Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-25-46Product:DrugsRecipient:Mr. Stephen SaadGroup Chief ExecutiveAspen Pharmacare Holdings Limited9 Rydall Vale ParkDouglas Saunders Drive, La Lucia RidgeDurbanKwaZulu-Natal4051South AfricaSSaad@aspenpharmaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-46February 24, 2025Dear Mr. Saad:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Aspen SA Sterile Operations (Pty) Ltd. (an Aspen Pharmacare Holdings Limited subsidiary), FEI 3007490529, at 8B Gibaud Road, Kortsen, Gqeberha, South Africa 6020, from September 9 to 17, 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 8, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to 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 did not establish appropriate specifications or test your sterile over-the-counter (OTC)(b)(4)drug products to monitor impurities at release and throughout expiry. For example:You did not perform impurity testing prior to release and during stability for(b)(4).You did not establish scientifically justified specifications to monitor impurities during stability testing of drug products containing Naphazoline Hydrochloride or Tetrahydrozoline Hydrochloride active pharmaceutical ingredient (API).In your response, you state that the impurity limits were established based on your customer’s requirements and that no limits were included for release testing. You provide your customer’s health hazard evaluation (HHE) which concluded that the presence of Impurity(b)(4)at stability levels of up to(b)(4)% of the labeled(b)(4)content would not pose any safety risk for those that use the products according to directions. The Agency disagrees with the HHE assessment and concludes that the presence of impurity levels at(b)(4)% may pose a risk to patient safety at the recommended dosage. It is your responsibility to ensure that appropriate specifications are established to monitor impurities throughout the expiry period.Your response is inadequate. You lack adequate scientific rationale for the current impurity specifications of your drug products. A similar deficiency for the lack of impurity specifications for release and stability testing for(b)(4)API containing products was also identified during the 2016 inspection. However, this deficiency has not been fully addressed to date. Additionally, your risk assessment does not include an evaluation of reserve samples of potentially impacted product batches distributed to the United States.Drug product batches must be tested for identity, strength, quality, and purity prior to release. Insufficient release and stability testing to appropriately detect impurities in your drug products could potentially impact product quality and patient safety.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.Degradation study protocols and reports for your drug products, which should include impurities that will be monitored throughout the product life cycle as well as your scientific justification for the acceptance criteria and study design.A list of current and revised specifications for release and stability testing, including test methods, used to analyze each batch of your drug products before a batch disposition decision.o An action plan and timelines for conducting full chemical testing of reserve 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 reserve samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.2. Your firm failed to 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)).Poor Aseptic PracticesDuring the inspection of your facility, we observed poor practices and behaviors in ISO 5 areas during the manufacturing of sterile(b)(4)drug products. These poor practices included, but were not limited to:Operators blocked first air by placing their gloved hands directly over open sterilized bottles without clearing them from the aseptic filling line.Operators used their gloved hands instead of using appropriate sterile tools to remove jammed bottles.Operator movements in the critical areas were not always slow and deliberate.Operators used goggles that had numerous open holes and therefore had exposed skin during line set-up and aseptic processing.In 2022, your firm identified contamination in two media fill batches one on the “(b)(4)” aseptic filling line and another on the “(b)(4)” aseptic filling line. You identified the root cause as poor aseptic behavior. These contamination events along with the poor aseptic practices observed during our inspection indicate your aseptic manufacturing operations may lack adequate control. Your firm did not perform a sufficiently comprehensive evaluation of aseptic behavior of operators as part of this recurrent trend.We also note that open door interventions required a large door to be opened. On numerous occasions, the door remained opened for extended periods of time while the line was still in-operation. When opened, the door was exposed to the ISO 7 area, and when being closed, there was a significant risk of the lower quality room air sweeping into the ISO 5 aseptic processing area. Empty sterile containers were located extremely close to the door. In addition, operators did not adequately disinfect the open door. While spraying disinfectant on the(b)(4), operators failed to consider open sterilized bottles on the line, exposing them to potential contamination.Inadequate Smoke Studies and Cleanroom DesignYour smoke studies did not adequately demonstrate unidirectional air flow in the ISO 5 classified areas used for the aseptic filling of ophthalmic drug products on the “(b)(4)” and “(b)(4)” aseptic filling lines. For example:Your smoke studies lacked simulation of aseptic line set-up, dynamic operations, and interventions that occur during aseptic manufacturing operations.Generation of smoke was not sufficient to demonstrate unidirectional air flow.We also note that there were multiple aspects of your cleanroom and aseptic processing line design which represented fundamental contamination risks:There was no physical barrier between the operator and the open(b)(4)-sterilized bottles on the conveyor. Your production operator remained inside the ISO 5 aseptic processing area, sitting or standing next to the conveyor line where open, exposed bottles pass.There were extensive manual interactions with the aseptic processing line and its exposed sterile drug product and containers/closures.Operators performed multiple manual interventions during filling by(b)(4)or(b)(4)due to(b)(4)not being installed on these(b)(4). These interventions may pose inherent risks to your aseptic processes.The ISO 5 area is critical because sterile product is exposed and therefore vulnerable to contamination. Your aseptic filling process should be designed, and operations executed, to prevent contamination hazards to your sterile product. The flawed design of the filling line and execution of the aseptic operations promote influx of contamination into the critical filling areas.In your response, you indicate that you temporarily suspended manufacturing on the “(b)(4)” aseptic filling line. You acknowledge that the design of your aseptic filling lines is not optimal and indicate that an independent review of your design and remediation plans for both “(b)(4)” and “(b)(4)” aseptic filling lines will be performed. You also commit to perform new smoke studies under static and dynamic conditions and evaluate associated risks. You indicate that you have engaged a third-party consultant to assist in improving aseptic practices.Your response is inadequate because it does not sufficiently address the lack of oversight of aseptic behavior of operators. Further, you do not adequately investigate poor aseptic practices to determine the impact on sterile drug products manufactured and aseptic processing areas. You also do not clearly specify how you will improve your smoke studies, including what interventions will be included, and how you will address potential deficiencies.For additional guidance on aseptic processing see FDA’s guidance document,Sterile Drug Products Produced by Aseptic Processing - Current Good Manufacturing Practiceto help you meet the CGMP requirements when manufacturing sterile drugs using aseptic processing at https://www.fda.gov/media/71026/download.In response to this letter, provide:Your plan to ensure appropriate aseptic practices and cleanroom behavior during production. Include steps to ensure routine and effective supervisory oversight for all production batches. Also describe the frequency of quality unit (QU) oversight (e.g., audit) during aseptic processing and its support operations.A thorough retrospective review and risk assessment that evaluates how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.Comprehensive risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including an independent assessment that includes, but is not limited to:o All human interactions within the ISO 5 areao Equipment placement and suitability, including ergonomics for each human interaction.o Air quality in the ISO 5 area, and surrounding room including, but not limited to, air volume, air flow, and microbial/particulate levelso Reduction or elimination of aseptic manipulations and connections (e.g., replacing post-filtration aseptic connections with sterilize-in-place system)o Facility layouto Personnel Flows and Material Flows (throughout all rooms used to conduct and support sterile operations)A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible improvements to be made to aseptic processing operation design and control.Smoke studies under dynamic conditions, with thorough and complete evaluations of aseptic interventions and operator positioning within the critical filling areas. After you remediate your aseptic operation, provide smoke studies that visualize airflow and critically evaluate unidirectional airflow. Include a video of your dynamic smoke studies.3. Your firm failed to exercise appropriate controls over computer or related systems to assure that only authorized personnel institute changes in master production and control records, or other records (21 CFR 211.68(b)).Your Production and QU did not review electronic raw data and audit trails to ensure data integrity prior to batch release. Your operators obtained and printed a passing result after multiple production filter integrity tests failed. Your operators did not record or print the failing results. For example:On August 8, 2024, two operators performed four post-use sterilizing filter integrity tests for(b)(4)batch(b)(4). The four tests included three failing results and the final passing result. Your operators only reported the passing result.On July 25, 2024, two operators performed nine filter integrity tests associated with(b)(4), bulk batch(b)(4). The nine tests included five failing results, three aborted tests, and the final passing result. Your operators only reported the passing result.In your response, you acknowledge the deficiency and commit to perform a full audit trail review of your production equipment. You also indicate that you are completing the investigations into anomalous filter integrity tests.Your response is inadequate as you do not provide details of the investigation outcome or explain whether effective corrective actions and preventive actions (CAPAs) have been implemented. Further, you do not provide the scope and time period of the retrospective review to ensure all batches potentially affected are part of the assessment.See FDA’s guidance document,Data Integrity and Compliance With Drug CGMPfor guidance on establishing and following CGMP compliant data integrity practices athttps://www.fda.gov/media/97005/download.We strongly recommend that you retain a qualified consultant to assist in your remediation. In response to this letter, provide:A comprehensive investigation into the extent of the inaccuracies in data records and reporting including results of the data review for drugs distributed to the United States. Include a detailed description of the scope and root causes of your data integrity lapses.o 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.o A management strategy for your firm that includes the details of your global CAPA plan. The detailed corrective action plan should describe how you intend to ensure the reliability and completeness of all data generated by your firm including manufacturing records.