Oravive™ is a fluoride-free toothpaste product intended for cleaning the tooth surface on a daily basis. Clinical studies have shown that Oravive™ also provides relief from tooth sensitivity due to cold, heat, acids, sweets, or contact by the occlusion of dentin tubules.

Device Description

Oravive™ is a daily-use, fluoride-free toothpaste device that incorporates NovaMin® as its active ingredient. The non-aqueous formulation is designed to clean your teeth as well as give your whole mouth a fresh feeling we call REVITALIZING! Oravive™ is also designed to physically occlude dentin tubules for the management of sensitive teeth. NovaMin® (calcium sodium phosphossilicate) is composed of elements that occur naturally in the body (Ca, Na, Si, P, and O). When exposed to an aquoous environment, NovaMin® undergoes a rapid surface reaction, allowing it to physically occlude tubules. Within a short period of time, essentially all of the NovaMin® reacts to form hydroxycarbonate apatite (HCA), which is chemically and structurally similar to natural tooth mineral.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets the acceptance criteria, based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state formal "acceptance criteria" for clinical performance in a quantifiable, pre-defined manner. Instead, it describes findings that support the device's efficacy and safety compared to controls and a predicate device. The performance claims are primarily related to reduction in tooth sensitivity and abrasivity.

Acceptance Criteria (Implied)	Reported Device Performance
Safety: Biocompatibility	No evidence of hazardous effects if used as directed.
Occlusion Efficacy (in vitro): Significant tubule occlusion compared to controls	Oravive™ occludes a statistically significant number of tubules compared to controls.
Abrasivity: RDA value < 250 (safe for daily use)	Mean RDA value of 125.55 (well under the limit of 250).
Clinical Efficacy (Tooth Sensitivity): Significant reduction in sensitivity (implied comparison to placebo and equivalent to predicate)	- Mean VAS scores for air stimulus and cold water were reduced significantly (p < .01) in Oravive™ group compared to placebo after six weeks.- Reduction in VAS for Oravive™ was 36% for air stimulus and 39% for cold water stimulus at six weeks.- Performed equivalently to a SrCl2 containing, commercially available desensitizing toothpaste.
Adverse Events: No reported adverse events	No adverse events in any of the groups were reported.

2. Sample Size and Data Provenance for the Test Set

Sample Size:
- Clinical Efficacy Study: A total of 75 patients were accepted into the study, with 25 in each of the three groups (Oravive™, placebo, and SrCl2 desensitizing toothpaste). 67 patients completed the six-week study.
- In vitro tubule occlusion: Not specified, but mentioned results indicate statistical significance.
- Abrasivity: Not specified, but performed according to ADA recommended procedure.
Data Provenance:
- Clinical Efficacy Study: Conducted in Wuhan University, Wuhan, China. The study was prospective (randomized, double-blind, placebo-controlled, six-week clinical trial).
- Abrasivity Test: Conducted at Indiana University School of Dentistry.
- Biocompatibility and In Vitro Tubule Occlusion: Location not specified.

3. Number of Experts and Qualifications for Ground Truth (Test Set)

The document does not explicitly state the number or specific qualifications of experts used to establish "ground truth" for the clinical efficacy test set.

Clinical Efficacy Study: The primary outcome measure was patient-reported tooth sensitivity using a Visual Analog Scale (VAS) after stimulation. While clinicians performed the stimulation, the "ground truth" here is the patient's subjective experience of pain, not an expert's diagnosis. The study was overseen by the Medical Ethics Committee of the School of Stomatology, Wuhan University.

4. Adjudication Method for the Test Set

Clinical Efficacy Study: No explicit adjudication method (like 2+1 or 3+1 consensus) is described. The study was randomized, double-blind, and placebo-controlled. This design inherently aims to minimize bias in data collection and interpretation. The VAS scores were directly recorded from patients.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No, an MRMC comparative effectiveness study was not done. This type of study is more common for diagnostic imaging devices where multiple readers interpret cases with and without AI assistance. This device is a toothpaste where the primary outcome is patient-reported sensitivity.

