Delivery Method:VIA UNITED PARCEL SERVICE AND VIA E-MAILReference #:26-HFD-45-03-02Product:DrugsRecipient:Jayesh ChaudharyCEOVedic Lifesciences Pvt. Ltd.203, Morya Landmark 1, Off New Link RoadAndheri WestMumbai400053MaharashtraIndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERFDA Ref. No.: 26-HFD-45-03-02Dear Mr. Chaudhary:This Warning Letter informs you of objectionable conditions observed during the U.S. Food and Drug Administration (FDA) inspection conducted between January 13 and 15, 2025. The investigators representing FDA reviewed the role of Vedic Lifesciences Pvt. Ltd. (Vedic) as the testing facility of the following nonclinical laboratory studies of the investigational drug(b)(4), performed for(b)(4).:• Study No.(b)(4): “(b)(4)”• Study No.(b)(4): “(b)(4)”• Study No.(b)(4): “(b)(4)”This inspection was conducted as part of FDA’s Bioresearch Monitoring Program, which includes inspections designed to evaluate the conduct of research and to help ensure the quality and integrity of study data, in accordance with Title 21 of the Code of Federal Regulations, part 58 (21 CFR 58), Good Laboratory Practice for Nonclinical Laboratory Studies.At the conclusion of the inspection, the FDA investigators presented and discussed with you the Form FDA 483, Inspectional Observations. We acknowledge receipt of your February 3, 2025, written response to the Form FDA 483.From our review of the FDA Establishment Inspection Report, the documents submitted with that report, and your written response dated February 3, 2025, it appears that you did not adhere to the applicable statutory requirements in the Federal Food, Drug, and Cosmetic Act (FD&C Act) and applicable regulations contained in 21 CFR 58 governing the conduct of nonclinical laboratory studies. We wish to emphasize the following:You failed to prepare a final report for each nonclinical laboratory study that includes, but is not limited to, the following: (1) name and address of the testing facility; (2) name of the study director and other scientists or professionals involved in the study; (3) locations where all specimens, raw data, and final reports are to be stored; and (4) study director’s signature and date [21 CFR 58.185(a)(1), 58.185(a)(10), 58.185(a)(13), and 58.185(b)].A final report must be prepared for each nonclinical laboratory study and must contain certain information, including but not limited to: (1) the name and address of the testing facility performing the study; (2) the names of the study director and other scientists or professionals involved in the study; and (3) the location where all specimens, raw data, and the final report are stored. The final report must also be signed and dated by the study director.You failed to adhere to these requirements. Specifically, the final reports for studies(b)(4)that Vedic submitted to the sponsor did not contain complete and accurate information for the above-described items that were required to be included in the final report. Examples include but are not limited to the following:1. The final reports for studies(b)(4)did not accurately identify the testing facility that performed the studies. Specifically, the testing facility that performed studies(b)(4)was(b)(4)((b)(4)), and the testing facility that performed Study(b)(4)was(b)(4)((b)(4)). However, before submitting the final reports to the sponsor, Vedic changed the final reports to falsely include the name and address of Vedic as the testing facility that performed the study.2. The final reports for studies(b)(4)did not include the correct names of the study director and other scientists or professionals involved in the study, such as the quality assurance unit (QAU) personnel. Specifically, before submitting the final reports to the sponsor, Vedic changed the final reports provided by the testing facilities that performed the study to falsely include the names of Vedic personnel as the study director or QAU personnel.3. The final reports for studies(b)(4)did not accurately identify the storage location for all specimens, raw data, and final reports. Specifically, before submitting the final reports to the sponsor, Vedic changed the final reports to falsely identify Vedic as the storage location; however, all specimens, raw data, and final reports were stored at(b)(4)for studies(b)(4), and at(b)(4)for Study(b)(4), the testing facilities that actually performed these studies.4. The study directors for studies(b)(4)and(b)(4)did not sign the final reports for these studies. In accordance with 21 CFR 58.33, the study director is the individual responsible for the overall conduct of the study. For these three studies, Vedic personnel signed the final reports. However, the Vedic personnel who signed the final reports were not involved in the conduct of these studies because the studies were performed at other testing facilities. Therefore, the Vedic personnel who signed the final reports were not the individuals responsible for the overall conduct of the studies. As a result, the final reports for studies(b)(4), and(b)(4)did not include accurate study director signatures.We acknowledge that some of these findings were not included on the Form FDA 483 you received, and therefore your written response does not directly address all the violations discussed in this letter.However, during the inspection, the Manager of Quality Assurance stated that Vedic personnel do not serve as study directors, Vedic does not maintain study archives, Vedic has never had an animal facility, and Vedic is not a testing facility where the toxicology studies are conducted. Additionally, in your February 3, 2025, written response to the Form FDA 483, you acknowledged that Vedic outsourced Studies(b)(4)to(b)(4), and Study(b)(4)to(b)(4). You stated that Vedic is not a toxicology testing facility and instead operates as a liaison to prospective clients who are looking to conduct toxicology studies. You stated that it was your earlier practice to withhold from sponsors the names and contact information of partner testing facilities, study directors, QAU personnel, and archive locations to “prevent circumvention by the testing facility.” You further stated that in accordance with Vedic’s standard operating procedure (SOP), the Vedic study monitor was the single point of study control and therefore was captured as the single point of study control in the reports.In your written response, you stated that as part of your corrective and preventive actions, since 2022, you have stopped mentioning Vedic as a testing facility, and the details of the testing facility are now shared with the study sponsors. You also stated that you realized that your practice of listing the Vedic study monitor as the single point of study control in reports is not correct, and that the actual study director is now mentioned in final reports. You also stated that you amended the final report for Study(b)(4)to add the name of the correct testing facility and study director. However, since the(b)(4)testing facility has closed its operations, you were unable to retrieve and amend the study reports for Studies(b)(4). Additionally, you stated that you revised your SOP for Toxicological Operations to implement the following practices: (1) The name and address of the study director will be included in the final report; (2) Vedic will be identified as the sponsor representative in the study plan and report; (3) the Vedic study monitor will sign the study plan and report; and (4) testing facility management of the GLP facility will ensure that the study director approves the study plan and report.While we acknowledge the actions that your site has taken and plans to take, your written response is inadequate because you did not provide sufficient details about your corrective action plan. Specifically, you did not provide sufficient details about the procedures and practices for preparing final reports that have been or will be implemented at your site to prevent similar violations in the future. For example, you did not provide details regarding any training for Vedic personnel on your updated procedures and practices. Also, the SOP that you provided does not include all the practices identified in your written response, such as including the name and address of the study director in the final report. Without this information, we cannot undertake an informed evaluation of your written response, and it is not clear whether your corrective and preventive actions will adequately ensure that ongoing and future studies will be conducted in compliance with applicable FDA regulations, including the requirements for preparing final reports.Failure to include accurate and complete information in the final study report raises significant concerns about the quality and integrity of the study records and data from Studies(b)(4). The final study report of an investigation is crucial to the reconstruction of the events that led to the collection and reporting of the data, and it must contain accurate and complete information regarding the conduct of the study. The information in these essential documents forms the basis for establishing scientific interpretations and conclusions and must therefore reflect all circumstances affecting the quality and integrity of the data.We further emphasize that nonclinical laboratory studies submitted to FDA must be accurately and completely reported in accordance with FDA regulations, to ensure the quality and integrity of study data. Your failure to provide final reports for all three studies, containing accurate and complete information that is required to be submitted to support FDA’s review of a nonclinical laboratory study, raises significant concerns about the validity and integrity of the data that were collected and submitted for these nonclinical laboratory studies.This letter is not intended to be an all-inclusive list of deficiencies with the nonclinical laboratory studies of investigational drugs for which Vedic was the testing facility, as represented in final reports submitted to FDA. It is your responsibility to ensure adherence to each requirement of the law and relevant FDA regulations. You should address any deficiencies and establish procedures to ensure that any ongoing or future studies comply with FDA regulations.This letter notifies you of our findings and provides you with an opportunity to address the deficiencies noted above. Within 15 business days of your receipt of this letter, you should notify this office in writing of the actions you have taken to prevent similar violations in the future. Failure to address this matter adequately may lead to regulatory action without further notice to you. If you believe that you have complied with the FD&C Act and relevant regulations, please include your reasoning and any supporting information for our consideration.Should you have any questions or concerns about this letter or the inspection, please email FDA at CDER-OSI-Communications@fda.hhs.gov.Your written response and any pertinent documentation should be addressed to:Brittany L. Garr, MPHBranch ChiefCompliance Enforcement BranchDivision of Enforcement and Postmarketing SafetyOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug AdministrationBuilding 51, Room 535210903 New Hampshire AvenueSilver Spring, MD 20993Sincerely,{See appended electronic signature page}David C. Burrow, Pharm.D., J.D.DirectorOffice of Scientific InvestigationsOffice of ComplianceCenter for Drug Evaluation and ResearchU.S. Food and Drug Administration--------------------------------------------------------------------------------------------This is a representation of an electronic record that was signed electronically. Following this are manifestations of any and all electronic signatures for this electronic record.--------------------------------------------------------------------------------------------/s/------------------------------------------------------------DAVID C BURROW03/09/2026 10:48:01 AM

Delivery Method:VIA Electronic MailProduct:Medical DevicesRecipient:Timothy P. MoranPresident and CEOAvertix Medical, Inc.40 Christopher Way, Ste 201Eatontown,NJ07724United Statestmoran@avertix.comIssuing Office:Center for Devices and Radiological HealthUnited StatesWARNING LETTERCMS # 711080September 3, 2025Dear Mr. Moran:During an inspection of your firm located in Eatontown, NJ from February 19, 2025, through March 11, 2025, an investigator from the United States Food and Drug Administration (FDA) determined that your firm manufactures The Guardian System, an implantable coronary syndrome event detector. The Guardian System consists of three main system components: an implantable device used to monitor a patient’s electrogram (IMD); a hand-held telemetry device that provides alarms and alerts and interfaces between the IMD and programmer (EXD); and a programmer utilized by healthcare professionals to program the IMD and alarm/alert settings and retrieve and review IMD data (Programmer). 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 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 responses from David Keenan, Chief Technology Officer, dated March 31, 2025, and June 20, 2025, concerning our investigator’s observations noted on the Form FDA 483 (FDA 483), List of Inspectional Observations, that was issued to your firm. We address these responses below, in relation to each of the noted violations. These violations include, but are not limited to, the following:1. Failure to maintain complaint files; and failure to adequately establish and maintain procedures for receiving, reviewing, and evaluating complaints by a formally designated unit as required by 21 CFR 820.198(a). Specifically, the firm’s procedure, Complaint Procedure, #1716-002, Rev Q (dated February 25, 2022) to Rev R (dated April 11, 2022) has not been adequately established in that:a. Your firm failed to adequately maintain complaint files, as required by 21 CFR 820.198(a).Specifically, section 5.1.2 of your complaint procedure requires all employees to report any product complaint or feedback from the field. Section 5.1.3 of the complaint procedure covers the review of “ISSUES” to disposition them as a “COMPLAINT” or “REJCT/No ACTION REQUIRED”. The FDA investigator identified 11 issues which meet the definition of a complaint and were not dispositioned as a complaint as required by your procedure. For example:i.(b)(4), reported on November 6, 2023, listing the patient effect description as “Guardian Device was removed from the patient due to a recurrent pocket infection post implant.”ii.