The BcSs-PICNI-2000 Sensor is intended for the monitoring of variation in intracranial pressure in patients with suspected alteration of intracranial pressure (ICP) or change in brain compliance, by providing ICP waveforms for interpretation.

Device Description

The BcSs-PICNI-2000 Sensor ("the Braincare Sensor") 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 brain compliance. It consists of a sensor, headband, and adapter cable. 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. The proposed device does not measure absolute intracranial pressure values, but produces waveform morphology and its trend reflecting changes in ICP. The BcSs-PICNI-2000 Sensor and waveform output do not substitute ICP monitoring methods when measurement of the absolute value of ICP is required to make a clinical decision.

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 signals through an adapter cable to a compatible multi-parameter monitor that has piezoresistive pressure transducer sensitivities of 5uV/Vex/mmHg or greater and automatic amplitude window adjustment capability. The multi-parameter monitor's inherent software interprets the signal received from the BcSs-PICNI-2000 Sensor and displays a waveform that allows for assessment of suspected intracranial hypertension or changes in brain compliance based on the characteristic Percussion (P1), Tidal (P2), and Dicrotic (P3) peaks of the ICP waveform morphology.

The BcSs-PICNI-2000 Sensor is not intended to be a standalone diagnostic tool. The waveform output does not replace a comprehensive clinical evaluation, but only provides an element for preliminary assessment. The clinician is responsible for determining the additional clinical information that may be required to make a diagnosis.

AI/ML Overview

Here's an analysis of the acceptance criteria and the studies performed for the BcSs-PICNI-2000 Sensor, based on the provided document:

Acceptance Criteria and Device Performance

The document doesn't explicitly state a table of "acceptance criteria" with specific thresholds for performance metrics. Instead, it details various tests and their "Pass" or "Results" that demonstrate the device meets expected performance and safety standards, largely by showing substantial equivalence or demonstrating proper functioning. The "Results" column in the table below is derived from the Table 3 Summary of Non-Clinical Performance Data and the Study Outcomes sections of the clinical studies.

Test / Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance
Biocompatibility
In vitro cytotoxicity	Non-cytotoxic	Pass: Non-cytotoxic
Irritation & skin sensitization	Non-sensitizing, Non-irritating	Pass: Non-sensitizing, Non-irritating
Electrical Safety & EMC
IEC 60601-1	Compliance with standard	Pass
IEC 60601-1-2	Compliance with standard	Pass
Disinfection
Low-Level disinfection method (70% ethanol)	6-log microbial reduction	Pass: 6-log microbial reduction
Bench Testing
Monitor Compatibility	Compatible with patient monitors	Pass
Stability and Reproducibility (waveform)	Stable and reproducible waveform characteristics	Excellent stability, some variance in reproducibility.
Animal Studies
Rat Model (iICP vs. nICP correlation)	Positive correlation (r > 0)	Pearson's correlation coefficient r = 0.8 ± 0.2 (positive correlation)
Swine Model (iICP vs. nICP correlation)	Positive correlation (r > 0)	Spearman's correlation coefficient r = 0.81 ± 0.24 (positive correlation)
Clinical Studies (Observational)
HIV-associated Cryptococcal Meningitis (waveform changes consistent with clinical status)	Waveform morphology indicative of clinical status and response to treatment	Waveforms showed P2>P1 with neurological symptoms, P1<P2 after LP, and P1>P2>P3 resembling normal brain compliance post-treatment; consistent with clinical status.
Traumatic Brain Injury (iICP vs. nICP similarity)	Greater similarity between iICP-nICP than nICP-ABP (statistically significant)	Difference between iICP-nICP and nICP-ABP statistically significant for all 7 patients (p<0.05). Greater similarity between subject and predicate device waveforms than between subject device and ABP.

