The Butterfly iQ+ Ultrasound System is indicated for use by trained healthcare professionals in environments where healthcare is provided to enable diagnostic ultrasound imaging and measurement of anatomical structures and fluids of adult and pediatric patients for the following clinical applications: Peripheral Vessel (including carotid, deep ven thrombosis and arterial studies), Procedural Guidance, Small Organs (including thyroid, scrotum and breast), Cardiac, Abdominal, Lung, Urology, Fetal/Obstetric, Gynecological, Musculoskeletal (conventional), Musculoskeletal (superficial) and Ophthalmic. Modes of operation include B-mode + M-mode, B-mode + Color Doppler, B-mode + Power Doppler, Spectral Pulsed Wave Doppler.

Device Description

The Butterfly iQ/Butterfly iQ+ Ultrasound System is a hand-held general-purpose diagnostic imaging system for use by trained healthcare professionals in environments where healthcare is provided to enable visualization and measurement of anatomical structures and fluid of adult and pediatric patients. The system consists of a single transducer with broad imaging capabilities connected to a standard handheld commercial off the shelf (COTS) mobile device compatible with the Butterfly iO/iO+ mobile application (app). The subject device introduces the Auto B-line Counter, a software application backed by an image analysis algorithm. The purpose of the Auto B-line Counter is to provide automated detection and automatic calculation of the number of B-lines to a user in a given rib space and also provides the users the capabilities of reviewing the detected B-lines (via visual overlays). The overlay of B-lines does not mark images for detection of specific pathologies. The Auto B-line Counter enables the automated identification and count of B-lines during a lung scan and is integrated into the existing Butterfly iQ/iQ+ mobile application for use with the Butterfly iQ or iQ+ transducers.

AI/ML Overview

The provided text describes the Butterfly iQ/iQ+ Ultrasound System, which introduces an "Auto B-line Counter" software application. The information below summarizes the acceptance criteria and the study that proves the device meets these criteria.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Auto B-line Counter algorithm's performance are primarily established through analytical validation and clinical performance evaluation.

Metric	Acceptance Criteria (Non-inferiority to clinician annotators)	Reported Device Performance
Analytical Validation	Algorithm performance non-inferior to clinician annotators (Ground Truth)	Met acceptance criteria for all tests. Performance assessed by: - Intraclass Correlation Coefficient (ICC) between annotators for Quality Indicator. - Dice Coefficient Score (DSC) for conformance of automatic B-line segmentation to ground truth. (Specific numerical thresholds for ICC and DSC for acceptance are not provided in the text, but the claim is that criteria were met.)
Clinical Performance Evaluation	Algorithm performance non-inferior to clinician annotator ground truth	Demonstrated non-inferiority. Performance assessed by calculating the Intraclass Correlation Coefficient (ICC) between the tool and the ground truth. Algorithm's performance was consistent among clinically meaningful subgroups: age, gender, and BMI. (Specific numerical thresholds for ICC for acceptance are not provided, but the claim is that non-inferiority was shown).

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

Analytical Testing Test Set:
- Sample Size: 6000 de-identified cines.
- Data Provenance: Acquired from 253 sites. The datasets spanned many demographic variables including gender (male, female, and unidentified), age (20-90 years), and ethnicity via collection from a multitude of clinical sites with diverse and distinct racial patient populations. The data included various clinical subgroups and confounders such as congestive heart failure, heart failure with reduced ejection fraction, diabetes (with and without chronic complications), myocardial infarction, peripheral vascular disease, and renal disease. This suggests a retrospective, multi-center, multi-national (implied by "diverse and distinct racial patient populations") data provenance, although explicit country of origin is not stated.
Clinical Performance Evaluation Test Set:
- Sample Size: 99 subjects.
- Data Provenance: Not explicitly detailed beyond being used for clinical performance evaluation. Given the context, it is likely also retrospective data from a similar pool as the analytical test set, or specifically collected for this evaluation.

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

Number of Experts: The text refers to "expert annotators" (plural) for determining ground truth locations of B-lines and for establishing ICC. While a specific number isn't provided, the use of "annotators" and "experts" in plural implies a group.
Qualifications of Experts: The text states, "The ground truthing for B-line counts was determined by the ICC among expert annotators presented with lung cines and instructions to determine the maximum number of B-Lines using the instant percent method. The ground truth locations of B-lines were then determined by expert annotator segmentations." The exact qualifications (e.g., number of years of experience, specialty like radiologist or emergency physician) are not detailed.

