The BISTM Advance Monitoring System is intended for monitoring the state of the brain by data acquisition of EEG signals under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The BISTM Advance Monitoring System, and all its associated parameters, is intended for use on adults and pediatric patients (4 years old and above) within a hospital or medical facility.

For Adult patients, the BIS™ Index, one of the BIS™ Advance Monitoring System's output parameters, may be used to guide anesthetic administration of desflurane, propofol and sevoflurane with balanced anesthetic techniques in order to monitor the anesthetic effects on the brain.

The use of the BIS™ Index for monitoring may be associated with the following when used with propofol anesthesia: reduction in primary anesthetic use; reduction in emergence and recovery time; and reduction in incidence of awareness with recall.

For pediatric patients, ages 4 and above, the BIS™ Index, one of the BIS™ Advance Monitoring System's output parameters, may be used to guide anesthetic administration of sevoffurane with balanced anesthetic techniques in order to monitor the anesthetic effects on the brain.

The use of the BIS™ Index in pediatric patients, when used with sevothurane anesthesia, has demonstrated a reduction in primary anesthetic use.

Device Description

The BIS™ Advance Monitoring System is a user-configurable patient monitoring system designed to monitor the hypnotic state of the brain based on acquisition and processing of EEG signals. It processes raw EEG signals to produce a single number, called the Bispectral Index, or BIS value, which correlates with the patient's level of hypnosis.

The BIS™ Advance Monitoring system is comprised of the following components: BIS™ Advance Monitor, BIS™ Advance Docking Station, BIS™ Advance Adapter Cable, GCX Mounting Accessory, BISx/BISx4 Module, Patient Interface Cable (PIC) and Monitor Interface Cable (MIC).

The BIS™ Advance Monitor displays:

The current BIS™ number .
. Raw EEG waveforms in real time
. Various signal quality indicators (EMG. SQI)
트 Trend graphs of processed EEG parameters (including various options)
I Processed EEG variables:
- . Electromyography (EMG)
- Signal Quality Index (SQI)
- . Suppression Ratio (SR)
- . Burst Count (BURST) (for Extend Sensor and four-channel monitoring only)
- . Suppression Time (ST)
- I Spectral Edge Frequency (SEF)
- Median Frequency (MF)
- EEG Power Asymmetry Index (ASYM) (for four-channel monitoring only)
I Alarm Indicator and Messages

The BIS™ Advance Monitor displays 2 channels of EEG when connected to the BISx module and a unilateral BIS sensor (BIS™ Extend Sensor, BIS™ Pediatric Sensor and BIS™ Quatro Sensor) and displays 4 channels of EEG, two from each side of the brain, when connected to the BISx4 module and BIS™ Bilateral Sensor.

For both the 2-channel and the 4-channel systems, BIS monitoring is implemented as follows:

A sensor placed on the patient's head transmits EEG signals to the BISx module. The BISx module filters the data, analyzes it for artifacts and processes it using digital signal processing techniques, then sends the data to the monitor for display. The purpose of processing the EEG waveform data is to extract characteristic features from the complex signal in order to provide easier pattern recognition of changes over time during the recording.

AI/ML Overview

The acceptance criteria for the BIS™ Advance Monitoring System are primarily related to its proposed changes: a narrowed indication for use and a new monitor design. The submission aims to demonstrate substantial equivalence to the predicate device (BIS EEG Vista Monitor System and BISX, K072286).

Here's an analysis of the acceptance criteria and the studies presented:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly present a table of acceptance criteria with corresponding performance metrics in a pass/fail format. Instead, it relies on demonstrating that the new device's performance is equivalent or better than the predicate, especially for the new monitor design, and that the narrowed indications for use are clinically supported.

