Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:728783Product:DrugsRecipient:Lus Essentials LLC605 Ravoux RoadChaska, MN 55318United Statesningdeleon482@gmail.cominfo@lusessentials.storeIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesMay 14, 2026WARNING LETTERTo Lu’s Essentials:This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) review of your website. 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 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 has observed that you offer products marketed on your firm’s website as skin treatment and skin lightening products, including, but not limited to, “Dr. Yanhee Acne Treatment Set (Green)” and “Dr. Yanhee Cream Set (Pekas & Melasma Treatment) – Blue” (hereinafter “your products”) for sale in the United States. Additionally, FDA obtained a sample of these products and has serious safety concerns about them. FDA confirmed through laboratory analysis that these products contain high levels of mercury. Applying products that contain mercury to the skin repeatedly can allow mercury to be absorbed into the bloodstream, potentially causing serious and permanent health problems, including kidney damage and neurological damage. Children and pregnant individuals face heightened risks and should avoid exposure to these products.FDA ReviewViolations were identified and documented during a review of your website https://lusessentials.store in April 2026. Based on our review, your products are unapproved new drugs and misbranded drugs under sections 505(a) and 502(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 352(a). As explained further below, introducing or delivering these products for introduction into interstate commerce violates sections 301(a), 301(d), and 505(a) of the FD&C Act, 21 U.S.C. 331(a), 331(d), and 355(a).This review was conducted under FDA’s public health responsibilities to protect the public from unsafe, ineffective, and poor-quality drugs.Violations of the Federal Food, Drug, and Cosmetic ActUnapproved New Drug ViolationsThe following are violations identified during our review. As a reminder, this is not an allinclusive list of violations that may exist in connection with your products or operations.Based on a review of your website, your products 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, including on your website, that provide evidence of the intended use (as defined in 21 CFR 201.128) of these products as drugs include, but may not be limited to, the following:Dr. Yanhee Acne Treatment Set (Green)On the webpage https://lusessentials.store/products/dr-yanhee-acne-treatment-setgreen?variant=45027938828483:“Reduce acne, freckles, dark spots and tighten pores.”“Benefits: [t]reatment for [p]imples and [s]ever [sic] acne problems, [d]ark spots, reduce visible scars.”“Protects skin from the sun and skin whitening.”Dr. Yanhee Cream Set (Pekas & Melasma Treatment) - BlueOn the webpage https://lusessentials.store/products/dr-yanhee-whitening-cream-set-reduceacne-dark-spot-freckles-result-in-7-day?variant=44387523657923:“Dr.Yanhee [sic] Whitening Cream Set Reduce Acne Dark Spot Freckles Result in 7 day original Formula.”“Helps to eliminate dead cells, tighten pores, reduce acne, freckles, dark spots, dark circles, make your face bounce.”“Doctor YanHee Set (Blue Box) Original Formula is a popular face cream to help treat acne, freckles, good grade, original formula.”Your products are “new drugs” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because they are not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in their 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 approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for these products. Accordingly, these products are unapproved new drugs. The introduction or delivery for introduction into interstate commerce of these unapproved new drug products violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).Misbranded Drug ViolationsYour products are misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). Under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), a drug is misbranded if its labeling is false or misleading in any particular. Section 201(n) of the FD&C Act, 21 U.S.C. 321(n), provides that, in determining whether an article's labeling or advertising "is misleading there shall be taken into account . . . not only representations made or suggested . . . but also the extent to which the labeling or advertising fails to reveal facts material in light of such representations."The labeling for your products does not declare that they contain mercury. As previously mentioned, FDA confirmed through laboratory analysis that your products contain high levels of mercury. Consumers may purchase and use these products without knowing that they contain mercury, an ingredient that may cause serious harm, including kidney damage and neurological damage. The failure to disclose mercury in the product labeling renders your products misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a).The introduction or delivery for introduction into interstate commerce of these misbranded drug products is a prohibited act under section 301(a) of the FD&C Act, 21 U.S.C. 331(a).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 compliance so that these violations and any others do not occur.Send your written response to FDAAdvisory@fda.hhs.gov within fifteen (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 “728783” 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/Tina Smith, M.S.Captain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs and Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration

Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:26-HFD-45-05-01Product:DrugsRecipient:Naseem A. Jaffrani, M.D.3311 Prescott Road, Suite 310Alexandria, LA 71301United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERFDA Ref. No.: 26-HFD-45-05-01Dear Dr. Jaffrani:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at your clinical site between February 24 and March 13, 2025. The investigator representing FDA reviewed your conduct of the following clinical investigations:Protocol (b)(4), “(b)(4),” of the investigational drug (b)(4), performed for (b)(4)Protocol (b)(4), “(b)(4),” of the investigational drug (b)(4), performed for (b)(4)This inspection was conducted as a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.At the conclusion of the inspection, the FDA investigator presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your March 31, 2025, written response to the Form FDA 483.From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated March 31, 2025, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, part 312 (21 CFR 312), governing the conduct of clinical investigations and the protection of human subjects. We wish to emphasize the following:You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].As a clinical investigator, you are required to ensure that your clinical investigations are conducted in accordance with the investigational plan. The investigational plans for Protocol (b)(4) and Protocol (b)(4) required you to report all serious adverse events (SAEs) to the sponsor within 24 hours of your knowledge of the occurrence.You failed to adhere to this requirement. Specifically:1. The investigational plan for Protocol (b)(4) required every SAE, regardless of causality, occurring after the subject has provided informed consent and until 16 weeks after the last dose of study drug, to be reported to (b)(4) safety team immediately, without undue delay, but under no circumstances later than 24 hours after your learning about the events1.Specifically, Subject (b)(6) was consented on July 6, 2020, and the last dose of study drug occurred on July 8, 2024. This subject experienced the following SAEs, which were not reported to the sponsor’s safety team within the required time frame:a. The subject experienced an SAE of non-ST elevation myocardial infarction (NSTEMI) between September 1 and 3, 2022, which you became aware of on September 2, 2022. However, this SAE was not initially reported to the sponsor’s safety team until September 26, 2022.b. The subject experienced SAEs of COVID-19 pneumonia, chronic obstructive pulmonary disease exacerbation, and hospitalization for congestive heart failure between January 5 and 9, 2023, which you became aware of on January 5, 2023. However, these SAEs were not initially reported to the sponsor’s safety team until February 21, 2023; April 3, 2023; and May 1, 2023, respectively.c. The subject experienced SAEs of pulmonary embolism and deep vein thrombosis post-COVID-19 pneumonia between January 13 and 17, 2023, which you became aware of on January 13, 2023. However, these SAEs were not initially reported to the sponsor’s safety team until May 1, 