Study Details

2. Sample sizes and Data Provenance

Animal Studies:
- Rat Model: 7 rats. Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but implied to be prospective due to controlled experimental setup.
- Swine Model: 1 swine animal model. Data provenance not explicitly stated, implied to be prospective.
Clinical Studies:
- HIV-associated Cryptococcal Meningitis: 1 critically ill adult patient. Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but implied to be prospective as it's an "early study" evaluating the device.
- Traumatic Brain Injury: 7 adult patients. Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but implied to be prospective for validation. Total acquisition time of 608 hours (337 hours analyzed).

3. Number of experts used to establish the ground truth for the test set and their qualifications

The document implies that the "predicate device" (Codman® Microsensor Basic Kit) served as the primary reference or "ground truth" for comparison in the animal and TBI clinical studies, as it represents the "standard of care" for invasive ICP monitoring.
For the HIV-associated Cryptococcal Meningitis study, the "patient's clinical status" and response to treatment, likely determined by treating clinicians, served as the ground truth against which the non-invasive ICP waveforms were assessed.
No specific number of experts or their qualifications for establishing ground truth are explicitly stated beyond the use of the invasive predicate device and general clinical judgment.

4. Adjudication method

There is no explicit mention of an adjudication method (like 2+1, 3+1, or none) for establishing ground truth in any of the studies. The comparisons are largely quantitative against the invasive predicate or qualitative against clinical observations.

5. 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 MRMC comparative effectiveness study was done. The device does not involve AI assistance for human readers; it provides waveform data for direct clinician interpretation, similar to the predicate device. The focus is on the device's ability to provide comparable waveform information.

6. If a standalone (i.e. algorithm only without human-in-the loop performance) was done

Given that the device's output is "waveform morphology and its trend reflecting changes in ICP" for "qualitative evaluation by the clinician" and "does not substitute ICP monitoring methods when measurement of the absolute value of ICP is required," the device is inherently not a standalone diagnostic tool. Its performance is validated in providing signals consistent with clinical status, with the expectation that a human clinician will interpret these waveforms in conjunction with other clinical parameters. Therefore, a standalone algorithm-only performance study, as typically understood for diagnostic AI, was not performed or applicable in this context.

7. The type of ground truth used

Animal Studies & Traumatic Brain Injury Clinical Study: Invasive intracranial pressure (iICP) measurements obtained from the predicate device (Codman® Microsensor Basic Kit) served as the de facto ground truth against which the non-invasive ICP (nICP) signals from the BcSs-PICNI-2000 Sensor were compared. This is a form of reference standard comparison.
HIV-associated Cryptococcal Meningitis Clinical Study: The "patient's clinical status" and response to "standard treatment," likely assessed by treating physicians and based on neurological symptoms and other clinical parameters, served as the ground truth. This can be categorized as a form of clinical outcome/expert consensus.

8. The sample size for the training set

The document does not mention a training set or a machine learning component for the BcSs-PICNI-2000 Sensor itself. The device functions based on strain gauge sensors and mechanical principles, not through a learned algorithm or AI model that requires a discrete training set. The studies described are validation and performance testing, not model training.

9. How the ground truth for the training set was established

As no training set is mentioned or implied for an AI/ML algorithm within the device, this question is not applicable.

Summary

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Braincare desenvolvimento e Inovacao Tecnologica S.A. % Ms. Connie Oiu Regulatory Consultant M Squared Associates, Inc. 575 8th Ave, Suite 1212 New York, New York 10018

Re: K182073

Trade/Device Name: BcSs-PICNI-2000 Sensor Regulation Number: 21 CFR 882.1620 Regulation Name: Intracranial Pressure Monitoring Device Regulatory Class: Class II Product Code: GWM Dated: September 16, 2019 Received: September 17, 2019

Dear Ms. 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 requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for

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devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device (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.