(b)(4), reported on March 4, 2022, listed the programmer battery connector broke when trying to remove the battery.iii.(b)(4), reported on September 6, 2023, listed the USB Drive for Programmer was not connected and required formatting each time to use.Additionally, six of eleven “nonconforming material reports” (NCMRs) reviewed during the inspection that met the definition of complaints were not considered complaints and as such were handled according to your nonconforming material process. For example:iv.(b)(4), created April 30, 2024, states that a Programmer (PROG-003) was returned from the field due to issues with the battery charging indicator light.v.(b)(4), created September 6, 2023, states a USB flash drive was not functioning properly in the field and was returned.vi.(b)(4), created November 22, 2022, states that a field clinical engineer reported that a Programmer Battery was damaged while being inserted into the Programmer.The above “issues” and “nonconforming product reports” were not evaluated for MDR reportability and were not reviewed to determine if an investigation is necessary, since they were not considered complaints.b. Your firm failed to adequately establish and maintain procedures to ensure that all complaints are processed in a uniform and timely manner, as required by 21 CFR 820.198(a)(1).Specifically, your firm’sComplaint Procedure, #1716-002, does not include a requirement for timely and uniform complaint handling. For example, the following complaints were entered as issues and were not escalated to complaints in a timely manner:i. Complaint-00077: On July 17, 2024, your firm became aware of a reported issue where the physician was unable to retrieve data from the IMD implant. The complaint record was not opened until September 5, 2024 (50 days after becoming aware).ii. Complaint-00066: On February 13, 2024, your firm became aware of an IMD explant due to an infection. The complaint record was not opened until March 28, 2024 (44 days after becoming aware).iii. Complaint-00059: On November 30, 2023, your firm became aware of a reported “flat line IMD” event. The complaint record was not opened until January 5, 2024 (36 days after becoming aware).iv. Complaint-00039: On October 28, 2022, your firm became aware of an IMD explant due to an infection. The complaint record was not opened until December 1, 2022 (34 days after becoming aware).c. Your firm failed to review, evaluate, and investigate any complaint involving the possible failure of a device, labeling, or packaging to meet any of its specifications, unless such investigation has already been performed for a similar complaint and another investigation is not necessary, as required by 21 CFR 820 820.198(c).Specifically, Section 5.1.4 of yourComplaint Procedurerequires investigation of complaints. Your firm failed to adequately review, evaluate, and investigate the following complaints that reported patient infection and subsequent explant of the implantable cardiac monitoring device (IMD), the implantable portion of The Guardian System:i.(b)(4), reported on February 13, 2024, that subsequently became Complaint-00066, documents the justification for not performing an investigation as: “Physician determined patient had a pocket infection and made the decision to explant and device. No investigation needed.”ii.(b)(4), reported on October 28, 2022, that subsequently became Complaint-00039, documents the “Initiate Investigation Process” option was selected but no investigation was performed and the “Review for Closure” section of the complaint records lists “no investigation needed.”We reviewed your firm’s responses and conclude that they are not adequate. In the response, your firm states that CAPA 00015 was opened to capture all corrective and preventive work performed in relation to this observation. As part of CAPA 00015, your firm promised to(b)(4). Your firm also promised to(b)(4). However, the response does not address performing a retrospective review of all issues and nonconforming product reports to determine if other complaints exist and if investigations need to be performed. Several of the items promised by your firm continue to be in-progress (including but not limited to(b)(4).2. Failure to adequately establish and maintain procedures to control product that does not conform to specified requirements. The procedures shall address the identification, documentation, evaluation, segregation, and disposition of nonconforming product. The evaluation of nonconformance shall include a determination of the need for an investigation and notification of the persons or organizations responsible for the nonconformance. The evaluation and any investigation shall be documented, as required by 21 CFR 820.90(a).Specifically, yourNonconformance Material Procedure, #1707-002, does not include a provision for the determination of the need for an investigation. For example, the following two nonconformances did not include a documented investigation or evaluation:a.(b)(4)was created on June 27, 2024, for IMD batteries that were sent to your contract manufacturer for use in production were returned due to nonconformances (bent prongs). The disposition of the batteries was recorded as being scrapped. However, there was no investigation conducted into the cause of the bent probes and the nonconformance record does not include a rationale for not investigating.b.(b)(4)was created on June 7, 2023, for the EXD-001 Battery Packaging Label (p/n(b)(4)) on the EXD-001 Battery, 10 Packs (p/n(b)(4)) listing an incorrect expiration date and battery lot code in finished goods inventory. Your firm reworked the nonconforming product. However, there was no investigation conducted into the cause of the incorrect labeling and the nonconformance record does not include a rationale for not investigating.We reviewed your firm’s responses and conclude that they are not adequate. Your response promises to(b)(4)as well as plans to(b)(4). All activities are captured in CAPA 00017 and all work is promised by(b)(4). However, your response fails to address if a retrospective review of NCMRs will be conducted. Several of these promised actions (including CAPA 00017) remain in-progress with a tentative CAPA Effectiveness Verification planned due date of(b)(4).3. Failure to adequately establish and maintain procedures for validating the device design to include adequate risk analysis, as required by 21 CFR 820.30(g). Specifically, section 6.14 of yourRisk Management Procedure, #1701-011, covers the information collection, information review, and actions related to the use of the Corrective and Preventive Action System and the Complaint System to monitor the device in the clinical and post-production phase to determine if reassessment of risks and/or assessment of new risks is necessary. Your firm failed to reassess the risk when estimated risks from a hazard differed from the actual risk observed in post-market CAPA and complaint data. For example:a. Your firm has received three complaints of infection with the IMD portion of the Guardian System out of a total of(b)(4)IMDs implanted as of February 25, 2025. The observed rate of infection is(b)(4)%. In your device risk file,Guardian System Risk Assessment– P18, #0201-0200-001#P18, Rev B, dated November 13, 2023, the rate of infection was estimated to be(b)(4)%. The risk was not reassessed.b. Your firm has received 24 complaints of battery failure due to electrical short before the device reached its expected service life of 6 years, causing patients to opt for early explant and/or replacement. The observed rate of battery failure is(b)(4)%. In your device risk file,IMD AMSG3-E Hardware FMECA Report – P16, #0212-0201-001#P16, Rev A; dated February 24, 2015, the rate of battery failure was estimated to be(b)(4)%. Further, your firm initiated CAPA-00012 in response to the battery failures. The “Process Impacts” section of this CAPA indicates that no updates to risk management were needed. The risk was not reassessed.We reviewed your firm’s responses and conclude that they are not adequate. In the response, your firm indicates that CAPA 00016 was opened to address any corrective and preventive work taken as result of the observation including to assess the risk associated with infection using current performance data against historical data and to address the need to perform risk reviews on a regularly scheduled basis to keep the risk data current by July 1, 2025. However, your firm did not indicate if you intend to review, and update as necessary, the risk file utilizing post-market data for items other than risk of infection. Several of the items promised by your firm continue to be in-progress, including but not limited to(b)(4)which has a(b)(4)planned due date of(b)(4).4. Failure to adequately establish and maintain procedures for implementing corrective and preventive action, as required by 21 CFR 820.100(a). Specifically, your firm failed to follow your procedure, Corrective and Preventive Action Procedure, #1708-001, Rev J, dated October 23, 2020, when taking corrective and preventive actions. Two examples of lack of CAPA procedure implementation are as follows:a. Your firm failed to follow your CAPA process for a corrective action taken as a result of a consumer complaint which led to a revision made to manufacturing procedure Process Specification, PROG-004 Final Shipping Manufacturing, #0217-1200-020#P18, Rev F, dated November 19, 2024. These actions were taken outside of the CAPA system and lack a documented CAPA investigation as well as verification of implementation and effectiveness.b. Your firm failed to verify or validate the corrective and preventive action to ensure that such action is effective and does not adversely affect the finished device, as required by 21 CFR 820.100(a)(4). Specifically, section 5.9 of the Corrective and Preventive Action Procedure, #1708-001, Rev J, dated October 23, 2020, describes your firm’s process for establishing verification of effectiveness plans with predetermined criteria that verify if corrective and/or preventive actions were effective. Additionally, section 5.10 of the Corrective and Preventive Action Procedure, #1708-001, Rev J, dated October 23, 2020, describes the process for conducting the verification of effectiveness (VOE) phase to demonstrate effectiveness.Review of five CAPAs closed between January 2022 and the time of the current inspection disclosed that four CAPAs (CAPA-00007, CAPA-00008, CAPA-00010, and CAPA-00014) lacked evidence that your firm verified or validated that the action taken was effective.For example, CAPA-00007, was opened as a result of the previous inspection on March 15, 2022, related to a complaint involving EXD batteries having expired shelf life. Your firm implemented several corrective actions to correct the issue which were documented utilizing the complaint record (complaint number 00013) instead of through the CAPA system. CAPA-00007 was closed on March 31, 2022, without verifying the effectiveness of the correction and preventive actions taken.We reviewed your firm’s responses and conclude that they are not adequate. In this response, your firm opened CAPA 00016 to document actions taken for this observation. Your firm promises to(b)(4). For the 5 CAPAs lacking VOE plans and reports, your firm asks our Agency if(b)(4)(2021 or earlier). The decision to(b)(4)remains your firm’s decision as long as it is based on a rationale you determine to be appropriate given the 21 CFR 820.100(a)(4) and your own procedural requirement to demonstrate effectiveness of a CAPA action. You are also going to(b)(4). Your response does not address if other CAPAs will be reviewed to determine if(b)(4). Several of the items promised by your firm continue to be in-progress (including but not limited to(b)(4).5. Failure to validate with a high degree of assurance and approve according to established procedures, a process whose results cannot be fully verified by subsequent inspection and test, as required by 21 CFR 820.75(a). Specifically, your firm’s Process Validation Procedure, #1705-002, Rev E, dated October 23, 2020, and Process Qualification Procedure, #1705-001, Rev F, dated October 23, 2020, were not adequately established in that both procedures fail to address sterilization validation. Your firm’s implantable cardiac monitoring device (IMD) undergoes(b)(4)sterilization. Further, the two procedures fail to document the process of requalification and revalidation (if necessary) of the sterilization cycle.For example, the(b)(4)sterilization process for your firm’s IMD was last performed in June 2022 by a 3rd party in accordance with FDA-recognized standard ANSI/AAMI/ISO 11135:2014. Your firm has not reviewed the(b)(4)sterilization process since the 2022 requalification.We reviewed your firm’s responses and conclude that they are not adequate. In the responses, you indicate that CAPA 00019 was opened as a result of the observation and that your firm promises to(b)(4). However, your responses do not address if your firm’s plans to revise your process validation procedures to include sterilization. Additionally, supporting evidence (including CAPA 00019) of these promised actions remain in progress with a CAPA Effectiveness Verification planned due date for CAPA 00019 of(b)(4).6. Failure to adequately establish and maintain the requirements, including quality requirements, that must be met by suppliers, contractors, and consultants, as required by 21 CFR 820.50(a). Specifically, yourSupplier Management Procedure(#1703-003), has not been fully implemented. For example:a. Your firm’sSupplier Management Procedure(#1703-003) describes a process for supplier evaluation and acceptance using a supplier evaluation form. The Supplier Evaluation Form for the IMD battery supplier, (dated February 13, 2020), indicated your firm’s contract manufacturer would perform receiving inspections of these batteries and provide(b)(4)to Avertix. Your QA/QC manager stated these(b)(4)were not completed.b. Your firm failed to adequately establish and maintain records of acceptable suppliers, contractors, and consultants, as required by 21 CFR 820.50(a)(3). Specifically, section 7.1.12 of Supplier Management Procedure, Rev K, states that “Quality Assurance is responsible for revising the Approved Supplier List with changes made based on acceptance/rejection of potential suppliers/re-evaluated suppliers/deactivated suppliers…” A software supplier used by your firm since 2023 to meet the requirements of the Medical Device Tracking regulation was not listed on your Approved Supplier List (Rev L, dated June 15, 2023).We reviewed your firm’s responses and conclude that they are not adequate. In the responses, your firm promises and provided revisions to your Supplier Management Procedure (Document 1703-003) removing the requirement for(b)(4)for your contract manufacturer and to evidence of a new supplier evaluation for the software supplier utilized for medical device tracking by July 1, 2025. The responses do not indicate if other supplier evaluations will be evaluated and updated, as needed. Further, CAPA 00023 remains in progress with a CAPA Effectiveness Verification planned due date of December 1, 2025.Medical Device Reporting (MDR) ViolationsOur inspection also revealed that your firm’s Guardian System 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. 