(171 days)
The Ulthera® System is indicated for use as a non-invasive dermatological aesthetic treatment to:
- lift the eyebrow
- lift lax submental (beneath the chin) and neck tissue
- improve lines and wrinkles of the décolleté
The Ulthera System in conjunction with the Ulthera DeepSEE transducer allows for ultrasonic visualization of depths up to 8 mm below the surface of the skin. The indicated use of the imaging is to visualize the dermal layers of tissue to:
- ensure proper coupling of the transducer to the skin
- confirm appropriate depth of treatment such as to avoid bone
The Ulthera® System consists of the following components:
• Ulthera® Control Unit
• Handpiece
• Transducers
The Ulthera® System, which uses focused ultrasound for aesthetic treatment, was evaluated for an expanded indication to improve lines and wrinkles of the décolleté.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and the Reported Device Performance:
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Primary Endpoint: Improvement in lines and wrinkles of the décolleté as evaluated by a masked assessment of pre and post-treatment photographs. (Note: No pre-specified success criteria were established for this primary endpoint at the beginning of the trial due to issues with the initial Fabi-Bolton Scale validation). | 36 out of 54 evaluable subjects (~67%) showed improvement by masked assessment of pre- and post-treatment photographs at 180 days post-treatment. |
| Safety: No serious adverse events (SAEs) or unanticipated adverse device effects (UADEs) related to the treatment. | No SAEs or UADEs related to treatment were reported. All adverse events were mild, with the exception of two moderate events (one of which was not device-related), and all resolved. |
| Treatment Efficacy at Specific Energy Levels: Efficacy achieved at Level 4 for 7-3.0 and 4-4.5 transducers, and Level 3 for 10-1.5 transducer. | Treatment efficacy was achieved at the pre-set energy levels: Level 4 for the 7-3.0 and 4-4.5 transducers, and Level 3 for the 10-1.5 transducer. |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size for Test Set:
- Initial Enrollment: Up to 130 female subjects.
- Subjects Completing Protocol: 108 subjects.
- Evaluated Photo Sets (Test Set): 54 subjects. This subset was chosen as their day 180 photos were identified as "most consistent in photo quality" after excluding 54 photos with inconsistencies.
- Data Provenance: The study was a prospective safety and efficacy study. The document does not specify the country of origin of the data, but the submission is to the US FDA, implying it was conducted to meet US regulatory requirements.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:
The document mentions "masked assessment of pre and post treatment photographs" but does not specify the number or qualifications of the experts who performed this masked assessment. It also states that the initial Fabi-Bolton Scale, a published validated scale, could not be successfully validated during the clinical trial due to low kappa scores for both intra-rater and inter-rater reproducibility, leading to the change in primary endpoint to a post-hoc masked assessment.
4. Adjudication Method for the Test Set:
The document mentions "masked assessment," which implies multiple raters, but it does not explicitly state the adjudication method used to arrive at the final assessment (e.g., 2+1, 3+1, majority vote, etc.). The mention of inter-rater reproducibility issues with the Fabi-Bolton scale suggests that inter-rater agreement was a consideration, but the method for resolving discrepancies in the masked assessment is not detailed.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:
No, an MRMC comparative effectiveness study comparing human readers with and without AI assistance was not conducted or reported. This study evaluates the device's direct clinical effect on patients, not the performance of an AI algorithm assisting human readers.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:
Not applicable. The Ulthera® System is a medical device for treatment, not an AI algorithm for diagnostic interpretation in a standalone context. The "performance data" refers to the clinical outcomes of patients treated with the device.
7. The Type of Ground Truth Used:
The ground truth for the expanded indication of improving lines and wrinkles on the décolleté was established through:
- Expert Consensus (implied): "Masked assessment of pre and post treatment photographs." While not explicitly stated as "consensus," this type of assessment by presumably trained evaluators serves as the "ground truth" for visual improvement.
- Clinician Global Aesthetic Improvement Scores (CGAIS): An unmasked assessment performed by clinicians.