4. Adjudication Method for the Test Set

Adjudication Method: The ground truthing involved assessing the "Intraclass Correlation Coefficient (ICC) among expert annotators." This suggests that multiple experts independently provided assessments, and their agreement (measured by ICC) was used to establish the ground truth or validate its reliability. It doesn't explicitly state a specific adjudication method like 2+1 or 3+1 for resolving discrepancies, but rather implies consensus or high agreement as the basis for ground truth.

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

The document does not describe a Multi-Reader Multi-Case (MRMC) comparative effectiveness study where human readers' performance with and without AI assistance is compared. The studies described focus on the standalone performance of the AI algorithm against human annotator ground truth.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Yes, standalone performance was done. The analytical validation and clinical performance evaluation sections explicitly describe testing the "Auto B-line Counter algorithm performance" as being "non-inferior to clinician annotators (Ground Truth)" and calculating the ICC between "the tool and the ground truth." This indicates a direct comparison of the algorithm's output against established ground truth, representing standalone performance.

7. Type of Ground Truth Used

Expert Consensus / Expert Annotation: The ground truth for B-line counts was determined by the "ICC among expert annotators" and by "expert annotator segmentations" for the locations of B-lines. This strongly indicates an expert consensus or expert annotation approach, where human experts interpret the images to establish the reference standard.

8. Sample Size for the Training Set

The document does not specify the sample size for the training set. It only states that the "data used for verification is completely distinct from that used during the training process and there is no overlap between the two."

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

The document does not explicitly describe how the ground truth for the training set was established. It only ensures the independence of training and testing data and mentions the process for establishing ground truth for the verification/test sets.

Summary

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Image /page/0/Picture/0 description: The image shows the date March 31, 2023. The text is written in a clear, sans-serif font. The date is written in a standard format, with the month, day, and year clearly indicated. The text is centered and takes up most of the image.

Butterfly Network, Inc. % Lynda Ikejimba Senior Regulatory Affairs Program Manager 1600 District Ave BURLINGTON MA 01803

Re: K220068

Trade/Device Name: Butterfly iQ\ Butterfly iQ+ Ultrasound System Regulation Number: 21 CFR 892.1550 Regulation Name: Ultrasonic pulsed doppler imaging system Regulatory Class: Class II Product Code: IYN, IYO, ITX, OIH Dated: March 6, 2023 Received: March 6, 2023

Dear Lynda Ikejimba:

We have reviewed vour 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

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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/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 medical devices and radiation-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,

Yanna S. Kang -S

Yanna Kang, Ph.D. Assistant Director Mammography and Ultrasound Team DHT8C: Division of Radiological Imaging and Radiation Therapy Devices OHT8: Office of 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) K220068

Device Name Butterfly iQ/iQ+ Ultrasound System

Indications for Use (Describe)

Abdominal, Lung, Urology, Fetal/Obstetric, Gynecological, Musculoskeletal (conventional), Musculoskeletal (superficial) and Ophthalmic. Modes of operation include B-mode + M-mode, B-mode + Color Doppler, B-mode + Power Doppler, Spectral Pulsed Wave Doppler.

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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Image /page/3/Picture/0 description: The image shows the logo for Butterfly Network, a medical imaging company. The logo consists of a blue butterfly icon on the left, followed by the word "Butterfly" in bold, black letters. Below the word "Butterfly" is the tagline "The New Image of Health" in a smaller font.

1600 District Ave Burlington, MA 01803

(781) 557-4800

This 510(k) Summary is submitted in accordance with 21 CFR §807.92 K220068

I. SUBMITTER

Manufacturer:

Butterfly Network, Inc. 1600 District Ave Burlington, MA 01803 Phone: 1-781-557-4800

Contact Person:

Lynda Ikejimba, PhD Senior Regulatory Affairs Program Manager E-mail: likejimba(@butterflynetinc.com

Date Prepared: March 6, 2023

II. DEVICE

Trade Name: Butterfly iQ/ Butterfly iQ+ Ultrasound System Common Name: Ultrasound Imaging System Classification Name(s): Ultrasonic Pulsed Doppler Imaging System (21 CFR 892.1550) Ultrasonic Pulsed Echo Imaging System (21 CFR 892.1560) Diagnostic Ultrasound Transducer (21 CFR 892.1570) Automated Radiological Image Processing Software (21 CFR 892.2050) Regulatory Class: II Primary Product Code: IYN Secondary Product Codes: IYO, ITX, QIH Classification Panel: Radiology

III. PREDICATE DEVICE

Primary Predicate: Butterfly iQ Ultrasound System (K202406) This predicate has not been subject to a design-related recall.

