autoSCORE

K231068 · Holberg Eeg AS · OMB · Jan 7, 2024 · Neurology

Device Facts

• Record ID: K231068
• Device Name: autoSCORE
• Applicant: Holberg Eeg AS
• Product Code: OMB · Neurology
• Decision Date: Jan 7, 2024
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 882.1400
• Device Class: Class 2
• Attributes: AI/ML, Software as a Medical Device, Pediatric

Intended Use

autoSCORE is intended for the review, monitoring and analysis of EEG recordings made by electroencephalogram (EEG) devices using scalp electrodes and to aid neurologists in the assessment of EEG. This device is intended to be used by qualified medical practitioners who will exercise professional judgment in using the information. The spike detection component of autoSCORE is intended to mark previously acquired sections of the patient's EEG recordings that may correspond to spikes, in order to assist qualified clinical practitioners in the assessment of EEG traces. The spike detection component is intended to be used in patients at least three months old. The autoSCORE component has not been assessed for intracranial recordings. autoSCORE is intended to assess the probability that previously acquired sections of EEG recordings contain abnormalities, and classifies these into pre-defined types of abnormalities, including epileptiform abnormalities. autoSCORE does not have a user interface. autoSCORE sends this information to the EEG reviewing software to indicate where markers indicating abnormality are to be placed in the EEG. autoSCORE also provides the probability that EEG recordings include abnormalities and the type of abnormalities. The user is required to review the EEG and exercise their clinical judgment to independently make a conclusion supporting or not supporting brain disease. This device does not provide any diagnostic conclusion about the patient's condition to the user. The device is not intended to detect or classify seizures.

Device Story

Software-only decision support tool for EEG review; processes raw EEG data from external systems; uses Convolutional Neural Network (CNN) to identify/categorize epileptiform (focal/generalized) and non-epileptiform (focal/diffuse) abnormalities; outputs probability scores and markers to host EEG software; used in hospital/EEG lab settings by neurologists/qualified practitioners; assists clinical workflow by highlighting potential abnormalities; does not provide diagnostic conclusions or detect seizures; requires user to exercise clinical judgment for final assessment; benefits patient by streamlining EEG analysis.

Clinical Evidence

Retrospective clinical validation across five datasets (total N=6,305 EEGs). Compared autoSCORE against human expert (HE) consensus and predicate devices. Primary endpoints: sensitivity, specificity, PPV, NPV for abnormality detection. Results showed high correlation with HEs (r=0.95-0.99). Recording-level sensitivity for abnormal EEG ranged 71.6%-100% across studies. Benchmarking against predicates showed comparable or superior performance in identifying epileptiform abnormalities.

Technological Characteristics

Software-only; Convolutional Neural Network (CNN) algorithm; processes raw scalp EEG data; post-hoc analysis; integrates with host EEG software (e.g., Natus NeuroWorks); no user-defined parameters for spike detection; moderate level of concern software.

Indications for Use

Indicated for review, monitoring, and analysis of scalp EEG recordings to aid neurologists in assessment. Spike detection component indicated for patients >= 3 months old. Not for intracranial recordings, seizure detection, or seizure classification. Intended for use by qualified medical practitioners.

Regulatory Classification

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.

Predicate Devices

• encevis (K171720)
• Persyst 13 (K151929)

Submission Summary (Full Text)

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January 7, 2024

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Holberg EEG AS Smriti Franklin QA/RA Manager Fjøsangerveien 70A 5068 Bergen, Norway

#### Re: K231068

Trade/Device Name: autoSCORE Regulation Number: 21 CFR 882.1400 Regulation Name: Electroencephalograph Regulatory Class: Class II Product Code: OMB Dated: December 8, 2023 Received: December 8, 2023

Dear Smriti Franklin:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

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Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review. the OS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

Jay R. Gupta -S

Jay Gupta Assistant Director DHT5A: Division of Neurosurgical, Neurointerventional and Neurodiagnostic Devices OHT5: Office of Neurological and Physical Medicine Devices

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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) K231068

Device Name autoSCORE

#### Indications for Use (Describe)

1. autoSCORE is intended for the review, monitoring and analysis of EEG recordings made by electroencephalogram (EEG) devices using scalp electrodes and to aid neurologists in the assessment of EEG. This device is intended to be used by qualified medical practitioners who will exercise professional judgment in using the information.