- Patient Satisfaction Questionnaires: Patient-reported improvement.
The primary endpoint shifted to the masked assessment due to issues with the initial validated scale.
8. The Sample Size for the Training Set:
This information is not provided in the document. The study described is a clinical trial to evaluate the device's effectiveness, not an AI model's development. Therefore, there isn't a "training set" in the context of machine learning. The "training" for this device would refer to the development and engineering process, which is not detailed in terms of data sets.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no mention of a "training set" for an AI algorithm in this context. The study focuses on evaluating the clinical performance of the Ulthera® System treatment itself.
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5. 510(k) Summary
This 510(k) Summary for the Ulthera "System is submitted in accordance with the requirements of the Safe Medical Device Act (SMDA) of 1990 and follows the Office of Device Evaluation (ODE) guidance concerning the organization and content of a 510(k) summary.
| Applicant: | Ulthera, Inc. | |||
|---|---|---|---|---|
| Address: | 1840 South Stapley DriveSuite 200Mesa, AZ 85204 | |||
| Contact Person: | Ashley Fickett, Regulatory Affairs Manager | |||
| Telephone: | (480) 619-4069 | |||
| Fax: | (480) 214-0330 | |||
| Submission Date: | February 19, 2014 | |||
| Device Trade Name: | Ulthera® System | |||
| Common Name: | Focused Ultrasound For Tissue Heat Or Mechanical Cellular DisruptionSystem, Imaging, Pulsed Echo, Ultrasonic | |||
| Classification: | Regulatory Class II | |||
| Classification Name: | Focused Ultrasound Stimulator Use System for Aesthetic Use | |||
| Regulation Number: | 878.4590 | |||
| Product Code: | OHVIYO | |||
| Legally Marketed | Name: Ulthera® System | |||
| Predicate: | Ulthera, Inc., Ulthera System - K132028510(k): | |||
| Applicable Guidance: | The following guidance is applicable to the Ulthera System: | |||
| The Class II Special Controls Guidance Document: Focused UltrasoundStimulator System for Aesthetic Use was developed in response to | ||||
| Ulthera's DeNovo submission and 510(k) clearance K072505 for theUlthera System. | ||||
| Conformance to Guidance for Industry and FDA Staff: Information forManufacturers Seeking Marketing Clearance of Diagnostic UltrasoundSystems and Transducers was determined in the predicate 510(k)submission clearance K132028 for the Ulthera System. | ||||
| Guidance for the Content of Premarket Submission for SoftwareContained in Medical Devices. | ||||
| Device Description: | The Ulthera® System consists of the following components: | |||
| • Ulthera® Control Unit | ||||
| • Handpiece | ||||
| • Transducers | ||||
| Indications for Use: | The Ulthera® System is indicated for use as a non-invasive dermatologicalaesthetic treatment to: | |||
| • lift the eyebrow (current cleared indication) | ||||
| • lift lax submental (beneath the chin) and neck tissue (current clearedindication) | ||||
| • improve lines and wrinkles of the décolleté (requested indication) | ||||
| The Ulthera System in conjunction with the Ulthera DeepSEE transducerallows for ultrasonic visualization of depths up to 8 mm below the surface | ||||
| of the skin. The indicated use of the imaging is to visualize the dermal andsubdermal layers of tissue to: | ||||
| • ensure proper coupling of the transducer to the skin (current clearedindication) |
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- confirm appropriate
cleared indication)
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Substantial Equivalence Comparison:
| Predicate Device :Ulthera® System(K132028) | Subject DeviceUlthera® System;Expanded Indication for Use | |
|---|---|---|
| Regulation | 878.4590 | 878.4590 |
| Product Code | OHV, IYO | SameOHV, IYO |
