各区县（自治县）医疗保障局、财政局、税务局，高新区政务服务和社会事务中心、财政局，万盛经开区人力社保局、财政局：为贯彻落实《中华人民共和国医疗保障法》，根据《国家医保局财政部国家税务总局关于做好2026—2027年城乡居民基本医疗保障有关工作的通知》（医保发〔2026〕24号）和《重庆市人民政府办公厅关于印发〈重庆市建立健全长期护理保险制度实施方案〉的通知》（渝府办发〔2026〕36号）工作要求，为做好2027年度全市城乡居民基本医疗保险（以下简称“居民医保”）、长期护理保险（以下简称“长护险”）参保筹资工作，现将有关事项通知如下。一、明确参保筹资标准未参加职工基本医疗保险且未享有国家其他医疗保障的公民应当参加居民医保。参加我市居民医保时同步参加长护险，同步缴纳长护险费。（一）居民医保筹资标准。个人缴费标准，参加我市2027年度居民医保个人缴费标准为一档400元/人·年、二档775元/人·年。财政补助标准，2026年，居民医保人均财政补助标准较上年增加24元，达到724元/人·年，市级财政按规定结合中央财政资金对各区县（自治县）实行分档补助，各区县财政按规定足额安排本级财政补助资金，并及时拨付到位。（二）长护险筹资标准。居民参加我市2027年度长护险个人缴费标准为31元/人·年，2027年1月1日前未满18周岁居民跟随父母或其他法定抚养人等参加长护险，不单独筹资。财政补助按照个人缴费标准1:1补助，由中央、市与区县财政共同承担。（三）集中参保期。2027年度居民医保和长护险集中参保期从2026年10月开始，2027年1月底结束。除新生儿、医疗救助对象等特殊群体外，未在集中参保期内参保或未连续参保的人员，按规定设置参保后待遇等待期。二、落实分类资助参保参加居民医保的特殊困难人群个人缴费部分按规定落实分类资助政策。参加长护险的困难人群个人缴费部分，对特困人员给予全额资助，对低保对象按照90%给予定额资助，对符合条件的防止返贫致贫对象按照70%给予定额资助。本通知自发文之日起执行。重庆市医疗保障局 重庆市财政局国家税务总局重庆市税务局2026年9月29日

Delivery Method:Via Email Return Receipt RequestedReference #:320-26-41Product:DrugsOver-the-Counter DrugsRecipient:Ms. Autumn P. BlumCEO & FormulatorStream2Sea, LLC2498 Commerce Ct.Bowling Green, FL 33834United States (b)(4)Issuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-41February 2, 2026Dear Ms. Blum:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Stream2Sea, LLC, FEI 3015234524, located at 2498 Commerce Ct., Bowling Green, FL, from July 9 to 15, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your August 5, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific violations including, but not limited to, the following:1. Your firm failed to have, for each batch of drug product, appropriate laboratory determination of satisfactory conformance to final specifications for the drug product, including the identity and strength of each active ingredient, prior to release (21 CFR 211.165(a)).Your firm failed to perform adequate analytical and microbiological release testing for each batch of your over the counter (OTC) drug products prior to distribution. For example, your “(b)(4)” batch (b)(4), was manufactured on October 3, 2024. Samples were collected for pH, microbiological and assay testing between October 3 and October 7, 2024. Two months later, on December 23, 2024, this bulk batch underwent additional manufacturing by (b)(4). No testing of the resulting final drug product, “(b)(4)” batch (b)(4), was conducted.In addition, you released the same finished drug product batch prior to obtaining documented product release approval by the quality unit.Drug product batches must be tested for identity, strength, quality, and purity prior to release. Testing is an essential part of ensuring that the drug products you manufacture conform to all predetermined quality attributes and are appropriate for their intended use. Without adequate testing, you lack basic data to support that each drug product batch conforms to appropriate specifications before release.In your response, you acknowledge lack of understanding of the regulations. You commit to implement a comprehensive finished drug product testing plan. You state that all active finished drug products in-house have been sent for microbial testing and active pharmaceutical ingredient (API) analytical testing. You also commit to perform retrospective testing for all active and recently distributed lots using third-party analytical and microbiological verification.Your response is inadequate because your firm did not provide a procedure describing how you will ensure your finished drug products, not only the bulk products, meet the appropriate quality standards prior to release. You did not provide details on the acceptance criteria of the tests performed by the third party and did not provide an impact assessment for products on the market and within expiry.In response to this letter, provide:A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods used to analyze each lot of your drug product before making a batch disposition decision and the associated written procedures.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm failed to perform identification testing on raw materials and components including APIs prior to use in your OTC drug products. For example, your firm did not perform any testing on the raw material (b)(4), lot# (b)(4).In addition, you relied on your suppliers’ certificates of analysis (COAs) in lieu of testing each component lot for purity, strength, identity, and quality. You also did not establish a supplier qualification program to assess (i.e., initially and periodically) the reliability of your suppliers’ test results for these attributes.In your response, you acknowledge the failure to conduct identity testing on incoming raw materials. You commit to confirming that the bulk lot was fully tested for identity and quantification by a third party before further processing. You also commit to performing identity testing for all API lots currently in inventory and retain samples.Your response is inadequate. Your response provides no assurance that all incoming materials will be tested for identity as required. In addition, you did not provide any procedures or testing methods for review. Your test report for incoming raw material is unclear on who performs the identification test or whether the results recorded are from the supplier’s COA. Also, you did not provide a plan for your supplier qualification program.In response to this letter, provide: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 components 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 suppliers’ COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your suppliers’ 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 SOP that describes this COA validation program.3. Your firm failed to establish and follow adequate written procedures for cleaning and maintenance of equipment (21 CFR 211.67(b)).You failed to adequately validate your cleaning procedures to ensure the removal of API residue and cleaning agents, as well as control of potential microbial contamination for your non-dedicated manufacturing equipment.In addition, you failed to adequately document the type of cleaning performed or the specific cleaning agent used to clean your equipment that is shared to manufacture both your OTC drug products and cosmetics.In your response, you acknowledge the weakness in your cleaning validation and cleaning documentation practices and commit to revalidating your cleaning process and updating your cleaning procedure.Your response is inadequate. You fail to provide sufficient details on the proposed cleaning revalidation and product impact assessment.In response to this letter, provide:Appropriate improvements to your cleaning validation program with special emphasis on incorporating conditions identified as worst case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case:o drugs with higher toxicitieso drugs with higher drug potencieso drugs of lower solubility in their cleaning solventso drugs with characteristics that make them difficult to cleano swabbing locations for areas that are most difficult to cleano maximum hold times before cleaningIn addition, describe the steps that must be taken in your change management system before introduction of new manufacturing equipment or a new product.A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices and encompass each piece of manufacturing equipment used to manufacture more than one product including both API and finished products.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, we strongly recommend that your firm 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 address this matter promptly and adequately 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 3015234524 and ATTN: Joan Johnson.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA UNITED PARCEL SERVICEReference #:320-26-126Product:DrugsOver-the-Counter DrugsRecipient:Mr. James BurkePresidentBentley Laboratories LLC111 Fieldcrest AvenueEdison, NJ 08837-3622United Statesjames.burke@bentleylabs.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesUnited StatesSeptember 17, 2026WARNING LETTERReference number: 320-26-126To Mr. James Burke:This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your products, processes, facilities, and records. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.FDA Inspection and ReviewViolations were observed and documented during an inspection of your drug manufacturing facility, Bentley Laboratories LLC, FDA Establishment Identifier (FEI) 2244819, at 111 Fieldcrest Avenue, Edison, from March 16 to 27, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).In addition, violations were identified and documented during a review of product labeling collected during the onsite inspection. Based on our review, “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” are unapproved new drugs under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). In addition, these products are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). As explained further below, introducing or delivering these products for introduction into interstate commerce is prohibited under sections 301(a) and 301(d) of the FD&C Act, 21 U.S.C. 331(a) and 331(d).We reviewed your April 21, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.Violations of the Federal Food, Drug, and Cosmetic ActThe following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.CGMP Violations1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).(b)(4) drug products such as (b)(4). Your firm failed to adequately investigate several out-of-specification (OOS) laboratory results. For example:You failed to adequately investigate and scientifically identify the root cause for OOS assay results for lot (b)(4) at the (b)(4) at the 24-month stability timepoint of (b)(4). You also did not adequately evaluate the impact to products on the market.You failed to adequately investigate an OOS result for (b)(4), lot (b)(4), for pH at the 36-month stability timepoint. Moreover, as a corrective action and preventive action (CAPA), your firm expanded the pH specification range without scientific justification.You did not thoroughly investigate these failures of a component or drug product to meet any of its specifications. Your investigations were inadequate because you failed to identify the root cause, implement appropriate CAPA, and expand the investigation to evaluate the impact on other batches or products.In your response, you state the root cause of inadequate investigations was due to deficiencies in your investigation procedures. Your response is inadequate. You fail to include changes to your investigation procedures to require root cause assessment for OOS results. Inadequate investigations can lead to unidentified root causes, ineffective CAPA, and recurring problems that compromise the ability to manufacture safe and effective drug products.For more information about handling out-of-specification and failing test results, and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/media/158416/download.