The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore Sapphire device is indicated for:

· The preventive treatment of migraine headache in adolescent (aged 12 and older) and adult patients
The acute treatment of pain associated with migraine headache in adolescents (aged 12 and older) and adult patients
· Adjunctive use for the preventive treatment of cluster headache in adult patients
· The acute treatment of pain associated with episodic cluster headache in adult patients
· Treatment of hemicrania continua in adults
· Treatment of paroxysmal hemicrania in adults

Device Description

The gammaCore Sapphire (gammaCore) is a multi-use, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and -amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).

The gammaCore Sapphire:

. Includes a charging station incorporated into the "clamshell" storage case connected to a power adapter for charging of the device as necessary by the end user.
Provides visible (light and display) and audible (beep) feedback regarding device and stimulation . status.
Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, after . which the device automatically turns off unless turned off earlier by the user/operator. Note: One dose is defined as one stimulation cycle lasting 120 seconds (2 minutes).
Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily number . of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
Indicates on the display the number of remaining doses available in a 24-hour period.

The device will be provided to the patient/user with an initial 10-, 31-, or 93-day RFID card on the basis of the health care provider's prescription. Additional (refill/reload) cards will be provided in response to a user/patient request based on a prescription from his or her health care provider. The refill/reload RFID cards will be programmed by electroCore or its authorized agent. This is a specialized application for dispensing the device therapy.

When a 10-, 31-, or 93-day refill/reload card is requested by a patient/user (in accordance with a prescription from a health care provider) for a unique device serial number, an RFID card is encoded with the appropriate dosage according to the prescription. The gammaCore RFID card-loading application uses a proprietary encoding algorithm to encrypt the therapy days and doses per day on the refill/reload RFID card using near field communication protocols.

The encoded refill/reload RFID card is then provided to the user/patient who requested the refil/reload of the device, along with 1 to 6 additional tubes of conductive gel (the number of conductive gel tubes provided is based on the 10-, 31-, or 93-day refill/reload being provided). On receipt of the RFID card, the user/patient refills/reloads his or her gammaCore device by placing the RFID card across the face of the device (with the device turned on). The device will display "rd" and the "refill" icon as the device reads the RFID card. The device will signal (beeping twice) when it has been loaded with the programmed doses. The device will now be ready for use as treatment. The RFID card can be used for only one refill/reload; upon completion of the device refill/reload, the card can be thrown away.

In addition, a Bluetooth® feature will be enabled to facilitate diagnostics of any devices returned by patients/users to the manufacturer, to allow determination of the number of days the device was used and/or the number of doses as well as any days/doses remaining on the device. The Bluetooth feature will not be accessible to the patient/user; it is accessible only to the device manufacturer.

The subject device delivers the same energy and maintains the same operational characteristics as the gammaCore Sapphire device cleared in K203546. No changes in design or manufacturing process have been made that could affect device functionality. All functional aspects of the device remain the same as K203546, including the strength and nature of the device outputs.

AI/ML Overview

The provided document is a 510(k) summary for the gammaCore Sapphire device, which is an external vagal nerve stimulator. It focuses on demonstrating substantial equivalence to a predicate device (gammaCore Sapphire, K203546) rather than detailing a study that proves the device meets specific acceptance criteria based on performance.

The submission is for an expanded labeling (additional indications for use), and the key argument for substantial equivalence is that the technology of the device itself is identical to the previously cleared predicate device. Therefore, no new performance testing or clinical studies were conducted to prove the device meets new acceptance criteria for its core technical performance. Instead, the "study" proving its acceptance is the demonstration that the expanded indications are supported by existing clinical data and that the device remains safe and effective for these new uses, given its proven performance characteristics.

Here's how to break down the information based on your request, focusing on the expanded indications rather than new hardware performance metrics:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a submission based on substantial equivalence for expanded indications and not a new device with novel performance criteria, the "acceptance criteria" are implicitly tied to demonstrating that the device is as safe and effective as a legally marketed predicate for the new indications.