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 Ensure that appropriate procedures are in place regarding the review of all critical electronic data (e.g., filter integrity testing).o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.4. Your firm failed to establish an adequate system for monitoring environmental conditions in aseptic processing areas (21 CFR 211.42(c)(10)(iv)).You did not establish an adequate system for monitoring environmental conditions on the “(b)(4)’ aseptic filling line. For example:You did not conduct viable monitoring of the air and surfaces in ISO 5 areas where an operator was continuously present removing fallen bottles.You did not place the non-viable particle monitoring (NVPM) probes in representative ISO 5 areas where the product and primary components were exposed. Our investigators noted the following:o The NVPM probe closest to the(b)(4)was located approximately(b)(4)above the level of the(b)(4).o The NVPM probe nearest to the sterile cap(b)(4)was located approximately(b)(4)above the level of the(b)(4).Your operators routinely placed mobile NVPM devices in locations different from those specified in your procedures to monitor the ISO 5 areas. As such, NVPM data may not accurately represent the critical areas in operation.In your response, you commit to upgrade your “(b)(4)” aseptic filling line and perform a Quality Risk Assessment for NVPM in Suite(b)(4).Your response is inadequate. While you commit to conducting a Quality Risk Assessment for NVPM to identify, assess, and mitigate all gaps, you have not provided any updates on the status of risk assessment. Vigilant and responsive environmental monitoring programs should be designed to provide meaningful information on the state of control of your aseptic processing environment. Operations that include highly manually intensive aseptic activities warrant a more extensive environmental and personnel monitoring program, including but not limited to, heightened emphasis on well-timed sampling to appropriately monitor batch manufacturing conditions.In response to this letter, provide:A thorough, independent assessment, and CAPA for your environmental monitoring program. Include a comprehensive evaluation of monitoring, recording, alarm documentation, deviation investigation, data retention, and overall environmental control in your assessment.Your CAPA plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.An independent, retrospective evaluation of all ISO 5 NVPM deviations, root causes, and a relevant CAPA plan.Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors, such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.CGMP Consultant RecommendedWe acknowledge you engaged a consultant to assist your firm in meeting CGMP requirements. You are responsible for ensuring consultants you use are qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements and to correct repeat violations. 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 Production SuspendedWe acknowledge your commitment to suspend production of all drugs for the U.S. market.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 CAPAs.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 (IA) 66-40 on February 10, 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 Aspen SA Sterile Operations (Pty) Ltd., 8B Gibaud Road, Kortsen, Gqeberha, South Africa 6020 into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days1. Specify what you have done to address any 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. We request you email CDER-OC-OMQ-Communications@fda.hhs.gov, within 5 days of receipt of this letter to schedule a regulatory meeting.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3007490529 and ATTN: Anita Narula, Ph.D.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research____________________1Under program enhancements for the Generic Drug User Fee Amendments (GDUFA) reauthorization for fiscal years (FYs) 2023-2027, also known as the GDUFA III Commitment Letter, your facility may be eligible for a Post-Warning Letter Meeting to obtain preliminary feedback from FDA on the adequacy and completeness of your corrective action plans.

Delivery Method:VIA Electronic MailReference #:320-25-54Product:DrugsRecipient:Mr. Ahmet KoyuncuCEO and Chairman of the Board of DirectorsNeva Global Grup Sanayi Ic Ve Dis Ticaret Anonim Sirketi14/1 Akcaburgaz Mahallesi, 137. Sokak34522Esenyurt/İstanbulTurkeyIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-54March 12, 2025Dear Mr. Koyuncu:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Neva Global Grup Sanayi Ic Ve Dis Ticaret Anonim Sirketi, FEI 3018589922, at 14/1 Akcaburgaz Mahallesi, 137. Sokak, Esenyurt, Istanbul, from September 16 to 20, 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 4, 2024 response to our Form FDA 483 in detail.CGMP ViolationsDuring our inspection, our investigator observed specific violations including, but not limited to, the following.1. 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 manufactures over-the-counter (OTC) drug products such as(b)(4). You failed to perform adequate identity testing of each component lot used in the manufacture of your OTC drug products, including for(b)(4)and active ingredients(b)(4)and(b)(4). You also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals.(b)(4)You failed to adequately test your incoming(b)(4), used as an active pharmaceutical ingredient, for(b)(4). The use of(b)(4)contaminated with(b)(4)has resulted in various lethal poisoning incidents in humans worldwide.(b)(4).(b)(4)You failed to adequately test each shipment of each lot of(b)(4)for identity, a component at high-risk of(b)(4)contamination. Identity testing for(b)(4)and certain other high-risk drug components1includes a limit test in the United States Pharmacopeia (USP) to ensure 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 this component for use in the manufacture of your drug products.The use of ingredients contaminated with(b)(4)has resulted in various lethal poisoning incidents in humans worldwide.(b)(4)contamination at(b)(4).In your response, you state that you will acquire a high-performance liquid chromatograph (HPLC) to perform analysis of incoming materials to verify compliance with FDA’s testing requirements. Your response is inadequate. You did not provide a detailed plan for how components will be tested, including test methods and review of compendial requirements. You also did not adequately detail how you will verify the reliability of your suppliers’ COA, nor how you will perform qualification of your suppliers. Further, you did not consider a retrospective assessment, such as identity testing of reserve samples, or assessment by other methods, of the components used in your OTC drug products that were distributed in the United States within expiry.Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications before use in the manufacture of your drug products. Historically, we note that the Agency has detected(b)(4)in(b)(4)originating in Turkey.In your response, provide: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.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 lots 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 actions and preventive actions (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.The chemical and microbiology quality control specifications you use to test each incoming lot of each incoming lot of components, including, 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 summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure that describes this COA validation program.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.2. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a))You failed to adequately validate your production and process controls used in the manufacture of your OTC drug products. You also lacked adequate documentation that the equipment used to manufacture and test your drug product was qualified and suitable for its intended use.In your response, you state that you will establish critical process parameters and a written procedure and protocol to perform process validation of OTC drugs.Your response is inadequate. You did not provide supportive documentation for your drug process validation, and your equipment qualification program and interim production plans are unclear. You also did not consider a retrospective impact assessment of these deficiencies on the quality of your products currently in U.S. distribution.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure that you maintain a stable manufacturing operation throughout the product lifecycle.Without adequate process validation, incorporating all manufacturing inputs and parameters that can affect product quality, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA's guidance for industry,Process Validation: General Principles and Practicesfor general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures.Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing appropriate PPQ for each of your marketed drug products.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.3. Your firm failed to establish an adequate written testing program designed to assess the stability characteristics of drug products. (21 CFR 211.166(a)).Your firm did not establish an adequate ongoing stability testing program to demonstrate that your OTC drug products met established specifications for identity, strength, quality, and purity for the duration of their labeled(b)(4)shelf lives.In your response, you state that you will create a stability protocol outlining the stability, testing, objectives, methodologies, and responsibilities. You also state that you will train your employees accordingly.Your response is inadequate. You did not provide data to demonstrate that the chemical and microbiological properties of your drug products will remain within specification throughout their expiry period. You also failed to provide interim measures to address whether your drug products that remain on the market are supported by adequate stability data.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 theirlabeled expiry.In your response, provide:A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability-indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid o detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability program.4. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not provide adequate oversight for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:Adequate written records for major equipment cleaning and maintenance (21 CFR 211.182).Adequate written procedures for laboratory controls that include scientifically sound and appropriate specifications for finished drug products (21 CFR 211.160(b)).Performance of periodic (i.e., at least annual) product reviews (21 CFR 211.180(e)).Your QU and management stated multiple times during the inspection to our investigator that you were unaware that OTC products are considered drugs based on U.S. regulations, despite the labeling of your products as drugs.An adequate QU overseeing all manufacturing operations is necessary to consistently ensure drug quality. Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR parts 210 and 211, at https://www.fda.gov/media/71023/download.In your response, 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.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.Drug Import InformationBased on information collected during the inspection and FDA import records, there appear to be discrepancies in the electronic import entry submissions for your drug products, specifically regarding the declaration of the correct manufacturer. Prior to distributing products intended for the United States, you should ensure that the firms shipping or importing your drug products, and the entry filers transmitting the electronic data to U.S. Customs and Border Protection and FDA, are declaring your firm as the manufacturer, as well as using your registration number and product listing number(s). If other firms are shipping your products they may be declared as the shipper; however, your firm needs to be declared as the manufacturer. See 21 CFR 1.74(a)(1).Cosmetics Manufactured for Distribution in the United StatesIn addition, we note that some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act (21 U.S.C. 321(i)). Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. 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 of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA). Information on MoCRA requirements may be found at https://www.fda.gov/cosmetics/cosmetics-laws-regulations/modernization-cosmetics-regulation-act-2022-mocra.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 February 12, 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 Neva Global Grup Sanayi Ic Ve Dis Ticaret Anonim Sirketi, at 14/1 Akcaburgaz Mahallesi, 137. Sokak, Esenyurt, Istanbul, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3018589922 and ATTN: Daniel W. Brisker.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCc:Registered U.S. Agent:Mehmet Akif TutuncuKYNC Design, LLCmehmet@kyncdesign.com_____________________1Components with higher risk of(b)(4)contamination compared to other drug components.

