Delivery Method:Via EmailReference #:320-25-102Product:DrugsRecipient:Dr. K Suresh BabuHead – Corporate Quality and Regulatory AffairsHikal Limited72 - 82 / A Kiadb Industrial AreaJigani560105KarnatakaIndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-102August 20, 2025Dear Dr. Babu:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Hikal Limited, FEI 3003560263, at 72 - 82 / A Kiadb Industrial Area, Jigani, Karnataka, 560105, India, from February 3 to February 7, 2025.This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs 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 March 3, 2025 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigator observed specific deviations including, but not limited to, the following.1. Failure of your quality unit to ensure that quality-related complaints are investigated and resolved.Inadequate root cause determinationYour firm failed to adequately determine the root cause of approximately 22 complaints since 2020 related to metal contamination in your APIs. For example, your investigation into a complaint of black particles in(b)(4)API identified this was the first lot manufactured after a facility modification. You stated some particles may have not been removed completely during equipment cleaning but concluded “no exact root cause identified.” You also stated the particles were metallic in nature and were beyond the detection limit of your metal detector used to remove metallic particles in your API. However, our inspection determined you did not have a “(b)(4)” to adequately qualify your metal detector’s performance for(b)(4)particles, even though most of your manufacturing equipment is composed of(b)(4).We also note your investigation determined the contamination to be technically unavoidable particles. You referenced an industry standard on technically unavoidable particles in excipients as applicable. According to this guideline, technically unavoidable particles are inherent to the product and are not foreign contamination introduced by incomplete cleaning. Not only is this standard not applicable to your active ingredient manufacturing process, it also specifies that appropriate evaluation of materials of construction and particle mitigation strategies are required. Based on your investigation indicating a cleaning deficiency as a likely root cause, you do not have evidence to support that the metallic particles present are inherent to the manufacturing process. Your firm remains responsible for establishing and following adequate cleaning procedures.In your response, you state you have now obtained a “(b)(4)” and determined the metal detector is working satisfactorily. You then concluded there is “no impact on the performance of the metal detector.”Your response is inadequate. The current performance of the metal detector does not provide adequate assurance that previous API lots met established safety and quality standards. Also, your conclusion that your metal detector works adequately stands in contrast to customer complaints indicating contamination with metallic particles. Additionally, your investigation fails to adequately assess whether your manufacturing equipment’s design and materials are suitable for API production without introducing contamination risks. Furthermore, you lack an adequate evaluation of your cleaning procedures and in-process controls to prevent the presence of metal particles in your API.Ineffective corrective actions and preventive actions (CAPAs)Your firm failed to implement effective CAPAs after receiving numerous complaints of foreign material contamination of your APIs. For example, a customer reported foreign material contamination involving eight lots of(b)(4)API. Your investigation found CAPAs were implemented for similar complaints prior to the manufacture of the complaint lots. However, our inspection found approximately 28 additional complaints reporting foreign material contamination after you completed your investigation.Inadequate investigations can result in unidentified root causes, ineffective CAPAs, and recurring problems that compromise your ability to manufacture safe and effective APIs.We also note that during our review we found the risk assessment included in your complaint investigation is not scientifically sound, as you ranked this(b)(4)API complaint as an unlikely failure with the lowest probability of occurrence despite repeated similar complaints.In your response, you state you hired a third-party consultant to evaluate contamination, investigations, risk assessments, and CAPAs related to foreign material contamination.Your response is inadequate. You do not provide sufficient evidence of a comprehensive evaluation of potential contamination sources and process controls.In response to this letter, provide:An action plan and timelines for conducting full evaluation of retain samples for particulate contamination to determine the quality of all lots of drug product distributed to the United States that are within retest dating as of the date of this letter.A summary of all results obtained from evaluating retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality assurance unit oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An evaluation of the suitability of equipment including, but not limited to, metal detectors, for intended use, ensuring quality of input materials, determining the capability and reliability of each manufacturing process step and its controls, and vigilant ongoing monitoring of process performance and product quality.A remediation plan that details your impact assessment of previously distributed lots for foreign contamination when your equipment was not properly calibrated.A detailed assessment of your methodology for categorizing complaints into low, medium, and high-risk categories that accounts for complaint frequency and provides clear escalation triggers for repeated complaints of the same nature. Summarize how your revised risk categorization system will prevent and respond to foreign material contamination complaints. Provide your timeline for implementing the revised risk categorization system, including appropriate training.A comprehensive review and reclassification, if necessary, of all contamination-related complaints related to APIs within expiry using your revised methodology. Identify any additional corrective actions that should be implemented based on any revised risk categorization.2. Failure to have a system for evaluating suppliers of critical materials.Your firm's supplier qualification procedure stated corrective action is required when a supplier's rejection rate exceeds(b)(4)% during incoming inspection. However, it did not incorporate mechanisms for re-evaluation of an approved supplier when quality deficiencies or complaints are detected after initial qualification.This deficiency in your supplier qualification procedure allowed you to continue using materials from qualified suppliers after you determined their materials were found defective. For example, your firm received repeated customer complaints about particles in your APIs that you concluded most likely originated from your supplier of(b)(4)drums and lids. Despite notifying the supplier of these quality issues and continuing to receive customer complaints, your firm failed to implement timely corrective actions, such as qualifying alternate suppliers, enhancing supplier oversight, or discontinuing use of defective materials from this supplier.An adequate supplier qualification program includes ongoing monitoring of supplier performance beyond incoming inspection and prompt implementation of corrective actions when quality issues are identified at any point in the manufacturing process.In your response, you provide an updated supplier qualification procedure that accounts for quality issues identified during manufacturing and customer complaint investigations. You also state you have suspended the use of your drum supplier, and you are qualifying additional suppliers.Your response is inadequate. You do not provide quality data for the new supplier, which you state was providing(b)(4)% of your drums prior to the inspection. Furthermore, you lack a comprehensive root cause analysis of your supplier qualification system’s failure to identify and respond to ongoing quality issues.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, 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, comprehensive review of your material system to determine whether all suppliers of components, containers, and closures, are appropriately qualified; materials are of consistently acceptable quality; and appropriate expiration or retest dates are assigned. Based on this systemic review, provide a summary of a systemic CAPA that remediates your supplier qualification program and prevents use of unsuitable components, containers, and closures.A summary of quality metrics of your new supplier of(b)(4)drums and lids including, but not limited to, incoming inspection data for(b)(4)drums and lids, with acceptance/rejection rates, defect types, complaint frequencies, and trending analysis in the previous three years.Additional API CGMP GuidanceFDA considers the expectations outlined in ICH Q7 when determining whether APIs are manufactured in conformance with CGMP. See FDA’s guidance documentQ7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredientsfor guidance regarding CGMP for the manufacture of API at https://www.fda.gov/media/71518/download.CGMP Consultant RecommendedBased upon the nature of the 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.ConclusionThe deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.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 deviations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any deviations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any deviations.Failure to address any deviations may also result in the FDA refusing admission of articles manufactured at Hikal Limited, Jigani, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any 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 3003560263 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.