| Intended Use/Indications for Use | Non-invasive dermatological aesthetictreatment to:• lift the eyebrow (current clearedindication)• lift lax submental (beneath the chin)and neck tissueThe Ulthera System in conjunction withthe Ulthera DeepSEE transducer allowsfor ultrasonic visualization of depths upto 8 mm below the surface of the skin.The indicated use of the imaging is tovisualize the dermal and subdermallayers of tissue to:• ensure proper coupling of thetransducer to the skin• confirm appropriate depth oftreatment such as to avoid bone | SameNon-invasive dermatological aesthetictreatment to:• lift the eyebrow (current clearedindication)• lift lax submental (beneath the chin)and neck tissue• improve lines and wrinkles of thedécolleté (requested indication)The Ulthera System in conjunction withthe Ulthera DeepSEE transducer allowsfor ultrasonic visualization of depths upto 8 mm below the surface of the skin.The indicated use of the imaging is tovisualize the dermal and subdermallayers of tissue to:• ensure proper coupling of thetransducer to the skin• confirm appropriate depth of treatmentsuch as to avoid boneClinical Performance Data Provided forExpanded Indication |
| Where Used | Clinic/doctor's office | Clinic/doctor's office |
| Anatomical Site | Skin | SameSkin |
| Type of Energy | Thermal< 2 J | SameThermal< 2 J |
| Biological Effect | Lifting of tissue via High IntensityFocused Ultrasound (HIFU)directed beneath the outer dermis inlocalized points at a specified depth anddistance between points | SameReduction of lines and wrinkles via HighIntensity Focused Ultrasound (HIFU)directed beneath the outer dermis inlocalized points at a specified depth anddistance between points. |
| Predicate Device :Ulthera® System(K132028) | Subject DeviceUlthera® System;Expanded Indication for Use | |
| Same method of action | ||
| Demonstrated Safetyand Efficacy in treatedarea | Provided in K072505 cleared September11, 2009Provided in K121700 cleared October 2,2012Provided in K132028 cleared December11, 2013 | Performance Testing - ClinicalClinical Performance Data Provided forExpanded Indication |
| Patient ContactMaterial | Biocompatible | Biocompatible |
| Same | ||
| ElectromagneticCompatibilityStandards | Compliant | Compliant |
| Same | ||
| Medical ElectricalEquipment SafetyStandards | Compliant | Compliant |
| Same | ||
| Thermal CoagulationPoint | Confined to focal zone;shallow (< 5 mm); no thermalcoagulation below focal zone | Confined to focal zone;shallow (< 5 mm); no thermalcoagulation below focal zone |
| Same | ||
| Epidermal Impact | Non-invasive; no cooling required | Non-invasive; no cooling required |
| Same | ||
| Pigmentation Effect | Chromophore insensitive | Chromophore insensitive |
| Same | ||
| Packaging | Nylon / Aluminum foil laminate bag withvery low water vapor transmission rate.The bag is enclosed within a cardboardbox for storage. | Nylon / Aluminum foil laminate bag withvery low water vapor transmission rate.The bag is enclosed within a cardboardbox for storage. |
| Same | ||
| Sterilization | Provided non-sterile | Provided non-sterile |
| Same | ||
| Shelf Life | 12 months | 12 months |
| Same |
Image /page/2/Picture/3 description: The image shows a stylized logo or wordmark that reads "Ulthera". The letters are bold and have a textured appearance, giving them a slightly rough or vintage feel. Above the "era" portion of the word, there are three small circles arranged horizontally, adding a design element to the logo.
. .
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:
Image /page/3/Picture/2 description: The image shows the word "ulthera" in a stylized font. The letters are tall and thin, and there are three small circles above the "e" in "ulthera". The circles are arranged horizontally and are evenly spaced. The word "ulthera" is in a dark color, and the background is white. There is a trademark symbol to the right of the word.
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Performance Data:
Clinical analysis was conducted in clinical trials to support the clinical performance of the Ulthera® System. Sufficient safety data has been gathered to determine that the Ulthera® System performs as clinically intended.