Delivery Method:VIA UPSReference #:320-25-35Product:DrugsRecipient:Mr. Mark LovilPresidentRite-Kem Incorporated703 Westmoreland DrTupelo,MS38801United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-35January 28, 2025Dear Mr. Lovil:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Rite-Kem Incorporated, FEI 1000337046, at 703 Westmoreland Dr, Tupelo, Mississippi, from September 9 to 12, 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 acknowledge receipt of your response to our Form FDA 483.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).Your firm manufactures over-the-counter (OTC) drug products including hand sanitizers antimicrobial hand soap, and antimicrobial towels. Your firm failed to adequately test batches of your drug products for the identity and strength of your active ingredients (e.g.,(b)(4), benzalkonium chloride, and chloroxylenol) before release and distribution. According to your batch records, your finished product testing only includes pH, viscosity, color, appearance, and odor. Additionally, it appears your firm is not performing microbiological testing for each batch of your drug products prior to release.In your response, you state that you will develop a system to test your finished products, and that it will take approximately 9 months to implement. Your response is inadequate, as it only discusses the active ingredient ethanol, and does not provide sufficient information or documentation. Additionally, your response states that it will take approximately 9 months to create and fully implement adequate finished product testing without justification. Furthermore, you did not consider a risk assessment or retrospective review of products that have been released without appropriate testing and remain within expiry.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.In response to this letter, provide the following:A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.o An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.o A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.2. Your firm failed to 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)).You failed to perform adequate identity testing of each component lot used in the manufacture of your OTC drug products. You also relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals.GlycerinYou failed to adequately test each shipment of each lot of glycerin for identity, a component at high-risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination. Identity testing for glycerin and certain other high-risk drug components1includes a limit test in the United States Pharmacopeia (USP) to ensure the component meets the relevant safety limits for levels of DEG or EG. 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 this component for use in the 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/regulatory-information/search-fda-guidance-documents/testing-glycerin-propylene-glycol-maltitol-solution-hydrogenated-starch-hydrolysate-sorbitol.(b)(4)You failed to adequately test your incoming(b)(4), used as an active pharmaceutical ingredient, for methanol. The use of(b)(4)contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document(b)(4).In your response, you state that you will develop a system to test your components and qualify your suppliers, and that it will take approximately 9 months to implement. Your response is inadequate as it does not provide sufficient information or documentation. Additionally, your response states that it will take approximately 9 months to create and fully implement adequate component testing without justification. Furthermore, you did not consider retrospective identity testing of reserve samples, or assessment by other methods, of the components used in your OTC drug products that were manufactured, distributed, and remain within expiry.Furthermore, we note that you are using(b)(4)as a component in the manufacture of your drug products. At a minimum, you must use(b)(4)(refer to USP General Chapter(b)(4)) to manufacture your topical, non-sterile drug products.(b)(4)must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes.Without adequate testing, you do not have scientific evidence that components conform to appropriate specifications prior to use in the manufacture of your drug products. As a manufacturer, you have a responsibility to sample, test, and examine drug components before use in production to assure adequate quality.In response to this letter, provide the following: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.The chemical and microbiological quality control specifications you use to test and release each incoming lot of component for use in manufacturing.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 re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot.A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your standard operating procedure (SOP) that describes this COA validation program.A commitment to provide DEG and EG 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 DEG and EG.A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, 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.Provide scientific justification to demonstrate the(b)(4)you use is suitable for use in drug manufacturing operations. If you determine the(b)(4)you used to manufacture drugs was not suitable, provide a detailed risk assessment addressing the potential effects on the quality of all drug product lots currently in U.S. distribution and within expiry. Specify actions you will take in response to the risk assessment.3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not provide adequate oversight for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:Adequate validation of your production and process controls used in the manufacture of your drug products, including to qualify the equipment used to manufacture your drug products (21 CFR 211.100(a)).The establishment of adequate QU procedures including, but not limited to, complaint handling, cleaning and maintenance of equipment, employee training, and labeling operations (21 CFR 211.22(d)).Adequate training for employees engaged in the manufacture, processing, packing, or holding of drug products (21 CFR 211.25(a)).Appropriate batch production and control records that include documentation of the accomplishment of each significant step in manufacturing of your drug products (21 CFR 211.188(b) & 211.22(c)).Establishment of an adequate, ongoing stability program (21 CFR 211.166(a)).Adequate equipment cleaning and cleaning procedures, as well as appropriate cleaning validation (21 CFR 211.67(a) and 67(b)).Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.In response to this letter, provide the following: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 comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.o Detailed definition of the specific attributes to be tested at each station (timepoint).All procedures that describe these and other elements of your remediated stability program.A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing PPQ for each of your marketed drug products.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.Your firm also manufactures non-pharmaceutical products, including industrial chemicals such as anti-freeze, concrete cleaner, urinal blocks, and asphalt release. It is unclear if your manufacturing equipment and surrounding areas are dedicated to drug manufacturing. Confirm:o Whether the equipment utilized in drug product manufacturing is dedicated. If not, provide a list of all other products manufactured on the equipment, including all their components.o Whether the area used for manufacturing drug products are utilized to manufacture, process, pack, or hold any non-drug products. If so, provide a list of all other products manufactured, processed, packed, or held in this area, including all their components.Drug Production SuspendedWe acknowledge your commitment to temporarily cease the production of drugs at this facility while you implement corrective actions.When you 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 CAPAs.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. 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 1000337046 and ATTN: CDR Frank Verni.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.

