Delivery Method:VIA UPSReference #:320-25-72Product:DrugsRecipient:Mr. Atul B. MehtaPresident, Co-Chairman, and Co-FounderAACE Pharmaceuticals, Inc.15 Gardner RoadFairfield,NJ07004United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-25-72May 13, 2025Dear Mr. Mehta:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, AACE Pharmaceuticals, Inc., FEI 3013433273, at 15 Gardner Road, Fairfield, from November 12 to 22, 2024, after an FDA inspection revealed violative conditions at Brassica Pharma Private Limited, a contract manufacturing organization (CMO) used to manufacture ophthalmic drugs for AACE Pharmaceuticals, Inc.The FDA inspection of this foreign facility revealed significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals, Title 21, Code of Federal Regulations, Parts 210 and 211 (21 CFR Parts 210 and 211), causing these drug products to be adulterated, including 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).The inspection of your facility revealed that you operated as a distributor of AACE Pharmaceuticals brand name products, including Lubricant PM Ointment. Your receipt in interstate commerce of adulterated drugs, and the delivery or proffered delivery thereof, is a violation of section 301(c) of the FD&C Act, 21 U.S.C. 331(c), and your introduction into interstate commerce of adulterated drugs violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Inspection of Your CMOAn inspection of Brassica Pharma Private Limited (“Brassica”), FEI 3014129013, conducted from January 15 to 19, 2024, revealed multiple CGMP violations, including but not limited to poor aseptic practices for the manufacture of sterile drugs; fabrication of microbiology laboratory records; microbial recoveries of incubating samples from ISO 5 manufacturing areas and sterility tests exhibiting turbidity during incubation; inadequate media fill program and airflow visualization studies; and use of ripped and visibly dirty gowning in the aseptic processing areas. These CGMP violations render the products manufactured by Brassica adulterated within the meaning of section 501(a)(2)(B) of the FD&C Act.On January 30, 2024, Brassica was placed on Import Alert 66-40 and recalled all drug products within expiry on February 22, 2024. On July 11, 2024, Brassica received a warning letter (Warning Letter #320-24-52).Receipt and Distribution of Adulterated DrugsOur inspection of your firm and review of your import records indicated that(b)(4)shipments of AACE Pharmaceuticals Lubricant PM Ointment were imported from a third-party,(b)(4), manufactured by your CMO Brassica Pharma Private Limited, received by AACE Pharmaceuticals, and further distributed to customers. Your receipt in interstate commerce of adulterated drugs, and the delivery or proffered delivery thereof, is a violation of section 301(c) of the FD&C Act, 21 U.S.C. 331(c), and your introduction into interstate commerce of adulterated drugs violates section 301(a) of the FD&C Act, 21 U.S.C. 331(a).Inspection of AACE Pharmaceuticals, Inc.We reviewed your December 11, 2024, 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 establish an adequate quality control unit with the responsibility and authority to approve or reject all components, drug product containers, closures, in-process materials, packaging materials, labeling, and drug products and the authority to review production records to assure that no errors have occurred or, if errors have occurred, that they have been fully investigated (21 CFR 211.22(a)).Your ophthalmic drug product, Lubricant PM Ointment, is intended to be sterile. Your firm utilized a CMO to manufacture your ophthalmic drug products. However, your quality unit failed to have adequate supplier qualification procedures to ensure that the drug products received from your CMO were manufactured in compliance with CGMP prior to being distributed in the United States.For example, our investigators observed that your firm identified several CGMP deficiencies with Brassica in September 2020, such as a failure to maintain raw testing data. Despite identifying these deficiencies, your firm qualified Brassica as an approved CMO. Furthermore, you requalified Brassica in 2023, without evaluating whether subsequent corrective actions and preventive actions adequately addressed the identified deficiencies.Your firm’s quality unit released Lubricant PM Ointment for distribution without adequate procedures to ensure that the ophthalmic drug products produced for your firm met appropriate quality attributes.In your response, you state that your procedures have been revised to assess CGMP findings of your CMOs, and that your Quality Assurance must evaluate corrective action and preventive action (CAPA) plans implemented by CMOs.Your response is inadequate. While you have revised your procedures, you did not provide sufficient details on how you will assess findings that include CGMP deficiencies. Your procedure lacks a process for disqualifying CMOs or maintaining disqualification across product lines. Also, you did not propose evaluating the qualification status of your other CMOs.In addition, you state that you will be comparing the data reported on the certificate of analysis (COA) against the pre-approved specification before releasing finished product. We note that your quality unit is ultimately responsible for ensuring that your drug products are manufactured in accordance with CGMP. Comparing a COA from a CMO to pre-approved specifications does not overcome your responsibility to evaluate, qualify, audit, and monitor your contract manufacturers. The suitability and competence of potential contractors should be assessed, based on quality risk management principles, before outsourcing operations, and should implement any needed improvements. Your firm should have a robust qualification process of your CMOs, commensurate with risk, ahead of making product disposition determinations based on a COA.You are responsible for ensuring that the drugs you distribute are not adulterated and are manufactured in accordance with CGMP requirements.In response to this letter, provide a detailed plan to ensure you do not receive or deliver adulterated drugs in interstate commerce, in violation of sections 301(a) and 301(c) of the FD&C Act, 21 U.S.C. 331(a) and 331(c). Items in your plan should minimally include the following:A thorough evaluation of your current CMOs’ qualification. If gaps are identified, include your plan for remediation or discontinuation of use of that CMO.A description of improvements to your procedures for qualifying your contract manufacturers to ensure that they operate in compliance with CGMP, including a plan to conduct periodic audits of your CMOs.o Provide sufficient details on how you will assess findings that include CGMP deficiencies or disqualification from use.Ophthalmic Drug Product Recall and Distribution CeasedOn January 30, 2024, you notified your customers that Brassica recalled Lubricant PM Ointment batches A2G01, A2G02, A3F08, A3F09, A3J17, and A3J18. We acknowledge that as of January 31, 2024, you commit to discontinue distributing AACE Pharmaceuticals Lubricant PM Ointment manufactured by Brassica. In response to this letter, clarify whether you intend to distribute ophthalmic or sterile drugs for the U.S. market.If you plan to distribute ophthalmic or sterile products regulated under the FD&C Act, notify this office. You are responsible for resolving all deficiencies and systemic flaws to ensure your firm and CMOs are capable of ongoing CGMP compliance. In your notification to the Agency, provide a summary of your remediations to demonstrate that you have appropriately completed all CAPA.Use of Contract ManufacturersDrugs 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 your drugs regardless of agreements in place with your contract facilities. You are required to ensure that the drugs you deliver into interstate commerce are not adulterated. See FDA’s guidance documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.