Bindex measures apparent cortical bone thickness at the proximal tibia and can be used in conjunction with other clinical risk factors or patient characteristics as an aid to the physician in the diagnosis and other medical conditions leading to reduced bone strength and in the determination of fracture risk.

Device Description

The Bindex Bl-2 system consists of handheld ultrasound transducer and software. Bindex Bl-2 is connected to the USB port of a computer and controlled with computer software. Bindex Bl-2 is used for measurement of cortical bone thickness and it provides Density Index (DI), a parameter which estimates bone mineral density at the hip as measured with DXA. For measurements, gel is applied on skin and ultrasound transducer is manually placed on the measurement location. Standardized measurement location is at proximal tibia (1/3 length of tibia). Transducer is manually oriented perpendicularly to the surface of the cortical bone to achieve accepted measurement. Measurement is repeated five times at each measurement location. Finally, transducer is disinfected by wiping gel off with isopropyl alcohol moistened cloth.

The associated accessories include:

. Measurement stick
Ultrasound gel (optional)

AI/ML Overview

The Bindex BI-2 device underwent performance testing to demonstrate its safety and effectiveness, especially concerning its use in a home healthcare environment and its applicability to Hispanic individuals.

Here's a breakdown of the acceptance criteria and study details:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance	Study Type/Context
Electromagnetic Interference: Essential performance and Basic Safety maintained according to IEC 60601-1-2 Edition 4.0.	Test samples passed the tests with intact Essential Performance and Basic Safety.	EMC Testing for home healthcare environment (Table 2).
Environmental Hazards: Essential performance and Basic Safety maintained according to IEC 60601-1:2005 +Am1:2012 (Clause 5.7, 8.8.3, 8.7) and IEC 60601-1-11:2015 (Clause 4.2.2, 4.2.3.1, 8.3.1, 10.1.2).	Test samples passed the tests with intact Essential Performance and Basic Safety.	Environmental Testing for home healthcare environment (Table 2).
Biocompatibility: Device in skin contact for <24 hours, low risk.	Cytotoxicity, Sensitization, and Irritation testing conducted in accordance with ISO 10993-1. Safety of manufacturing and used materials further discussed in Biocompatibility report.	Biocompatibility testing.
Electrical Safety: Compliance with IEC 60601-1 and IEC 60601-2-37 standards.	System complies with the stated standards.	Electrical safety and EMC testing.
Software Verification and Validation: Compliance with FDA guidance for "moderate" level of concern software.	Documentation provided as recommended by FDA guidance.	Software Verification and Validation Testing.
Mechanical & Acoustic Testing: Equivalence of acoustic output to predicate device, successful drop test, ball pressure test, and moulding stress relief test.	Acoustic equivalency shown for predicate device. Passed drop test (1m), ball pressure test (20N for 1hr at 75°C), and moulding stress relief test (70°C for 7hr).	Mechanical and Acoustic Testing.
Clinical Performance (Hispanic Population): Sensitivity and specificity for DI thresholds to distinguish women with total hip or femoral neck T-score <-2.5 or > -2.5 similar in Caucasians and Hispanics.	Sensitivity 80%, Specificity 91% for Hispanics. Sensitivity 80%, Specificity 86% for Caucasians.	Clinical trial in Albuquerque, New Mexico, USA.
Overall Clinical Performance (Predicate): Statistically at least 80% sensitivity and specificity for hip osteoporosis with 95% confidence.	90% sensitivity (patients in yellow/red area). 90% specificity (patients in green/yellow area).	Established in previous predicate device study (K161971) and published study (Karjalainen et al., Osteoporosis International 2016).

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

EMC/Environmental/Biocompatibility/Electrical/Software/Mechanical/Acoustic Testing: The specific sample sizes for these engineering tests are not explicitly stated in the provided text. They typically involve a small number of devices or components representing the product. The data provenance is from internal testing conducted by the manufacturer or certified labs.
Clinical Performance (Hispanic Population Study):
- Sample Size: 293 postmenopausal women (153 Caucasian, 140 Hispanic).
- Data Provenance: Prospective clinical trial conducted in Albuquerque, New Mexico, USA.

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

This document does not specify the number or qualifications of experts used to establish ground truth for the engineering tests (EMC, environmental, etc.).

For the clinical performance study aiming to validate DI thresholds in Hispanic populations:

The ground truth for osteoporosis diagnosis was established using DXA (Dual-energy X-ray Absorptiometry) measurements of total hip or femoral neck T-score <-2.5. DXA is considered the gold standard for bone mineral density measurement and osteoporosis diagnosis, and its interpretation is typically done by trained radiologists or other certified medical professionals. The document mentions the method and protocol were "well-established (several publications, suggested by International society for clinical densitometry)," indicating reliance on widely accepted medical standards rather than a specific number of new experts adjudicating data in this particular 510(k) submission.

