Delivery Method:VIA Electronic MailReference #:320-25-81Product:DrugsRecipient:Mr. Anil PatelOwner and DirectorKenil Healthcare Private LimitedPlot No. 319, Village Acharasan, Ankhol-Vamaj RoadTal-Kadi, District Mehsana382715GujaratIndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-81June 12, 2025Dear Mr. Patel:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Kenil Healthcare Private Limited, FEI 3022380309, at Plot No. 319, Village Acharasan, Ankhol-Vamaj Road, Tal-Kadi, District Mehsana, Gujarat, from December 5 to 11, 2024.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B). We reviewed your December 30, 2024 response and subsequent correspondences 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 clean, maintain, and, as appropriate for the nature of the drug, sanitize and/or sterilize equipment and utensils at appropriate intervals to prevent malfunctions or contamination that would alter the safety, identity, strength, quality, or purity of the drug product beyond the official or other established requirements (21 CFR 211.67(a)).You failed to adequately clean and maintain your filling rooms and tube filling equipment used to manufacture your(b)(4)and(b)(4)over-the-counter (OTC) drug products. For example, our investigators observed the following:The presence of mold and dirt on the walls in your filling and sealing rooms.Soiled and stained air handling units.Unidentified product buildup inside your(b)(4)manufacturing vessel and tube filling equipment.More than one drug product was found on the packaging line.In addition, your firm did not have validated cleaning procedures, including written equipment usage and cleaning logs to demonstrate that your drug product manufacturing equipment was adequately cleaned and maintained.In your response, you state that you revised your cleaning procedures and logbooks and commit to retrain your staff on cleaning practices and procedures. You also state that cleaning and sanitization of the filling and sealing rooms was conducted and building maintenance will be performed. Your response is inadequate because you failed to provide supporting data to demonstrate that your cleaning practices are sufficient to remove contaminants from the product surfaces of your drug product manufacturing equipment. You also failed to provide any documentation that the above-mentioned activities occurred. Furthermore, you failed to assess the impact of your inadequate cleaning processes on products that are currently on the market and within expiry.It is essential that your facility and equipment are cleaned, and sanitary conditions are maintained, to ensure ongoing suitability for drug manufacturing, and to protect drug products from contamination.In response to this letter, provide: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.Your corrective action and preventive action (CAPA) plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.A CAPA plan, based on the retrospective assessment of your cleaning program, that includes appropriate remediations to your cleaning processes and practices, and timelines for completion. Provide a detailed summary of vulnerabilities in your process for lifecycle management of equipment cleaning. Describe improvements to your cleaning program, including enhancements to cleaning effectiveness; improved ongoing verification of proper cleaning execution for all products and equipment; and all other needed remediations.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 standard operating procedures that ensure an appropriate program is in place for verification and validation of cleaning procedures for products, processes, and equipment.Additional photographic evidence that demonstrates thorough cleaning of your filling and sealing areas, including but not limited to Rooms(b)(4)and(b)(4), and the completion of all necessary building maintenance in those areas.2. Your firm failed to have buildings used in the manufacture, processing, packing, or holding of drug products with adequate space for the orderly placement of equipment and materials to prevent mix-ups and contamination (21 CFR 211.42(b)).Your firm’s packaging and labeling operations are performed without adequate controls to prevent mix-ups and cross-contamination. For example, our investigators observed employees performing manual packaging and labeling operations on the floor of the manufacturing room. Investigators also noted that multiple drug products were packaged simultaneously without adequate separation and spacing. The drug products were also packaged without the use of batch records.Our investigators also observed that your reserve samples were improperly stored, commingled with expired products, and lacked routine monitoring.In your response, you state that you implemented procedures for dispensing and issuing packaging materials. Your response also includes plans to expand your warehouse. Your response is inadequate because you failed to address the interim plans to prevent labeling mixups in your current packaging area while you remediate your lack of adequate facility spacing. You also do not describe how you intend to ensure that the procedural updates are effective.In response to this letter, provide:Your CAPA plan to improve packaging and labeling operations, including equipment and facility upgrades, effective preventive and corrective maintenance, enhanced performance monitoring, improved operations management oversight, and any other needed actions. Your CAPA plan should also assure the proper segregation and sufficient space for the orderly storage of samples.An action plan and timeline for conducting retrospective assessment of all your reserve samples in your sample storage area. Include supporting documentation to ensure that no product or package mix-ups have occurred, and any corrective actions, such as notifying customers of identified product mix-ups.3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not provide adequate oversight for the manufacture of your drug products. For example, your QU failed to ensure the following:Review and approval of written procedures for production and process controls that are designed to assure the quality of your drug products, i.e., process validation (21 CFR 211.100(a)).Establishment of an adequate, ongoing stability program (21 CFR 211.166(a)).Adequate batch production and control records that include complete documentation of the accomplishment of each significant step in the manufacture, processing, packing, or holding of the batch, for each batch of drug product (21 CFR 211.188).Adequate review and approval of production and control records before a batch is released or distributed (21 CFR 211.192)Production and process control activities, such as equipment qualification, are documented at the time of performance (21 CFR 211.100(b)). Specifically, investigators observed your quality assurance manager generating and completing equipment qualification documents investigators previously requested. This practice raises concerns about the integrity and reliability of your firm’s data and documentation.Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.Your quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance documentData Integrity and Compliance With Drug CGMPfor guidance on establishing and following CGMP compliant data integrity practices atData Integrity and Compliance With Drug CGMP:Questions and Answers | FDAWe acknowledge that you are using an independent third-party consultant to audit your operation and assist in meeting FDA requirements.In response to this letter, provide:A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global CAPA plan.Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate, including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses, including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding batches to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).o A status report for any of the above activities already underway or completed.A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision.o Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.Drug RecallOn March 26, 2025, FDA held a teleconference with you and your U.S. Agent, JMM Services LLC. We recommended that you recall all your drug products within expiry currently in distribution to the U.S. market. On April 9, 2025, your firm committed to recall the products within expiry. After several subsequent attempts were made to contact you and your registered U.S. Agent regarding the recall, you initiated the recall of all your drug products on April 24, 2025.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.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. A cosmetic is deemed adulterated under section 601(c) of the FD&C Act (21 U.S.C. 361(c)) if it has been prepared, packed, or held under insanitary conditions whereby it may have become contaminated with filth or whereby it may have been rendered injurious to health. Some conditions that cause the drug products you manufacture to be adulterated may also cause any cosmetics you manufacture to be adulterated. 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. Further, your facility may be subject to requirements under the Modernization of Cosmetics Regulation Act of 2022 (MoCRA). You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on April 4, 2025.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Kenil Healthcare Private Limited, located at Plot No. 319, Village Acharasan, Ankhol-Vamaj Road Ta-Kadi, District Mehsana, Gujarat, 382715, India, into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3022380309 and ATTN: Yvette Johnson.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCc: Registered U.S. AgentMs. Julia Moffitt, JMM ServicesEmail: julia@jmm.one; Info@jmm.one

