The B4C System is intended for the monitoring of variation in intracranial pressure in patients with suspected alteration of intracranial pressure (ICP) or change in intracranial compliance, by providing surrogate ICP waveforms and associated parameters (estimated P2/P1 ratio, normalized Time-to-Peak, derived useful ICP pulses and cardiac pulses) for interpretation.

Device Description

The B4C System is a non-invasive device intended for the monitoring of variation in intracranial pressure, including patients with suspected alteration of intracranial pressure (ICP) or change in intracranial compliance. It consists of a sensor with Bluetooth wireless module, headband, mobile device software application, receiver, external battery pack and charger, as well as processing and analytical software. The sensor contains four strain gauges situated on a metal bar that detects variations in skull deformation through tension and compression of the metal bar in response to changes in intracranial pressure. These resistance measures are converted to a digital signal using a high-resolution ADC (Analog to Digital Converter) in the sensor that is transmitted to software components for viewing, processing and analysis. The proposed device does not measure absolute intracranial pressure values, but produces surrogate waveform morphology, its trend, and associated parameters reflecting changes in ICP. The B4C System and surrogate waveform and associated outputs do not substitute ICP monitoring methods when measurement of the absolute value of ICP is required to make a clinical decision.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the B4C System meets them, based on the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

The acceptance criteria for the B4C System's clinical performance are implicitly derived from the study objectives and the statistical analyses performed. The primary objective was to demonstrate a "consistent correlation" and "reliability and accuracy of the correlation" between the B4C System's surrogate ICP waveform and parameters and those from invasive ICP monitoring.

Acceptance Criteria (Implicit)	Reported Device Performance
P2/P1 Ratio Correlation: Statistically significant correlation with invasive ICP monitoring.	Spearman correlation: 0.495 [0.471, 0.517], p<.0001. Normalized Mutual Information: 0.561 [0.531, 0.606]. Deming regression estimates: Y = -0.67 [-1.85, 0.02] + 1.60 [0.97, 2.69]X.
P2/P1 Ratio Agreement: Acceptable limits of agreement with invasive ICP monitoring.	Bland-Altman limits of agreement: -0.723 to 0.761 (mean distance/bias 0.019; 95% CI: -0.060, 0.101). Instances observed where P2/P1 differed by >0.7.
Normalized Time-to-Peak (TTP) Correlation: Statistically significant correlation with invasive ICP monitoring.	Spearman correlation: 0.318 [0.291, 0.345], p<.0001. Normalized Mutual Information: 0.612 [0.564, 0.643]. Deming regression estimates: Y = 0.00 [-0.11, 0.09] + 0.84 [0.38, 1.39]X.
Normalized Time-to-Peak (TTP) Agreement: Acceptable limits of agreement with invasive ICP monitoring.	Bland-Altman limits of agreement: -0.183 to 0.245 (mean distance/bias 0.031; 95% CI: 0.011, 0.050). Instances observed where TTP differed by >0.2.
Safety: No serious adverse events related to the device.	No adverse events were reported.
Substantial Equivalence: Demonstrate comparable performance to predicate device with respect to ICP waveform morphology monitoring.	The study concluded that results demonstrated a statistically significant correlation in the ICP signal and waveform parameters between the B4C System and the gold standard invasive ICP monitoring device. The outcomes demonstrate comparable effectiveness between the Braincare device and commonly used invasive ICP devices for monitoring and assessing variations in ICP waveform associated parameters over time. Based on performance testing and comparison, it was deemed substantially equivalent to the predicate device.

Detailed Study Information:

