2025年 第44号　　根据国家药监局关于做好地方药品抽检相关工作部署要求，现发布2024年广东省药品监督抽检年报（见附件）。　　附件：2024年广东省药品监督抽检年报广东省药品监督管理局2025年5月29日附件2024年广东省药品监督抽检年报2024年，省药品监督管理局（以下简称"省药品监管局"）坚持以习近平新时代中国特色社会主义思想为指导，全面贯彻落实党的二十大及二十届三中全会精神，坚决执行省委、省政府和国家药品监督管理局有关部署，以“四个最严”要求为根本遵循，立足“守底线保安全、追高线促发展”工作定位，紧密结合我省医药产业实际，系统谋划、精准实施药品质量监督抽检工作。组织各地级以上市市场监督管理局（以下简称各地市局）与药品检验机构，对药品生产、流通、使用全链条开展穿透式监督抽检，形成“评估质量状况、严打违法违规、提升监管效能、防控风险隐患”的闭环管理体系，有力推动药品安全巩固提升行动走深走实，实现质量安全与产业高质量发展的动态平衡。2024年我省药品抽检结果显示，我省药品质量安全形势持续向好，总体处于稳中可控的良好态势。一、概述药品监督抽检是对上市后药品监管的重要技术手段，能够及时反映药品在生产、经营和使用过程中的质量状况，是发现药品质量风险评价药品质量的重要手段，是有效打击假冒伪劣药品保障公众用药安全的重要举措。2024年，结合我省药品产业规模、人口数量、临床用药以及药品质量状况的监管实际，省药品监管局进一步优化抽检计划，规范抽检管理，严格抽检处置，提升抽检效能。一是坚持服务大局，贯彻落实省政府关于做好“十大民生实事”相关工作部署，高质量完成2024年民生实事任务。二是坚持防控风险，聚焦社会舆论和人民群众关切、监管过程发现的风险隐患、上一年度抽检不合格等品种，着力排查风险隐患。三是坚持统筹兼顾，强化与国家药品抽检工作协同，健全完善目标统一、各有侧重、互为补充的抽检机制，织密、织牢药品抽检网络。全年共完成药品监督抽检15557批次，其中符合规定15501批次，不符合规定56批次，合格率99.6%。药品监督管理部门已要求相关企业和单位采取暂停销售使用、召回等风险控制措施并对不符合规定原因开展调查及整改，组织对相关企业和单位的涉嫌违法行为开展立案调查。二、抽检数据分析（一）抽样数据分析2024年全省药品监督抽检共抽样15557批，涉及3208个品种，涵盖化学药品、中成药、中药饮片、生物制品、药用原料/辅料等类别（见图1）。在经营、使用和生产环节分别抽取样品9768批次、3404批次和2385批次，涉及513家药品生产企业、3486家药品经营企业和1236家药品使用单位（见图2）。各地市抽样情况见图3。图1 各类样品抽样批次及占比图图2 生产、经营和使用环节抽样批次及被抽样企业数图3 2024年广东省药品抽检各地市抽样批次情况分布图（二）检验数据分析2024年广东省药品监督抽检共完成检验15557批次，其中化学药品7191批次，中成药6153批次，中药饮片2149批次、生物制品52批次、药用原料/辅料12批次。经检验，15501批次样品符合规定，56批次不符合规定；合格批次中含化学药品7184批次，中成药6141批次、中药饮片2112批次，生物制品52批次、药用原料/辅料12批次。1.化学药品2024年化学药品共抽检7191批次，其中生产环节1229批次、经营环节4039批次（含网络销售环节138批次）、使用环节1923批次。经检验，不符合规定样品7批次，在生产、经营和使用环节分别检出不符合规定样品1批次、5批次和1批次，分别占对应环节全部样品的0.08%、0.12%和0.05%（见图4）。图42024年化学药品各环节抽检信息示意图按剂型分析，2024年广东省药品抽检化学药品共涉及片剂、注射剂、胶囊剂、颗粒剂、口服溶液剂等剂型。共有4个剂型存在不符合规定样品，其中，片剂2批次、注射剂2批次、胶囊剂2批次、口服混悬剂1批次，分别占对应剂型全部样品的0.06%、0.11%、0.17%和1.12%（见图5）。图5化学药品各剂型（按抽样量排前15）检验信息示意图2.中成药2024年中成药共抽检6153批次，经检验，符合规定6141批次，不符合规定12批次。除执法抽检5批次外，在生产、经营、使用环节分别抽样699批次、4693批次（含网络销售环节278批次）和756批次，分别检出不符合规定样品1批次、6批次和2批次，占对应环节全部样品的0.14%、0.13%和0.26%（见图6）。图6中成药各抽样环节抽检信息示意图按剂型分析，2024年广东省药品抽检中成药共涉及片剂、颗粒剂、丸剂、胶囊剂、合剂等剂型，共有4个剂型存在不符合规定样品，其中，颗粒剂5批次、丸剂4批次、胶囊剂2批次和洗剂1批次，分别占对应剂型全部样品的0.29%、0.43%、0.25%和5.26%（见图7）。图7中成药各剂型（按抽样量排前15）检验信息示意图3.生物制品2024年生物制品共抽检52批次，其中生产、经营、使用环节分别抽取47批次、1批次和4批次（见图8）。剂型涉及注射剂、眼用制剂、凝胶剂。经检验，所检项目均符合规定，合格率为100%。图8生物制品各环节抽检信息示意图4.中药饮片抽检数据分析2024年中药饮片共抽检2149批次。除执法抽检1批次外，在生产、经营、使用环节分别抽样409批次、1018批次（含网络销售环节11批次）和721批次。经检验，符合规定2112批次，不符合规定37批次，在生产、经营和使用环节分别检出不符合规定样品3批次、17批次（含网络销售环节1批次）和17批次，分别占对应环节全部样品的0.73%、1.67%和2.36%（见图9）。图9中药饮片各抽样环节检验信息示意图按不符合规定项目分析，不符合规定项目包括性状、水分、含量测定、显微鉴别、杂质、总灰分、其他有机氯类农药残留量、金胺O、镁盐和铝盐，不符合规定样品数量依次为17批次、16批次、8批次、4批次、4批次、2批次、1批次、1批次、1批次，分别占全部不符合规定项目31.48%、29.63%、14.81%、7.41%、7.41%、3.70%、1.85%、1.85%和1.85%（见图10）。图102024年中药饮片抽检不符合规定项目分布图三、抽检工作成效（一）强化守土尽责，紧盯源头质量安全。坚持讲政治、顾大局，贯彻落实国家及省重大政策要求，聚焦广东省辖区“省管环节”药品生产及批发环节的药品质量安全，实施对重点企业、重点品种的抽检，切实把好源头质量安全关口。包括对在产的广东省药品上市许可持有人、生产企业、医疗机构制剂室，广东省药品上市许可持有人持有的国家集采中选药品，药品批发企业和零售连锁总部（2022年—2024年）等实施全面抽检。（二）强化问题导向，排查质量安全风险。坚持以排查防控质量风险为目标，增强抽检靶向性，及时发现药品质量安全风险。工作中做到“四聚焦”，一是聚焦监管需求；二是聚焦问题及风险品种；三是聚焦重点品种及重点地区，加强对注射剂和中药饮片抽检，对单体药店、社区卫生中心、卫生服务站、门诊部、个体诊所实施重点抽检；四是聚焦新业态、新问题，开展网络销售药品线上抽检。（三）强化风险管控，严管严控风险隐患。及时消除风险隐患，让监管跑在风险的前面。一是做好对抽检不符合规定或存在风险隐患产品的核查处置，监督指导相关企业深入排查原因，采取有效风险控制措施，严控质量安全风险。二是依法调查处置涉嫌存在的违法违规行为，符合立案条件的予以立案查处，涉嫌犯罪的，依法移送公安机关。三是做好药品抽检结果公示工作，完善抽检信息公开管理制度，发布8期药品抽检结果信息通告。四、结语 2024年广东省药品抽检工作顺利完成。抽检结果显示，我省药品质量持续处于较高水平，整体安全形势稳中向好。2025年是实施“十四五”规划收官之年，也是全面深化药品监管改革再出发的一年。省药品监管局将贯彻落实习近平总书记关于加强药品监管一系列重要指示精神，以落实省政府关于民生实事工作部署要求为牵引，全方位加强药品抽检组织管理，科学规范抽检、强化核查处置、深化改革创新、防范化解风险，筑牢药品安全底线，助推产业高质量发展，切实保障人民群众用药安全。

