行政处罚案件信息摘要行政处罚决定书文号湘药监药罚〔2025〕78号当事人湖南兴盟中药饮片有限公司统一社会信用代码91430611MA4RCLWG6K法定代表人谭倩违法行为类型生产销售劣药地龙行政处罚内容1.没收批号为250201地龙7.5kg；2.没收违法所得 4469.6元。作出行政处罚决定的行政机关湖南省药品监督管理局作出行政处罚决定的日期2025年12月5日备注

医疗机构中药制剂是中药传承创新的重要载体。近年来，宁夏药监局聚焦特色中药材资源优势，通过精准服务、靶向培训、全程指导，持续推进医疗机构中药制剂备案管理、标准提升与研发转化工作，取得阶段性成效。全区注册、备案医疗机构中药制剂84个，覆盖消化、皮肤、骨科、妇科、呼吸、泌尿、综合调理等多个诊疗领域，为广大患者提供了多种用药选择。一是政策维度强支持。《中华人民共和国中医药法》实施以来，宁夏药监局高度重视医疗机构中药制剂发展，对应用传统工艺配制中药制剂实行备案管理，两次修订《医疗机构应用传统工艺配制中药制剂备案管理实施细则》，压减办理时限，支持调剂使用，进一步便利中药制剂临床使用。同时，积极配合医疗保障、中医药管理等部门出台相关政策，将53个医疗机构中药制剂纳入医保支付范围，推动中医医院制剂能力建设项目落地。二是标准维度促提升。为全面提高医疗机构制剂质量标准，宁夏药监局持续开展医疗机构制剂标准提升行动，指导各机构积极开展制剂标准研究，运用高效液相色谱法（HPLC）等方法确定中药制剂关键指标成分含量范围，逐步实现质量控制从“定性为主”向“定量为主”转变。截至2025年12月，已通过专家评审的中药制剂品种达60个；同时，指导相关医疗机构积极参与制定《中药制剂内服膏方生产技术规范》《中药制剂内服膏方质量要求》等团体标准，推动区域制剂标准规范化建设。三是研发维度助转化。在“三结合”中药注册审评证据体系框架下，宁夏药监局积极支持各医疗机构、药品上市许可持有人，基于古代经典名方、名老中医方等具有丰富人用经验的品种开展研制与转化，目前共有4家医疗机构的15个品种具有新药转化意向，1家持有人正在开展古代经典名方研究。邀请国家药监局药审中心来宁举办优化中药上市后变更技术要求座谈会，鼓励各医疗机构加强人才队伍建设，充实药物化学、药物分析、药理毒理等专业技术人员力量，进一步提高质量分析方法研究能力，为中药制剂转化新药取得突破性进展储备人才力量。下一步，宁夏药监局将进一步加大研发转化支持力度，优化调剂程序，加强人才培养，引导医疗机构与高校、科研机构、企业建立产学研协同合作机制，进一步调动医疗机构积极性，加速成果转化，带动全区医疗机构中药制剂高质量发展。

“十四五”期间，宁夏药监局坚持以人民为中心，统筹发展和安全、监管和服务，聚焦药物临床试验、药品生产及中药传承创新等关键领域，出台系列政策举措，完善监管服务体系，严格风险隐患管控，推动宁夏医药产业规模稳步增长、质量持续提升。一是扩量提质，服务产业发展举措更优。坚持深化药品审评审批制度改革，鼓励药品创新，打造“服务进园区 监管有温度”服务品牌，在生产许可、上市后变更等事项中实施“提前介入、沟通交流、研审结合”，宁夏药品生产企业数量由“十四五”初期的32家增至43家，增长34%，形成制剂、原料药、医用氧、中药饮片多元发展格局，放射性药品、B证企业、CDMO企业等领域实现新突破。“十四五”期间，区内药品上市许可持有人新获批药品批准文号9个，原料药登记人登记并通过审评原料药4个；宁夏康亚药业用于糖尿病肾病治疗的Ⅰ类创新药物WJ-39获批临床试验，实现创新药研发新突破。持续推进仿制药一致性评价，并逐步向滴眼剂等剂型拓展，过评品规累计达15个，配合科技、财政等部门落实奖补资金3200万元，引导企业不断提升产品质量。二是守正强基，中药传承创新发展底色更足。聚焦枸杞子、甘草、银柴胡等宁夏特色优势品种，积极推动实施中药材GAP。规范医疗机构应用传统工艺配制中药制剂备案，支持中药制剂调剂使用，“十四五”期间共备案中药制剂48个，持续开展医疗机构制剂标准提高行动，已有3批60个提高后的质量标准通过专家评审。加强中药监管科学研究，完善省级中药标准体系，累计制定省级中药标准625件，其中中药饮片炮制规范195个、中药材标准41个、中药配方颗粒标准389个，发布2批7个趁鲜切制品种。按照“主动对接、一品一策、全程跟踪、专班帮扶”的原则，邀请张伯礼院士等医药领域专家来宁召开培植牛黄研究推进会，邀请国家局药审中心专家实地调研、座谈指导，支持培植牛黄、发酵冬虫夏草菌粉等珍稀濒危中药材替代品的研究和开发利用。推动成立国家枸杞产品质量检验检测中心（宁夏），与香港STC签订技术合作协议，为枸杞等特色产品开拓国际市场提供技术支撑。推广使用“宁药码”中药饮片信息化追溯系统，全区24家中药饮片生产企业基本实现重点品种赋码追溯，中药传承创新发展底色更足。三是监管为民，药品质量安全防线更牢。落实药品全生命周期监管，紧盯集采中选、无菌制剂、特殊管理药品等高风险品种，药物临床试验、药品生产、药品上市后变更等关键环节，“十四五”期间对药物临床试验机构实行年度“全覆盖”检查，对在产药品生产企业开展监督检查226家次，采取告诫、约谈、暂停生产等风险控制措施24家次。强化特殊药品监管，联合公安、卫生健康等部门开展专项整治，实施信息化追溯和流向追查，集中监督销毁不能正常销售的右美沙芬等新列管药品147批次9924盒，筑牢禁毒防线。持续完善常态化药品安全风险隐患排查化解机制，压茬开展药品安全专项整治行动、药品安全巩固提升行动、中药专项检查等，每季度开展风险会商，面向企业开展警示教育。组织企业开展“查找身边风险隐患”活动和警示教育，推动企业落实质量安全主体责任，连续5年举办药品生产企业关键岗位人员培训班，实现关键岗位人员和从业人员“两个培训”全覆盖，全过程、全链条筑牢药品安全防线。“十四五”期间，宁夏医药产业高质量发展迈出坚实步伐，下一步，宁夏药监局将以“十五五”规划编制为契机，持续深化药品医疗器械监管改革，强化创新策源能力，完善产业支持政策，筑牢质量安全防线，推动全区医药产业实现更高质量发展。

Delivery Method:Via EmailReference #:320-26-32Product:DrugsRecipient:Mr. Dinesh PatelPresidentUnipack LLC111 Coolidge StSouth Plainfield,NJ07080-3801United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-32December 19, 2025Dear Mr. Patel:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Unipack LLC, FEI 3008275696, at 111 Coolidge St., South Plainfield, NJ 07080-3801, from June 11 to June 30, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your July 22, 2025 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm failed to conduct adequate investigations into out-of-specification (OOS) results and unknown peaks in chromatograms. For example:A. Your(b)(4)suppositories batch #(b)(4)three-month long-term (25ºC / 60% relative humidity) stability sample assay result was(b)(4)mg(b)(4)per suppository (acceptable range:(b)(4)mg). Your investigation included multiple retests with results ranging from(b)(4)to(b)(4)mg per suppository. You invalidated the original OOS result with no identified laboratory error and no explanation for the significant differences in assay results. Your investigation also lacked root cause identification before releasing the product for distribution and you failed to implement corrective action. We note the stability sample at the intermediate condition (30ºC / 65% relative humidity) for the same batch also failed to meet the assay specification.B. You obtained an OOS content uniformity test result of(b)(4)%(b)(4)for your(b)(4)suppository batch #(b)(4)(acceptable range:(b)(4)%). Your investigation included reanalysis of the original sample, which resulted in an OOS result of(b)(4)%. However, your investigation lacked scientific justification to invalidate the OOS result and ultimately release the batch.C. Unknown peaks were not integrated or properly investigated in HPLC chromatograms of multiple drug products, including, but not limited to,(b)(4)suppository batch #(b)(4). You also inhibited peak retention time between(b)(4)and(b)(4)for the same drug product. Inhibiting peak integration and restricting integration parameters must be scientifically justified and documented in the validated method to prevent data manipulation.Inadequate investigations can result in unsupported root causes, ineffective corrective actions, and recurring problems that compromise your ability to manufacture safe and effective drug products.In your response, you attribute the(b)(4)suppositories batch #(b)(4)OOS stability result to improper processing of the injection. Your response regarding the OOS results for(b)(4)suppositories batch #(b)(4)reiterates the original investigation’s conclusion and fails to provide additional evidence or analysis beyond what was reviewed during the inspection. Additionally, you state you have discontinued HPLC testing throughout your facility. You also explain the unknown peaks in(b)(4)suppository batch #(b)(4)are attributable to excipients but fail to address your practice of inhibiting peak integration and restricting integration parameters.Your response is inadequate. You fail to provide additional details of your investigation into OOS results of your(b)(4)suppositories and(b)(4)suppositories, including determination of root causes and CAPAs. Additionally, you do not explain the root cause of your QU’s failure to thoroughly investigate unknown peaks before releasing the product. Furthermore, your commitment to discontinue HPLC testing at your facility does not address how you will ensure future deviations are investigated by following robust procedures.