Sample sizes used for the test set and data provenance:
- Total enrolled subjects: 123
- Subjects after device label check: 107
- Subjects after data quality check: 85 (78 adults, 7 pediatric)
- Analyzed participants (test set): 78 adults (due to reduced quantity of pediatric subjects, enabling statistically relevant performance only for adults).
- Total acquisition time analyzed: 4695 minutes (98% adult, 2% pediatric across the broader dataset).
- Data Provenance: Not explicitly stated, but the mention of "4 centers" suggests a multi-center study. The sponsor is Braincare Desenvolvimento e Inovacao Tecnologica S.A. based in Brazil, suggesting the origin of the data is likely within Brazil or other international sites. The study was described as "combined prospective, multi-center, observational study."
Number of experts used to establish the ground truth for the test set and qualifications of those experts:
- The document implies that the ground truth was established using "gold standard invasive ICP monitoring methods such as the external ventricular drain or intraparenchymal micro transducers."
- It does not explicitly state the number of experts or their qualifications for establishing the ground truth from these invasive methods. It relies on the inherent validity of the invasive measurements as the "gold standard."
Adjudication method for the test set:
- No adjudication method (e.g., 2+1, 3+1) is mentioned for the test set ground truth. The ground truth was established directly from invasive ICP devices. This type of data does not typically involve multiple human readers or adjudication in the same way as, for example, image interpretation.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly performed or described. This study focused on the technical correlation and agreement between the device's output and invasive ICP measurements. It did not directly assess the impact of the B4C System on human reader performance or diagnostic accuracy.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The study primarily focused on the standalone performance of the B4C System's ability to produce surrogate ICP waveforms and associated parameters that correlate with invasive ICP measurements. The analysis (Spearman correlation, normalized mutual information, Bland-Altman, Deming regression) evaluates this algorithm-only performance.
- The device is intended to provide "surrogate ICP waveforms and associated parameters... for interpretation," implying a human-in-the-loop for interpretation, but the study itself is about the accuracy of the device's output compared to ground truth.
The type of ground truth used:
- Objective/Physiological Data: The ground truth was established using "gold standard invasive ICP monitoring methods such as the external ventricular drain or intraparenchymal micro transducers." This represents direct physiological measurement rather than expert consensus on subjective interpretation.
The sample size for the training set:
- The document does not specify a separate training set size. The clinical study described appears to be a validation study (test set) for the pre-existing B4C System, which includes processing and analytical software. Given the description, the models and algorithms within the B4C System would have been developed and trained using other data, but that training data and its size are not disclosed in this 510(k) summary.
How the ground truth for the training set was established:
- As the training set details are not provided, the method for establishing its ground truth is also not described in this document.

Summary

{0}------------------------------------------------

Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in a blue box, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

October 8, 2021

Braincare Desenvolvimento e Inovacao Tecnologica S.A. % Connie Oiu Regulatory Consultant M Squared Associates,Inc. 127 West 30th Street, 9th Floor New York, New York 10001

Re: K201989

Trade/Device Name: B4C System Regulation Number: 21 CFR 882.1620 Regulation Name: Intracranial Pressure Monitoring Device Regulatory Class: Class II Product Code: GWM Dated: September 9, 2021 Received: September 10, 2021

Dear Connie Qiu:

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

{1}------------------------------------------------

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 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,

for Jay Gupta Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

{2}------------------------------------------------

Indications for Use

510(k) Number (if known) K201989

Device Name B4C System

Indications for Use (Describe)

Refer to device labeling for more information regarding the derivation of the output of the device.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

{3}------------------------------------------------

510(k) Summary

B4C System

Sponsor:	Braincare desenvolvimento e Inovacao Tecnologica S.A.Avenida Bruno Ruggiero Filho, 971São Carlos, SP - Brazil13562-420
Contact:	Connie QiuM Squared Associates, Inc.127 West 30th Street, 9th FloorNew York, New York 10001Ph. 703-562-9800Fax. 703-562-9797
Date Prepared:	October 8, 2021
Proprietary Name:	B4C System
Common Name:	Intracranial pressure monitoring device
Regulatory Class:	II
Regulation:	21 CFR 882.1620
Product Code:	GWM
Predicate Device(s):	BcSs-PICNI-2000 Sensor K182073

Device Description

{4}------------------------------------------------

K201989, Page 2 of 12

The sensor component is supported on a plastic headband worn by the patient, such that the sensor is in contact with the scalp and is perpendicularly positioned in the temporoparietal transition, 2 inches (5-6 cm) above the entrance of the external auditory canal on the coronal plane. Slight pressure is applied so that the sensor pin maintains contact with the scalp throughout the monitoring session. The sensor continuously records and transfers acquired data to the B4C analytical and processing software, and back to the mobile device application or to a compatible multi-parameter monitor that has piezoresistive pressure transducer sensitivities of 5uV/Vex/mmHg or greater and automatic amplitude window adjustment capability via a paired receiver. Data is transferred wireless via Bluetooth connection between sensor and mobile application and HTTPs protocol between mobile application and analytics software. The clinician may view the visualized waveform on the mobile device along with an intermediate or final report of surrogate waveform and associated parameters including surrogate waveform trend line, average waveform per minute and estimated P2/P1 ratio, normalized time-to-peak, as well as derived useful ICP pulses and cardiac pulses. Alternatively, the paired monitor's inherent software interprets the signal received from the B4C System's sensor and displays a surrogate waveform that allows for viewing the same ICP waveform on the monitor's display. Clinicians review the B4C System outputs to assess patients with suspected intracranial hypertension or changes in intracranial compliance based on the characteristic Percussion (P1), Tidal (P2), and Dicrotic (P3) peaks of the waveform morphology and associated parameters.