21 CFR Part 803 - Medical Device Reporting was promulgated under section 519 of the Act, among other provisions. Significant violations include, but are not limited to, the following:1. Failure to report to the FDA the information required by 21 CFR 803.52 in accordance with the requirements of 21 CFR 803.12(a), no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that it markets may have caused or contributed to a death or serious injury, as required by 21 CFR 803.50(a)(1).For example, the information included for Complaint-00066, Issue-00091, and Complaint-00039 reasonably suggests that each patient sustained an injury or illness (i.e., infection) following implantation of your firm’s Guardian System. These infections constituted serious injuries within the meaning of 21 CFR 803.3(w) because they necessitated surgical intervention (i.e., explantation) to preclude permanent impairment of a body function or permanent damage to a body structure. Your firm became aware of information that reasonably suggests that the Guardian System may have caused or contributed to a serious injury on February 13, 2024, for Complaint-00066, on November 6, 2023, for Issue-00091, and on October 28, 2022, for Complaint-00039. As such, Complaint-00066, Issue-00091, and Complaint-00039 represent MDR reportable events, as defined in 21 CFR 803.3(o)(2)(i). However, the FDA did not receive an MDR for each referenced event until April 10, 2025, which exceeded the required 30 calendar day reporting timeframe.The adequacy of your firm’s responses cannot be determined at this time. We acknowledge that the FDA received the manufacturer reports, submitted using the electronic equivalent of Form 3500A, for the referenced serious injury events after the 30 calendar day reporting timeframe had elapsed. However, although the response referenced the updated MDR procedure “Medical Device Vigilance Procedures,” Document No. 1716-005, as part of its correction action for the late reporting issue, a copy of the updated MDR procedure was not included.2. Failure to report to the FDA the information required by 21 CFR 803.52 in accordance with the requirements of 21 CFR 803.12(a), no later than 30 calendar days after the day that your firm received or otherwise became aware of information, from any source, that reasonably suggests that a device that it markets has malfunctioned and this device or a similar device that your firm markets would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur, as required by 21 CFR 803.50(a)(2).For example, the information included for Complaints No. 00057, 00065, 00070, 00071, 00072, 00074, 00077, 00079, 00080, 00082, 00083, and 00086, reasonably suggests that your firm’s Guardian System malfunctioned while in use. Specifically, the device prematurely reached its end of service due to early battery depletion, meaning that it failed to meet its performance specifications or otherwise perform as intended under 21 CFR 803.3(k). Your firm initiated recall Z-1140-2025 for the referenced malfunction. A malfunction is reportable if the manufacturer takes or would be required to take an action under sections 518 or 519(g) of the Act as a result of the malfunction of the device or other similar devices. See Medical Devices; Medical Device User Facility and Manufacturer Reporting, Certification and Registration, 60 Fed. Reg. 63585 (Dec. 11, 1995) (referring to section 519(f), which has since been redesignated as section 519(g)). As such, the referenced complaints represent MDR reportable events, as defined under 21 CFR 803.3(o)(2)(ii).Your firm became aware of information on the following dates that reasonably suggests that the Guardian System had malfunctioned and this device or a similar device your firm markets would be likely to cause or contribute to a death or serious injury, if the malfunction were to recur: October 10, 2023, for Complaint No. 00057; February 26, 2024, for 00065; May 28, 2024, for 00070; May 14, 2024, for 00071; May 5, 2024, for 00072; May 14, 2024, for 00074; July 17, 2024, for 00077; August 29, 2024, for 00079; August 21, 2024, for 00080; November 19, 2024, for 0008; November 19, 2024, for 00083; and December 3, 2024, for 00086. Your firm submitted a report for each event using the MedWatch Online Voluntary Reporting Form. Specifically, MW5149541 (Complaint No. 00057), MW5153561 (Complaint No. 00065), MW5159171 (Complaint No. 00070), MW5159172 (Complaint No.00071), MW5159173 (Complaint No. 00072), MW5159805 (Complaint No. 00074), MW5160629 (Complaint No. 00077), MW5160632 (Complaint No. 00079), MW5160633 (Complaint No. 00080), MW5164478 (Complaint No. 00082), MW5164476 (Complaint No. 00083), and MW5164481 (Complaint No. 00086). The submission of reports using the voluntary MedWatch Online Voluntary Reporting Form does not fulfill reporting obligations arising under 21 CFR Part 803. An electronic submission of a mandatory report from a manufacturer must contain the information from the applicable blocks of Form FDA 3500A. All medical device reports must be submitted within the required timeframes. However, the FDA did not receive the corresponding MDRs until April 14, 2025, which exceeded the required 30 calendar day reporting timeframe.The adequacy of your firm’s responses cannot be determined at this time. We acknowledge that the FDA received the manufacturer reports, submitted using the electronic equivalent of Form 3500A, for the referenced malfunction events based on your firm’s retrospective review on April 14, 2025, after the 30 calendar day reporting timeframe had elapsed.However, although the response referenced the updated MDR procedure “Medical Device Vigilance Procedures,” Document No. 1716-005, as part of its correction action for the late reporting issue, a copy of the updated MDR procedure was not included.In addition, the inspection revealed that your firm failed to develop, maintain, and implement written MDR procedures as required by 21 CFR 803.17. For example, your firm presented the document titled “Medical Device Vigilance Procedures,” Document No. 1716-005, Rev. F, dated June 25, 2024, as its MDR procedure. Upon review, we conclude that the MDR procedure does not develop, maintain, and implement written MDR procedures for internal systems that provide for timely transmission of complete medical device reports to FDA, as required by 21 CFR 803.17(a)(3). Specifically, the procedure 1716-005, Rev. F does not include instructions for how your firm will comply with the 21 CFR 803.12(a) requirement to submit reports to FDA in an electronic format that FDA can process, review, and archive. As a manufacturer, you must submit reports of individual adverse events to FDA in an electronic format in accordance with 21 CFR 803.12(a) and 803.20, unless granted an exemption under 21 CFR 803.19.The adequacy of your firm’s responses cannot be determined at this time. While your response included a copy of the updated Complaint Procedure, Document No.1716-002, and staff training records, it referenced an update to the MDR procedure “Medical Device Vigilance Procedures,” Document No. 1716-005, without including a copy. Without the referenced document, we cannot fully assess the adequacy of the response.Corrections and Removals ViolationOur inspection also revealed that your firm’s Guardian System Model AMSG3‐E IMD implant 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. 21 CFR Part 806 – Medical Devices; Reports of Corrections and Removals was promulgated under section 519 of the Act, among other provisions. Violations include, but are not limited to, the following:Failure to submit to the FDA within 10 working days of initiating a correction or removal a report required by 21 CFR 806.10.Specifically, on September 18, 2023, Avertix Medical, Inc., delivered a letter to physicians who have patients implanted with a Model AMSG3‐E IMD manufactured during the period when a contamination issue was occurring on the battery production line. This issue led to premature battery depletion in the Guardian System implants, which can result in failure to monitor and earlier‐than‐expected implant replacement surgery. The letter recommends reducing the interval of regular follow-up visits and reinforcing the patient training. FDA determined that shorter device implant life leading to sooner than expected replacement surgery may present a risk to health. This action constitutes a medical device correction or removal initiated to reduce a risk to health posed by the device or remedy a violation of the Act caused by the device which may present a risk to health under 21 CFR 806.10(a). Accordingly, you were required to submit a Report of Correction or Removal to FDA within 10 working days of initiation, under 21 CFR 806.10(b). You submitted a Medical Device Report of Correction or Removal to FDA for this action on December 11, 2024.We reviewed your firm’s responses and conclude that they are not adequate. The responses do not contain evidence that your firm’s procedures will result in compliance with the medical device correction and removal reporting requirements in 21 CFR 806. CAPA 00020 states that management failed to recognize that it needed to submit a Report of Correction or Removal within 10 working days of initiation. Your corrective action was retraining personnel in two procedures, Complaint Procedure (1716-002) and Vigilance Procedure (1716-005). You stated that your Quality Management System (QMS) procedure specifies that recalls or corrections must be reported within 10 days. However, your responses did not include a new revision of 1716-005 nor procedure 1716-004, PRODUCT RECALLS, CORRECTIONS AND REMOVALS. Procedure 1716-004 Rev F, collected in the inspection, notes that the Recall Coordinator is responsible for communicating with regulatory agencies within defined reporting times as per the Vigilance procedure. The procedure titled MEDICAL DEVICE VIGILANCE PROCEDURES, 1716-005 Rev F, collected during the inspection, does not describe Reports of Corrections or Removals, required by 21 CFR 806. Therefore, training personnel on 1716-005 will not help personnel know the timeframe for reporting a Medical Device Correction or Removal to FDA.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 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 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. 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 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 Establishment Assessment Team 1 Assistant Director Gina Brackett at CDRHEnforcement@fda.hhs.gov. Please include in the subject line, “CMS Case 711080” when replying. If you have any questions about the contents of this letter, please contact: Sean Moynihan, Compliance Officer at sean.moynihan@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,/S/Matthew G. HillebrennerDeputy DirectorOffice of Product Evaluation and QualityCenter for Devices and Radiological Health

Delivery Method:VIA UPSReference #:320-26-52Product:Drugs,Over-the-Counter DrugsRecipient:Mr. Vimal Patel DirectorDirectorPatcos Cosmetics Pvt. Ltd.Survey No. 659 A Kevdi Falia RoadDaman396210Dadra and Nagar Haveli and Daman and DiuIndiaIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-52March 12, 2026Dear Mr. Patel:The United States Food and Drug Administration (FDA) conducted an unannounced inspection of your drug manufacturing facility, Patcos Cosmetics Pvt. Ltd., FEI 3009250196, at Survey No. 659, A Kevdi Falia Road, Daman, Dadra and Nagar Haveli and Daman, India, from July 14 to 18, 2025.Your drug products are adulterated under section 501(a)(2)(A) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(A), in that they have been prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health.This warning letter also summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your August 11, 2025, response to our Form FDA 483 in detail. 