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 assist your firm in meeting CGMP requirements.Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3013433273 and ATTN: Sena G. Dissmeyer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Delivery Method:Via EmailProduct:Medical DevicesRecipient:S. Manuel Martinez GarcíaPresident and CEOSedecal S.A.C/Pelaya, 9-13 Pol Industrial Rio De Janeiro28110ALGETEMadridSpainmmartinez@sedecal.commmartinezjr@sedecal.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERMay 5, 2025Dear Mr. Martinez García:During an inspection of your firm located in Madrid, Spain on January 20, 2025, through January 24, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures DX-D 100, DX-D 600, and MobileDiagnost wDR systems. 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 function of the body.This inspection revealed that these devices are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,Code of Federal Regulations(CFR), Part 820. We received a response from Maria Luisa Gomez de Aguero, Director of Quality and Regulatory Affairs dated February 14, 2025, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to adequately establish and maintain procedures for implementing corrective and preventative action (CAPA), as required by 21 CFR 820.100(a). Specifically, your firm initiated CAPA 20/028 to address customer complaints reporting DXD100 mobile x-ray units self-propelling crashing into x-ray control panel in one case and almost running into the patient, in the other case. This issue affects all mobile x-ray unit models. However, your firm failed to document an assessment of the risk of the affected units in the field for this issue, when investigating the cause of nonconformities relating to the product.We reviewed your response and conclude that the adequacy of your firm’s response cannot be determined at this time. You stated that you will revise procedures PG-031 Customer complaint and PG-020 Risk management procedures to ensure that an investigation is documented properly. You also stated that you will revise procedure PG-019 Corrective and Preventive action and conduct training for the relevant personnel. Although your firm’s response states you will revise the relevant procedures, the revised procedures were not included in the response for evaluation. Your firm’s response does not include a retrospective review of related documentation to ensure compliance with the updated procedures and how these will be implemented moving forward. Documentation of corrective action, retrospective review as well as training is needed in order to adequately address this observation.2. Failure to adequately establish and maintain procedures for validating the device design, as required by 21 CFR 820.30(g). Design validation shall include risk analysis, where appropriate. Specifically, your firm conducted a recall to address unintended movement of MobileDiagnost wDR that could result in life threatening situations and cause the device to stop working as intended. However, the risk analysis for MobileDiagnost wDR (Document IH0532RA_Annex, dated April 26, 2022) fails to include this increased hazard severity (life threatening) to ensure that appropriate risk control measures are implemented.We reviewed your response and conclude that the adequacy of your firm’s response cannot be determined at this time. Your response states that you will re-evaluate and document the risk analysis for the recall. You also state that you will revise procedures PG-031 Customer complaint and PG-020 Risk management procedures to account for risk analysis. Although your firm’s response states you will revise the relevant procedures, the revised procedures were not included in the response for evaluation. Your firm’s response does not include a retrospective review of related documentation to ensure compliance with the updated procedures and how these will be implemented moving forward. Documentation of corrective action, retrospective review as well as training is needed in order to adequately address this observation.Our inspection also revealed that your firm’s DX-D100 devices are misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), in that your firm failed or refused to furnish material or information respecting the device that is required by or under section 519 of the Act, 21 U.S.C. § 360i, and 21 CFR Part 806 – Medical Device; Reports of Corrections and Removals. Significant violations include, but are not limited to, the following:3. Failure to submit a written report of a correction or removal of a device to FDA, initiated to reduce a risk to health or to remedy a violation which may present a risk to health, as required by 21 CFR 806.10. Specifically, your firm initiated CAPA 20/028 to address customer complaints reporting DXD100 mobile x-ray units self-propelling crashing into x-ray control panel in one case and almost running into the patient, in the other case. This issue affects all mobile x-ray unit models. Your firm implemented two corrective actions to address this issue and issued a service note to be distributed to customers. However, your firm failed to submit a report of correction or removal to FDA for these actions.We reviewed your response to Observation 1 and conclude it is not adequate. Your investigation of the issue concluded that this issue does not pose a risk to safety due to the low speed of the movement and did not consider it as a reportable recall. However, your firm implemented two corrections to address this issue and issued a service note to be distributed to the customers. Our assessment concluded that the unintended movement presents a risk to health and your firm’s actions were initiated to reduce the risk to health.Your firm’s devices are also electronic products subject to compliance with Subchapter C of the Act, Electronic Product Radiation Control, the requirements at 21 CFR 1000-1005, and the performance standards at 21 CFR 1020.30 and 1020.31. Your firm failed to comply with the regulations regarding reporting and recordkeeping.4. Failure to conduct certification of an electronic product, based upon a testing program which is in accordance with good manufacturing practices, as required by 21 CFR 1002.30(a)(1). Specifically, a review of the design control records revealed that the wDR2.2 was approved and released for distribution in the US without documentation to show that the required performance standard checklist (Technical Report Subchapter J of 21 CFR MobileDiagnost wDR 2.2, Doc #R01005_21CKL) was completed to demonstrate compliance with the performance standard requirements prior to release of the product. The performance standard checklist was not completed until Jan. 14, 2025.We reviewed your response and conclude that the adequacy of your firm’s response cannot be determined at this time. You stated that you will review and revise procedures PE-062 Design Verification, PG-044 Organization of Project Teams among others. Although your firm’s response states you will revise the relevant procedures, the revised procedures were not included in the response for evaluation. Your firm’s response does not include a retrospective review of related documentation to ensure compliance with the updated procedures. Documentation of corrective action, retrospective review as well as training is needed in order to adequately address this observation.Other federal agencies may take your compliance with the FD&C Act and its implementation 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.