The C.A.R.E. Appliances are intended to reduce nighttime snoring and to treat mild and moderate obstructive sleep apnea in adults, 18 years of age and older. The C.A.R.E. Appliances are also intended to treat moderate and severe obstructive sleep apnea (OSA) in adults, 18 years of age and older along with positive airway pressure (PAP) devices and/or myofunctional therapy, as needed.

Device Description

The C.A.R.E. appliances are intended to reduce nighttime snoring and to treat mild and moderate obstructive sleep apnea in adults, 18 years of age and older. The C.A.R.E. appliances are also intended to treat moderate and severe obstructive sleep apnea (OSA) in adults, 18 years of age and older along with positive airway pressure (PAP) devices and/or myofunctional therapy, as needed. They consist of an upper tray and a lower tray and is designed to open the airway during sleep. The device is customized to each patient, and features an adjustment mechanism to allow it to be further customized to each patient.

The DNA appliance does not connect the upper and lower trays, while the mRNA and mmRNA appliances connect the trays with a flange and hinge respectively.

The devices are identical to the already-marketed predicates of the same name.

AI/ML Overview

This document is a 510(k) summary, which is a premarket notification for a medical device to demonstrate that the device is at least as safe and effective as a legally marketed device (predicate device). It does not contain information about the acceptance criteria of a specific study nor does it describe a study that proves the device meets the acceptance criteria. Instead, it outlines the device's indications for use and provides real-world clinical data and a peer-reviewed study to support an expanded indication for use by demonstrating substantial equivalence to predicate devices.

Therefore, many of the requested items, such as acceptance criteria for device performance, details of a specific test set, ground truth experts, adjudication methods, MRMC studies, standalone performance, and training set details, are not explicitly present as this document serves a different regulatory purpose.

However, based on the provided text, I can extract and infer some relevant information:

Key Takeaway: This document is not a report of a study designed to establish acceptance criteria or prove a device meets them in the manner typically seen for AI/ML device clearances. It is a 510(k) summary for a physical medical device (oral appliance) seeking an expanded indication for use, primarily relying on clinical data and substantial equivalence to previously cleared devices. The "performance" is demonstrated through real-world clinical outcomes and a comparative study, rather than specific acceptance criteria for an AI algorithm's output.

Here's an attempt to answer the questions based on the provided text, noting where information is not available:

1. A table of acceptance criteria and the reported device performance

The document does not specify "acceptance criteria" in a quantitative, pre-defined manner for the device's efficacy. Instead, it presents observed performance from clinical data and a study, which implicitly served to demonstrate sufficient efficacy for an expanded indication.

Implicit "Performance Metrics" from Studies:

Metric / Objective	Reported Device Performance (C.A.R.E. Appliances based on RWD)	Implied "Acceptance" (demonstrates equivalence/efficacy for expanded indication)
AHI Reduction (Severe OSA)	- AHI Pre-Treatment: 46.1 ± 15.1 - AHI Post-Treatment: 21.7 ± 14.8 - AHI Change: -24.3 ± 18.1 - Percent Decrease: 50.8%	Demonstrates significant reduction in AHI.
Patients Improved by at least 1 Classification (Severe OSA)	78% (57/73 patients)	High percentage of patients show clinical improvement.
Patients Improved by 45% or 1 classification (Severe OSA)	80% (58/73 patients)	High percentage of patients show clinical improvement.
Patients Resolved (Severe OSA)	14% (10/73 patients)	Some patients achieve full resolution.
AHI Reduction (Moderate OSA)	- AHI Pre-Treatment: 21.6 ± 4.5 - AHI Post-Treatment: 12.0 ± 10.5 - AHI Change: -9.5 ± 10.8 - Percent Decrease: 44.4%	Demonstrates significant reduction in AHI.
Patients Improved by at least 1 Classification (Moderate OSA)	80% (28/35 patients)	High percentage of patients show clinical improvement.
Patients Improved by 45% or 1 Classification (Moderate OSA)	80% (28/35 patients)	High percentage of patients show clinical improvement.
Patients Resolved (Moderate OSA)	20% (7/35 patients)	Some patients achieve full resolution.
Transpalatal Width Same or Improved (Severe OSA)	99% (72/73 patients)	Demonstrates positive or stable anatomical change.
Transpalatal Width Same or Improved (Moderate OSA)	100% (35/35 patients)	Demonstrates positive or stable anatomical change.
AHI Same or Improved (Severe OSA)	97% (71/73 patients)	Very high consistency in AHI not worsening, often improving.
AHI Same or Improved (Moderate OSA)	91% (32/35 patients)	Very high consistency in AHI not worsening, often improving.
Safety	10% of patients had inadvertent tooth movement and/or changes in bite that were treated with braces or aligners.	No persistent safety issues, manageable side effects.