However, based on the comparative effectiveness study for the Indications for Use, we can infer some performance aspects:

Acceptance Criteria (Inferred from Indications for Use)	Reported Device Performance (from Clinical Studies)
For Adult patients: BIS™ Index guides anesthetic administration (desflurane, propofol, sevoflurane with balanced anesthetic techniques) to monitor anesthetic effects on the brain.	OLIVER Study: BIS™ values were highly correlated with the level of sedation. Prediction probabilities for correctly predicting unresponsiveness to a verbal command were very high, suggesting BIS™ is an excellent predictor for the level of consciousness for sevoflurane, sevoflurane with remifentanil, sevoflurane with fentanyl, desflurane, or isoflurane. (This supports the broader claim for adults using these agents).
For Adult patients with propofol anesthesia: Reduction in primary anesthetic use, reduction in emergence and recovery time, reduction in incidence of awareness with recall.	OLIVER Study: While it demonstrated high correlation for BIS™ with level of sedation for various anesthetics, the document does not explicitly state the direct measured reduction in primary anesthetic use, emergence/recovery time, or awareness with recall specifically for propofol in the context of Oliver study. It states that "The use of the BIS™ Index for monitoring may be associated with the following when used with propofol anesthesia." This is a cautious statement.
For Pediatric patients (4 years and above) with sevoflurane anesthesia: BIS™ Index guides anesthetic administration to monitor the anesthetic effects on the brain.	BTIGER Study: Provided clinical evidence that the BIS™ index can be used to guide the anesthetic administration of sevoflurane in pediatric patients aged 4-18 years.
For Pediatric patients with sevoflurane anesthesia: Demonstrated reduction in primary anesthetic use.	BTIGER Study: Mean end-tidal sevoflurane (ETSevo) administration was statistically significantly lower in the BIS™ guided treatment group compared to the standard practice group.
General Device Performance (New Monitor Design): Equivalence in fundamental technology, principle of operation, safety, and performance with predicate monitor, as well as compliance with relevant electrical safety, EMC, and software standards.	Various Bench Tests: Electrical safety and EMC testing compliant with standards (ANSI/AAMI ES 60601-1, IEC 60601-1-2, IEC 80601-2-26). All performance bench testing complied with requirements. Software complies with all software requirements and design specifications. Hazard analysis concluded residual risks were acceptable.

2. Sample Size for the Test Set and Data Provenance

OLIVER Study (Adults):
- Sample Size: 143 subjects
- Data Provenance: Multicenter, prospective study conducted across 3 sites in the United States.
BTIGER Study (Pediatrics):
- Sample Size: 170 subjects
- Data Provenance: Multicenter, prospective, randomized control study conducted across 8 sites in the United States.

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

The document does not detail the number or qualifications of experts used to establish ground truth for the clinical studies. However, for studies involving "level of consciousness" and "unresponsiveness to verbal command" in the OLIVER study, and "anesthetic administration" in the BTIGER study, licensed healthcare practitioners would have been involved in assessing these clinical endpoints. The studies were conducted under the "direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use," as stated in the Indications for Use.

4. Adjudication Method for the Test Set

The document does not specify any adjudication method (e.g., 2+1, 3+1) for establishing ground truth in the clinical studies.

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

Was an MRMC study done? The document describes two clinical studies (OLIVER and BTIGER) that compare BIS™ guidance to standard practice or assess the correlation of BIS™ with clinical endpoints. While these are comparative studies, they are not framed as "multi-reader multi-case" studies in the typical sense of AI-assisted image interpretation. The comparison is between a device-guided approach and non-device-guided approaches or correlation with physiological states, rather than human readers interpreting cases with and without AI assistance.
Effect size of human reader improvement with AI vs. without AI assistance: Not applicable in the traditional MRMC context, as the studies are not designed to measure improved human reader performance with AI assistance for interpretation. Instead, the BTIGER study showed that the BIS™ guided treatment group achieved statistically significantly lower end-tidal sevoflurane administration compared to the standard practice group, indicating a direct effect on patient management rather than an improvement in human interpretation.

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

The core of the BIS™ Advance Monitoring System is mentioned as processing raw EEG signals to produce a single number, the Bispectral Index (BIS value), which correlates with the patient's level of hypnosis. The device also displays raw EEG waveforms, signal quality indicators, and processed EEG parameters. The clinical studies (OLIVER and BTIGER) inherently evaluate the performance of this algorithm output (BIS Index) in a clinical setting, effectively testing its "standalone" diagnostic utility in influencing anesthetic administration and correlating with consciousness levels. The output (BIS index) as a predictor of consciousness or a guide for anesthetic use is evaluated.