Product:DrugsRecipient:www.buycodeine.usUnited StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesTO: www.buycodeine.usFROM: The United States Food and Drug AdministrationRE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the InternetDATE: May 5, 2025WARNING LETTERThis is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet address www.buycodeine.us and has observed that your website introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)].As discussed below, FDA has observed that www.buycodeine.us introduces into interstate commerce unapproved and misbranded opioid drug products. Opioid addiction and abuse have created an immense public health crisis, and the death toll is staggering. Given the severity of the opioid epidemic, the easy availability of opioids via the Internet poses significant risks to U.S. consumers.FDA has also observed that www.buycodeine.us introduces into interstate commerce misbranded Schedule II stimulants. Schedule II stimulants have an acknowledged high potential for abuse, and it is important to address the public health impact of their diversion and nonmedical use. Diversion is the primary source of prescription stimulants for nonmedical use, and nonmedical use is most frequent among young adults and college students. Polysubstance use is common among those who use prescription stimulants nonmedically, with individuals frequently co-using illicit drugs and/or prescription opioids. These concerns come against a backdrop of rising mortality from psychostimulant-involved overdoses, which involve illicit stimulants the vast majority of the time, but sometimes involve prescription stimulants. The easy availability of Schedule II stimulants via the Internet poses additional significant risks to U.S. consumers.There are 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.buycodeine.us cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to shielding the American public from harm.Unapproved New Drugs:Evidence obtained from your website establishes that certain products offered for sale by www.buycodeine.us are drugs intended for human use. Examples of claims that provide evidence of the intended use (as defined in 21 CFR 201.128) of these products as drugs for human use include the following:Toseina: “The active ingredient, codeine, is a narcotic that works by reducing the activity in the part of the brain that triggers coughing. This makes Toseina highly effective for individuals suffering from respiratory conditions like colds, bronchitis, and flu, where dry, unproductive coughing is a major symptom.”Ritalina: “It is a prescription medication commonly use [sic] to treat attention deficit hyperactivity disorder (ADHD) and narcolepsy. As a central nervous system stimulant, Ritalin works by affecting chemicals in the brain that contribute to hyperactivity and impulse control.”These products 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 [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FD&C Act.For example, on www.buycodeine.us, you offer codeine phosphate hemihydrate oral solution marketed as “Toseina.” While there are FDA-approved drug products containing codeine phosphate on the market in the U.S., there are no FDA-approved versions of codeine phosphate hemihydrate oral solution. Furthermore, www.buycodeine.us markets “Toseina” under the “PROMETHAZINE CODEINE” category. While there are FDA-approved versions of promethazine hydrochloride (HCl) and codeine phosphate oral solution on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Toseina” offered by www.buycodeine.us. FDA-approved promethazine HCl and codeine phosphate oral solution is a combination of codeine, an opioid agonist; and promethazine, a phenothiazine, indicated for the temporary relief of cough and upper respiratory symptoms associated with allergy or the common cold in patients 18 years of age and older. It is only available pursuant to a prescription from a licensed practitioner. Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, promethazine HCl and codeine phosphate oral solution is reserved for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks associated with use of promethazine HCl and codeine phosphate oral solution, and in whom an adequate assessment of the etiology of the cough has been made. FDA-approved promethazine HCl and codeine phosphate oral solution bears 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. This boxed warning addresses risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), and neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby). In addition, when promethazine HCl and codeine phosphate oral solution is taken in conjunction with other central nervous system (CNS) depressants, including alcohol and benzodiazepines, use may result in coma or death.As another example, on www.buycodeine.us, you offer methylphenidate hydrochloride tablets marketed as “Ritalina.” While there are FDA-approved versions of methylphenidate hydrochloride tablets on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Ritalina” offered by www.buycodeine.us. FDA-approved Ritalin is a CNS stimulant indicated for the treatment of attention deficit hyperactivity disorders (ADHD) and narcolepsy. It is only available pursuant to a prescription from a licensed practitioner. The use of Ritalin exposes individuals to the risks of abuse and misuse, which can lead to the development of a substance use disorder, including addiction. Ritalin can be diverted for non-medical use into illicit channels or distribution. Misuse and abuse of CNS stimulants, including Ritalin, can result in overdose and death, and this risk is increased with higher doses or unapproved methods of administration. FDA-approved Ritalin also bears a boxed warning indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. This boxed warning addresses risks including addiction, abuse, misuse, overdose, and death.Misbranded Drugs:A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] 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 [21 U.S.C. § 353(b)(1)] include those that, because of their toxicity or other potentiality for harmful effect, and/or the method of their use, and/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, can be used safely only at the direction, and under the supervision, of a licensed practitioner.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 the products safely for their intended uses. Consequently, the labeling for these drugs fail to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. In addition, because these drugs are not approved in the U.S., 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.buycodeine.us is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].Additionally, FDA has observed that the www.buycodeine.us offers prescription drugs for sale without a prescription. Under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering the aforementioned drugs without requiring a prescription, www.buycodeine.us jeopardizes patient safety and misbrands the drugs under section 503(b)(1) of the FD&C Act. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].FDA is sending this warning letter to www.buycodeine.us because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drugs noted above). We advise you to review your websites, product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded products in violation of the FD&C Act.Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. 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 within 15 working days.If you are not located in the U.S., 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 productsthat cannot be legally sold to consumers in the U.S.Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.Sincerely,/S/Sangeeta Vaswani Chatterjee, Pharm.D.Acting Director, Office of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and Research

Product:DrugsRecipient:www.buyprosoma.comUnited StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesTO: www.buyprosoma.comFROM: The United States Food and Drug AdministrationRE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the InternetDATE: June 10, 2025WARNING LETTERThis is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet address www.buyprosoma.com and has observed that your website introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)].As discussed below, FDA has observed that www.buyprosoma.com introduces into interstate commerce unapproved and misbranded opioids. Opioid addiction and abuse have created an immense public health crisis, and the death toll is staggering. Given the severity of the opioid epidemic, the easy availability of opioids via the Internet poses significant risks to U.S. consumers. FDA has also observed that www.buyprosoma.com introduces into interstate commerce unapproved and misbranded benzodiazepines. Benzodiazepines are drug products with an acknowledged potential for abuse, and it is important to address the public health impact of their nonmedical use. Benzodiazepine nonmedical use is widespread, and individuals frequently co-use benzodiazepines with alcohol, prescription opioids, and illicit drugs. Associated harms of benzodiazepine nonmedical use are substantial but occur primarily when people use benzodiazepines in combination with other drugs. Further, in cases where benzodiazepines were co-used with other substances, medical outcomes are typically more severe than in cases involving benzodiazepines alone. Polysubstance overdose deaths account for the vast majority of overdose deaths documenting involvement of benzodiazepines. The easy availability of benzodiazepines via the Internet poses additional significant risks to U.S. consumers.There are 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.buyprosoma.com cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to shielding the American public from harm.Unapproved New Drugs:Certain products offered for sale by www.buyprosoma.com 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 [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FD&C Act.For example, on www.buyprosoma.com you offer for sale tapentadol, marketed as “Tapentadol 100 MG (Aspadol)” and “Aspadol® Tab.” While there are FDA-approved versions of tapentadol on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the “Tapentadol 100 MG (Aspadol)” and “Aspadol® Tab” offered by www.buyprosoma.com. Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claim “Tapentadol 100 MG (Aspadol) is an improved medicine which is used to treat moderate and severe pain.” Currently, there are two tapentadol products that are FDA-approved for the U.S. market. FDA-approved tapentadol marketed under the brand name NUCYNTA is indicated for the management of acute pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. FDA-approved tapentadol marketed under the brand name NUCYNTA ER is indicated for the management of severe and persistent pain, including neuropathic pain associated with diabetic peripheral neuropathy, that requires an extended treatment period with a daily opioid analgesic and for which alternative treatment options are inadequate.As another example, on www.buyprosoma.com you offer for sale tramadol, marketed as “Topdol 50 MG (Tramadol)” “TOP DOL 50,” “Tramadol 50 MG (Capsules),” “Tramadol 50mg Online,” “Buy Best Tramadol 100MG (Top Dol 100MG),” “Tramadol 100 mg Tabletas,” “Tramadol 225 MG,” and “TRAMADOL-225.” Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claims “Topdol 50 MG (Tramadol) is used to relieve moderate to moderately severe pain, including pain after surgery,” “Tramadol 50 mg Online is also a painkiller and helps control secondary neurological in nature,” “Tramadol capsules work by sending the signals to the brain to change how your body feels and responds to pain,” and “Tramadol is a narcotic-like pain reliever.” While there are FDA-approved versions of tramadol on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Topdol 50 MG (Tramadol)” “TOP DOL 50,” “Tramadol 50 MG (Capsules),” “Tramadol 50mg Online,” “Buy Best Tramadol 100MG (Top Dol 100MG),” “Tramadol 100 mg Tabletas,” “Tramadol 225 MG,” and “TRAMADOL-225” offered by www.buyprosoma.com. FDA-approved tramadol is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.FDA-approved tapentadol and tramadol are opioid drug products only available pursuant to a prescription from a licensed practitioner. Furthermore, FDA-approved tapentadol and tramadol 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 risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), and neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby). In addition, when tapentadol and tramadol products are taken in conjunction with other central nervous system (CNS) depressants, including alcohol and benzodiazepines, use may result in coma or death.On www.buyprosoma.com you also offer for sale alprazolam, marketed as “Buy Xanax 1MG Online,” “Xanax® (Alprazolam) 1 mg,” “Xanax 2MG,” and “XANAX (ALPRAZOLAM) TABLETS, USP 2 mg.” Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claims “Alprazolam is a generic form of Xanax that is used to treat anxiety and panic disorders” and “Xanax is often recommended for: ANXIETY DISORDERS: It poops off symptoms of anxiety and unease, including high alertness or chronic stress (more than most).” While there are FDA-approved versions of alprazolam on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Buy Xanax 1MG Online,” “Xanax® (Alprazolam) 1 mg,” “Xanax 2MG,” and “XANAX (ALPRAZOLAM) TABLETS, USP 2 mg” offered by www.buyprosoma.com. FDA-approved alprazolam, including the brand name XANAX, is a benzodiazepine indicated for the acute treatment of generalized anxiety disorder and panic disorder with or without agoraphobia.Additional examples of benzodiazepines you offer for sale on www.buyprosoma.com include:Clonazepam marketed as “Klonopin 2MG (Clonazepam)” and “Rivotril® 2 mg Tabletten Clonazepam.” Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claims “Clonazepam is used in the prevention and management of various types of seizures,” “of panic attacks and related episodes of anxiety,” and “the treatment of a specific sleep disorder called REM sleep behavior disorder.” While there are FDA-approved versions of clonazepam on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Klonopin 2MG (Clonazepam)” and “Rivotril® 2 mg Tabletten Clonazepam” offered by www.buyprosoma.com. FDA-approved clonazepam, including the brand name KLONOPIN, is indicated for the treatment of certain seizures and of panic disorder, with or without agoraphobia, as defined in DSM-V.Diazepam marketed as “Valium 10MG (Diazepam)” and “Valium® 10 mg tabletten / comprimés / Tabletten.” Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claims “Valium 10mg is prescribed by the doctors to the patients who are undergoing Alcohol Withdrawal symptoms,” “for seizure ailments or disorders,” and “If you are suffering from an anxiety disorder, have trouble sleeping, feel continuous sweating in your hands and feet.” While there are FDA-approved versions of diazepam on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Valium 10MG (Diazepam)” and “Valium® 10 mg tabletten / comprimés / Tabletten” offered by www.buyprosoma.com. FDA-approved diazepam, including the brand name VALIUM, is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety and acute alcohol withdrawal.Lorazepam marketed as “Ativan 1MG (Lorazepam).” Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claim “Ativan (lorazepam)As [sic] a powerful benzodiazepine, Ativan is frequently prescribed for anxiety disorders and insomnia.” While there are FDA-approved versions of lorazepam on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Ativan 1MG (Lorazepam)” offered by www.buyprosoma.com. FDA-approved lorazepam, including the brand name ATIVAN, is indicated for the management of anxiety disorders or for the short-term relief of the symptoms of anxiety or anxiety associated with depressive symptoms.FDA-approved alprazolam, clonazepam, diazepam, and lorazepam are benzodiazepine drug products only available pursuant to a prescription from a licensed practitioner. Furthermore, FDA-approved alprazolam, clonazepam, diazepam, and lorazepam bear a boxed warning, addressing risks including abuse, misuse, addiction, and physical dependence. In addition, the concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death.Misbranded Drugs:A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] 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 [21 U.S.C. § 353(b)(1)] include those that, because of their toxicity or other potentiality for harmful effect, and/or the method of their use, and/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, can be used safely only at the direction, and under the supervision, of a licensed practitioner.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 the products safely for their intended use. Consequently, the labeling for these drugs fail to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. In addition, because these drugs are not approved in the U.S., 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.buyprosoma.com is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].Additionally, FDA has observed that www.buyprosoma.com offers prescription drugs for sale without a prescription. In addition to the aforementioned drugs, on www.buyprosoma.com you offer for sale hydrocodone, marketed as “Hydrocodone 10/325 MG” and “Hydrocodone Bitartrate and Acetaminophen Tablets, USP 10 mg / 325 mg” and oxycodone marketed as “Oxycodone 30MG (Hydrochloride)” and “Oxycodone Hydrochloride Tablets, USP 30 mg.” Evidence obtained from your website establishing that these products are drugs intended for human use (as defined in 21 CFR 201.128) includes the claims “Hydrocodone 10/325 mg helps in curing pain” and “Oxycodone 30 MG is a prescription opioid medication used to treat moderate to severe pain.” FDA-approved hydrocodone and oxycodone are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Furthermore, FDA-approved hydrocodone and oxycodone bear a boxed warning, addressing risks including addiction, abuse, misuse, life-threatening respiratory depression, neonatal opioid withdrawal syndrome, and accidental exposure resulting in death. In addition, when hydrocodone and oxycodone are taken in conjunction with other CNS depressants, including alcohol and benzodiazepines, use may result in coma or death.Under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering the aforementioned drugs without requiring a prescription, www.buyprosoma.com jeopardizes patient safety and misbrands the drugs under section 503(b)(1) of the FD&C Act. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].FDA is sending this warning letter to www.buyprosoma.com because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drugs noted above). We advise you to review your websites, product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded and unapproved drug products in violation of the FD&C Act.Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. 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 within 15 working days.If you are not located in the U.S., 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 U.S.Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.Sincerely,/S/Sangeeta Vaswani Chatterjee, Pharm.D.Acting Director, Office of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Mark TeufelActing CEOReset Technology Corporation4200 West Royal Lane, Suite # 125Irving,TX75063United StatesIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 704828June 9, 2025Dear Mark Teufel:During an inspection of your firm located in Englewood Cliffs, NJ, from October 29, 2024, through December 20, 2024, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures the ResetSmile Partial Denture Device and the at-home ResetSmile Impression Kit Device. The ResetSmile Partial Denture Device is a removeable dental appliance used to replace missing teeth and the ResetSmile Impression Kit Device is an impression kit used to help make the removeable dental appliance. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.Quality System Regulation Violation(s)This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21, Code of Federal Regulations (CFR), Part 820.We received a response from Mr. Justin S. Marks, VP Clinical Operations/Quality Representative, in an email dated January 13, 2025, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to ensure that when the results of a process cannot be fully verified by subsequent inspection and test, the process shall be validated with a high degree of assurance and approved according to established procedures, as required by 21 CFR 820.75(a).Specifically, you failed to define and document procedures for process validation. For example, you have no objective evidence that the following manufacturing and cleaning processes for your ResetSmile Partial Denture Devices, for which specifications such as anatomical features, mechanical strength, or residue removal cannot be verified without(b)(4)testing, consistently produce a result or product that meets predetermined specifications with a high degree of assurance:a.Scanning and CAD Designi. You utilize the(b)(4)Dental Scanner to generate an initial 3D scan of the model cast from the impression taken by the customer with your at-home ResetSmile Impression Kit Device but have no documented validation to support your intended use of this software application.ii. You utilize the(b)(4)to develop the patient-matched CAD design from the above 3D scan of the model cast but have no documented validation to support your intended use of this software application.b.3-Dimensional (3D) Printingi. You utilize(b)(4)3D Printers with the(b)(4)software to 3D print your ResetSmile Partial Denture Device based on the above CAD design but have no documented validations which establish the process parameter settings (e.g., filament diameter, fill density, extruder temperature, bed temperature, print speed, layer thickness, etc.) under which your 3D printers are able to consistently meet predefined specifications alongside your intended use of the(b)(4)software application.ii. You utilize the(b)(4)3D Printer;(b)(4)3D Printers; or(b)(4)3D Printers to 3D print the mold to trial fit your ResetSmile Partial Denture Device but have no documented validations which establish the process parameters (e.g., filament diameter, fill density, extruder temperature, bed temperature, print speed, layer thickness, etc.) under which your 3D printers are able to consistently meet predefined specifications.c.Post-printing Quality Control (QC) Validation (i.e., Test Method)i. You utilize the(b)(4)software, as a part of finished device acceptance, to identify conforming and nonconforming areas for your finished device through comparison of the overlay of the 3D scan of your ResetSmile Partial Denture Device ((b)(4)) with the initial 3D scan (via(b)(4)Dental Scanner software) of the model cast from the impression taken by the customer with your at-home ResetSmile Impression Kit Device but have no documented validation to support your intended use of this software application.d.Cleaningi. You utilize the(b)(4)to remove manufacturing material (e.g.,(b)(4)) applied to your ResetSmile Partial Denture Device prior to the Post-printing QC Validation above but have no documented validation that establishes the process parameter settings (e.g., clean time, water quality, degassing time, bath cycle, etc.) under which your(b)(4)is able to consistently meet predefined specifications for cleanliness.ii. You utilize the(b)(4)to(b)(4)clean your ResetSmile Partial Denture Device after(b)(4)but have no documented validation that this(b)(4)cleaner is able to consistently meet predefined specifications for cleanliness.We reviewed your firm's response and conclude that it is not adequate. You state process validations are not required as they have already been performed as part of the regulatory process for the FDA cleared materials used in your devices. You also state that you use FDA listed 3D scanners and computer assisted design and manufacturing (CAD/CAM) software to manufacture each patient specific device (which has been validated by the manufacturer as part of their regulatory process) and that internal validation and verification of the patient specific device is performed as part of the QC Validation Process to ensure that the partial denture fits the patient model since each product has different patient specifications. As such, no corrective actions were identified. However, it is unclear how you are able to ensure (1) that predetermined specifications are consistently met with a high degree of assurance during the scanning, 3D printing, and post-printing quality control process steps described above for your ResetSmile Partial Denture Devices without validation of the software workflow for its intended use according to an established protocol with predefined acceptance criteria and (2) quality for all devices built in a(b)(4)cycle,(b)(4)cycles, and(b)(4)machines, where the results of a process (output specifications) cannot be fully verified by subsequent inspection and test. In addition, you did not provide a response on how you plan to address the lack of cleaning validations for your(b)(4)and(b)(4)cleaning processes to ensure that manufacturing material is able to be consistently removed, with a high degree of assurance, from your devices which present challenges for residue removal due to the complex geometry prevalent with such devices (e.g.,(b)(4)with limited or no access, etc.). Therefore, please provide a response on how you plan to address the above deficiencies.2. Failure to adequately establish and maintain procedures to control product that does not conform to specified requirements, including the identification, documentation, evaluation, segregation, and disposition of nonconforming product, as required by 21 CFR 820.90(a).Specifically, the "Control of Nonconformity Process" procedure (8300-01; Rev.0; Effective: 10/25/24) and "Non-Confirming Material Report" form (8300-01-01; Rev.0; Effective: 10/25/24), which were implemented after the preannouncement of the FDA inspection on 10/24/24, are inadequate in that there are no requirements to document: Nonconformances in sufficient detail to describe what failed to meet specification(s); Evaluations of nonconformances to determine the need for investigations; and Dispositions of nonconformances.For example, there were no descriptions, evaluations for the need for investigations, and dispositions documented for(b)(4)cases of nonconforming product identified on the "Internal Remakes log" from 2/2/22 to 10/28/24 under three general categories: "Failed print" ((b)(4)cases); "Fabrication error" ((b)(4)cases); and "Failed QC" ((b)(4)cases).We reviewed your firm's response and concluded that it is not adequate. You plan to create a new procedure to include the definition of a nonconformance, visual identification of nonconforming product, and disposition instructions; develop a new disposition log; perform a statistical analysis of the rework cases to determine if additional corrective actions are needed; and schedule training on updated procedures under corrective action report # CA011 around January 31, 2025. However, you have not identified any corrective actions to ensure that (1) your procedures and forms require that nonconformances are recorded in sufficient detail to include what failed to meet specification(s) to allow determination of potential causes and evaluations of nonconformances to determine the need for investigations and (2) retrospective review of nonconformances, for a reasonable period of time, to document what failed to meet specifications, conduct evaluations to determine the need for investigations, and record dispositions. In addition, please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.3. Failure to establish and maintain procedures for rework, including retesting and reevaluation of the nonconforming product after rework to ensure that the product meets its current approved specifications and documentation of rework and reevaluation activities, including determination of any adverse effect from the rework upon the product, in the device history record (DHR), as required by 21 CFR 820.90(b)(2).Specifically, you failed to define and document procedures for rework which include requirements to retest and reevaluate reworked devices and document the rework and reevaluation, including adverse impact assessments on reworked devices, in the DHR. Per your VP of Clinical Operations and head Dental Technician, approximately(b)(4)of manufactured ResetSmile Partial Denture Devices undergo final adjustment (rework) during the Final Quality Control (QC) step of the "Quality Control Validation Process" (7506-01; Rev. 0; Effective: 2/19/24) which states that upon completion of the scan of the finished device, where(b)(4)areas indicate the need for readjustment, "***the finished device is brought to the quality control technician for final QC analysis, including possible adjustments, and cleaning***." All eleven (11) scans of the ResetSmile Partial Denture Devices reviewed (lot #: 20022199; 20023601; 20023705; 20024773; 20025934; 20026261; 20026272; 20026352; 20021720; 20018940; 20021572) revealed that these initial scans evaluated during the final QC step contained(b)(4)areas which required adjustment. However, none of the readjustments for these devices were treated as reworks which would require additional rescans and retention of the scans to confirm specifications are met before release