4. Adjudication Method for the Test Set

For the engineering tests (EMC, environmental, mechanical, etc.), the adjudication method is typically through comparison against pre-defined limits/standards (e.g., IEC standards). If the device meets these limits, it passes. No human adjudication is explicitly mentioned or generally required for these types of tests.
For the clinical study, the ground truth was objective DXA measurements, making explicit human adjudication of the ground truth (like 2+1 or 3+1 consensus) unnecessary once the DXA scans were acquired and analyzed according to standard clinical practice. The study compared the device's DI thresholds against these established DXA-based diagnoses.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, What was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

No MRMC comparative effectiveness study involving human readers improving with AI vs. without AI assistance was mentioned or appears to have been conducted for this 510(k) submission. The Bindex BI-2 device is a standalone measurement device that provides a Density Index (DI) to aid diagnosis; it does not involve an AI assisting human readers in interpreting images or data to improve their performance compared to unassisted reading. The device provides information, it doesn't assist interpretation of other modalities.

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

Yes, the core performance of the Bindex BI-2 device is essentially "standalone" in its measurement of cortical bone thickness and calculation of Density Index. The clinical study (Lewiecki, J Clin Densitom 2020) evaluated the standalone diagnostic performance of the DI thresholds (algorithm output) by comparing them directly against DXA-based osteoporosis diagnoses, demonstrating its utility in identifying women likely to have osteoporosis. The "human-in-the-loop" aspect here is the physician's use of the DI as an aid in diagnosis, not an interpretive assistance for another modality.

7. The Type of Ground Truth Used

Clinical Performance: The ground truth used for the clinical study validating the DI thresholds was DXA Bone Mineral Density (BMD) measurements, specifically total hip or femoral neck T-scores <-2.5, which is the established clinical standard for diagnosing osteoporosis. This can be categorized as outcomes data in the context of diagnostic accuracy, as it reflects the established clinical diagnosis.

8. The Sample Size for the Training Set

The document describes modifications to an already cleared device (K161971) and discusses a clinical study to expand the intended use population to include Hispanic individuals and validate existing thresholds. It does not describe a new training set for an algorithm. The "thresholds for osteoporosis for DI have been determined in comparison to DXA" based on previous work (Karjalainen et al. 2016). Therefore, the concept of a training set for a new algorithm is not directly applicable to this specific submission, which focuses on validating the existing device's performance in new contexts rather than developing a new algorithm.

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

As mentioned above, a new training set for an algorithm is not explicitly detailed in this submission. The established DI thresholds, which form the basis for the device's diagnostic output, were determined in comparison to DXA, the "gold standard Axial DXA." The foundational study (Karjalainen et al., Osteoporosis International 2016) would have established its ground truth using DXA measurements as well.

Summary

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Bone Index Finland Ltd. Janne Karjalainen CTO Savilahdentie 14 Kuopio 70700 FINLAND

Re: K211350

Trade/Device Name: Bindex BI-2 Regulation Number: 21 CFR 892.1180 Regulation Name: Bone Sonometer Regulatory Class: Class II Product Code: MUA Dated: April 13, 2022 Received: April 21, 2022

April 29, 2022

Dear Janne Karjalainen:

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 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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devices or postmarketing safety reporting (21 CFR 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 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 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).

Sincerely.

Jessica Lamb, Ph.D. Assistant Director Division of Radiological Health OHT7: Office of In Vitro Diagnostics and Radiological Health 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) K211350

Device Name Bindex BI-2

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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K211350

510(k) Summary

SUBMITTER

Bone Index Finland Ltd. Savilahdentie 14 Kuopio, Finland 70700 Establishment registration number: 3013328880 Phone: +358 45 896 2650 Contact Person: Janne Karjalainen Date Prepared: April 24th, 2022

Name of Device: Bindex, Model Bl-2 Common or Usual Name: Bone sonometer Classification Name: Bone sonometer (21 CFR 892.1180) Regulatory Class: II Product Code: MUA

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DEVICE DESCRIPTION l.

The associated accessories include:

. Measurement stick
Ultrasound gel (optional)

ll. PREDICATE DEVICES

Predicate devices:

(1) Bindex Bl-2 model (K161971).

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III. DEVICE CHANGE COMPARISON

Changes to legally marketed device are described in Table 1.