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.During our inspection, our investigators observed specific violations including, but not limited to, the following:Insanitary ConditionsYour firm manufactures over-the-counter (OTC)(b)(4)drug products that are marketed to(b)(4). Your drug products are adulterated under section 501(a)(2)(A) of the FD&C Act because they were prepared, packed, and held under insanitary conditions1. Your production operations, including filling lines, are conducted in a facility that lacks adequate separation barriers from the external environment. Specifically, our investigators observed evidence of harborage areas, broken windows, insanitary production-area sinks, and significant water damage in areas where open processing lines are located and where finished drug products are stored. Further, the investigators observed the following:Harborage areas immediately outside the first floor of the facility where filling, packaging, and(b)(4)production operations are performed. This area consisted of discarded piping with window-grate openings to the exterior of the facility.A broken window precluding the protection of open processing(b)(4)lines (lower right of photo) from the outside environment surrounding the facility.Sinks in the production area used as a source of water for cleaning production equipment.The insanitary conditions of your facility did not provide adequate protections of your(b)(4)manufacturing operations from potential contamination with filth.In your response, you state that facility cleaning and repairs will be carried out before restarting production. Your response is inadequate because no other details were provided including but not limited to the scope of repairs, timeframes for completion, or photographs documenting completed remediation. Nor did you include a comprehensive evaluation of your failure to maintain your facility and equipment in a clean and sanitary condition or the potential impact to your OTC drug products.In response to this letter, provide:A comprehensive plan to remediate the facility, given the pervasive nature of the insanitary conditions.Detailed procedures that demonstrate your firm can maintain buildings free from pests and that they remain in a clean and sanitary state.CGMP Violations1. Your firm failed to maintain buildings used in the manufacture, processing, packing, or holding of drug products in a good state of repair (21 CFR 211.58).Your firm failed to maintain your facility in a good state of repair. During a 2017 FDA inspection, our investigators noted that your facility was in disrepair and had experienced flood damage to your facility and(b)(4)system. Our current inspectional findings were commensurate with findings from 2017, indicating that you have not properly remediated and maintained your facility. For example, in addition to the previously mentioned insanitary conditions:The first floor of your facility contained dirt residue-covered flooring as well as water damage, which resulted in inadequate maintenance of the(b)(4)-production system.The(b)(4)floor of your facility showed evidence of significant water damage with brown discoloration of the ceiling and walls and green mold-like residue on the ceiling in retained product storage areas.Although you are not currently producing(b)(4)drug products for the United States (U.S.), the processing lines were previously used to produce(b)(4)for the U.S. and continue to supply other markets.To protect drug products from potential routes of contamination, your facility must be kept in a good state of repair and sanitary conditions must be maintained.In response to this letter, provide:Your corrective action and preventive action (CAPA) plan to implement routine, vigilant operations management oversight of facilities and equipment. This plan should ensure, among other things, prompt detection of equipment/facilities performance issues, effective execution of repairs, adherence to appropriate preventive maintenance schedules, timely technological upgrades to the equipment/facility infrastructure, and improved systems for ongoing management review.2. Your firm failed to conduct at least one test to verify the identity of each component of a drug product (21 CFR 211.84(d)(1)).Your firm repeatedly failed to adequately perform identity testing of incoming high-risk components for(b)(4)contamination. In response to our December 15, 2023, FDA Warning Letter 320-24-13 pertaining to the 704(a)(4) records request, you committed to updating your specifications and ensuring robust and documented testing procedures for each high-risk component, including but not limited to(b)(4)solution, used in the manufacture of your OTC(b)(4)drug products. During our recent inspection, we found your practices continued to be inadequate, in that:You continued to use the Indian Pharmacopoeia (IP-(b)(4)) specification for(b)(4)solution which did not require impurities or identity testing for(b)(4).You have not updated sampling procedures to ensure that sampling was properly documented and adequately represented each shipment of each lot of high-risk components.You affirmed that the methods used by your third-party lab to perform identity testing are neither validated nor verified.Your responses are inadequate and demonstrate a failure to meet commitments. In your response to Warning Letter 320-24-13, you claimed that testing would be implemented. In your August 2025 response you reiterate previous commitments, stating that you will initiate validation/verification of all analytical methods using ICH guidelines and that USP-compliant(b)(4)testing protocols will be adopted. Your current response is inadequate because you did not provide timeframes for completion, documented method validation, and an updated specification with sampling plan to ensure the quality of your high-risk components.The use of ingredients contaminated with(b)(4)has resulted in various lethal poisoning incidents in humans worldwide. See FDA’s guidance document(b)(4)to help you meet the CGMP requirements when manufacturing drugs containing ingredients at high-risk for(b)(4)contamination at(b)(4).In response to this letter, provide:A commitment to provide(b)(4)test results, no later than 30 calendar days from the date of this letter, from testing retains for all lots of high-risk drug components used in the manufacture of drug products. Alternatively, if a retain of a component lot is unavailable, perform retain sample testing of all implicated finished drug product batches for the presence of(b)(4).A full risk assessment for drug products that are within expiry which contain any ingredient at risk for(b)(4)contamination (including, but not limited to,(b)(4)). Take prompt and appropriate actions to determine the safety of all lots of the component(s) and any related drug product that could contain(b)(4), including customer notifications and product recalls for any contaminated lots. Identify additional appropriate 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 certificate of analysis (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(b)(4)and certain additional high-risk components we note that this includes the performance of parts A, B. and C of the United States Pharmacopeia (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.3. Your firm failed to establish adequate written procedures for production and process control designed to assure that the drug products you manufacture have the identity, strength, quality, and purity they purport or are represented to possess (21 CFR 211.100(a)).Inadequate(b)(4)SystemYour firm uses(b)(4)as a component to manufacture OTC(b)(4)drug products. You failed to adequately validate your(b)(4)-production process to ensure that the system was producing(b)(4)of appropriate quality for its intended use. Additionally, our investigators observed that your(b)(4)system contained several design flaws (e.g., ball valves,(b)(4)tubing with numerous joints, inadequate pipe sloping, threaded fittings and(b)(4)tape), and it was not adequately maintained and periodically sanitized. Furthermore, your(b)(4)system was inadequately monitored to ensure that it consistently produced(b)(4)that met appropriate chemical and microbial quality standards.In your response, you state that your(b)(4)-system remediation will take effect when you resume routine production. Your response is inadequate because you do not include timeframes for remediating your(b)(4)system’s poor design, completing microbiological and(b)(4)testing, nor validation or sanitization of your(b)(4)system. Further, you do not address the potential impact of a poorly designed(b)(4)system on drug products distributed within the United States that are within expiry.(b)(4)is(b)(4)which must be suitable for its intended use and routinely tested. To achieve an ongoing state of control in your(b)(4)system, you must conduct routine monitoring of(b)(4), and microbial levels and identify any contamination in the system.Inadequate Process ValidationYou failed to validate the processes you use to manufacture your OTC drug products. During our inspection, you affirmed that process validation was not performed. Furthermore, you provided records for eight batches of(b)(4)drug products tested in December 2023 and January 2024 that were super potent ((b)(4)% to(b)(4)%) for your active ingredient,(b)(4). Your failure to properly validate your manufacturing processes provides a lack of assurance that your finished products have met all quality attributes including specifications.In your response, you state that you will validate manufacturing processes once routine manufacturing resumes. Your response is inadequate because you do not provide documentation or timeframes for completing your process validation, nor do you consider a retrospective assessment of the potential impact to your products distributed within the U.S. 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(b)(4)system design, control, and maintenance.A thorough remediation plan to install and operate a suitable(b)(4)system. Include a robust ongoing control, maintenance, and monitoring program to ensure the remediated system design consistently produces(b)(4)adhering to(b)(4), United States Pharmacopoeia (USP) monograph, specifications and appropriate microbial limits.Regarding the latter, ensure that your total microbial count limit for(b)(4)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(b)(4)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.4. Your firm failed to establish an adequate quality unit and the responsibilities and procedures applicable to the quality control unit are not in writing and fully followed (21 CFR 211.22(a) and (d).The records and information you provided demonstrate that your quality unit (QU) did not effectively exercise its responsibilities to oversee the quality of your drug manufacturing operations. Specifically, your QU failed to:Ensure adequate control over laboratory data including deliberate alteration of original data to conceal out-of-specification results (21 CFR 211.194).Ensure that batch production and control records are complete (21 CFR 211.188)Ensure adequate specifications, sampling plans, and test methods for components and drug products to assure they conform to appropriate standards of identity, strength, quality and purity (21 CFR 211.160(b)).Ensure the establishment of a written testing program designed to assess the stability characteristics of drug products and to use the results of stability testing to determine appropriate storage conditions and expiration dates (21 CFR 211.166(a)).In your response, you state that you will perform certain corrective actions upon resumption of production but acknowledge that you have limited ability to fully implement the proposed systemic changes across the facility. Your response is inadequate because you did not provide documentation in support of any proposed changes or commit to compliance with CGMP before resuming operations. Furthermore, your response does not address the significant failures in data governance observed during our inspection.Significant findings in this letter demonstrate that your firm does not operate an effective quality system in accordance with CGMP. In addition to the lack of effective management oversight of your production and laboratory operations, we found that your QU was not enabled to exercise proper authority and insufficiently implemented its responsibilities. Executive management should immediately and comprehensively assess your company’s manufacturing operations to ensure that your systems, processes, and products meet CGMP.Your firm’s quality systems are inadequate. See FDA’s guidance documentQuality Systems Approach to Pharmaceutical CGMP Regulationsfor help in 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 appropriateo Provisions for QU oversight throughout your operations to evaluate adherence to appropriate practiceso A complete and final review of each batch and its related information before the QU disposition decisiono Oversight and approval of investigations and discharging of all other QU duties to ensure identity, strength, quality, and purity of all productsA comprehensive, independent assessment and CAPA plan to ensure the adequacy of your stability program. Your remediated program should include, but not be limited to:o Stability indicating methodso Stability studies for each drug product in its marketed container-closure system before distribution is permittedo 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 valido Detailed definition of the specific attributes to be tested at each station (timepoint)Responsibilities as a ContractorDrugs must be manufactured in conformance with CGMP. FDA is aware that many drug manufacturers use independent contractors such as production facilities, testing laboratories, packagers, and labelers. FDA regards contractors as extensions of the manufacturer. You are responsible for the quality of drugs you produce as a contract facility regardless of agreements in place with product owners. You are required to ensure that drugs are made in accordance with section 501(a)(2)(B) of the FD&C Act for safety, identity, strength, quality, and purity. See FDA’s guidance document Contract Manufacturing Arrangements for Drugs: Quality Agreements at https://www.fda.gov/media/86193/download.Data Integrity RemediationYour quality system does not adequately ensure the accuracy and integrity of data to support the safety, effectiveness, and quality of the drugs you manufacture. See FDA’s guidance document Data Integrity and Compliance With Drug CGMP for guidance on establishing and following CGMP compliant data integrity practices at https://www.fda.gov/files/drugs/published/Data-Integrity-and-Compliance-With-Current-Good-Manufacturing-Practice-Guidance-for-Industry.pdf.We strongly recommend that you retain an independent third-party qualified consultant to assist in your remediation. In response to this letter, provide:A comprehensive investigation into the extent of the inaccuracies in data records and reporting. Your investigation should include:o A detailed investigation protocol and methodology; a summary of all laboratories, manufacturing operations, and systems to be covered by the assessment; and a justification for any part of your operation that you propose to exclude.o Interviews of current and former employees to identify the nature, scope, and root cause of data inaccuracies. We recommend that these interviews be conducted by a qualified third party.o An assessment of the extent of data integrity deficiencies at your facility. Identify omissions, alterations, deletions, record destruction, non-contemporaneous record completion, and other deficiencies. Describe all parts of your facility’s operations in which you discovered data integrity lapses.o A comprehensive retrospective evaluation of the nature of the testing and manufacturing data integrity deficiencies. We recommend that a qualified third party with specific expertise in the area where potential breaches were identified should evaluate all data integrity lapses.A