(88 days)
gammaCore Sapphire (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore is indicated for:
- · 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.
- · The acute treatment of pain associated with migraine headache in adult patients.
The gammaCore Sapphire (gammaCore) is a multiuse, 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 "clam shell" 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 provided documentation describes the gammaCore Sapphire (non-invasive vagus nerve stimulator), which is indicated for:
- 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.
- The acute treatment of pain associated with migraine headache in adult patients.
The information primarily focuses on demonstrating substantial equivalence to predicate devices rather than defining specific acceptance criteria for performance benchmarks against a gold standard for a diagnostic AI device. However, based on the clinical study presented, we can infer a primary efficacy outcome as an "acceptance criteria" and the reported device performance from that study.
Here's the breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Inferred from Primary Endpoint) | Reported Device Performance (SoC + nVNS group vs. Control) |
|---|---|
| Significantly greater reduction in the mean number of Cluster Headache (CH) attacks per week. | Study Outcome: Mean reduction of 5.9 CH attacks per week for SoC + nVNS vs. 2.1 for Control. |
| Therapeutic Gain: 3.9 fewer attacks per week (95% CI: 0.5, 7.2; P=0.02). | |
| Higher 50% responder rates (proportion of subjects with ≥50% reduction in CH attacks). | Study Outcome: 40% responder rate for SoC + nVNS vs. 8.3% for Control (P<0.001). |
| Reduction in the use of abortive medications (Sumatriptan and Oxygen). | Study Outcome: Reduction observed in SoC + nVNS group from baseline (7.2 to 5.9 for Sumatriptan, 17.3 to 13.9 for Oxygen). Control group showed smaller or no reduction. |
| Clinically meaningful improvements in Quality of Life (QoL) outcomes (EQ-5D-3L Index, VAS, HIT-6 scores). | Study Outcome: Statistically significant improvements in several QoL measures for SoC + nVNS group compared to control (e.g., EQ-5D-3L Index score change of 0.113 vs -0.047; P=0.011). |
2. Sample Size Used for the Test Set and Data Provenance
- Test Set (Clinical Study):
- Sample Size:
- Safety Population: 48 subjects in the nVNS + SoC group and 49 subjects in the Control group (total 97 subjects).
- mITT (modified intent-to-treat) Population: Numbers vary slightly depending on the specific QoL measure evaluated (e.g., 35-37 for SoC + nVNS, 40-46 for Control).
- Data Provenance:
- Country of Origin: Europe (multicenter, across 10 sites).
- Retrospective or Prospective: Prospective, randomized, controlled study.
- Sample Size:
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The device is a therapeutic device (vagus nerve stimulator) for headache treatment, not a diagnostic AI device requiring expert-established ground truth for image or data interpretation. The "ground truth" in this context refers to the clinical outcomes and patient-reported data (e.g., number of headache attacks, abortive medication use, quality of life scores) observed and recorded during a clinical trial. These outcomes were assessed by clinical study personnel (e.g., investigators, nurses) and self-reported by patients, rather than adjudicated by independent experts in the same way a diagnostic image would be.
4. Adjudication Method for the Test Set
As this is a therapeutic device trial, standard clinical trial methodology was used. There isn't a stated adjudication method in the sense of multiple experts reviewing and reaching a consensus on individual patient outcomes or data points being "adjudicated." The outcomes (headache frequency, medication use, QoL scores) were derived from patient diaries and questionnaires, and then statistically analyzed. The study was described as "randomized, controlled," implying proper blinding where feasible to minimize bias in outcome reporting, though explicit details on blinding of outcome assessors weren't provided.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed to evaluate the diagnostic accuracy of imaging or AI algorithms when interpreted by multiple human readers, often with and without AI assistance. This device is a therapeutic device, not an interpretative diagnostic tool.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
The gammaCore Sapphire is a physical medical device (vagus nerve stimulator) that directly delivers therapy, not a standalone algorithm. Therefore, "standalone" algorithm performance without human interaction is not applicable. The device's performance is intrinsically tied to its use by a human patient.