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

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Indications for Use

510(k) Number (if known) K182073

Device Name BcSs-PICNI-2000 Sensor

Indications for Use (Describe)

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

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510(k) Summary

BcSs-PICNI-2000 Sensor

Sponsor: Braincare desenvolvimento e Inovacao Tecnologica S.A. Rua Cid Silva Cesar, 600 sala 6 Parque Jardim Santa Felicia Sao Carlos, 13562-400 Brazil
Contact: Connie Qiu M Squared Associates, Inc. 575 8Th Ave., Suite 1212 New York, New York 10018 Ph. 703-562-9800 Fax. 703-562-9797

Date Prepared:	September 16, 2019
Proprietary Name:	BcSs-PICNI-2000 Sensor
Common Name:	Intracranial pressure monitoring device
Regulatory Class:	II
Regulation:	882.1620
Product Code:	GWM
Predicate Device:	Codman® Microsensor Basic Kit K153347
Reference Device:	BrainPulse, Model 1100 DEN140040

Device Description

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Intended Use: The BcSs-PICNI-2000 Sensor is intended for the monitoring of variation in intracranial pressure in patients with suspected alteration of intracranial pressure (ICP) or change in brain compliance, by providing ICP waveforms for interpretation.

Comparison to Predicate Device

Comparison of technological characteristics between the BcSs-PICNI-2000 Sensor to the predicate device, Codman® Microsensor Basic Kit (K153347), is presented in Table 1. The differences between the two devices do not affect the intended use, and do not raise new questions of safety and effectiveness.

	Braincare BcSs-PICNI-2000 Sensor	CodmanMicrosensor BasicKit Refs. 62-6631	Substantial Equivalence
510k #	K182073	K153347	Not applicable
Product Code	GWM	GWM	All devices are IntracranialPressure Monitoringdevices.
Indication for Use	The BcSs-PICNI-2000Sensor is intended for themonitoring of variation in	Use of theCODMANMICROSENSOR	Both the BcSs-PICNI-2000Sensor and the Codman ®