and documented assessment of any adverse effects.We reviewed your firm's response and concluded that it is not adequate. You state the QC Validation Process (7506-01) is designed to identify and adjust potentially ill-fitting partial dentures prior to delivery to the dentist and consumer which surpasses requirements of the regulation and is in contrast to relying on the prescribing dentist to perform their own post-delivery adjustments, which is a universally accepted method. As such, no corrective actions were identified. However, your firm is not meeting the requirements of 21 CFR 820.90(b)(2) with regards to the handling of adjustments (reworks). Therefore, please provide a response on how you plan to address the above deficiencies.4. Failure to adequately investigate any complaint involving the possible failure of a device, labeling or packaging to meet any of its specifications, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820.198(c).Specifically, you failed to investigate or adequately investigate complaints alleged to not meet specifications, as noted in the following examples:i.Complaint # 22952 (lot # 20021720) dated 6/26/24: "***The device is really thick and I cannot get it in with out [sic] significant pain, and once it is in, I cannot close my mouth, as the new device doesn't allow room for my bottom teeth. It also sticks out forward and leaves a "v" shaped gap at the bottom between the device and my natural tooth***."You responded to customer by sending an adjustment kit to the patient. However, there was no documented investigation into what may have caused or contributed to the device thickness.ii.Complaint # 55465 (lot # 20027016) dated 10/16/24: "***The partials don't t [sic] fit properly and made my gums hurt and bleed. My front teeth hurt, feels like my teeth [as] being pushed forward. Both my upper and lower don't fit properly***."You requested photos and information on experienced issues from the customer and sent another impression kit to the patient for a remake. However, there was no documented investigation into what may have caused or contributed to the device fit issues.We reviewed your firm's response and conclude that it is not adequate. Your firm plans to assess all open complaints at regular intervals to determine the effectiveness of the complaint handling process, need for CAPA, and MDR under corrective action report # CA013 around January 31, 2025. However, there were no corrective actions identified to retrospectively review and evaluate complaints, for a reasonable period of time, to determine (1) the need for an investigation (including justification when an investigation was not needed) and (2) definitively investigate any complaints which allege failures of your device, labeling, or packaging to meet any of its specifications. Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.5. Failure to adequately maintain complaint files and adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit, including evaluation of complaints to determine whether the complaint represents an event which is required to be reported to FDA under part 803 of this chapter, Medical Device Reporting, as required by 21 CFR 820.198(a).Specifically, your "Complaint Handling Process" procedure (8202-01; Rev.0; Effective: 6/22/22) is inadequate in that it fails to:a. Outline the criteria for when your follow-up questionnaire should be sent to complainants. For example, you emailed customers questionnaires (uncontrolled), which listed questions such as “***Can you feel any roughness or sharp edges on the device that are contributing to sore spots in your mouth?***” or “***Does the device feel like it is placing too much pressure on the gums? In any specific area or overall tightness?***” to attempt to obtain details on customer experienced issues for Complaints # 21161 (lot # 20026782) and # 56207 (lot # 20027010) but not for the following complaints:i.Complaint # 22952 (lot # 20021720) dated 06/26/2024: “***The device is really thick and I cannot get it in with out [sic] significant pain, and once it is in, I cannot close my mouth, as the new device doesn't allow room for my bottom teeth. It also sticks out forward and leaves a "v" shaped gap at the bottom between the device and my natural tooth***.”ii.Complaint # 55465 (lot # 20027016) dated 10/16/2024: “***The partials don’t t [sic] fit properly and made my gums hurt and bleed. My front teeth hurt, feels like my teeth [as] being pushed forward. Both my upper and lower don’t fit properly***.”b. Ensure that complaints include evaluations of whether they represent events which require reporting to the FDA under 21 CFR 803 (Medical Device Reporting) based on sufficient information obtained from customers to determine whether the complaints meet the definition of MDR reportable events. For example, your VP of Clinical Operations acknowledged that none of your complaint records included documented evaluations on whether the complaints were reportable, including Complaints # 22952 and # 55465 above as well as the following:i.Complaint # 21161 (lot # 20026782) dated 10/14/24: “***The bottom is so tight, I have damaged the inside of my mouth after just one attempt. I tried again but my mouth was to [sic] sore.” The patient also stated that the device was “painful to clip in, cut me in the front of my lower teethbottom [sic]”. Your firm responded by sending an impression kit to the patient for a remake***.”ii.Complaint # 56207 (lot # 20027010) dated 10/23/24: “***the bottom teeth are coming on contact with the partial causing it to move. This friction is very painful and has caused blistering… The pain that I feel goes from pressure to scratching to stabbing***.”We reviewed your firm's response and conclude that it is not adequate. You plan to add the definition of a complaint to your MDR and complaint procedures; include a section for MDR evaluations to the complaint form; assess all open complaints at regular intervals to determine the effectiveness of the complaint handling process, need for CAPA, and MDR; and provide training on the revised processes under corrective action report # CA013 around January 31, 2025. In addition, you reported that none of the 1,840 complaints as of 11/21/24 were MDR reportable. However, there were no corrective actions identified to ensure uniformity of the complaint process by establishing criteria for when complainants are sent questionnaires and ensure that sufficient information is requested from customers to determine whether complaint events meet the definition of MDR reportability under 21 CFR 820.3(o). Please provide an update on the progress of your identified corrective actions, including any supporting evidence of completion for review, timelines for completion, and plan for how you will address the inadequacies pointed out in your response.6. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a).Specifically, your "Corrective & Preventive Action (CAPA) Process" (8502-01; Rev. 0; 6/22/22) and "Quality Objectives Management" (5401-01; Rev. 0; 10/7/24) procedures are inadequate in that:a. 8502-01 (nor any other procedure) does not require internal remakes of your ResetSmile Partial Denture Devices, arising from issues during manufacturing, as inputs into the CAPA process to identify existing and potential causes of nonconforming product or other quality problems, as required by 21 CFR 820.100(a)(1). For example, you remade 64 devices during the month of October 2024 due to issues categorized as failed 3D printing, fabrication errors, and failed quality control but none of this data was analyzed to identify existing and potential causes of nonconforming product or other quality problems.b. Neither 8502-01 nor 5401-01 require appropriate statistical methodology to detect recurring quality problems, as required by 21 CFR 820.100(a)(1). For example, you only evaluate complaint data by determining whether the(b)(4)percentage of rework (defined as the sum of adjustments kits, remakes, and refunds sent to customers divided by the number of customer orders received for the(b)(4)) exceeds(b)(4)%. However, the(b)(4)percentage of rework calculation includes non-quality data such as refunds and lots which are different that the lots ordered for the(b)(4). Therefore, you do not employ appropriate statistical methodology to any of your complaints, loosely categorized as "issue with fit in mouth;" "design preference;" "incorrect bite/occlusion;" "fabrication error;" "product not aesthetically pleasing;" "issue with fit on model;" "unknown;" and "wrong tooth shade," to detect recurring quality problems.c. 8502-01 does not require verification or validation of the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). For example, you did not verify or validate that the corrective action identified under CAPA # 002 (corrected date of 11/6/23) to use adjustment kits, to address the observed increase in adjustments and remake rates from fit issues, were effective and did not adversely affect your ResetSmile Partial Denture Devices prior to sending them to customers.We reviewed your firm's response and conclude that it is not adequate. You clarify that the quality data analysis is performed as part of the "Quality Objectives Management" (5401-01 Rev. 0) and "Management Review" (5600-M1 Rev. 0) processes and that there were no trends noted between May to October 2024 for the three (3) weeks where the value for percentage for rework was above(b)(4). As such, no corrective actions were identified. Therefore, please provide a response on how you plan to address the above deficiencies.7. Failure to establish and maintain procedures to adequately control environmental conditions, which could reasonably be expected to have an adverse effect on product quality and periodically inspect the environmental control system to verify that the