current risk assessment of the potential effects of the observed failures on the quality of your drugs. Your assessment should include analyses of the risks to patients caused by the release of drugs affected by a lapse of data integrity and analyses of the risks posed by ongoing operations.A management strategy for your firm that includes the details of your global corrective action and preventive action plan. Your strategy should include:o A detailed corrective action plan that describes how you intend to ensure the reliability and completeness of all the data you generate including analytical data, manufacturing records, and all data submitted to FDA.o A comprehensive description of the root causes of your data integrity lapses including evidence that the scope and depth of the current action plan is commensurate with the findings of the investigation and risk assessment. Indicate whether individuals responsible for data integrity lapses remain able to influence CGMP-related or drug application data at your firm.o Interim measures describing the actions you have taken or will take to protect patients and to ensure the quality of your drugs, such as notifying your customers, recalling product, conducting additional testing, adding lots to your stability programs to assure stability, drug application actions, and enhanced complaint monitoring.o Long-term measures describing any remediation efforts and enhancements to procedures, processes, methods, controls, systems, management oversight, and human resources (e.g., training, staffing improvements) designed to ensure the integrity of your company’s data.o A commitment to have a qualified consultant conduct extensive annual audits, for at least two years, to assist in evaluating CAPA effectiveness after you have executed your data integrity remediation protocol.o Inform FDA if you will be hiring a Chief Integrity Officer who is fully empowered to receive anonymous complaints from employees reporting data integrity concerns and with the authority to ensure any potential breach is promptly investigated (by independent quality assurance function, along with expertise from outside entities whenever needed).o A status report for any of the above activities already underway or completed.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 if your firm intends to resume manufacturing drugs for the U.S. market. The qualified consultant should also perform a comprehensive six-system audit of your entire operation for CGMP compliance and evaluate the completion and efficacy of your corrective actions and preventive actions before you pursue resolution of your firm’s compliance status with FDA. Your use of a consultant does not relieve your firm’s obligation to comply with CGMP. Your firm’s executive management remains responsible for resolving all deficiencies and systemic flaws to ensure ongoing CGMP compliance.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.FDA placed all drugs and drug products offered for import into the United States from your firm on Import Alert 66-40 on November 17, 2023, and issued an FDA Warning Letter on December 15, 2023, after review of your response to our 704(a)(4) Request for Records sent to you on July 12, 2023. Your response demonstrated CGMP violations related to controls for(b)(4)in high-risk components used in your drugs. In response to this previous Warning Letter, your firm elected to re-register your facility stating your readiness for inspection and emphasizing your “ongoing compliance with current Good Manufacturing Practices” and “adhering to the highest quality standards”.The inspectional findings detailed above further demonstrate your firm’s noncompliance, regardless of your affirmed compliance to CGMP and inspectional readiness status.Your firm remains on Import Alert 66-40.Correct any violations promptly. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to any violations.Failure to address any violations may also result in the FDA continuing to refuse admission of articles manufactured at Patcos Cosmetics Pvt. Ltd, 659 Kevdi Falia Road, Daman, India into the United States under section 801(a)(3) of the FD&C Act, 21 U.S.C. 381(a)(3). Articles under this authority that appear to be adulterated may be detained or refused admission, in that the methods and controls used in their manufacture do not appear to conform to CGMP within the meaning of section 501(a)(2)(B) of the FD&C Act, 21 U.S.C. 351(a)(2)(B).This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3009250196 and ATTN: Matthew R. Dionne.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and ResearchCC:Mr. Kantibhai PatelChairmanPatcos Cosmetics Pvt. Ltd.120 Mahal Industrial EstateMahakali Caves RoadMumbai, Maharashtra400093 India__________1CDER is including photographs of your facility in this warning letter to document the gross insanitary conditions violations.

Delivery Method:VIA ELECTRONIC MAIL READ/DELIVERY RECEIPT REQUESTEDProduct:DrugsRecipient:Priyanka RanaPresident and Chief Pharmacy OfficerApothecary Pharma, LLC1913 Evans RoadCary,NC27513-2041United StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERWL # 717972December 1, 2025Dear Ms. Rana:You registered your facility with the U.S. Food and Drug Administration (FDA) as an outsourcing facility under section 503B of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. § 353b]1on September 7, 2024, and most recently on January 11, 2025. From May 12, 2025, to May 15, 2025, FDA investigators inspected your facility, Apothecary Pharma, LLC located at 1913 Evans Road, Cary, NC 27513. During the inspection, the investigators noted that drug products you produced failed to meet the conditions of section 503B of the FDCA necessary for drugs produced by an outsourcing facility to qualify for exemptions from certain provisions of the FDCA. In addition, the investigators noted serious deficiencies in your practices for producing drug products intended or expected to be sterile, which put patients at risk.FDA issued a Form FDA 483 to your facility on May 15, 2025. FDA acknowledges receipt of your facility’s response, dated June 9, 2025, and related attachments received July 17, 2025. FDA acknowledges that your firm ceased sterile drug production as of May 12, 2025, and notified FDA of an intent to resume sterile drug production on August 1, 2025. Based on this inspection, it appears you produced drugs that violate the FDCA.A. Compounded Drug Products under the FDCAUnder section 503B(b) of the FDCA, a compounder can register as an outsourcing facility with FDA. Drug products compounded by or under the direct supervision of a licensed pharmacist in an outsourcing facility qualify for exemptions from the drug approval requirements in section 505 of the FDCA [21 U.S.C. § 355(a)], the requirement in section 502(f)(1) of the FDCA [21 U.S.C. § 352(f)(1)] that labeling bear adequate directions for use and the Drug Supply Chain Security Act requirements in section 582 of the FDCA [21 U.S.C. § 360eee-1] if the conditions in section 503B of the FDCA are met.2An outsourcing facility, which is defined in section 503B(d)(4) of the FDCA [21 U.S.C. § 353b(d)(4)], is a facility at one geographic location or address that — (i) is engaged in the compounding of sterile drugs; (ii) has elected to register as an outsourcing facility; and (iii) complies with all of the requirements of this section. Outsourcing facilities must comply with other applicable provisions of the FDCA, including section 501(a)(2)(B) [21 U.S.C. § 351(a)(2)(B)], regarding current good manufacturing practice (CGMP), and section 501(a)(2)(A) [21 U.S.C. § 351(a)(2)(A)], regarding insanitary conditions. Generally, CGMP requirements for the preparation of drug products are established in Title 21 of the Code of Federal Regulations (CFR) parts 210 and 211.For a compounded drug product to qualify for the exemptions under section 503B, the labeling of the drug must include certain information (section 503B(a)(10) of the FDCA [21 U.S.C. §353b(a)(10)]).In addition, for a compounded drug product to qualify for the exemptions under section 503B, it must be compounded in an outsourcing facility that is in compliance with the registration and reporting requirements in section 503B(b), including the requirement to submit adverse event reports to FDA “in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations)” (section 503B(a)(1), (b)(5) of the FDCA [21 U.S.C. § 353b(a)(1), (b)(5)]).B. Failure to Meet the Conditions of Section 503BDuring the inspection, FDA investigators noted that drug products produced by your facility failed to meet the conditions of section 503B. For example, the investigators noted:1. Some of your facility’s drug products, such as Tirzepatide Injection 10 mg/mL and Semaglutide Injection 2.5 mg/mL, did not include the following information on the label: a list of active and inactive ingredients, identified by established name and the quantity or proportion of each ingredient. Additionally, some of your facility’s drug products did not include the following information on the container: information to facilitate adverse event reporting and directions for use, including, as appropriate, dosage and administration.2. Your facility did not submit adverse event reports to FDA in accordance with the content and format requirements established through guidance or regulation under section 310.305 of title 21, Code of Federal Regulations (or any successor regulations).3Specifically, your facility’s procedures for reporting adverse events are inadequate. For example, your documented procedures for reporting adverse events do not include a definition of what constitutes a “serious” and “unexpected” adverse event (21 CFR 310.305(b)).Because your compounded drug products have not met all of the conditions of section 503B, they are not eligible for the exemptions in that section from the FDA approval requirements of section 505, the requirement under section 502(f)(1) that labeling bear adequate directions for use, and the Drug Supply Chain Security Act requirements described in section 582 of the FDCA.Specific violations are described below.C. Violations of the FDCAAdulterated Drug ProductsFDA investigators noted that drug products intended or expected to be sterile were prepared, packed, or held under insanitary conditions, whereby they may have become contaminated with filth or rendered injurious to health, causing your drug products to be adulterated under section 501(a)(2)(A) of the FDCA. For example, the investigators observed:1. An operator blocked first air by placing gloved hands directly over open sterile containers.2. An operator placed components within the ISO 5 work area that had the potential to block the movement of first air to critical in-process operations. Specifically, an operator positioned a second row of exposed vials behind a first row in the ISO 5(b)(4)laminar flow hood, obstructing first air to critical surfaces.3. An operator rested their arms on the work surface of the hood during aseptic production. This practice may introduce contamination into the ISO 5 work area.4. An operator placed their gloved hands outside the ISO 5 work area to retrieve supplies without sanitizing their gloved hands before re-entry into the ISO 5 hood.5. Personnel engaged in aseptic processing while exposing skin within the ISO 5 aseptic processing area.6. Your firm failed to perform adequate smoke studies under dynamic conditions to demonstrate unidirectional airflow within the ISO 5 area. Therefore, your products intended to be sterile are produced in an environment that may not provide adequate protection against the risk of contamination.7. Personnel moved quickly in a critical area such that unidirectional airflow is likely to be disrupted.8. Production areas or equipment have difficult to clean and visibly rusty equipment or surfaces.9. Lack of disinfection of equipment and supplies at each transition from areas of lower quality air to areas of higher quality air.10. Failing to disinfect or change gloves frequently enough given the nature of the operations to prevent contamination. More specifically, personnel were observed touching equipment or other surfaces located outside of the ISO 5 area with gloved hands and then proceeding with aseptic processing without changing or sanitizing gloves.FDA investigators also noted CGMP violations at your facility, that caused your drug products to be adulterated within the meaning of section 501(a)(2)(B) of the FDCA. The violations include, for example:1. Your firm failed to establish written responsibilities and procedures applicable to the quality control unit and to follow written procedures applicable to the quality control unit (21 CFR 211.22(d)).2. Your firm failed to establish and follow appropriate written procedures that are designed to prevent microbiological contamination of drug products purporting to be sterile, and that include validation of all aseptic and sterilization processes (21 CFR 211.113(b)).3. Your firm failed to ensure that manufacturing personnel wear clothing appropriate to protect drug product from contamination (21 CFR 211.28(a)).4. Your firm failed to establish an adequate system for maintaining equipment used to control the aseptic conditions (21 CFR 211.42(c)(10)(vi)).5. Your firm failed to establish an adequate system for cleaning and disinfecting the room and equipment to produce aseptic conditions (21 CFR 211.42(c)(10)(v)).6. Your firm failed to prepare batch production and control records with complete information relating to the production and control of each batch of drug product produced (21 CFR 211.188).Outsourcing facilities must comply with CGMP requirements under section 501(a)(2)(B) of the FDCA. FDA’s regulations regarding CGMP requirements for the preparation of drug products have been established in 21 CFR parts 210 and 211. FDA intends to promulgate more specific CGMP regulations for outsourcing facilities. FDA has issued a revised draft guidance,Current Good Manufacturing Practice — Guidance for Human Drug Compounding Outsourcing Facilities under Section 503B of the FD&C Act. This draft guidance, when finalized, will describe FDA’s expectations regarding outsourcing facilities and the CGMP requirements in 21 CFR parts 210 and 211 until more specific CGMP regulations for outsourcing facilities are promulgated.Under section 301(a) of the FDCA [21 U.S.C. § 331(a)], the introduction or delivery for introduction into interstate commerce of any drug that