic processing control becomes critical to ensuring product sterility.Notably, robust manufacturing design and control to prevent contamination also applies if(b)(4)are not intended to be sterile, when appropriate based on their indication. Such products must be free of microbes that may be objectionable in view of their intended use.See FDA’s guidance documentSterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practiceto help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.Your response states that you engaged an independent third-party expert to review and redesign your cleaning validation program and committed to implementing cleaning validation for equipment and product-contact surfaces. You identified the(b)(4)residue as(b)(4)used in certain(b)(4)and stated you evaluated chromatography data to confirm the absence of cross-contamination to other products. You conducted a risk assessment of your cleaning program and concluded that existing process controls at various manufacturing stages would detect and reject products containing residues, contaminants, or microorganisms beyond acceptable limits.Your response is inadequate. Your commitment to implement cleaning validation does not address products currently in distribution manufactured under the conditions documented during the inspection. Your conclusion that existing controls would robustly detect contamination is contradicted by the nature of the customer complaints received by your firm, particularly given the extent of contamination, debris, gowning violations, and EM excursions documented during the inspection. Additionally, your identification of the(b)(4)residue and review of chromatography data do not address why your cleaning procedures failed to prevent its accumulation.Inadequate removal of debris and residues from manufacturing equipment during cleaning can lead to contamination of drug products subsequently manufactured on the equipment. In addition, inadequate operational controls to prevent contamination can jeopardize patient safety by potentially compromising the sterility of products designed to(b)(4).In response to this letter, provide:A comprehensive, independent assessment of your bioburden control program for non-sterile components and finished drug products. This assessment should include:o Bioburden testing and trending data for each lot of incoming(b)(4)received over the last three years, including total aerobic microbial count (TAMC), total yeast and mold count (TYMC), as well as all identification testing performed and organisms detected.o Bioburden and sterility testing data for all finished product batches manufactured over the last three years, including all data obtained when testing in-process and finished product batch units, as well as complete microbial identification of all organisms detected.o A comprehensive review by the independent third party of all microbiological test results (TAMC, TYMC, sterility tests, and organism identifications) for the last three years, including any OOS results that were subsequently invalidated. For any invalidated OOS results, assess the adequacy of the scientific justification and evidence supporting the invalidation decision.o An independent third-party review of your laboratory’s microbiological methods. The review should determine whether the methods are scientifically sound and capable of reliably detecting, quantifying, and identifying any bioburden present in incoming(b)(4)and finished drug products.o A summary report of all bioburden and sterility data collected from the above assessments, including trend analysis, identification of any patterns or excursions, and corresponding CAPA to address any deficiencies identified.A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one product.A CAPA plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program including enhancements to cleaning effectiveness, improved ongoing verification of proper cleaning execution for all products and equipment, and all other needed remediations.Appropriate improvements to your cleaning validation program with special emphasis on incorporating conditions identified as worst case in your drug manufacturing operation. This should include but not be limited to identification and evaluation of all worst-case:o drugs with higher toxicitieso drugs with higher drug potencieso drugs of lower solubility in their cleaning solventso drugs with characteristics that make them difficult to cleano swabbing locations for areas that are most difficult to cleano maximum hold times before cleaningDescribe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.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, comprehensive review of your EM program to ensure vigilant, timely detection and response to potential product contamination hazards in your manufacturing environment. This assessment should include, but not be limited to:o establishing appropriate limitso sampling methodso sampling locations and frequencieso trend analysiso appropriate investigation of deviations and adverse trendso and a comprehensive CAPA plan based on the findings of the assessmentA procedure for your(b)(4)system monitoring that specifies routine microbial and chemical testing of(b)(4)to ensure its acceptability for use in each batch of drug products produced by your firm, as well as its use in sterilization processes.The current action/alert limits for total counts and objectionable organisms used for your(b)(4)system.