山西佳瑞医药有限公司严重违反《药品经营质量管理规范》的规定，为防控药品质量风险，依据《中华人民共和国药品管理法》第九十九条和《药品检查管理办法（试行）》第六十一条规定，现决定对该企业采取暂停销售的风险控制措施。待企业整改结束，通过省局组织的现场检查后解除风险管控措施。山西省药品监督管理局2025年3月26日（主动公开）相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

近日，运城市食药安办召开全市药物警戒与药品检测工作推进会，总结回顾2024年全市药物警戒与药品检测工作，安排部署下一步重点任务。市综检中心相关负责人参加。会议强调，药物警戒与药品检测工作关乎广大人民群众的生命健康，是药品监管工作的重要组成部分。要提高政治站位，强化底线思维。切实增强做好药物警戒与药品检测工作的责任感和使命感，拓宽药品不良反应监测信息收集渠道，深化监测评价体系建设，全力筑牢药品安全防线；要开展专业培训，加大宣传力度。强化基层培训，提升监测人员专业素质和业务能力，打造专业化监测队伍，提升医疗机构上报能力，注重风险信号收集、预警，确保药械化不良反应能够及时、准确上报，通过各类宣传，提高公众意识和参与度；要加强部门协作，形成工作合力。将药物警戒与药品检测工作与日常监管、执法办案有机结合，构建共治共享格局，推动全市药物警戒与药品检测工作再上新台阶，为保障公众用药安全提供坚实保障。相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

行政相对人名称密山市民康大药房有限公司行政相对人代码(统一社会信用代码)91230382MA18Y6TU8F法定代表人李庆阳行政处罚决定书文号密市监处罚〔2025〕32号违法行为类型未从药品上市许可持有人或者具有药品生产、经营资格的企业购进药品的行为违法事实经查，当事人在密山市医院给父亲购买的4瓶复方丹参滴丸，2瓶当事人父亲食用了，剩余2瓶为当事人销售，上述药品为处方药，但未凭处方销售且未录入计算机医药管理系统（GSP）。上述药品购进价格25元/瓶，销售价格22元/瓶，销售数量2瓶，货值金额44元，违法所得0元。处罚依据《中华人民共和国药品管理法（2019修订）》 / 第一百二十九条违反本法规定，药品上市许可持有人、药品生产企业、药品经营企业或者医疗机构未从药品上市许可持有人或者具有药品生产、经营资格的企业购进药品的，责令改正，没收违法购进的药品和违法所得，并处违法购进药品货值金额二倍以上十倍以下的罚款；情节严重的，并处货值金额十倍以上三十倍以下的罚款，吊销药品批准证明文件、药品生产许可证、药品经营许可证或者医疗机构执业许可证；货值金额不足五万元的，按五万元计算。;《药品经营和使用质量监督管理办法》 / 第七十二条 / 第一项　　　　药品零售企业有以下情形之一的，由药品监督管理部门责令限期改正；逾期不改正的，处五千元以上五万元以下罚款；造成危害后果的，处五万元以上二十万元以下罚款：　　（一）未按规定凭处方销售处方药的；;《中华人民共和国药品管理法（2019修订）》 / 第一百二十六条除本法另有规定的情形外，药品上市许可持有人、药品生产企业、药品经营企业、药物非临床安全性评价研究机构、药物临床试验机构等未遵守药品生产质量管理规范、药品经营质量管理规范、药物非临床研究质量管理规范、药物临床试验质量管理规范等的，责令限期改正，给予警告；逾期不改正的，处十万元以上五十万元以下的罚款；情节严重的，处五十万元以上二百万元以下的罚款，责令停产停业整顿直至吊销药品批准证明文件、药品生产许可证、药品经营许可证等，药物非临床安全性评价研究机构、药物临床试验机构等五年内不得开展药物非临床安全性评价研究、药物临床试验，对法定代表人、主要负责人、直接负责的主管人员和其他责任人员，没收违法行为发生期间自本单位所获收入，并处所获收入百分之十以上百分之五十以下的罚款，十年直至终身禁止从事药品生产经营等活动。;《中华人民共和国行政处罚法（2021修订）》 / 第二十八条 / 第一款行政机关实施行政处罚时，应当责令当事人改正或者限期改正违法行为。;《中华人民共和国行政处罚法（2021修订）》 / 第五条 / 第二款设定和实施行政处罚必须以事实为依据，与违法行为的事实、性质、情节以及社会危害程度相当。处罚类别警告;罚款处罚内容责令密山市民康大药房有限公司立即改正违法行为并作出行政处罚如下：1.警告；2.罚款10000元。罚款金额（万元）1处罚决定日期2025-03-26处罚有效期2099-12-31公示截止期2028-03-26处罚机关鸡西市密山市市场监督管理局相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

黑龙江省华源医药股份有限公司销售假药“四味脾胃舒颗粒”（批号：230780)的行为违反了《中华人民共和国药品管理法》第九十八条第一款之规定，依据《黑龙江省药品行政处罚裁量基准清单（试行）》及《中华人民共和国药品管理法实施条例》第七十五条之规定进行处罚。相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

相关推荐CIO提供以下相关文库下载、合规服务以及线上培训课程学习。

Delivery Method:VIA UPSReference #:320-25-53Product:DrugsRecipient:Mr. Chenguang XuOwner & CEOYangzhou Sion Commodity Co., Ltd.No. 168 Longwang Road, Hangji Industrial ParkYangzhou ShiJiangsu Sheng,225111ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-53March 12, 2025Dear Mr. Xu:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Yangzhou Sion Commodity Co., Ltd., FEI 3011346498, at No. 168 Longwang Road, Hangji Industrial Park, Yangzhou, Jiangsu, from September 23 to 27, 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 October 18, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.CGMP ViolationsDuring our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).You manufacture over-the-counter (OTC) drug products including(b)(4). Your firm failed to test incoming components used in manufacturing your finished OTC drug products to determine identity, purity, strength, and quality, and your firm did not establish a vendor qualification program for your raw material suppliers.Your firm used results from your suppliers’ certificates of analysis (COAs) without establishing the reliability of your suppliers’ analyses through appropriate validation and without conducting at least one specific identity test on each incoming lot of components. You may not rely on your suppliers’ COA to verify the identity of your components.In previous correspondence on September 28, 2023, associated with an FDA records request under section 704(a)(4) of the act, your firm committed to performing independent testing, to include identity testing for each shipment of high-risk component, as required by 21 CFR 211.84 (d)(1) & (2), using equivalent or better methods to those in the United States Pharmacopeia (USP).However during the inspection, and contrary to previous commitments, your firm failed to demonstrate that you adequately tested each shipment of each lot of the incoming components at high-risk of(b)(4)contamination. These include, but are not limited to, testing of(b)(4)solution you used in manufacturing drug products to determine their appropriate identity. Identity testing for these and certain other high-risk drug components1include a limit test in the USP to ensure that the component meets the relevant safety limits for levels of(b)(4). Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in manufacture of your drug products.The use of ingredients contaminated with(b)(4)has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document(b)(4)to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for(b)(4)contamination at(b)(4).Additionally, you failed to perform identity testing on the component(b)(4)and lacked adequate impurities testing on(b)(4)before being used in manufacturing. Furthermore,(b)(4)was not adequately monitored for(b)(4).In your response on October 18, 2024, you indicate that you have updated your procedures to mandate the testing of identity and purity of active ingredients and the testing of identity of nonactive ingredients. Your response is inadequate because you did not address your plans for qualification of your component suppliers, did not address your previous commitments to perform identity testing on high-risk components, and failed to clarify whether your firm tested all lots of drug products that you distributed to the United States for risk of(b)(4). You also failed to adequately address quality attributes of your components.In response to this letter, provide:A commitment to provide(b)(4)test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of(b)(4).A full risk assessment for drug products that are within expiry which contain any ingredient at risk for(b)(4)contamination (including, but not limited to,(b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain(b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective action and preventive action (CAPA) that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of(b)(4)and certain additional high-risk components we note that this includes the performance of parts A, B, and C of the USP monograph.The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures, are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your(b)(4)system consistently produces(b)(4)that meets(b)(4)USP monograph specifications and appropriate microbial limits.2. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your QU did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to:Perform assay testing for the strength of the active ingredient in(b)(4)drug products (21 CFR 211.165(b)).Ensure an adequate stability program (including assessment of product potency over the shelf life) to support your claimed(b)(4)expiry for(b)(4)drug products (21 CFR 211.166).Ensure that personnel had adequate training and experience for the production and analysis of(b)(4)drug products (21 CFR 211.25(a)).Testing is essential to ensure that the drug products you manufacture conform to all pre-determined quality attributes appropriate for their intended use. Because you lacked adequate testing of each batch of your drug products, you do not know whether they conform to all appropriate finished product specifications and are suitable for release to consumers.You did not ensure that your QU implemented its basic functions. Your management should immediately and comprehensively assess your company’s manufacturing operations to ensure that your systems, processes, and products meet CGMP.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/media/71023/download.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 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 Performing a retrospective analysis of all batches shipped to the United States for the past 3 years to ensure product in U.S. commerce meets specifications for potency and purity. Your action plan to address any product quality or patient safety risks for batches of(b)(4)drug products in U.S. distribution, including potential customer notifications and recalls or market withdrawals.o A copy of the quality agreement with the contract testing laboratories used for finished product testing. Indicate where in this agreement specifies potency testing and provide documentation supporting that potency testing occurs before release of your(b)(4)drug product.o Justification for the potency discrepancy noted in your response pertaining to product retained testing. Your response demonstrated a(b)(4)potency specification (≤(b)(4)%) for retained(b)(4)drug products as opposed to your label claim of(b)(4)%(b)(4).3. 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 lacked complete and original data to support the analyses performed. For example:Your laboratory records included missing data. Furthermore, there were discrepancies between the original and re-written versions of testing records and COAs pertaining to active and non-active ingredients used in the manufacture of OTC drug products.Your firm did not retain original data to support testing of components used to manufacture OTC drug products for the U.S. market. During our inspection, you confirmed that original data, including balance printout slips,(b)(4)times,(b)(4), sample preparations, and equipment logs were not maintained.The use of correction fluid (white-out) was also observed to make corrections on paper records documenting microbial analyses of finished products and raw materials. These documentation practices raise concerns about the integrity, authenticity, and reliability of all your data, and quality of your drug products. Document control is essential to maintaining an adequate quality system.In your response, you acknowledge that “QA management did not have a sound understanding of CGMP requirements.” You also commit to performing retrospective testing of “materials,” and state that you have updated procedures and re-trained personnel. Your response is inadequate, as you fail to fully consider comprehensive data integrity (DI) remediation to address the gaps and uncertainties caused by a significant adverse pattern of data that was discarded, lost, or not recorded contemporaneously. Additionally, your response did not consider plans to assess your manufacturing operation’s documentation system to determine where they are insufficient.Reliability of data is fundamentally compromised when there is a failure to record or maintain complete and accurate records of test results, or conditions associated with all tests. Furthermore, the lack of reliable data compromises the quality unit’s (QU) ability to exercise its function of ensuring compliance to applicable standards.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 CGMPfor guidance on establishing and following CGMP compliant DI practices at https://www.fda.gov/media/119267/download.We acknowledge that you are using an independent third-party consultant to perform DI training. However, we strongly recommend that you retain an independent third-party qualified consultant to audit your operation and assist in your DI remediation to meet FDA requirements. In response to this letter, provide:A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of DI 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 DI lapses.o A comprehensive retrospective evaluation of the nature of the testing and manufacturing DI deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all DI 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 DI and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global CAPA 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 DI 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 DI 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 2 years, to assist in evaluating CAPA effectiveness after you have executed your DI 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 DI 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 cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed products offered for import into the United States from your firm on Import Alert 66-40 on January 31, 2025.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Yangzhou Sion Commodity Co., Ltd., No. 168 Longwang Road, Hangji Industrial Park, Yangzhou, Jiangsu 225111, China, 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 [or misbranded] 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 3011346498 and ATTN: Samina Khan, Compliance Officer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Researchcc. US AgentCharles ShenManton Business and Technology Services37 Winding Ridge, Oakland, NJ, 07436Email: cyshen@aol.com___________________1Components with higher risk of(b)(4)contamination compared to other drug components.