is adulterated is a prohibited act. Further, it is a prohibited act under section 301(k) of the FDCA [21 U.S.C. § 331(k)] to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being adulterated.Unapproved New Drug ProductsYou do not have any FDA-approved applications on file for drug products that you compound.4Under sections 505(a) and 301(d) of the FDCA [21 U.S.C. §§ 331(d)] a new drug may not be introduced into or delivered for introduction into interstate commerce unless an application approved by FDA under section 505 of the FDCA is in effect for the drug. Marketing of these products, or other applicable products, without an approved application violates these provisions of the FDCA.Misbranded Drug ProductsYou compound drug products that are intended for conditions not amenable to self-diagnosis and treatment by individuals who are not medical practitioners; therefore, adequate directions for use cannot be written so that a layman can use these products safely for their intended uses. Consequently, their labeling fails to bear adequate directions for their intended uses causing them to be misbranded under section 502(f)(1) of the FDCA.5The introduction or delivery for introduction into interstate commerce of these products therefore violates section 301(a) of the FDCA. Further, it is also a prohibited act under section 301(k) of the FDCA to do any act with respect to a drug, if such act is done while the drug is held for sale after shipment in interstate commerce and results in the drug being misbranded.D. Corrective ActionsWe have reviewed your facility's response to the Form FDA 483. FDA acknowledges that your firm ceased sterile drug production as of May 12, 2025, and notified FDA of an intent to resume sterile drug production on August 1, 2025.Some of your corrective actions appear adequate; however, we are unable to fully evaluate some of your corrective actions due to lack of adequate supporting documentation:1. We acknowledge your corrective actions addressing operating with draft procedures and improper visual inspection techniques, including finalization of SOPs for Quality Unit responsibilities, Corrective and Preventive Action (CAPA), batch record review, out-of-specification (OOS) results, and retraining on the visual inspection SOP. However, your response remains inadequate because draft SOPs for Change Control, Deviations, and Risk Assessment were not addressed, and you did not assure that draft versions will not be used. In addition, you did not provide competency verification or supervisory oversight of retrained inspectors, nor a retrospective review of batches inspected under improper techniques.2. We acknowledge your actions regarding inadequate skin coverage posing a contamination risk to sterile drug products, including internal training to SOP 0003.00 with emphasis on mirror self-inspection. However, the adequacy of your response cannotbe fully evaluated because you did not provide supporting documentation, competency verification, post-retraining assessments, or updates to SOP 0003.00/procedures to enforce mirror checks. Further, although production was halted until August 1, 2025, you did not submit evidence of interim controls or monitoring results demonstrating proper gowning to assure ongoing compliance thereafter.Some of your corrective actions appear deficient:1. Regarding your firm’s failure to establish written responsibilities and procedures applicable to the quality control unit, we acknowledge your voluntary halt of production on May 12, 2025, and your commitment to implementing corrective actions by August 1,2025. However, your response is inadequate for the following reasons:a. Your response lacks a retrospective review plan for released batches(b)(4),(b)(4)and fails to include a root cause analysis for why incomplete records were initially released. You have not provided training records demonstrating staff understanding of the new SOP 1012.00 procedures or evidence that the enhanced batch record review process addresses all identified deficiencies.b. While you engaged(b)(4)Air for re-certification, you have not acknowledged(b)(4)' license revocation since 2014 or provided a plan to validate prior certifications. Your response lacks vendor qualification procedures (e.g., revising SOP 1009.00) and certification review processes. There is no assessment of previously released products manufactured in potentially uncertified environments, which compromises patient safety.2. We acknowledge your engagement of(b)(4)Air and your retraining efforts related to aseptic operations. However, your response is inadequate because:a. You did not provide detailed protocols to ensure dynamic smoke studies simulate true production with maximum equipment and personnel, nor did you define acceptance criteria or Quality Unit oversight for vendor-conducted studies.b. You failed to conduct a risk assessment for the(b)(4)Tirzepatide 10 mg/mL batches released without validated airflow studies, or to provide an impact evaluation or justification for their release.c. Critical validation gaps remain, including no commitment to perform smoke studies in the ISO 7 cleanroom and no methodologies to improve smoke volume, background contrast, or dynamic simulation.d. Aseptic technique retraining did not address specific behaviors that compromise first air (e.g., blocking critical surfaces, resting forearms on ISO 5 surfaces, leaning into hoods and exposing skin).e. You proposed no workspace/equipment modifications to ensure all vials receive unidirectional airflow, and you did not evaluate equipment configurations to mitigate this risk.3. We acknowledge your retraining to SOP 0003.00 with emphasis on mirror self inspection. However, your response is inadequate because:a. SOP 0003.00 was not updated to reflect the correct gowning sequence or to establish procedures that enforce mirror checks and supervisory oversight.b. You did not provide supporting documentation or competency verification demonstrating proper gowning technique; no post-retraining assessments were submitted.c. You did not address observed deficiencies (e.g., use of safety glasses instead of cleanroom goggles, crossing the demarcation line on the “dirty” side, and masks worn upside down).d. Procedural gaps remain regarding shoe covers over clogs when entering ISO-classified areas.e. Although operations resumed on August 1, 2025, you did not provide evidence of interim controls or monitoring results demonstrating continued compliance after August 1, 2025, or plans to assure ongoing compliance thereafter.4. We acknowledge your commitment to address the condition of the ISO 5 laminar airflow hood (LAFH) by August 1, 2025. However, your response is inadequate because:a. You did not provide essential supporting documentation such as photographic evidence, maintenance records, or updated SOPs, while providing only vague commitments to repair rust damage without specifying repair methods. No interim controls or monitoring were described to mitigate contamination risk while the compromised LAFH remained in service, including upon resumption of operations on August 1, 2025.b. The root cause analysis attributing rust to(b)(4)lacked supporting evidence and did not include revised cleaning protocols, verification, or preventive measures; dents and peeling paint were inappropriately characterized as “cosmetic.”c. Reliance on media fills, sterility tests, or prior certifications does not address equipment condition defects that can harbor contamination or disrupt airflow pattern.d. You failed to provide supporting documentation including photographs, maintenance records, engineering assessments, updated SOPs, or qualification protocols, to demonstrate the implementation and effectiveness of your proposed changes. You did not provide an impact assessment for distributed batches compounded on this LAFH or establish a robust preventive maintenance program to prevent recurrence.5. We acknowledge retraining to SOP 0004 (Ideal Conduct in Cleanroom) and SOP 2001.00 (Cleanroom Material Transfer). However, your response is inadequate because:a. You did not revise your SOPs to establish specific disinfection protocols with clear responsibilities and acceptance criteria.b. You did not provide a comprehensive CAPA plan that includes thorough root cause analysis, implementation evidence, or monitoring strategies to verify effectiveness of corrective actions.c. You failed to provide training documentation and competency assessments demonstrating that personnel can correctly perform material transfer procedures and maintain proper glove hygiene practices. The proposed sanitize-able metal tool for trash handling lacks specificity and does not mitigate immediate contamination risks during aseptic operation.d. You did not submit an ongoing compliance plan (e.g., routine observation, audit checklists, personnel monitoring targets) or interim controls upon resumption of operations on August 1, 2025.6. We acknowledge your retraining to SOP 2004 (Visual Inspection). However, your response is inadequate because:a. You failed to revise batch records and procedures to include proper defect classification (critical/major/minor), Acceptable Quality Levels (AQL) methodology, and acceptance criteria. Additionally, you did not provide an updated Form F-2004.00-01, and AQL documentation continues to be omitted from your quality control processes. You did not submit documentation demonstrating retraining effectiveness (e.g., training curriculum, attendance, competency assessments, completion dates) or supervisory oversight of inspectors.b. You failed to provide impact assessment or retrospective review of distributed lots AP-202505 through AP-202513 to determine whether visual inspection deficiencies affected product quality.c. You failed to provide finalized SOP revisions or evidence of implementation; Annexure-1 lacked sufficient detail to verify changes.d. The referenced CAPA lacked specific corrective actions, milestones, responsible owners, and effectiveness checks.Given the nature and significance of the violations identified, FDA remains concerned that your firm has not yet demonstrated that adequate correction has been properly implemented to sustain sterile drug product manufacturing in a manner fully consistent with CGMP. FDA strongly recommends that your management undertake a comprehensive assessment of operations, including facility design, procedures, personnel, processes, maintenance, materials, and systems. In particular, this review should assess your aseptic processing operations. A third-party consultant with relevant sterile drug manufacturing expertise should assist you in conducting this comprehensive evaluation.In addition to the issues discussed above, you should note that CGMP requires the implementation of quality oversight and controls over the manufacture of drugs, including the safety of raw materials, materials used in drug manufacturing, and finished drug products. See section 501 of the FDCA. If you choose to contract with a laboratory to perform some functions required by CGMP, it is essential that you select a qualified contractor and that you maintain sufficient oversight of the contractor’s operations to ensure that it is fully CGMP compliant. Regardless of whether you rely on a contract facility, you are responsible for assuring that drugs you produce are neither adulterated nor misbranded. [See 21 CFR 210.1(b), 21 CFR 200.10(b).]Should you continue to compound and distribute drug products that do not meet the conditions of section 503B, the compounding and distribution of your drugs would be subject to the new drug approval requirement, the requirement to label drug products with adequate directions for use, and the Drug Supply Chain Security Act requirements.E. ConclusionThe violations cited in this letter are not intended to be an all-inclusive statement of violations 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. It is your responsibility to ensure that your firm complies with all requirements of federal law, including FDA regulations.You should take prompt action to address any violations. Failure to adequately address any violations may result in legal action without further notice, including, without limitation, seizure and injunction.Within fifteen (15) working days of receipt of this letter, please notify this office in writing of the specific steps that you have taken to address any violations. Please include an explanation of each step being taken to prevent the recurrence of violations, as well as copies of related documentation. This letter notifies you of our concerns and provides you an opportunity to address them. If you believe your products are not in violation of the FDCA, include your reasoning and any supporting information for our consideration. If you cannot completely address this matter within fifteen (15) working days, state the reason for the delay and the time within which you will do so.All correspondence should refer to the Warning Letter Number above (# 717972) and include a subject line that clearly identifies the submission as a Response to Warning Letter. If you have questions regarding the contents of this letter, please contact compoundinginspections@fda.hhs.gov.Sincerely,/S/F. Gail Bormel, JD, RPhDirectorOffice of Compounding Quality and ComplianceOffice of ComplianceCenter for Drug Evaluation and Research______________________1SeePub. L. No. 113-54, § 102(a), 127 Stat. 587, 587-588 (2013).2We remind you that there are conditions, other than those discussed in this letter, that must be satisfied to qualify for the exemptions in section 503B of the FDCA.3For more information, see, FDA’s guidance, “Adverse Event Reporting for Outsourcing Facilities Under Section 503B of the Federal Food, Drug, and Cosmetic Act,” which can be found at https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM434188.pdf.4The specific products made by your firm are drugs within the meaning of section 201(g) of the FDCA [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of diseases and/or because they are intended to affect the structure or any function of the body. Further, they are “new drugs” within the meaning of section 201(p) of the FDCA [21 U.S.C. § 321(p)] because they are not generally recognized as safe and effective for their labeled uses.5Your compounded drug products are not exempted from the requirements of section 502(f)(1) of the FDCA by regulations issued by the FDA (see, e.g., 21 CFR 201.115).