天津融志医疗科技有限公司报告，由于因升级后的产品不能保证与经注册的医疗器械产品技术要求完全相同，故生产商东洋纺株式会社对其生产的全自动尿有形成分分析仪Automated Urine Cell Analyzer（国械注进20182220196）主动召回。召回级别为三级召回。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

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-25-73Product:DrugsRecipient:Alex HuaSales DirectorZhejiang Easyclean Daily Chemical Co., Ltd501168, Dongrui 4th RoadXintang StreetXiaoshan QuHangzhou ShiZhejiang Sheng,311200ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-73May 14, 2025Dear Mr. Hua:Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our March 11, 2024 request, and subsequent correspondence, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Zhejiang Easyclean Daily Chemical Co., Ltd, FEI 3016734050, at No. 501-168, Dongrui 4th Road, Xintang Street, Xiaoshan District, Hangzhou.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request 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)).1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).Your firm manufacturers over-the-counter (OTC) drug products, including(b)(4)with the FDA. Your response to our request for records and other information under section 704(a)(4) indicated that you did not conduct adequate finished drug product testing on drug products shipped to the United States (U.S.) market. Specifically, you indicated that you did not perform testing to verify the quantity of the active ingredients before release. Without adequate testing, there is no scientific evidence that your drug product batches conform to appropriate specifications prior to release.In response to the letter, provide the following:A comprehensive assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods, used to analyze each lot of your 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.2. Your firm failed to establish an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).Your firm failed to establish an adequate stability program and determine appropriate expiration dates for the OTC drug products that you manufacture. For example, you assigned a(b)(4)expiry date to your drug products. The records and information you provided for stability studies include only three months of accelerated stability data and did not include ongoing or long-term stability data, as required under 21 CFR 211.166(b). In addition, your stability data does not include testing for the active ingredient. Therefore, the data does not demonstrate that the drug’s active ingredient is stable throughout its shelf life.In response to this letter, provide:A comprehensive assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.o Detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability program.3. 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).The batch records you provided lacked adequate production details, including but not limited to, product formulation, identity of major equipment, duration of execution of each significant step, and identification of person(s) performing each significant step in the drug manufacturing operation. Without adequate and complete batch records, you cannot assure the uniformity of your drug products from batch to batch. In addition, this may impact your ability to adequately investigate any product deviations and complaints.In response to this letter, provide the following: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 attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.Your master production and control records for your drug products, to demonstrate that they fully document each significant and validated manufacturing step.4. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).In your 704(a)(4) records request response, you indicated that no validation activities had been performed for your drug products, including(b)(4).Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and ensure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.See FDA’s guidance documentProcess Validation: General Principles and Practicesfor general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71021/download.In response to this letter, provide the following:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing PPQ for each of your marketed drug products.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to continue manufacturing and shipping drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. 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 inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA refusing admission of articles manufactured at Zhejiang Easyclean Daily Co., Ltd, 501 168 Dongrui 4th Road, Xintang Street into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3016734050 and ATTN: Marva Taylor.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCC:Zhanwei Li, Firm Contactmt20121221@gmail.com

Delivery Method:VIA UPSReference #:320-25-56Product:DrugsRecipient:Mr. Ye Lin ChairmanGeneral Manager, and OwnerHuangshi Hygienic Material Medicine Co., Ltd.386 Shenxia RoadHuangshi ShiHubei Sheng,435003ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-56March 24, 2025Dear Mr. Lin,The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Huangshi Hygienic Material Medicine Co., Ltd., FEI 3005543486, at 386 Shenxia Road, Huangshi, Hubei, 435003, from August 26 to 30, 2024.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 September 20, 2024 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 have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).Your firm failed to perform appropriate testing on your drug products prior to release for distribution. Your facility management stated to our investigator that testing for identity and strength of each active ingredient prior to release had not been performed for approximately(b)(4)batches manufactured for the U.S. market.Full release testing, including for identity, strength, and purity, must be performed prior to batch release and distribution. Without adequate finished product release testing, you do not have scientific evidence that each batch of drug product conforms to appropriate specifications before release.In your response, you state that exported products are manufactured using the same process and formulation as domestic products. As a result, the internal quality standards for export products are based on those for domestic sales products, which does not require testing for identity or quantity of active ingredients.Your response is inadequate. You state that your internal quality standards and operating procedures for export products will be revised to include the identity or quantity of active ingredients. Both identity and quantity of active ingredients testing are required to be performed prior to release. You fail to assess the risk of drugs products that were released to the U.S. market without adequate testing. In addition, you do not discuss your plan to perform validation (or verification, as appropriate) of your test methods.