按照《医疗器械监督管理条例》规定，根据企业申请，国家药品监督管理局现注销以下3家企业共5个产品的医疗器械注册证：　　一、上海安翰医疗技术有限公司的1个产品：胃肠标记物胶囊，注册证编号：国械注准20223061386。　　二、施乐辉外科植入物（北京）有限公司的3个产品：非骨水泥柄，注册证编号：国械注准20173134519；陶瓷球头，注册证编号：国械注准20173134280；骨水泥柄，注册证编号：国械注准20183131538。　　三、西安一体医疗科技有限公司的1个产品：伽玛射线立体定向回转聚焦放疗机，注册证编号：国械注准20173050733。　　特此公告。　　国家药监局　　2025年9月30日

Delivery Method:VIA UPS and Electronic MailReference #:CBER 25-711102Product:BiologicsRecipient:Joshua M. MansavageChief Executive OfficerNew Life Medical Services, LLC244 Crystal Grove BlvdLutz,FL33548-6460United StatesJoshm@newliferegen.comIssuing Office:Center for Biologics Evaluation and Research (CBER)United StatesWARNING LETTERSeptember 24, 2025CBER 25- 711102Dear Mr. Mansavage:The United States Food and Drug Administration (FDA) inspected your facility, located at the above address, between May 14, 2024, and May 20, 2024. During the inspection, FDA documented that your company sells human products derived from umbilical cord (Restor+1, Regain, and Renyte), an amniotic fluid derived product (ReCyte/Cytosomes2), and an exosome product (also referred to as an “extracellular vesicle” product, named Rexo) for allogeneic use (collectively, “your products”).This letter is to advise you that your products are unapproved new drugs in violation of section 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. §355(a). Your products are also unlicensed biological products in violation of section351(a)(1) of the Public Health Service Act (PHS Act), 42 U.S.C. § 262(a)(1). A biological product for which a biologics license application (BLA) has been approved undersection 351(a) of the PHS Act is not required to have an approved application undersection 505 of the FD&C Act, 21 U.S.C. § 355; 42 U.S.C. § 262(j). Otherwise, with certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act. Your introduction or delivery for introduction of your products into interstate commerce, or the causing thereof, is prohibited under section 301(d) of the FD&C Act, 21 U.S.C. § 331(d).Based on information and records reviewed by FDA, including your website, www.newliferegen.com, (last visited September 2025) and your Instagram page (newliferegen, last visited September 2025), your products are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease or conditions in humans and/or are intended to affect the structure or function of the body. For example:Your website states that “Restor+ facilitates healing by secreting powerful bioactive molecules, creating an optimal environment for tissue repair and regeneration.”Your Physician Guide states Restor+ “has a strong anti-inflammatory effect reducing the expression of inflammatory cytokines.”Your training videos demonstrate use of Restor+, occasionally in conjunction with Rexo, in the treatment of several conditions, including neuropathy and bone spurs, as well as treating pain and inflammation.Your package insert for Regain states it is intended “to supplement the recipient’s tissue and assist in the body’s natural regenerative functions.”Your Physician Guide states:o “Higher concentration of growth factors in Renyte act as anti-inflammatory and have been shown to prevent cell death.”o Renyte is intended to “supplement or replace damaged or inadequate connective tissue.”Your product update for Cytosomes to ReCyte indicates that “Recyte is intended to help with inflammation and to enhance the healing process.”Your website states that “Rexo is an innovative extracellular vesicle product derived from Wharton’s Jelly that offers advanced healing properties.”One of your Instagram posts states, “Flagship Products … Restor+ and Rexo … Ideal Applications” and lists orthopedic procedures, paraspinal treatments, hair restoration therapies, and neuropathy interventions.In addition, evidence obtained during the inspection documents your representation that, “[New Life Medical Services] products across the board are utilized for pain management, inflammation of soft tissue, … and non-union fractures. ‘The application for all products are copy, paste.’”Therefore, your products are drugs as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and biological products as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i).Your Restor+, Regain, and Renyte products are also human cells, tissues, or cellular or tissue-based products (HCT/Ps) as defined in 21 CFR 1271.3(d) and are subject to regulation under 21 CFR part 1271, issued under the authority of section 361 of the PHS Act, 42 U.S.C. § 264. HCT/Ps that do not meet all the criteria in 21 CFR 1271.10(a) are not regulated solely under section 361 of the PHS Act and the regulations in 21 CFR part 1271. Unless an exception in 21 CFR 1271.15 applies, such products are regulated as drugs, devices, and/or biological products under the FD&C Act and/or the PHS Act and are subject to additional regulation, including applicable premarket review. Based on a review of relevant materials, New Life Medical Services does not qualify for any exception in 21 CFR 1271.15, and Restor+, Regain, and Renyte fail to meet all criteria in 21 CFR 1271.10(a).For example, your Restor+, Regain, and Renyte products fail to meet the minimal manipulation criterion set forth in 21 CFR 1271.10(a)(1) and defined for structural tissue in 21 CFR 1271.3(f)(1), because the processing alters the original relevant characteristics of the umbilical cord tissue related to its utility for reconstruction, repair, or replacement. The processing of the umbilical cord from the form of a conduit into an injectable form, significantly alters the physical state of the HCT/P. The umbilical cord is more than minimally manipulated because such processing alters the original relevant characteristics of the HCT/P relating to its utility to serve as a conduit by effectively altering or eliminating its physical integrity and tubular form.In addition, your Restor+, Regain, and Renyte products fail to meet the criterion that the HCT/Ps be “intended for homologous use only,” which means that the “labeling, advertising, or other indications of the manufacturer’s objective intent” demonstrate that the HCT/P is intended to perform “the same basic function or functions in the recipient as in the donor” (21 CFR 1271.3(c) and 1271.10(a)(2)). Your product is not intended solely to perform the same basic function or functions of the HCT/P in the recipient as in the donor (e.g., serving as a conduit for umbilical cord). Rather, your products are intended for use in healing/supplementing tissue, orthopedic procedures, treating neuropathy, and reduction of inflammation which are not basic functions of umbilical cord in the donor.Therefore, these HCT/Ps are not regulated solely under section 361 of the PHS Act, 42 U.S.C. § 264, and the regulations in 21 CFR part 1271.3See 21 CFR 1271.20. In addition to being regulated under section 361 of the PHS Act and 21 CFR part 1271, your Restor+, Regain, and Renyte products are regulated as drugs as defined in section 201(g)(1) of the FD&C Act, 21 U.S.C. § 321(g)(1), and biological products as defined in section 351(i) of the PHS Act, 42 U.S.C. § 262(i), as stated above.Subject to certain exceptions not applicable here, to lawfully introduce or deliver for introduction into interstate commerce a drug that is a biological product, a valid BLA must be in effect under section 351(a)(1) of the PHS Act, 42 U.S.C. § 262(a)(1). Such licenses are issued only after showing that the product is safe, pure, and potent. Your products are not the subject of an approved BLA.Additional ConcernsIn addition to the violations described above, we have concerns about the following products:FDA’s review of your website and other records found that you market additional products, an umbilical cord derived product named Restor Charge and an exosome-based product named Rexo Charge4. Based on our review, these products are drugs and/or biological products, which are subject to premarket review and approval requirements. In your response, please provide a customer list for each of these products and indicate whether you believe you sell them in compliance with the FD&C Act. If so, include your explanation why; if not, include your plan for coming into compliance.We also direct your attention to FDA’s Public Safety Notification on Exosome Products, available at https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/public-safety-notification-exosome-products. FDA issued this public safety notification following multiple reports of serious adverse events experienced by patients who were treated with exosome products.ConclusionThis letter is not intended to be an all-inclusive list of deficiencies that may exist in connection with your products. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations. It is your responsibility to ensure full compliance with all applicable requirements in the FD&C Act, PHS Act, and all applicable regulations.This letter notifies you of our concerns and provides you an opportunity to address them. Failure to adequately address these matters may result in action without further notice including, without limitation, seizure and/or injunction.Please submit your response in writing within fifteen (15) working days from your receipt of this letter, outlining the specific steps you have taken or plan to take to address any violations and prevent their recurrence. Include any documentation necessary to show that the matters have been addressed. If you cannot address these matters within fifteen (15) working days, please explain the reason for your delay and the timeframe for completion. If you do not believe your products are in violation of the FD&C Act, PHS Act, or applicable regulations, include your reasoning and any supporting information for our consideration.Send your electronic response to CBERDCMRecommendations@fda.hhs.gov. If you have questions regarding this letter, contact the Division of Case Management, CBER at CBERDCMRecommendations@fda.hhs.gov.Sincerely,/S/Melissa J. MendozaDirectorOffice of Compliance and Biologics QualityCenter for Biologics Evaluation and Research__________________________1Restor+ is also referred to as restor+, restor, Restor, Restor Plus Wharton’s Jelly, and Restor+ Wharton’s Jelly.2You explained during the inspection that the product Cytosomes was renamed Recyte in 2023 and provided a “Product Update” that states “Cytosomes gets a new name recyte®[.] New name, same quality product.”3Because Restor+, Regain, and Renyte fail to meet at least one criterion in 21 CFR 1271.10(a), this letter does not evaluate all other criteria in 21 CFR 1271.10(a).4Your Instagram post from December 19, 2024, states that “Restor Charge and Rexo Charge provide strong healing potential at a lower price, making regenerative treatments accessible for everyone.”