行政相对人名称四川宏康源药业有限公司行政相对人类别法人及非法人组织行政相对人代码(统一社会信用代码)91510181MA61T9YH7F法定代表人代世刚行政处罚决定书文号川药监罚决〔2025〕1038号 违法行为类型生产、销售假药违法事实2025年3月6日-7日期间，生产销售性状、薄层色谱不符合规定中药饮片降香伪品（批号：230301）55.50㎏，后召回33.5㎏，货值金额5944.50元，违法所得2148.25元。处罚依据《中华人民共和国药品管理法》第一百一十六条处罚类别罚款、没收违法所得、没收非法财物处罚内容1.没收违法生产的“降香”（批号：230301）33.50Kg；2.没收违法所得2148.25元；3.罚款300000元。 罚款金额（万元）30没收违法所得、没收非法财物的金额（万元）0.59445处罚决定日期2025年12月19日处罚机关四川省药品监督管理局处罚机关统一社会信用代码11510000MB1808933T

为加强药品质量监管，保障公众用药安全，湖南省药品监督管理局及长沙市市场监督管理局依据药品监督抽检计划，组织对辖区内生产、经营、使用的药品进行了抽查检验，检出不符合规定药品5批次。现将5批次不符合规定药品信息（见附件）予以通告。对上述不符合规定的药品，湖南省药品监督管理局和长沙市药品监督管理部门已依法进行了核查处置，要求相关企业和单位采取暂停销售使用、产品召回等风险控制措施，并督促其查明问题原因，制定落实整改措施，切实消除风险隐患。特此通告。附件：5批次不符合规定药品信息湖南省药品监督管理局2026年2月11日   （公开属性：主动公开）