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final QU decisions, and is fully supported by executive management.A thorough assessment of the adequacy of your test methods used for testing and retesting OOS samples.A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for U.S. products currently in the U.S. market and within expiry as of the date of this letter and a report summarizing the findings of the analysis, including the following for each OOS:o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include, but not be limited to, addressing the following:o QU oversight of laboratory investigationso Identification of adverse laboratory control trendso Resolution of causes of laboratory variationo Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequately scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediations2. Your firm failed to ensure that laboratory records included complete data derived from all tests necessary to ensure compliance with established specifications and standards (21 CFR 211.194(a)).Your laboratory records did not include all testing data to support the drug product analyses performed.Incomplete laboratory recordsOur investigator observed entries were not entered contemporaneously in your laboratory notebook. For example, our investigators observed volumetric flasks of(b)(4)suppository finished product release and stability samples in your quality control laboratory with no date of preparation documented. Your analyst stated the samples were prepared on June 9, 2025.However, the last entry in your laboratory notebook was dated June 4, 2025. Furthermore, the sample weights were recorded on an adhesive note, and no standard weight was recorded. All raw data must be recorded in a controlled document at the time they are observed or measured to ensure data integrity.Our investigators also noted multiple high-performance liquid chromatography (HPLC) injections were not adequately processed in the chromatographic system. For example, electronic records stored in a folder titled “(b)(4)” indicate that approximately(b)(4)sample injections were performed. However, results were generated only for approximately(b)(4)injections. Your firm lacked evidence to demonstrate your laboratory manager and quality unit (QU) reviewed the raw data for these injections. Furthermore, HPLC audit trails revealed the(b)(4)suppositories batch #(b)(4)three-month stability sample was injected on September 25, 2023, but results were neither processed in your HPLC system nor documented in your laboratory notebook. In addition, the(b)(4)suppositories batch #(b)(4)24-month stability sample was initially injected on April 29, 2025, with no reported results, then re-injected later that same day, with passing results subsequently reported.All laboratory records must be complete, accurate and contemporaneously documented to ensure processes are consistently followed and reproducible. Additionally, incomplete laboratory records deprive you of the ability to adequately investigate deviations.Inadequate electronic records controlsYour firm did not have proper controls in place to prevent the deletion or manipulation of your laboratory's electronic data. For example, your analysts had administrative rights on your chromatographic systems that allowed them to alter and delete data, files, and folders, including your spreadsheet used for assay calculations. In addition, during a review of system audit trails, our investigator observed multiple “deleted system” and “deleted project” errors with no assessment report completed as required by your procedure. Deficiencies in your electronic data security controls were identified and discussed during previous FDA inspections, yet your firm has failed to implement adequate corrective measures. The lack of proper electronic records controls undermines the reliability and integrity of your laboratory data.Manual IntegrationYour analysts conducted manual integration of HPLC assay peaks without scientific justification or procedural controls. For example, our review of chromatograms for(b)(4)suppositories stability batch #(b)(4)revealed the use of inconsistent integration for the main peak of interest for HPLC assay testing. This inconsistent integration of HPLC peaks is not suitable for quantitative analysis.All data must be complete, accurate, and retained to enable appropriate assessments and decisions by the QU. The lack of control over the integrity of your data raises questions about the authenticity and reliability of your analytical data and the quality of your drug products.In your response, you state all internal HPLC testing is permanently discontinued, and all chromatographic analysis transitioned to qualified third-party laboratories.Your response is inadequate. Your elimination of internal HPLC testing does not address your fundamental breaches of data integrity. In addition, you lack a comprehensive assessment to determine the full extent and impacts of your data integrity deficiencies, including a retrospective review of your manual integration practices.In response to this letter, provide:A complete assessment of documentation systems used throughout your manufacturing and laboratory operations to determine the adequacy of your documentation practices. Include a detailed CAPA plan that comprehensively remediates your firm’s documentation practices to ensure you retain attributable, legible, complete, original, accurate, contemporaneous records throughout your operation.3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).Your firm lacked appropriate testing to ensure finished drug products conform to appropriate standards of identity, strength, quality, and purity. For example, the United States Pharmacopeia (USP) monograph for(b)(4)suppositories includes specific testing for identification and(b)(4)determination, but your finished product release specifications did not include these required tests. Your firm manufactured and distributed approximately(b)(4)batches of(b)(4)suppositories since March 2022 without adhering to USP testing standards. Additionally, your finished product release specifications for(b)(4)suppositories did not include the specific identification testing required in the USP monograph.You failed to establish that your test methods and specifications are scientifically sound and appropriate or that they are equivalent to or better than the current USP compendial methods.In your response, you acknowledge comparing your product specifications against USP and CGMP requirements to identify testing gaps for remediation. You then revised your product specifications to meet analytical requirements and shared the updated specifications with your third-party laboratories. You also state you are implementing a “risk-based confirmatory testing plan across relevant product lines.”Your response is inadequate. You fail to provide an adequate timeline for transferring testing to contract laboratories. Additionally, you propose to continue risk-based retroactive testing in-house despite acknowledged testing deficiencies. Furthermore, you continue manufacturing and releasing products without having fully remediated your laboratory deficiencies.In response to this letter, provide:A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a batch disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.