Delivery Method:VIA Electronic MailProduct:DrugsRecipient:Adedayo AkinbiFounder and CEOAnnovex Pharma, Inc.7403 Lockport PI, Suite C-DLorton,VA22079United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERWL # 698115March 5, 2025Dear Dr. Akinbi:You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]1on October 14, 2021, and most recently on November 22, 2024. From August 26, 2024, to September 6, 2024, FDA investigators inspected your facility, Annovex Pharma, Inc. located at 7403 Lockport PI, Suite C-D, Lorton, VA 22079. During the inspection, the investigators noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigators noted serious deficiencies in your practices for producing drug products which put patients at risk.FDA issued a Form FDA 483 to your facility on September 6, 2024. FDA acknowledges receipt of your facility’s response, dated September 25, 2024, October 24, 2024, November 27, 2024, and December 27, 2024. Based on this inspection, it appears you produced drugs that violate the FDCA.A. Compounded Drug Products under the FDCAUnder section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.2An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.For a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b), including the requirement to submit a report to FDA upon initially registering as an outsourcing facility, once in June of each year, and once in December of each year identifying the drug products compounded during the previous 6-month period (section 503B(b)(2) of the FDCA [21 U.S.C. §353b(b)(2)]) and the requirement to submit adverse event reports to FDA “in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations)” (section 503B(a)(1), (b)(5) of the FDCA [21 U.S.C. § 353b(a)(1), (b)(5)]).B. Failure to Meet the Conditions of Section 503BDuring the inspection, FDA investigators noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigators noted:1. Your facility failed to submit a report to FDA in June 2024 identifying the drug products that you compounded during the previous 6-month period, including Heparin 4 units/mL in 0.9% Sodium Chloride(b)(4)IV bag, Phenylephrine 100 mcg/ml in 0.9% Sodium Chloride Solution 10ml syringe, and Phenylephrine HCl 25 mg in 0.9% Sodium Chloride 250 mL Bag.2. Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations).3Specifically, your facility’s procedures for reporting adverse events are inadequate. For example, your documented procedures for reporting adverse events (1) do not include a definition of what constitutes a “serious” and “unexpected” adverse event (21 CFR 310.305(b)); (2) do not include a requirement to report each adverse drug experience received or otherwise obtained that is both serious and unexpected as soon as possible, but in no case later than 15 calendar days of initial receipt of the information (21 CFR 310.305(c)(1)(i)); (3) do not include a requirement to promptly investigate and submit a follow-up report regarding a serious, unexpected adverse event within 15 calendar days of receipt of new information or as requested by FDA (21 CFR 310.305(c)(2)); (4) do not include a requirement that the firm investigate four data elements when an adverse event report is received – Identifiable Patient, Identifiable Reporter, Suspect Drug Product, Serious Adverse Event (21 CFR 310.305(d)); and (5) do not provide that adverse events should be reported utilizing FDA’s Safety Reporting Portal (SRP) or Electronic Submission Gateway (ESG) (21 CFR 310.305(e)).Because your compounded drug products have not met all of the conditions of section 503B, they are not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.Specific violations are described below.C. Violations of the FDCAAdulterated Drug ProductsFDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigators observed that:1. Your media fills were not performed under the most challenging or stressful conditions. In addition, your firm continued to produce and distribute drug products intended to be sterile despite positive growth being identified in 10% of filled units during your January 2024 media fill. Your firm failed to investigate the positive growth and discarded all units that showed signs of microbial contamination. Therefore, there is a lack of assurance that your firm can aseptically produce drug products within your facility.2. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.FDA investigators also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:1. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).2. 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).3. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).4. 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)).Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance,Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.Unapproved New Drug ProductsYou do not have any FDA-approved applications on file for drug products that you compound.4Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. §§ 331(d)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.Misbranded Drug ProductsYou compound drug products that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FDCA.5The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Further, it is also a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.Failure to Report DrugsAs noted above, your facility failed to submit a report to FDA in June 2024 identifying the drug products that you compounded during the previous 6-month period (section 503B(b)(2) of the FDCA). The failure to report drugs by an entity that is registered with FDA in accordance with section 503B(b) is a prohibited act under section 301(ccc)(3) of the FDCA [21 U.S.C. § 331(ccc)(3)].D. Corrective ActionsWe have reviewed your facility’s responses to the Form FDA 483.Some of your corrective actions appear adequate; however, we cannot fully evaluate the adequacy of the following corrective actions due to lack of adequate supporting documentation: Regarding your smoke studies, we acknowledge your commitments, including your plan to perform updated dynamic smoke studies during your(b)(4)cleanroom certification; however, you have not provided sufficient supporting documentation for our review, such as your smoke study protocol.Some of your corrective actions appear deficient:1. Regarding your media fills, we acknowledge your commitments going forward and the revised procedures provided in your responses. However, we remain concerned with your firm’s failure to investigate the positive growth observed during your January 2024 media fill simulation. Any contaminated unit should be considered objectionable and investigated. The investigation should survey the possible causes of contamination and should assess the impact of products produced since the last successful media fill.In addition, your responses do not include data to adequately demonstrate a consistent ability to maintain aseptic operating conditions. During your latest media fill simulation, conducted in July 2024, you did not incubate all(b)(4)units, but instead only incubated(b)(4)randomly selected units. Your firm has provided no evidence that you have successfully performed additional media fill runs to ensure your aseptic processing operation is validated and your firm continues to produce via aseptic processing and distribute drug products intended to be sterile.2. Regarding your firm’s failure to provide our investigators with your 2023 media fill records due to technical issues, you provided a new procedure, SOP-0261 Retention of Records, which details document retention requirements; however, this procedure does not specify how and where documents will be retained or how these retained documents will be controlled. We acknowledge your statement that you have purchased a dedicated secure server system and that you have hired a validation consult to complete installation, operational, and performance qualification; however, you have not provided details on how you are currently retaining and securing documents while waiting for the server to be qualified. Complete and accurate records are necessary to ensure that manufacturing processes are consistently followed and reproducible. Additionally, incomplete manufacturing records deprive you of the ability to reliably conduct batch record review, adequately investigate deviations and batch failures, and to ensure a continued state of validation processes.3. Your firm provided several updated written procedures with your responses; however, they appear to be in draft form as the approval signature manifests are incomplete. Therefore, the effective date of these revised procedures cannot be verified.In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b).]Regarding issues related to the conditions of section 503B of the FDCA, some of your corrective actions appear adequate: You state that you are “implementing improved tracking and reporting systems to ensure that all compounded products are accurately and timely reported in future submissions.”In addition, regarding issues related to the conditions of section 503B of the FDCA, some of your corrective actions appear deficient: Your revised procedures for reporting adverse event reporting do not adequately address adverse event reporting. For example, your revised procedures do not include a requirement to promptly investigate and submit a follow-up report regarding a serious, unexpected adverse event within 15 calendar days of receipt of new information or as requested by FDA.Should you continue to compound and distribute drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.E. ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.Your response and any questions regarding the contents of this letter should be sent to compoundinginspections@fda.hhs.gov. In your response, refer to the Warning Letter Number above (# 698115) and include a subject line that clearly identifies the submission as a Response to Warning Letter.Sincerely,/S/F. Gail Bormel, JD, RPhDirectorOffice of Compounding Quality and ComplianceOffice of ComplianceCenter for Drug Evaluation and Research____________________1See Pub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).2We remind you that there are conditions, other than those discussed in this letter, that must be satisfied to qualify for the exemptions in section 503B of the FDCA.3For more information, see, FDA’s guidance, “Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act,” which can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM434188.pdf.4The specific products made by your firm are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.5Your compounded drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Kevin R. SayerCEO & PresidentDexcom, Inc.6340 Sequence DriveSan Diego,CA92121United Statesksayer@dexcom.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS# 700835March 4, 2025Dear Mr. Sayer:During inspections of your firms located in San Diego, CA on October 21, 2024, through November 7, 2024, and Mesa, AZ on June 10, 2024, through June 14, 2024, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the G6 and G7 continuous glucose monitors. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.These inspections revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,Code of Federal Regulations(CFR), Part 820. We received responses from Charles R. Donlon, Senior Vice President, Quality Assurance on July 9, 2024; October 9, 2024; December 3, 2024; January 7, 2025; and January 10, 2025, concerning our investigators’ observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that were issued to your firm on June 14, 2024, and November 7, 2024. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to establish procedures for monitoring and control of process parameters for a validated process, as required by 21 CFR 820.75(b).Specifically, your firm conducts functional acceptance testing,(b)(4), on your Dexcom G6 and G7 Continuous Glucose Monitoring Systems. This testing accepts or rejects the glucose sensors based on values of glucose sensitivity slope, accuracy in the presence of acetaminophen (G6 only), and low oxygen response (G6 only); however, your firm has not established procedures to adequately monitor and control the glucose and acetaminophen concentrations used during the(b)(4)process.For example,a. Our investigators observed your firm does not monitor the glucose concentration of the glucose test dishes throughout production runs which run for approximately(b)(4). The investigators also observed conditions which may cause fluctuation in concentration such as evaporation, carry over, and spillage.b. Your procedures require dish(b)(4)to have an acetaminophen concentration of(b)(4)mg/dL; however, your firm does not have requirements to monitor this concentration during manufacturing of your devices. Additionally, your firm does not conduct monitoring for acetaminophen bias for your G7 devices.We have reviewed your firm’s responses and determined they are not adequate. Your firm’s responses describe you have implemented(b)(4)and(b)(4)glucose concentration monitoring for each of your three manufacturing facilities for both G6 and G7 devices. Your responses also identify that your firm has implemented low O2 and acetaminophen testing across all Dexcom sensor manufacturing lines at your three manufacturing sites.In addition to these changes your firm conducted a health hazard assessment HHA-SD-24-045 provided in your December 3, 2024, response as attachment E. This HHA shows your firm calculated the probability of the hazardous condition occurring using the global code “(b)(4)” for all hazardous situations covered under the HHA. However, multiple hazardous situations are evaluated which are likely to have different frequencies of occurrence and impact on glucose reading accuracy. In response to this letter, please provide a justification for this hazard assessment method.In your firm’s December 3, 2024, response, you provided a “Acetaminophen Specification Assessment RPT-1005056” report (Attachment D) to support that your firm’s acetaminophen specification is associated with your(b)(4)testing. You provided the report to support your new specification that no less than(b)(4)mg/dL of acetaminophen concentration in dish(b)(4)is adequate to sufficiently challenge the sensor during(b)(4)testing. However, data in this report appears to be based on an allowable Maximum Interference Effect (MIE) of(b)(4)mg/dL of glucose equivalent as your(b)(4)acetaminophen acceptance criteria, and we are unable to determine, from your response, how this MIE was established. Further, an MIE of(b)(4)mg/dL is wider than the clinical interference performance with an MIE of(b)(4)mg/dL from the clinical interference study provided as part of DEN170088, assuming an interstitial fluid (ISF) acetaminophen concentration of(b)(4)mg/dL stated on your provided literature. Therefore, the Acetaminophen Specification Assessment RPT-1005056 report does not appear to show the established acetaminophen setpoint of(b)(4)mg/dL is adequate to show manufactured sensors will demonstrate the same clinical performance as established in the premarket clinical study. Additionally, please provide PTL-902020 and RPT-905004 in response to this letter.2. Failure to establish procedures to adequately validate a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a).For example,a. Your firm’s test method validation for the(b)(4)System is documented in Test Method Validation for(b)(4)System (PTL-902713, Rev. 001) and reported in(b)(4)Test Method Validation Report (RPT-904480, Rev. 001). The documents show your firm conducted this validation by testing(b)(4)sensors by(b)(4)operators and documented the results as pass/fail, rather than documenting the measured results. The test method validation does not support the method is capable for producing repeatable or reproducible results.b. During this inspection, your firm provided a memo stating the error in the glucose slope generated by the(b)(4)system is approximately(b)(4)based on the uncertainty in experimental conditions. Furthermore, the permissible deviation from linearity when calibrating the(b)(4)analyzer used to measure the concentration of the glucose solutions in the(b)(4)system is(b)(4). Your firm failed to incorporate this measurement uncertainty of your(b)(4)process into the acceptance criteria for slope to ensure that nonconforming sensors are not inadvertently accepted on the lower and/or upper bounds of the test.c. Your firm failed to validate the manufacturing specifications for the concentration of glucose in the dishes used as part of your(b)(4)test.We have reviewed your responses and cannot determine the adequacy of your response at this time. Your responses state your firm is investigating the variability in your(b)(4)test method and provided the