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Dr. Bruce R. Coren, DVM, MSChief Executive OfficerTechnological Medical Advancements LLC1601 Belvedere Rd Ste E-180West Palm Beach,FL33406-1541United Statesbcoren@diowavelaser.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 712715September 26, 2025Dear Dr. Coren:During an inspection of your firm located in West Palm Beach, Florida from April 9, 2025, through April 21, 2025, investigators from the United States Food and Drug Administration (FDA) determined that your firm manufactures the Diowave 250 WLS and Diowave 100 WLS laser system. 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.Unapproved Device ViolationsFDA has reviewed the information collected during the April 2025 inspection and information on your firm’s website at www.diowavelaser.com (last accessed on July 1, 2025). FDA has reviewed the Physician Brochure (TMA, Physician Brochure, February 2024), AI Instructions for Use (TMA, Diowave 100 WLS & Diowave 250 WLS, IMPOS-AI User Instructions, Undated, 1 page.pdf ), Diowave Life Without Pain Brochure (Diowave Laser Treatment Center, Imagine Life Without Pain Brochure), and an Operating Manual (TWA, Diowave Stealth Micro-Pulse Laser System Operating Manual Version 2024-5), and has determined that the Diowave 100 WLS and Diowave 250 WLS 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 an approved application for premarket approval (PMA) in effect pursuant to section 515(a) of the Act, 21 U.S.C. § 360e(a), or an approved application for an investigational device exemption (IDE) under section 520(g) of the Act, 21 U.S.C. § 360j(g) for the device as described and marketed. The Diowave 100 WLS and Diowave 250 WLS 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). Specifically, the Diowave 100 WLS and the Diowave 250 WLS are in violation of the Act for the reasons discussed below.Technological Characteristics:Devices classified under 21 CFR 890.5500 Infrared Lamp are devices intended for medical purposes that emits energy at infrared frequencies to provide topical heating and are exempt from premarket notification requirements unless they exceed the limitations on exemption at 21 CFR 890.9. However, there is evidence that the Diowave 250 WLS and Diowave 100 WLS operate using a different fundamental scientific technology than that generic type of device. Specifically, your firm’s Care Provider Brochure states that “all heat during a stealth treatment is inhibited, allowing for deep penetration as there is no heat during treatment.” Further, the Diowave 100 WLS and Diowave 250 WLS appear to utilize stealth micro-pulse laser technology, which does not provide topical heating. For example, your distribution includes materials with claims such as:o“Diowave is pleased to reveal the Stealth Micro-Pulsed Laser System™. SMPLTallows you to hold a hand piece static over a focal pathology without heating tissue..”o “Our Stealth Micro-Pulse Technology allows care providers to treat various pathologies by Micro-Pulsing at appropriate power levels without introducing heat.”o “The Doctor can remove all heat from the laser beam allowing him to hold thelaser directly over the injury for an indefinite amount of time.”As shown by the evidence, the Diowave 100 WLS and Diowave 250 WLS devices do not provide topical heating. Instead, they use a different fundamental scientific technology. Therefore, the premarket notification requirements apply.Intended Use:Generic devices classified under 21 CFR 890.5500 emit energy at infrared frequencies (approximately 700 to 50,000 nanometers) to provide topical heating and are intended for medical purposes including, but not limited to, temporary increase in local blood circulation and temporary relief of: muscle spasms, minor joint pain and stiffness, minor muscle pain and stiffness, and minor arthritis pain. Devices classified under 21 CFR 890.5500 are exempt from premarket notification unless they exceed the limitations on exemption at 21 CFR 890.9(a). However, there is evidence that the Diowave 250 WLS and Diowave 100 WLS are intended for uses that are different from the intended use of the type of devices classified under 21 CFR 890.5500 Infrared Lamp. For example, your distribution of the Diowave 100 WLS and Diowave 250 WLS devices includes the following claims:o “a painless, non-surgical, and side-effective way to treat conditions previously refractive to traditional medical care”o “treatment of various pathologies, including those refractive to traditional therapy”o “Because laser therapy is the only treatment in medicine that actually heals living tissue, most conditions respond favorably to repeated laser therapy treatments. It has been proven to deliver results when all other forms of insurance-based medicine have failed.”o “This technology has shown great promise in healing conditions which are refractive or non-responsive to all other forms of treatment and surgery, including HPLT [High Power Laser Therapy]”o “peripheral neuropathy” case study: “An 80-year-old male with advance circulatory disease in his lower extremities presents with numbness in his feet and toes. He cannot drive because he cannot feel his feet…by the end of 12 visits, his proprioception to the bottom of his feet returned”o “Summation of Various Main Treatment Indications for Diowave:…abdominalpain, pelvic pain, wound care”o “Difficult to treat pathologies that are adequately treated by Diowave: post-surgical pain, implantable device pocket pain, surgically fused areas in which insurance will not cover further treatment, areas that do not respond well to nerve blocks or joint injections, “disc pathology, wounds refractory to conventional medical treatment, after regenerative medicine treatment: using laser to amplify effects of regenerative medicine treatments by kickstarting the process.”o “results come from the laser’s ability to stimulate tissue growth and repair…results in accelerated wound healing with a dramatic decrease in…inflammation, and scar tissue formation”Further, we note that your firm has an existing clearance (K121363) under 21 CFR 890.5500 with the following indications:“The Diowave Laser System is intended to emit energy in the infrared spectrum to provide topical heating for the purpose of elevating tissue temperature for temporary relief of minor muscle and joint pain, muscle spasm, pain and stiffness associated with minor arthritis, promoting relaxation of muscle tissue, and to temporarily increase local blood circulation.”Your firm’s promotion of the device provides evidence that the device is intended for conditions beyond the indications for which it was cleared. Examples of these claims are included above. This constitutes a major change or modification in the intended use. Thus, a new premarket notification is required. Additionally, your firm’s promotion of the device provides evidence that your firm made a technological change to the device that could significantly affect the safety or effectiveness of the device. Examples of these claims are included above. This change is a significant change or modification for which a new premarket notification is required.For a device requiring premarket approval, the notification required by section 510(k) of the Act, 21 U.S.C. § 360(k), is deemed satisfied when a PMA is pending before the agency. 21 CFR 807.81(b). The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/d efault.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.Our office requests that Technological Medical Advancements LLC cease any activities that result in the misbranding or adulteration of the Diowave 100 WLS and Diowave 250 WLS devices, such as the commercial distribution of the device, for the uses discussed above.Quality System Regulation ViolationsThis 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. Your firm’s response dated May 23, 2025, to the Form FDA 483 (FDA 483) was not received within fifteen business days of issuance of the FDA 483 however we performed a review of your response. These violations include, but are not limited to, the following:1. Failure to adequately establish procedures to ensure that all purchased or otherwise received products and services conform to specified requirements, as required by 21 CFR 820.50.Specifically,A. Your firm has failed to perform supplier evaluations as required by Purchasing Control Standard Operating Procedure, TMAQSP007, Revision 2.0. These include evaluations for critical suppliers, comprised of your contract manufacturer and designer(b)(4)and your contract service firm(b)(4), as required by Section 3 of your procedure. Additionally, no(b)(4)evaluations were conducted for any suppliers despite procedural requirements, and no justification was provided for not performing them.B. Your firm failed to maintain supplier agreements as required by your Supplier Evaluation and Monitoring Standard Operating Procedure, TMA_QSP_023. For example, section 6.1.2 of your procedure states that “a Quality Agreement/Critical Supplier Quality Agreement is drafted and signed between both parties.” However, your firm has unsigned agreements with your contract manufacturer, including both the Critical Supplier Quality Agreement and Software Agreement. During the inspection, your contract manufacturer was unable to provide required design control records for review.C. The inspection noted that your firm failed to have adequate purchasing controls and supplier oversight of your firm’s contract manufacturer,(b)(4), responsible for design controls. Your firm's inability to retrieve basic design control records from your contract designer/manufacturer during the FDA inspection, despite claims that these documents existed, demonstrates inadequate oversight of critical supplier activities. For example:i. Your firm could not provide the Design History File (DHF) records for the Diowave 250 WLS and Diowave 100 WLS medical devices. The inspection found no evidence of essential design control records including design planning, design inputs, design outputs, design reviews, design verification, design validation, design change or design transfer, representing a comprehensive failure to maintain adequate design control records as required by FDA regulations. As such, FDA is concerned that the medical devices will not consistently meet intended use and safety requirements, that design changes are not properly controlled and documented, and that the finished device design may not meet user needs and intended use.ii. The design risk management files for the Diowave 250 WLS and Diowave 100WLS laser device were not available for review. No records were available toreview by FDA investigators for design risk analysis despite your proceduralrequirements in section 3.4 of Risk Management Standard Operating Procedure,TMAQSP043, Revision 1.0, to incorporate risk analysis into your firm’s DesignReview. No risk assessment was available for review for the power increase from(b)(4)W to(b)(4)W. No evaluation on the potential need to submit a new premarket application was performed.iii. Your firm’s Supplier Evaluation and Monitoring Standard OperatingTMA_QSP_023, Revision 1 states in section 6.2 that “(b)(4). ”There have been significant modifications to your devices without notification from critical supplier or oversight and approval of changes by your firm. This includes the review of design control records such as design verification and design validation to include risk analysis. For example, design control records for changes to software ((b)(4)for 250 WLS,(b)(4)for 100 WLS), as well as an identified power increase for the Diowave laser systems from(b)(4)W to(b)(4)W were not available for review during the inspection.