7. Type of Ground Truth Used

OLIVER Study: The ground truth for correlating BIS™ with the level of sedation appears to be based on clinical assessment of patient responsiveness, specifically "response to a verbal command."
BTIGER Study: The ground truth for evaluating the impact of BIS™ guidance was the clinical outcome of "mean end-tidal sevoflurane (ETSevo) administration" during the maintenance phase of anesthesia, and the clinical decision-making by practitioners.

8. Sample Size for the Training Set

The document focuses on the performance of the current BIS™ algorithm and its new monitor. It states that "no software changes were performed to the BISx/BISx4 module (the unit that performs the computation for EEG acquisition), the BIS algorithm nor to the algorithm database structure." This suggests the core BIS algorithm was developed and trained prior to this submission. The document does not provide information on the sample size for the training set of the BIS algorithm itself. It only provides information for the clinical validation studies (test sets).

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

As with the training set sample size, the document does not provide information on how the ground truth was established for the training set of the BIS algorithm, as the algorithm itself was not modified in this submission. The core algorithm's development and training would have occurred during the development of earlier versions of the BIS monitoring system (e.g., the predicate device K072286).

Summary

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Image /page/0/Picture/0 description: The image shows the logo for the U.S. Food & Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Covidien LLC Moshe J Cohen Senior Regulatory Specialist 6135 Gunbarrel Ave Boulder, Colorado 80301

March 4, 2024

Re: K230693 Trade/Device Name: BISTM Advance Monitoring System Regulation Number: 21 CFR 882.1400 Regulation Name: Electroencephalograph Regulatory Class: Class II Product Code: OLW, OMC, OLT, ORT

Dear Moshe J Cohen:

The Food and Drug Administration (FDA) is sending this letter to notify you of an administrative change related to your previous substantial equivalence (SE) determination letter dated February 26, 2024. Specifically, FDA is updating this SE letter due to incomplete contact name, which was incorrectly stated as Moshe Cohen as an administrative correction.

Please note that the 510(k) submission was not re-reviewed. For questions regarding this letter please contact Bradley Quinn, OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental Devices, 301-796-5575, bradley.quinn@fda.hhs.gov

Sincerely,

Bradley Q. Quinn -S

Bradley Quinn Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthsia Devices OHT1: Office of Ophthalmic, Anesthesia. Respiratory, ENT and Dental Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

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Image /page/1/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, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

February 26, 2024

Covidien LLC Moshe Cohen Senior Regulatory Specialist 6135 Gunbarrel Ave Boulder, Colorado 80301

Re: K230693

Trade/Device Name: BISTM Advance Monitoring System Regulation Number: 21 CFR 882.1400 Regulation Name: Electroencephalograph Regulatory Class: Class II Product Code: OLW, OMC, OLT, ORT Dated: February 18, 2024 Received: February 20, 2024

Dear Moshe Cohen:

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.

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

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

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Bradley Q. Quinn -S

Bradley Quinn Assistant Director DHT1C: Division of Sleep Disordered Breathing, Respiratory and Anesthsia Devices OHT1: Office of Ophthalmic, Anesthesia, Respiratory, ENT and Dental 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) K230693

Device Name BISTM Advance Monitoring System

Indications for Use (Describe)

The use of the BIS™ Index in pediatric patients, when used with sevothurane anesthesia, has demonstrated a reduction in primary anesthetic use.

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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BIS™ Advance Monitoring System 510(k) Summary

This summary of 510(k) safety and effectiveness information for the BISTM Advance Monitoring System is submitted in accordance with the Food and Drug Administration Rule to implement provisions of the Safe Medical Devices Act of 1990 and in conformance with the requirements of 21 CFR §807.92.