To support the expanded indication, the Ulthera System was evaluated in a prospective safety and efficacy study investigating the clinical response following treatment with the Ulthera System to achieve improvement of lines and wrinkles of the décolleté. The clinical study's protocol was approved under IDE G120004 for enrolling up to 130 female subjects between the ages of 35-60 at up to 4 sites with a 90 and 180 day follow up. The Fabi-Bolton Scale, a published validated scale, was prospectively defined to evaluate wrinkle improvement. However, successful validation of the Fabi-Bolton Scale during the clinical trial could not be accomplished due to kappa scores for both intra-rater and inter-rater reproducibility being low. Therefore, the primary endpoint was changed from the Fabi-Bolton Scale to a post-hoc retrospective masked assessment of pre and post treatment photographs. There were no pre-specified success criteria of the masked assessment established at the beginning of the clinical trial. In addition to masked assessment, there was also an unmasked assessment called the Clinician Global Aesthetic Improvement Scores (CGAIS). Finally, patient satisfaction questionnaires were also measured to assess improvement.
| Table 1. Patient Accountability | ||||||||
|---|---|---|---|---|---|---|---|---|
| -- | -- | -- | -- | -- | --------------------------------- | -- | -- | -- |
| N | 125 |
|---|---|
| Subject Drop out | 17 |
| Subject Per Protocol | 108 |
| Subject Eliminated based onPoor Quality Photographs | 54 |
| Evaluable Subjects | 54 |
Upon analysis of the all the photographs used in the clinical study, 54 of 108 day 180 photos were identified as having inconsistencies in photo quality (changes in lighting, color, focus, patient positioning, cropping, etc.). Therefore a sub-set analysis was conducted using the primary endpoint of masked assessment on the remaining 54 day 180 evaluable photo sets that were deemed the most consistent in photo quality.
Image /page/4/Picture/7 description: The image shows the word "Ulthera" in a stylized font. The letters are tall and thin, with a slightly distressed or textured appearance. Above the "thera" portion of the word, there are three small, circular shapes, possibly representing dots or spheres. The overall design has a modern and somewhat minimalist aesthetic.
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Table 2 provides results from the masked assessment of the evaluable subject photos.
| N | 54 |
|---|---|
| Improvement | 36 (~67%) |
| Incorrect | 13 (24%) |
| No Change | 5(9%) |
| Table 2. Masked Assessment Results of Evaluable Subject Photos | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| -- | -- | -- | ----------------------------------------------------------------- | -- | -- | -- | -- | -- | -- | -- |
in the sub-set of evaluable photos, there were 36 of 54 (~67%) subjects that showed improvement by masked assessment of pre and post treatment photographs at the primary endpoint of 180 days.
Table 3 provides CGAIS and Patient Assessments stratified by results of the primary endpoint of masked assessment for the subject sub-set with the most consistent photo quality.
Table 3. CGAIS and Patient Assessments Stratified By Masked Assessment Results for Sub-Set of Evaluation Photos
| D180 | ||||||||
|---|---|---|---|---|---|---|---|---|
| CGAIS | Patient Satisfaction | Patient ReportedImprovement | ||||||
| Masked Assessment | Improved (improved,much improved, verymuch improved) | No Change | Worse | Satisfied(satisfied & verysatisfied) | Neither Satisfiednor Dissatisfied | Dissatisfied(dissatisfied &very dissatisfied) | Yes | No |
| Improvement n=36 | 27 (75%) | 9 (25%) | 0 (0%) | 23 (64%) | 9 (25%) | 4 (11%) | 32 (89%) | 4 (11%) |
| Incorrect n=13 | 5 (38%) | 7 (54%) | 1 (8%) | 8 (61%) | 4 (31%) | 1 (8%) | 10 (77%) | 3 (23%) |
| No Change n=5 | 3 (60%) | 2 (40%) | 0 (0%) | 4 (80%) | 0 (0%) | 1 (20%) | 4 (80%) | 1 (20%) |
| TOTAL - n = 54 | 35 (65%) | 18 (33%) | 1 (2%) | 35 (65%) | 13 (24%) | 6 (11%) | 46 (85%) | 8 (15%) |
The results of the sub-set analysis demonstrate improvement of lines and wrinkles based on masked assessment of pre and post treatment photographs in 36 of 54 evaluable subjects with the most consistent photo quality after one Ultherapy treatment 180 days post-treatment.