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your(b)(4)system consistently produces(b)(4)meeting appropriate chemical and microbial limits for use in(b)(4)process.Assurance of Sterility – Terminal SterilizationIt should be noted that although the sterility test is a critical final quality control for(b)(4)finished products that purport to be sterile, it cannot be solely relied upon as justification to release each drug product batch. The sterility test is only the last in a series of design and control provisions intended to protect the consumer from distribution of an unsafe batch. Sample sizes for sterility testing are typically small compared to the total number of units in a batch and may not detect sporadic non-sterility. For example, a failure to consistently execute a terminal sterilization cycle of the finished product within its validated state, or a sporadic container-closure issue, may go undetected for substantial periods if your firm places too much reliance on the final quality control test for sterility to identify a sterility assurance problem. It is also essential to note that any positive sterility test result represents a serious CGMP issue that requires a comprehensive investigation into the cause and extent of the problem, and prompt review of the validated status of your terminal sterilization process.Repeat Observations at FacilityIn previous inspections occurring in 2023 and 2016, FDA has repeatedly cited similar CGMP observations. In 2016, FDA cited your firm for failure to perform adequate investigations of product failures. In 2023, FDA cited your firm for failure to ensure adequate laboratory controls and failure to maintain facilities in a good state of repair. The current inspection reveals these deficiencies have persisted or recurred, demonstrating that executive management oversight and control over the manufacture of drugs is inadequate.Quality Unit AuthoritySignificant findings in this letter indicate that your quality unit is not fully exercising its authority and/or responsibilities. Your firm must provide the quality unit with the appropriate authority and sufficient resources to carry out its responsibilities and consistently ensure drug quality.For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA’s guidances:Q8(R2) Pharmaceutical Developmentat https://www.fda.gov/media/71535/download,Q9(R1) Quality Risk Managementathttps://www.fda.gov/media/167721/download, andQ10 Pharmaceutical Quality Systemat https://www.fda.gov/media/71553/download.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3004932373 and ATTN: Bryce Hammer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-26-64Product:DrugsRecipient:Dr. Ram P. ChakrobortyPresident & Chief Executive OfficerAva Inc.7051 S. Adams St.Willowbrook,IL60527-7592United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-64April 14, 2026Dear Dr. Ram P. Chakroborty:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Ava Inc., FEI 3008736380, at 7051 S. Adams St., Willowbrook, IL, from October 6 to October 21, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals, Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211), and significant deviations from CGMP for active pharmaceutical ingredients (APIs).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drugs 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 12, 2025 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations and deviations including, but not limited to, the following.Finished Drug CGMP Violations1. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).Your firm lacked adequate system security and access controls over your laboratory equipment used to test drug products prior to release. For example, your firm utilized a common username and password to access high performance liquid chromatography (HPLC) equipment used for impurity testing of drug products. Additionally, analysts had administrator privileges to modify and delete data. Our investigators also found multiple deleted gas chromatography (GC) analytical sequences in the recycle bin, including sequences used for system suitability and stability analysis.In your response, you state your employee violated your procedure and training by deleting sequence files without informing the supervisor or quality assurance (QA). You also state a software update allowed users to bypass “User-Security Access Restrictions” and that you have disabled the automatic software update function. You also state that you have implemented security parameters to enhance access controls to electronic data files.Your response is inadequate. You do not provide adequate details of management oversight to ensure effectiveness of the corrective actions implemented. You also lack a comprehensive assessment of all electronic and paper-based documentation systems to ensure their adequacy.In response to this letter, provide:A complete, independent assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed corrective action and preventive action (CAPA) plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.A comprehensive, independent assessment of computer system security and integrity. Provide a report that identifies vulnerabilities in the design and controls and a thorough CAPA plan for each of your laboratory computer systems and that addresses the following elements:o A list of all hardware (both standalone and networked) and software used by your laboratory.o Identify and evaluate vulnerabilities in performance and security of all of these computer systems including, but not limited to, their configurations, administrative rights, password controls, audit trail capabilities and state of implementation for each system, qualification/validation status, deviation history, backup capabilities, network requirements, completeness of data records, suitability of current hardware/software for its intended use(s), change management, and management oversight.o Detail the associated user privileges for each system. Specify user roles and associated user privileges for all staff levels who have access to the laboratory computer system, and provide organizational affiliations, responsibilities, and titles. Clearly specify all staff who have administrator privileges. Fully describe how you will ensure segregation of firm personnel involved with laboratory testing from those with administrator rights. For all staff roles that are permitted to have administrative rights, specify the scope and type of privileges.o Assess each system to determine if unique usernames and passwords are used.o Evaluate policies and procedures regarding computers and data governance with special emphasis on audit trails, prohibiting data deletion, and appropriate modifications of results. Specify how your firm prevents data deletion and undocumented/inappropriate modifications of data. Also describe how you ensure original data and information are always preserved. Provide your procedures for audit trail review.o Provide requirements for data retention and backup for all laboratory systems.o Describe how you will ensure that all quality control (QC) tests are performed by an analyst and receive second-tier review from a separate qualified individual (e.g., lab manager). Provide related procedure(s).o Summarize your interim controls to assure reliable performance and security while your CAPA plan is being implemented.2. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).Your laboratory records did not include complete and accurate data to support the analyses performed. For example:The audit trail for the Fourier Transform Infrared (FTIR) spectroscopy equipment showed no activity from September 23 to 30, 2025. However, your testing records, including the FTIR daily usage log, showed drug testing was performed with this equipment during this time frame. Furthermore, your analyst stated your FTIR system frequently crashes.Our investigators found chromatograms for testing performed at HPLC location 61, which your analyst stated was used for trial injections, although your HPLC procedure had been updated in 2022 to remove the requirement to perform trial injections. For example, your analyst performed a trial injection of a sample of(b)(4)%(b)(4)topical solution(b)(4)impurity content at HPLC vial location(b)(4). The(b)(4)content result was(b)(4)parts per million (ppm) which met your specification of equal to or less than(b)(4)ppm. Your analyst then repeated the injection at vial location(b)(4)and obtained a result of less than(b)(4)ppm. Both results were within your acceptable specification range. However, the more favorable result was reported. Furthermore, your laboratory notebook contained no details of the sample preparation for the initial injection at location(b)(4).Our investigators found chromatograms for testing performed at GC location(b)(4), which your analyst stated was used for trial injections. For example, your analyst performed a trial injection of an in-process sample of(b)(4)%(b)(4)topical solution(b)(4)content determination at GC location(b)(4). The(b)(4)result was(b)(4)%, which exceeded the specification of(b)(4)to(b)(4)%. A second trial injection was performed with a result of(b)(4)%. Your analyst then repeated the injections using GC location(b)(4)and obtained a result of(b)(4)%, which was within your acceptable specification range. The favorable result was reported, and out-of-specification (OOS) results from the trial injections were not reported or investigated. Furthermore, your laboratory notebook contains no record of the sample preparations associated with the OOS results. We also note your GC procedure requires a trial injection to “be performed to ensure the system is equilibrated before beginning a sequence. The trial injection is only for information purposes and is not processed as a part of raw data.” It is particularly concerning that you included these unacceptable practices in written procedures, as they had the effect of directing staff to deviate from basic CGMP requirements.Your systematic use of trial injections indicates a fundamental lack of oversight of data integrity in your laboratory. This practice also enables performance of undocumented analytical work, justifying unfavorable results, and indicates your laboratory system is not under control.In your response, you state trial injections were performed to verify the condition of the system. Additionally, you state, “The Operator did not record the trial injection, nor did they inform their Supervisor nor QA, violating Company procedure and their training.” To correct gaps in your procedures related to trial injections and audit trail review, you conducted data integrity training and created a written procedure to outline general expectations on data integrity.Your response is inadequate. Your proposed corrective actions do not adequately address your practice of performing trial injections. The injection of trial samples is not acceptable, in part, because all data from analysis of product samples must be retained and reviewed. You generally reported trial injections when passing results were recorded and disregarded when less favorable or OOS results were obtained. Furthermore, you do not adequately address the capability of your system suitability to determine the readiness of the equipment for analysis.In response to this letter, provide:A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine where documentation practices are insufficient. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain contemporaneous, attributable, legible, complete, original, and accurate records throughout your operation.Describe your plans to prevent manipulation and enhance control of all CGMP records. Specifically, describe your reconciliation and integrity improvements for all CGMP records that may be in loose form or otherwise vulnerable to manipulation. Based on an independent review by a qualified consultant, provide a gap analysis and specific CAPA measures you will take to safeguard integrity of records (e.g., recording data in logbooks, pre-paginated documents, and validated electronic systems).3. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).Your quality unit (QU) did not provide adequate oversight for the manufacture, testing, and release of your drug products. For example:Analysts frequently conducted trial injections. This practice is not scientifically sound. (21 CFR 211.160(b)).Your QU failed to perform investigations into OOS results obtained during trial injections. (21 CFR 211.192)Your QU failed to establish a written procedure to review audit trails and raw analytical data captured by analytical instruments to ensure data reliability for batch release (21 CFR 211.160(a)).We also noted your procedure requires quality assurance personnel to have “unbiased responsibility, separate from quality control.” However, your quality control unit has performed the finished product quality assurance approval function since at least 2023.Your firm’s quality systems are inadequate. See FDA’s guidance document, as well as, for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-system and https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations, respectively.In