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating (b)(4), discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit (QU) oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigation trends, improves the CAPA program whenever needed, ensures final QU decision authority, and is fully supported by executive management.A comprehensive, independent assessment of your change management system. This assessment should include, but not be limited to, your procedures to ensure changes are justified, reviewed, and approved by your QU. Your change management program should also include provisions for determining change effectiveness.Your action plan to address any product quality or patient safety risks for your drug products in U.S. distribution, including customer notifications and recalls.2. Your firm failed to test samples of each component for identity and conformity with all appropriate written specifications for purity, strength, and quality. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm failed to ensure that components were suitable for use in manufacturing your OTC (b)(4) drug products. For example, you did not perform adequate identity testing on each shipment of each lot of incoming components (e.g., (b)(4)). Additionally, you relied on your suppliers’ certificates of analysis (COA) without establishing the reliability of each of your component suppliers’ test analyses at appropriate intervals.Products Containing (b)(4)You manufacture multiple drugs that contain (b)(4) (e.g., (b)(4)). You failed to adequately test your incoming (b)(4) for (b)(4) contamination. The use of (b)(4) contaminated with (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document (b)(4).In your response, you state that you initiated a change control request “to modify the system to ensure (b)(4) impurity testing is included” and tested raw materials for (b)(4) impurities. Your response is inadequate because you do not provide sufficient detail about your updated raw material specifications and how you will ensure performance of appropriate incoming testing for each component. Also, you failed to indicate whether you lack retain samples of any batches and are therefore unable to test them for impurities. Additionally, you failed to demonstrate that the (b)(4) you used as a component to manufacture your drug products met USP monograph specifications including those for impurities (e.g., (b)(4)).Products Containing (b)(4)You also failed to adequately test your incoming components at high risk of (b)(4) contamination for identity before using them to manufacture your drug products. This includes, but is not limited to, testing of (b)(4) to determine its appropriate identity before using it in manufacturing your OTC (b)(4) drug products.Identity testing for glycerin and certain other high-risk drug components includes a limit test in the USP to ensure that the component meets the relevant safety limits for (b)(4) or (b)(4) levels. 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 ensure the acceptability of these components 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. See FDA’s guidance document (b)(4) to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for (b)(4) contamination at (b)(4).In your response, you state that you initiated a change control request “to modify the test procedure to ensure the inclusion of (b)(4)” and tested raw materials for (b)(4). Your response is inadequate because you do not provide sufficient documentation of your updated raw material specifications and how you will ensure performance of appropriate testing on incoming components. Also, you failed to indicate whether you lack retain samples of any batches and are therefore unable to test them for hazardous impurities.Without adequate testing, you do not have scientific evidence that the components conform to the appropriate specifications before their use in the manufacture of your drug products. You are responsible for sampling, testing, and examining drug components before their use in production to ensure that acceptable quality parameters are met.In response to this letter, provide: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. In the case of (b)(4), and certain additional high-risk components, we note that this includes the performance of parts (b)(4) of the USP monograph.Based on a thorough review, provide a summary of your systems CAPA to remediate the vendor qualification program and prevent use of unsuitable components, containers and closures.A commitment to perform reconciliation of retains tested versus all lots used in production. If retain samples are unavailable, a commitment to test finished drug product batches for the presence of (b)(4). Also include your analytical methods.A summary of your program for qualifying and overseeing contract facilities that test the components and drug products you manufacture.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 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.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 failed to adequately validate your manufacturing processes for OTC drug products. You did not revalidate your manufacturing processes after making major process changes, nor did you fully execute validation protocols through the completion of all batches. For example, you changed the manufacturing process for (b)(4) to rephase the formulation without revalidation and outside of your change management system. Also, for (b)(4), your process validation execution deviated from your Validation Master Plan (VMP) which requires validating your manufacturing processes with three batches. Furthermore, you did not retain stability samples from any of the three batches.Your firm also failed to adequately validate your cleaning processes for non-dedicated equipment used to manufacture (b)(4). For the two validation batches where cleaning validation swab samples were collected, OOS results for residual of active pharmaceutical ingredients were not adequately investigated.In your response, you state a change control will be conducted for the (b)(4) and, if required, a process validation will be performed for the revised process. You also state you will complete the validation for the (b)(4) and will update your VMP as well as applicable standard operating procedures (SOPs).Your response is inadequate because you do not commit to revalidating the (b)(4) process. Additionally, you do not evaluate the roles and responsibilities of your QU, including change management and document control, to ensure comprehensive oversight functions.Also, it appears that you used a maximum allowable carryover limit of (b)(4) ppm in your cleaning validation calculations without adequate scientific justification. Without adequate process validation that incorporates all manufacturing inputs and parameters that can affect product quality, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications.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.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, and ongoing vigilant monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing appropriate process performance qualification for each of your marketed drug products.A risk assessment for the distributed drug products produced using inadequately validated processes.Appropriate improvements to your cleaning validation program, with special emphasis on incorporating conditions identified as worst case in your drug manufacturing operation. This should include, but not be limited to, identification and evaluation of all worst-case:o drugs with higher toxicitieso drugs with higher drug potencieso drugs of lower solubility in their cleaning solventso drugs with characteristics that make their manufacturing equipment difficult to cleano swabbing locations for areas that are most difficult to cleano maximum hold times before cleaningA description of the steps that will be taken in your change management system before introduction of new manufacturing equipment or a new product.A summary of updated SOPs that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.A comprehensive, independent retrospective assessment of your cleaning effectiveness to evaluate the scope of cross-contamination hazards. Include the identity of residues, other manufacturing equipment that may have been improperly cleaned, and an assessment whether cross-contaminated products may have been released for distribution. The assessment should identify any inadequacies of cleaning procedures and practices, and encompass each piece of manufacturing equipment used to manufacture more than one product.Quality SystemsYour firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA’s guidance documents Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/media/71023/download.Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accord with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found your quality unit is not enabled to exercise proper authority and/or has insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s global manufacturing operations to ensure that your systems, processes, and products conform to FDA requirements.Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.Unapproved New Drug ViolationsBased on a review of the product labeling, “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” are “drugs” under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or intended to affect the structure or any function of the body. Examples from your product labeling that provide evidence of the intended use (as defined in 21 CFR 201.128) of these products as a drug include, but may not be limited to, the following:Geologie Acne Control Body Wash“2% Salicylic Acid…1.5% Glycolic Acid…Clears Skin Fast…Prevents New Breakouts… Drug Facts…Uses…For the treatment of acne. Penetrates pores to eliminate most acne blemishes, whiteheads, & blackheads. Helps prevent new acne blemishes.” [from the product label]Perricone MD Acne Relief Maximum Strength Spot Gel“Acne Relief…Drug Facts…Uses…For the treatment of acne…KEY INGREDIENTS Lactic & Succinic Acids: Target Acne-Causing Bacteria…help minimize blemishes…Citrulline: Fight & Visibly Reduce Redness…Tea Tree Oil: Clarify & Soothe… helps soothe the skin & visibly reduce redness.” [from the product label]Based on the above labeling evidence, “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” are intended for use as acne drug products. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these drug products identified above.Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "OTC monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription acne drug products, such as your “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel”, in order to be GRASE and not new drugs, the products must, among other things, conform to the conditions in the applicable OTC monograph(s), here M006 (Topical Acne Drug Products for Over-the-Counter Human Use).1 However, “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” do not conform to the conditions specified in M006 for the reasons described below.Your product "Geologie Acne Control Body Wash" includes the active ingredient Glycolic Acid, which is not a permitted active ingredient under M006.10. 