2023.d. The subject experienced an SAE of worsening ischemic cardiomyopathy between October 3 and November 16, 2024, which you became aware of on November 13, 2024. However, this SAE was not initially reported to the sponsor’s safety team until November 24, 2024.2. The investigational plan for Protocol (b)(4) required all SAEs occurring from the time of informed consent until End of Study to be reported to Medpace Clinical Safety within 24 hours of knowledge of the occurrence, regardless of the investigator’s determination as to relatedness. The IRB suspended enrollment and dosing for Protocol (b)(4) on November 27, 2024. Specifically:a. Subject (b)(6) was consented on January 18, 2023. This subject experienced an SAE of post-operative neck hematoma, after a right carotid endarterectomy, between August 29 and September 2, 2023, which you became aware of on September 11, 2023. However, this SAE was not initially reported to the safety team until September 15, 2023.b. Subject (b)(6) was consented on July 17, 2023. This subject was hospitalized for hypotension between (b)(6), which you became aware of on January 30, 2025. However, this SAE was not initially reported to the safety team until February 7, 2025.In your March 31, 2025, written response to the Form FDA 483, you acknowledged that you failed to meet your responsibilities as a clinical investigator by relying on the clinical research coordinators to comply with all research requirements without sufficiently overseeing their day-to-day activities to ensure compliance. As corrective and preventive actions, you plan to participate with the new site management in the review of all studies for which you were the clinical investigator, and you plan to implement internal corrective action plans for future studies. You also stated that you attended mandatory training sessions related to, among other things, Good Clinical Practice for clinical trials. You further stated that you plan to develop and implement a system to determine at each subject’s visit whether an SAE has occurred. You plan to use this system to receive notifications from other health care professionals if an SAE has occurred, and to notify the study sponsor and IRB when an SAE occurs, no more than 12 hours (or as provided by the applicable protocol) after becoming aware of its occurrence.While we acknowledge the corrective and preventive actions that you have taken and plan to take, your response is inadequate because you have not provided sufficient details on how you, as a clinical investigator, will ensure adequate supervision and oversight of study personnel to whom you have delegated study procedures and tasks (for example, verifying that study activities performed by study personnel adhere to the protocol requirements), and how you plan to prevent similar violations from occurring in the future. You also did not provide sufficient details about how you will implement a system for reporting SAEs to ensure that the SAEs are reported in accordance with protocol requirements. Without these details, we are unable to determine whether your preventive action plan is adequate to prevent similar violations in the future.We emphasize that as the clinical investigator, it is your responsibility to ensure that studies are conducted in accordance with the investigational plan, both to protect the rights, safety, and welfare of subjects and to ensure the integrity of study data. Your failure to conduct the clinical investigation in accordance with the investigational plan, and specifically, your failure to report all SAEs to the sponsor within 24 hours of your knowledge of their occurrence, raises significant concerns about your protection of the study subjects enrolled at your site, and raises concerns about the reliability of the data collected at your site.This letter is not intended to be an all-inclusive list of deficiencies with your clinical studies of an investigational drug. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of receiving this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address this matter adequately may lead to regulatory action without further notice to you. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.Your written response, and any questions or concerns about this letter or the inspection, should be sent via email to the FDA at CDER-OSI-Communications@fda.hhs.gov.Sincerely yours,{See appended electronic signature page}David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration--------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.--------------------------------------------------------------------------------------------/s/------------------------------------------------------------DAVID C BURROW05/04/2026 01:05:05 PM_________________________1 See Protocol (b)(4), Version 5, effective September 19, 2023. We note that Protocol (b)(4), Version 3, effective October 9, 2020, which was applicable during the occurrence of some of the SAEs included in this letter, stated that every SAE, regardless of causality, occurring after the subject has provided informed consent and until 16 weeks after the last dose of study drug, must be reported to (b)(4) safety within 24 hours of learning of its occurrence. However, we note that the regulatory violations exist regardless of which protocol version was in effect.

Delivery Method:Via Electronic Mail - Delivery and Read Receipt RequestedProduct:DrugsRecipient:John W. Polley, MDPolleyMed, LLC1248 Hastings StreetTraverse City, MI 49686United States(b)(6), (b)(7)(C)Issuing Office:Center for Drug Evaluation and Research (CDER)United StatesMay 14, 2026WARNING LETTERTo Dr. John W Polley:This warning letter advises you of significant violations observed during a U.S. Food and Drug Administration (FDA) review of your product labeling and website. 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 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 has observed that you market SaniiSwab™ on your firm’s website, where SaniiSwab™ is available for purchase in the United States without a prescription.FDA ReviewViolations were identified and documented during a review of your product labeling, including your website, www.saniiswab.com, in April 2026. We also reviewed your social media websites at Facebook, https://www.facebook.com/people/SaniiSwab/61583517491065/, and Instagram, https://www.instagram.com/Sanii.Swab, which direct consumers to your website to purchase your product. Based on our review, your SaniiSwab™ product is an unapproved new drug under section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a). In addition, this product is misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a). As explained further below, introducing or delivering this product for introduction into interstate commerce is prohibited under sections 301(d) and 301(a) of the FD&C Act, 21 U.S.C. 331(d) and 331(a).This review was conducted under FDA’s public health responsibilities to protect the public from unsafe, ineffective, and poor-quality drugs.Violations of the Federal Food, Drug, and Cosmetic ActUnapproved New Drugs ViolationsThe 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.Based on a review of your product labeling, including your website and social media sites, your SaniiSwab™ product is a drug under section 201(g)(1) of the FD&C Act, 21 U.S.C. 321(g)(1), because it is 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 this product as a drug include, but may not be limited to, the following:“Uses Two-step method to clean and sanitize the skin of the lower inner nostrils ● cleans ● sanitizes” [from the product label]“Clean & Sanitize 2-step nasal protection” [from the product label]“Your nose is an entry point for infection-which is why daily nasal cleaning is as important as washing your hands. My 2-step method-used in over 2,000 nasal surgeries with ZERO infection-is now available for anytime, anywhere use… SaniiSwab™” [from the product label]“Learn how SaniiSwab helps prevent airborne pathogens from incubating and infecting . . . “Why should I clean my nose if other people around me are wearing masks? Our nasal passages are constantly bombarded with contaminants and allergens. In addition, we know that 30% of the population carry staph, as well as other bacteria and viruses. Daily nasal decolonization (just like daily hand-washing) helps reduce these contaminants during their incubation period to keep us healthy and minimize the spread of disease and infection.” [from the FAQs on your website at www.saniiswab.com/faqs]“Why is it important to do a 2-step nasal cleaning and disinfection process? … The period of time from contaminants first entering the nose to starting the infectious process is known as the incubation period. The goal in nasal decolonization is to eliminate these contaminants during their incubation period, prior to them becoming infectious, as well as, causing allergic reactions. Because our noses are continuously being bombarded by contaminants, the best way to protect ourselves is to clean our noses daily before incubation begins. How long are incubation periods for various contaminants? Incubation periods (virus/bacteria) Staph A: 20-50% of population colonized, MRSA: 10-20% of population colonized, Pneumococcus: 103 days, Covid 19: 3-6 days RSV: 3-7 days, Influenza A: 1-4 days, Influenza B: 1-2 days, Rhinovirus: 2-4 days” [from the FAQs on your website at www.saniiswab.com/faqs]“SaniiSwab transcends simple nasal sprays and sanitizing devices, offering a new standard for safeguarding public health and helping to reduce hospital acquired infections (HASIs).” [from the Medical Facilities USAGE on your website at https://www.saniiswab.com/medical-facilities]“Flu season is still peaking…Preventing illness and stopping the spread of germs is key. Do both with SaniiSwab! SaniiSwab cleans and sanitizes where 90% of the air we breathe (and germs) enter first. In just 30 seconds: … Wash away germs …” [from Facebook post https://www.facebook.com/photo.php?fbid=122127036507117249&set=pb.61583517491065.