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Mr. William C. Paske, PhDOwnerRed Oak Instruments, LLC3331 Prosperity CourtMissouri City,TX77459United StatesIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 692368February 21, 2025Mr. William C. Paske, PhD, OwnerRed Oak Instruments, LLC3331 Prosperity CourtMissouri City, TX 77459Dear Mr. Paske:During an inspection of your firm, Red Oak Instruments, LLC (Red Oak, ROI, or “the firm”), located in Missouri City, Texas, on July 15, 2024, through July 26, 2024, an investigator from the United States Food and Drug Administration (FDA) determined that your firm is a manufacturer and distributor of the AC Powered Dynamometer RU-Fit (Model SR-3053) medical device. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these are devices 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.We received your responses dated August 13, 2024, November 7, 2024, and February 5, 2025 concerning our investigator’s observations on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address the responses below, in relation to each of the noted violations, and any additional responses will be reviewed as part of your warning letter response.Misbranded and/or Unapproved Device ViolationsFDA has reviewed your website at https://www.redoakinstruments.com on January 15, 2025, and determined that the RU-FIT (Model SR-3053) is 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 (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed. The RU-FIT (Model SR-3053) is 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 this device with major changes or modifications to the intended use 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)(ii).Devices classified under 21 CFR 888.1240 AC-powered dynamometer are exempt from premarket notification unless they exceed the limitations on exemption at 21 CFR 886.9(a). However, there is evidence that the RU-FIT (Model SR-3053) is intended for uses that are different from those of legally marketed devices classified under 21 CFR 888.1240 AC-powered dynamometer. Generic devices of this type are intended “to assess neuromuscular function or degree of neuromuscular blockage by measuring, with a force transducer (a device that translates force into electrical impulses), the grip-strength of a patient's hand.” 21 CFR 888.1240 However, your firm is marketing the RU-FIT (Model SR-3053) for a different intended use, namely the device is intended to screen for possible mild traumatic brain injury (mTBI), also known as concussion.Examples include:From the RU-Fit (Model SR-3053) User Guide• This device is intended to screen for possible head injuries in the cases of head impact where there is not any visible blood, other than minor scraps [sic].• The SR-3053 should be used…to compare recognition and choice reaction times of an injured or non-injured individual.From the RU-Fit (Model SR-3053) Training Presentation“Head Impact Trauma Screen: Analysis”“Recognition reaction times for the small, index fingers and thumb”“Cognitive reaction times for the small, index fingers and thumb”“Summary Sheet For Concussive Impact”From the Red Oak Instruments website (https://www.redoakinstruments.com)Since denial is a strong symptom of mTBI subjects, the necessary compliance is not always achievable. A better technology is needed. RedOak Instruments provides the needed technology.Physicians, clinicians, military medics, emergency responders, coaches and trainers can now immediately evaluate the severity of a bloodless head injury on-site. This is especially important in the case of mTBI and other head injuries because denial of injury is a common reaction, and visible symptoms may be difficult to assess in the absence of visible blood such that the injury goes undetected.RedOak Instruments, LLC is a USA based biomechanical and software-based company which provides objective physiological measurements to screen for injuries, ailments and to monitor recovery. The test will document the reduction or improvement of factors related to head injury including fine motor control, coordination and reaction time.Additionally, ROI's RU-Fit model SR-3053 SensoKinetoGram offers objective monitoring for sports training programs to aid trainers and coaches as they develop and improve the coordination and reaction times of their athletes.Test the hands and protect the brain.You state that “all systems are FDA cleared…” however you device is not cleared as presently marketed.Assessments of reaction time and cognitive function are not measurements of the grip-strength of a patient’s hand, and screening for, or detection of, mTBI is a neurological evaluation following head injury, not an assessment of neuromuscular function following hand injury.Further, we note that the RU-FIT (Model SR-3053) was previously cleared under K012492 with the following indications:Any situation where the hand grip or pinch strength would be a valuable piece of data in the evaluation of a person who has sustained an injury or suffers a disease of his/her hand(s).To measure grip or pinch strength in an injured and uninjured hand.To conduct pre-employment screening for physically demanding job activities.To establish an industrial strength testing program in general, and to match the strength of workers to the strength demands of specific job duties in the workplace.Thus, your firm’s promotion of the device provides evidence that the device is intended for to screen for possible mild traumatic brain injury (mTBI), also known as concussion, which would constitute a major change or modification to its intended use, for which your firm lacks clearance or approval.For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(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.Medical Device Reporting ViolationsOur inspection also revealed that your firm has failed to adequately develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. For example, during the inspection, the firm identified the document titled “Complaint MDR SOP ROI-000-0007,” dated 12/11/2019 as its written MDR procedure. After reviewing the procedure, the following deficiencies were noted:1. Your procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example:a. There are no definitions of what your firm will consider to be a reportable event under 21 CFR Part 803. The exclusion of definitions from 21 CFR 803.3 for the terms ‘become aware’, ‘caused or contributed’, ‘malfunction’, ‘MDR reportable event’, and ‘serious injury’, and the definition for the term ‘reasonably suggests’, found in 803.20(c)(1) may lead your firm to make an incorrect reportability decision when evaluating a complaint that may meet the criteria for reporting under 21 CFR 803.50(a).b. Your procedure does not include instructions for how your firm will evaluate information about an event to make MDR reportability determinations in a timely manner.2. Your procedure does not establish internal systems that provide for a standardized review process to determine when an event meets the criteria for reporting under this part, as required by 21 CFR 803.17(a)(2). For example,a. There are no instructions for conducting an investigation of each MDR reportable event and evaluating the cause of the event.b. Your procedure, as written, does not specify who makes the decision for reporting events to FDA.c. The flowchart in your firm’s procedure does not reference a process for investigating events identified as MDRs to ensure that MDRs are submitted to FDA within the required reporting timeframes, as required under 21 CFR 803.17(a)(1).3. Your procedure does not establish internal systems that provide for timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3). Specifically, the procedure does not include:a. Instructions for how to obtain and complete the FDA 3500A form.b. The circumstances under which your firm must submit an initial 30 days, supplemental or follow-up, 5-day report and the requirements for such reports.c. A process for submitting initial and supplement or follow-up reports to FDA in an electronic format that FDA can process, review and archive. Information about the Final Rule for eMDR and the eMDR set-up process can be found on the FDA website at: https://www.fda.gov/medical-devices/mandatory-reporting-requirements-manufacturers-importers-and-device-user-facilities/emdr-electronic-medical-device-reportingd. How your firm will submit all information reasonably known to it for each event. Specifically, which sections of the 3500A will need to be completed to include all information found in your firm’s possession and any information that becomes available as a result of a reasonable follow up within your firm.4. Your procedure does not describe how your firm will address documentation and record-keeping requirements, as required by 21 CFR 803.17(b), including:a. Documentation of adverse event related information maintained as MDR event files.b. Information that was evaluated to determine if an event was reportable.c. Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable, as required under 21 CFR 803.18(b)(1)(i).d. Systems that ensure access to information that facilitates timely follow-up and inspection by FDA.A device is deemed to be misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), if there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, which includes adverse event reports required under 21 CFR Part 803, respecting the device.Additionally, based on our records, as of October 29, 2024, there is no evidence that your firm established an active Electronic Submissions Gateway (ESG) production account for the electronic submission of MDR reports. Information about the ESG can be found at: How to Enroll in eMDR Program | FDA.The adequacy of your firm’s response dated August 13, 2024, cannot be determined at this time. Your firm’s response outlined plans to implement corrections and corrective actions, including creating an eMDR account and updating their MDR procedure. However, your firm did not provide documentation confirming the completion of these systemic corrective actions, including its revised MDR procedure, as they are still ongoing.Quality System Regulation (QSR) ViolationsOur inspection also revealed that the RU-Fit model SR-3053 is 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 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. These violations include, but are not limited to, the following:1. Failure to adequately establish design change procedures as required by 21 CFR 820.30(i).Specifically, you did not document a(b)(4). You also did not document the design verification of the(b)(4).The adequacy of your firm’s responses cannot be determined at this time. Your firm stated that it will update your Design Procedures to clarify when an ECO must be validated, or not, including training and that hardware changes will be documented that were not previously. You also state that you have rewritten your procedures, updated ECO forms, and “begun” documenting previously undocumented modifications. However, you have not provided evidence of corrective actions to show how you document design changes to ensure they are in compliance with 21 CFR 820.30(i).2. Failure of design verification to confirm that design output meets design input requirements as required by 21 CFR 820.30(f).Specifically, your firm lacks a Development Procedure Form to document design verification as required by section 9.3 of your Design Control procedure. Your firm did not document an update of acceptance limits for the(b)(4)based on statistical test results in version 1.1 of your Test Plan.The adequacy of your firm’s responses cannot be determined at this time. Your firm stated that it updated form ROI 001-0030-3 to show that the requisite measured uncertainties are within the specified range and that you(b)(4). Your firm stated that multiple calibration tests were carried out to demonstrate stability and that(b)(4)specifications are in the DMR and components used in manufacturing of(b)(4)are listed in the Inspection Acceptance Form. Your firm also stated it has(b)(4). However, your firm has not provided evidence of corrective actions to show how your design verification confirms that design output meets design input requirements.3. Failure to establish device acceptance procedures as required by 21 CFR 820.80(d).Specifically, you provided calibration test data but did not have a finished device acceptance procedure with complete product specifications.The adequacy of your firm’s responses cannot be determined at this time. You state that manufacturer certificates and testing data will be appended