Relivion

K212106 · Neurolief , Ltd. · PCC · Aug 2, 2021 · Neurology

Device Facts

• Record ID: K212106
• Device Name: Relivion
• Applicant: Neurolief , Ltd.
• Product Code: PCC · Neurology
• Decision Date: Aug 2, 2021
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 882.5891
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

The Relivion® transcutaneous electrical nerve stimulator is indicated for the acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription device to be self-used at home.

Device Story

Relivion is a non-invasive, wearable neurostimulator headset for migraine treatment. Device features three pairs of electrodes contacting forehead and occiput to stimulate trigeminal (supraorbital/supratrochlear) and greater occipital nerve branches. Powered by rechargeable 3.7V Li-Po battery; delivers electrical pulses to induce neuromodulation. User operates device via onboard interface to activate/deactivate and adjust intensity; treatment runs for 60 minutes. Optional mobile app connects via Bluetooth for status display, alerts, and patient migraine status reporting. New modification adds Physician Interface for remote follow-up on patient migraine attacks and treatment history. Healthcare providers use data from Physician Interface to monitor patient progress. Device benefits patients by providing non-pharmacological acute migraine relief.

Clinical Evidence

No clinical data presented. Substantial equivalence supported by bench testing and software verification/validation of the modified Physician Interface and mobile application. Testing confirmed output parameters meet specifications and cybersecurity risks were addressed.

Technological Characteristics

Transcutaneous electrical nerve stimulator; plastic PA and silicone housing; 90g weight; 209mm x 128mm x 39mm. Rechargeable 3.7V Li-Po battery. Bluetooth connectivity. Single-use replaceable electrode pads with water-releasing covers. Standards: IEC 60601-1, IEC 60601-1-2, IEC 60601-1-6, IEC 60601-1-11, IEC 60601-2-10, IEC 62366. Software-controlled with one fixed program.

Indications for Use

Indicated for acute treatment of migraine with or without aura in patients 18 years of age or older. Prescription device for home self-use.

Regulatory Classification

Identification

A transcutaneous electrical nerve stimulator to treat headache is a device used to apply an electrical current to a patient's cranium through electrodes placed on the skin.

Special Controls

*Classification.* Class II (special controls). The special controls for this device are:(1) The patient-contacting components of the device must be demonstrated to be biocompatible. (2) Appropriate analysis/testing must validate electromagnetic compatibility and electrical, mechanical, and thermal safety. (3) The technical parameters of the device, including waveform, output modes, maximum output voltage and current (with 500, 2,000, and 10,000 ohm loads), pulse duration, frequency, net charge (µC) per pulse, maximum phase charge at 500 ohms, maximum current density (mA/cm 2 , r.m.s.), maximum average current (mA), maximum average power density (W/cm2 ), and the type of impedance monitoring system must be fully characterized.(4) Electrical performance, adhesive integrity, shelf life, reusability, and current distribution testing of the electrodes must be conducted. (5) Appropriate software verification, validation, and hazard analysis must be performed. (6) Clinical performance data must demonstrate that the device is safe and effective as a treatment for headache in the indicated patient population. (7) Labeling must include the following: (i) Appropriate contraindications such as not for use in subjects with an implanted metallic or electronic device in the head, a cardiac pacemaker, or an implanted or wearable defibrillator. (ii) Appropriate warnings such as not to apply the device on the neck or chest, not to use the device in the presence of electronic monitoring equipment, not to use in the bath or shower, not to use while sleeping, not to use while driving, not to use while operating machinery. (iii) Appropriate precautions such as the long-term effects of chronic use of the device are unknown. (iv) A summary of the expected risks and benefits of using the device. (v) A summary of the clinical performance data, including information on the patient population for which the device has and has not been demonstrated to be effective, and any adverse events and complications. (vi) Information on how the device operates and the typical sensations experienced during treatment. (vii) A detailed summary of the device technical parameters. (viii) An expiration date/shelf life for the electrodes and the number of times they can be reused. (ix) Disposal instructions.

In combination with the general controls of the Food Drug & Cosmetic Act, the Transcutaneous Electrical Nerve Stimulator to Treat Headache is subject to the following special controls:

Predicate Devices

• Relivion (K203419)

Submission Summary (Full Text)

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August 2, 2021

Neurolief Ltd. % Janice Hogan Partner Hogan Lovells US LLP 1735 Market Street, Suite 2320 Philadelphia, Pennsylvania 19103

Re: K212106

Trade/Device Name: Relivion Regulation Number: 21 CFR 882.5891 Regulation Name: Transcutaneous Electrical Nerve Stimulator To Treat Headache Regulatory Class: Class II Product Code: PCC Dated: July 6, 2021 Received: July 6, 2021

Dear Janice Hogan:

We have reviewed vour Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Patrick Antkowiak Acting Assistant 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

Enclosure

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| DEPARTMENT OF HEALTH AND HUMAN SERVICES |
|-----------------------------------------|
| Food and Drug Administration |

# Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2023 See PRA Statement below.