2. The spike detection component of autoSCORE is intended to mark previously acquired sections of the patient's EEG recordings that may correspond to spikes, in order to assist qualified clinical practitioners in the assessment of EEG traces. The spike detection component is intended to be used in patients at least three months old. The autoSCORE component has not been assessed for intracranial recordings.

3. autoSCORE is intended to assess the probability that previously acquired sections of EEG recordings contain abnormalities, and classifies these into pre-defined types of abnormalities, including epileptiform abnormalities. autoSCORE does not have a user interface. autoSCORE sends this information to the EEG reviewing software to indicate where markers indicating abnormality are to be placed in the EEG. autoSCORE also provides the probability that EEG recordings include abnormalities and the type of abnormalities. The user is required to review the EEG and exercise their clinical judgendently make a conclusion supporting or not supporting brain disease.

4. This device does not provide any diagnostic conclusion about the patient's condition to the user. The device is not intended to detect or classify seizures.

| Type of Use (Select one or both, as applicable) | | |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------|
| <table><tr><td><div> <span> <span style="font-size: 20px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div></td><td><div> <span>☐ Over-The-Counter Use (21 CFR 801 Subpart C)</span> </div></td></tr></table> | <div> <span> <span style="font-size: 20px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span>☐ Over-The-Counter Use (21 CFR 801 Subpart C)</span> </div> |
| <div> <span> <span style="font-size: 20px;">☑</span> Prescription Use (Part 21 CFR 801 Subpart D) </span> </div> | <div> <span>☐ Over-The-Counter Use (21 CFR 801 Subpart C)</span> </div> | |

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Image /page/4/Picture/1 description: The image contains a logo for Holberg EEG. The logo consists of a purple circle with a stylized EEG waveform inside it. To the right of the circle, the text "HOLBERG EEG" is written in a simple, sans-serif font.

# 510(K) Summary

#### 1. SUBMITTER

Holberg EEG AS Fjøsangerveien 70A 5068 Bergen, Norway Phone: [phone] Contact Person: Smriti Franklin Date Prepared: March 23rd, 2023

#### 2. DEVICE IDENTIFICATION

Trade Name: autoSCORE

Common Name: Automatic event detection software for full-montage electroencephalograph Classification Name and Regulation Number: Electroencephalograph, 21 CFR 882.1400 Regulatory Class: II Product Code: OMB

#### 3. PREDICATE DEVICES

#### Primary Predicate Device

Trade/Device Name: encevis, K171720

Additional Predicate Device

Trade/Device Name: Persyst 13, K151929

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Image /page/5/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized waveform inside, followed by the text "HOLBERG EEG" in a simple, sans-serif font. The waveform graphic is meant to represent brain activity, which is related to the EEG acronym.

#### 4. DEVICE DESCRIPTION

autoSCORE is a software-only decision support product intended to be used with compatible electroencephalography (EEG) review software. It is intended to assist the user when reviewing EEG recordings, by assessing the probability that previously acquired sections of EEG recordings contain abnormalities, and classifying these into pre-defined types of abnormality. autoSCORE sends this information to the EEG software to indicate where markers indicating abnormality are to be placed in the EEG. autoSCORE uses an algorithm that has been trained with standard deep learning principles using a large training dataset.

autoSCORE also provides an overview of the probability that EEG recordings and sections of EEG recordings include abnormalities, and which type(s) of abnormality they include. This is performed by identifying spikes of epileptiform abnormalities (Focal epileptiform and Generalized epileptiform) as well identifying non-epileptiform abnormalities (Focal Nonepileptiform and Diffuse Non-epileptiform).