#	Item	Bindex BI-2 (Legally marketed,K161971)	Bindex BI-2 (Modified, subjectdevice)
1	Indications for use	Bindex measures apparent corticalbone thickness at the proximal tibiaand can be used in conjunction withother clinical risk factors or patientcharacteristics as an aid to thephysician in the diagnosis ofosteoporosis and other medicalconditions leading to reduced bonestrength and in the determination offracture risk.	Bindex measures apparent corticalbone thickness at the proximal tibiaand can be used in conjunction withother clinical risk factors or patientcharacteristics as an aid to thephysician in the diagnosis ofosteoporosis and other medicalconditions leading to reduced bonestrength and in the determination offracture risk.
2	Intended use	Bindex measures apparent corticalbone thickness at the upper shaft oftibia (See Figure 1) and reportsdiagnostic parameter, Density Index(DI), an estimate of hip Bone MineralDensity measured with goldstandard Axial DXA. Thresholds forosteoporosis for DI have beendetermined in comparison to DXA.The DI reported by Bindex is used asan aid in osteoporosis diagnostics byapplying pre determined thresholds.DI can help the clinician inestimation of fracture risk.After the measurement, Bindex®software gives an estimation of thepresence of osteoporosis marked inthe color bar: Green (Low Probabilityof Osteoporosis), Yellow (AdditionalInvestigations Needed) or Red area(High Probability of Osteoporosis). Atotal of 90% of osteoporotic patientsdiagnosed by hip BMD are in theyellow or red area (90% sensitivity)and 90% of non osteoporotic	Bindex measures apparent corticalbone thickness at the upper shaft oftibia (See Figure 1) and reportsdiagnostic parameter, Density Index(DI), an estimate of hip BoneMineral Density measured with goldstandard Axial DXA. Thresholds forosteoporosis for DI have beendetermined in comparison to DXA.The DI reported by Bindex is used asan aid in osteoporosis diagnostics byapplying pre determined thresholds.DI can help the clinician inestimation of fracture risk.After the measurement, Bindex®software gives an estimation of thepresence of osteoporosis marked inthe color bar: Green (LowProbability of Osteoporosis), Yellow(Additional Investigations Needed)or Red area (High Probability ofOsteoporosis). A total of 90% ofosteoporotic patients diagnosed byhip BMD are in the yellow or redarea (90% sensitivity) and 90% of non osteoporotic

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		patients are in the green or yellowarea (90% specificity). Statistically atleast 80% sensitivity and specificityfor hip osteoporosis will be reachedwith 95% confidence. Patientclassification is based on thresholds(separating red/yellow/green areas)published in a study by Karjalainenet al. "New method for point of careosteoporosis screening anddiagnostics" in OsteoporosisInternational 2016.Currently the use of Bindex® DIthresholds are validated forCaucasian women at the agebetween 50 to 90 years. Bindex®measurement takes about oneminute. Bindex® device should beoperated by a physician, or undersupervision of physician by a nurse,pharmacist or trained person with asuitable background education andskills.	non osteoporotic patients are in thegreen or yellow area (90%specificity). Statistically at least 80%sensitivity and specificity for hiposteoporosis will be reached with95% confidence. Patientclassification is based on thresholds(separating red/yellow/green areas)published in a study by Karjalainenet al. "New method for point of careosteoporosis screening anddiagnostics" in OsteoporosisInternational 2016.Currently the use of Bindex® DIthresholds are validated forCaucasian and Hispanic women atthe age between 50 to 90 years.Bindex® measurement takes aboutone minute. Bindex® device shouldbe operated by a physician, or undersupervision of physician by a nurse,pharmacist or other healthprofessional who has gone throughtraining. Bindex should not be usedby patients.
3	Measurementmode	Cortical Thickness (Ct.Th.).	Same
4	Probe compatibility	One transducer, centre frequency =3.0 MHz (nominal)	Same
5	Electrical safety	IEC 60601-2-37:2001 includingAmendments 1 and 2; and IEC60601-1:2005	Same
6	Electromagneticcompatibility	Complies with IEC 60601-1-2:2007	Updated to IEC 60601-1-2 Edition4.0, 2014
7	Power supply	PC USB port powered.	Same
8	OperatingEnvironment	Temperature: +10°C to +40°CHumidity: 5% to 85% RH, non-condensingAtmospheric Pressure: 600 to 1060Pc	Temperature: +15°C to +40°CHumidity: 5% to 90% RH, non-condensingAtmospheric Pressure: Same
9	StorageEnvironment	Temperature: +10°C to +40°CHumidity: 5% to 85% RH, non-condensing	Temperature: +15°C to +40°CHumidity: 5% to 90% RH, non-condensingAtmospheric Pressure: Same
10	Calibration	Calibration before each use.	Same

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IV. PERFORMANCE DATA SUMMARY

This section describes the performance data generated to show safe and effective use of Bindex Bl-2 device. The data for the use in home healthcare environment is summarized in table 2. and described below in more detail.

