The Biovitals Analytic Engine (BA Engine) is intended to be used with continuous biometric data from already cleared sensors measuring heart rate, respiratory rate, and activity in ambulatory patients being monitored in a healthcare facility or at home, during periods of minimal activity. The device learns the correlation between multiple vital signs during the patient's daily activity and builds an individualized biometric signature which is dynamically updated based on incoming data. The device computes a time series Biovitals Index (BI), which reflects changes in the patient's measured vital signs from their measured baseline, which is derived from the individualized biometric signature of the patient.

The BA Engine is a cloud-based software engine, intended to be an adjunct to and is not intended to replace vital signs monitoring. The BI is intended for daily intermittent, retrospective review by a qualified practitioner. The BA Engine is intended to provide additional information for use during routine patient monitoring. The BI is not intended for making clinical decisions regarding patient treatment or for diagnostic purposes.

The device is intended for an adult population.

Device Description

Biovitals Analytics Engine consists of:

An automated proprietary algorithm to analyze data and generate Biovitals Index.
A cloud-based database to store the input, intermedium output and the final output
A web application programming interface (API) which handle the continuous physiology data.
A web application programming interface (API) query the databases and get output.
A web dashboard to render the BA Engine output in a continuous graph format, which can help intended users to monitor a patient's Biovitals Index.

Biovitals Analytics Engine works in the following sequence:

Accept input data via secure API;
Analyze the input data using Biovitals Analytics Engine proprietary algorithm, which generate Biovitals Index:
Personal physiology signature data base initialization (at the early stage on the algorithm when the engine learns the patients and builds the personal baseline)
Biovitals Index calculation
Biovitals Analytics engine generates the Biovitals Index which is a time series scalar value from 0 to 1.
The output of BA Engine is stored in a cloud-based database.
The output API queries the databases and gets the output, and the output shall be reviewed by the qualified practitioner via a dashboard.

AI/ML Overview

The Biovitals Analytics Engine (BA Engine) computes a time series Biovitals Index (BI) that reflects changes in a patient's vital signs from their measured baseline. The device's performance was evaluated through clinical testing to show its correlation with changes in the relationship among vital sign parameters as assessed by a panel of physicians.

Here's a breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Correlation with changes in vital sign parameters (PPA)	The Biovitals Index (BI) was correlated to the changes in relationship among vital sign parameters, with a lower bound of the 95% confidence interval of the positive percent agreement (PPA) greater than 0.7.
Within-subject variability for BI categories	Low (BI ≤ 0.3): 0.11 Moderate (0.3 < BI ≤ 0.7): 0.27 Significant (BI > 0.7): 0.17

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

Sample Size: 50 subjects.
Data Provenance: The subjects were patients presenting at an Emergency Department and were deemed appropriate for home monitoring. The document does not specify the country of origin, but given the FDA review, it is likely from the US, or data collected in a manner suitable for US regulatory submission. The study appears to be prospective as it describes patients presenting at an ED and being monitored.

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

Number of Experts: A panel of three physicians.
Qualifications: The document only states "a panel of three physicians" and does not provide specific qualifications (e.g., years of experience, sub-specialty).

4. Adjudication Method for the Test Set

The document states that the performance was compared "against a panel of three physicians evaluating the changes in the relationship among the patients' vital sign parameters." This implies a consensus or majority opinion (e.g., 2+1, where at least two physicians agree). However, the specific adjudication method (e.g., 2+1, 3+1, none) is not explicitly stated.

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

No, a formal MRMC comparative effectiveness study was not explicitly described for evaluating how human readers improve with AI vs. without AI assistance. The study described focuses on the standalone performance of the BI in correlating with physician assessments of vital sign changes, rather than comparing human reader performance with and without AI assistance. The device is intended as an "adjunct" for "daily intermittent, retrospective review," suggesting it provides additional information to a practitioner, which could imply human-in-the-loop, but the study design does not directly evaluate this human improvement.

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

Yes, a standalone performance evaluation of the algorithm was conducted. The study evaluated the Biovitals Index (BI) directly against the assessment of a panel of physicians. The PPA (Positive Percent Agreement) of the BI itself was measured against the physician panel's assessment, indicating a standalone performance evaluation.

7. The Type of Ground Truth Used

The ground truth used was expert consensus / clinical assessment from a panel of three physicians. They evaluated the "changes in the relationship among the patients' vital sign parameters."