2. Sample sizes used for the test set and the data provenance

Real-World Clinical Data (RWD):
- Sample Size:
  - Severe OSA: 73 patients
  - Moderate OSA: 35 patients
  - Total RWD patients: 108 patients
- Data Provenance: Obtained from a research database.
  - Country of Origin: Not specified.
  - Retrospective/Prospective: "Real Word Clinical Data obtained from a research database over a period of 5 years (2018-2023)" implies a retrospective analysis of existing data.
Peer-Reviewed Study:
- Sample Size: 15 consecutive patients.
- Data Provenance: Not specified for country of origin or retrospective/prospective outside of being a "blinded, controlled, randomized study."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document. The "ground truth" here is the clinical diagnosis of OSA and AHI values from pre- and post-treatment sleep studies, not expert annotations of images for an AI algorithm.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not provided as this is not an AI/ML clinical study requiring adjudication of interpretations. The "ground truth" is measured AHI from sleep studies.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

There was no MRMC comparative effectiveness study done with AI assistance described. This device is an oral appliance, not an AI software. The provided peer-reviewed study compared two types of C.A.R.E. appliances (DNA vs mRNA) to each other regarding AHI reduction.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This question is not applicable as the device is a physical oral appliance, not an AI algorithm.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The ground truth used for assessing the device's effectiveness was clinical outcomes data, specifically:

Apnea-Hypopnea Index (AHI) values derived from pre- and post-treatment sleep studies.
Transpalatal Width changes.
Patient Classification improvements (e.g., severe to moderate OSA).
Resolution of OSA.

8. The sample size for the training set

This question is not applicable. This document describes a physical medical device (oral appliance) for which there is no "training set" in the context of machine learning. The "training" for the device's design comes from medical and engineering principles, and its efficacy is evaluated through clinical studies/data, not through training a model.

9. How the ground truth for the training set was established

This question is not applicable as there is no training set for an AI algorithm in this context.

Summary

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Image /page/0/Picture/0 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 consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.

November 28, 2023

Vivos Therapeutics, Inc % Colette Cozean Regulatory Consultant Eyedeas Company 21581 Midcrest Dr Lake Forest, California 92630

Re: K230947

Trade/Device Name: C.A.R.E. Appliance (DNA, mRNA, mmRNA) Regulation Number: 21 CFR 872.5570 Regulation Name: Intraoral Devices For Snoring And Intraoral Devices For Snoring And Obstructive Sleep Apnea Regulatory Class: Class II Product Code: LRK, LQZ Dated: November 26, 2023 Received: November 27, 2023

Dear Colette Cozean:

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 (the 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 available at https://www.accessdata.fda.gov/scripts/cdrb/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.

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Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30. Design controls; 21 CFR 820.90. Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 mediation-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).