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 data integrity practices at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/data-integrity-and-compliance-drug-cgmp-questions-and-answers.We strongly recommend you retain an independent third-party qualified consultant with experience identifying and remediating data integrity issues. In response to this letter, provide:Copies of any agreement describing the roles and responsibilities of your independent third-party consultant. Include copies of any protocol developed, system-based assessment, and report as part of your remediation effort.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.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 data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.o A comprehensive retrospective evaluation of the nature of the data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating corrective action and preventive action (CAPA) effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).o A status report for any of the above activities already underway or completed.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3008275696 and ATTN: Matthew Jensen.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Product:Medical DevicesRecipient:S. Ramamoorthy, Ph.D.Chief Executive Officer (CEO)Palamur Biosciences Private LimitedBoothpur MandalMahabubnagar509382TelanganaIndiaram.murthy@palamurbio.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERDecember 11, 2025Dear Dr. Ramamoorthy:This Warning Letter is to inform you of objectionable conditions observed during the United States Food and Drug Administration (FDA) inspection conducted at Palamur Biosciences Private Limited (PBS) from January 20, 2025, to January 27, 2025, by investigators from the FDA’s Office of Bioresearch Monitoring Inspectorate (OBMI) Foreign Inspection Cadre. This inspection was conducted to determine whether activities and procedures related to your participation in Good Laboratory Practice (GLP) nonclinical studies complied with applicable federal regulations. Specifically, FDA investigators focused on the list of studies below including, but not limited to, implantation, acute systemic toxicity, material mediated pyrogenicity (MMP), and guinea pig maximization tests conducted at your facility.The list of studies below is not an all-inclusive list of studies impacted by the inspection or by the violations cited in this letter.Study numberTest231918Implantation Study24636Implantation Study231192Acute Systemic Toxicity231165Acute Systemic Toxicity231809Acute Systemic Toxicity231868Acute Systemic Toxicity24085Acute Systemic Toxicity24110Acute Systemic Toxicity24005MMP24084MMP24378MMP231866Guinea Pig Maximization Test231586Guinea Pig Maximization Test231191Intracutaneous Reactivity231196In Vitro CytotoxicityThese tests are used in nonclinical studies for the development of devices as that term is defined in section 201(h)(1) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h)(1), 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 function of the body.The inspection was conducted under a program designed to ensure that data and information contained in requests for Investigational Device Exemption, Premarket Approval applications, and Premarket Notification submissions are scientifically valid and accurate. Another objective of the program is to ensure that human subjects are protected from undue hazard or risk during the course of scientific investigations.Our review of the inspection report prepared by the OBMI revealed serious violations of Title 21, Code of Federal Regulations (CFR) Part 58 - Good Laboratory Practice for Nonclinical Laboratory Studies, which concerns, among other things, requirements prescribed under section 520(g) of the Act, 21 U.S.C. § 360j(g). Compliance with Part 58 is intended to assure the quality and integrity of the safety data filed in a premarket submission. At the close of the inspection, the FDA investigators presented an inspectional observations Form FDA-483 for your review and discussed the observations listed on the form with you.We received the initial response from your firm dated February 17, 2025, concerning our investigators’ observations noted on the Form FDA-483. We have since received follow-up responses to the initial response from your firm on the following dates:April 13, 2025May 12, 2025July 8, 2025August 12, 2025September 16, 2025This letter discusses your written responses to the noted investigators’ observations and requests prompt corrective action to address violations of 21 CFR Part 58. These violations include, but are not limited to, the following:1. Failure of the study director to assure that all experimental data, including observations of unanticipated responses of the test system are accurately recorded and verified [21 CFR 58.33(b)].The study director has overall responsibility for the technical conduct of the study, as well as for the interpretation, analysis, documentation and reporting of results, and represents the single point of study control. The study director’s responsibilities include ensuring that all experimental data are accurately recorded and verified. Examples of the study director’s failures to adhere to this requirement include, but are not limited to, the following:a. For study 231918, the Animal/Bird Requisition and Issuance Record shows that the rabbits were 7-8 months old, but the breeding records do not include birth dates. Additionally, the animals were only given identification (R1 through R12) when they were enrolled in and throughout the study, and this identification cannot be traced back to the Animal Issue Record maintained by the Animal Breeding and Husbandry (ABH) department. The Animal Issue Record lists species/strain, sex, age range and body weight range for a group of rabbits issued for a particular study. However, there are no medical records associated with the individual rabbits and no way of verifying the accurate age of each animal. Because