to calibration data, and you will confirm(b)(4)specifications. However, you have not provided evidence of corrective actions as to how you will develop and maintain a device acceptance procedure to ensure that each production run, lot, or batch of finished devices meets acceptance criteria.4. Failure to maintain device history record procedures as required by 21 CFR 820.184.Specifically, your Device History Record procedure states that you will record production run data, but you did not have such data for 107 RU-Fit devices you manufactured. You only had a bill of materials (BOM) provided as a Device Master Record (DMR).The adequacy of your firm’s responses cannot be determined at this time. You state that your data is available in excel charts and printed to pdf files. However, you have not provided evidence of the files stored electronically in your DMR folder.5. Failure to perform quality audits as required by 21 CFR 820.22.Specifically, your Internal Audit procedure states that you will conduct audits annually, but you did not have evidence of the performance of quality audits from 2018 to 2023.The adequacy of your firm’s responses cannot be determined at this time. You state that you could not perform audits due to staffing and funding but that conducted an audit in December of 2024 and is in your form ROI 001-0024-0 as a pdf file. you will conduct and document an audit in 2024. However, you have not yet provided evidence of the conduct of the audit in December 2024.6. Failure of management with executive responsibility to review the suitability and effectiveness of the quality system at defined intervals and with sufficient frequency as required by 21 CFR 820.20(c).Specifically, your Management Responsibility procedure states that you will conduct reviews annually, but you did not have evidence of the performance of management reviews from 2018 to 2023.The adequacy of your firm’s responses cannot be determined at this time. You state that you will update your Management Responsibility procedure and will conduct and document a review in 2024, including a minimum of one per quarter. However, you have not yet provided evidence of the conduct of your three review meetings stated as conducted since August 2024.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 at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, CMS case #692368 when replying. If you have any questions about the contents of this letter, please contact: Raymond W. Brullo, Compliance Officer at raymond.brullo@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 Boyd, MPH, USPHSDirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA UPSReference #:320-25-55Product:DrugsRecipient:Mr. Frank M. BardaniPresidentAdvanced Pharmaceutical Technology132 South Central AvenueElmsford,NY10523United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-55March 14, 2025Dear Mr. Bardani:The U.S. Food and Drug Administration (FDA) inspected your drug manufacturing facility, Advanced Pharmaceutical Technology Inc., FEI 3009963974, at 132 South Central Avenue, Elmsford, from July 10 to August 1, 2024. The products you manufacture at this facility are combination products under section 503(g) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 353(g) as your products include drug and device constituent parts.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) requirements for combination products1. See Title 21 Code of Federal Regulations (CFR) part 4, 21 CFR parts 210 and 211 (drug CGMP), and 21 CFR part 820 (Quality System or QS Regulation).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to drug CGMP requirements, 21 CFR parts 210 and 211, your combination products are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).In addition, information and records gathered during the course of the inspection reflect that your products,(b)(4), are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease in humans. Therefore, these products meet the definition of drug as defined in section 201(g)(1) of the FD&C Act [21 U.S.C. 321(g)(1)].We reviewed your August 22, 2024 response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence. We also acknowledge that you recently registered as a 503B Outsourcing Facility. However, you have been distributing your drug products in the United States since 2023, prior to registering as a 503B Outsourcing Facility.During our inspection, our investigator observed specific violations including, but not limited to, the following.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 sterilization processes (21 CFR 211.113(b)).You lacked appropriate controls to ensure the sterility of(b)(4)drug products that purport to be sterile. For example, you relied on the(b)(4)sterilization process without monitoring pre-sterilization bioburden. In addition, you failed to establish an adequate system, as was required by your standard operating procedure (SOP), for monitoring environmental conditions (including the frequency performed) to ensure your manufacturing areas were suitable for sterile drug production.In your response, you state that you plan to test for bioburden, prior to release, and will reject lots that fail to meet appropriate specifications for endotoxin. You also state that environmental monitoring is not required because your drug products are(b)(4)sterilized, and that you tested product that was manufactured more than(b)(4)prior for microbial content and the samples showed no signs of positive cultures.Your response is inadequate because you failed to include relevant details for pre-sterilization bioburden testing, including limits you have established, and the steps you will take in the event these limits are exceeded. In addition, appropriate environmental conditions for the manufacture of your drugs, including appropriate air quality, must be provided to protect products from microbiological contamination, even when(b)(4)sterilized, in order to minimize sterilization challenges and the byproducts of excessive bioburden.It should be noted that although the sterility test is a critical final quality control for products that purport to be sterile, it cannot be solely relied upon as justification to release each drug product batch, as the test is only the last in a series of design and control provisions intended to protect the consumer from distribution of an unsafe batch. Sample sizes for sterility testing are typically small compared to the total number of units in a batch and may not detect issues that result in sporadic non-sterility. For example, inadequate(b)(4)sterilization validation studies or failure to consistently execute a(b)(4)sterilization cycle within its validated state may go undetected for substantial periods if your firm places too much reliance on the final quality control test for sterility to identify a sterility assurance problem. It is also essential to note that any positive sterility test result represents a serious CGMP issue that requires a comprehensive investigation into the cause and extent of the problem, and prompt review of the qualification status of your(b)(4)sterilization process.This is a repeat violation from your 2019 and 2021 inspections.2. Your firm failed to have, for each batch of controlled-release dosage form, appropriate laboratory determination of satisfactory conformance to the specifications for the rate of release of each active ingredient (21 CFR 211.167(c)).You failed to provide adequate data demonstrating your drug products,(b)(4), have a(b)(4)of the active ingredient. For example, you claim your(b)(4)lasts for up to(b)(4)and that your(b)(4)products have(b)(4)effect for(b)(4). Your release and stability data for dissolution does not provide data that drug(b)(4). Drug products should not be released without appropriate determination of conformance to final specifications and intended use. There is a lack of assurance of appropriate quality and that your drug will have the intended effect it purports to possess.In your response, you state that you estimated the therapeutic duration and that you will remove(b)(4)claims until you perform adequate studies. Your response is inadequate because you did not provide a retrospective assessment of your drug products on the U.S. market within expiry to identify and take appropriate action on any product quality or patient safety risks.3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Your firm manufactures(b)(4)sterilized,(b)(4). You lacked adequate scientific rationale to demonstrate that your drug manufacturing processes are appropriately validated, reproducible, and controlled to consistently yield drug products of uniform character and quality. For example, you increased the commercial production batch size and released drug product without appropriate validation. You also failed to include critical process parameters in your batch records.In your response, you plan to revalidate manufacturing processes and include more detailed production steps. Your response is inadequate because you failed to provide a detailed plan or supportive documentation for adequately validating your drug production process.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluate batches to determine whether an initial state of control has been established.Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.This is a repeat violation from your 2019 and 2021 inspections.4. Your firm failed to establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products (21 CFR 211.22(a)).Contract Testing LaboratoriesYour quality unit (QU) did not exercise its responsibility to oversee your contract testing laboratory to ensure the appropriate finish product testing was being conducted. For example, you failed to ensure your contract testing laboratory completed the method validation protocol for(b)(4). The Method Validation Report did not identify potential impurities of(b)(4)referenced in the method validation protocol. You did not adequately ensure the executed test method was suitable to monitor all potential impurities.In your response, you provided an impurity method that did not adequately identify and characterize the potential impurities of your drug products. Your response is inadequate because the method validation protocol should include all potential impurities with the scientific justification for which ones would be included in the test method. You did not commit to performing a retrospective assessment of all the product lots currently on the market within expiry once new method validations are completed.In addition, your contract testing laboratory was conducting a single dissolution test point for your drug products without scientific justification that a single time point demonstrates a consistent drug absorption over an extended period of time.Your response states that the(b)(4)label claims were removed. Your response is inadequate because you did not provide sufficient scientific justification to support inadequately testing your finished drug product.Your firm’s quality systems are inadequate. See the 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.Contract Manufacturing OrganizationsYour firm utilizes a contract manufacturing organization (CMO) to manufacture your prescription sterile(b)(4)drug product,(b)(4). You stated to our investigators that you received a batch of(b)(4)from(b)(4). You received this drug product without performing an evaluation of(b)(4). You do not have adequate procedures to ensure that the sterile(b)(4)produced for your firm met appropriate quality attributes.In your response, you provide documentation indicating that the CMO of(b)(4)is(b)(4)and provided documentation of an audit performed at this facility. Your response is inadequate because your QU did not ensure the drug product was manufactured in accordance with CGMP requirements.Drugs 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.FDA sent an electronic request for records and other information pursuant to section 704(a)(4) of the FD&C Act, 21 U.S.C. 374(a)(4) to your CMO of(b)(4)Injection USP),(b)(4). After multiple follow-up requests, your CMO failed to respond to these attempted communications or otherwise provide the requested records or other information. It is a prohibited act under section 301(e) of the FD&C Act (21 U.S.C. 331(e)) to refuse to permit access to or copying of any record as required by section 704(a). Because your CMO failed to respond to the section 704(a)(4) records requests and associated communication attempts, FDA placed all drugs and drug products manufactured by your CMO on Import Alert 66-79. Drugs manufactured by facilities on Import Alert 66-79 are subject to refusal of admission pursuant to section 801(a)(3) of the FD&C Act in that all drugs from their facility appear to be adulterated under section 501(j) because they have been manufactured, processed, packed, or held in any factory, warehouse, or establishment and the owner, operator or agent of such factory, warehouse, or establishment delays, denies, or limits an inspection, or refuses to permit entry or inspection.