7. The Type of Ground Truth Used
The "ground truth" for evaluating the efficacy of the gammaCore Sapphire (for the preventive treatment of cluster headache) was based on patient-reported clinical outcomes and objective measures of disease activity, including:
- Change in mean number of cluster headache attacks per week.
- 50% responder rates (proportion of patients experiencing a ≥50% reduction in attacks).
- Reduction in abortive medication use (sumatriptan and oxygen).
- Quality of life outcomes (EQ-5D-3L Index score, EQ-5D-3L VAS score, HIT-6 score).
8. The Sample Size for the Training Set
The provided documentation does not detail a "training set" in the context of an AI algorithm. The device's efficacy was established through a clinical trial in which the treatment group received the active device. There is no mention of a pre-market "training set" for an AI component.
9. How the Ground Truth for the Training Set Was Established
Since there is no mention of an AI algorithm "training set," this question is not applicable based on the provided text. The device's efficacy was established through the clinical study described, where the "ground truth" was the observed clinical improvement in the patient population.
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November 27, 2018
Electrocore, Inc. Mike Romaniw VP. Quality Assurance & Regulatory Affairs 150 Allen Road, Suite 201 Basking Ridge, New Jersey 07920
Re: K182369
Trade/Device Name: gammaCore Sapphire Regulation Number: 21 CFR 882.8592 Regulation Name: External Vagal Nerve Stimulator For Headache Regulatory Class: Class II Product Code: PKR, QAK Dated: August 30, 2018 Received: August 31, 2018
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
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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Timothy A. Marjenin -S
Carlos L. Peña, PhD, MS For Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K182369
Device Name gammaCore Sapphire
gammaCore Sapphire (non-invasive vagus nerve stimulator) is intended to provide non-invasive vagus nerve stimulation (nVNS) on the side of the neck. gammaCore is indicated for:
- · 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.
- · The acute treatment of pain associated with migraine headache in adult patients.
| 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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5 510(K) SUMMARY
The following information is provided as required by 21 CFR §807.87 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.150 Allen Road, Suite 201Basking Ridge, New Jersey 07920Ph: 973-290-0097Fax: 973-290-9171 |
|---|---|
| Establishment Registration Number: | 3009060963 |
| Contact: | Mike RomaniwVP, Quality Assurance & Regulatory AffairsOffice: 973-355-6702Fax: 973-290-9171Mike.Romaniw@electroCore.com |
| Alternate Contact: | Eric J. LieblerSVP, NeurologyMobile: 908-938-9780Eric.Liebler@electroCore.com |
| Alternate Contact: | Deborah Lavoie GrayeskiSr. Project ManagerM Squared Associates, Inc.Office: 347-954-0418Fax: 703-562-9797dgrayeski@MSquaredAssociates.com |
| Alternate Contact: | Janice M. Hogan, Esq.PartnerHogan Lovells US LLPDirect: 267-675-4611Janice.Hogan@HoganLovells.com |
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| Date of Submission: | August 30, 2018 |
|---|---|
| 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, K180538 |
| Reference Device: | gammaCore-S, K173442 |
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:
- . 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.
- . The acute treatment of pain associated with migraine headache in adult patients.
Device Description: The gammaCore Sapphire (gammaCore) is a multiuse, 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 "clam shell" 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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The device will be provided to the patient/user with an initial 10-, 31-, or 93-day RFID card on the basis of the healthcare 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 healthcare provider. The refill/reload RFID cards will be programmed using the gammaCore Dispensing and Ordering Terminal (gammaCore DOT) 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 healthcare provider) for a unique device serial number, an RFID card is encoded with the appropriate dosage according to the prescription. The encoded RFID card is matched to a specific gammaCore device serial number residing in a database maintained by electroCore. The gammaCore DOT application, running on a Sony Xperia® tablet, uses a proprietary encoding algorithm to encrypt the therapy days and doses per day on the refill/reload RFID card using near field communication (NFC) protocols.
