EchoS is a non-invasive ultrasound (US) bone sonometer. EchoS works together with EchoStudio software. EchoStudio analyzes the ultrasound signals in order to compute the diagnostic parameters (BMD13, T-sore, and Z-sore) and to assess fracture risk through the integrated FRAX® software.

The BMDgs Index is a clinical measure based on ultrasound variables of the lumbar spine or femoral neck which is highly correlated with the value of BMD as provided by DXA at the same anatomical location (BMDnxA), with a standard error of the estimate of 0.044 grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements. BMDris Index is expressed in grams/cm² and it is based on a proprietary internal database, obtained from clinical data on adult white females and males, while T- and Z-score are derived from comparison to a normative X-ray absorptiometry reference database (NHANES). BMDus Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in women.

Device Description

The subject device, EchoS, consists of two main parts: the equipment EchoS device with its own probe and the software EchoStudio.

The EchoS device consists of EchoS device together with its probe,
. The software EchoStudio: user interface and algorithmic calculation software provided in installation disc.

The EchoS device is connected to the computer via the USB port, and it is controlled by the EchoStudio to send the transmitting parameters to the EchoS device and to acquire the ultrasound (US) signals from EchoS device in order to calculate the BMDus and the other diagnosis parameters.

The EchoS System is a PC-based device that employs an ultrasound probe to collect ultrasound (RF) signals for echographic applications. During the measurement, the ultrasound convex probe, connected by a standard connector to the EchoS device, is applied directly to the skin in correspondence of the lumbar vertebrae or proximal femur, applying a thin layer of ultrasound gel between the probe surface and the skin to facilitate acoustic coupling. The ultrasound waves emitted by the probe are reflected by the bone, and then detected by the same probe.

During the scan, the algorithm automatically detects the bone interfaces and calculates the region of interest (ROIs) for data analysis. The automatic data processing is performed through the following steps: a custom developed signal pre-processing chain performs filtering, amplification and A/D conversion operations on the RF signals that are then passed to the EchoStudio software.

EchoStudio includes RF signal analysis and spectral comparison with reference models for the calculation of diagnostic parameters (BMDus, T-score, Z-score), and generation of the final medical report. The relevant scan depth, focus position, and visualization parameter settings can be adjusted and set by the interface of the software - EchoStudio.

EchoStudio software provides BMDus (in g/cm²), T-score and Z-score. It also estimates the 10-year osteoporotic fracture risk calculated with the original FRAX® algorithm that is integrated in the device.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the EchoS device, based on the provided text:

EchoS Acceptance Criteria and Device Performance

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the EchoS device are primarily based on its correlation with DXA measurements, particularly the standard error of the estimate (SEE) for BMD.

Acceptance Criteria Category	Acceptance Criteria (from text)	Reported Device Performance (from text)
BMD Correlation with DXA	The BMDus Index is a clinical measure based on ultrasound variables of the lumbar spine or femoral neck which is highly correlated with the value of BMD as provided by DXA at the same anatomical location (BMDdxa), with a standard error of the estimate of 0.044 grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements.	For EchoS, a standard error of the estimate of 0.044 grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements was detected. This is stated to be "comparable with the standard error of 0.041 grams/cm² detected by the primary predicate device in a similar comparison test vs the same reference device."
Precision	BMDus Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in women. (This is a qualitative statement of the acceptance criteria)	The text states, "BMDus Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in women." This implies the device met this qualitative criterion through its overall performance but no specific quantitative metric for precision is provided other than the SEE for correlation.
Safety and Performance	Electrical safety, EMC, basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment (including acoustic performances), biocompatibility, and software requirements as per various standards (AAMI/ANSI ES60601-1, IEC 60601-1-2, IEC 60601-2-37, ISO 10993-1, IEC 62304) and FDA guidances. (These are overarching compliance requirements rather than specific performance metrics directly from the device's output like BMD).	The text explicitly states: "EchoS system has been evaluated for electrical safety, for EMC, to satisfy specific requirements for basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment, including also acoustic performances; for biocompatibility and for Software. This evaluation has been executed performing non clinical performance tests in compliance to the voluntary standards and to the FDA guidance listed below." This indicates that these non-clinical performance criteria were met.

Study Proving Device Meets Acceptance Criteria:

The key study for proving the device meets the acceptance criteria for BMD correlation is a clinical performance test comparing EchoS to DXA.