animal age can impact the analysis and interpretability of test results, it is important that the age of each animal in a study is accurately recorded and can be verified.b. The raw study data for the acute systemic toxicity studies (231192, 231165, 231809, 231868, 24085, and 24110) and MMP studies (24005, 24084, and 24378) did not have the rate of intravenous administration of the bolus in each animal recorded. Additionally, the start and end time of intravenous injection are not recorded. Study plans for all acute systemic toxicity and MMP studies require that intravenous injections be administered consistent with the guidelines outlined in the International Organization for Standardization (ISO) 10993, Biological Evaluation of Medical Devices, and/or the United States Pharmacopeia (USP) Chapter 151, Biological Tests – Pyrogen Test, as applicable. The rates of intravenous injections were not recorded; therefore, it cannot be verified whether these tests were conducted according to the testing guidelines.c. For study 24636, there were no records of physical examinations of Guinea Pigs 1 through 12 upon receipt of the animals from the vendor, upon release from quarantine, or before the surgical procedure. The health of the animals was not comprehensively examined and recorded at the start of the study and anesthesia status was not assessed before the surgical procedure. Therefore, it cannot be confirmed whether the animals were healthy or showing any abnormal clinical signs. Clinical observations are important to record for the reliability of the subsequent analysis of the responses of the animal to the test article, as well as for evaluating whether the animal needs any treatment or intervention.As the principal point of study control, the study director did not ensure that all experimental data were accurately recorded and verified, which in turn yields questionable study results. Based on this failure, the FDA has concerns about the quality and integrity of data generated from the nonclinical laboratory studies conducted at your testing facility. Complete and accurate study data are necessary to allow FDA to fully assess the overall safety and risk of a device with an associated premarket submission. The unreliable data raises concerns about the quality and integrity of associated premarket submissions, which may put public health and safety at risk.Your written responses are inadequate. The written responses provided revised standard operating procedures (SOPs), forms, and staff training records, but they do not include any planned preventive actions such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while you provided a copy of the form, PRM/PBS/TOX/014, “Animal/Bird Requisition and Issuance Record” as evidence of the health status of the animals, the form lacks detailed documentation of physical examinations conducted by qualified personnel (e.g. veterinarian). Furthermore, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your procedures will be conducted to identify and correct any systemic issues. Your explanation, when taken into consideration with the violations described above, which occurred in multiple studies, suggests systemic failures in study director oversight of nonclinical laboratory studies and brings into question the quality and integrity of safety data collected at your testing facility. Thus, your responses do not provide assurance that similar violations would not occur again.2. Failure of the testing facility to have standard operating procedures in writing setting forth nonclinical laboratory study methods that management is satisfied are adequate to ensure the quality and integrity of the data generated in the course of a study. [21 CFR 58.81(a)].SOPs should be adequate to ensure the quality and integrity of data generated in a study. However, not all SOPs appear to be adequate. Examples of your failures to adhere to this requirement include, but are not limited to, the following:a. SOP/PBS/TOX/001, Recording of Body Weight and Procedure for Feed and Water Consumption, does not include procedures for calibration of the balance used for weighing animals. Section 5.1 of the SOP states that, “[t]he balance will be set and calibrated as specific to the balance in use.” However, there is no specific information as to who is responsible for calibration (e.g., study personnel assigned to each study) or when calibration should be performed (e.g., whether the calibration should be performed prior to body weight measurement or whether it should be performed at specific dates/intervals).b. SOP/PBS/GEN/047, Sample and Reference Material Preparation for Biological Evaluation of Medical Devices, does not include detailed procedures for extraction depending on the test article (e.g., test articles indicated for prolonged or long-term tissue contact may require different extraction conditions than those with limited contact). Additionally, the SOP does not provide detailed instructions for monitoring of changes in the color of the test extract. Sample preparation is one of the crucial steps in biocompatibility testing of medical devices. Conditions of medical device extraction, such as extraction temperature, duration of extraction, and vehicle use can significantly impact the outcomes of a biocompatibility study.c. SOP/PBS/PAT/012, Euthanasia of Laboratory Animals/Birds, does not contain sufficiently detailed procedures for administration of carbon dioxide (CO2) for inhalation euthanasia for rodents to fulfill the objective of rapid unconsciousness with minimal distress to the animals. For example, the SOP does not contain information about the settings of the flowmeter for the delivery of the CO2 gas or include specific procedures for using CO2 inhalation in rodents.Failure of a testing facility to have adequate SOPs raises questions about the reliability and accuracy of the data and does not ensure the quality and integrity of data generated in a study. Inadequate SOPs yield inadequate protocols that introduce ambiguity and uncertainty as to how study requirements are to be followed, as well as inconsistent execution of studies and unreliable study results. Inadequate SOPs could result in study data with a high level of variability that challenges the ability to effectively interpret the study results associated with a device. This in turn adversely impacts a manufacturer’s and FDA’s ability to assess the overall safety and risk of the subject device prior to