510(k) Number (if known)

Device Name Relivion®

Indications for Use (Describe)

The Relivion® transcutaneous electrical nerve stimulator is indicated for the acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription device to be self-used at home.

Type of Use (Select one or both, as applicable)

| | Prescription Use (Part 21 CFR 801 Subpart D)

- Over-The-Counter Use (21 CFR 801 Subpart C)

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### SPECIAL 510(k) SUMMARY

Image /page/3/Picture/1 description: The image shows the logo for Neuroleaf Brain Innovation. The logo consists of a stylized brain shape on the left, colored in a light blue. To the right of the brain shape, the word "Neuroleaf" is written in a larger, light blue font. Below "Neuroleaf", the words "Brain Innovation" are written in a smaller, light blue font.

| Applicant Name: | Neurolief Ltd. |
|-----------------|-------------------------|
| | 12 Giborei Israel St. |
| | Netanya, Israel 4250412 |
| | Tel: [phone] |

- Contact Person: Michal Kedar-Datel Clinical & Regulatory Affairs Director Neurolief Ltd. Tel: [phone]
- Date Prepared: July 6, 2021
- Relivion® Trade Name:

Classification Name: 21 CFR 882.5891 Transcutaneous electrical nerve stimulator to treat headache

- Product Code: PCC
- Classification: Class II
- Classification Panel: Neurology
- Neurolief Ltd's Relivion® Device (K203419) Predicate Device:

### Intended Use/Indication for Use:

The Relivion® transcutaneous electrical nerve stimulator is indicated for the acute treatment of migraine with or without aura in patients 18 years of age or older. It is a prescription device to be self-used at home.

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## Device Description:

The modified Relivion® is an external non-invasive neurostimulator designed for transcutaneous electrical nerve stimulation. The modified Relivion® headset integrates three pairs of output electrodes which come in contact with the subject's scalp at the forehead and occiput. The electrodes deliver the stimulation pulses produced by the headset's stimulation unit to the subject's scalp. The frontal electrodes stimulate the trigeminal (supraorbital and supratrochlear) nerve branches and the posterior electrodes stimulate the greater occipital nerve branches.

The modified Relivion® includes single-use replaceable electrode pads that are positioned on-top of the electrodes prior to treatment and are wetted by the user before use, in order to provide proper conductivity between the electrodes and the scalp.

The modified Relivion® is powered by a rechargeable battery and the headset incorporates an onboard user interface that enables the user to activate/deactivate the device and to adjust the stimulation intensity. Upon treatment activation, the treatment automatically runs and ends after 60 minutes or alternatively, the user can stop the treatment when desired.

The modified Relivion® can communicate via a low energy Bluetooth link with the modified Relivion®'s dedicated mobile application on the patient's smartphone. The modified Relivion®'s mobile application is optional, and it is used by the patient to display the device status and provide indications and alerts. Additionally, the modified Relivion® mobile application also enables the patient to report their migraine headache status.

The main modification introduced in the Relivion® Device compared to the cleared predicate device (K203419) is an added optional Physician Interface that enables physicians to remotely follow-up on the patient's migraine attacks status and the treatments they performed using the Relivion device, based on the data transferred to it via the modified mobile application.

Both the modified Relivion®'s mobile application (for patients) and added physician interface (for physicians) are referred together as the optional "Patient Management Interface" (PMI) of the modified Relivion® Device.

## Technological Characteristics:

The modified Relivion® treats migraines by stimulating the trigeminal and occipital nerve branches by a transcutaneous electrical nerve stimulation. Trigeminal and occipital electrical nerve stimulation induces neuromodulation of these nerve pathways and by that reduces pain associated with migraine and associated symptoms.

The modified Relivion® includes single-use, replaceable electrode pads that are positioned on-top of the headset electrodes and are wetted by the user before each use. Water releasing covers are located on the outer side of each back occipital electrode and are used to release moisture from the

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electrode pads to the scalp in order to provide proper electrical conductivity between the electrodes and the scalp.

The modified Relivion® headset adjusts to various head sizes and contours and can be worn comfortably. The headset includes two flexible arms that penetrate under the hair layers while the headset is worn.

The modified Relivion® headset incorporates an on-board user interface and can communicate via a low energy Bluetooth link with the modified Relivion®'s dedicated mobile application on the patient's smartphone. The user interface and mobile app display the device status and provides indications and alerts, in addition to an optional Physician Interface that enables physicians to remotely follow-up on the patient's migraine attacks status and treatments performed with the Relivion device.

## Performance Data:

Neurolief conducted several performance tests to demonstrate that the modified Relivion® device complies with performance standards and that it functions as intended.