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, including 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 action (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. Please provide a translation of documentation not in English to facilitate our review. We will notify you regarding the adequacy of your firm’s responses and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made. 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 CDRHWarningLetterResponses@fda.hhs.gov. Refer to CMS case 707156 when replying. If you have any questions about the contents of this letter, please contact: Lu Jiang at +1(240)402-5779.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 yours,/S/Robert Ochs, Ph.D.DirectorOHT8: Office of Radiological HealthOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCC:Devan MoserU.S. AgentSedecal USA Inc.7555 N. Caldwell AvenueNiles, Illinois 60714dmoser@sedecalusa.com

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Jörg SchlöβerManaging DirectorDRG Instruments GmbHFrauenbergstr. 18Marburg35039HassiaGermany(b)(6)@drg-diagnostics.deIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERMarch 31, 2025Dear Mr. Schlöβer:During an inspection of your firm located in Marburg, Germany on November 4 through 7, 2024, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures in vitro diagnostic devices including the Salivary Cortisol ELISA (REF No. SLV-2930), the Salivary Testosterone ELISA, and the Salivary Cortisol ELISA RUO (REF No. SLV-2930R). 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 evidence collected during the inspection and your firm’s website and determined that the Salivary Cortisol ELISA (REF No. SLV-2930) and Salivary Cortisol ELISA RUO (REF No. SLV-2930R) 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). The Salivary Cortisol ELISA and Salivary Cortisol ELISA RUO 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 these devices into commercial distribution, with major changes or modifications to the intended use, without submitting a new premarket notification to FDA as required by section 510(k) of the Act, 21 U.S.C. § 360(k).Salivary Cortisol ELISAYou currently have clearance dated December 7, 2005, for a version of the Salivary Cortisol ELISA which was cleared under K051733 as a class II device under 21 CFR 862.1205 with the following indications:“An enzyme immunoassay for the quantitative in vitro diagnostic measurement of active free cortisol (hydrocortisone and hydroxycorticosterone) in saliva. Measurements of cortisol are used in the diagnosis and treatment of disorders of the adrenal gland.”However, as discussed in FDA’s Warning Letter dated September 19, 2017 issued to your firm, your firm has failed to submit a premarket notification submission to the Food and Drug Administration for significant changes that could significantly affect the safety or effectiveness of the device, as required by 21 CFR 807.81(a)(3)(i). As discussed in the 2017 Warning Letter, a new 510(k) is needed due to the use of a new monoclonal (mouse) antibody for the Salivary Cortisol ELISA. In addition, a new 510(k) is needed because of the change to the assay measuring range. As described in the FDA’s Decision Summary, the device that was reviewed and cleared by FDA under K051733 included 8 wells coated with rabbit anti-cortisol antiserum and had an assay measuring range of 0.537 - 80 ng/mL. However, the package insert of the IVD-labeled Salivary Cortisol ELISA obtained during the 2024 inspection is described as containing microtiter wells that are coated with a monoclonal (mouse) antibody and the assay measuring range is described as 0.09 – 30 ng/mL. The modified measuring range is narrower than the clinically relevant range. This change raises concerns that some patient samples with salivary cortisol higher than 30 ng/mL may yield inaccurate results using the new assay which could place patients with normal cortisol levels at increased risk of misdiagnosis (e.g. elevated cortisol may be an indicator of Cushing Syndrome) or could lead to missed diagnosis of Cushing Syndrome if results are erroneously low. Such changes could significantly impact the safety and effectiveness of the device because such devices are often used in people with cortisol levels greater than 30 ng/mL. Your firm was notified in the 2017 Warning Letter that the Salivary Cortisol ELISA devices manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated and that, as a result, FDA was taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations were corrected. To date, your firm has not received 510(k) clearance for your Salivary Cortisol ELISA devices that incorporate this significant change.Salivary Cortisol ELISA RUOThe inspection revealed that your firm also markets and distributes the Salivary Cortisol ELISA RUO. Based on labeling collected during FDA’s inspection, the Salivary Cortisol ELISA RUO, like the Salivary Cortisol ELISA for in vitro diagnostic use, is designed to include monoclonal mouse antibodies and has an assay measuring range of 0.09 - 30 ng/mL. Specifically, your firm's website www.drg-international.com describes the Salivary Cortisol ELISA RUO as “an enzyme immunoassay for the quantitative in vitro diagnostic measurement of active free cortisol (hydrocortisone and hydroxycorticosterone) in saliva.”Based on evidence obtained during the inspection and a review of your firm’s website, the Salivary Cortisol ELISA RUO appears intended for clinical diagnostic use instead of for research use only. Such evidence includes:Your firm’s website includes product descriptions, images, and statements that suggest the Salivary Cortisol ELISA RUO device is intended for clinical diagnostic use. [https://store.drg-international.com/pc_product_detail.asp?key=2EAFBB068F3341EF8772F433DA7255B4]. For example:o A statement on your firm’s product page for the Salivary Cortisol ELISA RUO says that the “intensity of colour developed is inversely proportional to the concentration of cortisol in the patient sample.”Labeling collected during the inspection which your firm distributes with the Salivary Cortisol ELISA RUO device includes information that appears to conflict with RUO and suggests the device is actually intended for clinical diagnostic use despite the RUO labeling. For example:o The instructions for use that your firm distributes with the Salivary Cortisol ELISA RUO contains a specimen collection and preparation section that describes how samples should be collected from individuals (e.g. “Eating, drinking, chewing gums or brushing teeth should be avoided for 30 minutes before sampling.”) and gives directions on how saliva samples should be collected and over what time period to collect samples from individuals. The instructions for use also contain a Quality Control section which notes that “[a] statistically significant number of controls should be assayed to establish mean values and acceptable ranges to