Delivery Method:Via Electronic Mail - Return Receipt RequestedReference #:320-26-50Product:Drugs,Over-the-Counter DrugsRecipient:Mr. Gary SchlatterCEOOraLabs, Inc.18685 East Plaza DriveParker,CO80134-9061United Statesgschlatter@oralabs.comIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWarning Letter320-26-50March 11, 2026Dear Mr. Schlatter:The United States Food and Drug Administration (FDA) inspected your drug manufacturing facility, OraLabs Inc., FEI 3001237145, at 18685 East Plaza Drive, Parker, from September 22 to 26, 2025.This warning letter summarizes significant violations of Current Good Manufacturing Practice (CGMP) regulations for finished pharmaceuticals. See Title 21 Code of Federal Regulations (CFR), parts 210 and 211 (21 CFR parts 210 and 211).Because your methods, facilities, or controls for manufacturing, processing, packing, or holding do not conform to CGMP, your drug products are adulterated within the meaning of section 501(a)(2)(B) of the Federal Food, Drug, and Cosmetic Act (FD&C Act), 21 U.S.C. 351(a)(2)(B).We reviewed your October 17, 2025, response to our Form FDA 483 in detail.During our inspection, our investigators observed specific violations including, but not limited to, the following.1. Your firm failed to conduct, for each batch of drug product, appropriate laboratory testing, as necessary, required to be free of objectionable microorganisms (21 CFR 211.165(b)).Your firm operates as both a contract and own label manufacturer of over-the-counter (OTC) drug products, including(b)(4)marketed to(b)(4). Your firm released multiple batches of OTC drug products without performing appropriate microbiological release testing. For example, on February 4, 2025, you manufactured over(b)(4)units of(b)(4)(Lot(b)(4)) without performing microbiological testing for release. Your quality unit (QU) approved and released this lot on(b)(4), and distributed it to your customer on(b)(4).In your response you confirmed that you perform microbiological testing only at your customer’s request. You also provided a justification memo which concluded “no testing required” for total aerobic microbial count, total combined yeasts/molds, and specified microorganisms based on your products being(b)(4). Your response is inadequate. FDA has encountered recalls for microbial contamination in(b)(4)drug products. Your justification memo reveals microbial growth in your drug products. While microbial proliferation risk may be lower, microorganisms can persist in your drug products. Eliminating microbial testing of your drug products is unacceptable. CGMP regulations require written procedures be established to prevent introduction of objectionable microbiological contamination in the manufacture of drug products not required to be sterile.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 (i.e., total counts, identification of bioburden to detect objectionable microbes), including test methods, used to analyze each lot of your drug products before a lot disposition decision.o 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 within the United States that are within expiry as of the date of this letter.o A summary of results from testing retain samples of all 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 out-of-specification (OOS) result, indicate the corrective actions you will take, including notifying customers and initiating recalls.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).Your investigations into microbiological testing failures when your customers requested such testing frequently lacked thorough root cause analysis and appropriate corrective actions and preventive actions (CAPAs). For example, you investigated total aerobic counts exceeding specification limits for(b)(4)drug product and identified the microorganism asBacillus cereus. However, you invalidated this excursion because the specific pathogens listed on the certificate of analysis were not detected. You concluded that the “most likely source of contamination would be from environmental contamination during the manufacturing process.” You lacked adequate scientific rationale to invalidate this excursion.Additionally, multiple investigations resulted in inconclusive root causes or were invalidated with inconsistent approaches that often lacked thorough manufacturing investigations, environmental sampling, and other potential sources of contamination. Your investigations inappropriately minimized the risk of these microbial excursions by stating that products had lower(b)(4)content and “product does not support growth.” Your conclusions contradict the microbial excursions detected in your test results, and your QU released the associated lots for distribution.In your response, you commit to evaluating procedures and including additional documentation for OOS results, as well as training employees. Your response does not adequately demonstrate that your firm has remediated its investigational capabilities to ensure comprehensive, well-documented, and scientifically rigorous investigations to effectively identify root causes and result in appropriate CAPAs.In response to this letter, provide: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.A detailed risk assessment addressing the hazards posed by distributing drug products with potentially objectionable contamination. Specify actions you will take in response to the risk assessment, such as customer notifications and product recalls.Complete investigations into all batches with potential objectionable microbial contamination or a microbial excursion (whether or not later invalidated or inconclusive). The investigations should detail your findings regarding the root causes of the contamination.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 documentContract Manufacturing Arrangements for Drugs: Quality Agreementsat https://www.fda.gov/media/86193/download.ConclusionThe violations cited in this letter are not intended to be an all-inclusive list of violations that exist at your facility. You are responsible for investigating and determining the causes of any violations and for preventing their recurrence or the occurrence of other violations.Correct any violations promptly. Failure to promptly and adequately address this matter may result in regulatory or legal action without further notice including, without limitation, seizure and injunction. Unresolved violations may also prevent other Federal agencies from awarding contracts.Failure to address violations may also cause FDA to withhold issuance of Export Certificates. FDA may withhold approval of new applications or supplements listing your firm as a drug manufacturer until any violations are completely addressed and we confirm your compliance with CGMP. We may re-inspect to verify that you have completed corrective actions to address any violations.This letter notifies you of our findings and provides you an opportunity to address the above deficiencies. After you receive this letter, respond to this office in writing within 15 working days. Specify what you have done to address any violations and to prevent their recurrence. In response to this letter, you may provide additional information for our consideration as we continue to assess your activities and practices. If you cannot complete corrective actions within 15 working days, state your reasons for delay and your schedule for completion.Send your electronic reply to CDER-OC-OMQ-Communications@fda.hhs.gov. Identify your response with FEI 3001237145 and ATTN: Bryce Hammer.Sincerely,/S/Francis GodwinDirectorOffice of Manufacturing QualityOffice of ComplianceCenter for Drug Evaluation and Research

Product:DrugsRecipient:Citra100mgUnited StatesIssuing Office:Center for Drug Evaluation and Research (CDER)United StatesWARNING LETTERMarch 4, 2026RE: Notice of Unlawful Sale of Unapproved and Misbranded Drugs to United States Consumers Over the InternetCitra100mg:This is to advise you that the United States (U.S.) Food and Drug Administration (FDA) recently reviewed your website at the Internet address www.citra100mg.com and has observed that your website introduces into interstate commerce misbranded and unapproved new drugs in violation of sections 301(a), 301(d), 301(k), 502(f)(1), 503(b)(1), and 505(a) of the Federal Food, Drug, and Cosmetic Act (FD&C Act) [21 U.S.C. §§ 331(a), 331(d), 331(k), 352(f)(1), 353(b)(1), and 355(a)].As discussed below, FDA has observed that www.citra100mg.com introduces into interstate commerce unapproved and misbranded opioids. Opioid addiction and abuse have created an immense public health crisis, and the death toll is staggering. Given the severity of the opioid epidemic, the easy availability of opioids via the Internet poses significant risks to U.S. consumers.There are inherent risks to consumers who purchase unapproved new drugs and misbranded drugs. Unapproved new drugs do not carry the same assurances of safety and effectiveness as those drugs subject to FDA oversight. Drugs that have circumvented regulatory safeguards may be contaminated, counterfeit, contain varying amounts of active ingredients, or contain different ingredients altogether. Accordingly, FDA requests that www.citra100mg.com cease offering any unapproved and misbranded drugs for sale to U.S. consumers. This is critical to shielding the American public from harm.Unapproved New Drugs:Certain products offered for sale by www.citra100mg.com are drugs within the meaning of section 201(g) of the FD&C Act [21 U.S.C. § 321(g)] because they are intended for use in the diagnosis, cure, mitigation, treatment, or prevention of disease and/or because they are intended to