-2207520000&type=3]“Flu season is still in full swing. SaniiSwab, your daily nasal hygiene routine, helps stop the spread of germs. 2-step clean/sanitize process in just 30-seconds … Surgically-proven method …” [from Instagram post https://www.instagram.com/p/DVgUaatFIvL/]Your SaniiSwab™ is a “new drug” under section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here,1 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 approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for this product. Accordingly, this product is an unapproved new drug. The introduction or delivery for introduction into interstate commerce of this unapproved new drug product violates sections 301(d) and 505(a) of the FD&C Act, 21 U.S.C. 331(d) and 355(a).Misbranded Drug ViolationsYour SaniiSwab™ product is also misbranded under section 502(a) of the FD&C Act, 21 U.S.C. 352(a), because your product’s website falsely states that the FDA has approved your product. On this website (https://www.saniiswab.com/order-medical), you display the phrase “…FDA OTC approved…,” which creates the impression that the drug product is approved or legally marketable (see 21 CFR 207.77(b)). As previously noted, your SaniiSwab™ is not the subject of an FDA approved application. Therefore, labeling suggesting that your SaniiSwab™ product is FDA-approved is false or misleading.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).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 compliance so that these violations and any others do not occur.Send your written response to FDAAdvisory@fda.hhs.gov within fifteen (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 response with reference number “726018” 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/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:Kim Young-joo (CEO)IDO Pharm Co., Ltd.41 Beonnyeong-ro 15beon-gilDanwon-gu DistrictAnsan-si, Gyeonggi-do, Republic of Korea (15616)(b)(6)__________________________1 The Over-the-Counter Monograph M003: First Aid Antiseptic Drug Products for Over-the-Counter Human Use (M003) is limited to topical application to the skin to help prevent infection in minor cuts, scrapes, and burns. Your product is intended for nasal administration, which is not a permitted route of administration under M003. Even if considered under the broader rulemaking history for topical antiseptics, such as the Tentative Final Monograph (TFM) for Topical Antimicrobial Drug Products (59 FR 31402, June 17, 1994), the product is not permitted, as the 1994 TFM and its subsequent amendments do not include provisions for antiseptic products intended for administration inside the nostrils. Moreover, claims to prevent infection from "airborne pathogens" and specific diseases like COVID-19 and Influenza go far beyond any permissible claim under any monograph. SaniiSwab does not conform to M003, the 1994 TFM, or any other final administrative order.

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-26-66Product:DrugsRecipient:Mr. Jack ChaiGeneral ManagerHangzhou Yiqi Biotechnology Co., LtdRoom 204, Building 3, No. 66 Xixiang Road, Puyan StreetHangzhou Shi Zhejiang Sheng, 310018ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-66April 15, 2026Dear Mr. Chai:Your facility is registered with the United States Food and Drug Administration (FDA) as a manufacturer of active pharmaceutical ingredients (APIs). FDA has reviewed the records you submitted in response to our June 16, 2025, request and subsequent correspondence, for records and other information pursuant to section 704(a)(4) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) for your facility, Hangzhou Yiqi Biotechnology Co., Ltd, FEI 3035145155, at Room 204, Building 3, No. 66 Xixiang Road, Puyan Street, Hangzhou, Zhejiang 310018, China.This Warning Letter summarizes significant deviations from Current Good Manufacturing Practice (CGMP) for APIs.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 APIs are adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).Following review of records and other information provided pursuant to section 704(a)(4) of the FD&C Act, significant deviations were observed including, but not limited to, the following:1. Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes.Based on the records and information you provided, your firm failed to conduct process validation for the (b)(4) APIs manufactured at your facility. These APIs are for use in further processing to produce sterile drug products and for pharmaceutical compounding operations.Process validation evaluates the soundness of design and state of control of a process throughout its life cycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.Without adequate process validation, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA’s guidance for industry Process Validation: General Principles and Practices for general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing 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 APIs.Also provide a risk assessment and any follow up actions to be taken for the distributed APIs produced without performing any process validation studies.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.2. Failure to validate and verify the suitability of analytical methods.Based on the records and information you provided, your firm failed to perform test method validation or verification for each test method used for drugs distributed to the United States.Test methods must be validated to show that they are suitable for their intended use or verified to show at least equivalence with United States Pharmacopeia (USP) compendial methods. Method validation and verification are necessary to support reliable determinations of identity, strength, quality, purity, and potency of drugs. Without evaluating the validity of methods, you lack the basic assurance that the data provided to customers were an accurate reflection of pharmaceutical product quality and safety.In response to this letter, provide:A comprehensive, independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial test methods and specifications used to analyze each lot of your APIs before making a lot of disposition decisions, and the associated written procedures.3. Failure to design a documented, ongoing stability testing program to monitor the stability characteristics of API and to use the results to confirm appropriate storage conditions and retest or expiry dates.Based on the records and information you provided, your firm failed to perform routine stability testing to demonstrate that the quality attributes of your APIs remain acceptable throughout the labeled expiry period. For example, your firm did not provide sufficient stability test data for (b)(4), or other APIs manufactured at your facility.Without an appropriate stability program, you lack adequate scientific evidence to support that your APIs meet established specifications and retain their quality attributes throughout their labeled expiry.In response to this letter, provide:A retrospective risk assessment showing how you will ensure that marketed APIs meet stability specifications throughout their shelf life.A comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include but should not be limited to:o Stability indicating methodso Stability studies for each API in its marketed container/closure system before distribution is permittedo An ongoing program in which representative lots of each product are added each year to the program to determine if the shelf-life claim remains valido A