assure proper performance” and that users should ensure that assay results fit the established range of control materials or else be considered invalid. This type of language is typically included for IVDs that are intended for clinical diagnostic use, as this type of information is consistent with the prospective testing of patients and is not the type of information that is necessary for an assay in the laboratory research phase of development.A review of the customer records collected during the 2024 inspection shows that your firm sold and shipped Salivary Cortisol ELISA RUO to multiple companies in the business of performing clinical analysis. There is no indication that these companies also conduct research.Your firm’s website (last accessed March 11, 2025) https://drg-international.com/salivary-elisa-kits/ describes the Salivary Cortisol ELISA RUO, along with other Salivary ELISA Kits, as having clear advantages, including:o “Simple, painless collection”o “Simple and patient-friendly measurement of hormone profiles”o “Can be performed also by patients”o “Easy sampling in babies and kids”o “Provides accurate, low level detection”o Clinical applications such as: “Diagnosis of systemic/local conditions” Obstetrics & Gynecology” “Drug Monitoring”Your firm’s website also provides a comparison of the Salivary Cortisol ELISA RUO to a reference test and states it provides “Industry Leading Accuracy with Kit Components Calibrated to Mass Spectrometry,” which implies that the Salivary Cortisol ELISA RUO is intended for clinical diagnostic use and not for research use only.In addition, during the inspection, your firm provided to the FDA investigator copies of certification letters from certain customers of the Salivary Cortisol ELISA RUO as evidence that these customers were aware that they were only supposed to use these products for research purposes. However, your firm admitted no such certification letter was received from one customer. A review of these customers’ websites strongly suggests that these customers are engaged in clinical diagnostic testing. As such, your statements that Salivary Cortisol ELISA RUO is intended for research use only are inconsistent with the evidence obtained during the inspection and the statements on your firm’s website, and FDA has determined that your Salivary Cortisol ELISA RUO is intended for clinical diagnostic use.Your Salivary Cortisol ELISA RUO appears to be intended for the quantitative in vitro diagnostic measurement of active free cortisol (hydrocortisone and hydroxycorticosterone) in saliva. You were required to submit to FDA a 510(k) for this device, because either it is a new device (21 CFR 807.81(a)(1)) or, if your Salivary Cortisol ELISA RUO represents a change or modification from the device cleared in K051733, it has been significantly changed or modified in design, components, method of manufacture, or intended use (21 CFR 807.81(a)(3)). For a device requiring premarket approval, the notification required by section 510(k) is deemed satisfied when a PMA is pending before the agency [21 CFR 807.81(b)]. The kind of information that your firm needs to submit in order to obtain approval or clearance for the device is described on the Internet at http://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/HowtoMarketYourDevice/default.htm. The FDA will evaluate the information that your firm submits and decide whether the product may be legally marketed.Separately, we also note that your firm’s website includes a tab called “FDA Cleared Tests” (https://drg-international.com/) and lists several devices for which there is no record of a 510(k) clearance held by your firm. For example, a Thyroid Stimulating Hormone (TSH) assay for in vitro diagnostic use is included on your firm’s website. However, a review of our records indicates that DRG Instruments does not have a 510(k) for a TSH assay. FDA requests that you review those devices listed under the “FDA Cleared Tests” tab on your website and either provide FDA with evidence that those devices are legally marketed or take corrective actions to address any additional uncleared devices marketed on your website.Further, during our review of your firm’s website (https://drg-international.com/hybrid-xl/) we also noted that your firm states that DRG Hybrid XL is “Now FDA Approved” but also separately indicates that the DRG Hybrid XL is “FDA exempt for Class I.” We request that you clarify this statement on your website because indicating that a class I 510(k) exempt product has been reviewed and approved by FDA could be misleading. We request that your firm address these two additional issues in your response to this Warning Letter.Quality System Regulation (QSR) ViolationsThis inspection also revealed that the devices manufactured in your facility are adulterated within the meaning of section 501(h) of the Act, 21 U.S.C. § 351(h), in that the methods used in, or the facilities or controls used for, their manufacture, packing, storage, or installation are not in conformity with the current good manufacturing practice requirements of the Quality System regulation found at Title 21,Code of Federal Regulations(CFR), Part 820. We received a response from Ina Hairston, U.S. Agent, DRG Instruments GmbH and Head of Regulatory Affairs, DRG International, Inc. dated November 26, 2024 concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, CAPA No. 2024-14 was initiated July 1, 2024 due to a customer complaint of the low-level quality control for their Salivary Testosterone ELISA being invalid. However, your firm did not adequately investigate the cause of the nonconformity. Your firm confirmed the complaint by testing the remaining kits in inventory from two lots and found 21.3% (17 out of 80 bottles) of the low controls were out-of-specification (OOS). Your firm determined that the cause was due to the operator not washing the filling tube, nor discarding the first ten bottles, after switching from a higher to lower concentration of bulk solution, which were typical but not defined in the manufacturing procedure. Your firm's corrective action was to revise procedure aa-9131 to define a rinsing step and to require discarding of the first 20 bottles. However, the determined root cause of incomplete rinsing instructions does not demonstrate how such a lack of written procedures would reasonably be expected to result in 21.3% of retained low controls being OOS. Further, during the inspection, Mr. Polleichtner, Head of Quality Management & Regulatory Affairs, indicated that there may be additional causes for the nonconformity and that your firm did not confirm that the operator failed to perform the rinse and discard step.The adequacy of the response dated November 26, 2024 cannot be determined at this time. Your firm has opened CAPA# 2024-22 and planned the following actions:update of root cause analysis for CAPA 2024-14 by December 20, 2024;review of all open CAPAs and all CAPAs which actions are completed, but the effectiveness check is still pending regarding comprehensive root cause analysis by January 31, 2025; andupdate CAPAs identified to have inadequate root cause analysis to update the process of determining the root cause and affirm the root cause by February 28, 2025.Your firm should provide an update on the above actions, including evidence of implementation. Copies of revised procedures and evidence of training on new or revised procedures should also be provided. Additionally, your firm should