Acceptance Criteria Category	Specific Criteria (Implicit for Substantial Equivalence)	Reported Device Performance / Evidence Provided
Technological Characteristics	- Identical waveform/frequency to predicate	"Sinusoidal wave, symmetrical biphasic 5000-Hz pulses at a rate of 25 Hz" (Same as predicate)
	- Identical maximum output to predicate	"30 V (peak), 60 mA(peak)" (Same as predicate) -----------------------------------------------------------------------------------
	- Identical load impedance to predicate	"450-550 ohms" (Same as predicate)
	- Identical power supply to predicate	"3V LiFePo4 battery" (Same as predicate)
	- Identical service life to predicate	"3 years from date of manufacture" (Same as predicate)
	- Identical patient-contacting materials to predicate	"SS, ABS-PC, SignaGel electrode gel" (Same as predicate)
Safety	- No new issues of safety or effectiveness	"The subject device delivers the same energy and maintains the same operational characteristics as the gammaCore Sapphire device cleared in K203546. No changes in design or manufacturing process have been made that could affect device functionality. All functional aspects of the device remain the same... No serious or unexpected adverse events were reported [in clinical data related to new indications]."
Effectiveness for Expanded Indications	- Clinical support for new indications (Hemicrania Continua, Paroxysmal Hemicrania)	Clinical data extrapolated from RCTs for cluster headache (DEN150048 and K182369), and collected from clinical audits and case series/case reports. "Fifteen of the 19 patients with hemicrania continua (79%) and 11 of the 14 patients with paroxysmal hemicrania experienced clinically meaningful benefits with nVNS therapy..." (References 5-10 listed).
Intended Use Relationship	- Consistent with predicate's intended use	"The gammaCore Sapphire is a device that provides nVNS when applied to the side of the neck... Same; no change in intended use." The new indications are a logical expansion within the existing mechanism of action.

2. Sample Size Used for the Test Set and Data Provenance

The "test set" in this context refers to the clinical data used to support the expanded indications, as no new hardware performance tests were conducted.

Sample Size:
- Hemicrania Continua: 19 patients across various clinical audits and case series/case reports.
- Paroxysmal Hemicrania: 14 patients across various clinical audits and case series/case reports.
Data Provenance: The document does not explicitly state the country of origin for the clinical audits and case series/reports. The references include publications in international journals (e.g., Cephalalgia, Headache, J Neurol Neurosurg Psychiatry, J Headache Pain, JAMA Neurol), suggesting a multi-national or at least broader clinical context. The data is presented as a combination of extrapolated data from randomized controlled trials (RCTs) (for cluster headache, DEN150048 and K182369) and retrospective clinical audits and case series/case reports.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not specify the number of experts or their qualifications involved in establishing the "ground truth" for the case series/audits. It refers to published literature (references 5-10) which would inherently involve clinical diagnoses made by medical professionals (neurologists, headache specialists). The diagnoses of hemicrania continua and paroxysmal hemicrania themselves serve as the "ground truth" for these conditions, and their treatment response to nVNS is observed.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method (e.g., 2+1, 3+1) for the clinical data from the case series/audits. These are real-world observational data and published case series, where patient outcomes are typically evaluated by the treating clinician(s) and potentially reviewed by the authors of the respective papers. The RCT data (for cluster headache) would have had their own internal adjudication processes, but these details are not provided here as the data is "extrapolated."

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

No, an MRMC comparative effectiveness study was not done. This device is a direct treatment device, not an AI-assisted diagnostic tool for human readers. Therefore, this type of study is not applicable.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This is a medical device for direct patient treatment, not a diagnostic algorithm. Therefore, "standalone performance" in the context of an algorithm or AI is not applicable. The device itself performs the function (nerve stimulation).

7. The Type of Ground Truth Used

The ground truth for the expanded indications (hemicrania continua and paroxysmal hemicrania) is based on clinical diagnoses of these conditions and patient-reported (or clinician-observed) outcomes reflecting "clinically meaningful benefits" from nVNS therapy (e.g., decreases in pain severity, reductions in frequency/severity/duration of attacks). This is essentially outcomes data from real-world clinical experience and existing published literature.

8. The Sample Size for the Training Set

This submission describes a medical device, not an AI/ML algorithm that requires a "training set" in the computational sense. Therefore, the concept of a training set sample size is not applicable to this 510(k) submission. The device's design and functionality were established through prior development and clearance (K203546).