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

Test Set Sample Size: The document does not explicitly state the numerical sample size for the test set used in the comparative performance test against DXA. It mentions "Clinical data has been collected by Echolight on the intended patient population for the subject device" and "real data from intended patient population are used to compare results of FRAX® original algorithm."
Data Provenance: The data was collected prospectively by Echolight. The country of origin is not specified, but Echolight S.p.a. is based in Italy, suggesting the data may have been collected in Italy or Europe. The patient population described for the proprietary internal database is "adult white females and males."

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

Number of Experts: The document does not specify the number of experts used.
Qualifications of Experts: The document does not specify the qualifications of the experts involved in establishing the ground truth.

4. Adjudication Method for the Test Set:

The document does not describe an adjudication method (e.g., 2+1, 3+1, none) for the test set. The ground truth seems to be established by the reference device (DXA) itself, not through an expert consensus requiring adjudication.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done:

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not conducted. The studies described are comparing the device's output (BMD, T-score, Z-score) to a gold standard (DXA), and the FRAX® algorithm's output using EchoS data versus DXA data. There is no mention of human readers improving with AI assistance.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done:

Yes, a standalone performance assessment was done. The "comparative performance test of EchoS vs DXA" and the comparison of FRAX® using EchoS-estimated T-score against DXA-measured T-score are examples of standalone algorithm performance. The device analyzes ultrasound signals and computes diagnostic parameters independently.

7. The Type of Ground Truth Used:

The primary ground truth used for the device's diagnostic parameters (BMDus, T-score, Z-score) is DXA measurements (X-ray Densitometry), which is referred to as "a recognized gold standard for bone densitometry applications."
For the FRAX® algorithm comparison, the ground truth for comparison was the FRAX® original algorithm using DXA-measured femoral neck T-Score.

8. The Sample Size for the Training Set:

The document does not explicitly state the numerical sample size for the training set. It mentions "Clinical data has been collected by Echolight on the intended patient population for the subject device, in order to create the proprietary internal database for the different ages and BMI."

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

The ground truth for the training set (referred to as the "proprietary internal database") was established through clinical data collection by Echolight. This would involve measuring BMD using DXA (the gold standard) and correlating these measurements with the ultrasound variables collected by the EchoS device across a diverse patient population (adult white females and males of different ages and BMI). This process allows the algorithm to learn the relationship between ultrasound signals and DXA-derived BMD values.

Summary

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October 19, 2018

Echolight S.p.a % Maurizio Pantaleoni CEO ISEMED srl Via P. Togliatti 19/X IMOLA, BO 40026 ITALY

Re: K180516

Trade/Device Name: EchoS Regulation Number: 21 CFR 892.1180 Regulation Name: Bone Sonometer Regulatory Class: Class II Product Code: MUA Dated: August 31, 2018 Received: September 21, 2018

Dear Maurizio Pantaleoni:

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/cfpmp/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

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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for 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 (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/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.

Hole 2. Mild

for Robert A. Ochs, Ph.D. Director Division of Radiological Health Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

510(k) Number (if known) K180516

Device Name EchoS

Indications for Use (Describe)

and to assess fracture risk through the integrated FRAX® software.

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

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

This 510(k) Summary is being submitted as required by 21 CFR 807.92.

1. General Information Submitter :

Submitter :	Echolight S.p.a.
	Via Raffaello Sanzio, 18,
	Lecce 73100 (ITALY)
	Tel.: +39 0832 15 92 607
	Fax: +39 0832 18 36 515
	E-mail: regulatory@echolight.it
Consultant/ Contact:	Maurizio Pantaleoni
	ISEMED srl
	Via P. Togliatti 19/X
	Imola, BO 40026 ITALY
	Mob. +39 348 4435155
	Tel. +39 0542 683803
	Fax +39 0542 698456
	Email: regulatory@isemed.eu
Summary Prepared Date:	February 15, 2018

1. Names
- Device Name: EchoS
- Common Name: Bone sonometer
- Regulation Number: 21 CFR 892.1180
- . Product Code: MUA ; class II

3. Predicate Devices

The EchoS is substantially equivalent to the following predicate devices:

Applicant	Device name	510(k) Number
CyberLogic, Inc.	Ultrascan 650	K161919 - Primary Predicate Device
Beam-Med Ltd.	Sunlight MiniOmni	K110646 - Secondary Predicate Device

4. Device Description

The subject device, EchoS, consists of two main parts: the equipment EchoS device with its own probe and the software EchoStudio.