SUBMITTER INFORMATION

Submitted Bv: Covidien, Ilc 6135 Gunbarrel Avenue Boulder. CO 80301 Date Prepared: 09 March 2023 Contact Person: Moshe J Cohen Senior Regulatory Affairs Specialist Phone: +972-507094475 Email: moshe.cohen2@medtronic.com

DEVICE

Trade Name: BIS™ Advance Monitoring System Common Name: BIS™ Advance Monitoring System Classification Requlation: 21 CFR 882.1400 Classification Name: Index-Generating Electroencephalograph Software Requlatory Class: Class II Primary Product Code: OLW Secondary Product Code: OMC, OLT, ORT Review Panel: Anesthesiology Devices

PREDICATE DEVICE

Predicate Manufacturer: Aspect Medical Systems, INC Predicate Trade Name: BIS EEG Vista Monitor System and BISX Predicate 510(k): K072286

PREVIOUS CORRESPONDENCE WITH FDA

Covidien held 2 Pre-Submission meetings with the FDA regarding this submission (Q200053 and Q200053 S001). Refer to VOL 020 Performance Testing Clinical for further details regarding previous correspondence with FDA.

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DEVICE DESCRIPTION

The BIS™ Advance Monitor displays:

The current BIS™ number .
. Raw EEG waveforms in real time
. Various signal quality indicators (EMG. SQI)
트 Trend graphs of processed EEG parameters (including various options)
I Processed EEG variables:
- . Electromyography (EMG)
- Signal Quality Index (SQI)
- . Suppression Ratio (SR)
- . Burst Count (BURST) (for Extend Sensor and four-channel monitoring only)
- . Suppression Time (ST)
- I Spectral Edge Frequency (SEF)
- Median Frequency (MF)
- EEG Power Asymmetry Index (ASYM) (for four-channel monitoring only)
I Alarm Indicator and Messages

For both the 2-channel and the 4-channel systems, BIS monitoring is implemented as follows:

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Image /page/6/Figure/2 description: This image shows a medical device with several labeled parts. The device includes a screen labeled as '1', a camera labeled as '2', and a cable labeled as '3'. The device is attached to a stand labeled as '4', and another cable labeled as '5' is connected to it.

Figure 1. BIS™ Advance Monitoring System Components

Number	Component
1	BIS TM Advance Monitor
2	BIS TM Docking Station
3	BIS TM Adapter Cable
4	GCX mounting accessory
5	Monitor Interface Cable (MIC)
6	BIS TM Sensor
7	Patient Interface Cable (PIC)
8	BISx/BISx4 module

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INDICATIONS FOR USE

The BIS™ Advance Monitoring System is intended for monitoring the state of the brain by data acquisition of EEG signals under the direct supervision of a licensed healthcare practitioner or by personnel trained in its proper use. The BIS™ Advance Monitoring System, and all its associated parameters, is intended for use on adults and pediatric patients (4 years old and above) within a hospital or medical facility.

For Adult patients, the BIS™ Index, one of the BIS™ Advance Monitoring System's output parameters, may be used to guide anesthetic administration of desflurane, isoflurane, propofol and sevoflurane with balanced anesthetic techniques in order to monitor the anesthetic effects on the brain.

The use of the BIS™ Index for monitoring may be associated with the followinq when used with propofol anesthesia: reduction in primary anesthetic use; reduction in emergence and recovery time; and reduction in incidence of awareness with recall.

For pediatric patients, ages 4 and above, the BIS™ Index, one of the BIS™ Advance Monitoring System's output parameters, may be used to guide anesthetic administration of sevoflurane with balanced anesthetic techniques in order to monitor the anesthetic effects on the brain.

The use of the BIS™ Index in pediatric patients, when used with sevoflurane anesthesia, has demonstrated a reduction in primary anesthetic use.

TECHNOLOGICAL CHARACTERISTICS COMPARISON

There are 2 proposed changes in this submission in regard to the predicate device. The first change is related to the indications for use, which will be narrowed down from the predicate device. The indications for use of the subject device now specify the minimum age of patients (4 years and above), as well as the specific anesthetic agents for which the BIS™ Advance Monitoring System may be utilized to guide administration of, and the clinical benefits that mav be associated with when utilizing the BIS™ Advance Monitoring System to quide administration of specified anesthetic agents. The revised indications for use do not introduce any new indications, claims or target populations. The indication for use changes are supported by clinical studies and detailed in this submission in VOL 020 Performance Testing Clinical.