The B4C System is not intended to be a standalone diagnostic tool. The surrogate waveform and associated parameter outputs do not replace a comprehensive clinical evaluation, but only provide an element for preliminary assessment. The clinician is responsible for determining the additional clinical information that may be required to make a diagnosis.

The B4C System is intended for use for adult patients ages 18 and older.

Indications for Use: The B4C System is intended for the monitoring of variation in intracranial pressure in patients with suspected alteration of intracranial pressure (ICP) or change in intracranial compliance, by providing surrogate ICP waveforms and associated parameters (estimated P2/P1 ratio, normalized Timeto-Peak, derived useful ICP pulses and cardiac pulses) for interpretation.

Refer to device labeling for more information regarding the derivation and interpretation of the output of the device.

{5}------------------------------------------------

Comparison to Predicate Device

The B4C System is an evolution of the first iteration, BcSs-PICNI-2000 Sensor (K182073). Comparison of technological characteristics between the B4C System to the predicate device, BcSs-PICNI-2000 Sensor is presented in Table 1. The differences compared to the currently marketed device do not affect the intended use and do not raise new questions of safety and effectiveness.

	B4C System	Braincare BcSs-PICNI-2000 Sensor	Substantial Equivalence
510k #	K201989	K182073	Not applicable
Product Code	GWM	GWM	Same
Indication for Use	The B4C System isintended for themonitoring of variationin intracranial pressurein patients withsuspected alteration ofintracranial pressure(ICP) or change inintracranial compliance,by providing surrogateICP waveforms andassociated parameters(estimated P2/P1 ratio,normalized Time-to-Peak, derived useful ICPpulses and cardiac pulse)for interpretation.Refer to device labelingfor more informationregarding the derivationand interpretation of theoutput of the device.	The BcSs-PICNI-2000Sensor is intended for themonitoring of variation inintracranial pressure inpatients with suspectedalteration of intracranialpressure (ICP) or changein brain compliance, byproviding ICP waveformsfor interpretation.	Same intended use.Similar indications for use.Brain compliance is replaced tointracranial compliance forconsistency with medicalterminology. Otherwise, theonly difference in theindications for use is that thesubject device is intended toprovide some associatedparameters about the ICPwaveform characteristics inaddition to the visualizedsurrogate waveform. However,these do not change theintended use, intended user, orclinical utility compared to theoriginally cleared device. Thisdifference does not raise newquestions of safety oreffectiveness.
Prescription Device	Yes	Yes	Same
DeviceDescription	Non-invasive ICPmonitoring deviceconsisting of straingauge pressure sensorssupported on a headbandto detect skulldeformations in responseto ICP changes. Systemwirelessly transmitsacquired signal for	Non-invasive ICPmonitoring deviceconsisting of strain gaugepressure sensors supportedon a headband to detectskull deformations inresponse to ICP changes.System requires a wiredconnection to a compatiblepatient monitor to view	SimilarThe operating principle of thesensor remains the same. This510(k) introducesmodifications primarilyconsisting of softwarecomponents that include:Bluetooth module andfirmware embedded in sensor

		Table 1 Comparison of B4C System to BcSs-PICNI-2000 Sensor
--	--	------------------------------------------------------------	--	--	--