			Table 1 Comparison of BcSs-PICNI-2000 Sensor to Codman® Microsensor Basic Kit


Prescription device	Yes	Yes	Both devices are intendedfor prescription use only.
Device Description	Non-invasive ICPmonitoring deviceconsisting of strain gaugepressure sensorssupported on a headbandto detect skulldeformations in responseto ICP changes.	ICP Transducerconsist of aminiature straingauge pressuresensor mounted in atitanium case at thetip of a 100cm 3french flexiblenylon tube.	Both devices utilize straingauge sensors and are usedin real-time ICPmonitoring.
ClinicalApplication	Non-invasive applicationof a sensor on the scalpperpendicularlypositioned in thetemporoparietaltransition, 2 inches (5-6cm) above the entrance ofthe external auditorycanal on the coronal plane	Subdural andintraparenchymalimplantation.	Braincare Sensor is appliednon-invasively, while theCodman® Microsensorrequires subdural andintraparenchymalimplantation. Both devicesshare the same intendeduse, and have satisfiedbiocompatibility andperformance testing. Thepotential differences forpatient application isrestricted to the non-invasiveness nature of theBcSs-PICNI-2000 Sensor,which is similar to theReference Device;therefore it does not raisenew questions in terms ofsafety and effectiveness.
Contraindications	The BcSs-PICNI-2000Sensor is contraindicatedfor use in patients whohave:•Undergonedecompressivecraniectomy orcraniotomy;	This kit is notdesigned, sold orintended for any useexcept as indicated.This kit is notdesigned, sold orintended for use as atherapeutic device.	Both the subject andpredicate devices aredesigned and intended onlyfor the use as indicated.The Braincare devicecarries additionalcontraindications specificto its use as a non-invasiveICP monitoring device.
Cranial defects (portion of skull missing); Any other conditions that the health practitioner deems to be unsuitable for use of this device.	However, these additional contraindications do not introduce new risks compared to the predicate device. The difference in contraindications do not raise new questions in terms of safety and effectiveness.
Device Materials	Polyoxymethylene sensor and headband. Adapter cable: TPU (thermoplastic polyurethane) and ABS (Acrylonitrile butadiene styrene) case.	PCB in plastic connector housing, solder wire, resistor in plastic housing, epoxy glue Silicone Catheter strain relief Ti case Silicone membrane	The Braincare Sensor and Codman® Microsensor devices are comprised of different patient contacting materials. Both devices have satisfied biocompatibility testing. The difference in materials do not raise new questions in terms of safety or effectiveness.
MRI Claim	MR Unsafe	1.5T and 3T Conditional	Braincare sensor is MR Unsafe. The difference in MR compatibility does not raise new questions in terms of safety and effectiveness.
Sterilization	Not applicable	Ethylene Oxide	Not applicable as the Braincare Sensor is a non-invasive device and is not provided sterile. The subject device contacts intact skin, and is to be disinfected between use with standard Ethanol 70%. Disinfection method of the Braincare device has been validated and does not raise new questions in terms of safety and effectiveness.
Shelf Life	Not applicable	2 years
Device dimensions	Sensor case: 18,7 x 18,5 x 66,5 mmSensor pin length: 18mmSensor pin diameter: 7.5 mm	Microsensor:Length: 100cm nominalTip diameter: 1.3mm max	The Braincare Sensor and Codman® Microsensor have different dimensions due to the nature of the patient application and
	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.	Catheter length(ventricular kit):38cmnominalCatheter diameter(ventricular kit):3.5mmmax	differences in dimension donot raise new questions ofsafety or effectiveness.
Biocompatibility	Prolonged contact (>24days but within ≤30 days)Non-cytotoxicNon-sensitizingNon-irritating	Prolonged contact(>24 days butwithin ≤30 days)Non-cytotoxicNon-sensitizingNon-irritating	Both the Braincare Sensorand Codman® Microsensorare categorized asprolonged contact (>24days but within ≤30 days).Both devices weredemonstrated to be non-cytotoxic, non-sensitizing,and non-irritating.
Energy modality	5 volts DC whenconnected to ICPmonitoring device	5 volts DC whenconnected to ICPmonitoring device	Both the Braincare Sensorand Codman® Microsensorshare the same energymodality.
Pressure outputdisplay parameters	Waveform	Millimeters ofMercury (mmHg)Waveform	The Braincare Sensor doesnot provide direct pressuremeasurement, as opposedto the Codman®Microsensor. However,both devices use straingauge sensors and generatewaveform outputs inresponse to mechanicalwaves generated by bloodflow in the brain. Animaland clinical study data haveshown similarities in theoutputs of both devices inreal-time ICP monitoring.The difference in pressureoutput display parametersdoes not raise newquestions in terms of safetyand effectiveness.
Sensing element	Strain gauge	Strain gauge siliconmicrochip	Both devices utilize a straingauge in the sensingelement.
Functional pressurerange	Not applicable, does notmeasure absolute valuesof pressure.	-50 mmHg to 250mmHg	The Braincare Sensor doesnot have a limit infunctional pressure range.Comparable performance tothe predicate device has
Functional overpressure rangewithout damage	Not applicable, does notprovide absolute values ofpressure, and does nothave a specifiedfunctional pressure range.	-700 mmHg to 1250mmHg	been demonstrated inanimal and clinical studies.This difference does notraise new questions interms of safety andeffectiveness.The Braincare Sensor doesnot have a limit infunctional pressure range.Comparable performance tothe predicate device hasbeen demonstrated inanimal and clinical studies.This difference does notraise new questions interms of safety andeffectiveness.
Input/ OutputImpedance	350 ohms nominal	1000 ohms nominal	The Braincare Sensor andCodman® Microsensordiffer in input/outputimpedance based on thedifferences in the devices'operating principles inmonitoring ICP and theirtechnical build. Bothdevices are designed tomeet acceptable safety andeffectiveness parameters,and present similar ICPmorphology (waveforms)information on theconnected patient monitor.Comparable performance tothe predicate device hasbeen demonstrated inanimal and clinical studies.This difference does notraise new questions interms of safety oreffectiveness.
Output signal(sensitivity)	10 mV	7.5 mV absolutevoltage span(Calculated basedon Microsensordevice's functionalpressure range of -50 to 250 mmHg,5V when connectedto ICP monitor, andoutput signal	The two devices differ insensitivity due todifferences in theirprinciple of operation ofmonitoring changes in ICP.Both devices arecompatible for use withcommercially availablepatient monitoring devices.Comparable performance tothe predicate device has
		sensitivity 5 uV/V/mmHg)	been demonstrated in animal and clinical studies. This difference does not raise new questions in terms of safety or effectiveness.
Zero Drift	The Adapter cable can be used to adjust offset ±20 mV.	No greater than 5 mmHg over 30 days	The Braincare Sensor generates output in mV and the signal is interpreted by the user in the form of waveform morphology, while the Codman® Microsensor directly measures and provides absolute ICP values in mmHg. Offset functionality for both devices have been defined based on their respective principle of operation. Comparable performance to the predicate device has been demonstrated in animal and clinical studies. This difference does not raise new questions in terms of safety and effectiveness.
Electrical Safety	Complies with IEC 60601-1	Not Known	Predicate device 510(k) summary does not provide electrical safety information for comparison.
Electromagnetic Compatibility	Complies with IEC 60601-1-2	Not Known	Predicate device 510(k) summary does not provide EMC information for comparison.