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Your firm’s response does not address deficiencies with the purchasing controls and oversight of the design control activities delegated to your contract manufacturer. In addition, while your firm provided some design control records from your contract manufacturer,(b)(4), you did not provide records that include the changes to the Diowave Laser System 100 WLS/250 WLS or design inputs, and therefore, we are unable determine if the device design outputs meet the design inputs. The design output records provided are missing complete device specifications, manufacturing specifications, software design specifications and labeling specifications. The design review documents are missing design reviews for all phases of the device design plan. There is no design change control for design changes previously described. The design transfer document does not include all required design transfer activities and any manufacturing process validations performed. Following our review of your response, you have not addressed the deficiencies in your firm’s design control subsystem and the requirement for a complete design history file (DHF) for your medical devices.2. Failure to establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit and to maintain complaint files, as required by 21CFR 820.198(a). For example:A. FDA investigators reviewed ten complaints from 2025 and identified comprehensive procedural failures for the receipt, review, and evaluation of complaints. Your firm failed to implement Customer Complaints procedure, TMAQSP003, Revision 3.0,and perform required procedural activities for all complaints reviewed, including complaint investigations, failure mode analysis, Management Representative approval, and completing all fields in the complaint forms.B. Your firm failed to handle all complaints in a timely manner. For example, your firm has not reviewed or evaluated(b)(4)servicing records from the third-party supplier as specified by your procedure TMA_QSP_009 Servicing, Rev 2.0, so that the Management Representative can determine if they meet the definition of a complaint so that they can be investigated as necessary.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Specifically, your firm’s response does not address this inspectional observation, and therefore is missing a corrective action plan, time frames for implementation, and documentation of activities performed to correct the underlying deficiency.3. Your firm has failed to adequately establish and maintain procedures for corrective and preventive action, as required by 21 CFR 820.100(a). Specifically, your firm has not adequately established CAPA Procedure, TMAQSP012, Revision 1.0. For example:A. Your procedure lacks requirements for analyzing processes, work operations, concessions, quality audit reports, quality records, service records, complaints, returned product, and other sources of quality data to identify existing and potential causes of nonconforming product, or other quality problems.B. Your firm has not implemented Section 3.2 of the CAPA procedure to identify actions needed to correct and prevent the recurrence of any non-conformity. For example, your firm has not opened any corrective and preventive actions, as required by your procedure, after it has been cited with the following: i. Fourteen inspectional observations from an FDA inspection conducted from August 4, 2021, to September 9, 2021; ii. Thirteen observations, along with seven verbal observations, from an FDA inspection conducted from February 19, 2020 to February 24, 2020; iii. Twelve violations cited in a letter sent to your firm on June 8, 2020, by FDA.This FDA inspection, along with previous FDA inspections, have identified repeat systemic deficiencies of your firm’s inability to identify actions to correct and prevent the recurrence of quality problems.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Specifically, your firm’s response does not address the inspectional observation, and therefore is missing a corrective action plan, time frames for implementation and documentation of activities performed to correct the underlying deficiency.4. Your firm has failed to establish and maintain adequate procedures for quality audits, as required by 21 CFR 820.22. Specifically, your firm did not conduct quality audits in 2023and 2024 as required by your Internal Audit Standard Operating Procedure, TMAQSP004,Revision 1.0. As of the date of the inspection, no quality audit has been conducted in 2025.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Specifically, your firm’s response does not address the inspectional observation, and therefore is missing a corrective action plan, time frames for implementation and documentation of activities performed to correct the underlying deficiency.5. Your firm has failed to establish procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90(a). Specifically, your firm does not have a procedure for addressing nonconforming products or materials. When the FDA investigator asked about procedures for nonconforming products or materials, you stated that such procedures did not exist. Without procedures to define nonconformance criteria and disposition processes, your firm cannot effectively identify or manage quality issues that may arise during manufacturing, incoming inspection, acceptance testing activities or as part of post-market surveillance activities.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Specifically, your firm’s response does not address the inspectional observation, and therefore is missing a corrective action plan, time frames for implementation and documentation of activities performed to correct the underlying deficiency.6. Your firm has failed to adequately establish and maintain procedures for management review, as required by 21 CFR 820.20(c). Specifically, your firm did not follow Management Review Standard Operating Procedure, TMAQSP010, Revision 1.0, which requires periodic management review at least(b)(4). Your firm did not conduct a management review in 2024, thereby failing to determine the effectiveness of your quality system. This inspection identified several inspectional observations and deficiencies that have gone uncorrected from the two previous FDA inspections or approximately 5 years.We reviewed your firm’s response dated May 23, 2025, and conclude that it is not adequate. Specifically, your firm’s response does not address the inspectional observation, and therefore is missing a corrective action plan, time frames for implementation and documentation of activities performed to correct the underlying deficiency.Unique Device Identifier Regulation (UDI) ViolationsThe 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 Diowave Pure Pulse Laser System devices do not bear such a UDI.Specifically, the labels for Diowave Pure Pulse Laser System 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 the device (see 21 CFR 801.40(a)(1)), and there is no UDI presented in machine-readable form that uses automatic identification and data capture (AIDC) technology on the label of the device (see 21 CFR 801.40(a)(2)).A follow-up inspection will be required to assure that corrections and/or corrective actions are adequate. Your firm should take prompt action to address any violations identified in this letter. Failure to adequately address this matter may result in regulatory action being initiated by the FDA without further notice. These actions include, but are not limited to, seizure, injunction, and civil money penalties.Other federal agencies may take your compliance with the FD&C Act and its implementing regulations into account when considering the award of federal contracts. Additionally, should FDA determine that you have Quality System regulation violations that are reasonably related to premarket approval applications for Class III devices, such devices will not be approved until the violations have been addressed. Should FDA determine that your devices or facilities do not meet the requirements of the Act, requests for Certificates to Foreign Governments (CFG) may not be granted.Please notify this office in writing within fifteen business days from the date you receive this letter of the specific steps your firm has taken to address the noted violations, as well as an explanation of how your firm plans to prevent these violations, or similar violations, from occurring again. Include documentation of the corrections and/or corrective actions (which must address systemic problems) that your firm has taken. If your firm’s planned corrections and/or corrective actions will occur over time, please include a timetable for implementation of those activities. If corrections and/or corrective actions cannot be completed within fifteen business days, state the reason for the delay and the time within which these activities will be completed. Your firm’s response should be comprehensive and address any violations included in this Warning Letter. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration as part of your response.Your firm’s response should be sent via email to Melissa Michurski, Assistant Director at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 712715” when replying. If you have any questions about the contents of this letter, please contact: Rafael Padilla at Rafael.Padilla@FDA.hhs.gov.Finally, you should know that this letter is not intended to be an all-inclusive list of the violations at your firm’s facility. It is your firm’s responsibility to ensure compliance with applicable laws and regulations administered by FDA. The specific violations noted in this letter and in the Inspectional Observations, FDA 483, issued at the close of the inspection may be symptomatic of serious problems in your firm’s manufacturing and quality management systems. Your firm should investigate and determine the causes of any violations and take prompt actions to address any violations and bring the products into compliance.Sincerely,/S/Barbara C. MarsdenActing DirectorOffice of Regulatory ProgramsOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA UPSReference #:320-25-115Product:Drugs、Over-the-Counter DrugsRecipient:Mr. Prakash C. PurohitPresident/OwnerNaturich Cosmetique Labs2505 Merritt DriveGarland,TX75041-6158United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-115September 25, 2025Dear Mr. Purohit:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Naturich Cosmetique Labs, FEI 3008480436, at 2505 Merritt Drive, Garland, from April 28 to May 2, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your May 22, 2025, response to our Form FDA 483 in detail. Your response is inadequate because you failed to provide supportive documentation for evaluation or adequate evidence of corrective actions taken to bring your operations into compliance with CGMP.1. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Inadequate Water SystemYour firm uses water as a component to manufacture topical over-the-counter (OTC) drug products including skin protectants applied to irritated and potentially broken skin of infants. You failed to adequately validate your water production process to ensure the system was consistently producing water of appropriate quality for its intended use. Additionally, your water system was not adequately maintained nor periodically sanitized. Furthermore, you failed to demonstrate that your water system was adequately monitored to ensure it consistently produced water that met appropriate chemical and microbial quality standards.In your response, you commit to hiring a third-party laboratory to perform conductivity and total organic carbon testing of your water system. However, your response is inadequate because you did not include timeframes for completing microbiological testing, including appropriate microbial enumeration and identification of water system sample isolates.Additionally, you failed to consider inadequate aspects of your water system design (e.g., ambient temperature not otherwise subjected to sanitization processes) to ensure it is suitable for producing water used in the formulation of your drug products. Further, you do not address the potential impact of a poorly designed water system to drug products distributed within the United States that are within expiry.(b)(4)water must be suitable for its intended use and routinely tested. To achieve an ongoing state of control in your(b)(4)water system, you must conduct routine monitoring of microbial levels and identify any contamination in the system.Inadequate Process ValidationYou have not validated the processes you use to manufacture your OTC drug products. You failed to ensure adequate documentation and control over critical processing steps (e.g., blend times, speeds, temperatures, durations, and specific equipment) used for your large-scale, weight-based manufacturing processes. You distributed drug products with intra-batch potency variability, which indicated inadequate controls for mixing to ensure uniformity. Examples included:A lot of sub-potent Acne Moisturizing lotion that was re-tested and subsequently released without adequate justification for the initial failing result.A lot of super-potent(b)(4)SPF 30 lotion that repeatedly failed in-process testing and finished product release testing. Additionally, this lot was released after attempts to reprocess the in-process material, including blending with additional inactive components.In your response, you commit to developing a master validation plan and a standardized process validation protocol for each of your OTC topical drug products. Your response is inadequate because you did not describe interim controls while process validation is pending or consider a retrospective assessment of the potential impact to your products distributed within the United States that are within expiry.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs.Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluates batches to determine whether an initial state of control has been established.Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance for industry, Process Validation: General Principles and Practices, for general principles and approaches that the FDA considers appropriate elements of process validation athttps://www.fda.gov/regulatory-information/search-fda-guidance-documents/process-validation-general-principles-and-practices.In response to this letter, provide:A comprehensive, independent, assessment of your water system design, control, and maintenance.A thorough remediation plan to install and operate a suitable water system. Include a robust ongoing control, maintenance, and monitoring program to ensure the remediated system design consistently produces water adhering to(b)(4)Water, United States Pharmacopoeia (USP) monograph, specifications and appropriate microbial limits.Regarding the latter, ensure that your total microbial count limit for water is appropriate in view of the intended use of the products produced by your firm.A detailed risk assessment addressing the potential effects of the observed water system failures on the quality of all drug product lots currently in U.S. distribution or within expiry. Specify actions that you will take in response to the risk assessment, such as customer notifications and product recalls.A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification, and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing process performance qualification for each of your marketed drug products.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling, and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.2. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).You failed to adequately investigate multiple microbiological out-of-limit (OOL) results from your(b)(4)water system used to manufacture topical drug products. For example, from May 2024 through April 2025, you did not adequately investigate several OOL testing results from your water system, including the recovery of objectionable microorganisms from multiple points of use. These microorganisms included, but were not limited toEnterobacter cloacae(a common fecal microbiota),Burkholderia cepacia, and multiplePseudomonas sp. Your investigation did not include an adequate corrective action and preventive action plan (CAPA) to prevent the use of components with potentially objectionable microbial contamination from being used in the manufacture of your drug product.Furthermore, your justification to release associated finished product relied on subjecting finished products to poorly documented processes you identified as a “(b)(4)step of mixing temperature above that which gram-negative bacteria can withstand.”In your response, you fail to include an adequate CAPA for controlling microbial recoveries from your water system, stating you continue to rely on “(b)(4)step” processes of(b)(4)batches to(b)(4)to ensure they are free of any microbial contamination. You also fail to consider how fundamental flaws in design, control, and maintenance of your water system may contribute to the OOL results of water.Your CAPA is not sufficient to ensure the production of water, used as a component, is suitable for its intended use. Your investigations are limited in scope and lack comprehensive review for potentially affected products produced with inadequate water as well as root cause determination. You also did not provide any supporting documentation, including details of your corrective actions with your response. Well-documented, thorough, and scientifically sound investigations are necessary to identify the root cause and implement the appropriate and effective CAPA.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, out-of-specification (OOS) results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, quality unit (QU) oversight, and written procedures. Address how your firm will ensure all phases of investigations are appropriately conducted.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigations trends, improves the CAPA program when needed, implements final QU decisions, and is fully supported by executive management.A comprehensive, independent assessment of the design and control of your firm’s manufacturing operations, with a detailed and thorough review of all microbiological hazards.Complete investigations into all batches with potential objectionable microbial contamination or an OOS microbiological result (whether or not later invalidated). The investigations should detail your findings regarding the root causes of the contamination.Appropriate microbiological batch release specifications (i.e., total counts, identification of bioburden to detect objectionable microbes) for each of your drug products.All chemical and microbial test methods used to analyze each of your drug products.A summary of results from testing retained samples of all(b)(4)Baby Diaper Cream drug product batches within expiry. You should test all appropriate quality attributes including, but not limited to, identity and strength of active ingredients and microbiological quality (total counts and identification of bioburden to detect any objectionable microbes) of each batch. If testing yields an OOS result, indicate the corrective actions you will take, including notifying customers and initiating recalls.3. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).Your firm manufactures OTC topical drug products, including but not limited to hand sanitizer and skin protectants. You failed to perform adequate identity testing on each shipment of each lot of incoming components (e.g., ethyl alcohol, glycerin) used in the manufacture of your OTC topical drug products. In addition, you relied on your suppliers’ certificate of analysis (COA) without establishing the reliability of your component suppliers’ test analyses at appropriate intervals.Products Containing Ethyl AlcoholYou failed to adequately test your incoming component ethyl alcohol (ethanol) at risk of methanol contamination for identity before using it as an active pharmaceutical ingredient (API) in manufacturing your OTC topical drug products. The use of ethanol contaminated with methanol has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentPolicy for Testing of Alcohol (Ethanol) and Isopropyl Alcohol for Methanolto help you meet the CGMP requirements when manufacturing drugs containing ethanol at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/policy-testing-alcohol-ethanol-and-isopropyl-alcohol-methanol.Furthermore, you failed to demonstrate that the component ethanol, used to manufacture your hand sanitizer drug products, meets USP monograph specifications or is of adequate quality for its intended use.Products Containing Ingredients at Risk for Diethylene Glycol or Ethylene Glycol ContaminationYou also failed to adequately test your incoming components at high risk of diethylene glycol (DEG) or ethylene glycol (EG) contamination for identity before using them to manufacture your drug products. This includes, but is not limited to, testing of glycerin to determine its appropriate identity, prior to use in manufacturing your OTC topical drug products.Identity testing for glycerin and certain other high-risk drug components includes a limit test in the USP to ensure the component meets the relevant safety limits for DEG or EG levels. Because you did not perform identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in the manufacture of your drug products.