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 batch 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.2. Your firm failed to assure that the drug product bore an expiration date that was supported by appropriate stability testing (21 CFR 211.137(a)).Your firm failed to establish an adequate stability program and lacked chemical and microbial testing data to demonstrate that your over-the-counter (OTC) drug products will remain acceptable throughout their assigned expiry period.You assigned U.S. marketed product expiration dates based on your domestic (China) product stability testing. However, the formulations and components for products intended for the U.S. market differed from your domestic product formulations.In your response, you state you communicated with distributors of products marketed in the United States to request samples of each product for stability testing.Your response is inadequate. You do not provide sufficient information regarding the batches, formulation, analytical method, and testing interval for the remaining expiry period. We acknowledge that you have not shipped product to the U.S. market since(b)(4). However, your drug products in the U.S. market will expire by(b)(4). For products without appropriate stability studies, you lack sufficient scientific evidence to support that the drug products will meet established specifications and retain their quality attributes throughout their labeled expiry. Please refer to 21 CFR 211.166, “Stability testing,” for the requirements of stability testing.In response to this letter, provide:A comprehensive assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid. Include your plan to ensure appropriate procedures are in place regarding maintaining reserve samples as required under 21 CFR 211.170.o Detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability program.Provide interim measures to ensure that products currently in the U.S. market meet the required quality attributes.A comprehensive, independent assessment of your chemical and microbiological drug test methods to determine the suitability of the method. If verification or validation is needed, provide a plan and timeline for completion of the appropriate activity.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system audit1of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA refusing admission of articles manufactured at Huangshi Hygienic Material Medicine Co. Ltd., 386 Shenxia Road, Huangshi, Hubei, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3005543486 and ATTN: Marva Taylor.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCc: Mr. Sen Lin, Vice President of Operationslinsen@hswcpharma.com_______________________1i.e. Quality System, Facilities & Equipment System, Materials System, Production System, Packaging & Labeling System, and Laboratory Control System per FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations.