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Differences from Predicate:

The BcSs-PICNI-2000 Sensor has minor technological differences from the predicate. The subject device is applied over the scalp to non-invasively capture a signal that is processed to generate a waveform output for qualitative evaluation by the clinician. However, there are other neurological devices that include similar technological characteristics.

The following table provides a comparison of the technological characteristics between the BcSs-PICNI-

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2000 Sensor and Reference Device BrainPulse (DEN140040).

	Braincare BcSs-PICNI-2000 Sensor	Reference Device:BrainPulse(DEN140040)	Remarks
Clinical Application	Non-invasiveapplication to scalp	Non-invasiveapplication to scalp	Same as ReferenceDevice
Sensor operatingprinciple	Strain gauge sensordetects skulldeformation resultingfrom ICP changes	Accelerometer detectsskull motion	Similar to ReferenceDevice
Device output	Signal is processed todisplay waveform forqualitative assessment	Signal is processed todisplay waveform forqualitative assessment	Similar to ReferenceDevice

Table 2 Technological Comparison to Reference Device

Discussion of Performance Data

The following performance data in Table 3 are provided in support of the substantial equivalence determination between the proposed device, BcSs-PICNI-2000 Sensor, and predicate device, Codman® Microsensor Basic Kit (K153347).

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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 60601-1ANSI AAMI ES 60601-1	Medical electrical equipment - Part 1:General requirements for basic safety and essential performance	Pass
IEC 60601-1-2	Medical electrical equipment - Part 1-2:General requirements for basic safety and essential performance - Collateral	Pass
Disinfection
DisinfectionValidation	Validation of Low-Level disinfection method using 70% ethanol.	Pass6-log microbial reduction
Bench Testing
MonitorCompatibility	Demonstration of compatibility for use with patient monitors.	Pass
Stability andReproducibility	Demonstration of stability of device output waveform for a patient throughout a single monitoring session, and reproducibility across multiple monitoring sessions including reapplication of device by different practitioners.	Determined estimated range of variability in waveform characteristics with respect to stability and reproducibility. Results indicate excellent stability and some variance in reproducibility.
Animal Studies
DirectComparisonStudy in RatAnimal Model	Simultaneous intracranial pressure monitoring with the proposed device and predicate device were applied to 7 rats that received saline injected into the spinal channel to produce dynamic ICP changes. The objective was to measure the linear correlation between the two ICP monitoring devices' outputs.	Pearson's correlation coefficient $r = 0.8\pm0.2$ indicates a positive correlation between the ICP monitoring outputs of the proposed and predicate devices.
DirectComparisonStudy in SwineAnimal Model	Simultaneous intracranial pressure monitoring with the proposed device and predicate device were applied to a swine animal model that underwent saline injected into the spinal channel to produce dynamic ICP changes. The objective was to measure the monotonic correlation between the two ICP monitoring devices' outputs	Spearman's correlation coefficient $r= 0.81 \pm 0.24$ indicates positive correlation between the ICP monitoring outputs of the proposed and predicate devices.