provide a summary of the results of their retrospective review.2. Failure to adequately maintain records of complaint investigations that include required information, according to 21 CFR 820.198(e). For example, records of complaint investigations do not include required information, including any unique device identifier (UDI) or universal product code (UPC). Your firm's complaint records consistently did not include adequate contact information for the complainant, to include telephone number and address, and consistently did not include the Unique Device Identifier (UDI) code for the device which was the subject of the complaint. Specifically, complaint records for Complaint Nos. 47 and 49 do not list the complainant’s telephone number, complainant’s address, or the UDI code for the device.The adequacy of your firm's response dated November 26, 2024 cannot be determined at this time. Your firm has opened CAPA# 2024-24 and planned the following actions:add UDI and contact information to all open complaint files by December 15, 2024;review of the complaint handling process and form regarding conformity with applicable regulations (EN ISO 13485, 21 CFR, IVDR) by December 15, 2024;file a change request based on finding(s) of complaint review process. At minimum, the requirement to provide the UDI/UPC and complete customer contact information with every complaint is required by December 15, 2024;inform and provide immediate information to the complaint-handling personnel emphasizing the importance of recording complete information;review of Medical Device Single Audit Program (MDSAP) guidance documents, as these outline US-specific requirements, and are based on EN ISO 13485 by December 31, 2024;request implementation of gaps identified to the MDSAP guidance if applicable by January 10, 2025; andtrain revised documentation as required by January 31, 2025.Your firm should provide an update on the above actions, including evidence of implementation. Copies of revised procedures and evidence of training on new or revised procedures should also be provided.Medical Device Reporting (MDR) ViolationsOur inspection also revealed that you have failed to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17. For example: during the inspection, your firm identified the document titled “Reporting to Regulatory Authorities (and recall), Document aa-8.2.3.1, Revision 1, undated,” as its written MDR procedure. After reviewing the procedure, the following deficiencies were noted:There is no evidence that the procedure has been implemented. For example, there is no effective date for your firm’s MDR procedure.The procedure does not establish internal systems that provide for timely and effective identification, communication, and evaluation of events that may be subject to MDR requirements, as required by 21 CFR 803.17(a)(1). For example:o The definition of the term “Reportable Event” in section 5 of your firm’s procedure only focuses on whether the device at issue would be likely to cause or contribute to a death or serious injury if the malfunction were to recur and does not include a consideration of whether a similar device marketed by your firm would be likely to cause or contribute to a death or serious injury if the malfunction were to recur, as required in 21 CFR 803.3(o)(2)(ii).o The procedure does not include instructions for how your firm will evaluate information about an event to make MDR reportability determinations in a timely manner.The procedure does not establish internal systems that provide for timely transmission of complete medical device reports, as required by 21 CFR 803.17(a)(3). Specifically, the following are not addressed:o Instructions for how to obtain and complete the FDA 3500A form.o The circumstances under which your firm must submit an initial 30 days, supplemental or follow-up, 5-day report and the requirements for such reports.o How your firm will submit all information reasonably known to it for each event. Specifically, which sections of 3500A will need to be completed to include all the information found in your firm’s possession and any information that becomes available as a result of a reasonable follow-up within your firm.The procedure does not describe how your firm will address documentation and record-keeping requirements, as required by 21 CFR 803.17(b), including:o Information that was evaluated to determine if an event was reportable.o Documentation of the deliberations and decision-making processes used to determine if a device-related death, serious injury, or malfunction was or was not reportable.o Systems that ensure access to information that facilitate timely follow-up and inspection by FDA.Your firm’s procedure includes references to annual certifications. We note that annual certifications are no longer required, and we recommend that all references to an Annual Certification be removed from your firm’s MDR procedure. See 65 Fed. Reg. 4112 (Jan. 26, 2000). Furthermore, the procedure includes references to submit paper MDR reports. Please note, paper reports are generally no longer accepted from manufacturers and importers. See 21 CFR 803.11(a). The manufacturer is generally required to electronically submit MDRs following its established electronic submission process. 21 CFR 803.11(a).The adequacy of your firm’s response dated November 26, 2024, cannot be determined at this time. The response notes that your firm plans to update its MDR procedure to include a reportability determination process, add evaluation recording process, and conduct staff training. However, your firm did not provide documentation or evidence demonstrating the implementation of these corrective actions, as they are still ongoing.We note that a device is deemed to be misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), if there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, which includes adverse event reports required under 21 CFR Part 803, respecting the device.Given the serious nature of the violations of the Act, the Salivary Cortisol ELISA and the Salivary Cortisol ELISA RUO devices manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as "Detention Without Physical Examination of Devices without Approved PMA's or IDE's and Other Devices Not Substantially Equivalent or Without a 510(k)," until these violations are addressed. To remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and address the violation(s) described in this letter. We will notify you regarding the adequacy of your firm’s response(s) and the need to re-inspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.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.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, including 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 should 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. Please provide a translation of documentation not in English to facilitate our review. 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 by email to CDRHWarningLetterResponses@fda.hhs.gov. Refer to CMS case 700918 when replying. If you have any questions about the contents of this letter, please contact: Kimberly Mapp at Kimberly.mapp@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 or associated with your firm’s devices. 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 yours,/S/Courtney H. Lias, Ph.D.DirectorOHT7: Office of In Vitro Diagnostic DevicesOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCC:Ina HairstonU.S. Agent, DRG Instruments GmbH andHead of Regulatory Affairs, DRG International, Inc.(b)(4)@drg-international.comMr. Simon W. Huang, Chief Executive OfficerBioCheck, Inc.(b)(4), (b)(6)@biocheckinc.comMr. Stephen A. Baliani, ComptrollerDRG International, Inc.(b)(4), (b)(6)@drg-international.com