9. How the Ground Truth for the Training Set Was Established

As explained above, there is no "training set" in the context of an AI/ML device. The "ground truth" for the device's original design and safety/effectiveness (as detailed in the predicate K203546) would have been established through a combination of engineering validation, non-clinical testing, and clinical studies for the original indications. The current submission simply leverages that established ground truth and applies it to new, similar indications based on existing clinical evidence.

Summary

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September 10, 2021

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the FDA logo is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Electrocore, Inc. Mike Romaniw VP, Quality Assurance & Regulatory Affairs 200 Forge Way, Suite 205 Rockaway, New Jersey 07866

Re: K211856

Trade/Device Name: gammaCore Sapphire Regulation Number: 21 CFR 882.5892 Regulation Name: External Vagal Nerve Stimulator For Headache Regulatory Class: Class II Product Code: PKR, QAK Dated: June 15, 2021 Received: June 16, 2021

Dear Mike Romaniw:

We have reviewed your 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 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

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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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Indications for Use

510(k) Number (if known) Not yet known

Device Name gammaCore Sapphire

Indications for Use (Describe)

The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore Sapphire device is indicated for:

· The preventive treatment of migraine headache in adolescent (aged 12 and older) and adult patients
The acute treatment of pain associated with migraine headache in adolescents (aged 12 and older) and adult patients
· Adjunctive use for the preventive treatment of cluster headache in adult patients
· The acute treatment of pain associated with episodic cluster headache in adult patients
· Treatment of hemicrania continua in adults
· Treatment of paroxysmal hemicrania in adults

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(K) SUMMARY

The following information is provided as required by 21 CFR §807.92 for the electroCore gammaCore Sapphire 510(k) premarket notification. In response to the Safe Medical Devices Act of 1990, the following is a summary of the information upon which the substantial equivalence determination is based.

Applicant: electroCore, Inc. 200 Forge Way, Suite 205 Rockaway, New Jersey 07866 Ph: 888-903-2673 Fax: 973-290-9171

Establishment Registration Number: 3015529603

Contact:	Mike Romaniw
	VP, Quality Assurance & Regulatory Affairs
	Office: 973-355-6702
	Fax: 973-290-9171
	Mike.Romaniw@electroCore.com
Alternate Contact:	Eric J. Liebler
	SVP, Neurology
	Mobile: 908-938-9780
	Eric.Liebler@electroCore.com
Alternate Contact:	Deborah Lavoie Grayeski
	Sr. Project Manager
	M Squared Associates, Inc.
	Office: 347-954-0418
	Fax: 703-562-9797
	dgrayeski@MSquaredAssociates.com
Date of Submission:	June 15, 2021
Proprietary Name:	gammaCore Sapphire
Common Name:	External vagal nerve stimulator for headache
Classification Status:	Class II
Product Codes:	PKR, QAK
Primary Predicate Device:	gammaCore Sapphire, K203546

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Indication for Use: The gammaCore Sapphire Non-invasive Vagus Nerve Stimulator is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. The gammaCore Sapphire device is indicated for:

. The preventive treatment of migraine headache in adolescent (aged 12 and older) and adult patients
. The acute treatment of pain associated with migraine headache in adolescents (aged 12 and older) and adult patients
. Adjunctive use for the preventive treatment of cluster headache in adult patients
The acute treatment of pain associated with episodic cluster headache in adult patients .
. Treatment of hemicrania continua in adults
Treatment of paroxysmal hemicrania in adults .

Device Description: The gammaCore Sapphire (gammaCore) is a multi-use, handheld, rechargeable, portable device consisting of a rechargeable battery and signal-generating and -amplifying electronics, with a slide control switch for user/operator control of the signal amplitude (relative range, 0-40 continuous).