Table 3 Summary of Non-Clinical Performance Data

Performance test results demonstrate that the BcSs-PICNI-2000 Sensor and predicate device, Codman® Microsensor Basic Kit (K153347), are substantially equivalent with respect to biocompatibility, and

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intended use in continuous intracranial pressure monitoring in two comparative animal studies. Additional non-clinical testing verified device performance characteristics that differed from the predicate.

Discussion of Clinical Testing

Braincare conducted two clinical studies during validation of the BcSs-PICNI-2000 Sensor. An overview of each study is provided below:

Non-Invasive ICP Monitoring for HIV-associated Cryptococcal Meningitis

Participants

A critically ill adult patient diagnosed with human immunodeficiency virus-associated cryptococcal meningitis underwent real-time ICP monitoring.

Dataset Description

Four non-invasive ICP monitoring sessions were conducted at defined time points before and after treatment to yield four ICP curves for assessment.

Study Objective

The goal of this early study was to evaluate the ability of the BcSs-PICNI-2000 Sensor to non-invasively monitor changes in ICP for a patient with suspected intracranial hypertension such that morphological changes are consistent with the patient's clinical status.

Study Procedures

The patient underwent standard treatment for cryptococcal meningitis over thirty-four (34) days. During this period, non-invasive ICP monitoring was performed on Day 12 and Day 34 prior to and following a programmed lumbar puncture procedure. Monitoring produced ICP waveforms at 4 timepoints. Waveform morphology of the ICP curves at these time points was visually assessed with other recorded clinical parameters to determine whether the waveforms were indicative of the clinical status of the patient.

Study Outcomes

The pulsatile waveform from ICP monitoring on Day 12 before lumbar puncture revealed P2>P1, amplitude of tidal wave greater than that of percussion wave, reflecting characteristics of relative peak height consistent with the presence of neurological symptoms. P1<P2 after lumbar puncture, demonstrating improvement towards the characteristic P1>P2>P3, where P3 is dicrotic wave, as expected with reduction in ICP post-treatment. Morphology of the waveforms obtained from Day 34 were more closely representing

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normal brain compliance (P1>P2>P3), which is consistent with reduction in ICP following the series of treatment and discharge that same day.

Study Conclusions

Results of this study demonstrated that the BcSs-PICNI-2000 Sensor is able to continuously monitor ICP changes to acquire signals consistent with the patient's clinical status.

Analysis of a Non-Invasive ICP Monitoring Method in Patients with Traumatic Brain Injury

Participants

Seven adult patients who were admitted to the neurointensive care unit and presented with severe or moderate brain injury with secondary neurological deterioration intubation and mechanical ventilation were enrolled in the study.

Dataset Description

Total number of subjects: 7 patients

Range of acquisition time: 68-282 hours

Total acquisition time: 608 hours

Total acquisition time analyzed: 337 hours

Collected data: Simultaneous and continuous recordings of invasive ICP (iICP), noninvasive intracranial pressure (nICP), arterial blood pressure (ABP).

Study Objective

The objective of the study was to verify the similarities between the iICP (predicate device) and nICP waveforms. This assessment sought to provide evidence for the noninvasive sensor as an alternative to invasive ICP assessments in situations where the waveform can provide supplementary clinical information. In addition, the noninvasive intracranial pressure and arterial blood pressure (ABP) waveforms were compared to verify the possible influence of the extracranial peripheral circulation into the noninvasive intracranial pressure signal, acknowledged as a potential limitation of the Braincare BcSs-PICNI-2000 sensor.

Study Procedures

Each patient underwent continuous ICP monitoring using both the predicate and subject devices concurrently from point of admittance throughout their stay in the neurointensive care unit, with acquisition time ranging from 68-282 hours. ABP measurement directly through the radial artery and partial pressure

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of carbon dioxide (PaCO2) were also recorded simultaneously during the monitoring sessions. Approximately 337 total hours of recordings were analyzed.