The second change is related to a new monitor design, the BIS™ Advance Monitor, which will replace the predicate monitor, the BIS VISTA Monitor. The BISx/BISx4 modules and the BIS™ Sensors are not modified as part of this submission and rely on the previously cleared 510k submissions, K072286 and K143506, respectively.

The BIS™ Advance Monitor is a customized off the shelf durable tablet designed for the same functionality as the predicate device, BIS VISTA Monitor: it displays EEG data and processed parameters computed by the BISx/BISx4 module either numerically and/or graphically, via user interface, and presents alarms when alarm thresholds are crossed. The new monitor is equipped with a larger display, additional user interface options and up-todate operating system.

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The BIS™ Advance Monitor is provided with a newly-developed software which integrates all key features of the predicate, while incorporating a user interface that closely mirrors it, along with minor changes and improvements, as summarized below:

Display and user-interface modifications, to implement minor . improvements and increased number of user-selection options
New low-priority alarms and additional battery life alert ●
Removal of two processed parameters, sEMG and sBIS, which have ● no clinical significance
New electromagnetic interference artifact detection .

The software change does not impact diagnosis and treatment, as no software changes were performed to the BISx/BISx4 module (the unit that performs the computation for EEG acquisition), the BIS algorithm nor to the algorithm database structure.

The change is mainly focused on the display of data while the principle of operation, main displayed parameters as well as the technology utilized for acquisition and processing of EEG waves are all unaffected by the change. The verification and validation tests enable the use of the BIS™ Advance Monitor for use with the existing BISx/BISx4 module and the BIS™ sensors. Based on the results of the verification and validation studies (including system verification), the subject device, the BIS™ Advance Monitor, is substantially equivalent to the predicate device.

The following technological characteristics comparison was performed on the BIS™ Advance Monitor of the subject device vs. the BIS Vista Monitor of the predicate device. The other components of both the subject and predicate devices are identical and will therefore be excluded from this comparison.

DeviceCharacteristic	Subject DeviceBIS™ AdvanceMonitoring System	Predicate DeviceBIS EEG VISTA MonitorSystem and BISX(K072286)	SimilaritiesandDifferences
Classification	II	II	Similar
DeviceClassificationName	Index-GeneratingElectroencephalographSoftware	Index-GeneratingElectroencephalographSoftware	Similar
Primary ProductCode	OLW	OLW	Similar
SecondaryProduct Code(s)	OMC, OLT, ORT	OMC, OLT, ORT	Similar

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FundamentalTechnology	Acquisition, processingand display of real-time EEG waveformsand processed EEGparameters	Acquisition, processing anddisplay of real-time EEGwaveforms and processedEEG parameters	Similar
Principle ofOperation	EEG signals aretransmitted fromsensors placed onpatient's head to theBISx/BISx4 Module.The BISx modulefilters the data,analyzes it for artifactand processes it usingdigital signalprocessing techniques,then sends the data tothe monitor for display.	EEG signals are transmittedfrom sensors placed onpatient's head to theBISx/BISx4 Module. TheBISx module filters the data,analyzes it for artifact andprocesses it using digitalsignal processingtechniques, then sends thedata to the monitor fordisplay.	Similar
RegulationNumber	882.1400	882.1400	Similar
Prescription/overthe counter use	Prescription	Prescription	Similar
IntendedPopulation	Adult and pediatric,from age 4 years andup	Adult and pediatric, withoutage limitation	Different:pediatricpatients ageis now limited
Intended Users	Professionally trainedhealth care providers	Professionally trainedhealth care providers	Similar
Environment ofUse	hospitals or medicalfacilities providingpatient care	hospitals or medicalfacilities providing patientcare	Similar
Monitor	BISTM AdvanceMonitor	BIS VISTA Monitor	Similar: SamefunctionalityDifferent:minorsoftwarechanges,mostly UI-related,SOUP andOS changes,updatedhardwaredesign