21. CFR 201.66(b)(2) defines “active ingredient” to mean “any component that is intended to furnish pharmacological activity or other direct effect in the diagnosis, cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body of humans.” Although the product label does not specifically list Glycolic Acid as an active ingredient in the Drug Facts labeling, your product labeling makes claims such as “1.5% Glycolic Acid…Clears Skin Fast…Prevents New Breakouts” which demonstrates that this is an “active ingredient” in your acne treatment product because it is intended to furnish pharmacological activity. Specifically, the ingredient for this product is not permitted or recognized as an acceptable active ingredient when used under M006. We note that while salicylic acid is a permitted active ingredient under M006, it is not permitted in combination with the above ingredient or other active ingredients.In addition, as labeled, "Perricone MD Acne Relief Maximum Strength Spot Gel" includes the active ingredients Lactic & Succinic Acids, Citrulline, and Tea Tree Oil, which are not permitted active ingredients under M006.10. Although the product label does not specifically list Lactic & Succinic Acids, Citrulline, and Tea Tree Oil as active ingredients in the Drug Facts panel. Label claims such as “KEY INGREDIENTS Lactic & Succinic Acids: Target Acne-Causing Bacteria…help minimize blemishes…Citrulline: Fight & Visibly Reduce Redness…Tea Tree Oil: helps soothe the skin & visibly reduce redness” demonstrate that these are “active ingredients” in your acne treatment product because they are intended to furnish pharmacological activity.Thus, the “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” products do not comply with the applicable conditions specified in M006 and have not otherwise been found to be GRASE.2 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there are no applications in effect for these products, these products are unapproved new drugs.The introduction or delivery for introduction of these unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Misbranded Drug ViolationsYour “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Cosmetics Manufactured for Distribution in the United StatesIn addition, some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. We note that under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.Drug Production SuspendedWe acknowledge your commitment to suspend production of OTC drug products “that do not meet the required testing and systemic rigor” at this facility.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 addition, based upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to assist your firm in meeting CGMP requirements. 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 all corrective action and preventive action, 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.In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.ConclusionAs previously stated, you are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.Unresolved violations may 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.Send your written response to CDER-OC-OMQ-Communications@fda.hhs.gov within fifteen (15) business days of receipt of this letter. Identify your written response with FEI 2244819 and ATTN: Sena G. Dissmeyer in the letter or in the subject line of the email.If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.FDA posts warning letters on www.FDA.gov.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration/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_______________________________1 M006, in the final administrative order, Over-the-Counter Monograph M006: Topical Acne Drug Products for Over-the-Counter Human Use, reflects the conditions in the relevant final order established and in effect under section 505G. See Order ID OTC000013, available at FDA’s website OTC Monographs@FDA, https://www.accessdata.fda.gov/scripts/cder/omuf/.2 FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that “Geologie Acne Control Body Wash” and “Perricone MD Acne Relief Maximum Strength Spot Gel” products are GRASE for use under the conditions prescribed, recommended, or suggested in their labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDReference #:320-26-128Product:DrugsOver-the-Counter DrugsRecipient:Dr. Dikran BabikianChief Executive OfficerBabikian Healthcare Products CJSCGevorg Chaush Highway 902413 Proshyan Community KotaykArmenia (b)(4)Issuing Office:Center for Drug Evaluation and Research (CDER)United StatesSeptember 21, 2026WARNING LETTERReference number: 320-26-128To Dr. Dikran Babikian:This warning letter advises you of significant violations identified during a U.S. Food and Drug Administration (FDA) review of records submitted from your facility. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory action without further notice.FDA ReviewViolations were identified and documented during review of your drug manufacturing facility, Babikian Healthcare Products CJSC, FDA Establishment Identifier (FEI) 3027526825.1 This review was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.Your facility is registered with the FDA as a manufacturer of over-the-counter (OTC) drug products. FDA has reviewed the records you submitted in response to our August 12, 2025 request for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations, parts 210 and 211 (21 CFR, parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding of drugs as described in your response to our 704(a)(4) request do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 351(a)(2)(B)).Violations of the Federal Food, Drug, and Cosmetic ActThe following are violations identified during our review. As a reminder, this is not an all-inclusive list of violations at your facility.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) & 211.84(d)(2)).Your firm manufactures OTC drug products, including (b)(4), intended for the U.S. market. Your response to our request for records and information under section 704(a)(4) indicated that you do not test the identity of each incoming component, (b)(4), used in the manufacture of your drug products prior to manufacturing. Your response also indicated that you accept your suppliers’ certificates of analyses without verifying the test results at appropriate intervals.You also did not provide evidence that (b)(4), the active ingredients in your drug products, meet USP limits for (b)(4). See FDA’s guidance document (b)(4).Without adequate testing and verification of supplier results, you do not have scientific evidence that your incoming components conform to appropriate specifications prior to use in the manufacture of your drugs. As a manufacturer, you have a responsibility to sample, test, and examine incoming materials before use in production to assure adequate quality.2. 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. Your firm also failed to conduct appropriate laboratory testing, as necessary, for each batch of drug product required to be free of objectionable microorganisms (21 CFR 211.165(a) and 211.165(b)).Based on the records and information you provided, you did not demonstrate that you adequately test your finished OTC drug products prior to release and distribution to the United States. For example, the finished product testing reports you provided did not include appropriate assay testing for the identity and strength of each active ingredient or for impurities prior to release. Additionally, the records you provided failed to demonstrate adequate microbiological testing for each batch of your drug product prior to release.Testing is an essential part of CGMP to ensure that the drug products you manufacture conform to all predetermined quality attributes appropriate for their intended use. Drug products must be tested for identity and strength of the active ingredient, prior to release and distribution. Without adequate testing, you do not have scientific evidence to assure that your drug products conform to appropriate specifications before release.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).Based on the records and information you provided, you did not demonstrate that your quality unit (QU) adequately exercised its authority and responsibilities for the manufacture of your OTC drug products. For example, your QU failed to ensure the following:Establishing appropriate written procedures for production and process controls to qualify process performance and for qualification of your (b)(4) system, which produces (b)(4) used as a component in your drug products (21 CFR 211.100(a)).Maintaining complete manufacturing information relating to the production and control in batch records (21 CFR 211.188).Providing appropriate stability data to support the labeled drug product expiration date (21 CFR 211.137(a)).Establishing adequate QU authority and procedures (21 CFR 211.22(a) & 211.22(d)).Your firm’s quality systems are inadequate. For help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211, see FDA guidance documents Quality Systems Approach to Pharmaceuticals CGMP Regulations at https://www.fda.gov/media/71023/download.Drug Registration and ListingWe note that two separate establishments are referenced in this warning letter. Under section 510(i) of the FD&C Act and 21 CFR 207.17(a) any establishment within any foreign country engaged in the manufacture, preparation, propagation, compounding, or processing of a drug that is imported or offered for import into the United States must be registered with FDA. Under section 301(p) of the FD&C Act, 21 U.S.C. 331(p), it is a prohibited act to fail to register an establishment as required by section 510 of the FD&C Act. Additionally, a drug may be considered misbranded within the meaning of section 502(o) of the FD&C Act, 21 U.S.C. 352(o) if it was manufactured in an establishment not duly registered under section 510 of the FD&C Act. It is your responsibility to ensure that all drugs manufactured at your establishment(s) comply with all establishment registration and drug listing requirements under section 510 of the FD&C Act, 21 U.S.C. 360, 21 CFR Part 207, and all other applicable FDA regulations.CGMP ConsultantBased upon the nature of the violations we identified in your response, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionAs previously stated, you are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.FDA placed all drugs and drug products offered for import into the United States from your firms, FEI 3027526825 and FEI 3032638909, on Import Alert 66-40 on June 22, 2026.FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Babikian Healthcare Products CJSC, Gevorg Chaush Highway 90, Proshyan Community, Kotayk 2413 Armenia 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).Send your written response to CDER-OC-OMQ-Communications@fda.hhs.gov within fifteen (15) business days of receipt of this letter. Identify your written response with FEI 3027526825 and ATTN: Christina Capacci-Daniel in the letter or in the subject line of the email.If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.FDA posts warning letters on www.FDA.gov.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration/S/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchFood and Drug Administrationcc:U.S. Agent: Mr. Michael SarianAmerican Healthcare Systems Corp., Inc.(b)(4)______________________________1 We note that Babikian Healthcare Products, 8 North Ave, Apartment 22, Yerevan, FEI 3032638909 was also listed as the manufacturer of record for several shipments to the U.S. but was not a registered FDA manufacturing facility. See the Facility Registration section below for guidance.