8. The Sample Size for the Training Set

The document does not specify the sample size used for the training set. It only describes the methodology for establishing the personalized baseline: "The baseline is initially established using data from the first 24 hours and updated periodically as new data is received." And for the within-subject variability calculation: "The expected within-subject variability was computed using data from a clinical study involving 50 emergency department patients that were deemed appropriate for home monitoring." This suggests the 50 patients mentioned for the test set might also be involved in data used for variability computation, but it doesn't describe the training set for the core algorithm that generates the BI.

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

The document does not explicitly describe how ground truth (or the equivalent "gold standard") for the training set was established. Instead, it explains how the BA Engine "learns the correlation between multiple vital signs during the patient's daily activity and builds an individualized biometric signature which is dynamically updated based on incoming data." This is described as a personalized, dynamic baseline for each patient, rather than a pre-established, universal ground truth from a large training dataset. The algorithm "learns" from the individual patient's own physiological data to establish their personal baseline.

Summary

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August 15, 2019

Biofourmis Singapore Pte. Ltd % Rakesh Lal Consultant Rakesh Lal 7 Courtyard Pl Lexington, Massachusetts 02420

Re: K183282

Trade/Device Name: Biovitals Analytics Engine Regulation Number: 21 CFR 870.2300 Regulation Name: Cardiac Monitor (Including Cardiotachometer And Rate Alarm) Regulatory Class: Class II Product Code: PLB Dated: July 18, 2019 Received: July 19, 2019

Dear Rakesh Lal:

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

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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 (OS) 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,

Stephen Browning Acting Assistant Director Division of Cardiac Electrophysiology, Diagnostics and Monitoring Devices Office of Cardiovascular Devices Office of Product Evaluation and Ouality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K183282

Device Name Biovitals Analytics Engine

Indications for Use (Describe)

The BA Engine is a cloud-based software engine, intended to be an adjunct to and is not intended to replace vital signs monitoring. The BI is intended for daily intermittent, retrospective review by a qualified practitioner. The BA Engine is intended to provide additional information for use during routine patient monitoring. The BL is not intended for making clinical decisions regarding patient treatment or for diagnostic purposes.

The device is intended for an adult population.

Type of Use ( Select one or both, as applicable )
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☑ Prescription Use (Part 21 CFR 801 Subpart D)
☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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Premarket Notification 510(k) Summary

This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

Applicant Information:

Date Prepared:	July 16, 2019
Name:	Biofourmis Singapore Pte. Ltd.
Address:	Vision Exchange, #07-152 Venture DriveSingapore 608526
Contact Person:	Rakesh M. Lal, Consultantrakesh.m.lal@gmail.com
Phone:	(817) 734-8303

Device Information:

Trade Name:	Biovitals Analytics Engine
Common Names:	BA Engine
Classification Name(s):	Cardiovascular
Product Code/ Regulation:	PLB/21 CFR 870.2300
Classification:	Class II

Predicate Device:

PhysIQ PPA Engine - K142512

Device Description:

Biovitals Analytics Engine consists of:

An automated proprietary algorithm to analyze data and generate Biovitals Index. ●
A cloud-based database to store the input, intermedium output and the final output ●
A web application programming interface (API) which handle the continuous physiology data.
A web application programming interface (API) query the databases and get output.
A web dashboard to render the BA Engine output in a continuous graph format, which can ● help intended users to monitor a patient's Biovitals Index.

Biovitals Analytics Engine works in the following sequence:

Accept input data via secure API;
Analyze the input data using Biovitals Analytics Engine proprietary algorithm, which ● generate Biovitals Index:

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Personal physiology signature data base initialization (at the early stage on the о algorithm when the engine learns the patients and builds the personal baseline)
Biovitals Index calculation o
Biovitals Analytics engine generates the Biovitals Index which is a time series scalar value from 0 to 1.
The output of BA Engine is stored in a cloud-based database.
The output API queries the databases and gets the output, and the output shall be reviewed by the qualified practitioner via a dashboard.

Interpretation of Biovitals Index:

The BA Engine computes a time series Biovitals Index (BI), which reflects changes in the patient's measured vital signs from their measured baseline, which is derived from the individualized biometric signature of the patient. The BI is displayed in 30-minute segments and ranges from 0 to 1. The BI is intended for daily intermittent, retrospective review by a qualified practitioner.

A BI closer to 0 indicates that the relationships among the patient's vital signs are similar to the baseline. A BI value closer to 1 indicates that the relationships among the patient's vital signs are different from the baseline is initially established using data from the first 24 hours and updated periodically as new data is received. The initial baseline comprises 3 to 13 hours of data and the updated baseline usually comprises the last 9 to 45 hours of data with low change in the relationship among the vital signs, depending on the monitoring duration.