affect the structure or function of the body. These drugs are also new drugs as defined by section 201(p) of the FD&C Act [21 U.S.C. § 321(p)], because they are not generally recognized as safe and effective for their labeled uses. With certain exceptions not applicable here, new drugs may not be legally introduced or delivered for introduction into interstate commerce without prior approval from FDA, as described in section 505(a) of the FD&C Act [21 U.S.C. § 355(a)]. No approved applications pursuant to section 505 of the FD&C Act are in effect for these products. Accordingly, their introduction or delivery for introduction into interstate commerce violates sections 301(d) and 505(a) of the FD&C Act [21 U.S.C. §§ 331(d) and 355(a)].An example of an unapproved opioid you offer for sale on www.citra100mg.com is tramadol marketed as “Citra 100mg”, “Clovidol 100mg”, “Jpdol 100mg”, “Ol tram 100mg”, “OL-tram Loose Pills”, and “Trakem 100 mg”. Evidence obtained from your website establishing that this product is a drug intended for human use (as defined in 21 CFR 201.128) includes the claim “Effective Painkillers to Treat Chronic Pain”. While there are FDA-approved versions of tramadol on the market in the U.S., there are no approved drug applications pursuant to section 505 of the FD&C Act in effect for “Citra 100mg”, “Clovidol 100mg”, “Jpdol 100mg”, “Ol tram 100mg”, “OL-tram Loose Pills”, and “Trakem 100 mg” offered by www.citra100mg.com. FDA-approved tramadol is indicated in adults for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.FDA-approved tramadol is only available pursuant to a prescription from a licensed practitioner. Furthermore, this drug product bears a boxed warning, commonly referred to as a “black box warning,” which is the strongest warning FDA requires, indicating that the drug carries a significant risk of serious or even life-threatening adverse effects. This boxed warning addresses risks including addiction, abuse, misuse, life-threatening respiratory depression (breathing problems), neonatal opioid withdrawal syndrome (withdrawal symptoms in newborn baby), and accidental exposure resulting in death. In addition, when these drug products are taken in conjunction with other central nervous system depressants, including alcohol and benzodiazepines, use may result in coma or death.Misbranded Drugs:A drug is misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)] if its labeling fails to bear adequate directions for use. “Adequate directions for use” means directions under which a layperson can use a drug safely and for the purposes for which it is intended (see 21 CFR 201.5). Prescription drugs, as defined in section 503(b)(1) of the FD&C Act [21 U.S.C. § 353(b)(1)] include those that, because of their toxicity or other potentiality for harmful effect, and/or the method of their use, and/or the collateral measures necessary for their use, are not safe for use except under supervision of a practitioner licensed by law to administer them. Prescription drugs, as defined in section 503(b)(1)(A) of the FD&C Act, can be used safely only at the direction, and under the supervision, of a licensed practitioner.Because the aforementioned drugs are prescription drugs intended for conditions that are not amenable to self-diagnosis and treatment by a layperson, adequate directions cannot be written such that a layperson can use the products safely for their intended use. Consequently, the labeling for these drug products fail to bear adequate directions for use, causing them to be misbranded under section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]. In addition, because these drugs are not approved in the U.S., they are also not exempt under 21 CFR 201.115(a) from the requirements of section 502(f)(1) of the FD&C Act [21 U.S.C. § 352(f)(1)]. By offering these drugs for sale to U.S. consumers, www.citra100mg.com is causing the introduction of misbranded drugs into interstate commerce in violation of section 301(a) of the FD&C Act [21 U.S.C. § 331(a)].Furthermore, under U.S. law, prescription drugs can be dispensed only pursuant to a prescription from a healthcare practitioner licensed by law to administer prescription drugs. By offering the aforementioned drug products without requiring a prescription, www.citra100mg.com jeopardizes patient safety and misbrands the drug products under section 503(b)(1) of the FD&C Act [21 U.S.C. § 353(b)(1)]. Dispensing a prescription drug without a prescription is an act which results in the drug being misbranded while held for sale, in violation of section 301(k) of the FD&C Act [21 U.S.C. § 331(k)].FDA is sending this warning letter to www.citra100mg.com because of the inherent risks to consumers who purchase misbranded and unapproved new drugs. This letter is not intended to identify all the ways in which your products or operations might be in violation of the law. It is your responsibility to ensure that all products you offer for sale are in compliance with the FD&C Act and its implementing regulations. You should take prompt action to address any violations of the FD&C Act (which may include the offer for sale of similarly misbranded and/or unapproved new drugs other than the drug products noted above). We advise you to review your websites, product labels, and other labeling and promotional materials to ensure that you are not misleadingly representing your products as safe and effective for a use for which they have not been approved by FDA and that you are not distributing misbranded and unapproved drug products in violation of the FD&C Act.Please notify this office in writing within 15 working days describing the specific steps you have taken to address any violations and to prevent their recurrence. Include an explanation of each step being taken to remedy and prevent the recurrence of any violations, as well as copies of related documentation. Failure to adequately address this matter may result in legal action, including, without limitation, seizure, and injunction, without further notice. If you cannot complete corrective action within 15 working days, state the reason for the delay and the time within which you will complete the corrections. This letter notifies you of our concerns and provides you with an opportunity to address them. If you believe that your products are not in violation of the FD&C Act, include your reasoning and any supporting information for our consideration within 15 working days.If you are not located in the U.S., please note that products that appear to be misbranded or unapproved new drugs may be detained or refused admission. We may advise the appropriate regulatory officials in the country from which you operate that your products referenced above appear to be unapproved and misbranded products that cannot be legally sold to consumers in the U.S.Please direct your response and any inquiries to FDA at FDAInternetPharmacyTaskForce-CDER@fda.hhs.gov.Sincerely,/S/Sangeeta Vaswani Chatterjee, Pharm.D.DirectorOffice of Drug Security, Integrity, and ResponseOffice of ComplianceCenter for Drug Evaluation and Research

行政处罚决定书文号：沈辽市监处罚﹝2026﹞19号处罚类别：没收违法所得处罚决定日期：2026-03-05处罚内容：没收违法所得1.5元违法行为类型：当事人的行为违反了《中华人民共和国药品管理法》第九十八条第一款“禁止生产（包括配制，下同）、销售、使用假药、劣药。"的规定，已构成销售劣药“清气化痰丸”的违法行为。违法事实：经查明，当事人于2024年9月14日从辽宁新润医药有限公司购进标示为湖北瑞华制药有限公司生产，批号为240529的“清气化痰丸”5盒，每盒进价9.5元；2025年1月17日上述批次“清气化痰丸”经四川省药品检验研究院（四川省医疗器械检测中心）检验（检验报告编号：YP2025A01274），结论为不符合《中国药典》规定。截至2025年12月15日我局立案时止，当事人已以11元/盒售出该药品1盒，剩余4盒药品被辽宁新润医药有限公司召回。处罚依据：依据《中华人民共和国药品管理法》第一百一十七条“生产、销售劣药的，没收违法生产、销售的药品和违法所得，并处违法生产，销售的药品货值金额十倍以上二十倍以下的罚款；违法生产、批发的药品货值金额不足十万元的，按十万元计算，违法零售的药品货值金额不足一万元的，按一万元计算；情节严重的，责令停产停业整顿直至吊销药品批准证明文件、药品生产许可证、药品经营许可证或者医疗机构制剂许可证。"和《中华人民共和国药品管理法实施条例》第七十五条“药品经营企业、医疗机构未违反《药品管理法》和本条例的有关规定，并有充分证据证明其不知道所销售或者使用的药品是假药、劣药的，应当没收其销售或者使用的假药、劣药和违法所得；但是，可以免除其他行政处罚”的规定。处罚机关：沈阳市辽中区市场监督管理局处罚机关统一社会信用代码：11210122MB0Q12814J数据来源单位：沈阳市辽中区市场监督管理局数据来源单位统一社会信用代码：11210122MB0Q12814J

按照《关于加强药品经营企业歇业管理有关问题的通知》（皖食药监市〔2008〕180号）规定，同意下列企业在《药品经营许可证》有效期内歇业。    企业歇业期间，不得开展药品经营活动。如企业在许可证有效期内恢复经营，须向省局提交恢复经营申请及恢复经营专项审计报告和企业严格执行《药品经营质量管理规范》的承诺，经同意后发还《药品经营许可证》正副本。企业名称法定代表人/负责人许可证编号许可证有有效期至经营地址仓库地址经营范围海王医药安庆有限公司鲍炳勇/张军皖AA5560004732029.05.25安庆市开发区晋熙路5号1栋5-6层安徽省安庆市开发区晋熙路5号1栋1-3层中成药、化学药（原料药及制剂）生物制品、麻醉药品、第一类精神药品、第二类精神药品、蛋白同化制剂、肽类激素（上述经营范围含冷藏药品）（麻醉、第一类精神药品供药责任区域为安庆市辖区）***               安徽省药品监督管理局                            2026年3月17日

经查，王自力等8人的执业药师注册单位与实际工作单位不符，属于《执业药师职业资格制度规定》第二十八条第二款、《执业药师注册管理办法》第三十四条规定的挂靠。我局依法定权限、程序作出了行政处理决定，现将行政处理结果公告如下：序号姓名注册单位注册证号行政处理结果备注1王自力福建晋江市济仁大药房有限公司352225051009三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统当事人执业注册证书已于行政处理决定前主动注销2王玲玲晋江市合隆堂大药房有限公司351222050555三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统当事人执业注册证书已于行政处理决定前主动注销3陈明菜龙海市浮宫回生堂药店351225060230撤销当事人《执业药师注册证》，三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统4吴丽丽加上（福建）医药有限公司352223060538撤销当事人《执业药师注册证》，三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统5郑燕梅漳州贤泽医药有限公司隆教分店352223060181撤销当事人《执业药师注册证》，三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统6王颖福州市鼓楼区双安药店湖头街店351222010180三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统当事人执业注册证书已于行政处理决定前主动注销7李晟福州市鼓楼区达康明药店351222010026三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统当事人执业注册证书已于行政处理决定前主动注销8周苏键福州市鼓楼区世安堂药房351221011658三年内不予注册，并将个人不良信息记入全国执业药师注册管理信息系统当事人执业注册证书已于行政处理决定前主动注销

　　根据《药品管理法》、《药品生产监督管理办法》有关规定，经现场检查并综合评定，现将福建省宝诺医药研发有限公司《药品生产质量管理规范》符合性检查结果公告。企业名称检查地址检查范围检查时间类型检查结果福建省宝诺医药研发有限公司（受托方：江苏万高药业股份有限公司）。1.持有人检查地址（持有人注册地址）：厦门市海沧区海沧大道567号厦门中心E座909单元；2.对受托方（延伸检查）：江苏省海门经济技术开发区定海路688号。1.检查范围：磷酸奥司他韦干混悬剂[规格：0.36g（按C16H28N2O4计）；批准文号：国药准字H20253011]；2.生产类型：委托生产；3.生产线：受托方固体制剂车间101生产线。1.持有人检查时间：2025年12月24日下午-12月26日上午；2.延伸检查时间：2026年01月27日-01月29日。依申请符合　　福建省药品监督管理局　　2026年3月17日