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDProduct:DrugsRecipient:CelmadeSouth KoreaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesSeptember 14, 2026www.celmade.co and www.celmade.netcelmadesales@gmail.com, no-reply@celmade.co, wholesale@celmade.coWARNING LETTERReference Number: MARCS-CMS 735876To Celmade:This warning letter advises you of significant violations identified during a U.S. Food and Drug Administration (FDA) review of your websites www.celmade.co and celmade.net. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that may exist in connection with your products or operations. It is your responsibility to ensure that you comply with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.As discussed below, FDA has observed that www.celmade.co and celmade.net introduce into interstate commerce unapproved and misbranded injectable botulinum toxin drug products. FDA has identified significant risks associated with unapproved botulinum toxin products, especially in the absence of appropriate medical supervision. Furthermore, injectable drug products can pose a serious risk of harm to users because they bypass many of the body's natural defenses against toxic ingredients, toxins, or dangerous organisms that can lead to serious and life-threatening conditions such as septicemia or sepsis.There are also inherent risks to consumers who purchase unapproved new drugs and misbranded drugs. Unapproved new drugs do not carry the same assurances of safety and effectiveness as those drugs subject to FDA oversight. Drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether.Accordingly, FDA requests that www.celmade.co and celmade.net cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to shielding the American public from harm.FDA ReviewViolations were identified and documented during a review of your websites www.celmade.co on August 4, 2026, and celmade.net on September 1, 2026 (FDA Establishment Identifier (FEI) 3038674250).Violations of the Federal Food, Drug, and Cosmetic ActOn your websites at internet address www.celmade.co and celmade.net, you introduce into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 502(f)(1), 503(b)(1), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 331(a), 331(d), 352(f)(1), 353(b)(1), and 355(a)).The following are violations identified during our review. As a reminder, this is not an all-inclusive list of violations that may exist in connection with your products or operations.Unapproved New Drug ViolationsCertain products offered for sale by www.celmade.co and celmade.net are drugs within the meaning of section 201(g) of the FD&C Act (21 U.S.C. 321(g)) because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These drugs are also new drugs as defined by section 201(p) of the FD&C Act (21 U.S.C. 321(p)), because they are not generally recognized as safe and effective for their labeled uses. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act.You failed to obtain approved applications pursuant to section 505 of the FD&C Act (21 U.S.C. 355) for these products that you have introduced into interstate commerce. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act.An example of an unapproved botulinum toxin drug product you offer for sale on www.celmade.co is botulinum toxin type A marketed as "Wonder tox 100." Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 Code of Federal Regulations (CFR) 201.128) includes the claim "Wonder Tox 100 works by relaxing targeted facial muscles responsible for expression lines, making it suitable for treating areas such as the forehead, crow's feet, frown lines, and neck bands. It can also be applied to the jawline to slim the face by relaxing the masseter muscles, offering versatility for facial contouring."An example of an unapproved botulinum toxin drug product you offer for sale on www.celmade.net is botulinum toxin type A marketed as "Wondertox 100 Unit." Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21CFR 201.128) includes the claim "Hyperhidrosis: For individuals experiencing excessive sweating, Wondertox offers relief for areas like the underarms and palms."While there are FDA-approved versions of botulinum toxin drug products on the market in the United States, there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for "Wonder tox 100” offered by www.celmade.co and “Wondertox 100 Unit” offered by celmade.net. Currently there are several botulinum toxin products FDA-approved for the U.S. market and these products are only available pursuant to a prescription from a licensed practitioner. Examples of FDA-approved botulinum toxin products with a summary of their indications are: BOTOX (onabotulinumtoxinA), indicated for the treatment of overactive bladder, neurogenic detrusor overactivity, chronic migraine, spasticity, cervical dystonia, severe primary axillary hyperhidrosis, strabismus, and blepharospasm and prophylaxis of headaches in adults with chronic migraines; DAXXIFY (daxibotulinumtoxinA-lanm), indicated for the temporary improvement in the appearance of glabellar lines and the treatment of cervical dystonia; and MYOBLOC (rimabotulinumtoxinB), indicated for the treatment of cervical dystonia and chronic sialorrhea.Furthermore, FDA-approved botulinum toxin drug products bear a boxed warning, commonly referred to as a “black box warning,” which is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. The boxed warning addresses the risk of distant spread of toxin effect to produce symptoms consistent with botulinum toxin effects. In addition, swallowing and breathing difficulties can be life threatening and there have been reports of death.Misbranded Drug ViolationsA drug is misbranded under section 502(f)(1) of the FD&C Act if its labeling fails to bear adequate directions for use. "Adequate directions for use" means directions under which a layperson can use a drug safely and for the purposes for which it is intended (see 21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1) of the FD&C Act include those that, because of their toxicity or other potentiality for harmful effect, or the method of their use, or the collateral measures necessary for their use, are not safe for use except under supervision of a practitioner licensed by law to administer them. Prescription drugs, as defined in section 503(b)(1)(A) of the FD&C Act (21 U.S.C. 353(b)(1)(A)), can be used safely only at the direction, and under the supervision, of a licensed practitioner.You failed to bear adequate directions for use on the labeling for these drug products that you have introduced into interstate commerce. Because the aforementioned drugs are prescription drugs intended for conditions that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use these products safely for their intended use. Consequently, the labeling for these drugs products fail to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. Because these drugs are not approved in the United States, they are also not exempt under 21 CFR 201.115(a) from the requirements of section 502(f)(1) of the FD&C Act. By offering these drugs for sale to U.S. consumers, www.celmade.co and celmade.net are causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act.ConclusionAs previously stated, you are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.Send your written response to FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov within 15 business days of receipt of this letter. Include the specific steps you have taken to correct any violations, an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. Identify your written response with reference number “MARCS-CMS 735876” in the subject line of the email.If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.If you are not located in the United States, please note that products that appear to be misbranded or unapproved new drugs may be detained or refused admission. We may advise the appropriate regulatory officials in the country from which you operate that your products referenced above appear to be unapproved and misbranded products that cannot be legally sold to consumers in the United States.Please note FDA posts warning letters on www.fda.gov.Sincerely,/S/Sangeeta Vaswani Chatterjee, PharmDDirectorOffice of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-44Product:DrugsRecipient:Mr. Joseph MizikovskyChief Executive OfficerVeganicSKN Limited243 Milton RoadBrisbane QLD 4064AustraliaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-44February 9, 2026Dear Mr. Mizikovsky:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, VeganicSKN Limited, FEI 3024609429, at 81 Shettleston Street, Unit III, Rocklea, Queensland, Australia, from July 15 to 21, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your August 11, 2025, response to our Form FDA-483 in detail, and we acknowledge receipt of your subsequent correspondence.During our inspection, our investigator observed specific violations, including but not limited to the following.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm failed to conduct an adequate and timely out-of- specification (OOS) investigation for your (b)(4) drug product. Your contract testing laboratory reported an OOS result for (b)(4) on August 28, 2024, but you did not initiate the Phase II investigation until December 4, 2024. Despite the ongoing investigation, your quality unit (QU) released the batch on (b)(4), and subsequently shipped the batch for the U.S. market on (b)(4), after your firm retested the sample and obtained passing results. A root cause was not determined for the OOS result, and the investigation was closed on July 11, 2025.In your response, you state that you opened a corrective action and preventive action (CAPA) plan that includes updating your procedure for releasing drug products, and you conducted a risk assessment to determine the final disposition of this lot, which is still within expiry and any subsequent market action.Your response is inadequate because it fails to provide a justification for not completing your OOS investigation for nearly 11 months. Additionally, while you state that the OOS drug product was shipped because of a breakdown in your drug product-release procedure, you did not determine the root cause for the actual OOS result, nor did you conduct a comprehensive assessment of your quality system to ensure that all OOS investigations have been adequately investigated.Inadequate investigations can lead to unidentified root causes, ineffective CAPAs, and recurring problems that compromise your ability to manufacture safe and effective drug products.For more information about handling failing, OOS, out-of-trend, or other unexpected results and documentation of your investigations, see FDA’s guidance document Investigating Out-of-Specification (OOS) Test Results for Pharmaceutical Production at https://www.fda.gov/media/71001/download.In response to this letter, provide:A retrospective, independent review of all invalidated OOS (including in-process and release/stability testing) results for U.S. products currently in the U.S. market and within expiry as of the date of this letter, and a report summarizing the findings of the analysis, including the following for each OOS:o Determine whether the scientific justification and evidence relating to the invalidated OOS result conclusively or inconclusively demonstrates causative laboratory error.o For investigations that conclusively establish laboratory root cause, provide rationale and ensure that all other laboratory methods vulnerable to the same or similar root cause are identified for remediation.o For all OOS results found by the retrospective review to have an inconclusive or no root cause identified in the laboratory, include a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history). Provide a summary of potential manufacturing root causes for each investigation, and any manufacturing operation improvements.A comprehensive review and remediation plan for your OOS result investigation systems. The CAPA should include but not be limited to addressing the following:o QU oversight of laboratory investigationso Identification of adverse laboratory control trendso Initiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Resolution of causes of laboratory variationsInitiation of thorough investigations of potential manufacturing causes whenever a laboratory cause cannot be conclusively identifiedo Adequately scoping of each investigation and its CAPAo Revised OOS investigation procedures with these and other remediations.