The gammaCore Sapphire:

. Includes a charging station incorporated into the "clamshell" storage case connected to a power adapter for charging of the device as necessary by the end user.
Provides visible (light and display) and audible (beep) feedback regarding device and stimulation . status.
Allows for multiple stimulations or doses; each stimulation or dose lasts 120 seconds, after . which the device automatically turns off unless turned off earlier by the user/operator. Note: One dose is defined as one stimulation cycle lasting 120 seconds (2 minutes).
Delivers up to a fixed number of doses within a 24-hour period; once the maximum daily number . of doses has been reached, the device will not deliver any more doses until the following 24-hour period.
Indicates on the display the number of remaining doses available in a 24-hour period.

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cards will be programmed by electroCore or its authorized agent. This is a specialized application for dispensing the device therapy.

Summary of Technological Characteristics:

There are no changes to the technological characteristics of the gammaCore Sapphire for this expanded labeling.

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Summary of Nonclinical Testing:

There are no changes to the technological characteristics of the gammaCore Sapphire for this expanded labeling; no additional nonclinical or performance testing is required.

Summary of Clinical Data:

Clinical data demonstrating the safety and effectiveness of the gammaCore Sapphire for the treatment of hemicrania continua and paroxysmal hemicrania in adults were extrapolated from randomized controlled trials of nVNS for the acute and preventive treatment of cluster headache' (DEN150048 and K182369) and collected from clinical audits and case series/case reports that included patients with hemicrania continua or paroxysmal hemicrania.2510 These included a total of 19 patients with hemicrania continua and 14 patients with paroxysmal hemicrania.5-10 The duration of nVNS therapy in these patients (where specified) ranged from 8 weeks to 5 years.610 Fifteen of the 19 patients with hemicrania continua (79%)68.00 and 11 of the 14 patients with paroxysmal hemicrania 210 experienced clinically meaningful benefits with nVNS therapy, including decreases in the severity of persistent pain and/or reductions in the frequency, severity, and/or duration of exacerbations or attacks. No serious or unexpected adverse events were reported.5-10

Substantial Equivalence Discussion:

gammaCore Sapphire technology is identical to the device technology cleared under K203546. There have been no changes in the technological characteristics or intended use of the gammaCore Sapphire. Therefore, there are no new issues of safety or effectiveness; thus, the subject gammaCore Sapphire is substantially equivalent to the predicate gammaCore Sapphire device.

Summary:

The following table establishes the substantial equivalence of the subject device to that of the predicate device.

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Substantial Equivalence Comparison Table