The user is required to review the EEG and exercise their clinical judgement to independently make a conclusion supporting or not supporting brain disease.

autoSCORE cannot detect or classify seizures. The recorded EEG activity is not altered by the information provided by autoSCORE. autoSCORE is not intended to provide information for diagnosis but to assist clinical workflow when using the EEG software.

### 5. INDICATIONS FOR USE/ INTENDED USE

#### 5.1 INDICATIONS FOR USE STATEMENT

- 1. autoSCORE is intended for the review, monitoring and analysis of EEG recordings made by electroencephalogram (EEG) devices using scalp electrodes and to aid neurologists in the assessment of EEG. This device is intended to be used by qualified medical practitioners who will exercise professional judgment in using the information.
- 2. The spike detection component of autoSCORE is intended to mark previously acquired sections of the patient's EEG recordings that may correspond to spikes, in order to assist qualified clinical practitioners in the assessment of EEG traces. The spike detection component is intended to be used in patients at least three months old. The autoSCORE component has not been assessed for intracranial recordings.
- 3. autoSCORE is intended to assess the probability that previously acquired sections of EEG recordings contain abnormalities and classifies these into pre-defined types of

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abnormalities, including epileptiform and non-epileptiform abnormalities. autoSCORE does not have a user interface. autoSCORE sends this information to the EEG reviewing software to indicate where markers indicating abnormality are to be placed in the EEG. autoSCORE also provides the probability that EEG recordings include abnormalities, and the type of abnormalities. The user is required to review the EEG and exercise their clinical judgement to independently make a conclusion supporting or not supporting brain disease.

- 4. This device does not provide any diagnostic conclusion about the patient's condition to the user. The device is not intended to detect or classify seizures.
### 5.2 INTENDED USE ENVIRONMENT

autoSCORE is intended to be used in environments where clinical EEGs are acquired or reviewed by suitably trained and qualified professionals.

autoSCORE is intended to be used for the analysis of EEG that has been recorded in environments suitable for adult and pediatric routine EEG acquisition according to best clinical practice, excluding acquisition environments for ICU and neonatal recordings. autoSCORE is not validated for EEG recorded in a home/ambulatory environment or any non-hospital/EEG laboratory setting.

### 5.3 INTENDED PATIENT POPULATION

autoSCORE use is restricted to EEG recordings from patients over 3 months of age. autoSCORE cannot be used for EEG recordings from neonatal patients. This restriction applies to all features of autoSCORE. There are no other restrictions regarding the patient population.

#### 6. SUBSTANTIAL EQUIVALENCE DISCUSSION

The following table 1 compares autoSCORE to the predicate device with respect to intended use, technological characteristics and operating principles. The comments section provides further information on the determination of substantial equivalence.