{6}------------------------------------------------

	System outputs surrogate ICP waveform and report of waveform's associated parameters on mobile device application and web portal. ICP waveform may also be viewed on compatible monitor via paired wireless receiver.		transmission, ability to view the surrogate ICP waveform on a mobile device application, wireless transmission of acquired signal to compatible monitor, and reports with associated waveform parameters. Neither the subject nor the predicate devices produce absolute value of ICP, and neither is intended to be used as a standalone diagnostic tool. Performance testing demonstrate that the modified device does not raise new questions of safety and effectiveness.
Clinical Application	Non-invasive application of a sensor on the scalp perpendicularly positioned in the temporoparietal transition, 2 inches (5-6 cm) above the entrance of the external auditory canal on the coronal plane	Non-invasive application of a sensor on the scalp perpendicularly positioned in the temporoparietal transition, 2 inches (5-6 cm) above the entrance of the external auditory canal on the coronal plane	Same
Contraindications	The B4C System is contraindicated for use in patients who have:Undergone decompressive craniectomy or craniotomy; Cranial defects (portion of skull missing); Any other conditions that the health practitioner deems to be unsuitable for use of this device.	The BcSs-PICNI-2000 Sensor is contraindicated for use in patients who have:Undergone decompressive craniectomy or craniotomy; Cranial defects (portion of skull missing); Any other conditions that the health practitioner deems to be unsuitable for use of this device.	Same
Device Materials	Polycarbonate sensor casing and contact pin Silicone base around sensor Polypropylene headband	Polyoxymethylene sensor and headband. Adaptor cable: TPU (thermoplastic polyurethane) and ABS (Acrylonitrile butadiene styrene) case.	DifferentWhile there are differences in specific device materials, the patient contacting surfaces continue to be comprised of materials that are commonly used in medical devices. Both

			devices have satisfiedbiocompatibility testing for thepatient contacting surfaces. Thedifference in materials do notraise new questions in terms ofsafety or effectiveness.
MRI Claim	MR Unsafe	MR Unsafe	Same
Sterilization	Not applicable	Not applicable	Same
Device dimensions	Sensor case: 75.6 X 51.5X 27.7 mmReceiver case: 94 X 17.5X 15 mmReceiver cable andconnector length: 20 cm	Sensor case: 18.7 x 18.5 x66.5 mmSensor pin length: 18mmSensor pin diameter: 7.5mmSensor cable length: 200cm.	The differences in dimensiondo not raise new questions ofsafety or effectiveness.
	Headband size withturnbuckle :XXS: 49.5 cm, XS: 52cm, S: 54.5 cm, M: 57cm, L: 59.5 cm, XL: 52cm, XXL: 64.5 cm	Headband Perimeter:Extra Small: 50-55cm,Small: 52.5-57.5 cm,Medium: 55-60 cm,Large: 57.5-62.5 cm.Adaptor cable length: 180cm.
Biocompatibility	Limited duration contact(≤24) with intact skinNon-cytotoxicNon-sensitizingNon-irritating	Prolonged contact (>24hours but within ≤30 days)with intact skinNon-cytotoxicNon-sensitizingNon-irritating	SimilarThe device continues to beintended only for contact withintact skin. While the predicatedevice was assessed forprolonged contact as aconservative risk managementapproach, it is expected that thedevice will only be applied forlimited duration (≤24 hours) inactual use. Biocompatibilityevaluation demonstrate that thidifference does not raise newquestions of safety andeffectiveness.
Energy modality	Sensor contains internalrechargeable battery andexternal rechargeablebattery pack	5 volts DC whenconnected to ICPmonitoring device	DifferentThe modified device introducesinternal and external batteries,while the predicate device hadpower supplied by theconnected patient monitor.Battery safety, electrical safety,and electromagneticcompatibility testing