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Sincerely,

Michael E. Adjodha -S

Michael E. Adjodha, MChE, RAC, CQIA Assistant Director DHT1B: Division of Dental and ENT Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental 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) K230947

Device Name

C.A.R.E. Appliances (DNA, mRNA, mmRNA)

Indications for Use (Describe)

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 - K230947

Applicant:	Vivos Therapeutics300 S. 5th StreetMurray, KY, 42017, USA(270)-226-9237
Contact Person:	Colette Cozean, PhD21581 Midcrest DriveLake Forest, CA92630 (949) 855-2885colettecozean@gmail.com
Date Prepared	November 18, 2023
Proprietary Name	C.A.R.E. Appliances (DNA, mRNA, mmRNA)
Common Name	Dental Device - Anti Snoring /Obstructive Sleep Apnea Device
Classification Name	Anti Snoring/ Obstructive Sleep Apnea Device
Product Code	LRK, LQZ
Primary Predicate	DNA (K222872)
Reference Device	mRNA (K130067)
Reference Devices	mmRNA (K210203)

Device Description

The DNA appliance does not connect the upper and lower trays, while the mRNA and mmRNA appliances connect the trays with a flange and hinge respectively.

The devices are identical to the already-marketed predicates of the same name.

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Scientific Principles

During sleep, the muscles in the tongue and back of the throat relax, which can cause them to sag and narrow the airway. Airflow through a narrow airway is the cause of snoring. When this narrowing of the airway is severe, it results in Obstructive Sleep Apnea (OSA), where the airway closes. This can happen up to hundreds of times during the night, lasting for a minute or longer.

With these closures, the brain detects the lack of oxygen and disturbs sleep to draw breath. In many cases, the individual isn't completely aware of the stoppages, which don't fully awaken the sleeper. Sleep apnea has been linked to major medical conditions, including hypertension, headaches, heart disease, diabetes, depression, and more.

Device Function

The C.A.R.E. appliances are customized oral devices featuring a lower tray and an upper trav. These trays put gentle pressure on the back of the throat to prevent the airway from collapsing during sleep.

Studies have shown that customized oral devices that function by increasing the patency of the airway show comparable efficacy to continuous positive airway pressure (CPAP) devices, considered the gold standard of treatment for OSA (Oral appliance therapy in Olstructive Sleep Aprea-Hypopnea syndrome - A clinical study on therapeutic outcomes Hoekema A PhD thesis, University Medical Centre Groningen Department of Oral and Maxillofacial Surgery. pp 110, 2007). On the basis of these studies, use of oral devices has been recommended by the American Academy of Sleep Medicine for patients with mild or moderate OSA, or for those with severe OSA who are unable to tolerate the CPAP device.

The C.A.R.E. Appliances aim to expand the nasal airway through jaw expansion and mid-facial redevelopment. In doing so, an oral device may be able to permanently improve the oropharyngeal airway. Studies have shown that the C.A.R.E. appliances can increase nasal cavity volume and reduce the incidence of apnea-hypopnea episodes. The mRNA and mmRNA also increase air cavity volume by mandibular advancement.

The C.A.R.E. appliances are customized on models of the patient's teeth, using standard orthodontic acrylics and standard orthodontic wires for clasps and retention. The C.A.R.E. appliances allow for six degrees of freedom in customization, including antero-posterior (AP) adjustment, transverse (TV) adjustment, as well as permitting adjustments of the vertical dimension of occlusion (VDO).

The addition of an optional extender on the back of the device further prevents the patient's airway from collapsing during sleep.

Intended Use

Target Population: Patients 18 years of age and older with obstructive sleep apnea.

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Environment of Use: Fitting of the C.A.R.E. appliances in the dental office for patient use at home.

Comparison to Predicate Devices: Each of the C.A.R.E. appliances (DNA, mRNA and mmRNA) are identical to the previously cleared predicate devices of the same name. This is a request for an expanded Indication of Use only.

The cleaning instructions, instructions for use, and labeling are those currently used for the already-marketed predicate device. The have been reworded, but the indications for use, contraindications, warnings and cautions are the same. The precautions, warnings, risk analysis and other critical statements have been changed only slightly to allow for simultaneous treatment with other modalities as was done with the DNA appliance in K222872) according to the Vivos Method.

Shelf Life: The devices are provided non-sterile. Shelf life will be identical to the predicate devices. No shelf life is required as the device is custom-manufactured and immediately fitted to the patient by the dentist.

Non-clinical Testing: A risk analysis was performed, which considered soreness, obstruction of breathing, tooth movement, and breakage. The product was compared to predicate devices in each area to show the risks were equivalent to the predicate devices. No biocompatibility testing was done as all the components are the same as the predicate device.