Delivery Method:VIA UPSReference #:320-25-75Product:DrugsRecipient:Daniel Ramirez, General ManagerDylan Kim, Vice President of R&DCTK OTC Laboratories LLC formerly FMK LABS, Inc.1690 N. Delilah StreetCorona,CA92879United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-75May 19, 2025Dear Mr. Ramirez and Mr. Kim:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, CTK OTC Laboratories LLC (formerly FMK LABS, Inc.), FEI 3014253278, at 1690 N Delilah St., Corona, California, from December 16 to 31, 2024.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your January 21, 2025 response to our Form FDA 483 in detail.During our inspection, our investigator 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 failed to conduct adequate investigations into out-of-specification (OOS) results. For example, an OOS for bulk base batch(b)(4), documented low potency for one of the active pharmaceutical ingredients (APIs). The corrective action was to re-mix the batch on November 15, 2024, “to make it more uniform.” Upon retesting the batch, it remained sub-potent.You then adjusted the potency by adding additional APIs and re-mixing the batch. The batch was retested, and the potency assay was found within specification. However, the root cause of the low potency was not determined. Moreover, the bulk base batch had a subsequent OOS result for high viscosity. You failed to investigate the viscosity OOS and the bulk base batch was released and further used to manufacture(b)(4)finished drug batches.(b)(4)of the finished drug batches were tested during stability and again were determined to fail with high viscosity. This failure was not investigated.You did not thoroughly investigate these unexplained discrepancies or identify failures in a drug product to meet any of its specifications. When an investigation was performed, it was inadequate as you failed to identify the root cause(s), implement appropriate corrective action and preventive action (CAPA), and expand the investigation to evaluate the impact on other batches or products.In your response, you commit to improve your investigation process. Your response is inadequate. You did not propose to perform any retrospective impact assessment of previously distributed drug products. As a manufacturer, you have a responsibility to fully investigate unexplained discrepancies and failures to assess impact to product quality.For more information about handling failing, OOS, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document:Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Productionat https://www.fda.gov/media/158416/download.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 (QU) oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.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 QU oversight of laboratory investigations.o Identification of adverse laboratory control trends.o Resolution of causes of laboratory variation.o Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identified.o Adequately scoping of each investigation and its CAPA.o Revised OOS investigation procedures with these and other remediations.2. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Inadequate Process ValidationYou manufacture over-the-counter (OTC) drug products, such as topical creams, including sunscreens. You failed to demonstrate you have adequately validated the manufacturing processes used to manufacture your OTC drug products. For example, you were unable to provide blend uniformity studies to demonstrate your mixing processes assure uniformity and homogeneity. Your lack of process validation is a likely contributing factor to your OOS results detailed earlier in this letter.While you commit to perform process validation for each product that you currently market, your response is inadequate. You did not include any further supporting documentation. Additionally, you did not provide a timeline for completing the validation of your processes and did not consider a retrospective impact assessment for previously distributed drug products.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluates batches to determine whether an initial state of control has been established.Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance for industry,Process Validation: General Principles and Practices, for general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.Inadequate Water System ValidationYour firm used water as a component in your OTC drug product manufacturing and equipment cleaning. However, you did not validate your water production process nor was routine maintenance performed on your water system as specified by your procedures. You did not adequately demonstrate that your water was suitable for its intended use, and, at a minimum, meets the(b)(4)Water United States Pharmacopoeia (USP) monograph and appropriate microbial limits. Additionally, your water system was not routinely sanitized. Furthermore, we noted that microbiological water samples demonstrated the presence of bacterial and fungal organisms. However, the samples were not further analyzed to identify any objectionable microorganisms.While you commit to perform validation of your water production process, your response is inadequate. For example, you did not provide a detailed remediation plan or timeline for implementation, nor did you consider retrospective testing of retained finished drug products that used water as a component.Water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. Routine monitoring of microbial counts and identity of contamination in the system is integral to ensuring oversight of ongoing state of control and suitability of water for use in pharmaceutical manufacturing operations.