The encoding algorithm is based on a seed-value pair of numbers specific to a device ID (unique device serial number) that is registered in the gammaCore DOT database. The gammaCore DOT application ensures that only legitimate seed values allow refilling/reloading of the device through validation of the prescription and seed values in the gammaCore DOT database using the unique device and patient IDs.
The encoded refill/reload RFID card is then provided to the user/patient who requested the refil/reload of the device, along with one to six 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.
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Summary of Technological Characteristics:
There are no changes to the technological characteristics of the gammaCore Sapphire for this expanded indication.
Summary of Non-clinical Testing:
There are no changes to the technological characteristics of the gammaCore Sapphire for this expanded indication; no additional non-clinical or performance testing is required.
Summary of Clinical Data:
Clinical data demonstrating the safety and effectiveness of the gammaCore Sapphire for the prophylactic/preventive treatment of cluster headache were collected from a multicenter, randomized, controlled study that took place across 10 sites in Europe from November 23, 2012, to April 30, 2014. The study was designed to compare two parallel groups, standard of care (SoC) plus nVNS (active treatment) versus SoC alone (control). The study began with a 2-week run-in period, followed by a 4week comparative period when the subjects were randomized 1:1 to either active treatment or control. The comparative period was followed by an open-label period during which all subjects received active treatment with gammaCore in addition to the SOC for 4 weeks.
Subject demographics were similar among the SoC plus nVNS and control groups that comprised the study population (Table 3).
| Characteristic | nVNS plus SoC (n=48) | Control (n=49) |
|---|---|---|
| Age, y, mean (SD) | 45.4 (1.0) | 42.3 (11.0) |
| Sex, no. (%)Male | 34 (71) | 33 (67) |
| Race, no. (%)Caucasian | 48 (100) | 49 (100) |
Table 3. Subject Demographic Characteristics (safety population)
Abbreviations: nVNS, non-invasive vagus nerve stimulation; SD, standard deviation; SoC, standard of care.
Consistent with previous studies of nVNS for the treatment of primary headache, nVNS was safe and well tolerated. The primary endpoint of the study was the change in mean number of CH attacks per week. The mean number of CH attacks per week was calculated as the sum of all attacks during the 2-week run-in period divided by 2 and as the sum of all attacks during the last 14 days of the randomized period divided
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by 2. The change in mean number of attacks was calculated as the number of CH attacks per week during the randomized period (last 14 days) minus the number of CH attacks per week during the run-in period. Subjects treated with SoC plus nVNS had a significantly greater reduction in the number of cluster attacks per week versus the control arm (5.9 vs 2.1, respectively) for a mean therapeutic gain of 3.9 fewer attacks per week (95% CI: 0.5, 7.2; P=0.02). Higher 50% responder rates were also observed among subjects using SoC plus nVNS (40%) versus controls (8.3%) (P<0.001). SoC plus nVNS led to a reduction in the use of abortive medications from baseline to the last 2 weeks of the randomized phase (Figure 1). nVNS and SoC use was also associated with clinically meaningful improvements in the quality of life outcomes evaluated (Table 4). There was no change in CH duration or severity of acute attacks reported in this trial.
Figure 1. Abortive Medication Use (mITT Population)
Image /page/7/Figure/4 description: The image is a legend for a graph or chart. The title of the chart is "Use of Sumatriptan and Oxygen: Baseline Versus the Last 2 Weeks of the Randomized Phase". The legend indicates that the color dark blue represents the baseline and the color orange represents the randomized phase.
Image /page/7/Figure/5 description: The image shows two bar charts comparing the number of times medication was used for subcutaneous sumatriptan and inhaled oxygen. For subcutaneous sumatriptan, SoC Plus nVNS had a value of 7.2 with N=32, while the control had a value of 6.8 with N=42. For inhaled oxygen, SoC Plus nVNS had a value of 17.3 with N=32, while the control had a value of 12.6 with N=42.