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/testing-glycerin-propylene-glycol-maltitol-solution-hydrogenated-starch-hydrolysate-sorbitol.In your response, you state that your vendors for glycerin and ethyl alcohol are qualified and their COAs are accurate. You also commit to implement additional tests for a few incoming glycerin and ethyl alcohol batches specifically used in your topical OTC drug products. Your response is inadequate because you do not provide sufficient details and supporting data to demonstrate that your components meet all compendial requirements.Furthermore, your response does not address testing each shipment of each lot, including each container, of your high-risk drug components for DEG or EG contamination and ethanol for the presence of methanol contamination. Also, you do not commit to retrospective testing of retained components or finished products, and you do not address potential impact on drug products in the U.S. market within expiry.Without adequate testing, you do not have scientific evidence that the components conform to appropriate specifications before use in the manufacture of your drug products. You have a responsibility to sample, test, and examine drug components before use in production to ensure acceptable quality parameters are met.In response to this letter, provide:A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.The chemical and microbiological quality control specifications you use to test and release each incoming lot of components for use in manufacturing.A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic re-validation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of alcohol, isopropyl alcohol, glycerin, and certain additional high-risk components, we note that this includes the performance of parts A, B, and C of the USP monograph.A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.A summary of your program for qualifying and overseeing contract facilities that test the drug products you manufacture.A commitment to provide methanol test results, no later than 30 calendar days from the date of this letter, for retains for all lots of components of manufactured drug products within expiry. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of methanol.A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination, including, but not limited to, glycerin. Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.Quality SystemsYour firm’s quality systems are inadequate. For guidance on establishing and maintaining CGMP-compliant quality systems, see these FDA guidance documents:Q8(R2) Pharmaceutical Developmentat https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q8r2-pharmaceutical-developmentQ9 Quality Risk Managementat https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q9r1-quality-risk-managementQ10 Pharmaceutical Quality Systemat https://www.fda.gov/regulatory-information/search-fda-guidance-documents/q10-pharmaceutical-quality-systemCGMP 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 corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. See FDA’s guidance document Quality Systems Approach to Pharmaceutical CGMP Regulations at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/quality-systems-approach-pharmaceutical-current-good-manufacturing-practice-regulations.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.Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer.You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/regulatory-information/search-fda-guidance-documents/contract-manufacturing-arrangements-drugs-quality-agreements-guidance-industry.Cosmetics Manufactured for Distribution in the United StatesIn addition, we note that some of the products you manufacture may be regulated as cosmetics, as defined in section 201(i) of the FD&C Act [21 U.S.C. 321(i)]. Any cosmetics you manufacture must comply with applicable statutory and regulatory requirements, including the FD&C Act. Under section 301(a) of the FD&C Act [21 U.S.C. 331(a)], it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.Further, your facility may be subject to requirements of the Modernization of Cosmetics Regulation Act of 2022 (MoCRA). Information on MoCRA requirements may be found at https://www.fda.gov/cosmetics/cosmetics-laws-regulations/modernization-cosmetics-regulation-act-2022-mocra.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3008480436 and ATTN: Matthew R Dionne, Compliance Officer.Sincerely,Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCC:Kevin M. HilbertDirector, Regulatory AffairsNaturich Cosmetique Labs2505 Merritt DriveGarland, TX 75041-6158

Delivery Method:VIA Electronic MailReference #:320-15-111Product:DrugsRecipient:Mr. John Gordon DixonPresidentDixon Investments Inc. dba ARI2523 South McDonough RoadOrchard Hill,GA30266United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-15-111September 17, 2025Dear Mr. Dixon:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Dixon Investments Inc. dba ARI, FEI 1037559, at 2523 South McDonough Road, Orchard Hill, from March 5 to 11, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).In addition,(b)(4), and(b)(4)are unapproved new drugs introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 355(a) and 331(d). Additionally,(b)(4)and(b)(4)are misbranded under sections 502(f)(1) and 502(f)(2) of the FD&C Act, 21 U.S.C. 352(f)(1) and 352(f)(2). Furthermore,(b)(4), and(b)(4)are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of misbranded products into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.We reviewed your March 27, 2025 response to our Form FDA-483 in detail.During our inspection, our investigator observed specific violations including, but not limited to, the following.1. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Your firm had not performed process validation for your over-the-counter (OTC) aerosol drug products. This is a repeat violation noted in previous inspections.In your response, you state that you will outline the control procedures to ensure that manufacturing processes are properly validated. You also state that you will follow your current standard operating procedure (SOP) for data collection on the drug products you manufacture.Your response is inadequate because it lacks specific timelines, including details of your interim plans, while working toward full and complete process validation.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies include intensive monitoring and testing throughout each significant process stage to characterize intra-batch variation and evaluates batches to determine whether an initial state of control has been established.Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle.See FDA’s guidance document Process Validation: General Principles and Practices for general principles and approaches that FDA considers appropriate elements of process validation, at https://www.fda.gov/media/71023/download.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification (PPQ), and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing appropriate PPQ for each of your marketed drug products.Process performance protocols, and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.2. Your firm failed to follow an adequate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).Your firm failed to test an adequate number of drug product batches as defined by your written stability procedure. This is a repeat violation noted in previous inspections.In your response, you state that you will continue placing batches of drug product on stability and commit to updating your stability procedure based on market demands.Your response is inadequate because you failed to address the lack of appropriate stability data to support the expiry dates of your drug products that are currently on the market. Further, you failed to provide sufficient details on the interim measures you will take to ensure product maintains its critical quality attributes throughout its shelf life.Without appropriate stability studies, you do not have scientific evidence to support whether your drug products meet established specifications and retain their quality attributes through their labeled expiry.In response to this letter please provide:A comprehensive, independent assessment and corrective action and preventive action (CAPA) plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability-indicating methods.o Stability studies for each drug product in its marketed container-closure system before distribution is permitted.o An ongoing program in which representative batches of each product are added each year to the program to determine if the shelf-life claim remains valid.o Detailed definition of the specific attributes to be tested at each station (timepoint).o All procedures that describe these and other elements of your remediated stability program.3. Your firm’s quality control unit failed to exercise its responsibility to ensure drug products manufactured are in compliance with CGMP, and meet established specifications for identity, strength, quality, and purity (21 CFR 211.22).Your quality unit (QU) did not adequately exercise its authority and responsibilities, including but not limited to, implementing effective procedures and conducting adequate oversight of the drug products you manufacture. For example, your QU failed to ensure:Adequate procedures for change controls, batch record release and CAPA.Adequate review of control records (i.e., finished product testing) prior to release and distribution.Appropriate procedures are established and followed for the cleaning and maintenance of your drug manufacturing equipment.Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.In response to this letter, provide:A comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:o A determination of whether procedures used by your firm are robust and appropriate.o Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practices.o A complete and final review of each batch and its related information before the QU disposition decision. Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all products.Unapproved New Drug and Misbranding Drug Violations(b)(4)and(b)(4)are “drugs” as defined by section 201(g)(1)(B), because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because they are intended to affect the structure or any function of the body.Examples from the(b)(4)and(b)(4)product labeling that provide evidence of the intended uses (as defined in 21 CFR 201.128) of the products as drugs include, but may not be limited to, the following:(b)(4)“(b)(4)” ; [from the product label](b)(4)“(b)(4)” [from the product label](b)(4)“(b)(4)” [from the product label](b)(4)“(b)(4)” [from the product label](b)(4)“(b)(4)” [from the product label]Unapproved New Drug ViolationsBased on the above labeling evidence,(b)(4)are intended for use as combination topical first aid antiseptic and external analgesic drug products, among other intended uses. As described below, these drug products are unapproved new drugs marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).A drug product is a “new drug” within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), if it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. With certain exceptions not applicable here, a new drug may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a). No FDA-approved applications pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, are in effect for the drug products identified above.Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application —commonly referred to as "over-the-counter (OTC) monograph drugs"—may be legally marketed if they meet applicable requirements. With respect to nonprescription combination first aid antiseptic and external analgesic drug products, such as your(b)(4), in order to be GRASE and not new drugs, the products must, among other things, conform to the conditions in the applicable OTC monographs, here M003: First Aid Antiseptic Drug Products for Over-the-Counter Human Use (henceforth “M003”) and M017: External Analgesic Drug Products for Over-the-Counter Human Use (henceforth “M017”).1However,(b)(4)do not conform to the conditions specified in M003 and M017 for the reasons described below.The name of(b)(4)includes “(b)(4)” and the label contains statements such as, “(b)(4),” and the “Uses” section of the drug facts panel includes the statement, “for help in control of(b)(4).” Likewise, the name of(b)(4)includes “(b)(4)” and the label contains statements such as, “Aids in control of(b)(4),” and the “Uses” section of the drug facts panel includes the statement, “for help in control of(b)(4).” These intended use claims are not permitted under either M003 or M017 and go beyond describing the general intended uses for a first aid antiseptic or an external analgesic drug product.(b)(4)is labeled to contain the active ingredients(b)(4), and(b)(4)in its formulation. However, this product does not conform to the conditions in M003 or M017, whether as a first aid antiseptic or as an external analgesic drug product. Specifically, this combination of active ingredients is not permitted under either M003.20 nor M017.20. Furthermore,(b)(4), which you label as topical anesthetic in your Drug Facts, is not a permitted external analgesic active ingredient under M017.10(a). In addition, the concentration of the active ingredient of(b)(4), which is labeled at(b)(4), is more than the allowed concentration of(b)(4)for a first aid antiseptic drug product under M003.10(d).Thus, your(b)(4), and(b)(4)products do not comply with the applicable conditions specified in M003 and M017 and have not otherwise been found GRASE.2 Accordingly, these products are new drugs within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), and there is no basis under section 505G of the FD&C Act under which these products would be legally marketed without an approved application. Because there is no application in effect for these products, they are unapproved new drugs.The introduction or delivery for introduction of such unapproved new drug products into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Misbranded Drug Violations(b)(4)and(b)(4)are misbranded under section 502(f)(1) of the FD&C Act, 21U.S.C. 352(f)(1) because the product labels fail to include all applicable directions for use required under M003.50(d). For example, the directions section for(b)(4)and(b)(4)do not include, “(b)(4)a small amount of this product on the area 1 to 3 times daily,” “May be covered with a sterile(b)(4),” and “If(b)(4), let dry first,” as required by M003.50(d)(4),(5), and (6).(b)(4)and(b)(4)are further misbranded under section 502(f)(2) of the FD&C Act, 21U.S.C. 352(f)(2), because their labeling do not “[bear]…such adequate warnings against use in those pathological conditions or by children where its use may be dangerous to health, or against unsafe dosage or methods or duration of administration or application, in such manner and form, as are necessary for the protection of users….” Here, the warning described in M003.50(c)(1)(ii), “Stop use and ask a doctor if the condition persists or gets worse. Do not use longer than 1 week unless directed by a doctor,” is required for first aid antiseptic drug products, such as your(b)(4)products, to be legally marketed under section 505G of the FD&C Act. This monograph warning also falls within the scope of the warnings described in section 502(f)(2) of the FD&C Act. Thus, omission of this monograph warning from the products’ labeling renders the products misbranded under section 502(f)(2).Additionally,(b)(4), and(b)(4)are misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because these products are nonprescription drugs subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but do not comply with the requirements for marketing under that section and are not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Repeat Violations at FacilityIn previous inspections, FDA cited similar CGMP violations. You proposed specific remediation for these violations in your response. Repeated failures demonstrate that executive management oversight and control over the manufacture of drugs is inadequate.CGMP Consultant RecommendedBased upon the nature of the violations we identified at your firm, you should engage a consultant qualified as set forth in 21 CFR 211.34 to evaluate your operations and to assist your firm in meeting CGMP requirements. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your CAPAs before you pursue resolution of your firm’s compliance status with FDA.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 1037559 and ATTN: Yvette Johnson.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research/S/Tina SmithCaptain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and Research____________________1M003 reflects the conditions set forth in the relevant final order(s) established and in effect under section 505G; see Order ID OTC000030, available at FDA’s website OTC Monographs@FDA [https://dps.fda.gov/omuf/ordersearch] M017 reflects the conditions set forth in the relevant final order(s) established and in effect under section 505G; see Order ID OTC000033, available at FDA’s website OTC Monographs@FDA [https://dps.fda.gov/omuf/ordersearch]2FDA is not aware of any adequate and well-controlled clinical trials in the published literature that support a determination that(b)(4), and(b)(4)are GRASE for use under the conditions prescribed, recommended, or suggested in their labeling, nor has FDA determined these drug products to be GRASE pursuant to an order issued under section 505G(b).

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDReference #:320-25-116Product:Drugs、Over-the-Counter DrugsRecipient:Mr. Alex D. DalivaPresidentCreative Essences, Inc.15320 Cornet StreetSanta Fe Springs,CA90670-5532United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-116September 25, 2025Dear Mr. Daliva:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, Creative Essences, Inc., FEI 3006349554, at 15320 Cornet St., Santa Fe Springs, from March 19 to 25, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).In addition, the “(b)(4)” drug product is an unapproved new drug introduced or delivered for introduction into interstate commerce in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d). Additionally, this product is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee). Introduction or delivery for introduction of a misbranded drug product into interstate commerce is prohibited under section 301(a) of the FD&C Act, 21 U.S.C. 331(a). These violations are described in more detail below.We reviewed your April 15, 2025, response to our Form FDA 483 in detail.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to thoroughly investigate any unexplained discrepancy or failure of a batch or any of its components to meet any of its specifications, whether or not the batch has already been distributed (21 CFR 211.192).Your firm is a manufacturer of over-the-counter (OTC) drugs for oral, nasal, rectal, and topical use. Your firm’s investigations into unexplained discrepancies are inadequate. Your quality unit (QU) failed to thoroughly investigate all finished product batches and components associated with unexplained discrepancies. When an investigation was performed, you failed to identify the root cause(s), implement appropriate corrective action and preventive action (CAPA), and expand the investigation to evaluate the impact on other batches or products. For example:Your QU did not investigate an out-of-specification (OOS) identification test for an incoming lot of active pharmaceutical ingredient (API), benzocaine, that was subsequently used to manufacture(b)(4)released(b)(4)drug product lots.Your QU failed to adequately investigate multiple microbial OOS results from your(b)(4)water system which is used as a component in your drug products.Your QU failed to adequately investigate multiple OOS stability failures (pH and viscosity) for a released batch of Nutrascreen Color Balanced SPF30 sunscreen.In your response, you state you will ensure that QU personnel provide the disposition for each component per the raw material specification sheet. You also state that there was a sampling error by the technician and because there were no OOS results in the finished product, you did not investigate the water system failures any further. Although your response indicates you opened a CAPA for the sunscreen stability failures, it does not appear you have initiated an investigation or actions to address the deficiency.Your response is inadequate. The completed investigations in your response are not sufficiently thorough and lack sufficient scientific justification to support your identified root cause. You also fail to provide supporting documentation or sufficient details about the CAPAs to ensure they will be effective in resolving the deficiency. Additionally, you fail to provide a retrospective review of all manufacturing and laboratory investigations.In response to this letter, provide:A comprehensive, independent assessment of your overall system for investigating deviations, discrepancies, complaints, OOS results, and failures. Provide a detailed action plan to remediate this system. Your action plan should include, but not be limited to, significant improvements in investigation competencies, scope determination, root cause evaluation, CAPA effectiveness, QU oversight, and written procedures. Address how your firm will ensure that all phases of investigations are appropriately conducted.An independent assessment and remediation plan for your CAPA program. Provide a report that evaluates whether the program includes effective root cause analysis, ensures CAPA effectiveness, analyzes investigation trends, improves the CAPA program when needed, implements final QU decisions, and is fully supported by executive management.2. Your firm failed to establish laboratory controls that include scientifically sound and appropriate specifications, standards, sampling plans, and test procedures designed to assure that components, drug product containers, closures, in-process materials, labeling, and drug products conform to appropriate standards of identity, strength, quality, and purity (21 CFR 211.160(b)).You lacked appropriate sampling and testing to ensure your drug products conform to appropriate standards of identity, strength, quality, and purity. For example, you failed to establish adequate procedures for finished drug product sampling to ensure adequate representation of each batch. Also, there were multiple instances where required finished drug product samples were either not taken or taken but not appropriately tested.Furthermore, your firm failed to demonstrate that your microbiological test methods were appropriate. Specifically, you could not provide evidence to demonstrate method suitability for microbiological tests used