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Andre KolpeManaging DirectorKabe Labortechnik GmbHJagerhofstr. 17Numbrecht51588North Rhine-WestphaliaGermany(b)(6)@kabe-labortechnik.deIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERMay 9, 2025Dear Mr. Kolpe:During an inspection of your firm located in Numbrecht, North Rhine-Westphalia, Germany, on January 6 through 9, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures blood collection tubes including the SAFE-TFILL Capillary Blood Collection Systems. Under section 201(h) of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. § 321(h), these products are devices because they are intended for use in the diagnosis of disease or other conditions or in the cure, mitigation, treatment, or prevention of disease, or to affect the structure or any function of the body.Quality System Regulation (QSR) 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. We received a response from Mr. Andre Kolpe, CEO and Managing Director, dated January 17, 2025, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, which was issued to your firm. We address this response below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to adequately ensure that when the results of a process cannot be fully verified by subsequent inspection and test that the process shall be validated with a high degree of assurance and approved according to established procedure, as required by 21 CFR 820.75(a). For example, your firm has not validated the manufacturing process of the SAFET-FILL Capillary Blood Collection Systems. The blood collection systems are manufactured and filled onsite with an anticoagulant which is coated in a capillary rod, a critical component for the device, and inspected using software. However, these processes were not validated.Specifically:a. Your firm’s procedure, “QM VA_0026”,Validation of Production Machines, Rev I, dated December 19, 2023, requires “existing machines and process equipment” that are “used for the production of medical devices and in-vitro diagnostics” to be validated using installation qualification, functional qualification, and performance qualification; however(b)(4)have not been validated. Mr. Sven Nahring, Supervisor of Quality, stated that since the machines(b)(4)30 years ago, your firm was still trying to figure how to retrospectively validate them.b. Your firm’s procedure, “VA_0002”Software Validation, Rev I, dated June 25, 2024, requires that “software used in the company that requires validation is validated or that only validated software is used in the company.” However, the software used to inspect the coated capillary rods and(b)(4)product is not validated. During a demonstration of the software during the inspection,(b)(4)capillary rods were(b)(4). When asked, the production employee and your firm’s management concurred that the software was not performing as it should. The software showed capillary rods outside the(b)(4)as accepted in the system which should(b)(4). Mr. Dirk Kogelheide, Quality Management, and Mr. Sabastian Bchner, Quality Manager Department, confirmed that this software was installed many years ago and has not been validated.The adequacy of your response dated January 17, 2025, cannot be determined at this time. Your response states that “to meet the requirements of our procedure for validating manufacturing processes, VA_0026, dated December 19, 2023, we are preparing a plan of the affected manufacturing processes.” However, you have not provided the plan and timeline for validation of the machines and software used to produce the SAFE-T-FILL Capillary Blood Collection Systems. Because the machines and software remain unvalidated, it is unclear how you ensure that the current production of the SAFE-T-FILL Capillary Blood Collection Systems meet quality specifications. Additionally, your response states that “the claimed deviation that the(b)(4).” However, you have not provided evidence to support this statement (e.g. such as(b)(4)). You have also stated in your response that a “(b)(4).” However, you have not provided evidence of this validation.Your firm should provide a systemic corrective action plan to address the validation of manufacturing processes for all devices manufactured at this facility including evidence of implementation. Copies of revised procedures and evidence of training on new or revised procedures should also be provided.2. Failure to adequately ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use, as required by 21 CFR 820.70(g). For example, it appears that(b)(4)machines used in manufacturing have not been qualified for their intended use. As a result, capillary tubes made by these(b)(4)machines were partially damaged. Specifically, your firm’s CAPA-ID 23G4429_1 described failure of(b)(4)machine that resulted in damaged capillaries in the finished products for batches 23G4429 and 23H4113. The root cause of the failure was identified as that the “(b)(4).” Mr. Nahring, Supervisor of Quality, provided a supplement to CAPA #06.2023 which stated under the section Detected Deviation “(b)(4).” The CAPA has already been closed, therefore it is not clear whether this(b)(4)machine has been qualified for its use. Mr. Nahring along with the management further stated the validation plans for those machines are still in process and have not been executed.The adequacy of your response dated January 17, 2025, cannot be determined at this time since you did not provide evidence that(b)(4)machines have been retroactively qualified nor a corrective action to ensure that all future equipment used during manufacturing will be qualified for their intended use. You also have not provided a systemic corrective action to ensure that all equipment used in the manufacturing process meets specified requirements and is appropriately designed, constructed, placed, and installed to facilitate maintenance, adjustment, cleaning, and use, as required by 21 CFR 820.70(g).3. Failure to adequately establish and maintain procedures to control the design of the device in order to ensure that specified design requirements are met, as required by 21 CFR 820.30(a). For example, your firm does not have a design control procedure that details design input, design output, design verification, design validation, design transfer, design review, and design history, specifically:a. Your firm provided flow charts to describe these design control processes in “QM_AA_0019,”Project Process, Rev. I, Effective Date June 19, 2024. Additionally, the design change procedure “AA_0011,”Change of a Medical Device, Effective Date August 07, 2024, and “VA_0028,”Change Management– Change Control, Effective Date March 12, 2024, simply list changes that need to be checked by management before implementation, but do not describe how your firm manage changes to the device to ensure the quality of their products are unaffected. The inspector requested written procedures that address 21 CFR 820.30 and Mr. Sven Nahring, Supervisor of Quality, confirmed that your firm does not have any other procedures other than QM_AA_0019, AA_0011, and VA_0028.b. Your firm has not maintained an adequate design history file for the SAFE-T-FILL Capillary Blood Collection