Performance - Bench Testing: The modified Relivion® device underwent performance testing for the modifications introduced, including software validation and device verification tests. It was successfully verified that the modified Relivion® output parameters meet the product's specifications.

Software Testing: The PMI software was also subject to verification and validation testing, and results demonstrated that the modified Mobile Application and added Physician Interface perform as intended. Cybersecurity risks were also identified and addressed.

Because the modification to the device impacted only the software, no further testing was required.

## Substantial Equivalence:

The following table compares the modified Relivion® device to its predicate device with respect to intended use, technological characteristics and principles of operation, providing detailed information regarding the basis for the determination of substantial equivalence.

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| Parameter | Neurolief Ltd.'s<br>Relivion®<br>(Subject Device) | Neurolief Ltd.'s<br>Relivion®<br>(Predicate) | Comparison |
|---------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | General Characteristics | | |
| 510(k) number | Pending | K203419 | N/A |
| Classification | 21 CFR § 882.5891 | 21 CFR § 882.5891 | Same |
| Product Code | PCC | PCC | Same |
| Product Class | Class II | Class II | Same |
| Regulation Name | Transcutaneous Electrical Nerve<br>Stimulator to Treat Headache | Transcutaneous Electrical Nerve<br>Stimulator to Treat Headache | Same |
| Indications for<br>Use | The Relivion® transcutaneous electrical<br>nerve stimulator is indicated for the acute<br>treatment of migraine with or without aura<br>in patients 18 years of age or older. It is a<br>prescription device to be self-usedat<br>home. | The Relivion® transcutaneous electrical<br>nerve stimulator is indicated for the acute<br>treatment of migraine with or without aura<br>in patients 18 years of age or older. It is a<br>prescription device to be self-used at<br>home. | Same |
| Technology | Transcutaneous Electrical<br>Nerve Stimulator | Transcutaneous Electrical<br>Nerve Stimulator | Same |
| Invasiveness | Non-Surgical | Non-Surgical | Same |
| Electrode<br>Locations | Forehead and Occiput | Forehead and Occiput | Same |
| Nerves over<br>which electrodes<br>are placed | Supratrochlear and supraorbital branches<br>of the trigeminal nerve bilaterally and<br>the occipital nerves | Supratrochlear and supraorbital branches<br>of the trigeminal nerve bilaterally and<br>the occipital nerves | Same |
| Energy | Electric | Electric | Same |
| Power Source | Rechargeable Li-Po 3.7 V Battery | Rechargeable Li-Po 3.7 V Battery | Same |
| Software-<br>controlled | Yes, 1 fixed program | Yes, 1 fixed program | Same |
| Constant Current | Yes | Yes | Same |
| Constant Voltage | No | No | Same |
| Software<br>Function | Controls the output of the device<br>and device indicators | Controls the output of the device<br>and device indicators | Same |
| Timer Settings | Yes | Yes | Same |
| Parameter | Neurolief Ltd.'s<br>Relivion®<br>(Subject Device) | Neurolief Ltd.'s<br>Relivion®<br>(Predicate) | Comparison |
| Patient override<br>control method | On/Off button | On/Off button | Same |
| Button Types | On/Off Button and buttons to adjust<br>intensity of electrical stimulus | On/Off Button and buttons to adjust<br>intensity of electrical stimulus | Same |
| Functional<br>features | Visual and auditory indicators inform the<br>user when the device is on vs. off and help<br>them troubleshoot if it is not working<br>properly (e.g., indicates if device is<br>active/non-active, low battery indication<br>and if electrical connection between device<br>and skin is unacceptable) | Visual and auditory indicators inform the<br>user when the device is on vs. off and help<br>them troubleshoot if it is not working<br>properly (e.g., indicates if device is<br>active/non-active , low battery indication<br>and if electrical connection between device<br>and skin is unacceptable) | Same |
| Bluetooth<br>Capable | Yes | Yes | Same |
| Associated<br>Mobile<br>Application<br>(for patients) | Yes | Yes | Similar<br>Both devices include an optional<br>mobile app to display device status.<br>treatment duration, and battery<br>status, with the modified device<br>application also enabling patients to<br>report their migraine headache<br>status, this feature does not alter the<br>therapeutic effect. |