your response, you state QC was signing as final approval “likely due to a temporary period of high turnover of these positions.” You also acknowledge observing entry errors or missing entries.Your response is inadequate. You lack a sufficient comprehensive evaluation of your quality unit’s capabilities to fulfill all required quality related functions.In response to this letter, provide:A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriateo Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decisiono Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productsA comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for products currently in the U.S. market and within expiry as of the date of this letter 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 OOS result:o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrate 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 OOS 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.A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include, but not be limited to, the following:o Quality unit oversight of laboratory investigationso Identification of adverse laboratory control trendso Resolution of causes of laboratory variationo Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequately scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediationsAPI CGMP DeviationFailure to maintain complete data derived from all laboratory tests conducted to ensure your API complies with established specifications and standards.Your firm did not include complete data to support the analysis performed. For example, your QC staff conducted API analysis at HPLC location(b)(4), which your analyst stated was designated for trial injections. In addition, chromatograms from trial injections were not saved in the analytical testing system or as part of your official batch record, creating opportunities to compromise the integrity of analytical data used for making batch release decisions. From October 12, 2023, to October 3, 2025, your system activity log listed approximately(b)(4)entries described as “instrument running sample from location(b)(4).”Furthermore, the audit trail for the FTIR spectroscopy equipment showed no activity from September 23 to 30, 2025. However, your testing records, including the FTIR daily usage log, showed you performed API testing with this equipment during this time frame on(b)(4)%(b)(4)API. Furthermore, your analyst stated your FTIR system frequently crashes.In your response, you indicate, “A test/trial injection was performed as needed to verify HPLC system conditioning. However, no documentation was performed for the trial/test runs.” You also state your procedures now outline general data integrity expectations including instructions on controlling and reviewing audit trails, and you have removed instructions to perform trial injections.Your response is inadequate. You fail to adequately address how the various issues associated with the unstable laboratory equipment will be handled by your deviation system in the future, and how you will ensure stability is restored only through appropriate systems suitability approaches. You lack an adequate retrospective review to determine the scope and impact of your data integrity issues throughout your facility. You also fail to provide a sufficient impact analysis of your past FTIR crashes.In response to this letter, provide:A comprehensive, independent review of all trial injections performed in the last five years for your API and finished drug testing. Include the initial results and all results that were used to release the API batches and finished drug lots. Indicate whether any of the affected batches remain in the market or were used to support a filing drug application. If used to support an application, notify our office at CDER-OC-OMQ-Communications@fda.hhs.gov.o As part of the comprehensive independent review by your third party (see Data Integrity Remediation paragraph below), note all results that were OOS from the trial injections and confirm whether an investigation was conducted at the time of testing. If not, perform a comprehensive investigation into the OOS result. At the time of the inspection, you had not conducted investigations into your practice of conducting trial injections. Therefore, provide your investigation into this practice and provide your CAPA to prevent its recurrence.CGMP Consultant RecommendedBased upon the nature of the violations and deviations we identified at your firm, you should engage 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.Data Integrity RemediationYour quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance documentData Integrity and Compliance With Drug CGMP: Questions and Answersfor guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers.We strongly recommend that you retain an independent third-party to assist in your remediation. In response to this letter, provide:A comprehensive, independent investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.o A comprehensive retrospective evaluation of the nature of the testing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).o A status report for any of the above activities already underway or completed.ConclusionThe violations and deviations cited in this letter are not intended to be an all-inclusive list of violations and deviations that exist at your facility. You are responsible for investigating and determining the causes of any violations and deviations and for preventing their recurrence or the occurrence of other violations and deviations.Correct any violations and deviations 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 and deviations may also prevent other Federal agencies from awarding contracts.Failure to address violations and deviations 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 and deviations 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 and deviations.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 days1. Specify what you have done to address any violations and deviations 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 3008736380 and ATTN: Matthew Jensen.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.