results of(b)(4)testing which confirms variability in the test method. The responses state additional investigation and testing is needed to reduce the variability and provide target timeframes for test method development and process specification changes through May 2025. We request you provide ongoing updates to these activities through completion.Additionally, your firm’s responses reference the same HHA described in item 1 of this letter. See above for a description of our evaluation.3. Failure to adequately establish procedures for design input, as required by 21 CFR 820.30(c).For example,a. The special controls for integrated continuous glucose monitoring systems defined in 21 CFR 862.1355(b) apply to your G6 and G7 CGMs. Your design inputs do not clearly define all of these requirements to ensure appropriate design control activities can be conducted. Specifically, your firm has not defined appropriate design input requirements for manufacturing controls and acceptance criteria for your(b)(4)system for slope and mean absolute relative distance (MARD).b. The predicted initial and finalin vivosensitivities of the glucose sensors (M0 and Mf, respectively) for the Dexcom G6 and Dexcom G7 CGM Systems are calculated usingin vitroslope measurements obtained through the(b)(4)system. Your firm documented design input for initial glucose sensor sensitivity; however, your firm failed to document requirements for the expected 10.5-day lifetime of the devices.We have reviewed your response and determined it is inadequate. Your firm’s response acknowledges your firm’s failure to adequately document the special control requirements as design inputs for the G6 and G7 CGMs. We acknowledge your firm has updated your primary design input documents to reference these special controls more explicitly. Your firm’s response commits to fully developing trace matrices for application of the special controls through CAPA-000464. We request you continue to provide updates to this CAPA through completion and include the established trace matrices when finalized.Your response states you have changed the(b)(4)MARD specification to(b)(4)% for both the G6 and G7 based on specification associated with the pivotal clinical study for the G6. However, your response does not adequately support the use of the same data from the G6 pivotal study to support the G7 device because the two sensors use different glucose algorithms which can impact the sensitivity to MARD. Additionally, only specifying the upper limit of MARD could result in all commercial sensors being released with borderline acceptable MARD. The clinical sensors’ MARD followed a certain distribution with only(b)(4)% as the extreme case from a few sensors. CGM sensors exhibit varying degree of clinical accuracy and MARD is an important parameter to ensure sensor accuracy. Therefore, a single parameter of maximum MARD is inadequate to ensure the labeled clinical performance. Additional parameters are needed to ensure that the mean/median MARD and standard deviation of commercial production is representative of the clinical performance as claimed in the premarket submission.Your response states you have established a new specification for Mo and Mf to be(b)(4)% based on data from numerical simulation studies. Your response states you have also initiated(b)(4)testing as of December 1, 2024, for your chemical formulation qualification (CFQ) and will be implementing sensor lot acceptance testing upon implementation of the(b)(4)Testing. We acknowledge your response states you will continue to evaluate enhancements to your test and requirements for sensitivity. However, as your firm has not been routinely collecting Mf data during production or during your pivotal studies, we remain concerned you do not have necessary data to support the basis for your new Mo and Mf specifications. In your response to this letter, please describe what specific actions your firm is planning to further evaluate and validate this specification.4. Failure to establish procedures for design changes, as required by 21 CFR 820.30(i).Specifically, your firm conducted a design change to a component used in the resistance layer of your sensors from(b)(4)to(b)(4). This change is a significant change and your firm failed to adequately evaluate and validate this change. Your firm conducted a clinical study ((b)(4)) to determine the equivalence of these two components; this study resulted in determining your primary endpoints were not met. You conducted additionalin vivostudies to attempt to further characterize the equivalence of these components; however, data from TDR-1000254 shows(b)(4)performs worse than(b)(4)for accuracy. Your firm began commercial manufacturing of Dexcom G7 CGMs with(b)(4)on(b)(4).We have reviewed your response and determined it is inadequate. In response to this observation your firm provided new testing, including Sensor Level Performance Equivalency of(b)(4)and(b)(4). Section 5.5 Glucose Sensitivity shows the standard deviation (SD) of(b)(4)glucose sensitivity is twofold that of(b)(4). This indicates significant variation in the clinical performance of sensors manufactured using(b)(4). Your response does not appear to include evidence to support sensors containing(b)(4)perform as claimed in the G7 original 510(k) K213919 where the pivotal clinical study used exclusively(b)(4)sensors.Additionally, your response states your firm has ceased commercial distribution of G7 sensors containing(b)(4); however, it does not address G6 sensors containing(b)(4). We request you provide information on how you will address any remaining sensors containing(b)(4)in commercial distribution.5. Failure to adequately establish procedures for design output, as required by 21 CFR 820.30(d).Specifically, your firm failed to establish adequate specifications for(b)(4)and(b)(4)of the sensor coating used in the manufacture of your G6 and G7 CGM devices. Your firm conducts in-process sampling of(b)(4)sensors and has acceptance criteria for an average thickness across the(b)(4)sensors; however, you have not established criteria for individual sensors.We have reviewed your response and cannot determine its adequacy at this time. Your response includes records showing you have not established CFQ and in-process acceptance criteria for thickness of the(b)(4)and(b)(4)of your sensors. We acknowledge your response states additional analysis of the ranges for this thickness specification are ongoing. We request you continue to provide updates into this analysis as your corrective actions progress.6. Failure to establish adequate procedures for design validation to ensure that devices conform to defined user needs and intended uses, as required by 21 CFR 820.30(g).Specifically, your firm failed to establish procedures for adequate risk analysis for your G6 and G7 CGM devices. For example, your hazard analyses for your G6 and G7 devices (RA-000258 Rev. 033 and RA-000548 Rev. 41, respectively) do not address hazards and risks associated with the use of your device with automated insulin dosing (AID) systems which are commonly used with your G6 and G7 CGM devices.We have reviewed your responses and cannot determine the adequacy at this time. Your responses provide records showing you have updated your various risk documents to include assessments of hazards and risks associated with the use of your devices with AID systems. We acknowledge your response states you are working with your AID pump partners to better inform this analysis and expect additional complaint data to inform this activity through March 2025 and plan for an update to the new AID Interoperability System Hazard Analysis, RA-1000096 by June 2025. We request you continue to provide updates in response to this letter.7. Failure to establish adequate procedures for corrective and preventive actions, as required by 21 CFR 820.100(a).For example, your firm initiated CAPA-000426 on April 19, 2024, after identifying a dissolved oxygen content in(b)(4)for the G6 was outside of specification. This CAPA investigation determined your firm was not consistently monitoring or recording the values of dissolved oxygen, notifying management of out of specification results, or consistently scrapping affected sensors when identified. The CAPA also found this deficiency was consistent across both your San Diego, CA and Mesa, AZ facilities. In your CAPA investigation