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			differentdimensionsand weight,new dockingstation,mountingaccessoriesand adaptercable toconnect to theBISx/BISx4
Monitor –Primary Externalmaterials	Glass, TPR(Thermoplasticrubber), ABS(Acrylonitrile butadienestyrene), PC(Polycarbonate),Acrylic, Zinc alloy,Lexan 8B35 film	Glass, ABS (Acrylonitrilebutadiene styrene), PC(Polycarbonate), Polyester,Polyutherane	Different(note - themonitor doesnot come incontact withthe patient)
User interface	Default display optionsalong with user-selection options fordisplay of EEG andprocessed parametersand graphs; Display ofalert messages; User-selection options forsetting and configuringalarms	Default display optionsalong with user-selectionoptions for display of EEGand processed parametersand graphs; Display of alertmessages; User-selectionoptions for setting andconfiguring alarms	Similar: mainfeaturesremainunchangedDifferent:More user-selectionoptionscompared topredicate,change todefaultsettings forspecificparameters,additionalexport-to-filesupport, newlow-priorityconfigurablealarms,additionalbattery life

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			displayimprovements
Electromagneticinterferenceartifact detection	Supported, systemadjusts the SignalQuality Indicatoraccordingly	Not supported	Different:allows for amoreaccurateSignal QualityIndicator
MonitorOperatingSystem	Windows 10 Enterprise	Windows CE	Different
Display size	Height: 5.3"Width: 8.5"	Height: 4"Width: 5.25"	Different
Module	BISX/BISX4	BISX/BISX4	Similar
Monitoraccessories	Docking Station;GCX Clamp Mount /GCX Desktop Mount;Adapter Cable	Pole Clamp	Different:differentmonitormountingaccessoriestoaccommodatethe differentmonitordesigns; NewAdapterCable to allowconnection ofthe newmonitor to theexistingMonitorInterfaceCable whichconnects totheBISx/BISx4module
Sensors	BISTM sensors (clearedunder K143506):Quatro / Pediatric /Extend / Bilateral	BISTM sensors (clearedunder K143506): Quatro /Pediatric / Extend / Bilateral	Similar
Displayed data	EEG, BIS index, SR,ST, SQI, EMG, BurstCount, DSA ASYM	EEG, BIS index, SR, ST,SQI, EMG, Burst Count,DSA ASYM SEMG sBIS	Different:sEMG andsBIS removed

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	artifact detection,alarm indicators andmessages, trendgraphs of processedEEG Parameters	artifact detection alarmindicators and messages,trend graphs of processedEEG Parameters	from subjectdevice displaydue to notbeingsupported byscientifically-provenclinicalsignificanceand deviceclaims
Energy Source	AC-power source;Internal lithium-ionbattery	AC-power source;Internal lithium-ion battery	Similar
Software level ofconcern	Moderate	Moderate	Similar
Sterility	Non-sterile	Non-sterile	Similar
Main Safety andPerformanceStandards	1. IEC 60601-1:2005+A1:2012 /ANSI/AAMIES60601-1:2005/(R)2012 andA1:2012,C1:2009/(R)2012andA2:2010/(R)20122. IEC 60601-1-2:20143. IEC 60601-1-6:2010 +A1:20134. IEC 60601-1-8:2006 + A1:20125. IEC 62366-1:20156. IEC 80601-2-26:20197. IEC 62133-2:2017	1.IEC 60601-1:2005+A1:2012+A2:20202.IEC 60601-1-2:2014+A1:20203.IEC 60601-1-6:2010 +A1:2013 +A2:20204.IEC 60601-1-8:2006 +A1:2012+A2:20205.IEC 62366-1:2015 +A1:20206.IEC 80601-2-26:20197.IEC 62133-2:2017	Similar, withthe exceptionof 2020amendmentsof severalstandards,which are stillundertransitionperiod - thepredicatedevicealreadycomplies withsuchamendments,while thesubjectdevice isscheduled tocomply withtheamendmentsbefore theend of thetransitionperiod

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PERFORMANCE DATA

The following performance data is provided to support the substantial equivalence determination with the predicate device:

Electrical Safety and EMC

Electrical safety and EMC testing were performed per ANSI/AAMI ES 60601-1:2005/(R)2012 & A1:2012, C1:2009/(R)2012 & A2:2010/(R)2012, IEC 60601-1-2:2014. Additionally, testing was performed in accordance with the deviceparticular safety and performance standard, IEC 80601-2-26:2019. Electrical Safety and EMC Test reports are provided in sections VOL 017 Electromagnetic Compatibility and Electrical Safety and VOL 018 Performance Testing Bench.