ICP WaveformOutputs	Waveform displayed oncompatible patientmonitorAnalytical software alsoproduces the followingassociated parametersabout the surrogate ICPwaveform displayed in areport and on theaccompanying mobilemedical application:• SurrogateWaveform• WaveformTrend line• Averagewaveform• Estimated P2:P1ratio• NormalizedTime-to-Peak• Derived usefulICP pulses• Derived CardiacPulseThese associatedparameters are derivedbased on well-established principles inscientific literature andclinical practice.	Waveform displayed oncompatible patientmonitor	demonstrate that thesetechnological differences donot raise new questions ofsafety and effectiveness.SimilarBoth the subject and predicatedevice produce display of ICPwaveforms in real-time. Themodified device also providesassociated parameters of thesurrogate waveform that maybe viewed in a convenientreport on the accompanyingmobile medical application orweb portal as an alternative to acompatible multiparametermonitor. The surrogatewaveform and associatedparameters continue to beinterpreted by the clinician perstandard clinical practice andwith other clinical evaluationsand parameters as deemednecessary by the clinician.Performance testingdemonstrates that thedifferences in displayedinformation do not raise newquestions of safety andeffectiveness.
Sensing element	Strain gauge	Strain gauge	Same
Functional pressurerange	Not applicable as it doesnot provide absolutevalues of pressure	Not applicable as it doesnot provide absolutevalues of pressure	Same
Functional overpressure rangewithout damage	Not applicable as it doesnot provide absolutevalues of pressure, anddoes not have a specifiedfunctional pressurerange.	Not applicable as it doesnot provide absolutevalues of pressure, anddoes not have a specifiedfunctional pressure range.	Same
Input/ OutputImpedance	The wireless sensor isnot physically connectedto any device and has aninternal resistive bridge	350 ohms nominal	The differences in input/outputimpedance do not raise newquestions of safety oreffectiveness.
	with input and outputimpedance of 1000Ohms.
Output signal(sensitivity)	Not applicable for thewireless sensor since it isnot physically connectedto any device.The receiver can outputa maximum signal of25mV and minimum of -2.5mV.	10mV	The differences do not raisenew questions of safety oreffectiveness.
Zero Drift	Not applicable for thesensor as it does notprovide absolute valuesand brain4care aAppperforms auto scale sothat the waveform isalways visible.The receiver is alsocapable of automaticallyreadjusting the signaloffset level so that thewaveform is alwaysvisible on the monitor.	The Adaptor cable can beused to adjust offset$\pm$ 20mV.	The differences do not raisenew questions of safety oreffectiveness.
Electrical Safety	Complies with IEC60601-1	Complies with IEC60601-1	Same
ElectromagneticCompatibility	Complies with IEC60601-1-2	Complies with IEC60601-1-2	Same
Software	This device modificationintroduces a mobiledevice application,firmware, analytical andprocessing software, andadministrative softwarecomponents.	None	DifferentWhile the predicate did notcontain software, the modifieddevice introduces severalsoftware components.The new software componentsare used to analyze the inputICP sensor data, view, store,and transfer device output.Software verification andvalidation met acceptancecriteria. There is no change tothe intended use of the device.This difference does not raisenew questions in terms ofsafety and effectiveness.
Sensor Connection toMonitor	WirelessBluetooth connection toa receiver or micro-USBconnection specific tocompatible patient	WiredAdaptor Cable withadaptor plug specific tocompatible patientmonitors	DifferentWhile the predicate utilizes awired connection to display theacquired waveform on thecompatible patient monitor, the
	monitors		modified device is able totransmit the signal to thepatient monitor wirelessly via aBluetooth connection andreceiver on the monitor.Performance testingdemonstrate that this differencedoes not raise new questions ofsafety and effectiveness.
Wireless Module	Bluetooth	None	DifferentThe modified device introducesa Bluetooth module to facilitatewireless transmission of theacquired ICP waveform signalto a mobile device and receiverto display the waveform on aconnected monitor, and to viewthe waveform and relatedparameters on a mobile device.Addition of wireless capabilitydoes not change the intendeduse, intended user, or intendeduse environment compared tothe predicate. Performance datademonstrate that thesetechnological differences donot raise new questions ofsafety and effectiveness.