system, including necessary equipment, is adequate and functioning properly, as required by 21 CFR 820.70(c).Specifically:a. You failed to define and document procedures to control environmental conditions for your production area consisting of(b)(4)3D Printers, used to manufacture your ResetSmile Partial Denture Devices. For example:i. On 11/6/24, the investigator observed out of specification temperatures of 92.3℉ (33.50℃) and 92.4℉ (33.56℃) on two separate temperature and humidity monitors, which were above the "Environment Requirements" of(b)(4)℃ specified in the "(b)(4)3D Printer User Guide." In addition, the humidity value for one of the monitors was below the requirement of(b)(4)in this same guide. These out of specification values affected(b)(4)production lots that were being printed across(b)(4)different(b)(4)3D Printers at the time.ii. On 11/19/24, the investigator also observed an out of specification temperature of 95.1℉ (35.06℃) and 14.4% humidity on one temperature and humidity monitor, which were outside the temperature ((b)(4)℃) and humidity ((b)(4)) ranges specified in the "(b)(4)3D Printer User Guide." This out of specification temperature and humidity affected(b)(4)production lots that were being printed across(b)(4)different(b)(4)3D Printers at the time.Moreover, you do not regularly log the temperature and humidity values or regulate the temperature in the production area.b. You failed to periodically inspect your temperature and humidity monitors to ensure that they are suitable for their intended use and calibrated or evaluated for accuracy.We reviewed your firm's response and conclude that the adequacy cannot be determined at this time. You plan to calibrate your temperature and humidity sensor; set up alerts when values exceed specified requirements; control ambient humidity and temperature of the room; and develop an "Environmental Requirements" procedure under corrective action report # CA012 around January 31, 2025. Please provide updates on the progress of these corrective actions and corrections, including # CA012, and any supporting evidence.8. Failure to ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use, as required by 21 CFR 820.70(g).Specifically, you failed to meet specified placement requirements for your(b)(4)3D Printers, which are used to manufacture your ResetSmile Partial Denture Devices. For example, on 11/19/24, the investigator observed that the distance between the sides of 3D printers(b)(4)and(b)(4)and(b)(4)and(b)(4)was approximately 8 cm and the distances between the corresponding(b)(4)and backs of 3D printers(b)(4)and(b)(4)were approximately 5.5 cm and 6 cm, respectively, which are all below the specified placement requirements noted in the "(b)(4)3D Printer User Guide" which requires that "***the distances of the left, right and back [sic] side space should be at least 20cm***."We reviewed your firm's response and conclude that the adequacy cannot be determined at this time. You plan to rearrange the printers and printer racks to accommodate the recommended spacing guidelines in the manufacturer's instructions for use; reposition the(b)(4); and document these parameters in "Environmental Requirements" under corrective action report # CA012 around January 31, 2025. Please provide updates on the progress of these corrective actions and corrections, including # CA012, and any supporting evidence.9. Failure to establish procedures for identifying training needs and ensure that all personnel are trained to adequately perform their assigned responsibilities, including documentation of training, as required by 21 CFR 820.25(b).Specifically, you failed to implement your "New Hire/Training of Personnel Process" (SOP 6202-01; Rev. 0; Effective: 6/17/24) which requires both acknowledgment of training on the "Training Acknowledgment Form" (6202-01-04; Rev. 0; Effective: none) and identification of training needs by the senior manager on the "Training Needs Assessment" form (6202-01-03). For example, there were no training forms completed for the following procedures: "Control of Nonconformity Process" (SOP 8300-01; Rev. 0; Effective: 10/25/24) "Complaint Handling Process" (SOP 8202-01; Rev. 0; Effective: 06/22/22) "Internal Rework Process" (SOP 8304-01; Rev. 0, Effective: 6/22/24) "External Rework Process" (SOP 8304-02; Rev. 0, Effective: 6/22/24)In addition, there was no documented training on the 6201-01-04 form from before 10/28/24, which is between the dates of preannouncement (10/24/24) and the start of the inspection (10/29/24) for procedures such as (but not limited to) "QC Validation" (7506-01), "Device Fabrication" (7501-01), and "Calibration Process" (7600-01). This applies to(b)(4)employees, including your VP of Clinical Operations;(b)(4)Customer Service Representatives;(b)(4)CAD Technician;(b)(4)3D Printing Technicians;(b)(4)Dental Technicians;(b)(4)Dental Lab Technicians; and(b)(4)Shipping/Receiving personnel.We reviewed your firm's response and conclude that the adequacy cannot be determined at this time. You plan to conduct a review in which 6202-01-03 will be completed for all employees and additional training will be scheduled for all affected personnel for procedures noted, including completion of the 6202-01-04 form under corrective action report # CA014 around January 31, 2025. Please provide updates on the progress of these corrective actions and corrections, including # CA014, and any supporting evidence.Corrections and Removals Violation(s)Our inspection also revealed that your ResetSmile Partial Denture Devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 806 – Medical Devices; Reports of Corrections and Removals.Significant violations include, but are not limited to, the following:Failure to submit any report required within 10 working days of initiating a correction or removal, initiated to reduce a risk to health posed by the device or remedy a violation which may present a risk to health, as required by 21 CFR 806.10.Your firm initiated a medical device correction by providing “adjustment kits” as a corrective measure, allowing customers to modify their ResetSmile Partial Denture Devices at home. This correction was initiated to remedy dentures that do not perform as intended, i.e., cause irritation or do not fit the patient. The adjustment kit is comprised of four items: a pink emery board, a blue emery board, a sanding stick, and a transfer stick to highlight problem areas. Your firm is instructing customers to use this kit to adjust the dentures that cause gum irritation or do not fit well. CDRH determined that the gum irritation being caused by the ResetSmile Partial Denture Devices may cause temporary or medically reversible adverse health consequences. Also, in some cases, there is a reasonable probability that ill-fitting dentures will cause serious adverse health consequences. Your firm’s actions thus meet the definition of a medical device correction or removal initiated to reduce a risk to health or remedy a violation which may present a risk to health. Therefore, this action is a medical device correction for which your firm is required to submit a Report of Correction or Removal to FDA.Unapproved Device Violation(s)Our inspection also revealed that your ResetSmile Partial Denture and the at-home ResetSmile Impression Kit Devices, are adulterated under section 501(f)(1)(B) of the Act, 21 U.S.C. § 351(f)(1)(B), because your firm does not have approved applications for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or approved applications for an investigational device exemption under section 520(g) of the Act, 21 U.S.C. § 360j(g). These devices are also misbranded under section 502(o) the Act, 21 U.S.C. § 352(o), because your firm did not notify the agency of its intent to introduce the devices into commercial distribution, as required by section 510(k) of the Act, 21 U.S.C. § 360(k). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.For your ResetSmile Partial Denture Devices, the inspection determined that you use(b)(4)manufacturing to produce ResetSmile Partial Denture Devices, comprised of a resin denture base material and preformed plastic denture teeth. The(b)(4)manufacturing process includes the following specific steps: customers take at-home impressions using your firm’s impression kit; a dentist virtually reviews the scans of these at-home impressions; your firm uses the resin denture base material to make the denture bases with a 3D printer; your firm chemically bonds the preformed plastic teeth to the denture bases to fabricate the dentures; and your firm ships approximately(b)(4)percent of these dentures directly to customers.We note that (1) partial denture devices and resin denture base material are class II devices classified under 21 CFR 872.3760 and require 510(k) clearance and (2) preformed plastic teeth are class II devices classified under 21 CFR 872.3590 and generally do not require 510(k) clearance. In your response, you do not identify a 510(k) clearance for your partial denture devices. Rather, your response seems to suggest that clearance for your partial denture devices is not required because your firm uses only cleared and 510(k) exempt materials in its manufacturing process and that the resin denture base material has a clearance. However, your firm did not provide a 510(k) number for the resin denture base material intended for use in a 3D printer—rather, your firm only provided a 510(k) number for preformed plastic teeth (K060507). Therefore, premarket notification or premarket approval is required for your ResetSmile Partial Denture Devices.Your response did not address your at-home ResetSmile Impression Kit Devices, which the inspection revealed are shipped from your headquarters facility, located in Irving TX, directly to customers for them to use without the supervision of a dentist or other