Reference Predicates: Philips Lumify Diagnostic Ultrasound System (K203406), GE Venue (K170714)

IV. DEVICE DESCRIPTION

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connected to a standard handheld commercial off the shelf (COTS) mobile device compatible with the Butterfly iO/iO+ mobile application (app).

The subject device introduces the Auto B-line Counter, a software application backed by an image analysis algorithm. The purpose of the Auto B-line Counter is to provide automated detection and automatic calculation of the number of B-lines to a user in a given rib space and also provides the users the capabilities of reviewing the detected B-lines (via visual overlays). The overlay of B-lines does not mark images for detection of specific pathologies. The Auto B-line Counter enables the automated identification and count of B-lines during a lung scan and is integrated into the existing Butterfly iQ/iQ+ mobile application for use with the Butterfly iQ or iQ+ transducers.

V. INDICATIONS FOR USE

The Butterfly iQ/Butterfly iQ+ Ultrasound System is indicated for use by a trained healthcare professional in an environment where healthcare is provided to enable diagnostic ultrasound imaging and measurement of anatomical structures and fluids of adult and pediatric patients for the following clinical applications:

Peripheral Vessel (including carotid, deep vein thrombosis and arterial studies), Small Organs (including thyroid, scrotum and breast), Cardiac, Abdominal, Lung, Procedural Guidance, Urology, Fetal/Obstetric, Gynecological, Musculoskeletal (conventional), Musculoskeletal (superficial) and Ophthalmic.

Modes of operation include B-mode + M-mode, B-mode + Color Doppler, B-mode + Power Doppler, Spectral Pulsed Wave Doppler.

VI. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

The subject device contains the same hardware technology as the previously cleared predicate device Butterfly iQ/iQ+(K202406), and the subject device is compatible with both the Butterfly iQ and iQ+ Ultrasound systems. There is an addition of "lung" to the Indications For Use statement and Spectral Pulsed Wave Doppler to the modes of operation. These additions do not introduce any additional risks as there have been no changes in the other modes or compatible transducer frequencies and Spectral Pulsed Wave Doppler is a well-established mode of operation. The differences do not alter the intended therapeutic use of the device nor do they affect the safety and effectiveness of the device relative to the predicate. Both the subject and predicate devices have the same intended use as a general-purpose diagnostic ultrasound imaging system. A comparison of the proposed Butterfly iQ/Butterfly iQ+ Ultrasound System to the currently marketed predicate is provided in the table below.

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ComparisonCategory	Butterfly iQ/iQ+Ultrasound System(Subject Device)	Butterfly iQUltrasound System(Primary Predicate)(K202406)	Comparison
General DeviceDescription	Hand held portablediagnostic ultrasoundsystem	Hand held portablediagnostic ultrasoundsystem	RemainsUnchanged
Indications forUse	The Butterfly iQ/ iQ+Ultrasound System isindicated for use bytrained healthcareprofessionals inenvironments wherehealthcare is provided toenable diagnosticultrasound imaging andmeasurement ofanatomical structures andfluids of adult andpediatric patients for thefollowing clinicalapplications:Peripheral Vessel(including carotid, deepvein thrombosis andarterial studies),Procedural Guidance,Small Organs (includingthyroid, scrotum andbreast), Cardiac,Abdominal, Lung,Urology, Fetal/Obstetric,Gynecological,Musculoskeletal(conventional),Musculoskeletal(superficial) andOphthalmic.Modes of operationinclude B-mode, B-mode+ M-mode, B-mode +Color Doppler, B- mode +	The Butterfly iQUltrasound System isindicated for use bytrained healthcareprofessionals inenvironments wherehealthcare is providedto enable diagnosticultrasound imaging andmeasurement ofanatomical structuresand fluids of adult andpediatric patients for thefollowing clinicalapplications:Peripheral Vessel(including carotid, deepvein thrombosis andarterial studies),Procedural Guidance,Small Organs(including thyroid,scrotum and breast),Cardiac, Abdominal,Urology,Fetal/Obstetric,Gynecological,Musculoskeletal(conventional),Musculoskeletal(superficial) andOphthalmic.Modes of operationinclude B-mode,B-mode + M-mode,B-mode + Color	Addition of "lung"to Indications forUse and SpectralPulsed WaveDoppler tooperating mode.
	Power Doppler, SpectralPulsed Wave Doppler.	Doppler, B-mode +Power Doppler.
Type	Single probe 2D phasedarray	Single probe 2D phasedarray	RemainsUnchanged
Sterility	Non-sterile	Non-sterile	RemainsUnchanged
Duration of Use	Limited (≤ 24 hours)	Limited (≤ 24 hours)	RemainsUnchanged
Reusable	Yes	Yes	RemainsUnchanged
Principles ofOperation(subject AutoB-Line Counter)	Automatic detection andcounting of B-lines fromlung ultrasound images	Manual counting ofB-lines from lungultrasound images	Auto B-LineCounter added toexisting ButterflyiQ/Butterfly iQ+Ultrasound SystemApp