use in humans as a legally marketed device or for purposes of beginning clinical trials.Your written responses are inadequate. The responses provided revised SOPs, forms, and staff training records, but they do not: (1) detail how your testing facility will ensure that applicable SOPs will be followed to ensure the quality and integrity of data generated in a study; and (2) address any planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your procedures will be conducted to identify and correct any systemic issues, including ensuring that there are existing SOPs that cover all relevant functions, as well as ensuring that all SOPs are sufficiently detailed to allow personnel to correctly perform these functions. Thus, your written responses do not provide assurance that similar violations would not occur again.3. Failure of the testing facility management to assure that personnel clearly understand the functions they are to perform [21 CFR 58.31(f)].An example of the testing facility management’s failure to adhere to this requirement includes, but is not limited to, the following:a. For Guinea Pig Maximization Test (GPMT) study 24838, the study personnel failed to identify and record adverse tissue responses to the injected adjuvant and clinical observations (e.g., difficulty breathing). SOP/PBS/TOX/008 indicates that after intradermal induction, skin reactions such as edema, erythema, and necrosis, along with other clinical signs will be recorded. However, the records that were reviewed did not indicate that clinical signs were recorded. In addition, there is no procedure that describes what clinical signs should be assessed to determine the health of the animal or how the technician would recognize skin reactions and distinguish between similar responses (e.g., between a “discrete” and “moderate” skin reaction). Furthermore, it was observed that study personnel training does not include species-specific in-life observations and when veterinarian oversight should be requested.Failure of testing facility management to assure that all personnel clearly understand the functions they are to perform and are adequately qualified and trained creates a high level of variability that does not ensure the validity and quality of the data. Personnel that do not clearly understand the functions they are to perform cannot consistently perform tasks according to the SOPs. This can have a negative impact on a study and calls into question the quality and integrity of studies conducted at your testing facility.Your written responses are inadequate. Your responses included revised SOPs, training records, and creating a new division for Ethology & Animal Welfare to focus on clinical sign observation, ethology, animal welfare training, and enrichment, in addition to appointing a technical consultant to assist with personnel training. However, it is not clear what oversight for the new head of Ethology and Animal Welfare will entail or what technical expertise will be provided by the technical consultant. Furthermore, your responses do not address planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your training program will be conducted to identify and correct any gaps in personnel training. Furthermore, while you have provided training records containing quizzes that test personnel’s recollection of the training received, you have not described how personnel’s ability to perform the tasks in question will be assessed to ensure that the training achieves its intended goal. Thus, your written responses do not provide assurance that similar violations would not occur again.4. Failure of the Quality Assurance Unit (QAU) to determine that no deviations from approved protocols or SOPs were made without proper authorization and documentation [21 CFR 58.35(b)(5)].The QAU is responsible for determining that no deviations from approved protocols or SOPs were made without proper authorization and documentation. An example of the QAU’s failures to adhere to this requirement includes, but is not limited to, the following:a. For study 231918, the study plan stated that the rabbits should have a supraglottic airway device inserted; however, the surgical records showed that an endotracheal tube was used for delivery of inhalant anesthesia. There is no record to indicate that this deviation was identified by the QAU, and there is no documentation to indicate that this deviation was made with proper authorization.A reliable QAU is integral to the successful understanding and completion of any GLP study. Without appropriate QAU oversight, neither the sponsor nor FDA reviewers have assurance that the data in the final study report is accurate and valid. Failure to perform QAU functions can have a negative impact on a study and calls into question the quality and integrity of studies conducted at your testing facility.Your written responses are inadequate. Your written responses include generating a record of an SOP deviation, performing a root cause analysis, and opening a corrective and preventative actions plan. However, your responses do not detail planned preventive actions, such as frequency (e.g., quarterly, annual) of audits to check for compliance of the QAU or future training for new staff and/or new procedures. Additionally, while your responses propose corrections for the specific observations noted, you have not indicated whether any systematic reviews of your QAU will be conducted to identify and correct any systemic issues.In addition to the device studies described above, FDA investigators also observed that your facility performs studies intended to support the approval of new animal drugs. The overall conditions and practices at your facility, as exemplified above, may impact the validity and integrity of the data obtained to support new animal drug applications. For example, in study 19278, your records indicate you centrifuged the majority of blood samples before they were actually collected. In your response, you indicated you were unable to reconstruct what happened. This calls into question the quality and integrity of data generated from the nonclinical laboratory studies conducted at your testing facility. You should ensure that you consider animal drug studies as part of your corrective and preventive actions.FDA investigators also observed that the exterior of the testing facility had significant accumulations of dirt, animal droppings, and potential pest harborage. Upon inspection of Block