detailed definition of the specific attributes to be tested at each station (time point)o All procedures that describe these and other elements of your remediated stability program.4. Failure to demonstrate that water used in the manufacture of your API is suitable for its intended use.Based on the records and information you provided, you failed to demonstrate that your (b)(4) water system is adequately monitored to ensure that it consistently produces water suitable for use in the manufacture of APIs intended for further processing into sterile drug products.Your (b)(4) water system must be adequately designed and properly maintained to minimize and control the potential for contamination. It must be suitable for its intended use and routinely tested at an adequate frequency to ensure ongoing conformance with appropriate chemical and microbiological attributes.In response to this letter, provide:A procedure for monitoring your water system that specifies routine microbial testing of water to ensure its acceptability for use in each lot of APIs produced by your firm.The current action/alert levels for total counts and objectionable organisms used for your (b)(4) Water system.A procedure governing your program for ongoing control, maintenance, and monitoring to ensure that the remediated system consistently produces water that meets (b)(4) Water, USP monograph specifications and appropriate microbial limits.Test methods, water-analysis frequency, diagrams of the water system, and the location of all sampling points.Additional API CGMP GuidanceFDA considers the expectations outlined in ICH Q7 when determining whether API are manufactured in conformance with CGMP. See FDA’s guidance document Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients for guidance regarding CGMP for the manufacture of API at https://www.fda.gov/media/71518/download.ConclusionThe deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.FDA placed all drugs and drug products offered from your firm for import into the United States on Import Alert 66-40 on January 30, 2026.Correct any deviations promptly. 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 verify that you have completed corrective actions to any deviations.Failure to address any deviations may also result in the FDA’s continuing to refuse admission of articles manufactured at Hangzhou Yiqi Biotechnology Co., Ltd, No. 66 Xixiang Road, Puyan Street, Hangzhou, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated or misbranded may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B), and are misbranded under section 502 of the FD&C Act, respectively.This letter notifies you of our findings and provides you with 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 deviations 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 3935145155 and ATTN: Chhaya Shetty.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA EMAIL WITH READ RECEIPTReference #:320-26-67Product:Drugs;Over-the-Counter DrugsRecipient:Mr. Jesse WindrixPresidentJW Nutritional LLC4700 S. Hardin Blvd., Suite 260McKinney, TX 75070-2411United Statesjesse@jwnutritional.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-67April 15, 2026Dear Mr. Windrix:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, JW Nutritional LLC, FEI 3031468435, at 4700 S. Hardin Blvd., Suite 260, McKinney, TX, from September 22 to 26, 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 October 17, 2025, response to our Form FDA 483 in detail and 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 test samples of each component for conformity with all appropriate written specifications for purity, strength, and quality (21 CFR 211.84(d)(2)).Your firm failed to ensure that components used in the manufacture of your over-the-counter (OTC) (b)(4) drug product “(b)(4)” are suitable for their intended use. You failed to perform adequate identity testing on each shipment of each lot of incoming components (e.g., (b)(4)).Products Contain Ingredients at Risk for (b)(4) ContaminationThe use of ingredients contaminated with (b)(4) has resulted in various lethal poisoning incidents in humans worldwide. 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).Identity testing for (b)(4), and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure 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 assure the acceptability of these components for use in the manufacture of your drug products.In your response, you state that you will perform additional testing for (b)(4).Your response is inadequate in that you did not provide a detailed plan for how your components will be assessed against compendial requirements. Also, you did not test all previous incoming components for presence of (b)(4).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 you use them in production to ensure that acceptable quality parameters are met.In response to this letter, provide:A commitment to provide (b)(4) test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of (b)(4).A full risk assessment for drug products that are within expiry which contain any ingredient at risk for (b)(4) contamination (including but not limited to (b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain (b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate corrective action and preventive action (CAPA) to secure supply chains in the future, including but not limited to ensuring that all incoming raw material lots are from fully qualified manufacturers and are 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’ certificates of analysis (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 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 (b)(4) of the USP monograph.2. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Lack of Process ValidationYou failed to validate your production and process controls.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluates batches to determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.See FDA’s guidance for industry, Process Validation: General Principles and Practices, for general principles and approaches that the FDA considers appropriate elements of process validation athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices.In your response, you state that you will perform process validation on the next purchase order batches by April 15, 2026.Your response is inadequate because you did not provide your interim plan for drugs distributed before process validation activities are complete to ensure you produced drug products of acceptable quality.Inadequate (b)(4) System ValidationYour firm failed to adequately qualify your (b)(4) system to ensure it produces (b)(4) that meets appropriate chemical and microbial attributes. You use (b)(4) as a component in your OTC drug product and to clean the manufacturing equipment.In addition, you do not adequately demonstrate that your (b)(4), at a minimum, meets (b)(4) USP monograph and appropriate chemical and microbiological limits. Specifically, you failed to perform (b)(4) testing as required. Furthermore, there is no indication that you monitor your (b)(4) for objectionable microorganisms (e.g., (b)(4)).(b)(4) must be suitable for its intended use. Each lot must be tested to ensure conformance with appropriate chemical and microbiological attributes. Routine monitoring of microbial counts, as well as characterization and identification of contamination, is integral to ensuring (b)(4) is of acceptable quality for use in manufacturing operations.In your response, you state that you have updated your procedures and plan to complete (b)(4) system validation within six weeks. You also state you will perform additional testing for (b)(4).Your response is inadequate because you did not provide adequate details regarding your plan for performing (b)(4) system validation, nor did you provide an interim plan to ensure that the (b)(4) is suitable for its intended use. Additionally, you did not provide a detailed plan for how you will access your plan against compendial requirements. The analytical test report you plan to use for (b)(4) inappropriately uses MPN/g (most probable number per gram) as the limit for total coliforms test. This methodology does not align with USP requirements or standard industry practice for (b)(4) testing.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 monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing process performance qualification for each of your marketed drug products. Also provide a risk assessment and any follow up actions to be taken for the distributed drug products produced without performing any process validation studies.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures your (b)(4) system consistently produces (b)(4) that meets (b)(4) USP monograph specifications and appropriate microbial limits.3. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).Your firm has inadequate microbiological release specifications for your OTC drug products. Specifically, your firm applied microbiological reference standards intended for foods and nutritional and dietary supplements to your (b)(4)-ounce tube. The applicable test standards for your product are USP ⟨61⟩ Microbial Enumeration Tests, USP ⟨62⟩ Tests for Specified Microorganisms.Your current specification establishes a Total Plate Count limit of not more than (NMT) (b)(4) cfu/g and a Yeast & Mold limit of NMT (b)(4) cfu/g, which are (b)(4)-fold higher than generally accepted levels for (b)(4) drug products (Total Aerobic Microbial Count NMT (b)(4) cfu/g and Total Combined Yeasts/Molds Count NMT (b)(4) cfu/g). Additionally, your specification fails to include testing for (b)(4).In response to this letter, provide:A list of microbial specifications, including test methods, used to analyze each batch of your drug product before a batch disposition decision.An action plan and timelines for conducting microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug product, take rapid corrective actions, such as notifying customers and product recalls.Clarification on whether you intend to continue production of your OTC drug product.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 at https://www.fda.gov/media/86193/download.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3031468435 and ATTN: Chhaya Shetty.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-73Product:DrugsRecipient:Mr. Guo Qing LengPresident and General ManagerHarbin Jixianglong Biotech Co., Ltd.North of Baoan Road, East of Changqing StreetHulan Qu Harbin Shi Heilongjiang Sheng, 150025ChinaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter 320-26-73May 1, 2026Dear Mr. Leng:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Harbin Jixianglong Biotech Co., Ltd., FEI 3024038751, at North of Baoan Road, East of Changqing Street, Liminzhen Hulan District, Harbin, Heilongjiang, from November 3 to 7, 2025.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).In addition, we reviewed your firm’s drug listing submissions in FDA’s electronic Drug Registration and Listing System (eDRLS) and found that you failed to provide drug listing information for your relabeled semaglutide as required under section 510(j) of the FD&C Act, 21 U.S.C. 360(j), and 21 CFR Part 207. Furthermore, your relabeled semaglutide was manufactured in an establishment not duly registered with FDA. Failure to provide listing information for a drug in accordance with 510(j) of the FD&C Act is prohibited under section 301(p) of the FD&C Act, 21 U.S.C. 331(p). Under section 502(o) of the FD&C Act, 21 U.S.C. 352(o), a drug is misbranded if, among other things, it was manufactured in an establishment not duly registered under section 510, or if it was not included in a list required by section 510(j). 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 any drug that is misbranded. These violations are described in more detail below.Your semaglutide API is also misbranded under sections 502(a) and 502(b)(1) of the FD&C Act, 21 U.S.C. 352(a) and 352(b)(1).We reviewed your November 26, 2025, response to our Form FDA 483 in detail and acknowledge receipt of your subsequent correspondence.During our inspection, our investigators observed specific deviations including, but not limited to, the following.1. Failure of your quality unit to exercise its responsibility to ensure that APIs manufactured at your facility are in compliance with CGMP and failure to maintain complete traceability of APIs in commercial distribution.Your firm is a manufacturer of peptide APIs, including Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist APIs. FDA investigators observed that your firm lacked adequate quality unit (QU) oversight for the receipt of materials, repackaging, relabeling, and related controls for APIs. Specifically, there is no quality unit approved procedure governing the repackaging and relabeling operations for APIs sourced from external manufacturers prior to distribution to the U.S. market. For example:On (b)(4), your firm purchased semaglutide API (batch (b)(4)) from (b)(4), a supplier that was not on your approved supplier list. You repackaged and relabeled this batch without documentation and created a new labeled batch number, CP-030-20250711. Furthermore, on the label of the container you identified your firm, “Harbin Jixianglong Biotech Co. Ltd.,” as the manufacturer of API rather than (b)(4), the firm from which you purchased the API. You also changed the manufacturing date of the API from (b)(4) to July 25, 2025, and the retest date from to (b)(4) to July 24, 2027, without appropriate supporting data. This GLP-1 API was distributed to the U.S. on August 23, 2025.On (b)(4), your firm purchased semaglutide API (batch (b)(4)) from (b)(4), another supplier that was not on your approved supplier list at time of purchase and release. You repackaged and relabeled this batch without documentation and created a new labeled batch number, CP-030-20250911. You changed the manufacturing date of the API from (b)(4) to September 25, 2025, and the retest date from (b)(4) to September 24, 2027. This GLP-1 API was distributed to the U.S. on October 3, 2025.We note that on September 5, 2025, FDA implemented the Green List of Import Alert 66-80 to help address GLP-1 API drugs offered for import into the United States that appear to be adulterated or misbranded. As part of this Import Alert, GLP-1 API drugs from facilities not on the Green List would be subject to detention without physical examination upon import into the United States. Your firm was added to the Green List on September 5, 2025, based upon previously provided quality information.However, your firm purchased GLP-1 API (semaglutide) from (b)(4), a facility that is not on the Green List of IA 66-80. You then labeled the GLP-1 API as manufactured by your firm and shipped this batch to the United States, even though it was not manufactured by a facility on the green list. FDA is concerned that identifying your firm and not the actual manufacturers may have been an attempt to circumvent safeguards associated with IA 66-80 and may pose a risk to consumers of receiving substandard GLP-1 APIs.On February 10, 2026, FDA held a teleconference with you recommending you consider removing the two relabeled batches of semaglutide API drugs currently in distribution from the U.S. market. At the teleconference meeting, you agreed to voluntarily recall the two batches of semaglutide API drugs in current distribution in the United States.We acknowledge that on February 19, 2026, you initiated a voluntary recall of the two semaglutide API batches distributed in the United States.Additionally, during the inspection, our investigators discussed with your firm your decision to release and distribute at least (b)(4) batches of tirzepatide API to the U.S. market prior to the completion of stability studies to support the (b)(4) retest date. Your firm did not have an adequate written scientific justification to support the tentative expiration date applied to these lots before distribution.In your response, you state that due to high demand of semaglutide API in the U.S., you “occasionally purchased the product externally for resale.” You acknowledge lacking appropriate procedures for the release of externally purchased products and lacking batch records for the repackaging and labeling operations.Your response is inadequate. Although you commit to prohibiting the sale of externally procured products moving forward, you failed to address actions to be taken on the two distributed semaglutide API batches in the U.S market.In response to this letter, provide:A risk assessment of all APIs you repackaged that are missing any required manufacturing documentation for release and distribution., notify your customers and determine if market actions, such as recall, is necessary.A summary of your systemic corrective action and preventive action (CAPA) plan to remediate the supplier qualification program and prevent use of unsuitable material suppliers.A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o a determination of whether procedures used by your firm are robust and appropriateo provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso a complete and final review of each lot and its related information before the QU disposition decisiono oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productsYour stability report and data to support the claimed retest date for all of your APIs intended for U.S. market.2. Failure to demonstrate that your manufacturing process can reproducibly manufacture an API meeting its predetermined