practitioner to take their own impressions for the partial dentures. Specifically, your firm’s impression kits include impression material, a retractor, a tray, and instructions which explain to customers how to take their own impressions.Impression material is a class II device classified under 21 CFR 872.3660 and required to have 510(k) clearance, whereas retractors and trays are class I devices and generally 510(k) exempt. Your firm claims that it has a clearance for its impression material (K221668). The 510(k) summary for K221668 states that it is “intended for use with all crowns, bridges, and orthodontic impression techniques to reproduce the structure of a patient’s teeth and gums,” and is for prescription use only. Your impression material is intended to be used by customers to take their own impression without the supervision of a dentist, and thus does not fall within this cleared indication for use. This change to the device could significantly affect the safety and effectiveness of the impression material because customers who use at-home impression kits to take their own impressions may be more likely to take improper impressions—and improper impressions can lead to improper fabrication of the denture, which can cause bone loss/resorption, irritation, sores, and TMJ dysfunction. Moreover, it is unclear whether your firm is sending the impression material to customers with a prescription from a dentist—and the labeling of the impression kit does not appear to state that it is for prescription use only. Changing a device for prescription use only to a device for over the counter use also could significantly affect the safety or effectiveness of the device.1Therefore, premarket notification or premarket approval is required for your at-home ResetSmile Impression Kit Devices.Unique Device Identification Violation(s)The inspection revealed that your devices are misbranded within the meaning of section 502(c) of the Act, 21 U.S.C. § 352(c), because a word, statement, or other information required by or under authority of section 519 of the Act, 21 U.S.C. § 360i, to appear on the label or labeling of the devices was not prominently placed thereon with such conspicuousness (as compared with other words, statements, designs, or devices, in the labeling) and in such terms as to render it likely to be read and understood by the ordinary individual under customary conditions of purchase and use. In particular, 21 CFR 801.20(a) – which was promulgated under authority of section 519 of the Act, among other provisions – requires, with exceptions not relevant here, that the label and device package of every medical device bear a unique device identifier (UDI) that meets the requirements of 21 CFR Part 801, subpart B, and 21 CFR Part 830. The labels of the ResetSmile devices do not bear such a UDI.Specifically, the labels for your ResetSmile Partial Denture and ResetSmile Impression Kit Devices do not include a device identifier within the meaning of 21 CFR 801.3 or 830.3, and there is no UDI presented in easily readable plain-text on the label of both of your ResetSmile devices (see 21 CFR 801.40(a)(1)), and there is no UDI presented in machine-readable form that uses(b)(4)technology on the label of both of your ResetSmile devices (see 21 CFR 801.40(a)(2)).In addition, your ResetSmile Partial Denture and ResetSmile Impression Kit Devices are misbranded within the meaning of section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, respecting these devices. In particular, 21 CFR 830.300(a) and 830.320(b) – both of which were promulgated under section 519 of the Act, among other provisions – require that the labeler of a device submit electronically to FDA’s Global Unique Device Identification Database (GUDID) the information required by 21 CFR Part 830, subpart E, for each version or model required to bear a UDI. FDA has determined that your firm causes a label to be applied to a device with the intent that the device will be commercially distributed without any subsequent replacement or modification of the label. Reset Technology Corporation is therefore a “labeler” within the meaning of 21 CFR 830.3, and has not submitted to GUDID any information required by 21 CFR Part 830, subpart E, respecting these devices.The failure or refusal to furnish any notification or other material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, also constitutes a prohibited act under section 301(q)(1)(B) of the Act, 21 U.S.C. § 331(q)(1)(B).Registration and Listing Violation(s)Under section 510 of the Act (21 U.S.C. § 360), manufacturers of medical devices are required to annually register with the FDA. In September 2007, section 510 of the Act was amended by the Food and Drug Administration Amendments Act of 2007 (Pub. L. 110-85) to require domestic and foreign device establishments to submit their annual establishment registration and device listing information to FDA by electronic means [section 510(p) of the Act (21 U.S.C. § 360(p))] during the period beginning October 1st and ending December 31st of each year.Your response states that you are exempt from registration and listing under 21 CFR 807.65(i) because you are a dental laboratory. Your response explains that your firm “manufactures patient specific restorative devices (removable partial dentures) based upon a prescription from a licensed dentist” and “use[s] FDA cleared materials . . . to manufacture each patient specific device and do[es] not commercially distribute these devices.” Your response further explains that you previously registered as a medical device manufacturer for preformed plastic denture teeth based on incorrect information from a regulatory consultant and have since deactivated your registration with the FDA for fiscal year 2025.21 CFR 807.65(i), among other things, exempts from registration and listing “[p]ersons who dispense devices to the ultimate consumer or whose major responsibility is to render a service necessary to provide the consumer (i.e., patient, physician, layman, etc.) with a device or the benefits to be derived from the use of the device; for example, a…dental laboratory…whose primary responsibility to the ultimate consumer is to dispense or provide a service through the use of a previously manufactured device.” Here, your firm is not providing a service through the use of previously manufactured devices. Rather, as discussed above, your firm manufactures and distributes partial denture devices using devices that lack required approval/clearance and manufactures and distributes impression kits comprised of devices that lack required approval/clearance.As of this date, our records indicate that your firm has not fulfilled annual registration and listing requirements for fiscal year 2025 for your facility located in Englewood Cliffs, NJ. 21 CFR 807.22(b). Therefore, your firm’s devices at your facility located in Englewood Cliffs, NJ, are misbranded within the meaning of section 502(o) of the Act (21 U.S.C. § 352(0)), in that the devices were manufactured, prepared, propagated, compounded, or processed in an establishment not duly registered under section 510 of the Act (21 U.S.C. § 360) and were not included in a list required by section 510(j) of the Act (21 U.S.C. § 360(j)).Your firm should take prompt action to correct the violations addressed in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.Please notify this office in writing, within fifteen business days from the date you receive this letter, of the specific steps your firm has taken to correct the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm's planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm's response should be comprehensive and address all violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.We also request your attendance at a virtual Regulatory Meeting to discuss the status of the specific steps you have taken since the inspection to correct the noted violations. This meeting will also give you an opportunity to ask any questions you may have and to provide FDA additional information regarding implementation of corrective actions. Please contact Gina Brackett, Establishment Assessment Team (EAT) 1, Assistant Director, by email at gina.brackett@fda.hhs.gov within 5 business days to set up a date and time for the meeting.Your firm’s response to the Warning Letter should be addressed to Gina Brackett, Establishment Assessment Team (EAT) 1, Assistant Director, and sent via email to CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 704828” when replying. If you have any questions about the contents of this letter, please contact: Sargum C. Morgan, Compliance Officer at sargum.morgan@fda.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm's facility. It is your firm's responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm's manufacturing and quality management systems. Your firm should investigate and determine the causes of the violations, and take prompt actions to correct the violations and bring the products into compliance.Sincerely,/S/Matthew G. HillebrennerDeputy DirectorOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCC: Justin S. Marks, VP Clinical Operations, justin@resetsmile.com_____________________________1SeeDeciding When to Submit a 510(k) for a Change to an Existing Device – Guidance for Industry and Food and Drug Administration Staff (Oct. 2017) (“FDA has found that the directions for use necessary for health care professionals to use a device safely and effectively can be significantly different from the directions for use necessary for lay users to use that same device safely and effectively. Therefore, changing a device labeled for prescription use only to a device that is labeled for OTC use typically could significantly affect the safety or effectiveness and would likely require submission of a new 510(k).”).