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’s guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.Unapproved DrugsYour(b)(4)products,(b)(4), as well as your(b)(4)injection product are listed in FDA’s electronic Drug Registration and Listing System (eDRLS) as “Export Only.” However, information obtained during the inspection of your firm indicates that your firm plans to distribute these products commercially in the United States. Please be advised that, based on review of the product labeling collected during the inspection of your firm and the labeling that your firm submitted to FDA’s eDRLS, these products are new drugs within the meaning of section 201(p) of the FD&C Act and require FDA premarket approval under section 505 of the FD&C Act [21 U.S.C. 355]. Distribution of an unapproved new drug in the United States is prohibited under section 301(d) of the FD&C Act [21 U.S.C. 331(d)].We encourage you to contact FDA’s Office of New Drugs at ONDCommunications@fda.hhs.gov for assistance with the application process for your unapproved drug products.503B RegistrationUnder section 503B(b) of the FD&C Act, 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 FD&C Act [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FD&C Act [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 FD&C Act [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FD&C Act are met. However, outsourcing facilities must comply with other applicable provisions of the FD&C Act, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding CGMP requirements.2,3Drugs Manufactured for Importation into the United StatesDrug products imported into the United States must comply with all applicable requirements under the FD&C Act and the corresponding regulations set forth in Title 21 of the Code of Federal Regulations. These requirements include compliance with labeling requirements, firm registration and drug listing, and adherence to CGMP. Facilities that manufacture drug products and drug components intended for importation into the United States are subject to inspection by the FDA to determine compliance with these regulatory standards. For drugs requiring NDA or ANDA approval, the application must be submitted to and approved by the FDA’s Center for Drug Evaluation and Research (CDER) prior to importation, as required by section 505(a) of the FD&C Act and 21 CFR part 314.Drugs Manufactured for Exportation out of the United StatesDrug products exported from the United States under section 802 of the FD&C Act, must comply with applicable requirements under the FD&C Act, including those specified in section 802(f) [21 U.S.C. § 382(f)]. Under this provision, a drug may not be exported if it is not “manufactured, processed, packaged, and held in substantial conformity with current good manufacturing practice requirements.” Furthermore, a drug is considered adulterated under section 501(a)(2)(B) of the FD&C Act [21 U.S.C. § 351(a)(2)(B)] if the methods, facilities, or controls used in its manufacture, processing, packaging, or holding do not conform to CGMP standards.We therefore encourage you to review your manufacturing processes to ensure that unapproved new drugs intended for export comply with CGMP requirements. Non-compliance with these requirements prevents your ability to export these drugs under section 802(f) of the FD&C Act [21 U.S.C. § 382(f)].Repeat Violations at FacilityIn previous inspections from September 10 to 27, 2019, and August 5 to 23, 2021, FDA cited similar CGMP violations. You proposed specific remediation for these violations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.CGMP Consultant RecommendedBecause you failed to correct repeat violations, 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 3009963974 and ATTN: Kevin Maguire.Sincerely,/S/Jill P. FurmanDirectorOffice of ComplianceCenter for Drug Evaluation and Research_______________1The terms combination product and drug are used interchangeably in this letter.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 FD&C Act.3For additional information, please see FDA’s “Information for Outsourcing Facilities” webpage, available at https://www.fda.gov/drugs/human-drug-compounding/information-outsourcing-facilities. Furthermore, FDA’s Compounding Quality Center Of Excellence (CQCOE) supports outsourcing facilities’ efforts to improve the quality of drugs they produce through training, research and engagement activities with FDA and other supporting stakeholders. For additional information on the CQCOE, please visit https://www.fda.gov/drugs/human-drug-compounding/compounding-quality-center-excellence.

Product:Drugs、Over-the-Counter DrugsRecipient:Kari Kenner, CEOShannon Kenner, CEOWaxhead Sun Defense Company614 Santa Maria DrFernandina Beach,FL32034United Statesmac@gowaxhead.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 12, 2025RE: 688286Dear Mr. and Mrs. Kenner:This letter is to advise you that in May 2024, the U.S. Food and Drug Administration (FDA) reviewed your product labeling, including on your website at the internet address https://gowaxhead.com/ where your “Waxhead SUN DEFENSE SHAMPOO + CONDITIONER + BODY WASH + UV PROTECTION SUN DEFENSE BODY WASH with zinc oxide” (hereinafter “Waxhead Sun Defense Body Wash”) product is available for purchase in the United States without a prescription.Your “Waxhead Sun Defense Body Wash” product is a drug as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is 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 it is intended to affect the structure or any function of the body.Examples of the claims from the product labeling, including your website listed above, that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the product include, but may not be limited to, the following:“Scalp Sunscreen…Our Zinc Shampoo provides your hair and skin with daily UVA/UVB/UVC protection, creating a barrier against the sun's harsh rays…” [from your “Waxhead Sun Defense Body Wash” product website]Embrace the Waxhead Experience…∙ Boosts daily UVA/UVB/UVC protection: Safeguard your face, skin, and hair from incidental sun exposure.” [from your “Waxhead Sun Defense Body Wash” product website]“Waxhead Zinc Body Wash and Shampoo is the game-changer you've been waiting for…With our innovative scalp sunscreen and zinc body wash combination, you can effortlessly protect your skin from the sun's harmful rays without the need for sunscreen lotions…” [from your “Waxhead Sun Defense Body Wash” product website]“Added Layer of UV Protection… Our Zinc Body Wash and Shampoo boosts UV protection for the face, skin, and hair and helps protect areas difficult to cover with sunscreen, such as the scalp and ears.” [from your “Waxhead Sun Defense Body Wash” product website]Based on the above labeling, your “Waxhead Sun Defense Body Wash” is intended for use as an over-the-counter (OTC) sunscreen drug product. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for your drug product. Section 505G of the FD&C Act, 21 U.S.C. 355h, governs the marketing of nonprescription drugs that are marketed without an approved application under section 505 of the FD&C Act, 21 U.S.C. 355, such as your product. Under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), a nonprescription drug is misbranded if the drug is subject to section 505G of the FD&C Act, 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.Section 505G of the FD&C Act, 21 U.S.C. 355h, provides that certain nonprescription drugs are deemed to be generally recognized as safe and effective (GRASE) and not new drugs if they, among other things, conform to the conditions in the applicable OTC monograph. In the case of OTC sunscreen drug products, the applicable OTC monograph is set forth in the final administrative order, OTC000006: Over-the-Counter Monograph M020: Sunscreen Drug Products for Over-the-Counter Human Use (hereinafter M020), which was deemed a final order by 505G(b)(8) and 505G(k)(2)(B).1,2 However, under section 505G(m)(2), “notwithstanding subsection [505G](a),” sunscreens in all dosage forms other than oil, lotion, cream, gel, butter, paste, ointment, stick, spray, and powder may only be lawfully marketed, without an application approved under section 505 of the FD&C Act, pursuant to an order issued under section 505G of the FD&C Act.3 To date, no final order has been issued by the Secretary under 505G(b) or 505G(c) that would authorize marketing of sunscreen in a shampoo or face/body wash dosage form. As previously stated, there is no FDA-approved application in effect for your drug product.Thus, even if your product were in conformity with the conditions set forth in M020 and all other applicable requirements to be deemed GRASE and not a new drug under section 505G(a)(1), it does not comply with the requirements under section 505G. Accordingly, your “Waxhead Sun Defense Body Wash” sunscreen drug product is a misbranded drug introduced or delivered for introduction into interstate commerce in violation of sections 502(ee) and 301(a) of the FD&C Act, 21 U.S.C. 352(ee) and 331(a).ConclusionThe violations cited in this letter are not intended to be an all-inclusive list 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 result in legal action including, without limitation, seizure and injunction.Please notify FDA in writing, within 15 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 15 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 and include your firm name in the subject line of your email.Sincerely,/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration____________________1See sections 505G(a)(1) and (2) of the FD&C Act and see Order ID OTC000006, available at FDA’s website OTC Monographs@FDA, https://dps.fda.gov/omuf. As required by section 505G(a)(2), M020 encompasses the requirements specified in part 352 of title 21, Code of Federal Regulations, as published on May 21, 1999, beginning on page 27687 of volume 64 of the Federal Register, except that the applicable requirements governing effectiveness and labeling shall be those specified in section 201.327 of title 21, Code of Federal Regulations.2We note that your “Waxhead Sun Defense Body Wash” also appears to include intended uses as an antifungal, for the control of dandruff and psoriasis, and for acne. OTC antifungal drug products, dandruff and psoriasis drug products, and acne drug products are deemed to be GRASE and not new drugs if, among other things, they conform to the conditions of use set forth in their respective final administrative orders: Over-the-Counter Monograph M005: Topical Antifungal Drug Products for Over-the-Counter Human Use; Over-the-Counter Monograph M032: Drug Products for the Control of Dandruff, Seborrheic Dermatitis, and Psoriasis for Over-the-Counter Human Use; and Over-the-Counter Monograph M006: Topical Acne Drug Products for Over-the-Counter Human Use, respectively. There are no provisions in any of the respective categories’ monographs, nor any monograph, that allow for a combination sunscreen, antifungal, control of dandruff and psoriasis, and acne drug product.3Section 505G(m)(2) provides that “[n]otwithstanding subsection [505G](a),” a drug that, “prior to the date of the enactment of this section [March 27, 2020], the Secretary determined in a proposed or final rule to be ineligible for review under the OTC drug review” (emphasis added) may not be legally marketed without an approved NDA or ANDA except as “pursuant to an order issued under this section”. In a 2019 proposed rule, FDA determined that sunscreens in all dosage forms other than oil, lotion, cream, gel, butter, paste, ointment, stick, spray, and powder were ineligible for review under the OTC Drug Review under the then-operative requirements because we did not receive data showing that they were marketed prior to 1972. 84 FR 6024 at 6229-6230 (Feb. 26, 2019); see also 84 FR 6024 at 6206 and 6272. Therefore, under section 505G(m)(2) of the FD&C Act, a sunscreen in any dosage form other than the ten dosage forms listed above may only be marketed with an approved application, unless FDA determines otherwise in an order issued under section 505G of the FD&C Act.