Abbreviations: mITT, modified intent-to-treat; nVNS, non-invasive vagus nerve stimulation; SoC, standard of care. Values are presented as means and were calculated from all subjects with evaluable data. Error bars denote standard error of the mean.
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| QoL Measures | Mean Change From Baseline toRandomized Phase | Mean Change From Baseline toExtension Phase | ||
|---|---|---|---|---|
| ITT Population | ||||
| SoC Plus nVNS(n=45) | Control(n=48) | SoC Plus nVNS(n=45) | Control(n=48) | |
| EQ-5D-3L Index score | 0.113c | -0.047 | 0.117 | 0.065 |
| EQ-5D-3L VAS score | 7.16 | 0.250 | 8.16 | 3.54 |
| HIT-6 score | -2.29 | -0.438 | -2.62 | -2.25 |
| mITT Population | ||||
| SoC Plus nVNSd | Controle | SoC Plus nVNSf | Controlg | |
| EQ-5D-3L Index score | 0.145h | -0.049 | 0.155 | 0.078 |
| EQ-5D-3L VAS score | 9.20i | 0.27 | 10.79 | 4.36 |
| HIT-6 score | -2.78 | -0.47 | -3.28 | -2.77 |
| Abbreviations: ITT, intent-to-treat; HIT-6, 6-item Headache Impact Test; mITT, modified intent-to-treat; nVNS, non-invasive vagus nervestimulation; QoL, quality of life; SoC, standard of care; VAS, visual analogue scale.aFor the ITT population, missing data were imputed to no change from baseline to the randomized phase or from baseline to the extensionphase, respectively.bAll mITT calculations were performed for subjects with available data. No imputation for missing data was performed.cP=0.011 versus control..dNumber of evaluated subjects in the SoC plus nVNS group was 35 for the EQ-5D-3L index score and the EQ-5D-3L VAS score and 37for the HIT-6 score.eNumber of subjects evaluated in the control group was 46 for the EQ-5D-3L index score and the EQ-5D-3L VAS score and for the HIT-6score:.fNumber of evaluated subjects in the SoC plus nVNS group was 34 for the EQ-5D-3L index score and the EQ-5D-3L VAS score and 36 forthe HIT-6 scoregNumber of evaluated subjects in the control group was 40 for the EQ-5D-3L index score and 39 for the EQ-5D-3L VAS score and theHIT-6 score..hP=0.007 versus control.iP=0.007 versus control. |
Table 4. Quality of Life Outcomes (ITTª and mITT Populations*)
nVNS was safe and well tolerated in both the randomized clinical trial as well as in the real-world study that supports this application. In the 2 months of treatment during the PREVA study, a similar proportion of participants in the SoC plus nVNS group and controls reported any AE. As with the studies supporting the currently cleared indications, the majority of AEs (>90%) were mild, transient, and self-limiting.
Clinical data demonstrating the safety and effectiveness of acute treatment of pain associated with migraine headache were provided in the gammaCore-S submission (K173442) and are applicable to the
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gammaCore Sapphire. The gammaCore-S and gammaCore Sapphire have the same fundamental scientific technology and intended use. The devices do not differ in output, waveform, or treatment protocol.
Substantial Equivalence Discussion:
gammaCore Sapphire technology is identical to the device technology cleared under K180538. There have been no changes in the technological characteristics or intended use of the gammaCore Sapphire in the proposed Indications for Use Statement. The instructions for the device associated with acute treatment of episodic cluster headache do differ from those for preventive treatment of cluster headache and those for migraine headache; however, for all indications, use of more than 24 stimulations per day has not been formally evaluated and continues to be listed as a precaution in the labeling.
Summary:
Table 5 establishes the substantial equivalence of the subject device to that of the predicate device.