	gammaCore Sapphire(predicate device)	gammaCore Sapphire(subject device)	Substantial equivalence
510(k) Number	K203546	TBD
Intended use	The gammaCore Sapphire is a device thatprovides non-invasive vagus nervestimulation (nVNS) when applied to theside of the neck. This is a mild electricalstimulation of the vagus nerve, whichruns through the neck and carriesinformation to the central nervoussystem. Each stimulation withgammaCore lasts 2 minutes. The patientcontrols the stimulation strength.	The gammaCore Sapphire is a device thatprovides nVNS when applied to the sideof the neck. This is a mild electricalstimulation of the vagus nerve, whichruns through the neck and carriesinformation to the central nervoussystem. Each stimulation withgammaCore lasts 2 minutes. The patientcontrols the stimulation strength.	Same; no change in intended use
Indication for use	The gammaCore Sapphire is indicatedfor:• The preventive treatment of migraineheadache in adolescent (aged 12 andolder) and adult patients• The acute treatment of pain associatedwith migraine headache in adolescents(aged 12 and older) and adult patients• Adjunctive use for the preventivetreatment of cluster headache in adultpatients• The acute treatment of pain associatedwith episodic cluster headache in adultpatients	The gammaCore Sapphire is indicatedfor:• The preventive treatment of migraineheadache in adolescent (aged 12 andolder) and adult patients• The acute treatment of pain associatedwith migraine headache in adolescents(aged 12 and older) and adult patients• Adjunctive use for the preventivetreatment of cluster headache in adultpatients• The acute treatment of pain associatedwith episodic cluster headache in adultpatients• Treatment of hemicrania continua inadults in adolescents (aged 12 andolder) and adult patients• Treatment of paroxysmal hemicraniain in adolescents (aged 12 and older)and adult patients	Clinical data support the expandedlabeling. Questions of safety oreffectiveness have been addressed in thesupporting data.
Rx vs OTC	Prescription use	Prescription use	No change
	gammaCore Sapphire(predicate device)	gammaCore Sapphire(subject device)	Substantial equivalence
510(k) number	K203546	TBD
	Acute treatment of migraine:120-second stimulation cycle, 2 bilateralstimulations up to 3times a day	Acute treatment of migraine:120-second stimulation cycle, 2 bilateralstimulations up to 3times a day	Change in treatment protocol to reflectdifferent forms of primary headache
Treatmentrecommendations	Preventive treatment of migraine:120-second stimulation cycle,2 consecutive stimulations on either sideof the neck as follows:• First daily treatment: within 1 hour ofwaking• Second daily treatment:4-6 hours after the first daily treatment• Third daily treatment: within 1 hourbefore going to sleep	Preventive treatment of migraine:120-second stimulation cycle,2 consecutive stimulations on either side ofthe neck as follows:• First daily treatment: within 1 hour ofwaking• Second daily treatment:4-6 hours after the first daily treatment• Third daily treatment: within 1 hourbefore going to sleepAcute treatment of eCH:120-second stimulation cycle,3 consecutive stimulations up to8 times a dayPreventive treatment of CH:120-second stimulation cycle,3 consecutive stimulations oneither side of the neck as follows:• First daily treatment: within 1 hour ofwaking• Second daily treatment: 7-10 hoursafter the first daily treatmentTreatment of hemicrania continua:120-second stimulation cycle,2 stimulations ipsilateral to the side of painup to 3 times a day
	gammaCore Sapphire(predicate device)	gammaCore Sapphire(subject device)	Substantial equivalence
	Treatment of paroxysmal hemicrania:120-second stimulation cycle,2 stimulations ipsilateral to the side of painup to 3 times a day
Patient-contactingmaterials	SS, ABS-PC, SignaGel electrode gel	SS, ABS-PC, SignaGel electrode gel	No change in materials
Electricalclassification	UL 60601-1 Class III Type BF AppliedPart	UL 60601-1 Class III Type BF AppliedPart	No change in classification
Waveform/frequency	Sinusoidal wave, symmetrical biphasic5000-Hz pulses at a rate of 25 Hz	Sinusoidal wave, symmetrical biphasic5000-Hz pulses at a rate of 25 Hz	No change in waveform or frequency
Maximum output	30 V (peak), 60 mA(peak)	30 V (peak), 60 mA(peak)	No change in outputs
Load impedance	450-550 ohms	450-550 ohms	No change in impedance
Power supply	3V LiFePo4 battery	3V LiFePo4 battery	No change in power supply voltage
Service life	3 years from date of manufacture	3 years from date of manufacture	No change in service life
Controls	Control slideIncrease slide up/decrease slide down	Control slideIncrease slide up/decrease slide down
Output regulation	Device software and control slide	Device software and control slide	No change in circuitry or controls of thesubject and predicate devices
Device status display	LED screen	LED screen
Battery charger	Qi-compatible wireless charger inclamshell storage case	Qi-compatible wireless charger inclamshell storage case
RFID refill/reloadcapability	Allows refilling/reloading of the numberof days/doses for which the device canprovide treatment; allows for continueduse of same device for extended periodsof time	Allows refilling/reloading of the number ofdays/doses for which the device canprovide treatment; allows for continueduse of same device for extended periods oftime
	gammaCore Sapphire(predicate device)	gammaCore Sapphire(subject device)	Substantial equivalence
Device diagnostics,Bluetooth	Provides for diagnostics by manufacturerof returned devices, including number ofdays device was used, number of dosesdelivered, and remaining days/doses	Provides for diagnostics by manufacturerof returned devices, including number ofdays device was used, number of dosesdelivered, and remaining days/doses
Startup	Yes	Yes	No change in available alarm signals
Session complete	Yes	Yes
Errors/depletedbattery	Yes	Yes
No doses left	Yes	Yes
Expired/no days left	Yes	Yes
Start-up(powered on)	Light on	Light on	No change to display/message in thesubject and predicate devices
Unit ready (poweredon)	LED doses remaining for 24-h period	LED doses remaining for 24-h period
Dose complete	LED days and doses remaining and lastamplitude	LED days, doses remaining, and lastamplitude
Errors/depletedbattery	E# display	E# display
No doses remaining	LED doses 00	LED doses 00	Differences between the subject deviceand reference device represent changesin the user interface. These changes donot impact the safety or effectiveness ofthe device.
Expired/no days left	LED doses/days remaining	LED doses/days remaining
Low battery	LED display battery charge indicator	LED display battery charge indicator
Reloading error	LED display if refill process fails	LED display if refill process fails
Card error	LED display if refill card fails	LED display if refill card fails