Biocompatibility testing

The biocompatibility evaluation for the Bindex Bl-2 device was conducted in accordance with the FDA Blue Book Memorandum #G95-1 "Use of International Standard ISO-10993, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing,"May 1, 1995, and International Standard ISO 10993-1 "Biological Evaluation of Medical Devices –Part 1: Evaluation and Testing Within a Risk Management Process," as recognized by FDA. The battery of testing along the ISO 10993-1 would recommend the following tests:

Cytotoxicity
Sensitization
Irritation

The Bindex Bl-2 is in skin contact for duration of less than 24 hours. Since the use of Bindex involves very short skin contact (typically less than 10 minutes) on a healthy skin and therefore poses a very low risk. Safety of the manufacturing and used materials has been further discussed in Biocompatibility report.

Electrical safety and electromagnetic compatibility (EMC)

Electrical safety and EMC testing were conducted on the measurement system, consisting of the Bindex Bl-2 and a laptop computer (on battery use or connected to power supply). The system complies with the IEC 60601-1, and IEC 60601-2-37 standards for safety and the IEC 60601-1-2 standard for EMC.

Software Verification and Validation Testing

Software verification and validation testing were conducted and documentation was provided as recommended by FDA's Guidance for Industry and FDA Staff, "Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices" and "Content of Premarket Submissions for Management of Cybersecurity in Medical Devices".

The software for this device was considered as a "moderate" level of concern.

Mechanical and acoustic testing

The acoustic output and mechanical properties have been tested along the principles presented in harmonized standards IEC 62359 and IEC 60601-1:

. Acoustic Testing has been conducted on the predicate device and test documentation shows equivalence of the devices on behalf of acoustic output.

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. Drop test (hand piece dropped from 1m on hard surface).
. Ball pressure test (pressed with steel ball 5mm in diameter with force of 20N one hour at a temperature of 75+2°C)
Moulding stress relief (device placed in circulating air oven at 70 °C for 7 hours and let cool down)

Device Change	Risks	Verification/ValidationMethods	Acceptance Criteria	SummaryResults
Use in homehealthcareenvironment	Electromagneticinterference	IEC 60601-1-2 Edition4.0Conducteddisturbances inducedby RF fields, Testmethod IEC 61000-4-6Radiated radiofrequency (RF)electromagnetic fields(EM) , Test method IEC61000-4-3	Essentialperformance andBasic Safetymaintained.	Test samplespassed the testswith intact EssentialPerformance andBasic Safety
	Environmentalhazards	Tests in accordance toIEC 60601-1:2005+Am1:2012; Clause5.7, 8.8.3 and 8.7IEC 60601-1-11:2015;Clause 4.2.2, 4.2.3.1,8.3.1 and 10.1.2	Essentialperformance andBasic Safetymaintained.	Test samplespassed the testswith intact EssentialPerformance andBasic Safety

Table 2. Performance data summary, home healthcare environment.

EMC testing according to IEC 60601-1-2 Edition 4.0, 2014:

-Changes in required test for Conducted disturbances induced by RF fields, Test method IEC 61000-4-6
-Changes in required tests for Radiated radio frequency (RF) electromagnetic fields, Test method IEC 61000-4-3

Home healthcare environment standard IEC 60601-1-11:2015 and main safety standard IEC 60601-1:2005 related tests have been conducted.

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Expanding the population in the Intended Use statement to include Hispanic individuals:

A clinical trial has been conducted in Albuquerque, New Mexico, USA to investigate whether the Density Index thresholds used with Bindex Bl-2 device need adjustments when applied in Hispanic population. The method and protocol for this study are same as used in previous clinical studies supporting the use of legally marketed device Bindex BI-2 (K161971), and well-established (several publications, suggested by International society for clinical densitometry). Key findings are summarized below, as written in publication by E. Lewiecki (J Clin Densitom 2020):
" The study enrolled 293 postmenopausal women (153 Caucasian, 140 Hispanic) with and without osteoporosis. The sensitivity and specificity for DI thresholds to distinguish women with total hip or femoral neck T-score <-2.5 or > -2.5 was similar in Caucasians (sensitivity 80%, specificity 86%) and Hispanics (sensitivity 80%, specificity 91%). The findings of this study confirm the utility of previously established DI thresholds to identify women who are likely to have osteoporosis and suggest that the same thresholds can be used for postmenopausal Caucasian and Hispanic women."
-The results are similar than those found in previous study by Schousboe et al. published in Osteoporos Int 2016, (Sensitivity 80% and specificity 82%). These results were included in previous submission for the legally marketed device (K161971).
The labelling of the Bindex Bl-2 have been changed to reflect above described additions in use environment and addition of Hispanic ethnicity to intended population.

V. CONCLUSIONS

The Bindex Bl-2 product has been reviewed for risks arising from the change of device use environment from PROFESSIONAL HEALTHCARE to HOME USE, in which the safe use is verified by tests. The changes in Bindex BI-2 described in this submission do not raise additional questions relating to safety and efficacy of the device. Thus, the device remains substantially equivalent to the previously cleared Bindex BI-2 device.

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.