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| Table 5. Substantial Equivalence Comparison Table | |||
|---|---|---|---|
| --------------------------------------------------- | -- | -- | -- |
| gammaCore Sapphire(Subject Device) | gammaCore Sapphire(Primary Predicate) | gammaCore-S(Reference Device) | Substantial Equivalence | |
|---|---|---|---|---|
| 510(k) number | TBD | K180538 | K173442 | |
| Intended use | The gammaCore Sapphire is adevice that provides non-invasive vagus nervestimulation (nVNS) whenapplied to the side of the neck.This is a mild electricalstimulation of the vagus nerve,which runs through the neckand carries information to thecentral nervous system. Eachstimulation with gammaCorelasts 2 minutes. The patientcontrols the stimulationstrength. | The gammaCore Sapphire is adevice that provides nVNSwhen applied to the side of theneck. This is a mild electricalstimulation of the vagus nerve,which runs through the neckand carries information to thecentral nervous system. Eachstimulation with gammaCorelasts 2 minutes. The patientcontrols the stimulationstrength. | The gammaCore-S is a devicethat provides nVNS whenapplied to the side of the neck.This is a mild electricalstimulation of the vagus nerve,which runs through the neckand carries information to thecentral nervous system. Eachstimulation with gammaCorelasts 2 minutes. The patientcontrols the stimulationstrength. | No change in intended use |
| Indication foruse | The gammaCore Sapphire isindicated for:• Adjunctive use for thepreventive treatment of clusterheadache (CH) in adultpatients• The acute treatment of painassociated with episodiccluster headache (eCH) inadult patients• The acute treatment of painassociated with migraineheadache in adult patients | The gammaCore Sapphire isindicated for the acute treatmentof pain associated with eCH inadult patients | The gammaCore-Sdevice is indicated for the acutetreatment of pain associatedwith eCH and migraineheadache in adult patients | The expansion of the indicationdoes not alter the intendedtherapeutic effect or otherwisecreate a new intended use, asexplained previously. Supportedby clinical data in Section 20 ofthis submission. |
| Rx vs OTC | Prescription use only | Prescription use only | Prescription use only | No change |
| gammaCore Sapphire(Subject Device) | gammaCore Sapphire(Primary Predicate) | gammaCore-S(Reference Device) | Substantial Equivalence | |
| Treatmentrecommendation | Preventive treatment of CH:120-second stimulation cycle,3 consecutive stimulations- oneither side of the neck as follows:o First daily treatment: within1 hour of wakingo Second daily treatment: atleast 7-10 hours after thefirst daily treatmentAcute treatment of eCH:120-second stimulation cycle,3 consecutive stimulations up to8 times a dayAcute treatment of migraine:120-second stimulation cycle, 2bilateral stimulations up to 3times a day | Acute treatment of eCH:120-second stimulation cycle,3 consecutive stimulations up to8 times a day | Acute treatment of eCH:120-second stimulation cycle,3 consecutive stimulations up to8 times a dayAcute treatment of migraine:120-second stimulation cycle, 2bilateral stimulations up to 3times a day | Change in treatment protocol toreflect different forms ofprimary headache |
| Patient-contactingmaterials | SS, ABS-PC, SignaGel®electrode gel | SS, ABS-PC, SignaGelelectrode gel | SS, ABS-PC, SignaGelelectrode gel | No change in materials |
| Electricalclassification | UL 60601-1 Class III Type BFApplied Part | UL 60601-1 Class III Type BFApplied Part | UL 60601-1 Class III Type BFApplied Part | No change in classification |
| Waveform/frequency | Sinusoidal wave, symmetricalbiphasic5000-Hz pulses at a rate of 25Hz | Sinusoidal wave, symmetricalbiphasic5000-Hz pulses at a rate of 25Hz | Sinusoidal wave, symmetricalbiphasic5000-Hz pulses at a rate of 25Hz | No change in waveform orfrequency |
| Maximumoutput | 30V (peak), 60 mA(peak) | 30V (peak), 60 mA(peak) | 30V (peak), 60 mA(peak) | No change in outputs |
| Load impedance | 450-550 ohms | 450-550 ohms | 450-550 ohms | No change in impedance |
| Power supply | 3V LiFePo4 battery | 3V LiFePo4 battery | 3V LiFePo4 battery | No change in power supplyvoltage |