| | | autoSCORE | encevis | Persyst 13 | Comments |
|-----------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | 510k Reference | Subject device | K171720 | K151929 | N/A |
| | Product Code | OMB | OMB | OMB | Identical |
| | Class | II | II | II | Identical |
| Device, regulation and sponsor details | Regulation<br>Number | 21 CFR 882.1400 | 21 CFR 882.1400 | 21 CFR 882.1400 | Identical |
| | Regulation<br>Name | Electroencephalograph | Electroencephalograph | Electroencephalograph | Identical |
| | | autoSCORE | encevis | Persyst 13 | Comments |
| Device Description and Features | Manufacturer | Holberg EEG AS | AIT Austrian Institute of<br>Technology GmbH | Persyst Development<br>Corporation | N/A |
| | Device Type | Software-only Device | Software-only Device | Software-only Device | Identical |
| | General Device<br>Description | EEG Review and Analysis<br>Software | EEG Review and Analysis<br>Software | EEG Review and<br>Analysis Software | Identical |
| | Identifies<br>Spikes | Yes | Yes | Yes | Identical |
| | Assessment<br>and<br>categorization<br>of<br>abnormalities<br>including<br>probability in<br>previously<br>acquired<br>sections of EEG | Yes | No | No | Different |
| | Type of EEG | Scalp EEG | Scalp EEG | Scalp EEG | Identical |
| | Intended Use<br>Environments | autoSCORE is intended to<br>be used in environments<br>where clinical EEGs are<br>acquired or reviewed by<br>suitably trained and<br>qualified professionals.<br><br>autoSCORE is intended to<br>be used for the analysis of<br>EEG that has been<br>recorded in environments<br>suitable for adult and<br>pediatric routine EEG<br>acquisition according to<br>best clinical practice,<br>excluding acquisition<br>environments for ICU and<br>neonatal recordings.<br>autoSCORE is not<br>validated for EEG<br>recorded in a<br>home/ambulatory<br>environment or any non-<br>hospital/EEG laboratory<br>setting. | encevis is intended to be<br>used in environments<br>where clinical EEGs are<br>acquired or reviewed by<br>suitably trained and<br>qualified professionals.<br><br>encevis Spike Detection<br>component is intended to<br>be used in adult patients<br>greater than or equal to<br>18 years. encevis Spike<br>Detection performance<br>has not been assessed for<br>intracranial recordings. | Persyst 13 is intended<br>to be used in<br>environments where<br>clinical EEGs are<br>acquired or reviewed by<br>suitably trained and<br>qualified professionals.<br><br>The Spike Detection<br>component is intended<br>to be used in patients at<br>least one month old.<br>Persyst 13 Spike<br>Detection performance<br>has not been assessed<br>for intracranial<br>recordings. | Similar. See<br>Patient age for<br>intended<br>population<br>comparison. |
| | Population age | > 3 months | Adults (age > 18 years) | > 1 month | Minimum<br>patient age<br>more than<br>the predicate<br>device. |
| | | autoSCORE | encevis | Persyst 13 | Comments |
| Device Operation | Design Input | Raw EEG Signal | Raw EEG signal | | Identical |
| | Design<br>Input files | Calculation is based on<br>EEG data recorded by<br>external EEG systems.<br>They are read from the<br>EEG data provided by<br>the EEG system | Calculation is based on<br>EEG data recorded by<br>external EEG systems.<br>They are either read<br>from the EEG file<br>provided by the EEG<br>system or can be sent<br>to encevis using the<br>interface provided by<br>AIT (AITInterfaceDLL) | Calculation is based<br>on EEG data<br>recorded by external<br>EEG systems. They<br>are read from the<br>EEG file provided by<br>the EEG system | Identical<br>(No AIT<br>interface) |
| | Algorithm | Convolutional Neural<br>Network | Convolutional Neural<br>Network | Neural Network | Identical |
| | User-defined<br>parameters | No parameters in spike<br>detection algorithm can<br>be changed by the user | No parameters in spike<br>detection algorithm<br>can be changed by the<br>user | | Similar |
| | Type of EEG-<br>Analysis | Post-hoc analysis | Post-hoc analysis | Post-hoc analysis | Identical |
| | Design Output | Spike Detection<br>component makes the<br>results available to the<br>user in form of<br>markers | Spike Detection<br>component makes the<br>results available to the<br>user in form of markers | Spike Detection<br>component makes the<br>results available to the<br>user in form of markers | Identical |
| | Device Outputs | Identification and<br>categorization of<br>epileptiform and non-<br>epileptiform<br>abnormalities<br>including probability<br>that EEG recordings<br>include abnormalities,<br>and the type of<br>abnormalities. These<br>outputs are given at<br>both recording Level<br>and marker Level. | Identification of<br>epileptiform<br>abnormalities (spikes).<br>These outputs are<br>given at marker level. | Identification of<br>epileptiform<br>abnormalities (spikes).<br>These outputs are<br>given at marker level. | Some predicate<br>device features<br>are not<br>included in<br>autoSCORE.<br>These include<br>seizure<br>detection,<br>burst<br>suppression,<br>aEEG, rhythmic<br>and periodic<br>patterns and<br>frequency<br>bands. |
| | Output Files | Results are returned<br>back to the host<br>software after analysis. | Results are stored in a<br>database and/or sent<br>over the interface<br>AITInterfaceDLL to an<br>external EEG system.<br>User output is given by<br>graphical user<br>interfaces. | Results are stored in<br>additional files in the<br>file system placed in<br>the same folder as the<br>EEG file. User output is<br>given by graphical<br>user interfaces. | Similar |
| | Diagnostic<br>conclusion | | | | Comments |
| | autoSCORE | encevis | Persyst 13 | | |
| User | This device is intended<br>to be used by qualified<br>medical practitioners<br>who will exercise<br>professional judgment<br>in using the<br>information. | This device is intended<br>to be used by qualified<br>medical practitioners<br>who will exercise<br>professional judgment<br>in using the<br>information. | This device is intended<br>to be used by qualified<br>medical practitioners<br>who will exercise<br>professional judgment<br>in using the<br>information. | Identical | |
| Compatible<br>and<br>interoperable<br>Equipment<br>and software | autoSCORE can read<br>and process EEG data<br>from Natus®<br>NeuroWorks®<br>software | encevis can read and<br>process EEG data from<br>several EEG vendors. A<br>list of compatible EEG<br>systems can be found<br>on<br>http://www.encevis.co<br>m | Persyst 13 can read<br>and process EEG data<br>from several EEG<br>vendors. A list of<br>compatible EEG<br>systems can be found<br>on<br>http://www.persyst.co<br>m/suppo<br>rt/supported-<br>formats/ | Similar | |