F, the HVAC equipment on the outside of the building was found to be surrounded by a large amount of dirt and debris that could attract and provide harborage for various pests and could potentially be caught up in the HVAC equipment, possibly causing failure. Such conditions may impact nonclinical studies conducted at your facility.The violations described above are not intended to be an all-inclusive list of problems that may exist with your facility. It is your responsibility as a nonclinical laboratory to ensure compliance with the Act and applicable regulations.Within 15 working days of receiving this letter, please provide documentation of the additional corrective and preventive actions that you have taken or will take to correct these violations and to prevent the recurrence of similar violations in current or future studies for which you are the testing facility. Any submitted corrective action plan should include projected completion dates for each action to be accomplished as well as a plan for monitoring the effectiveness of your corrective actions. In addition, please provide a complete list of all nonclinical laboratory studies of FDAregulated devices for the last five years, including the name of the study, the test article, the name of the study director and sponsor, and the current status of the study. Failure to respond to this letter and take appropriate corrective action could result in the FDA taking regulatory action without further notice to you. In addition, FDA could initiate disqualification proceedings against you in accordance with 21 CFR 58.202. If you believe that you have complied with the Act and FDA regulations, please include your reasoning and any supporting information for our consideration.Your response should reference “CTS# EC250128/E001” and be sent via email to: Irfan.Khan@fda.hhs.gov.A copy of this letter has been sent to FDA’s OBMI Foreign Inspection Cadre via email at FDAInternationalBIMO@fda.hhs.gov. Please send a copy of your response to that office.If you have any questions, please contact Amrin Chowdhury by phone at (240) 402-8318 or email at Amrin.Chowdhury@fda.hhs.gov.Sincerely yours,/S/Ouided Rouabhi, MSActing DirectorDCEA1: Division of Clinical Policy and QualityOffice of Clinical Evidence & AnalysisOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

　广东极客齿科器材有限公司生产的金刚砂车针，因在2025年广东省医疗器械质量抽查检验中，抽检的金刚砂车针(型号规格：TR-13 圆头锥型,产品编号/批号：202407310031；型号规格：BR-40 圆球型，产品编号/批号：20240613；型号规格：BR-31 圆球型，产品编号/批号：202503070049；型号规格：BR-45 圆球型，产品编号/批号：202503240046)，经广东省医疗器械质量监督检验所检验均被发现尺寸不符合技术要求(报告编号分别是:SJ25020183；SJ25020185；SJ25020194；SJ25020205)。公司决定主动发起三级召回处理。　　涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。　　附件：医疗器械召回事件报告表2025年12月30日

相关附件：安徽省中药饮片（含中药配方颗粒）生产省本级日常监督检查信息通告2025年12月 .xls

Delivery Method:VIA UPSReference #320-26-30Product:DrugsRecipient:Mr. Samuel D. RaoofPresident/CEOPrivate Label Skin Care, Inc.8200 Remmet Ave.Canoga Park,CA91304-4156United StatesIssuing Office:Center for Drug Evaluation andResearch (CDER)United StatesWarning Letter320-26-30December 18, 2025Dear Mr. Raoof:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Private Label Skin Care, Inc., FEI 3015274499, at 8200 Remmet Ave., Canoga Park, CA, from June 16 to 23, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).In addition, we reviewed your firm’s drug listing submissions in FDA’s electronic Drug Registration and Listing System (eDRLS) and found that you have not provided drug listings for at least 21 of your human over-the-counter (OTC) drugs as required by section 510(j) of the FD&C Act.Your firm has not fulfilled its drug listing obligations under section 510(j) of the FD&C Act, 21 U.S.C. 360(j), and 21 CFR Part 207, which is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), and will render a drug misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). In addition, failure to list a drug is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p). These violations are described in more detail below.CGMP ViolationsWe reviewed your July 15, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondences.During our inspection, our investigator observed specific violations including, but not limited to, the following.Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a)).You are the owner and labeler of numerous OTC drug products. Your firm uses a contract manufacturing organization (CMO) to perform various CGMP activities on your behalf. As the owner of the products, you were informed by your CMO of the elevated(b)(4)impurities in your(b)(4). After your CMO notified your firm of the elevated(b)(4)impurities, your firm continued distribution of identified batches of(b)(4).On August 25, 2025, FDA held a teleconference with you recommending that you consider removing adulterated batches of(b)(4)currently in distribution from the U.S. market. On(b)(4), you issued a voluntary recall of the adulterated batches of(b)(4)currently in distribution from the U.S. market due to elevated levels of(b)(4)that were discovered with(b)(4)products.In your response, you commit to incorporating(b)(4)testing into your release specifications and stability studies for all products containing(b)(4), assessing component suppliers of active ingredients and excipients for(b)(4)formulation and content, and exploring formulation changes that reduce or eliminate(b)(4)formation risks. Your response is inadequate. Your quality unit (QU) failed to determine the impact to other batches of(b)(4)products as well as other products containing(b)(4)that were previously released and remain on the market within expiry.When you use a CMO for all or part of the manufacturing of a drug product, your QU is responsible for approving or rejecting the CMO’s products and services, including the suitability of releasing batches for commercial distribution. An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. 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.Regarding drug products containing(b)(4), FDA has alerted drug manufacturers of products at risk for presence of(b)(4). For more information see(b)(4)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.A summary of all results obtained from testing retain samples from each batch of(b)(4)products that are currently on the U.S. market within expiry. If the testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.Use of Contract ManufacturersDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of your drugs regardless of agreements in place with your contract facilities. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act to ensure safety, identity, strength, quality, and purity. See FDA guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.Drug Listing ViolationsSection 510(j) of the FD&C Act, 21 U.S.C. 360(j), and 21 CFR Part 207 set forth the requirements for drug listing. Specifically, under section 510(j)(1) of the FD&C Act and 21 CFR 207.41(a), each registrant must list each drug that it manufactures, repacks, relabels, or salvages for commercial distribution. Further, under 21 CFR 207.53, each registrant must provide required listing information for each drug it repacks or relabels. Your firm has failed to provide drug listings for the following drugs:“Age Defense SPF 45,” “The Treatment On the Daily SPF 45,” “100% Mineral Tinted SPF,” “Healthy Glow Tinted BB Cream SPF 44+,” “The Treatment Let’s Get Physical Tinted SPF 44,” “Dermlogic Anti-Aging Resurfacing Peel Pads,” “Even GLO Brightening Pads,” “Physical Daily Defense SPF 40,” “Acne Clearing Serum,” “Matte Tinted SPF,” “Fresh Faced Tinted SPF 44,” “Hydralite Moisturizer,” “Pigment Correcting Pads,” “Bye, Bye Blemish,” “Papaya Enzyme Cleanser,” “Clear Defense SPF 45,” “Detox Mask,” “Pore Refining Cleanser 2% Salicylic Acid,” “Sheer Defense Tinted SPF 46,” “Hydro Essence SPF 40,” and “Micro Peel Pads” (collectively, "your firm’s OTC drugs”)Therefore, your firm’s OTC drugs are not properly listed under section 510(j) of the FD&C Act, 21 U.S.C. 360(j), rendering these drugs misbranded under section 502(o) of the FD&C Act, 21 U.S.C. 352(o). The introduction or delivery for introduction of a misbranded drug into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). Additionally, failure to list a drug is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p).Complete, accurate, and up-to-date establishment registration and drug listing information is essential for promoting and protecting patient safety. The FDA relies on this information for several critical programs, including drug establishment inspections, supply chain security, and post-market surveillance. Additionally, establishment registration and drug listing data are extensively utilized outside the FDA for purposes such as electronic prescribing systems, electronic health records, insurance reimbursement processes, and patient education initiatives.It is your responsibility to ensure that all drugs manufactured at your establishment comply with establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations. Registration and listing information, along with instructions on how to properly register an establishment or submit drug listings can be found at https://www.fda.gov/drugs/electronic-drug-registration-and-listing-system-edrls/electronic-drug-registration-and-listing-instructions.Cosmetic Manufactured for Distribution in the United StatesIn addition, some of the products you distribute may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you distribute must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.Further, your facility may be subject to requirements under the Modernization of Cosmetics Regulation Act of 2022 (MoCRA). You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3015274499 and ATTN: Paul Z. Balcer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research/S/Tina SmithCaptain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and Research

按照2025年全区药品生产监督检查计划， 自治区药监局对部分药品上市许可持有人 （药品生产企业）开展了现场检查。根据政务信息公开制度要求，现将检查情况予以通告。附件：药品上市许可持有人（药品生产企业）监督检查信息（2025年第3期）.doc 宁夏回族自治区药品监督管理局2025年12月26日    （此件公开发布）

Delivery Method:Via EmailProduct:DrugsRecipient:Wang ZhengAgebox Inc.108 W 13th StWilmington,DE19801-1145United Statesinfo@agebox.comcw3@agebox.comserv@agebox-ops.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERDecember 19, 2025RE: 718252Wang Zheng:This letter is to advise you that the U.S. Food and Drug Administration (FDA) reviewed your website at the Internet address https://agebox.com/ and your social media accounts, including Facebook at www.facebook.com/Agebox.Official, in September 2025. The FDA has observed that your website offered “iKids-Growth IGF-1 Support Day Formula” and “iKids-Growth IGF-1 Support Night Formula” (hereinafter iKids-Growth products) for sale in the United States. Additionally, FDA has obtained samples of your iKids-Growth products. As described below, these products are unapproved new drugs 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). Furthermore, your iKids-Growth products are misbranded drugs under section 502 of the FD&C Act, 21 U.S.C. 352, and introduced or delivered for introduction into interstate commerce in violation of section 301(a) of the FD&C Act, 21 U.S.C. 331(a).FDA confirmed through laboratory analysis that samples of both your iKids-Growth products contain the undeclared ingredient ibutamoren mesylate. Ibutamoren (also known as MK-677) is an active ingredient not approved by FDA, and therefore its safety and efficacy have not been established. Ibutamoren is a growth hormone secretagogue that stimulates the release of growth hormone. Use of ibutamoren may cause serious side effects including increased appetite, water retention, fatigue, muscle pain, potential alterations in glucose metabolism and insulin sensitivity, and even may increase the potential for congestive heart failure in certain individuals. Long-term effects of ibutamoren use are unknown and may pose additional health risks. This ingredient may also interact with medications and products a consumer may be taking in potentially harmful ways.Your iKids-Growth products are marketed as dietary supplements, according to information found on the labels and/or labeling of the products. However, FDA has concluded that ibutamoren is excluded from the dietary supplement definition under section 201(ff)(3)(B)(ii) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(ii). Under that provision, if an article has been authorized for investigation as a new drug for which substantial clinical investigations have been instituted and for which the existence of such investigations has been made public, then products containing that substance are outside the definition of a dietary supplement, unless the substance was marketed as a dietary supplement or as a conventional food before such authorization. Based on available evidence, ibutamoren has been authorized for investigation as a new drug, substantial clinical investigations of ibutamoren as a new drug have been instituted, and