 依据《国家药监局综合司关于加强医疗器械生产经营分级监管工作的指导意见》（药监综械管〔2022〕78号）和《辽宁省医疗器械生产分级监管实施细则》(辽药监告〔2023〕10号)，我局在全面梳理分析2025年全省医疗器械生产企业质量管理体系运行状况的基础上，结合质量监督抽查检验、不良事件监测、案件查办等情况，制定了《2026年度辽宁省医疗器械生产企业分级监管目录》，现予以发布。  特此公告。    辽宁省药品监督管理局   2026年2月11日

辽宁省药品监督管理局行政检查结果公示 序号：1企业名称沈阳义美医疗器械有限公司企业类型医疗器械生产企业检查时间2026年1月21日-2026年1月21日所在地市沈阳市检查依据《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》等法规规章和规范性文件检查事项医疗器械生产检查检查方式常规检查检查内容贯彻落实《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》情况存在问题在生产管理方面，存在生产记录中工艺参数记录不规范的问题。处理措施限期整改整改情况已按要求完成整改序号：2企业名称沈阳天航伟业机电设备安装工程有限公司企业类型医疗器械生产企业检查时间2026年1月29日-2026年1月30日所在地市沈阳市检查依据《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》等法规规章和规范性文件检查事项医疗器械生产检查检查方式常规检查检查内容贯彻落实《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》情况存在问题在人员机构方面，存在个别人员法规培训不完善的问题；在文件管理方面，存在原材料进货检验记录不规范的问题。处理措施限期整改整改情况已按要求完成整改序号：3企业名称沈阳上口义齿制作有限公司企业类型医疗器械生产企业检查时间2026年1月22日-2026年1月22日,2026年1月27日-2026年1月27日所在地市沈阳市检查依据《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》等法规规章和规范性文件检查事项医疗器械生产检查检查方式常规检查检查内容贯彻落实《医疗器械监督管理条例》《医疗器械生产监督管理办法》《医疗器械生产质量管理规范》情况存在问题在人员机构方面，存在个别人员法规培训不完善的问题；在生产管理方面，存在生产记录中工艺参数记录不规范的问题。处理措施限期整改整改情况已按要求完成整改

　　为做好医疗器械注册受理前技术问题咨询工作，指导行政相对人安排咨询时间，保证咨询工作质量，现就近期咨询工作安排通告如下:　　一、轮值部门时间安排：时间咨询部门2026年3月6日审评一部、审评二部、临床与生物统计一部2026年3月13日审评三部、审评四部、审评五部2026年3月20日审评六部、临床与生物统计二部、综合业务部2026年3月27日审评一部、审评二部、临床与生物统计一部2026年4月3日审评三部、审评四部、审评五部2026年4月10日审评六部、临床与生物统计二部、综合业务部2026年4月17日审评一部、审评二部、临床与生物统计一部2026年4月24日审评三部、审评四部、审评五部　　二、每个受理前技术问题咨询日各审评部、临床部、综合业务部可供预约的现场咨询号数量为20个，按照中心2025年12月23日发布的《关于调整医疗器械注册受理前技术问题咨询工作安排的通告》（2025年第30号）的要求申请和办理。未预约现场咨询或预约未成功的单位，可选择邮件方式提交咨询申请。各分中心咨询时间安排同器审中心，但不受轮值部门限制。　　咨询时间：工作日每周五下午1:30至4:30（法定节假日除外）,请申请人于下午3:00前取号。　　咨询地点：北京经济技术开发区广德大街22号院一区2号楼一层。国家药品监督管理局医疗器械技术审评中心2026年2月9日