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VII. PERFORMANCE DATA

Performance Testing

Butterfly Network's iQ/iQ+ Ultrasound System was developed and tested in accordance with company design control processes and safety and performance testing. Relevant non-clinical verification and validation testing was performed to address the introduction of the subject software algorithm for the Auto B-Lines Counter and to assure its safe and effective performance.

Analytical Testing

Analytical Validation testing was performed to demonstrate that the Auto B-line Counter algorithm performance is non-inferior to clinician annotators (Ground Truth). The Auto B-line Counter met the acceptance criteria for all tests. Performance was assessed by the widely accepted metrics, the intraclass correlation coefficient (ICC) between annotators for the Quality Indicator and Dice Coefficient Score (DSC), for the conformance of automatic B-line segmentation to ground truth.

A validation dataset was curated by random selection of 6000 de-identified cines acquired from 253 sites. The datasets spanned many demographic variables including gender (male, female, and unidentified), age (20-90 years), and ethnicity via collection from a multitude of clinical sites with diverse and distinct racial patient populations.

Clinical subgroups and confounders:

The algorithm performance was verified on all demographic subgroups and clinical subgroups with various confounders present including but not limited to congestive heart failure, heart

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failure reduced ejection fraction, diabetes with and without chronic complication, myocardial infarction, peripheral vascular disease, renal disease, and many other factors,

Truthing process:

The ground truthing for B-line counts was determined by the ICC among expert annotators presented with lung cines and instructions to determine the maximum number of B-Lines using the instant percent method. The ground truth locations of B-lines were then determined by expert annotator segmentations.

The data used for verification is completely distinct from that used during the training process and there is no overlap between the two. Independence of testing and training data was ensured by auditability-each study and associated images had unique dataset identification- and by sequestration-no study or its images could belong to multiple datasets.

Clinical Performance Evaluation

The clinical performance was evaluated on 99 subjects and demonstrated that the Auto B-line Counter algorithm performance is non-inferior to clinician annotator ground truth. Performance was assessed by calculating the intraclass correlation coefficient (ICC) between the tool and the ground truth. Additionally, the evaluation concluded that the algorithm's performance was consistent among clinically meaningful subgroups: age, gender, and BMI. Overall, the results support the generalizability of the Auto B-line Counter across the intended patient population.

Non-clinical Evaluation

The introduction of the Butterfly Auto B-Lines Counter was tested in accordance with internal Butterfly standards for safety and design quality 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." The software for this device is considered a "moderate" level of concern. The activities to ensure safe and effective performance of the subject software revision include but are not limited to Requirements Review, Risk Analysis and Management, Product Specifications, Design Reviews, Product Performance testing. Additional non-clinical evaluation demonstrated that the inclusion of the Auto B-Line Counter did not introduce any additional risks to the previously cleared Butterfly iQ/iQ+ Ultrasound System.

Summary

Based on the clinical performance as documented in the pivotal clinical study, the Butterfly Auto B-Lines Counter was found to have a safety and effectiveness profile that is similar to the predicate device.

VII. CONCLUSIONS

Based on the indications for use, technological characteristics, and performance testing, the subject device meets the requirements that are considered adequate for its intended use and is substantially equivalent in design, principles of operation and indications for use to the predicate device and does not raise new questions of safety or effectiveness to the predicate device. The subject device was found to have a safety and effectiveness profile that is similar to the predicate device.

Regulation Number and Section

§ 892.1560 Ultrasonic pulsed echo imaging system.

(a)
Identification. An ultrasonic pulsed echo imaging system is a device intended to project a pulsed sound beam into body tissue to determine the depth or location of the tissue interfaces and to measure the duration of an acoustic pulse from the transmitter to the tissue interface and back to the receiver. This generic type of device may include signal analysis and display equipment, patient and equipment supports, component parts, and accessories.(b)
Classification. Class II (special controls). A biopsy needle guide kit intended for use with an ultrasonic pulsed echo imaging system only is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 892.9.