6. Standalone (Algorithm Only) Performance

Yes, a form of "standalone" performance was effectively evaluated for certain aspects.
- In vitro tubule occlusion efficacy: This was an algorithm-only (device-only) test demonstrating its mechanical action.
- Relative Dentin Abrasivity (RDA): This was a standalone test of the product's physical property.
- Clinical Efficacy: While patients were involved, the study measured the effect of the device itself (Oravive™) compared to controls, rather than human interpretation aided by AI. This can be considered the "standalone" clinical performance of the product.

7. Type of Ground Truth Used

Clinical Efficacy: Patient-reported outcomes (subjective pain perception via Visual Analog Scale - VAS) were the primary ground truth for tooth sensitivity.
In vitro tubule occlusion: The ground truth was based on scientific observation and measurement of tubule occlusion in demin block models.
Abrasivity: The ground truth was based on standardized laboratory measurement according to the ADA recommended procedure.
Biocompatibility: Ground truth derived from laboratory test results indicating the absence of hazardous effects.

8. Sample Size for the Training Set

The document describes a clinical trial for testing the device's efficacy, but it does not mention a separate "training set" as would be typical for machine learning algorithms. The studies described are for the evaluation of the finished product. If there was any optimization or formulation work that involved data, it's not detailed as a "training set" in the context of this submission.

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

As no "training set" is described in the context of a machine learning algorithm, this question is not applicable based on the provided text. The studies mentioned are primarily for clinical validation and safety assessment of the developed product.

Summary

{0}------------------------------------------------

MAY 1 0 2004

510(k) Premarket Notification
NovaMin Technology, Inc.
Oravive™ Tooth Revitalizing Paste

the first the state of the states

. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1. SUBMITTER INFORMATION:

Name:	NovaMin Technology, Inc.
Address:	13709 Progress Blvd., #23Alachua, Florida 32615 USA
Phone:	(386) 418-1551
Facsimile:	(386) 418-1465
Contact:	David C. Greenspan, Ph.D.

February 23, 2004 Preparation Date:

2. DEVICE NOMENCLATURE:

Trade Name:	Oravive™ Tooth Revitalizing Paste
Common Name:	Dentifrice, Toothpaste
Classification Name:	Agent, Polishing, Abrasive, Oral Cavity

3. LEGALLY MARKETED PREDICATE DEVICE:

Device Name:	Butler GUM® Prophylaxis Paste with NovaMin®
510(k) Number:	K024343
Applicant:	USBiomaterials Corporation

4. DEVICE DESCRIPTION:

S. INTENDED USE:

ﺮ

{1}------------------------------------------------

6. TECHNOLOGICAL CHARACTERISTICS:

The technological characteristics of Oravive™ and Butler GUM® Prophylaxis Paste with NovaMine are very similar. Both devices are designed to relieve hypersensitivity associated with exposed dentin by the deposition of a calcium phosphate layer onto the tooth surface. Both devices use NovaMia" to produce a calcium phosphate layer that occludes dentinal tubules and blocks hydrodynamic flow. The primary difference between the two devices is that Oravive™ supplies the calcium and phosphate ions on a daily basis, whereas Butler GUM® Prophylaxis Paste with NovaMin supplies the ions once every professional tooth cleaning. In addition, there are some differences in the proportion of the ingredients in the two products.

7. SAFETY AND PERFORMANCE DATA:

Many different biocompatibility tests have been performed on NovaMin®, the active ingredient in Oravive The results of these tests indicate that there is no evidence of any hazardous effects to the patient if the product is used as directed.

The tubule occlusion efficacy of Oravive™ was evaluated using an in vitro demin block model. The results indicate that Oravive™ occludes a statistically significant number of tubules when compared to controls.