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Conclusion:

The gammaCore Sapphire device is the same as the predicate device and no technological or intended use changes have occurred. Therefore, no new issues of safety or effectiveness are raised. Thus, gammaCore Sapphire is substantially equivalent to the predicate device.

References

1. de Coo IF, Marin JC, Silberstein SD, et al. Differential efficacy of non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a meta-analysis. Cephalalgia. 2019;39(8):967-977. doi:10.1177/0333102419856607
1. Gaul C, Diener HC, Silver N, et al. Non-invasive vagus nerve stimulation for prevention and acute treatment of chronic cluster headache (PREVA): a randomised controlled study. Cephalalgia. 2016;36(6):534-546. doi:10.1177/0333102415607070
1. Goadsby PJ, de Coo IF, Silver N, et al. Non-invasive vagus nerve stimulation for the acute treatment of episodic and chronic cluster headache: a randomized, double-blind, sham-controlled ACT2 study. Cephalalgia. 2018;38(5):959-969. doi:10.1177/0333102417744362
1. Silberstein SD, Mechtler LL, Kudrow DB, et al. Non-invasive vagus nerve stimulation for the acute treatment of cluster headache: findings from the randomized, double-blind, sham-controlled ACT1 study. Headache. 2016;56(8):1317-1332. doi:10.1111/head.12896
న. Davies B, Chatterton K. Non-invasive vagus nerve stimulation for hemicrania continua: a case series of 3 patients. Cephalalgia. 2016;36(1S):93.
1. Eren O, Straube A, Schoberl F, Schankin C. Hemicrania continua: beneficial effect of noninvasive vagus nerve stimulation in a patient with a contraindication for indomethacin. Headache. 2017;57(2):298-301. doi:10.1111/head.12977
1. Kamourieh S, Lagrata S, Matharu MS. Non-invasive vagus nerve stimulation is beneficial in chronic paroxysmal hemicrania. J Neurol Neurosurg Psychiatry. 2019;90(9):1072-1074. doi:10.1136/jnnp-2018-319538
1. Nesbitt A, Goadsby P. Treatment of hemicrania continua by non-invasive vagus nerve stimulation in 2 patient with previously treated occipital nerve stimulation. J Headache Pain. 2013:14(suppl 1):P230.
1. Trimboli M, Al-Kaisy A, Andreou AP, Murphy M, Lambru G. Non-invasive vagus nerve stimulation for the management of refractory primary chronic headaches: a real-world experience. Cephalalgia. 2018;38(7):1276-1285. doi:10.1177/0333102417731349
1. Tso AR, Marin J, Goadsby PJ. Noninvasive vagus nerve stimulation for treatment of indomethacin-sensitive headaches. JAMA Neurol. 2017;74(10):1266-1267. doi:10.1001/jamaneurol.2017.2122

Regulation Number and Section

§ 882.5892 External vagal nerve stimulator for headache.

(a)
Identification. An external vagal nerve stimulator for headache is a prescription device used to apply an electrical current to a patient's vagus nerve through electrodes placed on the skin for the treatment of headache.(b)
Classification. Class II (special controls). The special controls for this device are:(1) 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 shall be fully characterized through non-clinical performance testing.(2) Software verification, validation, and hazard analysis shall be performed.
(3) Biocompatibility evaluation of the patient-contacting components of the device shall be performed.
(4) The device shall be tested for electrical, thermal, and mechanical safety, and for electromagnetic compatibility (EMC).
(5) The labeling must include:
(i) Instructions for proper use of the device, including placement of the device on the patient; and
(ii) Instructions on care and cleaning of the device.