quality attributes and failure to adequately validate written procedures for the cleaning and maintenance of equipment.Process ValidationYou failed to appropriately validate your processes prior to release and distribution of your API. Specifically, you manufactured and distributed two batches of semaglutide API to the U.S. market despite having conducted no process validation.Without adequate process validation, your firm lacks basic assurance that you can reproducibly deliver products that meet specifications. See FDA’s guidance document for general principles and approaches that FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/downloadIn your response, you acknowledge that you have not initiated process validation for semaglutide API that you repackage and relabel. You compared the critical process parameters with the planned process validation lots and concluded that releasing these products without process validation was low risk.Your response is inadequate. Your risk assessment lacks sound scientific testing data to conclude low impact of using non-validated processes on APIs already distributed to the United States. Additionally, you failed to provide a complete process validation protocol for review. Your CAPAs lacked metrics for effectiveness of bringing your operations into compliance with CGMP.Cleaning ValidationYou lacked adequate cleaning validation studies that demonstrate your cleaning procedures for your manufacturing equipment are effective. For example, your cleaning procedure requires calculation of a maximum allowed carry over limit based on API toxicity. However, you did not establish a maximum allowed carryover limit in your cleaning validation study for the equipment used to manufacture peptide APIs, including semaglutide and tirzepatide. Furthermore, your cleaning validation study did not provide justification for the swab sampling locations, nor did it contain results from the swab sample testing as required by the same cleaning procedure.Inadequately cleaned and maintained manufacturing equipment can lead to potential cross-contamination that could compromise your API quality and safety.In your response you commit to drafting and executing a new cleaning validation protocol during your next production campaign in the original API workshop to include chemical residue testing on both direct and indirect product surfaces. Your response is inadequate because you did not provide a systemic CAPA for the deficiencies related to the misalignment between your cleaning procedure requirements and your cleaning validation study.In response to this letter, provide:Your process validation protocols and reports for all APIs shipped to or intended for the U.S. market.An assessment of each API process to ensure that there is a data-driven and scientifically sound program that identifies and controls all sources of variability, such that your production processes, and will consistently meet appropriate specifications and manufacturing standards. This includes, but is not limited to, evaluating suitability of equipment for its intended use, sufficiency of detectability in your monitoring and testing systems, quality of input materials, and reliability of each manufacturing process step and control.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 drugs 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.3. Failure to ensure that all specifications and test procedures are scientifically sound and appropriate to ensure that your APIs conform to established standards of quality and purity.You failed to establish that your analytical test methods are appropriately validated and suitable for use in API release testing. For example, in 2024 your firm shipped (b)(4) lots of tirzepatide API (about (b)(4) total weight) to the U.S. market without completing analytical method validation for assay and related substances by high-performance liquid chromatography, high molecular weight aggregates by size-exclusion chromatography, and amino acid ratio by high-performance liquid chromatography. Furthermore, in 2025, your firm shipped (b)(4) lots of tirzepatide API drugs (about (b)(4) total weight) without completing method verification for the bacterial endotoxin test.FDA is also concerned that your analytical method validation for tirzepatide API, specifically for related substance test (R-VTP-TP-11-009-024), is not adequate. The test method validation data you provided indicates poor resolution, overlapping peaks, and absence of structural identification for (b)(4) specified impurities. lack of comparative approach using multiple, orthogonal, high-resolution analytical methods for peptide-related impurity characterization. Your microbial limit enumeration test (R-VTP-TP-04-001-2025) validation data includes inconsistencies. For example, your test data for Pseudomonas aeruginosa are shown twice, and data for Bacillus subtilis is missing.For FDA’s current thinking regarding analytical test method validation and impurity characterization in synthetic peptides, see Analytical Procedures and Methods Validation for Drugs and Biologics at https://www.fda.gov/media/87801/download and ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin at https://www.fda.gov/media/107622/downloadIn your response, you acknowledge that your semaglutide and tirzepatide API drugs are in the development stage and full validation of all analytical methods has yet to be completed. You also acknowledge deficiencies in your product release procedure and failure of your quality system processes to identify and correct these non-compliant practices in a timely manner.Your response is inadequate. Although you intend to implement a new procedure requiring your certificates of analysis to contain a statement of “Only for R&D use purpose” for “developmental drug products,” you did not mention any stipulations on the acceptable quantity to be released for R&D use. Based on your invoice and shipping documents, the quantity of API drugs (as much as (b)(4)) shipped into the U.S. is inconsistent with quantities typically used for research and development purposes.In response to this letter, provide:A comprehensive assessment of your laboratory practices, procedures, methods, equipment, and documentation. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.Your analytical validation protocols and reports for the release testing of all APIs shipped to or intended for the U.S. market.Appropriate microbiological batch release specifications (i.e., total counts, identification of bioburden to detect objectionable microbes) for each of your GLP-1 APIs.A detailed risk assessment addressing the hazards posed by distributing APIs with potentially objectionable microbial contamination. Specify actions you will take in response to the risk assessment, such as customer notifications and product recalls.A summary of results from testing retain samples of all API drugs distributed to the U.S market and within expiry. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients and microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each lot. If testing yields an out-of-specification result, indicate the corrective actions you will take, including notifying customers and initiating recalls.4. Failure to ensure that water used in the (b)(4) manufacturing steps of a non-sterile API intended for a sterile drug product is monitored and controlled for total microbial counts, objectionable organisms, and endotoxins.You manufacture GLP-1 APIs that were imported into the United States. These GLP-1 APIs are intended for use in sterile injectable drug products. Your firm failed to ensure that the (b)(4) water you used in the (b)(4) manufacturing steps of your APIs was suitable for its intended use. For example, your non-sterile semaglutide and tirzepatide API are intended for sterile injectable drug products, and your (b)(4) water system has not been evaluated for the absence of objectionable microorganisms. There is no indication that your (b)(4) water was tested for endotoxin during manufacturing processing. Furthermore, you failed to conduct sampling and microbial testing of the (b)(4) water you manually transported and stored for use in the (b)(4) manufacturing process of your APIs.