行政相对人名称×××公司行政相对人类别法人行政相对人代码_1(统一社会信用代码)×××法定代表人×××法定代表人证件类型身份证法定代表人证件号码×××行政处罚决定书文号粤药监械罚〔2025〕2001号违法行为类型生产销售不合格的医疗器械违法事实经查，×××公司于2024年2月22日生产的医用外科口罩（批号：20240222，型号规格：KZ41），经广东省医疗器械质量监督检验所检验和深圳市医疗器械检测中心复检，检验项目“口罩带”不合格。该批次生产总量为200000个，销售价格0.2元/个，其中当事人留样100个，执法抽样100个，未销售167800个，销售给3个客户合计32000个，召回11000个，库存178800个；涉案医用外科口罩货值金额40000元，违法所得4200元。处罚依据《中华人民共和国行政处罚法》第二十八条第二款、《医疗器械监督管理条例》第八十六条第（一）项、《药品监督管理行政处罚裁量适用规则》第十一条第（二）项和广东省药品监督管理局药品监督管理行政处罚裁量适用规则实施细则》（粤药监规〔2025〕1号）第十一条第（一）项和第（九）项、第十二条第（三）项、第十五条第（一）项。处罚类别罚款、没收违法所得、没收违法生产的医疗器械处罚内容1.没收违法生产的医用外科口罩（批号：20240222，型号规格：KZ41）178800个；2.没收违法所得人民币4200元；3.罚款人民币150000元；上述罚没款合计人民币154200元（人民币拾伍万肆仟贰佰元）。罚款金额（万元）15没收违法所得、没收非法财物的金额（万元）0.42处罚决定日期2025年3月18日处罚有效期10年处罚机关广东省药品监督管理局处罚机关统一社会信用代码11440000MB2D034421数据来源单位广东省药品监督管理局数据来源单位统一社会信用代码11440000MB2D034421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。

根据《药品管理法》《药品生产监督管理办法》《药品生产质量管理规范》等法律法规规章，按照药品生产监督检查工作计划，省药监局组织对31家次药品生产单位开展了监督检查，现将检查结果予以通告（见附件）。附件：药品生产监督检查结果汇总表（2025年第1号）山东省药品监督管理局2025年3月17日（公开属性：主动公开）附件药品生产监督检查结果汇总表（2025年第1号）序号企业名称检查时间检查范围及相关车间、生产线检查结果及措施1山东福牌阿胶股份有限公司2024.5.30-6.1胶剂（胶剂车间胶剂生产线（含中药前处理、提取））符合要求2山东红日康仁堂药业有限公司2024.5.30-6.1颗粒剂（中药配方颗粒）（炮制车间毒性饮片生产线、普通饮片生产线、中药前处理生产线；提取车间中药提取生产线；制剂包装车间中药配方颗粒生产线）符合要求3烟台鲁银药业有限公司2024.6.12-16小容量注射剂：102车间小容量注射剂生产线集采中选品种：硝苯地平缓释片（Ⅰ），104车间片剂生产线2022年后新上市品种：孟鲁司特钠咀嚼片，101车间片剂生产线；硝苯地平缓释片（Ⅰ），104车间片剂生产线注射剂受托生产：阿加曲班注射液，102车间小容量注射剂生产线高风险品种：葛根素注射液，102车间小容量注射剂生产线符合要求4山东华信制药集团股份有限公司2024.6.27-29大容量注射剂（委托生产）；片剂（健胃消食片）；胶囊剂（益中生血胶囊）；颗粒剂（阿奇霉素颗粒）；糖浆剂（强力枇杷露）符合要求5潍坊市中医院2024.7.5-6片剂、散剂、丸剂、膏药（黑膏药）、硬胶囊剂、糖浆剂、软膏剂、搽剂、颗粒剂、合剂符合要求6山东玉满坤生物科技有限公司2024.9.6-8小容量注射剂（委托生产品种：左卡尼汀注射液，受托生产企业：江苏九旭药业有限公司，受托生产地址：睢宁经济开发区九旭大道998号水针车间2小容量注射剂生产线，动态生产品种：左卡尼汀注射液（5ml：1g和5ml：2g））；国家集采品种：左卡尼汀注射液（5ml：1g，国药准字H20233153；5ml：2g，国药准字H20233154）符合要求7华仁药业（日照）有限公司2024.10.12-14大容量注射剂（输液一车间玻璃输液瓶生产线，盐酸曲马多氯化钠注射液；输液一车间多层共挤输液用袋西线，甘油果糖氯化钠注射液；五车间2413线、2414线，低钙腹膜透析液（乳酸盐-G2.5%））符合要求8山东博安生物技术股份有限公司2024.10.13-15治疗用生物制品：贝伐珠单抗注射液(原液：原液一车间一线生产线、原液一车间二线生产线；制剂：制剂车间西林瓶灌装线);地舒单抗注射液(原液：原液一车间一线生产线；制剂：制剂车间预灌封灌装线);符合要求9新发药业有限公司2024.10.22-24化学药品原料药（泛酸钙），泛酸钙车间，泛酸钙生产线符合要求10山东鸿杰中药饮片有限公司2024.10.29-10.31中药饮片(含毒性饮片、直接口服饮片)(普通饮片炮制范围:净制、切制、炒制、炙制、煅制、蒸制、煮制、燀制;毒性饮片炮制范围:净制、切制、炒制、蒸制、煮制)/普通饮片生产车间（普通饮片生产线）、直接口服饮片生产车间（直接口服饮片生产线）、毒性饮片生产车间（毒性饮片生产线）符合要求11临沂鑫皓中药饮片有限公司2024.10.29-31沂水县长安路北段689号：普通饮片生产车间，普通饮片1生产线，中药饮片(炮制范围:净制、切制、炒制、蒸制、煮制、炙制、发芽、发酵、制炭、煨制)；毒性饮片生产车间，毒性饮片生产线，毒性饮片(炮制范围:净制、切制、炒制、蒸制、煮制、炙制、水飞)。沂水县长安路北段687号：普通饮片生产车间，普通饮片2生产线，中药饮片(炮制范围:净制、切制、炒制、炙制、蒸制、煮制、煅制、燀制)。符合要求12山东池翔中药饮片有限公司2024.10.29-31中药饮片(含毒性饮片)(普通饮片炮制范围:净制、切制、蒸制、煮制、燀制、炒制、煅制、炙制、制炭；毒性中药饮片炮制范围：净制、切制、煮制、炙制) 普通饮片车间（普通饮片生产线）、毒性饮片车间（毒性饮片生产线）符合要求13仁和堂药业有限公司2024.11.1-3片剂（制剂车间生产线二）、原料药盐酸地芬尼多（合成车间A2区）、出口药品：盐酸地芬尼多符合要求14华润昂德生物药业有限公司2024.11.5-8治疗用生物制品：贝伐珠单抗注射液(原液：原液一车间一线生产线、原液一车间二线生产线；制剂：制剂车间西林瓶灌装线);地舒单抗注射液(原液：原液一车间一线生产线；制剂：制剂车间预灌封灌装线);符合要求15山东泰邦生物制品有限公司2024.11.5-8人血白蛋白，液体类生产线，相关车间：因子车间、蛋白车间、分装车间、包装车间。