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm did not adequately test your incoming component, (b)(4), for identity prior to use in manufacturing. (b)(4) is a component that is at high risk for (b)(4) contamination. Your firm also accepted the (b)(4) raw material based on the supplier’s certificate of analysis (COA), without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals. Additionally, the (b)(4) lot you utilized for drug product production had expired.In your response, you state that you opened a CAPA, performed a risk assessment, and sent all remaining drums of (b)(4) out for testing. In addition, you state that your firm is evaluating the (b)(4) of your (b)(4) products to a lower-risk excipient, to eliminate supply chain risk in all future productions.Your response is inadequate. Your risk assessment is theoretical. You conclude that the risk is low based on (b)(4) and (b)(4) application. You did not correlate the assessment to the actual test results for all affected lots. Additionally, your firm acknowledges that identity testing based on supplier COA plus FTIR was inadequate for high-risk materials like (b)(4), yet you still reference past acceptance decisions as part of your justification. Acknowledging the gap does not mitigate the fact that your product was released under a flawed system, without appropriate controls in place at the time. Further, while you describe retrospective testing of remaining drums, there is no clear discussion of drug product that had already been manufactured and potentially distributed using untested (b)(4). There is no mention of an impact assessment or of any market action.While your response states that you will reformulate your finished drug products to remove (b)(4), it lacks a retrospective assessment with supporting analytical testing for products containing materials at high risk for (b)(4) contamination that are still on the market and within expiry. Furthermore, your response did not include an assessment of your drug products to identify other components at risk for (b)(4) contamination and proposed corrective actions. Your response also lacks your interim plans, controls, or risk-mitigation strategies until you reformulate your finished drug products.Identity testing for (b)(4) and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for (b)(4) levels. 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 ensure the acceptability of these components 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. See FDA’s guidance document (b)(4) to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high risk for (b)(4) contamination at (b)(4)In your response to this letter, provide:A commitment to provide (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4).A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) contamination (including, but not limited to, (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your suppliers’ COAs instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your suppliers’ results through initial validation and periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of (b)(4), and certain additional high-risk components, we note that this includes the performance of parts A, B, and C of the USP monograph.The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine their 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 your program for qualifying and overseeing contract facilities that test the components you use to manufacture your drugs.A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.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 QU did not adequately exercise its authority and responsibilities, including but not limited to, implementing effective procedures and conducting adequate oversight of the drug products you manufacture. For example, your QU failed to ensure:Establishment of adequate procedures describing their roles, responsibilities, authorities, and oversight (e.g., production personnel perform functions that should be QA responsibilities (21 CFR 211.22(a) and 21 CFR 211.22(d)).That production and process control procedures are designed to assure the quality of drug products (e.g., completion of bulk hold time validation studies) (21 CFR 211.100(a)).Your firm’s quality systems are inadequate. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations for help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations (21 CFR parts 210 and 211) at https://www.fda.gov/media/71023/download.In response to this letter, provide a comprehensive assessment and remediation plan to ensure that your QU is given the authority and resources to function effectively. The assessment should also include but not be limited to:A determination of whether procedures used by your firm are robust and appropriateProvisions for QU oversight throughout your operations to evaluate adherence to appropriate practicesA complete and final review of each batch and its related information before the QU disposition decisionOversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products(b)(4)FDA identified significant concerns regarding the (b)(4), which appear to operate as closely integrated entities despite maintaining separate corporate identities. Both firms share the same physical location, use common manufacturing operations (utilities, equipment, document management system), and employ overlapping personnel, including key management oversight positions. This level of operationalintegration raises questions about the independence of your respective quality systems and regulatory compliance programs. Given that (b)(4), the shared resources and management structure between your firms create the potential for a risk that compliance deficiencies may be transferred or propagated across both organizations. The lack of clear operational separation between (b)(4) diminishes confidence in your ability to maintain independent quality-assurance functions and to implement effective corrective-action systems.Clarify the nature of this relationship and demonstrate how each entity maintains distinct and adequate control over its manufacturing operations, quality systems, and regulatory compliance responsibilities.CGMP Consultant RecommendedWe acknowledge that you have engaged a consultant to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should be qualified as set forth in 21 CFR 211.34 and should perform a comprehensive six-system audit of your entire operation for CGMP compliance, and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on January 9, 2026.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 VeganicSKN Limited, located at 81 Shettleston Street, Unit III, Rocklea, Queensland, 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 with an opportunity to address the deficiencies above. 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 3024609429 and ATTN: Yvette Johnson.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via Email Return Receipt RequestedProduct:DrugsRecipient:Zhiyu DuMarketing and Sales Center RepresentativeKellin Chemicals Co., Ltd. - ZhangjiagangNo. 5 Changjiang North RoadYangzijiang Chemical Industrial ParkZhenjiang Shi Jiangsu Sheng, 215634ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-15November 6, 2025Dear Zhiyu Du:Your firm is currently registered as a supplier of active pharmaceutical ingredients (API) (for example, (b)(4)) to manufacturers of finished drug products who have distributed to the U.S. market.The United States Food and Drug Administration (FDA) notified your site, Kellin Chemicals (Zhangjiagang) Co., Ltd., FEI 3017343300, at No. 5 Changjiang North Road, Yangzijiang Chemical Industrial Park, Zhangjiagana, Jiangsu, of a planned inspection of your drug manufacturing facility from July 7 to July 11, 2025. Your United States (U.S.) Agent, Registrar Corp., notified us that your firm refused the preannounced inspection.Under section 501(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(j), your drugs are adulterated in that they have been manufactured, processed, packed, or held in an establishment where the owner or operator has delayed, denied, limited, and/or refused to permit inspection.Until FDA is permitted to inspect your facility and confirms compliance with CGMP, we may withhold approval of any new applications or supplements listing your firm as a drug manufacturer. In addition, shipments of articles manufactured at Kellin Chemicals (Zhangjiagang) Co., Ltd., No. 5 Changjiang North Road, Yangzijiang Chemical Industrial Park, Zhangjiagana, Jiangsu, into the United States. that appear to be adulterated or misbranded are subject to being detained or refused admission pursuant to section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3).We recommend that you inform any U.S. customers of this letter. Introduction into interstate commerce of adulterated drugs violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a); and receipt in interstate commerce of adulterated drugs, and the delivery or proffered delivery thereof, such as by drug product manufacturers using adulterated API as a component, is a violation of section 301(c) of the FD&C Act, 21 U.S.C. 331(c).After you receive this letter, respond to this office in writing within 15 working days. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices, and/or submit a request to schedule an FDA inspection.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3017343300 and ATTN: Maria Pavco.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCc: Registrar Corp

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDReference #:320-26-127Product:DrugsRecipient:Philip MacnabbCEOCuria New York, Inc.223 South West StreetRaleigh, NC 27603United States (b)(4)Issuing Office:Center for Drug Evaluation and Research (CDER)United StatesSeptember 18, 2026WARNING LETTERReference number: 320-26-127To Mr. Philip Macnabb:This warning letter advises you of significant deviations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the deviations described herein without delay, including ensuring that appropriate resources are allocated to fully address the deviations and prevent their recurrence. This is not intended to be an all-inclusive list of the deviations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address deviations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.Deviations were observed and documented during an inspection of your drug manufacturing facility, Curia New York, Inc., FDA Establishment Identifier (FEI) 1310298 at 33 Riverside Avenue, Rensselaer, New York, from January 28 to February 5, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.This warning letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for active pharmaceutical ingredients (APIs).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your APIs are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your February 27, 2026, response to our Form FDA 483 in detail, and we also acknowledge receipt of your subsequent correspondence.Violations of the Federal Food, Drug, and Cosmetic ActThe following are deviations identified during our inspection and review. As a reminder, this is not an all-inclusive list of deviations at your establishment.1. Failure to have laboratory control records that include complete data derived from all laboratory tests conducted to ensure your API and intermediates comply with established specifications and standards.Not all electronic test results are included in your review to determine conformance of your API products.Your laboratory analysts routinely conducted unexplained injections in high-performance liquid chromatography (HPLC) and ultra-performance liquid chromatography (UPLC) without adequate documentation or supervision to ensure that product samples were not being tested. Your laboratory used Empower and TotalChrom software for chromatographic data processing and analysis. Your laboratory analysts performed thousands of unexplained injections using Empower over the last 30 months, and over 70 trial injections using TotalChrom in October 2025 alone. The injections that utilized the Empower software used the “Developer” role rather than the “Operator” role without appropriate documentation. For example:A. Our investigators found chromatograms for testing that was performed on January 14, 2026, on chromatography equipment HPLC 49, which showed four unexplained trial injections that were injected under the “Developer” role. Your analyst confirmed these trial injections could not be traced to any product, sample, or analysis. In your response you attributed the injections to the testing of (b)(4) swab samples. Pages from the associated laboratory notebook 830-7 contained no reference to the four trial injections. Your analyst did not document any rationale for performing the trial injections using the “Developer” role in the laboratory notebook.B. Your analyst conducted testing that showed two unexplained injections on February 1, 2026, on chromatography equipment UPLC 57, using the “Developer” role. Your analyst stated your QC supervisor tested (b)(4) cleaning swab samples that were reported in laboratory notebook 823-6. However, the laboratory notebook did not provide documentation on these unexplained injections.Your response regarding these two examples states that the trial injections were performed as part of a troubleshooting exercise assisted by your quality control supervisor, and that the trial injections had no impact. However, in your retrospective review of all trial injections you identified nine injections that lacked sufficient justification and need further investigations.You also stated in your response that nearly 20 percent of Empower trial injections were acquired or altered in “Developer” mode, which reflects inconsistent training or poor understanding of your procedure, SOP-RLS-000435. Allowing the use of the “Developer” role for analyst activities involving CGMP samples or regulated data fails to prevent analysts from performing unauthorized or undocumented sample analyses.Your response is inadequate because it does not include an investigation of all unexplained injections performed to determine the associated CGMP risk, and because it does not provide an explanation of why these trial injections were performed by analysts using the “Developer” role.We acknowledge your firm’s cessation of all trial injections, the removal of the “Developer” role in Empower, and your commitment to provide an additional retrospective assessment of all trial injections findings from January 2021 to October 2023.In response to this letter, provide the following:A comprehensive, independent investigation report for all trial injections, with supporting documentation showing that the trial injections were not sample injections. If an injection is identified as a sample injection, include a determination of the impact on the distributed API materials.A comprehensive, independent data-integrity assessment for all facilities, covering all computerized systems used in CGMP operations, that is, not limited to Empower and TotalChrom.2. Failure of your quality unit to exercise its responsibility to ensure the API and intermediates manufactured at your facility are in compliance with CGMP.Your Quality Unit failed to ensure adequate control over paper and electronic records. On January 29, 2026, our FDA investigator observed original laboratory records inside the shred bins maintained in your laboratory. For example, we found an original pH meter printout slip, indicating a pH reading of (b)(4); an original analytical balance printout slip, with a value of (b)(4) grams; and reviewer-signed Analytical Data Review Checklists.Your response states that there was negligible impact from these discrepancies; however, your response lacks evidence to support the conclusion of negligible impact for discarding these records. Your firm could not identify who generated the pH meter printout on December 19, 2025, and why they were discarded. Your analyst discarded a balance printout weight slip dated January 25, 2026, but did not document why this balance printout slip was discarded. Furthermore, you were unable to make batch associations with the discarded original sourced documents (for example, specific batch testing).Without attribution of the discarded records to defined test analyses, the conclusion of negligible impact lacks an adequate evidentiary basis. Although procedure SOP-RLS-000346 was updated to require the use of instrument logbooks, your quality unit failed to investigate why the generated records were discarded in the shred bins, indicating a lack of adequate oversight. The full scope of this traceability gap is not adequately included in your response.Additionally, our investigators found in the shred bin an excessive number of photocopies of your laboratory notebook pages, with CGMP activities documented. Your laboratory personnel reviewed photocopies of the original data rather than the original records, and subsequently they signed off on the original analyst notebooks without verifying any changes to the underlying data.Your response acknowledges that the photocopy review practice was a direct violation of your procedure SOP-RLS-000456, requiring that all electronic primary data be reviewed and verified against the analyst's notebook.In addition, your procedure RLS-SOP-PW-0047 GMP, “Document Storage, Control, and Retention,” requires that paper records pertaining to batch analysis be maintained. Your quality unit failed to ensure that all production control records were retained in accordance with this established procedure and failed to implement adequate controls to ensure the integrity of data generated at your facility.We acknowledge you removed (b)(4) shred bins from the locations in building (b)(4) and transferred them under the QU control. However, your response is inadequate. Your review of shred bin data appears not to include an analysis of the contents of all the shred bins identified during the inspection. Your protocol “Review of Shred Bin Contents” identified a bin that was not included in your summary report and did not provide an explanation for this omission.Your firm had indicated that the (b)(4) bins are collected (b)(4) by a third-party service provider for off-site destruction. You are unable to determine the scope of prior discarded material from the previous document destructions.Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drug substances you manufacture. See FDA's guidance document Data Integrity and Compliance with Drug CGMP at https://www.fda.gov/media/119267/download.In response to this letter, provide the following:A determination of how long the shred bin disposal of GMP documents has been occurring at your facility.A retrospective assessment of the scope and potential effect of the absence of instrument-use logbooks for all QC laboratory equipment over the applicable record-retention period, including an evaluation of whether any GMP testing results may be unattributable or unverifiable as a result.A retrospective assessment of the potential scope of records that may have been improperly destroyed before the inspection, given that shred bins were collected (b)(4) with no QA review.A broader data-integrity assessment, including a retrospective review of your QC laboratory operations to determine the extent to which uncontrolled documentation practices may have affected the integrity of GMP records.The complete final investigation report(s) regarding documents found in all shred bins. Include classification of documents, associated effect on product and manufacturing processes, and any deviation generated from the final assessment.A detailed, comprehensive data-integrity investigation protocol describing how your third-party consultants will evaluate electronic data.A comprehensive investigation into the extent of the inaccuracies and inconsistencies in data, records, and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of data-integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data-integrity deficiencies.o A comprehensive, retrospective evaluation of the nature of testing data-integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where the potential breaches were identified should evaluate all occurrences.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 data-integrity event and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global corrective action and preventive action (CAPA) plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all data, including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of each data-integrity deviation, including evidence that the scope and depth of the current action plan are commensurate with the findings of the investigation and the risk assessment. Indicate whether the individuals responsible for the data-integrity breaches can still influence CGMP-related or drug-application data at your firm.o Interim measures describing the actions you have taken or will take to ensure the quality of your drugs and to protect patients, such as notifying your customers, recalling product(s), conducting additional testing, adding lots to your stability programs to ensure stability, drug-application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (for example, training, staffing improvements) designed to ensure the integrity of your company’s data.o Confirmation that you will be hiring a data integrity compliance officer who is fully empowered to receive anonymous complaints from employees reporting data-integrity concerns, and with the authority to ensure that any potential breach is promptly investigated by an independent quality-assurance function, along with expertise from outside entities whenever needed.o A status report for any of the above activities already underway or completed.3. Failure to exercise sufficient controls over computerized systems to prevent unauthorized access or changes to data.Our investigators observed significant data-integrity violations at your facility involving the sharing of usernames and passwords that are used to gain access to your electronic computerized system for GMP analysis. For example, your electronic computerized system, (b)(4), interfaces with laboratory equipment (b)(4) and restricts access through individual, unique usernames and passwords. Despite this control, your laboratory analyst used another analyst's login credentials to conduct (b)(4) calibrations and to perform (b)(4)-sample testing.The sharing of credentials constitutes a serious violation of data-integrity principles and is inconsistent with GMP requirements. Your quality system failed to detect and prevent repeated occurrences of this practice.Your response acknowledges that your written procedure SOP-RLS-000438, “The Use of Computerized Systems for GMP Operations,” prohibited username and password sharing. Your retrospective review under Protocol RQA-P-0560 was limited to 12 stand-alone analytical instruments for the period from February 10, 2025, through February 4, 2026. This review does not encompass all computerized equipment requiring username and password access, nor does it evaluate discrepancies beyond the stated review period.In response to this letter, provide the following:A retrospective review of all computerized equipment for all your facilities, including but not limited to stand-alone systems that require username and password authentication to gain access, and all products for which the equipment was used for testing, limited to distributed products currently within expiry and on the U.S. market.A comprehensive, independent assessment covering all GMP-integrated computerized systems for a three-year period to fully characterize the scope of this data-integrity failure.A management strategy for your firm that includes the details of your global CAPA plan to implement attributable, legible, complete, original, accurate, contemporaneous (ALCOA) records throughout your operation. The detailed corrective action plan should describe how you intend to ensure the reliability and completeness of all data, including microbiological and analytical data, manufacturing records, and all data submitted to FDA.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.ConclusionYou are responsible for investigating and determining the root causes of any deviations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.Unresolved deviations may prevent other Federal agencies from awarding contracts. Failure to address deviations 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 deviations 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 deviations.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356c(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.Send your written response to CDER-OC-OMQ-Communications@fda.hhs.gov within fifteen (15) business days of receipt of this letter1. Identify your written response with FEI 1310298 and ATTN: Compliance Officer Sneha Patel in the letter or in the subject line of the email.If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.FDA posts warning letters to www.FDA.gov.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration_______________________________________1 Under 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 MAIL READ/DELIVERY RECEIPT REQUESTEDReference #:320-26-129Product:DrugsRecipient:Mr. Pierluigi AntonelliChief Executive OfficerFresenius Kabi USA LLC61346 Bad HomburgGermany (b)(4)Issuing Office:Center for Drug Evaluation and Research (CDER)United StatesSeptember 22, 2026WARNING LETTERReference number: 320-26-129To Mr. Antonelli:This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) inspection of your facility. Promptly address the violations described herein without delay, including ensuring that appropriate resources are allocated to fully address the violations and prevent their recurrence. This is not intended to be an all-inclusive list of the violations that exist at your facility. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations. Failure to adequately address violations may result in regulatory or legal action without further notice including, without limitation, seizure and injunction.FDA InspectionViolations were observed and documented during an inspection of your drug manufacturing facility, Fresenius Kabi USA LLC, FDA Establishment Identifier (FEI) 1450022, at 2085 N Hawthorne Ave, Melrose Park, IL from January 27 to February 18, 2026. This inspection was conducted under FDA’s statutory authority and public health responsibilities to protect the public from unsafe, ineffective, and poor quality drugs.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 March 11, 2026, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.Violations of the Federal Food, Drug, and Cosmetic ActThe following are violations identified during our inspection and review. As a reminder, this is not an all-inclusive list of violations at your facility.