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing PPQ for each of your marketed drug products.PPQ protocols and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling, and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.A comprehensive remediation plan for the design, control, and maintenance of the water system.o A(b)(4)water system validation report. Also include the summary of any improvements made to system design and to the program for ongoing control and maintenance.Your total microbial count limits to monitor whether this system is producing water suitable for the intended uses for each of your products.A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug product batches currently within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.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 firm failed to demonstrate that your microbiological test methods were appropriate to assure that your product conforms to appropriate standards of identity, strength, quality, and purity. Specifically, you could not provide evidence of method suitability for microbiological testing performed at your facility. Additionally, you were unable to show that you performed growth promotion studies or negative control testing to support the release testing of your OTC drug products.In your response, you commit to “validate” your methods in accordance with USP requirements. However, your response is inadequate because you did not provide sufficient detail or adequate evidence of corrective actions (e.g., protocol or procedure). You did not provide a timeline for verification of the methods or describe your plans for testing in the interim. Furthermore, you did not address whether a retrospective impact assessment would be performed for previously distributed drug products that are still within expiry.The ability of microbial testing methods to detect objectionable microorganisms in the presence of each drug product must be established. Results generated using unverified or unvalidated methods may put consumers at risk.In response to this letter, provide:A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods, used to analyze each batch of your drug products before a batch 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.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPA before you pursue resolution of your firm’s compliance status with FDA. See FDA’s guidance for industry,Quality Systems Approach to Pharmaceutical CGMP Regulations, at https://www.fda.gov/media/71023/download.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/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.After you receive this letter, respond to this office in writing within 15 working days. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices, and/or submit a request to schedule an FDA inspection.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3014253278 and ATTN: Frank Wackes.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

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姓名违法企业组织机构代码法定代表人姓名主要违法事实行政处罚的种类和依据行政处罚的履行方式和期限做出处罚的机关名称和日期备注1桂药监生稽罚〔2025〕 8号广西联禾生生药业有限责任公司生产销售劣药九维鱼肝油（批号: 230803）案广西联禾生生药业有限责任公司91450100MABQ4JBL64张勇   联禾生生公司委托北海蓝海洋生物药业有限责任公司生产的九维鱼肝油（批号: 230803），经山东聊城市检验检测中心，检验项目【含量测定】维生素C标示量为72.8%(标准规定:含维生素C应不得低于标示量的90.0%)，不符合规定。结论:本品按《国家药品标准》化学药品地标升国标第十三册及第十六册检验上述项目，结果不符合规定。上述批次九维鱼肝油(批号:230803)符合《中华人民共和国药品管理法》第九十八条第三款第一项的情形，为劣药。　　　　本案共生产出成品九维鱼肝油（批号: 230803），规格:10mlx16支/盒，批准文号:国药准字H45021263)9082盒。其中入库9072盒，用于成品检验4盒、成品留样6盒，货值87187.20元。2023年9月8日销往江西康强医药有限公司9072盒，销售单价9.6元/盒，违法所得为87091.20元。　依据《中华人民共和国行政处罚法》第二十八条的规定，责令当事人立即改正上述违法行为，并依据《中华人民共和国药品管理法》第一百一十七条第一款的规定，给予以下行政处罚:1.没收劣药九维鱼肝油6盒;2.没收违法所得87091.20元(捌万柒仟零玖拾壹圆贰角);3.处违法生产药品货值金额(货值金额为87187.20元，不足十万元，按十万元计算)的2倍罚款，即200000.00(贰拾万圆)。以上罚没款合计:287091.20元(贰拾捌万柒仟零玖拾壹圆贰角)。主动履行2025/6/9广西壮族自治区药品监督管理局2025年5月26日

Delivery Method:VIA UPSReference #:320-25-65Product:DrugsRecipient:Mr. Peter M. HoffmanChief Operating OfficerCosco International, Inc.1633 Sands Pl SEMarietta,GA30067-8785United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-65April 14, 2025Dear Mr. Hoffman:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Cosco International Inc, FEI 3000220439, at 1633 Sands Pl SE. Marietta, from October 15th to 25th 2024.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).In addition, the drug products “(b)(4),” “Carpe ANTIPERSPIRANT FOOT LOTION,” and “Carpe ANTIPERSPIRANT HAND LOTION” are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of section 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d). Additionally, these products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of such products into interstate commerce is prohibited under sections 301(d) and (a) of the FD&C Act, 21 U.S.C. 331(d) and (a). These violations are described in more detail below.We have not received a response from your firm stating the actions you are taking to address the deficiencies identified during the inspection and cited on our Form FDA 483.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Lack of Process ValidationYou manufacture over-the-counter (OTC) drug products including topical drugs intended for wound treatment in children. You failed to adequately validate your manufacturing processes to demonstrate that your processes are reproducible and controlled to consistently yield drug products of uniform character and quality. For example, your OTC drug products, Berberex Wound Gel, Asystem Pain Roll On, Forticept Antimicrobial Gel, and Forticept Antiseptic Ear Flush, were manufactured without adequate process qualification studies.