符合要求16山东辰欣佛都药业股份有限公司2024.11.7-9滴剂（滴耳剂，301车间2线）、膏剂（眼膏剂，302车间1线）符合要求17南京江原安迪科正电子研究发展有限公司聊城分公司2024.11.12-14小容量注射剂（体内放射性药品：氟[18F]脱氧葡糖注射液（氟[18F]生产车间，氟[18F]生产线））符合要求18迪沙药业集团有限公司2024.11.12-16集采中选（制造一部六车间，片剂线（洛索洛芬钠片、硝苯地平缓释片（Ⅱ））、第二类精神药品（右佐匹克隆片），中药品种（制造二部二车间中药饮片生产线、制造二部四车间中药前处理、提取生产线，制造二部五车间颗粒剂线（感冒清热颗粒）、硬胶囊剂线）符合要求19荣昌生物制药（烟台）股份有限公司2024.11.14-171.注射用泰它西普，规格：80mg/支（细胞培养（101车间、102车间、103车间）、纯化（201车间、203车间）、制剂（302车间），注射用泰它西普生产线，自行生产）；2.注射用维迪西妥单抗，规格：60mg/支（细胞培养（101车间）、纯化（201车间）、小分子合成（401车间）、偶联（501车间）、制剂（303车间），注射用维迪西妥单抗生产线，自行生产）。符合要求20山东省惠诺药业有限公司2024.11.19-23小容量注射剂（注射剂车间最终灭菌生产线（肝素钠封管注射液））符合要求21福安药业集团烟台只楚药业有限公司2024.11.22-24小容量注射剂（注射剂三车间，小容量注射剂生产线）符合要求22山东亦度生物技术有限公司2024.11.25-28预防用生物制品:冻干人用狂犬病疫苗(Vero细胞)符合要求23森淼（山东）药业有限公司2024.11.28-29片剂：叶酸片、盐酸倍他司汀片；受托生产企业：济南永宁制药股份有限公司（固体制剂车间，固体制剂生产线），受托生产地址：济南市历城区经十东路30766号符合要求24山东裕欣药业有限公司2024.11.28-30冻干粉针剂（2503车间冻干1线（注射用谷胱甘肽））；国家集采品种：注射用兰索拉唑、注射用艾司奥美拉唑钠符合要求25青岛国大生物制药股份有限公司2024.11.29-12.1冻干粉针剂（冻干粉针剂车间，冻干粉针剂生产线）符合要求26山东二叶制药有限公司2024.11.29-12.1粉针剂（青霉素类）：粉针剂车间（青霉素类）204生产线；混粉车间（青霉素类）201生产线；集采品种：注射用哌拉西林钠他唑巴坦钠（受托生产，持有人为苏州二叶制药有限公司）符合要求27齐鲁制药有限公司2024.12.3-5小容量注射剂（抗肿瘤类）（6100单元生产线）；冻干粉针剂（抗肿瘤类）（6100单元生产线（注射用硼替佐米））； 冻干粉针剂（7310生产线（注射用醋酸西曲瑞克））；片剂（6500单元生产线（卡维地洛片、维格列汀片、来氟米特片、枸橼酸西地那非片））；集采中选品种：氟维司群注射液、多西他赛注射液、注射用培美曲塞二钠、注射用比伐芦定、注射用硼替佐米；6.有因检查：集采中选品种：枸橼酸西地那非片。符合要求28青岛原子高通医药有限公司2024.12.3-5体内放射性药品(小容量注射剂，氟[18F]脱氧葡糖注射液生产车间氟[18F]脱氧葡糖注射液生产线（氟[18F]脱氧葡糖注射液）、锝药物生产车间锝药物生产线（高锝[99mTc]酸钠注射液、锝[99mTc]亚甲基二膦酸盐注射液、锝[99mTc]甲氧异腈注射液、锝[99mTc]喷替酸盐注射液））符合要求29山东辉成药业有限公司2024.12.3-5小容量注射剂一车间、小容量注射剂二车间、小容量注射剂三车间符合要求30青岛首和金海制药有限公司2024.12.6/不具备生产条件，处于长期停产状态31山东丹红制药有限公司2024.12.18-20中药注射剂（提取二车间中药前处理提取生产线，制剂Ⅰ车间小容量注射剂生产线)符合要求相关推荐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。

行政相对人名称扬州洋生医药科技有限公司行政相对人类别法人及非法人组织统一社会信用代码9132100072060147XE工商注册号组织机构代码税务登记号事业单位证书号社会组织登记证号法定代表人耿彪法定代表人证件类型身份证法定代表人证件号码3****************X证件类型证件号码行政处罚决定书文号苏药监扬处字〔2025〕2号违法行为类型生产不符合经注册的产品技术要求的一次性使用吸痰管的行为，违反了《医疗器械监督管理条例》第三十五条第一款规定。违法事实扬州洋生医药科技有限公司，生产不符合经注册的产品技术要求的一次性使用吸痰管的行为，违反了《医疗器械监督管理条例》第三十五条第一款规定，依据《中华人民共和国行政处罚法》第二十八条、《医疗器械监督管理条例》第八十六条第一项规定，应予处罚。处罚依据依据《中华人民共和国行政处罚法》第二十八条、《医疗器械监督管理条例》第八十六条第一项规定。处罚类别罚款;没收违法所得、没收非法财物处罚内容没收违法所得伍佰伍拾元整；处以罚款贰万肆仟伍佰元整。罚款金额（万元）2.45没收违法所得没收非法财物的金额（万元）0.055暂扣或吊销证照名称及编号处罚决定日期2025/03/17处罚有效期2025/09/17公示截止期2028/03/17处罚机关江苏省药品监督管理局处罚机关统一社会信用代码11320000014000394R数据来源单位江苏省药品监督管理局数据来源单位统一社会信用代码11320000014000394R备注公示截止期依据文件：市场监督管理行政处罚信息公示规定。罚款金额已确认。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。

行政相对人名称扬州市吉康医疗器械有限公司行政相对人类别法人及非法人组织统一社会信用代码913210027222142465工商注册号组织机构代码税务登记号事业单位证书号社会组织登记证号法定代表人蔡天鹏法定代表人证件类型身份证法定代表人证件号码3****************7证件类型证件号码行政处罚决定书文号苏药监扬处字〔2024〕39号违法行为类型生产不符合强制性标准及经注册的产品技术要求的一次性使用医用橡胶检查手套的行为，违反了《医疗器械监督管理条例》第三十五条第一款规定。违法事实扬州市吉康医疗器械有限公司，生产不符合强制性标准及经注册的产品技术要求的一次性使用医用橡胶检查手套的行为，违反了《医疗器械监督管理条例》第三十五条第一款规定，依据《中华人民共和国行政处罚法》第二十八条、《医疗器械监督管理条例》第八十六条第一项规定，应予处罚。处罚依据依据《中华人民共和国行政处罚法》第二十八条、《医疗器械监督管理条例》第八十六条第一项规定。处罚类别罚款;没收违法所得、没收非法财物处罚内容没收违法所得玖仟捌佰元整；处以罚款贰万捌仟元整。罚款金额（万元）2.8没收违法所得没收非法财物的金额（万元）0.98暂扣或吊销证照名称及编号处罚决定日期2025/03/17处罚有效期2025/09/17公示截止期2028/03/17处罚机关江苏省药品监督管理局处罚机关统一社会信用代码11320000014000394R数据来源单位江苏省药品监督管理局数据来源单位统一社会信用代码11320000014000394R备注公示截止期依据文件：市场监督管理行政处罚信息公示规定。罚款金额已确认。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。