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm is a manufacturer of sterile injectable drug products produced primarily through aseptic processing, including but not limited to, products for intravenous (b)(4) use. You failed to adequately investigate drug product failures and discrepancies.Your investigations lacked data-supported root causes, formal documentation, expansion to all potentially affected products, and corrective action effectiveness checks. In multiple investigations, you inappropriately concluded there was no product impact based on overreliance on passing finished drug product test results (e.g., sterility, endotoxin, and environmental monitoring). The following examples illustrate these failures:Endotoxin Test FailuresIn 2025 and 2026, your firm received reports of patients experiencing adverse drug events, including apparent pyrogenic reactions, following administration of famotidine for injection. Notably, famotidine injection manufacturing had experienced multiple (b)(4) bioburden action limit failures. However, your firm failed to sufficiently investigate this critical deviation and permitted batch release following passing finished drug product test results (i.e., sterility, endotoxin).Subsequent testing of finished product retains, as part of the investigation into the adverse event complaints, revealed an endotoxin failure. Your firm ultimately recalled three famotidine injection batches.Your response acknowledges that (b)(4) bioburden samples showed gram-negative confluent growth. You state that, at the time of disposition of the affected batches, your firm did not consider the excessive bioburden to constitute an elevated endotoxin risk. You commit to revising procedures to ensure enhanced endotoxin sampling and testing whenever action-level gram-negative bacteria are identified during (b)(4) bioburden testing.Your response is inadequate. You do not commit to comprehensive review and CAPA of your complaint system to increase vigilance, or to extensive CAPA effectiveness checks.In order to prevent parenteral drug contamination with pyrogenic substances, including endotoxins, it is critical that your firm build quality into manufacturing operations and maintain ongoing robust upstream control. It should be noted that endotoxins are not retained by (b)(4). Any batch testing that reveals atypical bioburden levels is a signal that necessitates prompt attention. Pyrogen contamination in parenteral drug products can lead to significant adverse events such as fever, hypotension, inflammatory reactions, anaphylactic shock or death.For more information about pyrogen and endotoxin testing, see FDA’s Guidance for Industry Pyrogen and Endotoxins Testing: Questions and Answers https://www.fda.gov/media/83477/download.Media Fill FailuresYour firm experienced media fill failures on your aseptic manufacturing Line (b)(4) with limited barrier protection in September and October 2024. Media fill failures also occurred on (b)(4) Restricted Access Barrier System manufacturing Line (b)(4) in April and October 2025. In each case, you determined the most probable contributing factors for each failure were deficient aseptic techniques by your operators. Your investigations did not consider how the poor aseptic practices went undetected by your firm’s aseptic observer program during commercial operations.Your response includes your ongoing effort to improve aseptic practices, especially on your aseptic processing lines with limited barrier protection. You commit to an aseptic operations program assessment, updating procedures, and training operators.Your response is inadequate because it does not provide clear timelines for addressing the fundamental design flaws of your aseptic processing lines with limited barrier protection which are inherently vulnerable to excessive contamination risk. Following your media fill failures, you placed (b)(4) commercial batches on hold, however, you did not act similarly for liquid products produced on your (b)(4) aseptic manufacturing lines with limited barrier protection. Notably, those processing lines shared operators from the processing lines associated with deficient aseptic techniques and media fill failures.Extrinsic Biological Contamination (e.g., hair)Beginning in May 2022, you documented at least nine incidences of extrinsic contamination (e.g., hair) during your visible particulate inspection. This contamination was described as free-floating and in direct contact with the drug product. Drug products contaminated with hair can have microbial contamination and are generally considered adulterated. You did not initiate timely investigations in response to this contamination.Your response acknowledges the significance of issues involving extrinsic biological particulates and recognizes a procedural gap in how you classified critical defects such as extrinsic biological contamination. You commit to continuous improvement of your investigations program. Additionally, you commit to revising your particulate management system, conducting targeted supplier audits, and discontinuing tailgate samples for incoming stopper lots.Your response is inadequate. You did not address why your quality unit (QU), your Corporate Expert Circle, and your Corporate Emergency Committee did not reject commercial batches associated with the extrinsic biological contamination and instead released them for distribution to your customers. Also, you did not provide details of your heightened incoming quality control of stoppers. Additionally, your response does not indicate that you examined retains of your distributed drug products for the presence of hair.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, out-of-limit results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, the following:o Significant improvements in investigation competencieso Root cause evaluation and scope determinationo Corrective action and preventive action (CAPA) effectivenesso Quality assurance unit oversight, and written procedureso Address how your firm will ensure all phases of investigations are appropriately conducted.A comprehensive review of root cause investigations for deviations related to biological particulate matter found in your products, including incoming inspection activities and subsequent CAPA activities. Provide supporting documents, including data generated and effectiveness evaluations.An independent, retrospective review of all critical investigations (including each in-process, release, and stability test specification failure) for the last three years as of the date of this letter. Evaluate the adequacy of each investigation, including but not limited to, the following:o Determine whether a thorough review of production (e.g., batch manufacturing records, adequacy of the manufacturing steps, suitability of equipment/facilities, variability of raw materials, process capability, deviation history, complaint history, batch failure history) was conducted.o Assess sufficiency of review of related data and investigations to identify if there are potential systemic linkages.o Evaluate adequacy of scope, rigor, staff competencies, scientific/analytical foundation, root cause determinations, and CAPA.o Summary of findings of the assessment for each of the above elements.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program whenever needed, ensures final quality assurance unit decision authority, and is fully supported by executive management.A comprehensive evaluation of your program to prevent endotoxin contamination risks and associated CAPA, including but not limited to:o Containers and Closures ((b)(4) packaging components)o Ingredientso (b)(4) systemso Process and procedural controlso Design and control of your equipment, including preventive maintenance and repairso Manufacturing environmentAn independent, comprehensive review of your environmental monitoring (EM) program to ensure vigilant, timely detection and response to potential product contamination hazards in your manufacturing environment. This assessment should include, but not be limited to, the following:o Establishing appropriate limitso Sampling methodso Sampling locations and frequencieso Trend analysiso Appropriate investigation of deviations and adverse trendso Comprehensive CAPA plan based on the findings of the assessmentA comprehensive, independent review of your process simulation (e.g., media fill) program to ensure accurate simulations of commercial aseptic manufacturing operations, including but not limited to appropriate incorporation of worst-case conditions.An independent assessment of vials rejected for hair contamination, and an update that summarizes all analyses performed on suspected foreign matter identified as part of batch production (within expiration date) or after testing retains related to complaints.The most updated status on your supplier quality investigations for stoppers and any remediation efforts. Include the following:o Incoming component inspection resultso Defect trends and Acceptable Quality Limit performanceo Whether biological particulates have been identified in any incoming (b)(4) packaging components in the last three years2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).Inadequate Aseptic Process Simulations (Media Fills)Your media fills failed to accurately simulate aseptic manufacturing operations.At the time of the inspection, your firm used a sampling approach to determine a representative number of each intervention necessary to simulate your aseptic processes. A review showed that your media fill simulations did not adequately represent your maximum aseptic intervention counts (e.g., clearing stoppers in the (b)(4)/track, (b)(4) application, (b)(4) adjustment, removing vials from the (b)(4)). Additionally, inherent interventions (e.g., stopper additions, vial loading) are not documented in your batch records, which has the consequence of inadequate assessment of the risks these interventions present during actual aseptic production. Also, data indicated that the number of units in your media fills was insufficient.Inadequate documentation of interventions was the subject of findings from FDA’s 2022 inspection.In your response, you acknowledge some interventions did not simulate the maximum risk to your aseptic processes. You commit to implement an intervention docking and tracking system and enhanced oversight of related data. You state that you will ensure thorough review of batch intervention data in the future to support simulation of inherent and corrective interventions using an appropriate worst-case approach.Your response is inadequate. We acknowledge your commitment to conduct appropriate media fill simulations for your aseptic processing lines. However, you do not address the need for sufficient media fill batch sizes and your response lacks sufficient detail on how you will document and track interventions.When the potential for contamination is higher, as it is with your (b)(4) processing lines surrounded by barrier (b)(4), the number of units in a media fill should be the same as, or approach, the maximum production batch size. If a media fill program fails to incorporate contamination risk factors and closely simulate actual drug product exposure, the state of process control and assurance of sterility cannot be accurately assessed. Furthermore, your (b)(4) aseptic processing lines require an inordinate number of interventions and there is a need for fundamental design remediations. Notably, media fills cannot justify unsuitable manufacturing lines and processing conditions.Aseptic Technique and Poor Cleanroom BehaviorWe observed poor aseptic practices and inadequate oversight. These deviations included, but were not limited to, the following:Operators opening and closing (b)(4) doors with sharp movements while performing (b)(4) aseptic loading of (b)(4).Operators repeatedly contacted the (b)(4) barrier (b)(4) with their head and upper torso, including during (b)(4) installation and (b)(4) set up.Operators (b)(4) clamps over the (b)(4) sterile end of tubing (which conveys the sterile formulation) during setup activities.In your response, you discuss your ongoing efforts to improve your aseptic operations, and you commit to engaging a third-party consultant to assess your aseptic operation oversight. Also, you commit to implementing a standardized interview template when investigations involving personnel activities or interventions relate to human error. Additionally, you commit to improving classified area material handling.Your response fails to sufficiently acknowledge design flaws including, but not limited to, inadequate processing line layout, ergonomic deficiencies, excessive need for (b)(4) manipulations, insufficient barrier protection to provide adequate separation from surrounding areas, and other fundamental issues.The ISO 5 (Grade A) area is critical because sterile products are exposed during aseptic production and therefore vulnerable to contamination if operations are not well designed