Product:DrugsRecipient:www.24hreup.bizGermanyIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesTO: www.24hreup.bizFROM: The United States Food and Drug AdministrationRE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the InternetDATE: April 23, 2025WARNING LETTERThis is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet addresses www.24hreup.biz and has observed that your website introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 503(b), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 353(b), and 355(a)].As discussed below, FDA has observed that www.24hreup.biz introduces into interstate commerce unapproved and misbranded semaglutide drug products. There are inherent risks to consumers who purchase unapproved and misbranded drug products. 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.24hreup.biz cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to protect the public from harm.Unapproved New Drugs:Certain products offered for sale by www.24hreup.biz 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 [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) [21 U.S.C. § 331(d)] and 505(a) of the FD&C Act.On www.24hreup.biz in the “Weight Management” and “Injectable” categories of your website, you offer semaglutide marketed as “Ozempic 0.5mg” packaged as “Оземпик 1,34 мг/мл,” “Ozempic 1mg” packaged as “Оземпик 1,34 мг/мл,” and “Rybelsus Semaglutide 14mg” packaged as “1 blister card of 10 tablets.” While there are FDA-approved versions of Ozempic and Rybelsus on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for the “Ozempic 0.5mg,” “Ozempic 1mg,” and “Rybelsus Semaglutide 14mg” offered by www.24hreup.biz. Currently there are three semaglutide products that are FDA-approved for the U.S. market and these products are only available pursuant to a prescription from a licensed practitioner. FDA-approved semaglutide injection marketed under the brand name Ozempic is indicated as an adjunct to diet and exercise to improve glycemic control in individuals with type 2 diabetes mellitus and to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established cardiovascular disease. FDA-approved semaglutide tablets marketed under the brand name Rybelsus are indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. FDA-approved semaglutide injection marketed under the brand name Wegovy is indicated as an adjunct to a reduced calorie diet and increased physical activity for chronic weight management in certain adult and pediatric patients. FDA-approved semaglutide 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 thyroid C-cell tumors.Misbranded Drugs:A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] 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 [21 U.S.C. § 353(b)(1)] 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) of the FD&C Act, can be used safely only at the direction, and under the supervision, of a licensed practitioner.FDA has observed that www.24hreup.biz offers “Ozempic 0.5mg,” “Ozempic 1mg,” and “Rybelsus Semaglutide 14mg” for sale without a prescription. Because these 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 the products safely for their intended use. Consequently, the labeling for these drugs fails to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act. In addition, because the drugs are not approved in the U.S., 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.24hreup.biz is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].Furthermore, under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering “Ozempic 0.5mg,” “Ozempic 1mg,” and “Rybelsus Semaglutide 14mg” without requiring a prescription, www.24hreup.biz jeopardizes patient safety and misbrands the drugs under section 503(b)(1) of the FD&C Act. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].Additionally, “Ozempic 0.5mg” and “Ozempic 1mg” offered by www.24hreup.biz are intended for injection, which heightens the public health concern associated with these products and may further contribute to the potential for patient harm. 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.FDA is sending this warning letter to www.24hreup.biz because of the inherent risks to consumers who purchase unapproved and misbranded drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drugs noted above). We advise you to review your websites (including www.24hreup.com which forwards to www.24hreup.biz), product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded products in violation of the FD&C Act.Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. 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 within 15 working days.If you are not located in the U.S., 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 U.S.Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.Sincerely,/S/Sangeeta Vaswani Chatterjee, Pharm.D.Acting Director, Office of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and Research

行政相对人名称扬州信诺日化有限公司行政相对人类别法人及非法人组织统一社会信用代码91321000742489984H工商注册号组织机构代码税务登记号事业单位证书号社会组织登记证号法定代表人许晨光法定代表人证件类型身份证法定代表人证件号码3****************4证件类型证件号码行政处罚决定书文号苏药监扬处罚〔2025〕19号违法行为类型化妆品生产企业许可条件发生变化、未按规定申请变更的行为，违反了《化妆品生产经营监督管理办法》第十七条、第十八条第一款规定。违法事实扬州信诺日化有限公司，化妆品生产企业许可条件发生变化、未按规定申请变更的行为，违反了《化妆品生产经营监督管理办法》第十七条、第十八条第一款规定，依据《化妆品生产经营监督管理办法》第五十八条第一款规定，应予处罚。处罚依据依据《化妆品生产经营监督管理办法》第五十八条第一款规定。处罚类别警告;罚款处罚内容警告；罚款壹万捌仟元整罚款金额（万元）1.8没收违法所得没收非法财物的金额（万元）暂扣或吊销证照名称及编号处罚决定日期2025/06/16处罚有效期2025/12/16公示截止期2025/09/16处罚机关江苏省药品监督管理局处罚机关统一社会信用代码11320000014000394R数据来源单位江苏省药品监督管理局数据来源单位统一社会信用代码11320000014000394R备注公示截止期依据文件：市场监督管理行政处罚信息公示规定。罚款金额已确认。

行政相对人名称扬州华祥医疗器械有限公司行政相对人类别法人及非法人组织统一社会信用代码91321002MA1WEUAL1T工商注册号组织机构代码税务登记号事业单位证书号社会组织登记证号法定代表人范如华法定代表人证件类型身份证法定代表人证件号码3****************4证件类型证件号码行政处罚决定书文号苏药监扬处罚〔2024〕43号违法行为类型生产不合格玻璃体温计的行为，违反了《医疗器械监督管理条例》第三十五条第一款的规定。违法事实扬州华祥医疗器械有限公司，生产不合格玻璃体温计的行为，违反了《医疗器械监督管理条例》第三十五条第一款的规定，依据《中华人民共和国行政处罚法》第二十八条第二款、《医疗器械监督管理条例》第八十六条第一项规定，应予处罚。处罚依据依据《中华人民共和国行政处罚法》第二十八条第二款、《医疗器械监督管理条例》第八十六条第一项规定。处罚类别罚款;没收违法所得、没收非法财物处罚内容没收违法所得陆仟伍佰元整；处以罚款叁万伍仟元整。罚款金额（万元）3.5没收违法所得没收非法财物的金额（万元）0.65暂扣或吊销证照名称及编号处罚决定日期2025/06/16处罚有效期2025/12/16公示截止期2028/06/16处罚机关江苏省药品监督管理局处罚机关统一社会信用代码11320000014000394R数据来源单位江苏省药品监督管理局数据来源单位统一社会信用代码11320000014000394R备注公示截止期依据文件：市场监督管理行政处罚信息公示规定。罚款金额已确认。

序号行政处罚决定书文号案件名称违法企业名称或违法自然人姓名违法企业组织机构代码法定代表人姓名主要违法事实行政处罚的种类和依据行政处罚的履行方式和期限做出处罚的机关名称和日期备注1河分械罚〔2025〕1号河池市立超齿科技术有限公司未取得《医疗器械注册证》生产销售医疗器械案河池市立超齿科技术有限公司91451281MA5MU5GL7N韦永钊当事人未取得《医疗器械注册证》进行生产销售医疗器械活动，违反了《医疗器械监督管理条例》第十三条第一款的规定。    依据《中华人民共和国行政处罚法》第二十八条的规定，责令当事人立即改正上述违法行为，并依据《医疗器械监督管理条例》第八十一条第一款第一项的规定，给予以下行政处罚：主动履行广西壮族自治区药品监督管理局2025年6月9日1.没收违法所得8245.00元（捌仟贰佰肆拾伍圆）；2025年6月23日2.并处罚款100000.00元（壹拾万圆）。

白求恩医学研究院（河南）有限公司仙桃分公司报告，由于产品描述不规范等原因，白求恩医学研究院（河南）有限公司仙桃分公司对其生产的疣体剥离刀（备案号：鄂仙桃械备20250001）主动召回。召回级别为三级。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2025年6月6日相关推荐：27.Z09医疗器械召回控制程序-医疗器械生产质量管理体系文件模板召回管理规定（XS-SMP-01）产品召回记录(XXX-QR-XS-13/04 )——医疗器械生产企业

咸宁医麦德实业有限公司报告，由于产品型号不规范等原因，咸宁医麦德实业有限公司对其生产的  医用隔离垫  （备案号：鄂咸宁械备20250003）主动召回。召回级别为三级。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                                                          2025年6月6日相关推荐：27.Z09医疗器械召回控制程序-医疗器械生产质量管理体系文件模板召回管理规定（XS-SMP-01）产品召回记录(XXX-QR-XS-13/04 )——医疗器械生产企业