Proliv™Rx System

{0} FDA U.S. FOOD & DRUG ADMINISTRATION December 31, 2025 Neurolief Ltd. Dganit Litinsky VP Regulatory Affairs & Quality Assurance 12 Giborei Israel St. Netanya, 4250412 Israel Re: P250010 Trade/Device Name: Proliv™Rx external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) (Proliv™Rx System) Product Code: JXK Filed: March 25, 2025 Amended (A001): June 6, 2025 Amended (A002): June 25, 2025 Amended (A003): October 3, 2025 Dear Dganit Litinsky: The Center for Devices and Radiological Health (CDRH) of the Food and Drug Administration (FDA) has completed its review of your premarket approval application (PMA) for the Proliv™Rx external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) (also referred to as the Proliv™Rx System). The Proliv™Rx System provides focal external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) treatment. It is intended as an adjunctive treatment for Major Depressive Disorder (MDD) in adults who failed to achieve satisfactory improvement from at least one previous antidepressant medication, for use at home or in clinic. It is a prescription-only device. Based upon the information submitted, the PMA is approved. You may begin commercial distribution of the device in accordance with the conditions of approval described below. Although this letter refers to your product as a device, please be aware that some approved products may instead be combination products. The Premarket Approval Database available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm identifies combination product submissions. The sale and distribution of this device are restricted to prescription use in accordance with 21 CFR 801.109 and under section 515(d)(1)(B)(ii) of the Federal Food, Drug, and Cosmetic Act (the act). FDA has determined that these restrictions on sale and distribution are necessary to provide reasonable assurance of the safety and effectiveness of the device. Your device is therefore a restricted device subject to the requirements in sections 502(q) and (r) of the act, in addition to all other applicable requirements, including those governing the manufacture, distribution, and marketing of devices. {1} P250010 - Dganit Litinsky Page 2 Continued approval of the PMA is contingent upon the submission of periodic reports, required under 21 CFR 814.84, at intervals of one year (unless otherwise specified) from the date of approval of the original PMA. This report, identified as "Annual Report" and bearing the applicable PMA reference number, should be submitted to the address below. The Annual Report should indicate the beginning and ending date of the period covered by the report and must include the information required by 21 CFR 814.84. In addition to the above, and in order to provide continued reasonable assurance of the safety and effectiveness of the PMA device, under 21 CFR 814.82(a)(9), the Annual Report must include, separately for each model number (if applicable), the number of devices sold and distributed during the reporting period, including those distributed to distributors. The distribution data will serve as a denominator and provide necessary context for FDA to ascertain the frequency and prevalence of adverse events, as FDA evaluates the continued safety and effectiveness of the device. This is a reminder that as of September 24, 2014, class III devices are subject to certain provisions of the final Unique Device Identification (UDI) rule. These provisions include the requirement to provide a UDI on the device label and packages (21 CFR 801.20), format dates on the device label in accordance with 21 CFR 801.18, and submit data to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). Additionally, 21 CFR 814.84 (b)(4) requires PMA annual reports submitted after September 24, 2014, to identify each device identifier currently in use for the subject device, and the device identifiers for devices that have been discontinued since the previous periodic report. It is not necessary to identify any device identifier discontinued prior to December 23, 2013. Combination Products may also be subject to UDI requirements (see 21 CFR 801.30). For more information on these requirements, please see the UDI website available at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-udi-system. Before making any change affecting the safety or effectiveness of the PMA device, you must submit a PMA supplement or an alternate submission (30-day notice) in accordance with 21 CFR 814.39. All PMA supplements and alternate submissions (30-day notice) must comply with the applicable requirements in 21 CFR 814.39. Additional information about changes that may require a PMA supplement are provided in the FDA guidance document entitled, "Modifications to Devices Subject to Premarket Approval (PMA) - The PMA Supplement Decision-Making Process" https://www.fda.gov/media/81431/download. Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production and process controls (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181). You are reminded that many FDA requirements govern the manufacture, distribution, and marketing of devices. For example, in accordance with the Medical Device Reporting (MDR) regulation, 21 CFR 803.50 and 21 CFR 803.52 for devices or post-marketing safety reporting (21 CFR Part 4, Subpart B) for combination products, you are required to report adverse events for this device. Manufacturers of medical devices, including in vitro diagnostic devices, are required to report to FDA no later than 30 calendar days after the day they receive or otherwise becomes aware of information, from any source, that reasonably suggests that one of their marketed devices: {2} P250010 - Dganit Litinsky Page 3 1. May have caused or contributed to a death or serious injury; or 2. Has malfunctioned and such device or similar device marketed by the manufacturer would be likely to cause or contribute to a death or serious injury if the malfunction were to recur. Additional information on MDR, including how, when, and where to report, is available at https://www.fda.gov/medical-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems and on combination product post-marketing safety reporting is available at https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-products. In accordance with the recall requirements specified in 21 CFR 806.10 for devices or the post-marketing safety reporting requirements (21 CFR Part 4, Subpart B) for combination products, you are required to submit a written report to FDA of any correction or removal of this device initiated by you to: (1) reduce a risk to health posed by the device; or (2) remedy a violation of the act caused by the device which may present a risk to health, with certain exceptions specified in 21 CFR 806.10(a)(2). Additional information on recalls is available at https://www.fda.gov/safety/recalls-market-withdrawals-safety-alerts/industry-guidance-recalls. CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading. CDRH will notify the public of its decision to approve your PMA by making available, among other information, a summary of the safety and effectiveness data upon which the approval is based. The information can be found at https://www.fda.gov/medical-devices/device-approvals-denials-and-clearances/pma-approvals. Written requests for this information can also be made to the Food and Drug Administration, Dockets Management Branch, (HFA-305), 5630 Fishers Lane, Rm. 1061, Rockville, MD 20852. The written request should include the PMA number or docket number. Within 30 days from the date that this information is placed on the Internet, any interested person may seek review of this decision by submitting a petition for review under section 515(g) of the act and requesting either a hearing or review by an independent advisory committee. FDA may, for good cause, extend this 30-day filing period. Failure to comply with any post-approval requirement constitutes a ground for withdrawal of approval of a PMA. The introduction or delivery for introduction into interstate commerce of a device that is not in compliance with its conditions of approval is a violation of law. You are reminded that, as soon as possible and before commercial distribution of your device, you must submit an amendment to this PMA submission with a copy of all final labeling. Final labeling that is identical to the labeling approved in draft form will not routinely be reviewed by FDA staff when accompanied by a cover letter stating that the final labeling is identical to the labeling approved in draft form. If the final labeling is not identical, any changes from the final draft labeling should be highlighted and explained in the amendment. All required documents should be submitted to the CDRH Portal and should reference the above PMA number to facilitate processing. For more information on the CDRH Portal, please visit {3} P250010 - Dganit Litinsky Page 4 https://www.fda.gov/medical-devices/industry-medical-devices/send-and-track-medical-device-premarket-submissions-online-cdrh-portal. If you have any questions concerning this approval order, please contact Eugene Civillico, PhD at 240-402-3263 or Eugene.Civillico@fda.hhs.gov. Sincerely, Heather L. Dean -S Heather Dean, PhD Acting Director DHT5B: Division of Neuromodulation and Physical Medicine Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health