Systems. Specifically, the design history file does not contain or refer to the initial design documents that address original design input, design output, verification and validation, design review and approval. During the inspection, such records were requested, however, Mr. Sven Nahring, Supervisor of Quality, stated that(b)(4)firm may not have maintained such documents.The adequacy of your response dated January 17, 2025, cannot be determined at this time. You stated in your response that you will review and amend all documents for recording the design control process. However, you did not provide corrected procedures for review. You also stated that “QM_AA_0019” is presented in more detail “in an existing Excel-based document created from a project work,” however, you did not provide the Excel file for review. Finally, you stated that specifically for the SAFE-T-FILL Capillary Blood Collection Systems, you plan to collect “all activities carried out to date in terms of creation, recording, specifications (design, intended use, etc.) and changes” in a database supported system that is yet to be developed by the(b)(4)department. However, you did not provide a record of these changes in the database for review.Your firm should provide a systemic corrective action to address design history files for all devices manufactured and sold in the US and provide your plans for remediation of those devices. You should also assess if the collected documents comprising the design history file support the current design and performance specifications for the SAFE-T-FILL Capillary Blood Collection Systems. Design changes, including the impact of cumulative changes should be assessed to determine if a new 510(k) is needed. For more information on the Agency’s current thinking for deciding whether to submit a new 510(k) for a change to an existing device, see FDA’s Guidance "Deciding When to Submit a 510(k) for a Change to an Existing Device".1Evidence that the software used to document the design history file is adequately validated should also be provided.4. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). For example, your firm’s CAPA procedure “QM_VA_0006,”Deviations, Complaints, and CAPA Management, Effective Date April 03, 2023, does not adequately describe the procedure for conducting root cause investigations, implementing corrective actions effectively, verifying the effectiveness of corrective and preventive actions, and using statistical methodology (to detect trends) where necessary. As a result, the CAPA investigations were inadequate to address problems in the device manufacturing. The following CAPAs were provided as examples of CAPAs not adequately handled:a. CAPA 06.2023 was initiated because your firm failed to assess the validation for assembling cannulas with extension tubes which was identified during the external audit conducted by(b)(4), an independent service company that inspects and certifies technical systems. This CAPA was closed on November 23, 2023, without establishing and implementing the corrective actions adequately.b. CAPA 23G4429-1 was initiated because the capillaries were getting damaged by an(b)(4)machine. The CAPA failed to reference the evidence of training activities as established by the CAPA action plan. The CAPA also failed to establish the verification of effectiveness check plan based on statistical rationale before verifying the CAPA as effective.c. CAPA 23B4355-1 was initiated on July 05, 2023, due to a customer complaint that the specified fill level in the tube was not reached and some of the blood samples could not be drawn completely. Your firm identified the diaphragm rubber had been pushed through the venting needles; however, your firm failed to identify why the diaphragm rubber was pushed. This CAPA failed to perform a complete root cause analysis and failed to establish and implement corrective actions effectively.Your firm’s response dated January 17, 2025, is not adequate. In your response you provided a brief plan to correct the CAPA process(b)(4), however, you have not corrected these CAPAs. You also stated in your response that you have revised QM_VA_0006 and your staff have been trained accordingly, however, you did not provide the revised QM_VA_0006 for review nor did you provide any training records of trained personnel. Your firm should provide a plan to correct the deficient CAPAs noted during the inspection and systemic corrective action to address other CAPAs that may also be deficient under the new revised procedure. Evidence to show that the new CAPA process is effective should also be provided for review.5. Failure to adequately establish and maintain procedures to control product that does not conform to specified requirements, as required by 21 CFR 820.90. Your firm did not address the identification, documentation, evaluation, segregation, and disposition of nonconforming product. For example, while the “QS_VA_0009,”Management of Defective Products, Rev. I dated June 01, 2023, defined the responsibility for review and the authority for the disposition of nonconforming product and its documentation, your firm did not document the disposition of nonconforming products in accordance with your standard operating procedures. As a result, nonconforming product identified during the(b)(4)as outlined in your standard operating procedure.You did not provide a response to this deficiency in your firm’s response dated January 17, 2025.6. Failure to adequately establish and maintain procedures to ensure that all purchased or otherwise received product and services conform to specified requirements, as required by 21 CFR 820.50. For example, the categorization of “primary suppliers” for materials to produce the SAFE-T-FILL Capillary Blood Collection Systems were not consistent. As a result, a review of quality agreements with two class A suppliers were found to have inconsistencies in the requirements to be met by the suppliers. The inconsistencies were also identified in the classification of suppliers who provide similar raw materials for the SAFE-T-FILL Capillary Blood Collection Systems. For example:a. Your firm’s supplier management procedure, “VA_0004,”Evaluation and Selection of Suppliers, Effective Date June 04, 2024, classifies suppliers into categories A to D (A being the highest risk supplier and D being the lowest risk supplier). However, suppliers of similar critical components were classified into different categories. For example, suppliers for “(b)(4)” used in the manufacturing of the SAFE-T-FILL Capillary Blood Collection Systems received from both category A and B designations: One supplier,(b)(4), received a Category A designation while another supplier,(b)(4)located at(b)(4)received a Category B designation. During the inspection Mr. Sebastian Bchner, Quality Manager Department, confirmed that both the suppliers provide(b)(4), for the SAFE-T-FILL Capillary Blood Collection Systems and both the(b)(4)have a direct influence on the conformity of the medical device and the quality of the device.The adequacy of your response dated January 17, 2025, cannot be determined at this time. You stated in your response that your firm has revised yourEvaluation and Selection of Suppliers, VA_0004 rev. II that addresses the classification of your suppliers, however, you did not provide this revised standard operating procedure and evidence of its implementation. You also stated in your response that you have worked with your Purchasing and