The relative abrasion level of Oravive™ was evaluated at Indiana University School of Dentistry. The procedure used was the ADA recommended procedure for determination of toothpaste abrasivity. The result was a mean Relative Dentin Abrasivity (RDA) value of 125.55, This RDA value is well under the limit considered safe for daily-use (RDA value < 250).

A randomized, double-blind, placebo-controlled, six-week clinical trial was conducted to evaluate the efficacy of Oravive™ Tooth Revitalizing Paste with a placebo and a commercially available StCl2 desensitizing toothpaste. The study was approved by the Medical Ethics Committee of the School of Stomatology, Wuhan University, Wuhan, China. Written informed consem and medical history were obtained prior to entering patients into the study. A total of seventy-five (75) patients were accepted into the study; twenty-five (25) in each group. There were no significant differences in the average ages between the test groups. Brushing regimen was twice daily for a six-week period. Tooth sensitivity was recorded by marking the degree of discomfort experienced by the patient on a 10cm visual analog scale (VAS) after stimulation of selected teeth by cold water and a metered air blast. The results were analyzed for statistical significance using ANOVA and Bonferonni post hoc tests.

Sixty-seven (67) patients completed the six-week study. No adverse events in any of the groups were reported. The results showed that the mean values of the VAS scores resulting from the air stimulus and cold water were reduced significantly (p < . 01) in both the test and positive control groups compared with the placebo group after six weeks of tooth brushing. Reduction in VAS for the NovaMin" containing toothpaste at six weeks was 36% for the air stimulus and 39% for the cold water stimulus.

The results of this study showed that the NovaMin® containing toothpaste reduced dentin sensitivity significantly over a six-week time period, and that it performed equivalently to a SrCl2 containing, commercially available desensitizing toothpaste.

{2}------------------------------------------------

Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract symbol that resembles an eagle or a bird in flight, composed of three curved lines.

MAY 1 0 2004

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Dr. David C. Greenspan Vice President & Chief Technology Officer NovaMin Technology, Incorporated 13709 Progress Boulevard #23 Alachua, Florida 32615 USA

Re: K040473

Trade/Device Name: Oravive™ Tooth Revitalizing Paste Regulation Number: Unclassified Regulation Name: None Regulatory Class: None Product Code: NRE Dated: February 23, 2004 Received: February 24, 2004

Dear Dr. Greenspan:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially cquivalent (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 gencral controls provisions of the Act. 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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such 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.

{3}------------------------------------------------

Page 2 -Dr. Greenspan

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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of Compliance at (301) 594-4613. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely yours.

Ques

Chiu Lin, Ph.D Director Division of Anesthesiology, General Hospital, Infection Control and Dental Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

{4}------------------------------------------------

510(k) Premarket Notification NovaMin Technology, Inc. Oravive™ Tooth Revitalizing P

OF INDICATIONS FOR USE

510(k) Number (if known): K040473

Oravive™ Tooth Revitalizing Paste Device Name: --

INDICATIONS FOR USE:

Oravive™ is a fluoride-free toothpaste product intended for cleaning the tooth surface on a Oravive - 15 & incelides have shown that Oravive™ also provides relief from tooth sensitivity due to cold, heat, acids, sweets, or contact by the occlusion of dentin tubules.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE) Suser (Division Sign-Off) Division of Anesthesiology, General Hospital, Infection Control, Dental Devices 510(k) Number:

Prescription Use -------

OR (Per 21 CFR 801.109) Over-The-Counter Use X

SECTION D -- STATEMENT OF INDICATIONS FOR USE

Regulation Number and Section

§ 872.3260 Cavity varnish.

(a)
Identification. Cavity varnish is a device that consists of a compound intended to coat a prepared cavity of a tooth before insertion of restorative materials. The device is intended to prevent penetration of restorative materials, such as amalgam, into the dentinal tissue.(b)
Classification. Class II (special controls). The device, when it is an external cleaning solution, is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 872.9.