Please note that treatment efficacy was achieved at the pre-set energy levels of Level 4 for the 7 - 3.0 and 4 - 4.5 transducers and energy Level 3 for the 10 - 1.5 transducer. Changes in energy may impact efficacy.
Device safety was demonstrated as there were no serious adverse events (SAEs) or unanticipated adverse device effects (UADEs) related to treatment with the Ulthera System. Of the adverse events, all but two were mild. Only
Image /page/5/Picture/11 description: The image shows the word "Ulthera" in a stylized font. The letters are tall and thin, with a dotted line above the "thera" portion of the word. The font appears to be outlined, giving it a distinct look.
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two events were moderate, one of which was not device related. All events resolved.
Based on the design, materials, principle of operation, and intended use, the Conclusion: subject device (Ulthera® System) is substantially equivalent to the legally marketed predicate device (Ulthera System, K132028) as demonstrated in the substantial equivalence comparison table. Clinical data determined that the subject device is as safe and effective and performs as well as the predicate device for the expanded indication.
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Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized eagle with three lines representing its wings. The eagle is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA", which is arranged in a circular fashion around the eagle.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
June 20, 2014
Ulthera Incorporated Ms. Ashley Fickett Regulatory Affairs Manager 1840 South Stapley Drive, Suite 200 Mesa, Arizona 85204
Re: K134032 Trade/Device Name: Ulthera System Regulation Number: 21 CFR 878.4590 Regulation Name: Laser surgical instrument for use in general and plastic surgery and in dermatology Regulatory Class: Class II Product Code: OHV, IYO Dated: December 30, 2013 Received: December 31, 2013
Dear Ms. Fickett:
We have reviewed your Section 510(k) promarket 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. 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 (reporting of medical
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Page 2 - Ms. Ashley Fickett
device-related adverse events) (21 CFR 803); 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYow/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
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) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.
Sincerely vours.
David Krause -S
for Binita S. Ashar, M.D., M.B.A., F.A.C.S. Director Division of Surgical Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.
510(k) Number (if known) K134032
Device Name Ulthera® System
Indications for Use (Describe)
The Ulthera System is indicated for use as a non-invasive dermatological aesthetic treatment to:
- · lift the eyebrow
- · lift lax submental (beneath the chin) and neck tissue
- · improve lines and wrinkles of the décolleté
The Uthera System in conjunction with the Ulthera DeepSEE transducer allows for ultrasonic visualization of depths up to 8 mm below the surface of the skin. The indicated use of the imaging is to visualize the dermal layers of tissue to:
- ensure proper coupling of the transducer to the skin
· confirm appropriate depth of treatment such as to avoid bone
Type of Use (Select one or both, as applicable)
区 Prescription Use (Part 21 CFR 801 Subpart D)
] Over-The-Counter Use (21 CFR 801 Subpart C)
PLEASE DO NOT WRITE BELOW THIS LINE – CONTINUE ON A SEPARATE PAGE IF NEEDED.
A LA FOR FOR FOR FOR FOA USE ONLY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9.6.3. Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)
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This section applies only to requirements of the Paperwork Reduction Act of 1995.
*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
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§ 878.4590 Focused ultrasound stimulator system for aesthetic use.
(a)
Identification. A Focused Ultrasound Stimulator System for Aesthetic Use is a device using focused ultrasound to produce localized, mechanical motion within tissues and cells for the purpose of producing either localized heating for tissue coagulation or for mechanical cellular membrane disruption intended for noninvasive aesthetic use.(b)
Classification. Class II (special controls). The special control for this device is FDA's “Class II Special Controls Guidance Document: Focused Ultrasound Stimulator System for Aesthetic Use.” See § 878.1(e) for the availability of this guidance document.