Table 1: Comparison of autoSCORE against predicate devices.

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Image /page/7/Picture/1 description: The image contains the logo for Holberg EEG. The logo consists of a purple circle with a stylized waveform inside, followed by the text "HOLBERG EEG" in a bold, sans-serif font. The waveform graphic is also purple, matching the color of the circle.

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Image /page/8/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized waveform inside, followed by the text "HOLBERG EEG" in a simple, sans-serif font. The waveform graphic likely represents brain activity, which is relevant to the EEG (electroencephalogram) service offered by Holberg.

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Image /page/9/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized waveform inside, followed by the text "HOLBERG EEG" in a sans-serif font. The waveform graphic is meant to represent an electroencephalogram (EEG), which is a test that measures electrical activity in the brain.

| Color Key | | | |
|-----------------------------------|--|----------------------------------|--|
| Identical/Similar Characteristics | | Different or N/A Characteristics | |

### Comparison of Intended Use/ Indications for Use

The Indications for Use statement for autoSCORE is similar to the predicate devices. However, autoSCORE does not contain certain predicate device features including seizure detection, burst suppression, and other quantitative measures. Indications for use statement point 1, 2, and 4 are identical to the respective parts of predicate devices indications for use statement. Point 3 of the indications for use statement describes autoSCORE's technological characteristics, including additional outputs that are different from the predicate devices.

These differences do not alter the intended use of the device, nor do they affect the safety and effectiveness of the device relative to the predicates. Both the subject and predicate devices have the same intended use for analyzing electroencephalograph data, identifying events including spike detection and producing outputs based on analysis of EEG for interpretation by a qualified user.

#### Comparison of Technological Characteristics

Technological differences between the subject and predicate devices have been highlighted in Table 1 above. There are additional features in the predicate devices, including seizure detection, analysis of additional quantitative features, and a different user interface, which Page 5 - 6

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Image /page/10/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized EEG waveform inside it. To the right of the circle, the words "HOLBERG EEG" are written in black, sans-serif font.

are outside the intended use of the subject device. These features are completely independent functions and do not affect the abnormality detection features of the subject device.