to test samples from your water system and finished drug products.In your response, you state that the laboratory technician pulled samples primarily based “by memory” and that you will send retains for testing. You also state your “investigation is underway” and due to resource issues, you will address this after implementing related CAPA regarding the microbiological testing deficiencies.Your response is inadequate. You do not provide sufficient detail or adequate evidence of corrective actions (e.g., protocol or procedure). You also do not provide a timeline for verification of the methods or describe your plans for testing in the interim. Furthermore, you do not address whether a retrospective impact assessment would be performed for previously distributed drug products that are still within expiry.The ability of microbial testing methods to detect objectionable microorganisms in the presence of each drug product must be established and validated. Results generated using unverified or unvalidated methods may put consumers at risk.In response to this letter, provide:A comprehensive independent assessment of your laboratory practices, procedures, methods, equipment, documentation, and analyst competencies. Based on this review, provide a detailed plan to remediate and evaluate the effectiveness of your laboratory system.A list of chemical and microbial specifications, including test methods, used to analyze each lot of your drug products before a lot disposition decision.An action plan and timelines for conducting full chemical and microbiological testing of retain samples to determine the quality of all batches of drug product distributed to the United States that are within expiry as of the date of this letter.A summary of all results obtained from testing retain samples from each batch. If such testing reveals substandard quality drug products, take rapid corrective actions, such as notifying customers and product recalls.3. Your firm failed to conduct at least one test to verify the identity of each component of a drug product. Your firm also failed to validate and establish the reliability of your component supplier’s test analyses at appropriate intervals (21 CFR 211.84(d)(1) and 211.84(d)(2)).You failed to conduct adequate identity testing on incoming components, including APIs, used in the manufacture of your drug products. For example, you failed to adequately test each shipment of each lot of glycerin and propylene glycol for identity, components at higher risk for diethylene glycol (DEG) and ethylene glycol (EG) contamination. Identity testing for glycerin, propylene glycol, and certain other high-risk drug components includes a limit test in the United States Pharmacopeia (USP) to ensure that the component meets the relevant safety limits for levels of DEG or EG. Because you did not perform adequate identity testing on each shipment of each lot using the USP identification test that detects these hazardous impurities, you failed to assure the acceptability of these components for use in manufacture of your drug product.The use of ingredients contaminated with DEG or EG has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance documentTesting of Glycerin, Propylene Glycol, Maltitol Solution, Hydrogenated Starch Hydrolysate, Sorbitol Solution, and Other High-Risk Drug Components for Diethylene Glycol and Ethylene Glycolto help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for DEG or EG contamination at https://www.fda.gov/media/167974/download.In addition, you relied on your suppliers’ certificates of analysis (COA) without establishing the reliability of each of your component suppliers’ analyses at appropriate intervals.In your response, you state you have validated the suppliers’ COA for some of your active ingredients and you will submit samples of your glycerin and propylene glycol raw material in stock for testing.Your response is inadequate because it does not indicate you will perform the required testing for each lot of incoming raw materials, nor does it provide sufficient details on how you will establish the reliability of your component suppliers’ COAs at appropriate intervals. Furthermore, your response lacks a retrospective review, analysis, and risk assessment for previously distributed drug products that are within expiry.Without adequate testing and confirmation of reliability of supplier test results, you lack scientific evidence that the components or drug products conform to appropriate specifications prior to use in the drug products you manufacture.In your response to this letter, provide:A commitment to provide DEG and EG test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of DEG and EG.A full risk assessment for drug products that are within expiry which contain any ingredient at risk for DEG or EG contamination (including, but not limited to, glycerin). Take prompt and appropriate actions to determine the safety of all lots of the components and any related drug product that could contain DEG or EG, including customer notifications and product recalls for any contaminated lots. Identify additional appropriate CAPA that secure supply chains in the future, including, but not limited to, ensuring that all incoming raw material lots are from fully qualified manufacturers and free from unsafe impurities. Detail these actions in your response to this letter.A description of how you will test each component lot for conformity with all appropriate specifications for identity, strength, quality, and purity. If you intend to accept any results from your supplier’s COA instead of testing each component lot for strength, quality, and purity, specify how you will robustly establish the reliability of your supplier’s results through initial validation as well as periodic revalidation. In addition, include a commitment to always conduct at least one specific identity test for each incoming component lot. In the case of glycerin, propylene glycol, and certain additional high-risk components we note that this includes the performance of parts A, B. and C of the USP monograph.The chemical quality control specifications you use to test each incoming lot of high-risk drug components to determine acceptability for use in manufacturing.A comprehensive, independent review of your material system to determine whether all suppliers of components, containers, and closures are each qualified and the materials are assigned appropriate expiration or retest dates. The review should also determine whether incoming material controls are adequate to prevent use of unsuitable components, containers, and closures.A summary of your program for qualifying and overseeing contract facilities that test the components you use to manufacture your drugs.A summary of results obtained from testing all components to evaluate the reliability of the COA from each component manufacturer. Include your SOP that describes this COA validation program.4. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).You lacked process validation data to demonstrate you have adequately validated your manufacturing processes used to manufacture your OTC drug products and to demonstrate your processes are reproducible and controlled to consistently yield drugs of uniform character and quality.In your response, you acknowledge that no actions or solutions have been implemented for this deficiency.Your response is inadequate. You did not provide a timeframe for completion of process validation activities for each of your drug products, nor did you provide your interim plans for any drugs distributed before validation activities are completed to ensure you produce drug products of acceptable quality.Process validation evaluates the soundness of design and state of control of a process throughout its lifecycle. Each significant stage of a manufacturing process must be designed appropriately and assure the quality of raw material inputs, in-process materials, and finished drugs. Process qualification studies determine whether an initial state of control has been established. Successful process qualification studies are necessary before commercial distribution. Thereafter, ongoing vigilant oversight of process performance and product quality is necessary to ensure you maintain a stable manufacturing operation throughout the product lifecycle. See FDA’s guidance for industry,Process Validation: General Principles and Practicesfor general principles and approaches that the FDA considers appropriate elements of process validation at https://www.fda.gov/media/71021/download.Additionally, based on inspection findings, it is unclear whether you had the ability to demonstrate that your water system was in a state of control due to inadequate qualification, inadequate sanitization, and inadequate monitoring. You use water as a component in your drug products and for equipment cleaning.Water for pharmaceutical purposes must be suitable for its intended use and routinely tested to ensure ongoing conformance with appropriate chemical and microbiological attributes. The lack of adequate validation provides no assurance the system performs as intended and subsequent use of deionized water in pharmaceutical manufacturing can adversely affect drug product quality and patient safety.In response to this letter, provide:A detailed summary of your validation program for ensuring a state of control throughout the product lifecycle, along with associated procedures. Describe your program for process performance qualification and ongoing monitoring of both intra-batch and inter-batch variation to ensure a continuing state of control.A timeline for performing process performance qualification for each of your marketed drug products.Process performance protocol(s), and written procedures for qualification of equipment and facilities.A detailed program for designing, validating, maintaining, controlling and monitoring each of your manufacturing processes that includes vigilant monitoring of intra-batch and inter-batch variation to ensure an ongoing state of control. Also, include your program for qualification of your equipment and facility.A procedure for your water system monitoring that specifies routine microbial testing of water to ensure its acceptability for use in each batch of drug products produced by your firm.The current action/alert limits for total counts and objectionable organisms used for your purified water system. Ensure that the total count limits for your(b)(4)water are appropriately stringent in view of the intended use of each of the products produced by your firm.A procedure governing your program for ongoing control, maintenance, and monitoring that ensures the remediated system consistently produces water that meets(b)(4)Water, USP monograph specifications and appropriate microbial limits.5. 