The EchoS device consists of EchoS device together with its probe,
. The software EchoStudio: user interface and algorithmic calculation software provided in installation disc.

The EchoS device is connected to the computer via the USB port, and it is controlled by the EchoStudio to send the transmitting parameters to the EchoS device and to acquire the ultrasound

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(US) signals from EchoS device in order to calculate the BMDus and the other diagnosis parameters.

5. Indications for Use

EchoS is a non-invasive ultrasound (US) bone sonometer. EchoS works together with EchoStudio software.

EchoStudio analyzes the ultrasound signals in order to compute the diagnostic parameters (BMDus, T-score, and Z-score) and to assess fracture risk through the integrated FRAX® software.

The BMDus index is a clinical measure based on ultrasound variables of the lumbar spine or femoral neck which is highly correlated with the value of BMD as provided by DXA at the same anatomical location (BMDoxa), with a standard error of the estimate of 0.044 grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements. BMDus is expressed in grams/cm² and it is based on a proprietary internal database, obtained from clinical data on adult white females and males, while T- and Z-score are derived from comparison to a normative X-ray absorptiometry reference database (NHANES). BMDus Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in women.

6. Comparison of technological characteristics with the predicate devices

The EchoS is substantially equivalent to the following predicate devices:

Applicant	Device name	510(k) Number
CyberLogic, Inc.	Ultrascan 650	K161919 - Primary Predicate Device
Beam-Med Ltd.	Sunlight MiniOmni	K110646 - Secondary Predicate Device

The comparison between the EchoS and the predicate devices is summarized in the following table and discussed below.

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	SUBJECT DEVICE	Primary Predicate Device(PD1)	Secondary predicatedevice (PD2)
PRODUCT NAME	EchoS System	Ultrascan 650(K161919)	Sunlight MiniOmni(K110646)
APPLICANT(MANUFACTURER)	Echolight S.p.a.	CyberLogic, Inc.	BeamMed Ltd.
FIGURE	Image: Echos System	Image: Ultrascan 650	Image: Sunlight MiniOmni
CLASSIFICATION:	Class IIReg. Number: 892.1180"bone sonometer"Product Code: MUA	Class IIReg. Number: 892.1180"bone sonometer"Product Code: MUA	Class IIReg. Number: 892.1180"bone sonometer"Product Code: MUA
INDICATIONS FOR USE:	EchoS is a non-invasive ultrasound (US) bone sonometer. EchoS works together with EchoStudio software. EchoStudio analyzes the ultrasound signals in order to compute the diagnostic parameters (BMDUS, T-score, and Z-score) and to assess fracture risk through the integrated FRAX® software.The BMDUS Index is a clinical measure based on ultrasound variables of the lumbar spine or femoral neck which is highly correlated with the value of BMD of the same anatomical location as provided by DXA (BMDDXA), with a standard error of the estimate of 0.044grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements. BMDUS Index is expressed in grams/cm² and as a T- and Z-score, derived from comparison to a normative x-ray absorptiometry reference database. BMDUS Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in women.	UltraScan 650 can be used to determine BMDUS Index in adult men and women and to assess appendicular fracture risk in postmenopausal women.The BMD US Index is a clinical measure based on ultrasound variables of the forearm which is highly correlated with the value of BMD of the 1/3 radius as provided by DXA, with a standard error of the estimate of 0.041 grams/cm². BMDUS Index is expressed in grams/cm² and as a T- and z-score, derived from comparison to a normative x-ray absorptiometry reference database. BMDUS Index has a precision comparable to that of x-ray absorptiometry, which makes it suitable for monitoring bone changes in postmenopausal women.	Sunlight MiniOmni Ultrasound Bone Sonometers is a non-invasive device. The output is also expressed as a T-score and a Z-score, and can be used in conjunction with other clinical risk factors as an aid to the physician in the diagnosis of osteoporosis and other medical conditions leading to reduced bone strength and, ultimately, in the determination of fracture risk.
PATIENT POPULATION	Women between the ages of 51 and 70 years	Assess appendicular fracture risk in postmenopausal women and for determination of BMDUS Index in adult men and women	Female 50-65 years old
TECHNOLOGY:FOUNDAMENTAL TECHNOLOGIES	Ultrasound	Ultrasound	Ultrasound
MEASUREMENT MODE	reflection	Through-transmission	Axial Transmission