Quality Management departments to ensure the agreements between suppliers are consistent, however, you did not provide an example or copies of the revised agreements. Your firm should provide an updated procedure for how you categorize suppliers, and an example of the revised agreement with your supplier as evidence that quality agreements, at the minimum, between category A suppliers are consistent across the different suppliers.Medical Device Reporting (MDR) ViolationsOur inspection also revealed that you have failed to develop, maintain, and implement written Medical Device Reporting (MDR) procedures, as required by 21 CFR 803.17. It was noted during the inspection that your firm has an agreement with ASP Global, your U.S. distributor, for ASP Global to file adverse event reports for devices received by ASP Global. However, your firm stated it, as the manufacturer of medical devices, does not have a written procedure that provides for timely and effective identification, communication, evaluation, and reporting to FDA of events that may be subject to MDR requirements. We note that a device is deemed to be misbranded under section 502(t)(2) of the Act, 21 U.S.C. § 352(t)(2), if there was a failure or refusal to furnish any material or information required by or under section 519 of the Act, 21 U.S.C. § 360i, which includes adverse event reports required under 21 CFR Part 803, respecting the device.You did not provide a response to this deficiency in your firm’s response dated January 17, 2025. You should develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17 and provide evidence that the procedure has been successfully implemented. Evidence of successful implementation may include providing a MDR standard operating procedure for review, staff training records and/or any MDR reports that were correctly addressed.Given the serious nature of the violations of the Act, all devices manufactured by your firm are subject to refusal of admission under section 801(a) of the Act, 21 U.S.C. § 381(a), in that they appear to be adulterated. As a result, FDA is taking steps to refuse entry of these devices into the United States, known as “detention without physical examination,” until these violations are addressed. In order to remove the devices from detention, your firm should provide a written response to this Warning Letter as described below and address the violation(s) described in this letter. We will notify you regarding the adequacy of your firm’s response(s) and the need to reinspect your firm’s facility to verify that the appropriate corrections and/or corrective actions have been made.Your firm should take prompt action to address any violations identified in this letter.Other federal agencies may take your compliance with the FD&C Act and its implementation 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.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, including 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. Please provide a translation of documentation not in English to facilitate our review. Your firm’s response should be sent via email to CDRHWarningLetterResponses@fda.hhs.gov.Refer to CMS case 704563 when replying. If you have any questions about the contents of this letter, please contact: Uyen Chu at uyen.chu@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 yours,/S/Courtney H. Lias, Ph.D.DirectorOHT7: Office of In Vitro Diagnostic DevicesOffice of Product Evaluation and QualityCenter for Devices and Radiological HealthCC:Diana RogersU.S. Agent, ASP Global(b)(6)@aspglobal.com__________________1https://www.fda.gov/regulatory-information/search-fda-guidance-documents/deciding-when-submit-510k-change-existing-device

为加强医疗器械监督管理，保障医疗器械安全有效，依据《医疗器械监督管理条例》《药品医疗器械飞行检查办法》《医疗器械生产质量管理规范》《医疗器械经营质量管理规范》《医疗器械使用质量监督管理办法》等要求，按照四川省药品监督管理局2024年医疗器械检查工作部署，我局对26家医疗器械生产企业、8家医疗器械经营企业、8家医疗机构组织开展了飞行检查工作。现发布结果通告，具体情况见附件。附件：2024年四川省医疗器械飞行检查结果统计表四川省药品监督管理局2025年5月27日序号被检查单位检查时间处理措施整改完成情况备注1成都太合生物材料有限公司2024年2月26日至28日限期整改已完成生产企业2乐山市嘉美冠牙科技术有限公司2024年3月11日至13日限期整改已完成生产企业3成都口口齿科技术有限公司2024年3月14日至15日限期整改已完成生产企业4四川恒明科技开发有限公司2024年3月19日至20日限期整改已完成生产企业5成都美创卓尔医疗科技有限公司2024年3月19日至20日限期整改已完成生产企业6成都贝施美生物科技有限公司2024年3月21日至22日限期整改已完成生产企业7成都市新兴内窥镜科技有限公司2024年3月21日至22日停产整改已完成并恢复生产生产企业8成都东美众科技有限公司2024年3月25日至27日限期整改已完成生产企业9四川维美医疗器械有限公司2024年4月15日至17日限期整改已完成生产企业10南充悠佳齿业有限公司2024年5月6日至8日限期整改已完成生产企业11南充市顺庆区艺美义齿加工中心2024年5月8日至10日限期整改已完成生产企业12四川省金优达医疗器械有限公司2024年5月14日至16日限期整改已完成生产企业13四川鸿政博恩口腔科技有限公司2024年5月20日至22日限期整改已完成生产企业14成都美益达医疗科技有限公司2024年6月13日至14日限期整改已完成生产企业15四川蓉康世圣药业有限责任公司新都分公司2024年6月18日至19日停产整改未完成生产企业16成都吉泰医疗器械有限公司2024年6月20日至21日限期整改已完成生产企业17四川友邦企业有限公司2024年7月2日至4日限期整改已完成生产企业18四川康宁医用器材有限公司2024年7月10日至11日限期整改已完成生产企业19奥克兰医疗科技（四川）有限公司2024年7月10日至12日限期整改已完成生产企业20四川省遂宁市康达卫生材料有限公司2024年7月17日停产整改已完成并恢复生产生产企业21绵竹耀隆医疗器械有限公司2024年7月17日至18日停产整改未完成生产企业22成都普什医疗科技有限公司2024年7月22日至26日限期整改已完成生产企业23成都瑞琦医疗科技有限责任公司2024年7月22日至26日限期整改已完成生产企业24四川国纳科技有限公司2024年8月7日至8日限期整改已完成生产企业25四川新世纪医用高分子制品有限公司2024年9月18日至20日停产整改已完成并恢复生产生产企业26成都稳健利康医疗用品有限公司2024年11月5日至8日限期整改已完成生产企业27四川乾宁医疗器械有限公司2024年10月15日至16日限期整改已完成经营企业28四川双钻科技有限公司2024年10月16日至17日限期整改已完成经营企业29内江市福奇林医疗器械有限责任公司2024年10月16日至17日限期整改已完成经营企业30四川景宏药械第三方仓储物流有限公司2024年10月17日至18日限期整改已完成经营企业31四川同昌冷链医药物流有限责任公司2024年10月22日限期整改已完成经营企业32甘孜州明亮眼镜有限责任公司泸定县分公司2024年10月22日至23日限期整改已完成经营企业33四川鼎康医疗器械有限公司2024年10月24日限期整改已完成经营企业34四川省广元市药业有限责任公司2024年10月24日至25日限期整改已完成经营企业35雅安鑫西华口腔整形医院2024年10月15日至16日限期整改已完成医疗机构36内江市妇幼保健院2024年10月15日至16日限期整改已完成医疗机构37西南医科大学附属医院2024年10月15日至16日限期整改已完成医疗机构38遂宁嘉慧妇产医院2024年10月17日至18日限期整改已完成医疗机构39达州市中心医院2024年10月22日至23日限期整改已完成医疗机构40成都市第五人民医院2024年10月23日限期整改已完成医疗机构41广元市中心医院2024年10月23日限期整改已完成医疗机构42甘孜藏族自治州人民医院2024年10月24日至25日限期整改已完成医疗机构

南昌市福康医疗器械有限公司报告，由于我公司收到贵局发出的关于产品医用棉签（赣械注准20162140132）的不合格品检测报告（报告编号：YQCY20250052，江西省医疗器械检测中心）。该报告显示：产品名称：医用棉签（赣械注准20162140132，10cm，生产批号：20241102，生产日期：20241102），不合格项为：2.6条款，环氧乙烷残留量。等原因，南昌市福康医疗器械有限公司对其生产的医用棉签(注册备案号:赣械注准20162140132)主动召回，召回级别为三级,涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。附件：医疗器械召回事件报告表2025-05-27

江西晶康宇医疗科技有限公司报告，由于气流阻力超差等原因，江西晶康宇医疗科技有限公司对其生产的一次性使用鼻氧管(注册备案号:赣械注准20162080226)主动召回，召回级别为三级,涉及产品的型号、规格及批次等详细信息见《医疗器械召回事件报告表》。附件：医疗器械召回事件报告表2025-05-26

行政处罚决定书文号：豫药监药处罚〔2025〕1-1号处罚名称：河南华益药业有限责任公司违反药品经营质量管理规范案处罚类别1：罚款;责令停产处罚类别2：处罚事由：违反药品经营质量管理规范处罚依据：当事人未遵守《药品经营质量管理规范》第四条、第八十九条、第九十一条，违反了《中华人民共和国药品管理法》第五十三条第一款的规定。依据《中华人民共和国药品管理法》第一百二十六条进行处罚。行政相对人名称：河南华益药业有限责任公司行政相对人代码_1 (统一社会信用代码) ：91410104728684409K行政相对人代码_2 (组织机构代码)：行政相对人代码_3 (工商登记码)：行政相对人代码_4 (税务登记号)：行政相对人代码_5 (居民身份证号)：法定代表人姓名：景兴月处罚结果：罚款;责令停产处罚决定日期：2025-05-26处罚机关：河南省药品监督管理局当前状态：正常地方编码：410000备注：

行政处罚决定书文号：豫药监械处罚〔2025〕4-1号处罚名称：夏邑县久之康医疗器械有限公司生产、经营不符合经注册的产品技术要求的医疗器械案处罚类别1：罚款;没收违法所得;没收非法财物处罚类别2：处罚事由：生产、经营不符合经注册的产品技术要求的医疗器械处罚依据：依据《中华人民共和国行政处罚法》第二十八条、《医疗器械监督管理条例》第八十六条第一项的规定,建议责令当事人改正违法行为，并给予当事人以下行政处罚： 1.没收违法所得1358.00元； 2.没收违法生产经营的热敷贴（批号20230902、20240102）5120贴； 3.并处20000.00元罚款。 罚没款合计21358.00（贰万壹仟叁佰伍拾捌元整）。行政相对人名称：夏邑县久之康医疗器械有限公司行政相对人代码_1 (统一社会信用代码) ：91411426MA3X55QA07行政相对人代码_2 (组织机构代码)：行政相对人代码_3 (工商登记码)：行政相对人代码_4 (税务登记号)：行政相对人代码_5 (居民身份证号)：法定代表人姓名：田亚飞处罚结果：罚款;没收违法所得;没收非法财物处罚决定日期：2025-05-26处罚机关：河南省药品监督管理局当前状态：正常地方编码：410000备注：

行政相对人名称xxx有限公司行政相对人类别法人及非法人组织行政相对人代码_1(统一社会信用代码)xxx法定代表人xxx行政处罚决定书文号粤药监妆罚〔2025〕3003号违法行为类型未按照化妆品生产质量管理规范的要求组织生产化妆品。违法事实我局化妆品企业监督检查组分别于2024年6月12日至13日和2024年10月24日至25日，对当事人开展监督检查，依据《化妆品生产质量管理规范检查要点及判定原则》的相关规定，判定当事人生产质量管理体系存在严重缺陷。当事人上述行为，违反了《化妆品监督管理条例》第二十九条第一款的规定。处罚依据《化妆品监督管理条例》第六十条第（三）项的规定。处罚类别没收违法所得，罚款。处罚内容1.没收违法所得406587.9元；2.罚款2441375.4元。罚款金额（万元）244.13754没收违法所得、没收非法财物的金额（万元）40.65879处罚决定日期2025年5月8日处罚有效期1年处罚机关广东省药品监督管理局处罚机关统一社会信用代码11440000MB2D034421数据来源单位广东省药品监督管理局数据来源单位统一社会信用代码11440000MB2D034421