| Associated<br>Physician<br>Interface<br>(for physicians) | Yes | No | Different<br>The modified device has an optional<br>a ssocia ted Physician Interface that<br>enables physicians to remotely<br>follow-up on the patient's migraine<br>attacks status and treatments<br>performed with the Relivion device.<br>this feature does not alter the<br>therapeutic effect. |
| Max leakage<br>current | None (battery operated) | None (battery operated) | Same |
| Parameter | Neurolief Ltd.'s<br>Relivion®<br>(Subject Device) | Neurolief Ltd.'s<br>Relivion®<br>(Predicate) | Comparison |
| Electrodes | Relivion® electrode | Relivion® electrode | Same |
| Indicator display:<br>Unit functioning | Yes | Yes | Same |
| Low battery<br>indicator | Yes | Yes | Same |
| Standards:<br>IEC 60601-1 | Yes | Yes | Same |
| IEC 60601-1-2 | Yes | Yes | Same |
| IEC 60601-1-6 | Yes | Yes | Same |
| IEC 60601-1-11 | Yes | Yes | Same |
| IEC 60601-2-10 | Yes | Yes | Same |
| IEC 62366 | Yes | Yes | Same |
| Weight | 90 gr | 90 gr | Same |
| Dimensions | 209mm x 128mm x 39mm | 209mm x 128mm x 39mm | Same |
| Housing<br>materials | Plastic PA + Silicone | Plastic PA + Silicone | Same |
| Maximum Time<br>Device Used | 60 minutes | 60 minutes | Same |
| Net Charge (µC)<br>per pulse | 0 | 0 | Same |
| Pulse Duration<br>(µsec) | 850 | 850 | Same |
| Frequency (Hz) | 80 | 80 | Same |
| Maximum output<br>voltage (V): @500<br>ohms @2000<br>ohms @10000<br>ohms | 3 front electrodes / 6 back electrodes<br>12 front electrodes / 24 back electrodes<br>60 front electrodes / 100 back electrodes | 3 front electrodes / 6 back electrodes<br>12 front electrodes / 24 back electrodes<br>60 front electrodes / 100 back electrodes | Same |
| Maximum output<br>current (mA):<br>@500 ohms<br>@2000 ohms<br>@10000 ohms | 6 front electrodes /12 back electrodes<br>6 front electrodes /12 back electrodes<br>6 front electrodes /10 back electrodes | 6 front electrodes /12 back electrodes<br>6 front electrodes /12 back electrodes<br>6 front electrodes /10 back electrodes | Same |
| Parameter | Neurolief Ltd.'s<br>Relivion®<br>(Subject Device) | Neurolief Ltd.'s<br>Relivion®<br>(Predicate) | Comparison |
| Max Phase<br>Amplitude | 6 mA front electrodes/ 12 mA back<br>electrodes; with a load of a 4.7 uF<br>capacitor parallel with 2.2K ohms<br>resistance | 6 mA front electrodes/ 12 mA back<br>electrodes; with a load of a 4.7 uF capacitor<br>parallel with 2.2K ohms resistance | Same |
| Maximum phase<br>charge (µC)<br>@500Ω | 4.8 | 4.8 | Same |
| Maximum<br>Current Density,<br>(mA/cm², r.m.s.)<br>@500Ω | 1.93 front electrodes/<br>2.78 back electrodes | 1.93 front electrodes/<br>2.78 back electrodes | Same |
| Maximum<br>Average Power<br>Density,<br>(W/cm²) @500Ω | 0.0000116 front electrodes /<br>0.000034 back electrodes | 0.0000116 front electrodes /<br>0.000034 back electrodes | Same |
| Maximum<br>Average Current<br>(average absolute<br>value, mA)<br>@500Ω | 0.38 front electrodes /<br>0.76 back electrodes | 0.38 front electrodes /<br>0.76 back electrodes | Same |
| Phase rise time | 5 µS | 5 µS | Same |
| Modulation<br>Options<br>Amplitude<br>Frequency<br>Duration | 0- 12 mA<br>Fixed @ 80 Hz<br>330- 400 µS | 0- 12 mA<br>Fixed @ 80 Hz<br>330- 400 µS | Same |
| Phase decay time | 2 µS | 2 µS | Same |
| Ramp<br>Modulations<br>Ramp Up<br>Ramp Down | Manually<br>Manually | Manually<br>Manually | Same |

## Table 1: Neurolief, Ltd.'s Modified Relivion® Substantial Equivalence

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As described in the comparison table above, the subject modified Relivion® and the predicate Relivion® device (K203419) share the same intended use and indications, technological characteristics, and same principles of operation. The minor differences in the technological characteristics do not alter the overall therapeutic effect of the device. Any differences between the modified Relivion® and its predicate (K203419) were carefully evaluated through performance testing. The modified Relivion® device underwent performance testing, including bench testing and software validation testing. These performance tests confirmed that the modified Relivion® complies with the same special controls and the same consensus and performance standards, on which FDA based its clearance of the company's Relivion® device (K203419). These tests demonstrated that the differences in the technological characteristics between the subject and predicate device do not adversely impact performance and that the subject modified Relivion® is substantially equivalent to its predicate device (K203419).

### Conclusions:

Therefore, based on the same intended use, indications, technological characteristics, and same principles of operation, the modified Relivion® device is substantially equivalent to its predicate device.