{7}------------------------------------------------

{8}------------------------------------------------

{9}------------------------------------------------

{10}------------------------------------------------

Differences from Predicate

Compared to the predicate device, the B4C System converts the analog signal to a digital signal, transfers the acquired signal wirelessly over Bluetooth and HTTPs connection rather than a cable, operates by battery, processes and analyzes the acquired signal to produce the surrogate ICP waveform and associated parameters, and allows the user to view the waveform on either a compatible patient monitor or a mobile application and the associated waveform parameters on either the mobile application or web portal. There are also some minor technological differences with respect to materials and dimensions. Despite these differences, the subject and predicate device share common intended use, sensor technology, operating principle, and clinical utility, and demonstrate comparable device performance.

Discussion of Performance Data

The following performance data in Table 2 are provided in support of the substantial equivalence determination between the proposed device, B4C System, and predicate device, BcSs-PICNI-2000 Sensor

{11}------------------------------------------------

(K182073).

TEST	TITLE/TEST METHOD SUMMARY	RESULTS
Biocompatibility
ISO 10993-5	Biological evaluation of medical devices - Part 5:Tests for in vitro cytotoxicity	PassNon-cytotoxic
ISO 10993-10	Biological evaluation of medical devices - Part 10:Tests for irritation and skin sensitization	PassNon-sensitizingNon-irritating
Electrical Safety and Electromagnetic Compatibility
IEC 60601-1	Medical electrical equipment - Part 1: Generalrequirements for basic safety and essentialperformance	Pass
ANSI AAMI ES60601-1	Medical electrical equipment - Part 1: Generalrequirements for basic safety and essentialperformance	Pass
IEC 60601-1-2	Medical electrical equipment - Part 1-2: Generalrequirements for basic safety and essentialperformance - Collateral	Pass
AAMI TIR69	Risk management of radio-frequency wirelesscoexistence for medical devices and systems	Testing not requiredbased on riskassessment
Disinfection
DisinfectionValidation	Validation of Low-Level disinfection method using70% ethanol.	Pass>6-log microbialreduction
Bench Testing
Monitor Compatibility	Demonstration of compatibility for use with patientmonitors.	Pass
Stability andReproducibility	Demonstration of stability, repeatability, andreproducibility between the ICP waveform outputs ofthe wireless and wired sensors.	Pass
Software
Software Verificationand Validation	Demonstrate that all software requirements wereappropriately implemented in the software.	Pass

Table 2 Summary of Non-Clinical Performance Data

Performance test results demonstrate that the subject device and predicate device, BcSs-PICNI-2000 Sensor (K182073), are substantially equivalent with respect to biocompatibility, electrical safety, electromagnetic compatibility, disinfection, monitor compatibility, and reproducibility for their shared intended use in monitoring of suspected variation in ICP and brain compliance.

Discussion of Clinical Testing

Braincare conducted a combined prospective, multi-center, observational study to assess the comparison of the acquired ICP waveform signal and parameters between the B4C System and standard of care invasive ICP monitoring methods. The study device consisted of the B4C processing and analytical software used with the wired sensor (K182073). Although the wired sensor was used in the

{12}------------------------------------------------

study, the results reflect the performance of the B4C System.

Dataset Description

Total number of centers: 4 ●
Total number of subjects: 123 enrolled, 107 after device label check, 85 after data quality check ● (78 adults, 7 pediatric)
Collected data: ICP Surrogate Waveform (BcSs-PICNI-2000 (K182073) or B4C System); ● Invasive Arterial Blood Pressure, Invasive ICP Waveform (EVD or Bolt)
Range of acquisition sessions time: 5 min to 3.5 hours
Total number of monitoring sessions that passed quality check: 159 ●
Total acquisition time that passed quality check: 4800 (98% adult, 2% pediatric)

Analyzed participants

Seventy eight adults (18+) who met all eligibility criteria and were admitted to the neurointensive care unit and underwent invasive ICP monitoring and invasive arterial blood pressure monitoring were considered in the dataset. Due to the reduced quantity of pediatric subjects, the analysis could only demonstrate statistically relevant performance for the adult population.

Total number of analyzed subjects: 78 adults ●
Total acquisition time analyzed: 4695 minutes
Age of analyzed subjects: 52.7±19.4 ●
Gender of analyzed subjects: 47% female ; 53% male ●

Study Objective

The goal of the analysis was to verify whether the new medical device developed by Braincare demonstrated a consistent correlation between its recorded waveform with the invasive devices waveform that are currently used in clinical practice. The objective was to evaluate the reliability and accuracy of the correlation between the Braincare device in monitoring ICP waveform in comparison to gold standard invasive ICP monitoring methods such as the external ventricular drain or intraparenchymal micro transducers that are currently used in clinical practice, and utilized in the target population in different centers and medical settings.

Study Procedures

All centers used Braincare's non-invasive sensors with identical principles of operations (3 centers are with BcSs-PICNI-2000 sensor (K182073), 1 with B4C System wireless sensor). The sensors at each site were positioned according to the same protocols, i.e., temporal region avoiding arteries and adjustment to the point that an acceptable waveform appears, a procedure that represents real case usage. Patients at all sites had invasive, non invasive and ABP waveforms captured.

Study Outcomes

{13}------------------------------------------------

The primary objective was to compare the ICP curve morphology obtained with the Braincare and invasive ICP sensors, with focus on the characteristics of peaks P1, P2, P3 amplitudes and their ratios, among other characteristics of the ICP pulse waveform including lags between wave peaks (time to peak) and the absolute curvature of the peaks to determine relative changes and trends over time in ICP and brain compliance.