为深入贯彻落实《国务院办公厅关于全面深化药品医疗器械监管改革促进医药产业高质量发展的意见》的精神，2025年，贵州省药品评价中心以提升医疗机构药物警戒能力为主线，持续完善监测报告体系，强化临床用药风险防控，推动药品安全治理向纵深发展，切实保障群众用药安全。全年工作围绕政策引领、风险预警、协同排查、技能提升、体系拓展五个方面展开，系统推进药物警戒体系建设。一、强化政策引领，系统部署集采品种风险监测2025年年初，省药品监督管理局、省卫生健康委员会、省医疗保障局联合印发《关于加强集采品种安全风险监测工作的通知》，明确以“四个最严”为导向，推动集采品种不良反应监测全覆盖，夯实全省药品安全风险防范体系。文件强调发挥“三医联动”机制优势，强化部门协同，突出对集采中选药品、中成药联盟采购品种及高值医用耗材等重点产品的安全性监测，筑牢集采产品质量安全底线。二、聚焦风险信号，联合发布药品使用风险提示针对监测中发现的某品种严重不良反应及临床不合理用药问题，省药品监督管理局与省卫生健康委员会联合下发风险提示通知，明确要求医疗机构加强合理用药管理、规范不良反应上报、强化人员培训。该通知以监测数据为依据，系统梳理超适用人群、配伍禁忌、输液过快等常见风险，为临床安全用药提供具体指引，体现了监测与监管的紧密衔接。三、深化“一体两翼”建设，协同高效排查产品风险我省黔东南州药品医疗器械不良反应监测中心在日常监测中发现某品种存在使用过程中的疑似质量问题风险，及时上报到省药品评价中心，随后对该品种组织进行抽检，最终该风险信号关闭。在本次事件中，医疗机构主动报告、监测机构及时响应、品种持有人积极配合调查，多方协同开展核实与抽检工作，充分彰显了持续提升“一体两翼”工作格局建设的有效性，为类似风险处置提供了参考。四、开展技能比武，激发医疗机构药物警戒内生动力2025年9月，省药品监督管理局、省卫生健康委员会联合举办“贵州省药物警戒技能大比武”活动，设置优秀报告、优秀课件及团体奖项，吸引全省监测机构与医疗机构相关专业技术人员积极参与。作为推动药物警戒体系建设的重要抓手，此次技能大比武不仅发掘出一批业务骨干和技术能手，为药物警戒队伍注入新活力，同时各单位分享了先进经验和创新做法，促进了全省药物警戒工作的协同发展，真正实现“以赛促学、以学促干、以干促效”。五、拓展监测网络，持续深化警戒体系建设2026年，省药品评价中心将继续贯彻落实国家关于深化药品医疗器械警戒制度建设的部署，计划在“十五五”期间开展药品、医疗器械警戒试点工作，持续完善“医疗机构-监测机构-持有人”协同机制，强化数据共享与风险会商，提升全省药械安全风险早发现、早预警、早处置能力，为公众用药用械安全提供更加坚实的技术支撑。贵州省药品评价中心将继续秉持“人民至上、生命至上”的理念，以高度的责任感和专业精神，持续推进药物警戒体系与能力现代化，全力守护全省人民群众健康安全。

自治区医疗保障局2026年2月10日

　　为深入贯彻落实中医药传承创新发展相关部署要求，牢牢守住中药质量安全底线，持续优化产业发展营商环境，2025年以来，市药品审查中心坚持监管与服务并重，夯实基础、精准施策，全力助推中药产业高质量发展。　　一是狠抓GMP检查，严守质量底线。始终将药品质量安全放在首位，严格落实药品生产质量管理规范检查要求，依托飞行检查、针对性检查等方式，加大检查深度，对存在弄虚作假、质量管控缺位等严重问题的企业，坚持零容忍，全面净化中药生产秩序，夯实产业发展安全根基。　　二是强化精准扶持，激活发展动能。聚焦企业发展需求，优化服务供给。针对中药新药落地、企业扩产升级等工作，指定专人对接，强化政策解读与技术指导；针对各类检查，深化跨部门联合，优化检查流程，提速响应与办理时间。　　三是深化调查研究，助力科学施策。常态化开展中药产业专题调研，针对中药企业发展现状、企业诉求与行业瓶颈组织骨干人员开展调查研究，通过实地走访、数据分析、总结归纳，形成详实调研成果，为中药科学监管建言献策。　　下一步，中心将持续拧紧监管责任链条，升级服务举措，以严管优服双向发力，护航我市中药产业行稳致远。