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7. Performance Data

EchoS system has been evaluated for electrical safety, for EMC, to satisfy specific requirements for basic safety and essential performance of ultrasonic medical diagnostic and monitoring equipment, including also acoustic performances; for biocompatibility and for Software. This evaluation has been executed performing non clinical performance tests in compliance to the voluntary standards and to the FDA guidance listed below:

AAMI/ANSI ES60601-1:2005/(R)2012 And A1:2012, C1:2009/(R)2012 And A2:2010/(R)2012 ● (IEC 60601-1:2005, Mod) (Consolidated text) Medical Electrical Equipment - Part 1: General Requirements for Safety (Iec60601-1:2005 and A1:2012)
. IEC 60601-1-2 Edition 4.0 2014-02, Medical Electrical Equipment - Part 1-2: General Requirements For Basic Safety And Essential Performance - Collateral Standard: Electromagnetic Disturbances - Requirements And Tests
. 60601-2-37 Edition 2.1:2015 Medical Electrical Equipment - Part 2-37: Particular Requirements For Basic Safety And Essential Performance of Ultrasonic Medical Diagnostic and Monitoring Equipment (Radiology)
. FDA Guidance "Class II Special Controls Guidance Document: Bone Sonometers - Guidance for Industry and FDA Staff" - issued on July 17, 2008
. FDA Guidance "Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers" - issued on September 9, 2008
. ISO 10993-1 Fourth Edition 2009-10-15 - Biological Evaluation Of Medical Devices - Part 1: Evaluation And Testing Within A Risk Management Process
. FDA Guidance "Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process", issued June 16, 2016
IEC 62304 First edition 2006-05, Medical device software – Software life cycle processes
"Guidance for the Content of Premarket Submissions for Software Contained in ● Medical Devices" – issued on May 11, 2005

Furthermore Echolight S.p.a. performed many clinical performance tests, in order to compare the clinical performances of the subject device to the performances of the X-Ray Densitometry that is a recognized gold standard for bone densitometry applications and it is used as reference device, as for the primary predicate device Ultrascan650.

The tests performed to validate the clinical performances in comparison to the reference device are listed below:

. Clinical data has been collected by Echolight on the intended patient population for the subject device, in order to create the proprietary internal database for the different ages and BMI; and in the same time verifications on reproducibility & estimation of BMDus has been performed on EchoS with respect to the gold standard DXA
. in order to demonstrate the high correlation of the BMDus index used by the subject device to the BMD from the gold standard DXA (BMDoxA), comparative performance test of EchoS vs DXA has been performed detecting for EchoS a standard error of the estimate of 0.044 grams/cm² for lumbar spine and 0.038 grams/cm² for femoral neck measurements,

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comparable with the standard error of 0.041 grams/cm² detected by the primary predicate device in a similar comparison test vs the same reference device.

. Simulation data and ad also real data from intended patient population are used to compare results of FRAX®original algorithm with the use of inputs from both DXAmeasured femoral neck T-Score and EchoS-estimated femoral neck T-score.

8. Conclusions

In light of the evidence discussed above, the subject device has similar indications for use, patient population, technology features and performances of the predicate devices, pointing out only few differences that have been addressed by the dedicated clinical performance tests, demonstrating that the diagnostic effectiveness and accuracy on lumbar vertebrae and femoral neck of EchoS system has a significant correlation with the reference device DXA. For all these reasons, the subject device may be found substantially equivalent to the predicate devices.

Regulation Number and Section

§ 892.1180 Bone sonometer.

(a)
Identification. A bone sonometer is a device that transmits ultrasound energy into the human body to measure acoustic properties of bone that indicate overall bone health and fracture risk. The primary components of the device are a voltage generator, a transmitting transducer, a receiving transducer, and hardware and software for reception and processing of the received ultrasonic signal.(b)
Classification. Class II (special controls). The special control for this device is FDA's “Guidance for Industry and FDA Staff; Class II Special Controls Guidance Document: Bone Sonometers.” See § 892.1(e) for the availability of this guidance document.