| gammaCore Sapphire(Subject Device) | gammaCore Sapphire(Primary Predicate) | gammaCore-S(Reference Device) | Substantial Equivalence | |
| Service life | 3 Years from date ofmanufacture | 3 Years from date ofmanufacture | 3 Years from date ofmanufacture | No change in service life |
| Device circuitry | ||||
| Controls | Control slideIncrease slide up/decrease slidedown | Control slideIncrease slide up/decrease slidedown | Increase (+) and decrease (-)push buttons | No change in circuitry orcontrols of the subject andpredicate devices.Differences between the subjectdevice and reference devicerepresent changes in the userinterface. These changes do notimpact the safety oreffectiveness of the device. |
| Outputregulation | Device software and controlslide | Device software and controlslide | Device software and pushbuttons | |
| Device statusdisplay | LED screen | LED screen | LCD screen | |
| Battery charger | Qi-compatible wireless chargerin clam shell storage case | Qi-compatible wireless chargerin clam shell storage case | Not applicable | |
| RFIDrefill/reloadcapability | Allows refilling/reloading of thenumber of days/doses for whichthe device can providetreatment; allows for continueduse of same device for extendedperiods of time | Allows refilling/reloading of thenumber of days/doses for whichthe device can providetreatment; allows for continueduse of same device for extendedperiods of time | Not applicable | |
| Devicediagnostics,Bluetooth | Provides for diagnostics bymanufacturer of returneddevices, including number ofdays device was used, numberof doses delivered, andremaining days/doses | Provides for diagnostics bymanufacturer of returneddevices, including number ofdays device was used, numberof doses delivered, andremaining days/doses | Not applicable | |
| gammaCore Sapphire(Subject Device) | gammaCore Sapphire(Primary Predicate) | gammaCore-S(Reference Device) | Substantial Equivalence | |
| Audible signals/alarms | ||||
| Start-up | Yes | Yes | Yes | No change in available alarmsignals |
| Sessioncomplete | Yes | Yes | Yes | |
| Errors/depletedbattery | Yes | Yes | Yes | |
| No doses left | Yes | Yes | Yes | |
| Expired/nodays left | Yes | Yes | Yes | |
| Visual indicators/status | ||||
| Start-up(powered on) | Light on | Light on | Light on | No change to display/message inthe subject and predicatedevices.Differences between the subjectdevice and reference devicerepresent changes in the userinterface. These changes do notimpact the safety oreffectiveness of the device. |
| Unit ready(powered on) | LED doses remaining for 24-hrperiod | LED doses remaining for 24-hrperiod | Light on/LCD amplitude "0" | |
| Dose complete | LED days and doses remainingand last amplitude | LED days, doses remaining, andlast amplitude | Light off/LCD days, dosesremaining, and last amplitude | |
| Errors/depletedbattery | E# display | E# display | LCD "Err"/flashing light | |
| No dosesremaining | LED doses 00 | LED doses 00 | Flashing light/LCD number ofdoses remaining | |
| Expired/nodays left | LED doses/days remaining | LED doses/days remaining | Flashing light/LCD daysremaining | |
| Low battery | LED display battery chargeindicator | LED display battery chargeindicator | No light/LCD display "Lo" | |
| Reloading error | LED display if refill processfails | LED display if refill processfails | Not applicable | |
| Card error | LED display if refill card fails | LED display if refill card fails | Not applicable |
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Conclusion:
There have been no changes in the technological characteristics or intended use of the gammaCore Sapphire. Clinical data demonstrating the safety and effectiveness of acute treatment of pain associated with migraine headache were provided previously for gammaCore-S in submission K173442 and are applicable to the gammaCore Sapphire. The addition of the preventive treatment of cluster headache to the Indications for Use does not raise new or different questions of safety or effectiveness compared to those raised with the predicate device. Therefore, the presented information demonstrates that the subject device is substantially equivalent to the predicate device.
§ 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.