(b)(4) water must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. Routine and representative monitoring of microbial counts and identification of contamination in the system and at the point of use are integral to maintaining a state of control and the suitability of water used in manufacturing operations.In your response, you acknowledge your failure to perform a risk assessment of objectionable microorganisms and your resulting failure to evaluate the requirements for controlling objectionable microorganisms in your (b)(4) water system. You commit to establishing a microbial identification strategy and to adding E. coli testing for both the (b)(4) water system monitoring and to the API specification. Your response is inadequate. You did not include monitoring of additional objectional organisms as required by the United States Pharmacopeia (USP) monograph for (b)(4) water.In response to this letter, provide:Your commitment to routinely monitor and control endotoxins in your (b)(4) water to ensure its suitability for API intended for sterile drug products. Include alert/action limits, test methods, water analysis frequency, and diagrams of the water system, and location of all sampling points.The identification and assessment of all other aspects of the manufacturing process (e.g., input materials, holding times, equipment quality) that can contribute endotoxin to your APIs that may be used in parenteral manufacturing.A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each lot of API produced by your firm.The current action/alert limits for total counts and objectionable organisms used for your (b)(4) water system. Ensure that the total count limits for your (b)(4) water are appropriately stringent in view of the intended use of each of the products produced by your firm.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces water that meets (b)(4) Water USP monograph specifications, USP monograph tests for specified microorganisms, and appropriate microbial limits.Water analysis test results for a period of six months, obtained after implementation of additional testing including, but not limited to, sampling procedures and results for total microbial counts, objectionable organisms, and endotoxins.Drug Listing ViolationsSection 510(j) of the FD&C Act and 21 CFR Part 207 set forth the requirements for the listing of drugs. Under section 510(j)(1) of the FD&C Act and 21 CFR 207.41(a), a registrant must list each drug that it manufactures, repacks, relabels, or salvages for commercial distribution. Upon review of your firm’s batch records, it was found that you relabeled semaglutide purchased from (b)(4) and (b)(4). You failed to list these relabeled drugs. Additionally, (b)(4) and (b)(4) are not referenced in any of Harbin’s drug listings for semaglutide as establishments where manufacturing is performed as required by 21 CFR 207.49(a)(12). Failure to provide listing information for a drug in accordance with 510(j) of the FD&C Act is prohibited under section 301(p) of the FD&C Act. Further, you relabeled semaglutide that you purchased from (b)(4), a firm whose establishment registration is expired and that has not listed any drugs. 21 CFR 207.29 requires annual review and update of registration information for an establishment involved in the manufacture of drugs. Under section 502(o) of the FD&C Act, a drug is misbranded if, among other things, it was manufactured in an establishment not duly registered under section 510, or if it was not included in a list required by section 510(j). Under section 301(a), it is a prohibited act to introduce or deliver for introduction into interstate commerce any drug that is misbranded.Complete, accurate, and up-to-date establishment registration and drug listing information is essential to promote and protect patient safety. FDA relies on establishment registration and drug listing information for several key programs, including drug establishment inspections, supply chain security, and post-market surveillance. Establishment registration and drug listing information is also widely used outside FDA for purposes such as electronic prescribing and electronic health records, insurance reimbursement, and patient education.It is your responsibility to ensure that all drugs manufactured at your establishment 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. Registration and listing information and instructions on how to properly register an establishment or submit drug listings can be found at Electronic Drug Registration and Listing Instructions.Misbranded DrugsThe semaglutide API labels for batch CP-030-20250711 and CP-030-20250911 bear the statement “Manufacturer: Harbin Jixianglong Biotech Co., Ltd.” This statement is misleading because it indicates that the manufacturer of the API in those batches isHarbin Jixianglong Biotech Co., Ltd. instead of (b)(4). and (b)(4). Therefore, the semaglutide APIs for batch CP-030-20250711 and CP-030-20250911 are misbranded under section 502(a) of the FD&C Act in that the labeling is false or misleading.In addition, section 502(b)(1) of the FD&C Act requires a drug to contain the name and place of business of the manufacturer, packer, or distributor of the drug. The labels of Harbin’s API products referenced above are misbranded under section 502(b)(1) because they misidentify Harbin, which is a distributor or packer, as the manufacturer. As evidenced by Harbin’s November 5, 2025 declarations, (b)(4). and (b)(4). are the manufacturers of the semaglutide API in batches CP-030-20250711 and CP-030-20250911, not Harbin Jixianglong Biotech Co., Ltd.Additional API CGMP GuidanceFDA considers the expectations outlined in ICH Q7 when determining whether APIs are manufactured in conformance with CGMP. See FDA’s guidance document Q7 Good Manufacturing Practice Guidance for Active Pharmaceutical Ingredients for guidance regarding CGMP for the manufacture of API at https://www.fda.gov/media/71518/downloadCGMP Consultant RecommendedBased upon the nature of the deviations identified at your firm, we strongly recommend engaging a consultant qualified to evaluate your operations to assist your firm in meeting CGMP requirements. We also recommend that the qualified consultant perform a comprehensive 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 obligations to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe deviations cited in this letter are not intended to be an all-inclusive list of deviations that exist at your facility. You are responsible for investigating and determining the causes of any deviations and for preventing their recurrence or the occurrence of other deviations.On February 27, 2026, your firm was placed on Import Alert 66-40 Detention Without Physical Examination of Drugs From Firms Which Have Not Met Drug GMPs and removed from the Green List of Import Alert 66-80 Detention Without Physical Examination of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist Bulk Drug Substances.This letter notifies you of our findings and provides you with an opportunity to address them. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any deviations and to prevent their recurrence. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration. If you cannot complete corrective 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 3024038751 and ATTN: Joan Johnson.Sincerely,/S/Jill P. Furman, JDDirectorOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:26-HFD-45-04-02Product:DrugsRecipient:Sourav K. Mishra, M.D.Sourav K. Mishra, M.D. / All India Institute of Medical SciencesSijua, PatrapadaBhubaneswar 751019 OdishaIndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERFDA Ref. No.: 26-HFD-45-04-02Dear Dr. Mishra:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted at All India Institute of Medical Sciences in Bhubaneswar, Odisha, India, between March 17 and March 20, 2025. The investigator representing FDA reviewed your conduct of a clinical in vivo bioequivalence study (Protocol 0270-22, “A Multicenter, Open Label, Balanced, Randomized, Two-Treatment, Two-Period, Two-Sequence, Single Dose, Crossover, Bioequivalence Study between two formulations of Doxorubicin Hydrochloride Liposome Injection 20 mg/10 mL (50 mg/m2 dose) (Doxorubicin-Test compared with Doxorubicin-Reference) in Patients with Advanced Ovarian Cancer”) of the investigational product doxorubicin hydrochloride liposome injection 20 mg/10 mL, performed for Qilu Pharmaceutical (Hainan) Co., Ltd.This inspection was conducted as a part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure that the rights, safety, and welfare of human subjects have been protected.From our review of the FDA Establishment Inspection Report and the documents submitted with that report, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in Title 21 of the Code of Federal Regulations, parts 312 (21 CFR 312) and 50 (21 CFR 50) governing the conduct of clinical investigations and the protection of human subjects.1 We wish to emphasize the following:1. You failed to ensure that the investigation was conducted according to the investigational plan [21 CFR 312.60].As a clinical investigator, you are required to ensure that your clinical investigations are conducted in accordance with the investigational plan. The investigational plan for Protocol 0270-222 required you to prohibit the use