To aid in understanding the magnitude of changes in the relationship among the patient's vital signs as compared to the baseline, the BI is divided into three categories. A BI less than or equal to 0.3 indicates that there has been little or no change in the relationship among the patient's vital signs as compared to baseline. A BI value greater than 0.3 and less than or equal to 0.7 reflects moderate change, and a BI value greater than 0.7 reflects significant change in the relationship among the patient's vital signs as compared to baseline.

The expected within-subject variability for each of the three ranges of the BI are shown in the table below.

BI Category	Expected within-subject variability
Low (BI ≤ 0.3)	0.11
Moderate (0.3 < BI ≤0.7)	0.27
Significant (BI > 0.7)	0.17

The expected within-subject variability was computed using data from a clinical study involving 50 emergency department patients that were deemed appropriate for home monitoring.

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Indications for Use:

The device is intended for an adult population.

Summary Comparison to Predicate:

The following tables provide a summary of substantial equivalence between the subject device and the cited predicate. The subject device has the same intended use and substantially equivalent characteristics that do not raise different questions of safety or effectiveness.

Comparison to Predicate Device:

The following table provides a comparison of the detection features of Biovitals Analytics Engine and the predicate device:

Features	BiofourmisBiovitals AnalyticsEngine	PhysIQPPA Engine(K142512)	Comparison
General Characteristics
Classification	Class II, 21 CFR 870.2300	Class II, 21 CFR 870.2300	Equivalent
Product Code	PLB	PLB	Equivalent
Intended Use	Patient Monitor (withoutalarms)	Patient Monitor (withoutalarms)	Equivalent
Indications forUse	The Biovitals AnalyticEngine (BA Engine) isintended to be used withcontinuous biometric datafrom already clearedsensors measuring heart	The PersonalizedPhysiology Engine (PPAEngine) is intended to beused with data fromalready cleared sensorsmeasuring physiological	Equivalent – both devicesare intended to provide anindex to a physician baseda patient's on vital signs,to provide additionalinformation during routine
Features	Biofourmis	PhysIQ	Comparison
	Biovitals AnalyticsEngine	PPA Engine(K142512)
	rate, respiratory rate, andactivity in ambulatorypatients being monitoredin a healthcare facility orat home, during periods ofminimal activity. Thedevice learns thecorrelation betweenmultiple vital signs duringthe patient's daily activityand builds anindividualized biometricsignature which isdynamically updatedbased on incoming data.The device computes atime series Biovitals Index(BI), which reflectschanges in the patient'smeasured vital signs fromtheir measured baseline,which is derived from theindividualized biometricsignature of the patient.	parameters, includingheart rate, respiratory rate,and activity in ambulatorypatients being monitoredin a healthcare facility orat home. The deviceprovides a time seriesMultivariate Change Index(MCI) which indicateswhether the relationshipsamong the patient'smonitored vital signschange from thosemeasured at baseline,which has been derivedfrom measurementspreviously obtained duringroutine activities of dailyliving. The MCI is basedon an integratedcomputation evaluatingchanges in the parametersand their relationships toeach other.	patient monitoring.Neither device is intendedto replace vital signsmonitoring, nor is eitherdevice intended to providea diagnosis to thephysician.
	The BA Engine is a cloud-based software engine,intended to be an adjunctto and is not intended toreplace vital signsmonitoring. The BI isintended for dailyintermittent, retrospectivereview by a qualifiedpractitioner. The BAEngine is intended toprovide additionalinformation for use duringroutine patient monitoring.The BI is not intended formaking clinical decisionsregarding patient treatmentor for diagnostic purposes.The device is intended foran adult population.	The PPA Engine is anadjunct to and is notintended to replace vitalsigns monitoring. TheMCI is intended for dailyintermittent, retrospectivereview by a qualifiedpractitioner. The PPAEngine is intended toprovide additionalinformation for use duringroutine patient monitoring.The MCI is not intendedfor making clinicaldecisions regarding patienttreatment or for diagnosticpurposes.
Features	BiofourmisBiovitals AnalyticsEngine	PhysIQPPA Engine(K142512)	Comparison
PatientPopulation &Environment	Ambulatory Non-pediatric	Ambulatory Non-pediatric	Equivalent
Technological Characteristics
Components	Cloud-based Softwareonly	Software only	Equivalent - the onlydifferences arise withregard to the specificimplementation (softwarearchitecture, programminglanguages, etc.). Theseminor differences do notraise new questions ofsafety and effectiveness.
IndexProduced	Non-linear combination ofvital parameters	Non-linear combination ofvital parameters	Equivalent - while thespecific combination ofthe index may be different,the general approach,meaning of the index anduse of baselineinformation are the same.
Index Meaning	Index represents howdifferent the relationshipsamong the patient's vitalsigns are with respect tonormality.A BI less than or equal to0.3 indicates that there hasbeen little or no change inthe relationship among thepatient's vital signs ascompared to baseline. ABI value greater than 0.3and less than or equal to0.7 reflects moderatechange, and a BI valuegreater than 0.7 reflectssignificant change in therelationship among thepatient's vital signs ascompared to baseline.	Index represents howdifferent the relationshipsamong the patient's vitalsigns are with respect tonormality.An MCI value closer tozero (0) indicates that themonitored relationshipsamong the vital signs aresimilar to the learnedbaseline. An MCI valuecloser to one (1) indicatesthat the patient'smonitored relationshipsamong the vital signs arelikely to be different fromthe learned baseline.	Equivalent - the deviceshave a differentinterpretation of the indexspecific to its softwareimplementation, but theinterpretation isconceptually similar, andthis difference does notraise new questions ofsafety and effectiveness.
IndexAlgorithmNormality	Normality is defined as thepatient's own baseline.The baseline is initiallyestablished using datafrom the first 24 hours and	Normality is defined as thepatient's own baseline	Equivalent - the subjectdevice's baseline isperiodically updated butstill reflects the samerelationship among vital
Features	BiofourmisBiovitals AnalyticsEngine	PhysIQPPA Engine(K142512)	Comparison
	updated periodically asnew data is received.		signs as initiallyestablished in the first 24hours. This difference doesnot raise new questions ofsafety and effectiveness.
Index Display	Single numeric value oflatest index	Single numeric value oflatest index	Equivalent - specificdifferences in the userinterface do not raisedifferent questions ofsafety and effectiveness.
	Trend graphs	Trend graphsTable
Vital SignsData Source	FDA cleared PatientMonitors and ClinicalInformation Systems	Clinical InformationSystems	Equivalent - the subjectdevice enables use of datacaptured directly fromFDA cleared patientmonitors. The predicatedevice also uses data fromFDA cleared devices butobtains the data throughintegration with ClinicalInformation Systems.Since the actual sensordata is the same, thisdifference does not raisenew questions of safetyand effectiveness.
Alarm System	No	No	Equivalent