your firm limited your evaluation to(b)(4)lots of G6 sensors potentially impacted by the deficiency, despite finding all lots may have been potentially impacted.We have reviewed your firm’s response and determined it is inadequate. Your firm’s response states you have now reviewed the DHRs for all G6 products manufactured in San Diego, CA and Mesa, AZ for the last(b)(4)and conducted a review of research studies which you state supports your firm’s assessment that no further action for impacted product is necessary. However, your response does not provide the support documentation of these reported reviews. Additionally, your firm’s response states your firm has revaluated the associated HHA (HHA-MA-24-002) and concluded that the residual risks are acceptable. The Benefit-Risk Analysis section of the HHA states that “(b)(4).” The HHA also references a publication (Facchinetti, A., Del Favero, S., Sparacino, G., & Cobelli, C. (2016). Modeling Transient Disconnections and Compression Artifacts of Continuous Glucose Sensors. Diabetes Technology & Therapeutics, 18(4), 264–272) based on clinical data extracted from the 2011 Dexcom G4 Platinum CGM pivotal study and concluded that the median ((b)(4)) percentiles) duration of a compression artifact is(b)(4)and therefore potential of a hyperglycemic event is minimal. However, we do not agree with your rationale that your algorithm provides adequate mitigation for low oxygen (compression) events by blanking sensor data or providing low glucose alarms. A hypoxic environment due to compression may develop slowly and, in many cases, will not result in either data blanking or a low glucose alarm. As presented in your referenced literature, the median ((b)(4)) bias during compression events is(b)(4)mg/dL, which means that these events do not result in data blanking and the magnitude of such negative biases would not necessarily lead to a low glucose alarm being triggered if the CGM value (EGV) is still above the low alarm threshold. Therefore, we do not agree that the residual risks are acceptable as users may be able to view the inaccurate CGM readings and make inappropriate diabetes management decisions if a non-conforming product is being used.Our inspection revealed that the G6 and G7 Continuous Glucose Monitoring Systems are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have approved applications for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or approved applications for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). The devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm introduced or delivered for introduction into interstate commerce for commercial distribution these devices with major changes or modifications to the devices without submitting a new premarket notification to FDA, as required by section 510(k) of the Act, 21 U.S.C. § 360(k), and 21 CFR 807.81(a)(3). Specifically, your firm modified the G6 and G7 sensors by replacing the(b)(4)with(b)(4)used in the(b)(4). The G6 device was originally cleared under K182041 and the G7 device was originally cleared under K213919. The pivotal clinical studies submitted in the original 510(k) submissions for these devices used exclusively(b)(4)sensors. The(b)(4)is a critical component in G6 and G7 sensors. Your firm also conducted two clinical studies which demonstrated that performance of sensors constructed with(b)(4)had significantly greater variability than that of sensors constructed with(b)(4). Additionally, as discussed in item 4 above, your December 3, 2024, response includes the Sensor Level Performance Equivalency of(b)(4)and(b)(4), which shows a significant difference in the standard deviation (SD) of glucose sensitivities between sensors built with(b)(4)and(b)(4). This difference in SD indicates greater clinical performance variation for sensors with(b)(4). The larger inaccuracies in(b)(4)-coated sensors cause higher risks for users who rely on the sensors to dose insulin or make other diabetes treatment decisions. Therefore, we do not agree your firm has shown equivalency between(b)(4)and(b)(4)to justify that such a change does not require a new premarket submission. The variability differences could significantly affect the safety or effectiveness of the device within the meaning of 21 CFR 807.81(a)(3). Accordingly, your firm was required to submit a new premarket notification submission under section 510(k) of the Act, 21 U.S.C. § 360(k), to FDA at least 90 days before you proposed to begin the introduction or delivery for introduction into interstate commerce for commercial distribution of the modified G6 and G7 sensors. Additionally, your response commits to ceasing distribution of the G7 sensors with(b)(4)until additional testing is completed; however, it does not address the G6 sensors with(b)(4). Your response also does not commit to submitting a new premarket submission for the change to(b)(4)for either the G6 or G7 devices.For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.A follow up inspection will be required to assure that corrections and/or corrective actions are adequate.Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.Your firm’s response should be sent to Jessica Mu, Assistant Director, Establishment Assessment Team 3. Refer to the Unique Identification Number CMS 700835 when replying. If you have any questions about the contents of this letter, please contact: Jeff Wooley, Compliance Officer at 214-253-5251 or Jeffrey.wooley@fda.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.Sincerely,/S/for RDML Sean M. Boyd, MPH, USPHSDirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Giuseppe VercellottiPresident & CEORex Implants Inc.850 Michigan AveColumbus,OH43215United Statesg.vercellotti@reximplants.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS#676429March 12, 2025Dear Giuseppe Vercellotti:During an inspection of your firm located in Columbus, OH on December 5, 2023, through December 14, 2023, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer of the following devices: the REX Mallet; the rexpander devices; and the PiezoImplant REX BL 2.9 implant system that consists of the REX BL 2.9 implant body, and the Straight, Angled, Healing, Provisional Cylinders, and Multi-Unit abutments. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body. Specifically, these devices are intended to treat an edentulous condition to restore chewing function.FDA has reviewed the information collected during the inspection as well as information on your website at www.reximplants.com; last accessed November 23, 2024, and determined that the devices listed above are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). The aforementioned devices are also misbranded under section 502(o) of the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the device into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.1. Your firm currently has a clearance for the Piezoimplant System, a tissue level blade form endosseous dental implant body and associated dental implant abutments under K211872 for the following indications:The Piezolmplant System is intended for use in dental implant applications for oral rehabilitation of edentulous and partially dentate patients in the maxilla and mandible. Implant retained restorations may consist of single crowns or bridges as well as complete or partial dentures. The prosthetic components are connected to the implants by the corresponding abutments. The Piezolmplant System is intended for delayed loading.The information on your website, demonstrates that the PiezoImplant REX BL 2.9 implant system is currently being marketed for uses that exceed or otherwise differ from your 510(k) clearance in K211872.- The Instructions for Use for the PiezoImplant REX BL 2.9 implant system indicate that if there is implant mobility upon placement, the surgeon has the option to place the implant body deeper, whereas the Instructions for the Piezoimplant System, as cleared in K211872, stated that the implant body should be removed if there is mobility upon placement. This change represents a significantly modified risk. See item A.1.5 of the FDA guidance document, “Deciding When to Submit a 510(k) for a Change to an Existing Device.” Placement of the implant body deeper in order to stabilize the implant body implies that the osteotomy has been overprepared – i.e., is too large. The process of placing the implant body deeper is not in line with the standard protocol of splitting the ridge down to the apical aspect of the osteotomy. This change in surgical procedure increases the risk of buccal plate fracture, due to increased bone bending and inferior alveolar nerve damage, leading to permanent nerve damage or sensory loss, if the device is placed too deep in the mandible. Additional concerns include sinus perforation and damage to the maxillary artery, necessitating emergency surgery, if the device is placed too deep in the maxilla. You have not conducted an adequate risk assessment to assess this change.