The analysis aimed evaluate the reliability and accuracy of the Braincare device in assessing ICP waveform in comparison to gold standard invasive ICP monitoring methods such as the external ventricular drain or intraparenchymal micro transducers as well as the ability to monitor relative changes in ICP as well as trends over time. The study hypothesis was that the ICP pulse morphology (waveform) detected by the Braincare noninvasive device presented a statistically significant correlation with the ICP pulse morphology (waveform) detected by the gold standard invasive method(s).

Bland-Altman plots and Deming regression analyses were used to quantify agreement between the invasive ICP waveform and Braincare surrogate ICP waveform parameters - estimated P2/P1 ratio and normalized time to peak (TTP), estimating the differences between the respective averages per minute. Additionally, spearman and normalized mutual information methods were utilized to assess non-linear behavior between waveforms. Considering the differences in positioning of the invasive and non-invasive sensors (inside the ventricle compared to outside the skull), strong agreement between the signals was not expected. Nevertheless, a relatively large region of agreement and presented correlation between the parameters was observed and demonstrated statistical significance confirmed by additional statistical tests.

Correlation analysis: ●
Spearman correlation and normalized mutual information were used to assess statistical dependence on the ICP waveform parameters between the Braincare sensor and invasive sensor. For the normalized time to peak, the Spearman correlation was 0.318 [0.291, 0.345], p<.0001. The statistical dependence between parameters - estimated using normalized mutual information - was 0.612 [0.564, 0.643]. For the estimated P2/P1 ratio, the Spearman correlation was 0.495 [0.471, 0.517], p<.0001. The statistical dependence between parameters - estimated using normalized mutual information - was 0.561 [0.531.0.606]. The joint distributions between ICP and B4C parameters showed statistical dependence between them, thus confirming the statistically significant correlation between the ICP pulse morphology (waveform) detected by the gold standard invasive method(s) and the B4C technology with regard to the P2/P1 ratio and Time to Peak.
Agreement analysis: ●
Bland-Altman plots and Deming regression models were used to quantify agreement between the invasive and Braincare measured ICP waveform parameters - estimated P2/P1 ratio and normalized time to peak, estimating the differences between the respective averages per minute. Considering the differences in positioning of the invasive and non-invasive sensors (inside the ventricle compared to outside the skull), strong agreement between the signals was not expected. Nevertheless, a relatively large region of agreement between the parameters was observed and demonstrate statistical significance confirmed by additional statistical tests. The Bland-Altman limits of agreement for the estimated P2/P1 ratio range from

{14}------------------------------------------------

-0.723 to 0.761 (mean distance/bias 0.019: 95% CI: -0.060, 0.101). The limits of agreement for the normalized Time to Peak range from -0.183 to 0.245 (mean distance/bias 0.031; 95% CI: 0.011, 0.050). The Deming regression estimates and 95% confidence intervals for P2/P1 ratio were Y = - 0.67 [-1.85, 0.02] + 1.60 [0.97, 2.69]X, and estimates and 95% confidence intervals for Time to Peak were Y = 0.00 [-0.11, 0.09] + 0.84 [0.38, 1.39]X. As can be seen when looking at the mean/bias and limits of agreement in the Bland-Altman results above, our device tends to generate larger observations for Time to Peak than invasive ICP. There are some observed instances where the Time to Peak measured by the device differed from that measured by invasive ICP by >0.2. Additionally, while the mean difference in P2/P1 between our device and invasive ICP is not significantly different from zero, we observed instances where P2/P1 measured by the device differed from that measured by invasive ICP by >0.7.

Both classes of analysis, Bland-Altman / Deming Regression which evaluate agreement, and Normalized Mutual Information / Spearman which evaluate correlation presented statistically meaningful results.

Safety

No adverse events were reported.

Study Conclusion

Results of this study demonstrated a statistically significant correlation in the ICP signal and waveform parameters between the B4C System and the gold standard invasive ICP monitoring device measured over time. The study outcomes demonstrate comparable effectiveness between the Braincare device and commonly used invasive ICP devices for use in monitoring and assessing variations in ICP waveform associated parameters over time.

Conclusion

Based on the results of the performance testing and substantial equivalence comparison, the B4C System has the same intended use as the predicate device. The presented information is sufficient to determine that the B4C System is substantially equivalent to the legally marketed predicate device.

Regulation Number and Section

§ 882.1620 Intracranial pressure monitoring device.

(a)
Identification. An intracranial pressure monitoring device is a device used for short-term monitoring and recording of intracranial pressures and pressure trends. The device includes the transducer, monitor, and interconnecting hardware.(b)
Classification. Class II (performance standards).