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 firm failed to establish an adequate QU with the responsibilities and authority to oversee the manufacturing of drug products. For example, your QU failed to ensure:Establishment of procedures describing roles and responsibilities of the QU including, but not limited to, batch release, investigations, change control, and periodic (i.e., at least annual) product reviews (21 CFR 211.22(d)).Establishment of an adequate equipment cleaning and maintenance program for your equipment (21 CFR 211.67(b)).Establishment of an appropriate written testing program designed to assess the stability characteristics of drug products and to use results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help implementing quality systems and risk management approaches to meet the requirements of CGMP regulations 21 CFR, parts 210 and 211 at https://www.fda.gov/media/71023/download.In response to this letter, provide a comprehensive assessment and remediation plan to ensure your QU is given the authority and resources to effectively function. The assessment should also include, but not be limited to:A determination of whether procedures used by your firm are robust and appropriateProvisions for QU oversight throughout your operations to evaluate adherence to appropriate practicesA complete and final review of each batch and its related information before the QU disposition decisionOversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productsUnapproved New Drug and Misbranding Drug Violations“(b)(4)” is a “drug” as defined by section 201(g)(1)(B) of the FD&C Act, 21 U.S.C. 321(g)(1)(B), because it is intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease, and/or under section 201(g)(1)(C) of the FD&C Act, 21 U.S.C. 321(g)(1)(C), because it is intended to affect the structure or any function of the body.Examples of claims observed on the “(b)(4)” product labeling, including from the “(b)(4)” website, that provide evidence of the intended use (as defined in 21 CFR 201.128) of the product as a drug include, but may not be limited to, the following:(b)(4)(b)(4)(b)(4)(b)(4)Unapproved New Drug ViolationsBased on the above labeling evidence, “(b)(4)” is intended for use as(b)(4)topical antiseptic drug product. This product is a new drug within the meaning of section 201(p) of the FD&C Act, 21 U.S.C. 321(p), because it is not generally recognized as safe and effective (GRASE) for use under the conditions prescribed, recommended, or suggested in its labeling. New drugs may not be introduced or delivered for introduction into interstate commerce without an approved application from FDA in effect, as described in section 505(a) of the FD&C Act, 21 U.S.C. 355(a), unless they are lawfully marketed under section 505G of the FD&C Act (which is not the case for this product, as further described below) or other exceptions not applicable here. No FDA-approved application pursuant to section 505 of the FD&C Act, 21 U.S.C. 355, is in effect for this drug product, nor are we aware of any adequate and well-controlled clinical studies in the published literature that support a determination that the “(b)(4)” drug product is GRASE for use under the conditions suggested, recommended, or prescribed in its labeling. Accordingly, this product is an unapproved new drug marketed in violation of sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C 355(a) and 331(d).Under section 505G of the FD&C Act, certain nonprescription drugs marketed without an approved application—commonly referred to as “over-the-counter (OTC) monograph drugs”—may be legally marketed if they meet applicable requirements. Under section 505G(a)(3) of the FD&C Act, drugs that (prior to enactment of section 505G) were classified as Category III1for safety or effectiveness in the preamble of a tentative final monograph (TFM) that is the most recently applicable proposal or determination for such drug issued under 21 CFR Part 330—and that were not classified as Category II for safety or effectiveness – are not required to have an approved application under section 505 in order to be marketed, as long as they are in conformity with the relevant conditions of use outlined in the applicable TFM, including the active ingredient and indication, and comply with all other applicable requirements.Consumer topical antiseptics, such as your(b)(4)product, were addressed in a TFM entitled “Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Tentative Final Monograph for Health-Care Antiseptic Drug Products,” Proposed Rule, 59 FR 31402 (June 17, 1994) (hereinafter “1994 TFM”), as amended by “Safety and Effectiveness of Consumer Antiseptics; Topical Antimicrobial Drug Products for Over-the-Counter Human Use; Proposed Amendment of the Tentative Final Monograph; Reopening of Administrative Record,” Proposed Rule, 81 FR 42912 (June 30, 2016) (hereinafter “Consumer Topical Antiseptics Proposed Rule”).2In the preamble of the 1994 TFM3as well as the preamble of the Consumer Topical Antiseptics Proposed Rule (the most recent amendment of the 1994 TFM with respect to such products), three active ingredients (benzalkonium chloride—the active ingredient in your(b)(4)product—ethyl alcohol (ethanol), and isopropyl alcohol) were classified as Category III for use in consumer antiseptic rub products.4However, “(b)(4)” does not meet the conditions under section 505G(a)(3) for legal marketing without an approved application because this product does not conform to conditions applicable to consumer topical antiseptic products under the 1994 TFM, as amended by the 2016 Consumer Topical Antiseptics Proposed Rule with respect to such products. Specifically, according to the product labeling, “(b)(4)” is intended to be applied(b)(4). Under the 1994 TFM as amended by the 2016 Consumer Topical Antiseptics Proposed Rule, only consumer topical antiseptic products intended for use on the hands without water are included in the scope of consumer topical antiseptic products covered by the TFM.5Thus, consumer topical antiseptic products with the active ingredient benzalkonium chloride intended for administration(b)(4)do not conform to the conditions for consumer topical antiseptic products under the 1994 TFM, as amended by the Consumer Topical Antiseptics Proposed Rule. Accordingly, your(b)(4)product does not meet the criteria under section 505G(a)(3) for legal marketing without an approved application and thus cannot be legally marketed as an OTC monograph drug under section 505G of the FD&C Act.The introduction or delivery for introduction of this unapproved new drug product into interstate commerce violates sections 505(a) and 301(d) of the FD&C Act, 21 U.S.C. 355(a) and 331(d).Misbranded Drug ViolationsAdditionally, “(b)(4)” is misbranded under section 502(ee) of the FD&C Act, 21 U.S.C. 352(ee), because this product is a nonprescription drug subject to section 505G of the FD&C Act, 21 U.S.C. 355h, but does not comply with the requirements for marketing under that section and is not the subject of an application approved under section 505 of the FD&C Act, 21 U.S.C. 355.The introduction or delivery for introduction of a misbranded drug into interstate commerce violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Additionally, we also note that conflicting information for the(b)(4)has been provided to the Agency based on the information collected by our investigator during the inspection and the labeling submitted to FDA for drug listing in the agency’s Electronic Drug Registration and Listing System (eDRLS) in accordance with section 510 of the FD&C Act. Specifically, nonprescription oral anesthetic products containing benzocaine or butacaine sulfate as active ingredients that are marketed under section 505G of the FD&C Act are required to bear the warning, “Do not use this product if you have a history of allergy to local anesthetics such as procaine, butacaine, benzocaine, or other ‘caine' anesthetics” on the Drug Facts panel. See section M022.52(c)(4) of Over-the-Counter Monograph M022: Oral Healthcare Drug Products for Over-the-Counter Human Use. However, the labeling provided to the investigator for the(b)(4)fails to include this required warning on its labeling. Please ensure that your OTC drug products have the required warnings and statements and comply with all applicable labeling requirements.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. We note that under section 301(a) of the FD&C Act (21 U.S.C. 331(a)), it is a prohibited act to introduce or deliver for introduction into interstate commerce a cosmetic that is adulterated or misbranded.We also note that the Modernization of Cosmetics Regulation Act of 2022 (MoCRA) provides new requirements with which facilities that manufacture cosmetic products must comply. You may find the FD&C Act, MoCRA, and FDA’s regulations through links on FDA’s website at www.fda.gov.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3006349554 and ATTN: Christopher M. Jenner.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research/S/Brad Pace, J.D.Associate DirectorOffice of Unapproved Drugs and Labeling ComplianceSigned on behalf of:/S/Tina SmithCaptain, U.S. Public Health ServiceDirectorOffice of Unapproved Drugs & Labeling ComplianceOffice of ComplianceCenter for Drug Evaluation and Research_____________________1As used under the OTC monograph system prior to enactment of section 505G (and as stated at 81 FR 42912, 42915), “[t]he OTC drug procedural regulations in § 330.10 use the terms ‘Category I’ (generally recognized as safe and effective and not misbranded), ‘Category II’ (not generally recognized as safe and effective or misbranded), and ‘Category III’ (available data are insufficient to classify as safe and effective, and further testing is required)”, 81 FR 42912, 42915.2As stated in the Consumer Topical Antiseptics Proposed Rule, “The Food and Drug Administration (FDA or Agency) is issuing this proposed rule to amend the 1994 tentative final monograph or proposed rule (the 1994 TFM) for over-the-counter (OTC) antiseptic drug products. In this proposed rule, we are proposing to establish conditions under which OTC consumer antiseptic products intended for use without water (referred to throughout as consumer antiseptic rubs or consumer rubs) are generally recognized as safe and generally recognized as effective(GRAS/ GRAE)”, 81 FR 42912.3The initial 1994 TFM included but did not distinguish between and separately address consumer antiseptic washes and rubs, and health care hand washes and rubs. The Consumer Topical Antiseptics Proposed Rule amended the 1994 TFM with respect to its treatment of consumer antiseptic rubs specifically. See 81 FR 42916.481 FR 42912, 42918. The Category III designation for these active ingredients means that additional safety and effectiveness data are needed to support a determination that a drug product containing one of these active ingredients would be GRASE for use as a consumer topical antiseptic product.5As stated in the Consumer Topical Antiseptics Proposed Rule, “we refer to the group of products covered by this proposed rule as ‘consumer antiseptics.’ Consumer antiseptic drug products addressed by this proposal include consumer antiseptic hand rubs (commonly called hand sanitizers) and antiseptic wipes”, 81 FR 42912, 42915.

近日，云南省药监局发布2025年云南省医疗器械“你用我检”抽检结果通告（2025年第2期）。通告涉及一次性使用无菌注射器、一次性使用输液器、电子血压计、医用电子体温计、血糖仪、天然胶乳橡胶避孕套、医用外科口罩、医用棉签、医用纱布块、无菌创口贴等9个品种72批次产品检验结果。据悉，为持续强化医疗器械质量抽检的针对性、靶向性，保障人民群众用械安全、有效，云南省药监局于2025年年初组织开展“你用我检”活动，对公众关注的12个品种、120批医疗器械进行质量监督抽检，前期已发布了1期48批次产品抽检结果的公告。至此，120批次产品抽检结果已全部向社会公开发布。附件：2025年云南省医疗器械“你用我检”抽检情况统计表（2025年第2期）