- As cleared in the K211872 submission, the labeling defined that the minimum buccolingual ridge that the Piezoimplant system can be used in is 3.5mm. The information provided in the K211872 submission did not support an indication for placement of the devices in a ridge less than 3.5mm. However, according to the Instructions for Use for the PiezoImplant REX BL 2.9 implant system, the BL implant bodies are intended for placement in ridges that are greater than or equal to 3mm, which constitutes a major change or modification to its intended use. Specifically, the labeling for the REX Piezoimplant BL device system allows for treatment of ridges that measure 3mm buccolingually. The use of the device system in a narrower ridge is a change in patient population, (i.e., a population with a more severely resorbed ridge). See FDA guidance document, “Deciding When to Submit a 510(k) for a Change to an Existing Device.” This new patient population includes patients with a buccolingual ridge of less than 3.5mm and presents an increased risk of buccal plate fracture, inferior alveolar nerve damage in the mandible due to proximity of this critical structure, and sinus perforation, with possible damage to the maxillary artery in the maxilla. Patients with limited alveolar bone have less bone available for stable implant placement, and if device failure occurs, will require significant revision surgeries through guided bone regeneration in order to regain lost bony support.- The K211872 clearance described only a tissue level blade-form implant design, with an external hex connection platform, along with abutments compatible with the external hex connection. The PiezoImplant REX BL 2.9 implant system is a bone level design with a different connection platform for attachment of abutment devices, which is a change in technology that could significantly affect the safety or effectiveness of the device. See FDA guidance document, “Deciding When to Submit a 510(k) for a Change to an Existing Device. The modified risks include an increased risk of implant fracture, requiring additional surgery to retrieve damaged implant parts, restoration failure or fracture, buccal plate fracture leading to loss of osseointegration, and permanent nerve damage. However, you have not conducted an adequate risk assessment to assess this change.2. Based on the evidence obtained from your firm’s website (https://catalog.reximplants.com), you are offering for sale the following devices: the “rexpanders” and “REX Mallet.” The “REX Mallet” is also called an “Implant Placement Device,” or “IPD.” We have reviewed our files and are unable to identify any FDA clearance or approval for the rexpanders and REX Mallet. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), the “rexpanders” and “REX Mallet” are devices because they are intended for use in the mitigation or treatment of disease, i.e., to treat an edentulous condition. Per the Instructions for Use for the Piezoimplant REX BL implant system, and the Instructions for Use for the rexpander devices, the rexpander devices are intended to be used for alveolar ridge splitting including use of force to expand the bone. Per the Instructions for Use for the REX mallet device, this device is intended to exert force in a surgical setting. Therefore, the REX Mallet and rexpanders are devices are used for alveolar ridge splitting, a surgical technique with a significant learning curve to prevent patient harm in the form of buccal plate fracture. Improper use of alveolar ridge splitting can lead to significant patient harm in the form of buccal plate fracture, damage to adjacent teeth, and damage to critical structures such as the inferior alveolar nerve, resulting in the need for revision surgery or permanent nerve damage.3. Based on evidence obtained from your firm’s website (https://catalog.reximplants.com/products/components-for-digital-workflow) as of April 3, 2024, your firm is marketing titanium bases intended for use with the REX Piezoimplant TL system. The K211872 submission only included abutments that are not intended to be used with a patient-specific top half. The titanium bases are intended to be used with a patient-specific top half that is cemented to the base. The titanium bases introduce a new biocompatibility concern compared to the devices cleared in the K211872 submission.Seeitem C4 of the FDA guidance document, “Deciding When to Submit a 510(k) for a Change to an Existing Device.”Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts.Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.Your firm’s response should be sent via email to Gina Brackett, Establishment Assessment Team (EAT) Assistant Director at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case # 676429” when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, EAT Compliance Officer at sargum.morgan@fda.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.Sincerely,/S/RDML Sean M. Boyd, MPH, USPHSDirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:Via EmailReference #:320-25-02Product:DrugsRecipient:Ai Hong RuanGeneral ManagerHangzhou Glamcos Biotech Co., Ltd.No 288 Xiufeng RoadTonglu XianHangzhou ShiZhejiang Sheng,311500ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-02October 7, 2024Dear Ai Hong Ruan: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 4, 2024 request 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, Hangzhou Glamcos Biotech Co., Ltd., FEI 3017053743, at No 288 Xiufeng Road Tonglu County, Hangzhou, Zhejiang, China.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 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, “disinpro multi-purpose ANTIBACTERIAL WIPES” is an unapproved new drug introduced or delivered for introduction into interstate commerce in violation of sections 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). This product is also misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Additionally, “disinpro multi-purpose ANTIBACTERIAL WIPES” and “Antibacterial Wet Wipes” are misbranded under section 502(f)(2) of the FD&C Act, 21 U.S.C. 352(f)(2). Introduction or delivery for introduction of misbranded products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant violations were observed including, but not limited to, the following:CGMP Violations1. 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)).Based on the records and information you provided, you did not demonstrate you conducted adequate finished drug product testing on your drug products before releasing them for distribution.Full release testing, including strength and identity testing of the active ingredient, must be performed before drug product release and distribution. Without adequate testing, you do not have adequate scientific evidence to assure your drug products conform to appropriate specifications before release.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm manufactured OTC drug products including antibacterial wet wipes used for reducing bacteria on skin. Based on the records and information you provided, you did not demonstrate you adequately performed identity testing on incoming components including, but not limited to, glycerin and propylene glycol, which are at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. Identity testing for these and certain other high-risk drug components1include a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform sufficient identity testing, you failed to assure the acceptability of these components for use in manufacture of your drug products.