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Summary of Performance Testing

Tests have been performed in compliance with the appropriate recognized consensus standards. Testing described in this 510(k) consisted of verification of all design input requirements and product specifications. No residual anomalies appeared during verification and software validation tests. General usability tests, analyzing the users' ability to login, upload, review and download were performed and met all requirements. All software validation testing was completed successfully and met all requirements.

Summary of Clinical Testing

Clinical testing was performed with the BA Engine to evaluate the performance of the Biovitals Index. The testing was performed on a total of 50 subjects presenting at an Emergency Department,

K183282

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who were deemed appropriate for home monitoring, and compared the performance of the BI against a panel of three physicians evaluating the changes in the relationship among the patients' vital sign parameters. The testing showed that the BI was correlated to the changes in relationship among vital sign parameters, with a lower bound of the 95% confidence interval of the positive percent agreement (PPA) greater than 0.7.

Software

Biofourmis followed IEC 62304:2015 and the FDA Guidance Document, "General Principles of Software Validation; Final Guidance for Industry and FDA Staff" (January, 2002) with respect to software development and validation. The Biofourmis software is classified as a "moderate level of concern" per the FDA guidance document.

Verification and validation testing were completed in compliance with the following standards and guidance documents:

AAMI ANSI IEC 62304:2015, Medical device software Software life cycle processes ●
General Principles of Software Validation; Final Guidance for Industry and FDA Staff" ● (January 2002)
IEC 62366-1 Edition 1.0 2015-02 Medical devices Application of usability engineering . to medical devices

Conclusion

Based upon the intended use, product technical information, clinical and non-clinical testing and standards compliance provided in this premarket notification, Biovitals Analytics Engine has been shown to be substantially equivalent to the legally-marketed predicate.

Regulation Number and Section

§ 870.2300 Cardiac monitor (including cardiotachometer and rate alarm).

(a)
Identification. A cardiac monitor (including cardiotachometer and rate alarm) is a device used to measure the heart rate from an analog signal produced by an electrocardiograph, vectorcardiograph, or blood pressure monitor. This device may sound an alarm when the heart rate falls outside preset upper and lower limits.(b)
Classification. Class II (performance standards).