Clinical Testing: This submittal relies on peer-reviewed literature and clinical data (RWD) demonstrating that C.A.R.E. Appliances can treat mild and moderate obstructive sleep apnea in adults, 18 years of age and older and treat moderate and severe obstructive sleep apnea (OSA) in adults, 18 years of age and older along with positive airway pressure (PAP) devices and/or myofunctional therapy, as needed. The C.A.R.E. appliances raise no new questions of safety and efficacy as compared to the predicate device.

A peer-reviewed, blinded, controlled, randomized study evaluated the reduction in AHI in 15 consecutive patients randomly assigned to a DNA or a mRNA treatment group. The sleep studies were conducted pre- and post-treatment (the average treatment period was 9.7 months) without an appliance in the mouth. AHI reduction in DNA patients was 70.2%, mRNA patients was 50.6% and C.A.R.E. appliances combined was 64.0%.

Real Word Clinical Data obtained from a research database over a period of 5 years (2018-2023) was filtered to include i) patients 18 years of age and older, ii) treated with a C.A.R.E. appliance, iii) pre-and post-sleep studies at least six months apart and iv) diagnosed with moderate (15≤AHI<30) or severe (AHI ≥ 30) Obstructive Sleep Apnea (OSA). Results were as follows:

	CAREsevere	CAREsevere	CAREmoderate	CAREmoderate
	Count	%	Count	%
Number of patients	73	100%	35	100%
No of Transpalatal Width Same orImproved	72	99%	35	100%
Number of AHI Same or Improved	71	97%	32	91%

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Improved by at least 1 Classification	57	78%	28	80%
Improved by 45% or 1 Classification	58	80%	28	80%
Resolved	10	14%	7	20%

AHI Changes

	AHIPre-Treatment(CAREappliances)	AHIPost-Treatment(CAREAppliances)	AHI Change(CAREappliances)	PercentDecrease
Severe CARE	46.1 ± 15.1	21.7 ± 14.8	-24.3 ± 18.1	50.8%
Moderate	21.6 ± 4.5	12.0 ± 10.5	-9.5 ± 10.8	44.4%

Eighty percent (80%) of patients with severe OSA improved by at least 45% or 1 classification (also by 50% or 1 classification). Eighty percent (80%) of patients with moderate OSA improved by at least 45% or 1 classification. Twenty percent (20%) of moderate patients and fourteen percent (14%) of severe patients completely resolved their OSA.

Thirty-seven (37 patients) were treated with the C.A.R.E. appliance alone resulting in an AHI improvement of 52.8%. Thirty-six (36) patients were treated with C.A.R.E. appliances and positive airway pressure and/or myofunctional therapy as prescribed by their dentist for all or a portion of their treatment.

While there were no persistent safety issues, 10% of patients had inadvertent tooth movement and/or changes in bite that were treated with braces or aligners.

Conclusion: The clinical data supports the finding that the C.A.R.E. appliances raise no new questions of safety and efficacy as compared to the predicate devices for the treatment of mild and moderate obstructive sleep apnea in adults, 18 years of age and older and the treatment of moderate and severe obstructuve sleep apnea (OSA) in adults, 18 years of age and older along with positive airway pressure (PAP) devices and/or myofunctional therapy, as needed.

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Regulation Number and Section

§ 872.5570 Intraoral devices for snoring and intraoral devices for snoring and obstructive sleep apnea.

(a)
Identification. Intraoral devices for snoring and intraoral devices for snoring and obstructive sleep apnea are devices that are worn during sleep to reduce the incidence of snoring and to treat obstructive sleep apnea. The devices are designed to increase the patency of the airway and to decrease air turbulence and airway obstruction. The classification includes palatal lifting devices, tongue retaining devices, and mandibular repositioning devices.(b)
Classification. Class II (special controls). The special control for these devices is the FDA guidance document entitled “Class II Special Controls Guidance Document: Intraoral Devices for Snoring and/or Obstructive Sleep Apnea; Guidance for Industry and FDA.”