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.We also note your active pharmaceutical ingredient supplier does not appear to be registered with the FDA, and the information you provided does not indicate you have adequately qualified your raw material suppliers.3. Your firm failed to establish and follow 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)).Based on the stability records and information you provided, you did not demonstrate the quality attributes of your drug products remain acceptable throughout the labeled expiry period. For example, you did not include active ingredient testing as part of your stability program.Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.4. 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).Based on the records and information you provided, your batch production records were inadequate. For example, your batch production records for OTC drug products lacked documentation that each significant step in the manufacture, processing, packing, or holding of the batch was accomplished.Without adequate and complete batch records, you cannot assure the uniformity of your drug products from batch to batch and may impact your ability to adequately investigate any product deviations.Unapproved New Drug Violations and Misbranded Drug ViolationsBased on their labeled intended uses, “disinpro multi-purpose ANTIBACTERIAL WIPES” and “Antibacterial Wet Wipes” 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. Specifically, these products are intended for use as consumer antiseptic rub drug products.Examples from the “disinpro multi-purpose ANTIBACTERIAL WIPES” and “Antibacterial Wet Wipes” product labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of these products include, but may not be limited to, the following:“disinpro multi-purpose ANTIBACTERIAL WIPES”“Drug Facts…Use: For handwashing to decrease bacteria on the skin. Kills 99.9% of germs.” [from the product label]“Antibacterial Wet Wipes”“Drug Facts…Use: For handwashing to decrease bacteria on the skin.” [from the product label]Unapproved New Drug Violations“disinpro multi-purpose ANTIBACTERIAL WIPES” is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. New drugs may not be introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a), unless they are lawfully marketed under section 505G of the FD&C Act (which not the case for this product, as further described below) or other exceptions not applicable here. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for this drug product, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that your “disinpro multi-purpose ANTIBACTERIAL WIPES” drug product is GRASE for use under the conditions suggested, recommended, or prescribed in its labeling. Accordingly, this product is an unapproved new drug marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).We note that over-the-counter (OTC) topical antiseptic products had been the subject of rulemaking under the Agency’s OTC Drug Review. In particular, such products were addressed in a tentative final monograph (TFM) entitled “Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Health-Care Antiseptic Drug Products,” Proposed Rule, 59 FR 31402 (June 17, 1994) (1994 TFM), as further amended by “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016) (2016 Consumer Antiseptic Rubs Proposed Rule). Over the course of these rulemakings, three active ingredients (benzalkonium chloride, ethyl alcohol (ethanol), and isopropyl alcohol) were classified as Category III for use in consumer antiseptic rub products, meaning that additional safety and effectiveness data are needed to support a determination that a drug product containing one of these active ingredients would be GRASE for use in a consumer antiseptic rub.Section 505G of the FD&C Act addresses nonprescription drugs marketed without an approved application. Under 505G(a)(3) of the FD&C Act, drugs that were classified as Category III for safety or effectiveness in a TFM that is the most recently applicable proposal or determination for such drug issued under 21 CFR Part 330 – and that were not classified as Category II for safety or effectiveness – are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM, including the active ingredient, and comply with all other applicable requirements.However, “disinpro multi-purpose ANTIBACTERIAL WIPES” does not conform to the 1994 TFM, as further amended by the 2016 Consumer Antiseptic Rubs Proposed Rule, nor any other TFM, proposed rule, or final rule, and does not meet the conditions under section 505G(a)(3) of the FD&C Act for marketing without an approved application under section 505. Specifically, the label states that “disinpro multi-purpose ANTIBACTERIAL WIPES” contain benzalkonium chloride at a concentration of 0.2%; however, benzalkonium chloride is only permitted at a concentration of 0.1% to 0.13%.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).Misbranded Drug ViolationsThe “disinpro multi-purpose ANTIBACTERIAL WIPES” and “Antibacterial Wet Wipes” drug products are misbranded under section 502(f)(2) of the FD&C Act, 21 U.S.C. 352(f)(2), because the product labels do not include all of the applicable warnings required under 21 CFR 330.1(g). Specifically, the labels do not include the complete warning statement that reads, “If swallowed, get medical help or contact a Poison Control Center right away.”Additionally, “disinpro multi-purpose ANTIBACTERIAL WIPES” is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because this product is a nonprescription drug subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but does not comply with the requirements for marketing under that section and is 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).Additional ConcernsWe note that the “disinpro multi-purpose ANTIBACTERIAL WIPES” and “Antibacterial Wet Wipes” drug products are marketed as “antiseptic wipes.” Antiseptic wipes generally refer to consumer antiseptic rub drug products that are not intended to be rinsed-off after use. However, the labels for both products suggests that they can be used as a consumer antiseptic wash. For example, both labels state, “For hand washing to decrease bacteria on the skin.” An antiseptic wipe drug product marketed under section 505G of the FD&C Act cannot also be a consumer antiseptic wash, as the directions for use conflict with each other and a wipe is not an acceptable dosage form for an antiseptic wash.2Discrepancy in Information ProvidedIn response to FDA’s initial records request, you asserted that you have not manufactured drugs for the United States in three years. After FDA provided you information regarding shipments of drugs from your facility as recent as of January 8, 2024, you then provided the requested information. FDA is concerned that you may have falsely alleged that you do not manufacture, process, pack, or hold drugs for the United States.3CGMP 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 audit4of 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.Drug ProductionIn response to this letter, clarify whether you intend to continue to manufacture drugs for the U.S. market at this facility in the future.If you plan to resume any manufacturing operations regulated under the FD&C Act, notify this office before resuming your drug manufacturing operations. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm is capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all corrective action and preventive action (CAPA).ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed your firm on Import Alert 66-40 on September 30, 2024.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Hangzhou Glamcos Biotech Co., Ltd. at No 288 Xiufeng Road Tonglu County, Hangzhou, Zhejiang, 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 or misbranded may be detained or refused admission.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 3017053743 and ATTN: Matthew Jensen.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research__________________1Components with higher risk of DEG or EG contamination compared to other drug components.2The permitted dosage forms for consumer antiseptic washes are set forth here: “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use,” Proposed Rule, 78 FR 76444 (December 17, 2013) and “OTC Safety and Effectiveness of Topical Antimicrobial Drug Products for Over-the Counter Human Use,” Final Rule, 81 FR 61106 (September 6, 2016).3See section IV of the FDA Guidance for Industry Circumstances that Constitute Delaying, Denying, Limiting, or Refusing a Drug or Device Inspection at https://www.fda.gov/media/86328/download.4i.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.