the existence of such investigations has been made public,1and ibutamoren was not marketed as a dietary supplement or as a conventional food prior to such authorization. Therefore, FDA has determined that ibutamoren is excluded from the definition of a dietary supplement under section 201(ff)(3)(B)(ii) of the FD&C Act, 21 U.S.C. 321(ff)(3)(B)(ii).Unapproved New DrugsYour iKids-Growth products are drugs as defined by section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or intended to affect the structure or any function of the body. Examples observed on your website and social media that provide evidence of the intended use of these products as drugs include, but may not be limited to, the following:On your webpage https://agebox.com/:“iKids-Growth doesn't add hormones or just nutrients—it works within this natural pathway to amplify your child’s own growth signals”“DaytimeSupports bone and muscle function associated with IGF-1 activity”“NighttimeSupports liver function involved in GH and IGF-1 pathways”On your webpage https://agebox.com/pages/help-faq?_pos=1&_psq=faq&_ss=e&_v=1.0:“Will iKids-Growth help my kid grow taller?Yes. iKids-Growth is designed to amplify the body’s own growth signals within the GH-IGF-1 axis, which plays a key role in healthy height development.”How does iKids-Growth work?It works within the GH-IGF-1 axis by directly amplifying the body’s own growth signals:o Helps the liver respond better to growth hormone, increasing IGF-1 productiono Helps bones and muscles respond better to IGF-1, promoting healty height gainBy gently enhancing both ends of this key growth pathway, iKids-Growth helps unlock children’s natural growth potential – through a science-backed, hormone-free solution.”On your webpage https://agebox.com/pages/join-investment?_pos=1&_psq=joint+inves&_ss=e&_v=1.0:“The formula of iKids-Growth is scientifically validated to effectively increase IGF-1 levels in children, promoting healthy bone growth.”“iKids-Growth by Agebox is specially formulated to support children’s height development by increasing GH sensitivity in liver cells to boost IGF-1 production. It also enhances IGF-1 utilization, promoting bone cell proliferation and differentiation for optimal growth and development.”On a September 4, 2024, post on your Facebook social media website https://www.facebook.com/photo?fbid=122152760630252675&set=a.122146580282252675:“iKids-Growth is a specialized dietary supplement that enhances insulin-like growth factor 1 (IGF-1) levels.”“IGF-1 has a direct and powerful role in promoting height increase.”“This process effectively regulates and increases height growth.”“Let's unlock the potential of our kids’ growth with the power of the GH–IGF-1 Axis!”On a September 25, 2024, post on your Facebook social media website https://www.facebook.com/photo?fbid=122157196292252675&set=a.122146580282252675:“Unlock Your Child's Growth Potential with Agebox iKids-Growth!”“iKids-Growth is specially formulated to enhance IGF-1 levels, promoting healthy bone development and height increase.”“Boosts Growth Hormones: Stimulates natural growth processes.”“[S]tart your journey towards a healthier, taller future with Agebox!”Your iKids-Growth products are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because they are not generally recognized as safe and effective (GRASE) for use under the above-described conditions prescribed, recommended, or suggested in their labeling. With certain exceptions not applicable here, a new drug may not be legally introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a). No approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, these products are unapproved new drugs. The introduction or delivery for introduction into interstate commerce of these unapproved new drug products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).Misbranded DrugsYour iKids-Growth products are misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). Under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), a drug is misbranded if its labeling is false or misleading in any particular. Section 201(n) of the FD&C Act, 21 U.S.C. 321(n), provides that, in determining whether an article’s labeling or advertising “is misleading there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in light of such representations.”The labeling for your iKids-Growth products do not declare that they contain ibutamoren mesylate. As previously mentioned, parents may give these products to their children without knowing that they contain an ingredient that may cause serious harm or dangerous product interactions. The failure to disclose ibutamoren mesylate in product labeling renders your iKids-Growth products misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).The introduction or delivery for introduction into interstate commerce of these misbranded drug products is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations that may exist in connection with your products. 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.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address this matter may lead to regulatory or legal action including, without limitation, seizure and injunction.Please notify FDA in writing, within fifteen working days of receipt of this letter, of the specific steps you have taken to correct any violations. Include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. 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. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.Your response should be sent to U.S. Food and Drug Administration, CDER/OC/Office of Unapproved Drugs and Labeling Compliance by email to FDAAdvisory@fda.hhs.gov. Please include your firm name and the unique identifier “718252” in the subject line of the email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administration____________________1See, e.g., Copinschi G, et al. Effects of a 7-day treatment with a novel, orally active, growth hormone (GH) secretagogue, MK-677, on 24-hour GH profiles, insulin-like growth factor I, and adrenocortical function in normal young men. J Clin Endocrinol Metab. 1996 Aug;81(8):2776-82. doi: 10.1210/jcem.81.8.8768828. PMID: 8768828 and Codner E, et al. Effects of oral administration of ibutamoren mesylate, a nonpeptide growth hormone secretagogue, on the growth hormone-insulin-like growth factor I axis in growth hormone-deficient children. Clin Pharmacol Ther. 2001 Jul;70(1):91-8. doi: 10.1067/mcp.2001.116514. PMID: 11452249.