Study Outcomes

The primary endpoint was the comparison of ICP waveform morphology obtained with the nICP and iICP sensors. A secondary endpoint was the comparison of the nICP waveforms. Waveforms were compared in a lower dimensional space constructed based on signals in the frequency domain. Similarity between the two devices' signals was inferred from the Euclidean distance between the non-linear projection in a lower dimensional space of the window power spectral densities (PSD) of the respective signals, in which PSD was calculated using the short-term Fourier transform. Intraindividual statistical comparisons were performed using the non-parametric Mann-Whitney U test for not normally distributed data points with a significance level set at p<0.05. Measurement of similarities are presented in the following table.

Patient ID
Similarities	1	2	3	4	5	6	7
iICP-niICP	35.0	27.2	26.9	16.9	36.3	54.7	30.3
ABP-nICP	117.3	86.6	86.9	77.9	78.1	106.6	76.3

Table 4 - Measure of similarities between i-ICP, nICP and ABP

The difference between the iICP-nICP and nICP-ABP was found to be statistically significant for all seven patients, p<0.05, using the Mann-Whitney U test.

Study Conclusions

The study results demonstrate that a greater similarity exists between the waveforms generated from the signals of the subject and predicate device, than between the subject device and ABP measurements. Although the study had a limited sample size, the intra-individual similarities of the invasive and noninvasive ICP signals as functions of time suggest comparable effectiveness of ICP monitoring between the Braincare Sensor and the invasive Codman Microsensor ICP (K153347), which is representative of the standard of care. Additionally, no adverse events related to use of the Braincare sensor were reported,

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supporting that the noninvasive device does not raise new questions of safety.

Benefit Risk Assessment

The main technological differences between the BcSs-PICNI-2000 Sensor and predicate device, Codman® Microsensor Basic Kit (K153347), are that the subject device noninvasively monitors ICP variation without measuring absolute ICP and outputs only the ICP waveform for qualitative review by the clinician. As such, the subject device presents reduced benefit by not offering the ICP value in addition to the waveform, but offers the clinician a method to initially assess patients with suspected variation in ICP or brain compliance to then determine the additional clinical assessments and parameters necessary to make an informed decision. Clinicians continue to use compatible patient monitors to view the ICP waveform and interpret and utilize the waveform in the same manner whether it is captured with the subject or predicate devices.

The subject device design and noninvasive application present reduced risk compared to the predicate by eliminating some known serious risks associated with invasive ICP monitoring devices such as infection, vascular complications, tissue lesions, device occlusion, and device migration. Accordingly, the device may be suitable for use to monitor some patients for whom benefits of monitoring with the predicate device, or similar invasive ICP monitoring devices, do not outweigh the potential risks.

The magnitude of benefits offered by the subject device is high. Foreseable potential risks are of low severity with high detectability, temporary duration in nature, and low uncertainty. Non-clinical testing data showed that the device satisfied all performance criteria to support its intended use and context including electrical safety, electromagnetic compatibility, monitor compatibility, stability and reproducibility of the device output, and effective mitigation of risks to acceptable levels. Animal and clinical studies directly compared performance of the subject device to the predicate, demonstrating that both devices effectively provide continuous waveform morphology consistent with the patient's clinical state, and revealed no occurrence of adverse events when using the subject device. As is true with utilization of the predicate device's output, the clinician is expected to have appropriate knowledge to assess the suitability of the output and to review the waveform together with other clinical parameters to make decisions. The sponsor thus concluded that the benefits of the subject device outweigh the potential risks and that the device is at least as safe and effective as the predicate device when used to monitor variation in ICP by providing waveforms for clinician interpretation.

Conclusion

In summary, the BcSs-PICNI-2000 Sensor and predicate device, Codman® Microsensor Basic Kit

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(K153347), are substantially equivalent with respect to intended use, biocompatibility, and performance. Non-clinical and clinical testing results support that the subject device and predicate device are equivalent in function for use in continuous intracranial pressure monitoring to produce waveform morphology reflective of alteration in ICP and changes in brain compliance. The differences between the two devices do not raise new questions regarding safety and effectiveness.

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).