General Performance

VOL 018 Performance Testing Bench contains a summary of all the performance bench testing performed on the subject device. The results of the bench performance testing demonstrate that the performance of the subject device, BIS™ Advance Monitor, complies with the requirements of testing standards applied.

Hazard/Risk Analysis

A hazard analysis was carried out on the BIS™ Advance Monitor's software in compliance with ISO 14971:2019. This hazard analysis concluded that any residual risks were judged as acceptable when weighed against the intended benefits of use of. The hazard analysis is detailed further in this submission in MISC FILES: 001 Extract of the monitor software-related items from BIS Advance Risk Management File.

Software

The software description and documentation, including test report, are provided in VOL 016 Software. The test report indicates that the BIS™ Advance Monitor software complies with all software requirements and design specifications.

Biocompatibility

The BIS™ Advance Monitor does not come into direct or in-direct contact with the patient. Therefore, no biocompatibility assessment is required.

Performance Testing - Animal

No animal performance testing was required to demonstrate subject device safety and effectiveness.

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Performance Testing - Clinical

Clinical studies were performed and outlined in section VOL 020 Performance Testing Clinical of this submission. The proposed changes to the indications for use are supported via performance of the following clinical studies:

1. Oliver (MDT19053OLIVER)

This multicenter, prospective study was conducted to investigate the relationship between BIS™ and inhaled anesthetics across a wide range of anesthetic concentration and hypnotic states.

This study was conducted across 3 sites in the United States, in 143 subjects. Healthy volunteers were randomized to one of five anesthetic regimen groups: sevoflurane, sevoflurane with remifentanil, sevoflurane with fentanyl, desflurane, or isoflurane. The OLIVER trial determined the BIS50 and BIS95 values at which 50% and 95% of patients were unresponsive and found that these values were similar across all treatment groups BIS™ values were highly correlated with level of sedation and the prediction probabilities for correctly predicting whether a subject would respond to a verbal command were very high, suggesting that BIS™ is an excellent predictor for the level of consciousness.

2. BTIGER (MDT20032BTIGER)

This multicenter, prospective, randomized control study was conducted to investigate the relationship between BIS™ values including EEG profile and anesthetic agents in the pediatric population.

This study was conducted across 8 sites in the United States, in 170 subjects. Pediatric subjects aged 4 - 18 years (ASA PS I - III) undergoing routine sevoflurane general anesthesia were included in the trial. The BTIGER study determined the mean end-tidal sevoflurane (ETSevo) administration during the maintenance phase of anesthesia during pediatric surgery. ETSevo was statistically significantly lower in the BIS™ guided treatment group compared to the standard practice group. This study provides clinical evidence that the BIS™ index can be used to quide the anesthetic administration of sevoflurane in pediatric patients aged 4 - 18 years.

Previous Correspondence With FDA

Covidien held 2 Pre-Submission meeting with the FDA regarding this submission (Q200053 BIS and Q200053 S001 BIS). Refer to VOL 020 Performance Testing Clinical for further details regarding previous correspondence with FDA.

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CONCLUSIONS

The subject device, BIS™ Advance Monitor is equivalent in intended use, technological characteristics and performance to the existing legally marketed predicate device. The subject device was tested to verify and validate the safety and performance of the new monitor and its substantial equivalence to the predicate device. From the evidence presented in this Premarket Notification, the subject device can be considered substantially equivalent to the predicate device.

Regulation Number and Section

§ 882.1400 Electroencephalograph.

(a)
Identification. An electroencephalograph is a device used to measure and record the electrical activity of the patient's brain obtained by placing two or more electrodes on the head.(b)
Classification. Class II (performance standards).