and diligently controlled. Your aseptic processes should be designed, and operations executed, to prevent contamination hazards to your sterile product. Flaws in the design of cleanrooms and aseptic processing lines, or improper execution of operations, can promote an influx of contamination into the critical processing area.See FDA’s guidance document Sterile Drug Products Produced by Aseptic Processing – Current Good Manufacturing Practice to 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:A comprehensive, independent risk assessment of all contamination hazards with respect to your aseptic processes, equipment, and facilities, including but not limited to, the following:o All human interactions within the ISO 5 area (e.g., risk reduction or elimination of (b)(4) interventions wherever possible)o Equipment suitability (e.g., reliability, capability, ergonomics, placement) and sufficient cleanroom spaceo Air quality in the ISO 5 area and surrounding room including, but not limited to, air volume and flowo Facility layouto Personnel flow and material flow (movement throughout all rooms used to conduct and support sterile operations and all material transfers)o Disinfection practices and procedureso Specific CAPA recommendations that will comprehensively address the design and control hazards identified in the risk assessmento A detailed remediation plan with timelines to address the findings of the contamination hazards risk assessment. Describe specific tangible, comprehensive improvements to be made to aseptic processing operation design and control of your (b)(4) processing lines surrounded by barrier (b)(4) and explain how this CAPA plan will thoroughly and robustly remediate your deficient (b)(4) aseptic processing lines.Your systematic plan to assure adherence to appropriate aseptic practices, cleanroom behavior, and written procedures, including but not limited to, an independent assessment of the following with accompanying CAPA:o Suitability of actual practices based on extensive retrospective review and prospective observation of aseptic processing operationso Deficiencies in production management oversight, and identification of specific improvements to ensure effective and routine supervisory oversight for all batcheso Frequency and depth of quality unit oversight (e.g., audit, ad hoc, daily interactions) of aseptic processing and its support operationso Adequacy of written procedures and operational ergonomicsThe assessment should also evaluate how poor aseptic technique and cleanroom behavior may have affected the quality and sterility of your drugs.In an easily searchable tabular format, your updated plan to expedite the transfer of manufacturing from your Building (b)(4) aseptic filling lines to your Building (b)(4) lines without creating drug shortages. Include a list of backup contract manufacturing organizations that would be utilized in the event you are unable to ensure supply chain continuity.3. Your firm failed to establish adequate control procedures to monitor the output and to validate the performance of those manufacturing processes that may be responsible for causing variability in the characteristics of in-process material and the drug. Your firm failed to perform operations within specifically defined areas of adequate size and to have separate or defined areas or such other control systems necessary to prevent contamination or mix-ups in aseptic processing areas (21 CFR 211.110(a) and 21 CFR 211.42(c)(10)).Inadequate Visual Inspection ProgramYour visual inspection program is inadequate to ensure your sterile injectable drug products are essentially free of visible particulates and defects. For example:You categorized all non-glass particulate, regardless of material type (i.e., hair) as major, which means more severe particulates of biological origin are not considered critical.(b)(4) visible particulate inspection systems often exhibited low detectability and high variability regardless of particle type (e.g., glass, white particulate, black particulate) and size.Your probability of detection (POD) of particulates using (b)(4) visual inspection was inadequate. Your methods often exhibit PODs significantly less than (b)(4)% for particulate matter defects. In addition, glass particulates in the visible range were not consistently detected.You lacked defect limits for specific types of non-glass particulate matter in the visual inspection program.In your response, you recognize that studies did not generate sufficient data across increasing particulate sizes to adequately qualify your visual inspection program and that comparison reports were not completed. Additionally, you indicated that all extrinsic particulates are now classified as critical defects and acknowledge the potential loss of sterility often associated with such particulates.Your response is inadequate. Although you commit to evaluating the visual inspection program with the assistance of an independent third-party consultant, your response lacks a sufficient assessment of products currently on the market.Visual detection of particulates is a probabilistic process that depends on, among other things, ensuring that visible particulates can be reproducibly detected by highly capable systems including, but not limited to, trained personnel with appropriate visual acuity. At a minimum, your visual inspection systems should reliably be capable of detecting particulates of 150 microns or greater at a 70% probability of detection. Furthermore, written procedures governing 100% inspections for visual particulates should clearly define the number of times re-inspection may be performed. You should limit and justify re-inspections. Generally, FDA does not recommend more than one re-inspection in an attempt to release a batch with atypical defect levels1.Inadequate Design of Facility and EquipmentWe observed your (b)(4) processing lines (b)(4) surrounded by barrier (b)(4) under ceiling-fed high efficiency particulate air (HEPA) systems. These processing lines required frequent (b)(4) activities during equipment setup and throughout routine production and did not provide appropriate separation and protection of the ISO 5 areas. For example, we observed the following regarding these aseptic processing lines:The use of (b)(4) tubing, (b)(4) clamps, and hand tools when making critical aseptic connections within the ISO 5 area that risk interruption of first-pass air and introduce contamination hazardsThe use of barrier (b)(4) of varying lengths across each line, which provided inadequate protection of the ISO 5 processing lineFrequent high-risk corrective interventionsIn your response, you emphasize that your firm has been focused on your plan to transition production from your current aseptic manufacturing lines (b)(4) to your (b)(4) lines rather than updating the sterility assurance controls on your original lines. You further commit to re-evaluating and improving your aseptic processing lines with the assistance of a third-party.Your response is inadequate. Your response lacks sufficient detail and corrective actions for sterility assurance improvements while you continue to use your (b)(4) processing lines with their inherent design flaws.In response to this letter, provide:A comprehensive, independent assessment and remediation plan for your visual inspection program to ensure compliance with CGMP. The assessment and remediation should include, but not be limited to, the following:o Implementing enhancements to your 100% visible inspection program, including defining critical, major, and minor defects and the individual defect limits for drug products.o Ensuring adequate methods, equipment, and personnel qualifications to reproducibly detect visible particulates, including particulates which historically have been identified in your operation.o Conducting rigorous qualification studies to ensure your (b)(4) visible particulate inspection systems consistently and reproducibly detects the variety of visible particulates encountered in your drug products.o For drug products that are difficult to inspect (e.g., (b)(4) containers), implementing destructive testing or other advanced technologies (e.g., (b)(4)) as appropriate, with statistically significant sample sizes to test for defects.o Incorporating product-specific knowledge, process experience, deviation investigation analysis, recall/complaint data, and quality risk management to improve the visual inspection program.Your associated remediations to your visual inspection program, including any newly established written procedures, equipment, and methods. Include a summary of the review and recommendations made by your independent consultant.Visible Particulate ContaminationWe encourage the use of suitable (b)(4) visual inspection for particulates to augment the (b)(4) visual inspection program. (b)(4) methods should be rigorously studied, and qualified, to assess their capability and robustness under various conditions, machine settings, container-closure sizes, defect types, product characteristic, and other variables. In addition, any use of (b)(4) particulate inspection as an adjunct method does not supplant the need for (b)(4) visual inspection for various other attributes (e.g., cracks; myriad defects of container or closure; (b)(4) issues, volume, atypical, (b)(4), or other appearance defects).Quality SystemsYour firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see FDA guidance documents: Q8(R2) Pharmaceutical Development at https://www.fda.gov/media/71535/download,Q9(R1) Quality Risk Management at https://www.fda.gov/media/167721/download, and Q10 Pharmaceutical Quality System at https://www.fda.gov/media/71553/download.CGMP ConsultantBased upon the nature of the violations we identified at your firm and because 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.Recall DiscussionOn July 9, 2026, FDA held a teleconference with your firm to discuss voluntary recall. During this call, FDA informed you that our inspection revealed that drug products produced at Fresenius Kabi USA LLC contain particulate of biological origin, do not meet CGMP requirements, and are considered adulterated. Your firm initially released these adulterated batches for distribution based on your assertion that product testing results were adequate. Following the recall discussion with FDA, your firm committed to recalling six batches of drug products. As a result, on July 16, 2026, recalls were initiated for:Glycopyrrolate Injection, USPLidocaine HCl Injection, USPRopivacaine Hydrocholoride Injection, USPLidocaine HCl Injection, USPRequest for a Meeting with FDAAfter you submit your response to this warning letter, we recommend you reach out to this office to arrange for a teleconference to discuss your corrective and preventive actions in detail. Please direct your request to Christina Reyes at christina.reyes@fda.hhs.gov and cc: CDER-OC-OMQ-Communications@fda.hhs.gov.ConclusionYou are responsible for investigating and determining the root causes of any violations and implementing corrective and preventative measures to ensure future and sustained compliance so that these violations and any others do not occur.Unresolved violations may 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.If you are considering an action that is likely to lead to a disruption in the supply of drugs produced at your facility, FDA requests that you contact CDER’s Drug Shortages Staff immediately, at drugshortages@fda.hhs.gov, so that FDA can work with you on the most effective way to bring your operations into compliance with the law. Contacting the Drug Shortages Staff also allows you to meet any obligations you may have to report discontinuances or interruptions in your drug manufacture under 21 U.S.C. 356c(b). This also allows FDA to consider, as soon as possible, what actions, if any, may be needed to avoid shortages and protect the health of patients who depend on your products.Send your written response to CDER-OC-OMQ-Communications@fda.hhs.gov within fifteen (15) business days of receipt of this letter2. Identify your written response with FEI 1450022 and ATTN: Carrie A. Hughes in the subject line of the email.If you have information that you believe demonstrates that your products are not in violation of the FD&C Act and FDA regulations, include that information for our consideration.Please note FDA posts warning letters on www.FDA.gov.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administrationcc: Mr. Steven R. NowickiPlant Manager, Fresenius Kabi USA LLCMelrose Park, IL(b)(4)_________________1 See FDA’s draft guidance document Inspection of Injectable Products for Visible Particulates to help you meet the CGMP requirements pertaining to visible particulate inspections of sterile injectable drug products at https://www.fda.gov/media/154868/download.2 Under 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.

为服务医药产业高质量发展，促进类器官/器官芯片等新方法（New Approach Methodologies，NAMs）的研究、验证和在药物研发中的应用，药审中心组织制定了《推进新方法（NAMs）研究和应用试点计划（“先锋计划”）》（见附件）。经国家药品监督管理局审核同意，现予发布，自发布之日起施行。 特此通告。 附件：推进新方法（NAMs）研究和应用试点计划（“先锋计划”）国家药监局药审中心2026年9月28日