of cytochrome P450 CYP3A4 and CYP2D6 inhibitors to subjects during the entire study duration, and before baseline for at least five half-lives of the given drug, if given prior to the first dose of the study intervention.You failed to adhere to this requirement. Specifically, all three enrolled subjects were orally administered Aprecap (aprepitant), a moderate inhibitor of CYP3A4, during the study. Examples of these failures include:a. Subject (b)(6) signed the informed consent on October 17, 2023, and was administered investigational product on November 1, 2023 (Period I) and on December 1, 2023 (Period II). However, this subject was administered Aprecap between November 1 and November 3, 2023, and between December 1 and December 3, 2023.b. Subject (b)(6) signed the informed consent on October 30, 2023, and was administered investigational product on November 10, 2023 (Period I). However, this subject was administered Aprecap between November 10 and November 12, 2023.c. Subject (b)(6) signed the informed consent on November 16, 2023, and was administered investigational product on November 29, 2023 (Period I) and on December 27, 2023 (Period II). However, this subject was administered Aprecap between November 29 and December 1, 2023, and between December 27 and December 29, 2023.During the inspection, you stated that it is the oncology department’s usual practice to administer Aprecap 125/80 capsules before a patient receives chemotherapy. You also stated that you would pay closer attention to the protocol requirements related to prohibited medication. While we acknowledge your statements made during the inspection, your statements are inadequate because you have not provided sufficient details about how you, as a clinical investigator, will prevent similar violations in the future.We emphasize that failure to conduct the clinical investigation in accordance with the protocol raises significant concerns about your protection of the study subjects enrolled at your site, and also raises concerns about the validity and integrity of the data collected at your site. Specifically, as stated in the protocol, Cytochrome P450 CYP3A4 and CYP2D6 inhibitors were prohibited during the study as they affect the pharmacokinetics of the study intervention, which is the primary objective of the clinical trial. In addition, the prohibited medication can interfere with the investigational product metabolism, which can increase the risk of side effects and reduce investigational product efficacy. As the clinical investigator, you are responsible for ensuring compliance with the protocol requirements for prohibited and concomitant medications.2. You failed to obtain informed consent in accordance with the provisions of 21 CFR part 50 [21 CFR 312.60 and 21 CFR 50.20].As a clinical investigator, you are required to obtain informed consent in accordance with 21 CFR part 50. FDA’s regulations at 21 CFR 50.20 state that, except as provided in 21 CFR 50.22, 50.23, and 50.24,3 no investigator may involve a human being as a subject in research covered by the regulations unless the investigator has obtained the legally effective informed consent of the subject or the subject’s legally authorized representative. Under 21 CFR 50.20, “an investigator shall seek…[informed] consent only under circumstances that provide the prospective subject or the representative sufficient opportunity to consider whether or not to participate and that minimize the possibility of coercion or undue influence”.You failed to seek informed consent for the above-referenced clinical investigation under circumstances that provided the prospective subject or the representative sufficient opportunity or information to consider whether or not to participate and that minimized the possibility of undue influence. Specifically, Section 1 of the informed consent form (ICF) stated that all reference to the words “study drug” throughout the ICF can mean Doxorubicin-Test and Doxorubicin-Reference. Section 10 of the ICF stated, “There is evidence that this study drug is effective and indicated in your disease condition.” In addition, Section 4 stated that liposomal doxorubicin is already approved by various regulatory authorities to treat the disease condition. Sections 4 and 10 also did not specify whether “liposomal doxorubicin” or “study drug”, and the statements concerning their approval or effectiveness, respectively, were applicable to the reference product or the test product. The lack of clarity may lead individuals to mistaken conclusions about the investigational product and whether it had already been demonstrated to be effective. Further, statements that overstate the possible benefit of the investigational product may unduly influence individuals to agree to participate when they might not otherwise do so.During the inspection, you stated that you understood the FDA investigator’s statements that you are ultimately responsible for all documentation provided to study subjects, regardless of who authored the informed consent form, and that safety or efficacy claims of the test drug were not allowed in the informed consent form. While we acknowledge your statement of understanding, your statement is inadequate because you have not provided sufficient details about how you, as a clinical investigator, will prevent similar violations in the future.We emphasize that as the clinical investigator, you are responsible for ensuring that legally effective informed consent is obtained from subjects before their enrollment. Your failure to obtain informed consent before involving subjects in research jeopardizes the rights, safety, and welfare of subjects and raises concerns about whether subjects had an adequate opportunity to fully assess the risks and benefits of their participation in the clinical investigation.We acknowledge that a Form FDA 483 citing the inspectional findings described in this letter was not issued, however, these concerns were discussed with your staff at the conclusion of the inspection.We emphasize that as the clinical investigator, you are ultimately responsible for compliance with all applicable FDA regulations governing the conduct of clinical investigations and the protection of human subjects, both to protect the rights, safety, and welfare of subjects and to ensure the integrity of study data. Your failure to conduct the clinical study in accordance with the protocol, and your failure to seek informed consent in accordance with the requirements in 21 CFR part 50, raise significant concerns about your protection of study subjects enrolled at your site and raise concerns about the reliability of the data collected at your site.This letter is not intended to be an all-inclusive list of deficiencies with your clinical study of an investigational product. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address this matter adequately may lead to regulatory action without further notice to you. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.Your written response, and any questions or concerns about this letter or the inspection, should be sent via email to the FDA at CDER-OSI-Communications@fda.hhs.gov.Sincerely yours,{See appended electronic signature page}David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchDavid Burrow Digitally signed by David BurrowDate: 4/29/2026 01:48:38 PM EDT_________________________1 In accordance with 21 CFR 320.31(c), the provisions of 21 CFR parts 312 and 50 are applicable to this bioequivalence study in humans because Protocol 0270-22 was conducted under an Investigational New Drug application (IND).2 Protocol 0270-22 (Version: 2.1, Document Release Date: 29-Nov-2022) was effective when the prohibited medication and study intervention were administered to the subjects.3 The exceptions provided in 21 CFR 50.22, 50.23, and 50.24 are not applicable here.

 按照《医疗器械监督管理条例》《医疗器械注册与备案管理办法》的相关规定，根据企业申请，我局现依法注销沈阳东亚医疗研究所有限公司骨科外固定支架《医疗器械注册证》（注册证号：辽械注准20202040296）。  特此公告。   辽宁省药品监督管理局   2026年5月18日

为强化医疗器械经营质量安全风险防控，今年以来，阿拉善盟各级市场监管部门立足属地监管责任，靶向聚焦高频风险，扎实推进医疗器械经营环节清查治理工作，阶段性成效显著。压实企业主体责任。推广使用医疗器械“智械自查码”开展经营质量管理规范线上自查工作，全盟205家经营企业完成线上年度自查，医疗器械质量管理体系文件规范率达94%，同时筛查锁定37家异常经营企业，纳入重点监管，夯实精准监管底数。强化质量安全检查。采取日常检查与专项检查相结合的方式，紧盯经营全链条关键节点，严查各类违规经营行为，累计出动执法人员96人次，检查经营企业45家次，对1家未建立进货查验记录的经营企业予以警告，严控经营环节风险。规范证照注销流程。联动行政审批科室建立协同处置机制，督促25家第二类器械经营单位、2家第三类器械经营企业主动注销证照，协助3家因客观原因暂无法注销的企业合规申请注销，将7家经营主体纳入重点监管，净化行业业态。深化宣讲普法赋能。采取上门核查+现场宣讲模式，解读相关法规条款，明确企业法定代表人、质量负责人岗位职责，现场一对一指导企业对标质量管理体系，全面排查重点薄弱环节，开展全维度自查自纠，及时帮扶整改风险隐患。下一步，全盟将健全长效机制，对发现的问题隐患建立销号清单，落实一问题一销号，常态化开展“回头看”，严防问题反弹，确保隐患全部清零，织密常态化监管网络。

雅培医疗用品（上海）有限公司报告，由于起搏阈值测试中出现偶发（0.001%）的遥测通信不稳定可能引发临时起搏无法正常终止的问题，雅培医疗器械Abbott Medical对其生产的心脏节律管理设备程控仪（注册证号：国械注进20182122213）主动召回。召回级别为二级。涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。附件：医疗器械召回事件报告表2026年05月19日