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA's guidance for industry,Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validationat https://www.fda.gov/media/71021/download.Lack of Cleaning ValidationYou failed to perform appropriate cleaning validation studies for non-dedicated equipment used to manufacture your OTC drug products. For example, you manufacture products on shared equipment using active ingredients such as Menthol, Benzalkonium Chloride, Lidocaine, or Ketoconazole, in addition to cosmetic products. You failed to demonstrate that your cleaning procedures can prevent potential cross-contamination between the various drug and cosmetic products mixed and filled on the same shared equipment.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing PPQ for each of the marketed drug products you produce.Process performance protocols and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling, and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.An assessment of each drug product process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes, will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.Timelines for completed PPQ for marketed drug products for which a state of control has not been adequately/fully established.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 cleaningIn addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.A summary of updated standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.2. Your firm failed to establish and follow an adequate written testing program designed to assess the stability characteristics of drug products (211.166(a)).Your firm did not have adequate stability data to demonstrate that the chemical and microbiological properties of your drug products met established specifications and remain acceptable throughout their labeled shelf-life. For example, you distributed drug products intended for wound treatment in children without conducting accelerated or long-term stability studies.Without appropriate stability studies, you lack adequate scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.In your response to this letter, provide:A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.o Detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability.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 (211.160(b)).You lacked appropriate sampling and testing to ensure the(b)(4)water used as a component in your drug products is suitable for the intended use, including in drug products intended for wound treatment in children. Specifically, you did not perform adequate testing for bacteria, fungi, and objectionable microorganisms on your(b)(4)water (e.g.,Burkholderia cepaciacomplex (BCC),Pseudomonas species, etc.). In addition, neither of your test methods have been validated to demonstrate that they are equal to or superior to the compendial methodology. For example, you used(b)(4), a(b)(4)based microbiological test method, but you did not demonstrate that it was equivalent to or better than USP(b)(4)water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. Routine and representative monitoring of microbial counts and identification of contamination in the system is integral to ensuring oversight of ongoing state of control and suitability of water for use in manufacturing operations.Inadequate design, control, and/or maintenance of(b)(4)water systems have led to contamination with BCC and other water-borne opportunistic pathogens. See FDA's guidance for industry,Microbiological Quality Considerations in Non-Sterile Drug Manufacturinghttps://www.fda.gov/media/152527/download.In response to this letter, provide:A comprehensive 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 procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.The current action/alert limits for total counts and objectionable organisms used for your(b)(4)water system. Ensure that the total count limits for your(b)(4)water are appropriately stringent in view of the intended use of each of the products produced by your firm.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the system consistently produces water that meets(b)(4)Water,(b)(4)monograph specifications and appropriate microbial limits.A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug product lots currently in U.S. distribution or within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.A comprehensive, independent assessment of your water system design, control, and maintenance.A(b)(4)water system validation report. Also include the summary of any improvements made to system design and to the program for ongoing control and maintenance.4. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure the following:Establishment of an adequate stability program (21 CFR 211.137).Establishment of adequate procedures for rejection or recertification of expired raw materials (21 CFR 211.87).Establishment of appropriate controls of computerized records and access permissions for authorized personnel (21 CFR 211.68(b)).Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.In your 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 appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.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.Also describe how top management supports quality assurance and reliable operations, including but not limited to timely provision of resources to proactively address emerging manufacturing/quality issues and to assure a continuing state of control.Unapproved New Drug Violations and Misbranding Drug Violations“(b)(4),” “Carpe ANTIPERSPIRANT FOOT LOTION,” and “Carpe ANTIPERSPIRANT HAND LOTION” are “drugs” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body.Examples from the “(b)(4),” “Carpe ANTIPERSPIRANT FOOT LOTION,” and “Carpe ANTIPERSPIRANT HAND LOTION” product labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products as drugs include, but may not be limited to, the following:(b)(4):“(b)(4)” [from the product label]Carpe ANTIPERSPIRANT FOOT LOTION:“Carpe . . . ANTIPERSPIRANT FOOT LOTION . . . CLINICALLY PROVEN TO REDUCE FOOT SWEAT . . . Directions . . . Wash and dry soles thoroughly before application . . . Apply a small, dime-sized amount of Carpe to soles . . . Rub Carpe into soles vigorously…” [from the product label]Carpe ANTIPERSPIRANT HAND LOTION:“Carpe . . . ANTIPERSPIRANT HAND LOTION . . . CLINICALLY PROVEN TO REDUCE HAND SWEAT . . . Directions . . . Wash and dry hands thoroughly before application . . . Apply a small, pea-sized amount of Carpe to palms . . . Rub palms together vigorously…” [from the product label]Based on the above labeling evidence, “(b)(4)” is intended for use as a skin protectant drug product and “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION” are intended for use as antiperspirant drug products. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these drug products identified above.Skin Protectant Drug ProductUnder section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription skin protectant such as “(b)(4),” in order to be GRASE and not classified as new drugs, the products must, among other things, conform to the conditions in the applicable OTC monograph, in this case, Over-the-Counter Monograph M016: Skin Protectant Drug Products for Over-the-Counter Human Use (hereafter referred to as “M016”).1However, “(b)(4)” does not conform to the conditions specified in M016 for the reasons described below.Specifically, the combination of active ingredients identified in the product label for “(b)(4)” does not conform to the conditions of use set forth in M016. For example, the product includes a combination of(b)(4)and(b)(4)as active ingredients in the same drug product. While each active ingredient is permitted by M016 individually at the listed concentration, the monograph does not permit this combination of active ingredients in a single drug product [see M016.20(a)].Thus, the “(b)(4)” product does not comply with the applicable conditions specified in M016 and has not otherwise been found GRASE.2Accordingly, this product is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which this product would be legally marketed without an approved application. Because there is no application in effect for this product, this product is an unapproved new drug.The introduction or delivery for introduction of this unapproved new drug product into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Antiperspirant Drug ProductsWith respect to nonprescription antiperspirant drug products such as “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION,” in order to be GRASE and not new drugs, the products must, among other things, conform to the conditions in the applicable OTC monograph Over-the-Counter Monograph M019: Antiperspirant Drug Products for Over-the-Counter Human Use (henceforth “M019”).1 However, “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION” do not conform to the conditions specified in M019 for the reasons described below.As labeled, “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION” have intended uses that are not permitted for antiperspirant drug products. For example, claims on these products for use as an antiperspirant on feet and hands, respectively, are not permitted by M019 or any other final administrative order in accordance with section 505G. M019 requires that the directions for use for antiperspirant products state “apply to underarms only” [see M019.50(d)].Thus, the “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION” products do not comply with the applicable conditions specified in M019 and have not otherwise been found GRASE.3 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no applications in effect for these products, these products are unapproved new drugs.The introduction or delivery for introduction of these unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Misbranded Drug ViolationsAdditionally, “(b)(4),” “Carpe ANTIPERSPIRANT FOOT LOTION,” and “Carpe ANTIPERSPIRANT HAND LOTION” are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).In addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.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 3000220439 and ATTN: Zachary Bogorad.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research/S/Tina SmithCaptain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and Research____________________1M016 and M019 reflect the conditions set forth in the relevant final orders established and in effect under section 505G; see Order IDs OTC000005 and OTC000015, respectively, available at FDA’s website OTC Monographs @ FDA, https://dps.fda.gov/omuf.2FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that the “(b)(4)” product is GRASE for use under the conditions prescribed, recommended, or suggested in its labeling, nor has FDA determined this drug product to be GRASE pursuant to an order issued under section 505G(b).3FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that the “Carpe ANTIPERSPIRANT FOOT LOTION” and “Carpe ANTIPERSPIRANT HAND LOTION” products are GRASE for use under the conditions prescribed, recommended, or suggested in their labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).

富士胶片和光纯耀（上海）化学有限公司报告，由于特定批号产品处于有效期后期时在低浓度区域的测定值存在偏高倾向，生产商富士胶片和光纯药株式会社 FUJIFILM Wako Pure Chemical Corporation对其生产的异常凝血酶原测定试剂盒（免疫荧光法）（国械注进20163402602）主动召回。召回级别为二级召回。具体型号、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　　2025年5月29日

强生（上海）医疗器材有限公司报告，由于特定批次产品中心孔偏移的原因，生产商辛迪思有限公司Synthes GmbH对其生产的空心钉系统Cannulated Screws System（国械注进20163131218）主动召回。召回级别为二级召回。具体型号、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　　2025年5月29日