Both the predicate devices and subject device detect features related to epileptiform abnormalities (e.g. spikes). In addition to detecting epileptiform abnormalities, the subject device also detects non-epileptiform abnormalities. The subject device also provides the probability of the detected abnormality being an epileptiform abnormality, such as a focal epileptiform or generalized epileptiform abnormality, or a non-epileptiform abnormality, such as a focal non-epileptiform or diffuse non-epileptiform abnormality. The identification of additional abnormalities and categorization of these abnormalities does not affect the intended use of the device and does not pose any additional risks as compared to the predicate devices as evidenced through performance validation.

#### 7. Performance Validation

Performance validation to evaluate autoSCORE performance was conducted in two parts:

- -Non-Clinical Validation – To validate autoSCORE outputs against defined autoSCORE design inputs and user requirements.
- -Clinical Validation – To validate autoSCORE performance against independent human experts and predicate devices.

These validations have been summarized below.

#### 7.1 Non-clinical Performance Validation

Software verification and validation testing was conducted and documented in accordance with 2005 FDA Guidance, Guidance for the Content of Premarket Submissions for Software Contained in Medical Devices.

Product Design and Software Requirements Traceability has been documented and verified against verification and validation test results.

Software verification and validation testing included:

- 1. Code Review
- 2. Unit level testing
- 3. System level testing
- 4. Integration level testing

The software for this device is determined as a "moderate" level of concern because a failure or latent flaw could indirectly result in minor injury to the patient or operator through incorrect information or through the action of a care provider.

Software verification and validation activities demonstrated that the device software meets

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Image /page/11/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized EEG waveform inside it. To the right of the circle, the text "HOLBERG EEG" is written in a simple, sans-serif font.

all software requirements.

### 7.2 Clinical Performance Validation

### 7.2.1 Clinical Performance Evaluation

A retrospective non-interventional comprehensive clinical validation was performed using de-identified data to evaluate performance of all autoSCORE features against Human Experts and predicate devices to establish substantial equivalence.

The following performance data have been provided in support of the substantial equivalence determination.

Table 2: Type of software performance test per feature. autoSCORE indicates the EEG as normal if it does not contain epileptiform or non-epileptiform abnormalities, and abnormal if it contains one or both of these abnormalities. Part 1, Part 2, and Part 5 of the clinical study show comparable results against Human experts where an EEG is marked as 'normal' by autoSCORE. Part 3 and 4 of the study include the assessment of presence and absence of epileptiform abnormalities in predicate devices and autoSCORE that feeds into the assessment of a normal or abnormal EEG.

| Validation<br>Tests<br>Performed | autoSCORE Features - Identification and categorization of following<br>abnormalities | | | | |
|---------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------|-------------------------------------------------|-----------------------------|-------------------------------|-----------------------------------|
| | | Spike Detection -<br>epileptiform abnormalities | | | Non-epileptiform<br>abnormalities |
| | Normal<br>EEG | Focal<br>epileptiform | Generalized<br>epileptiform | Focal non-<br>epileptiform | Diffuse non-<br>epileptiform |
| Direct<br>Comparison<br>against<br>predicate device | x | x | x | Not available<br>in predicate | Not available<br>in predicate |
| Benchmarking<br>against both<br>predicate<br>devices with<br>external gold<br>standard EEGs | x | x | x | Not available<br>in predicate | Not available<br>in predicate |
| Comparison<br>with Human<br>Expert<br>Evaluation | x | x | x | x | x |

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Image /page/12/Picture/1 description: The image shows the logo for Holberg EEG. The logo consists of a purple circle with a stylized waveform inside, followed by the text "HOLBERG EEG" in black. The waveform appears to represent brain activity, which is relevant to the company's focus on EEG technology.

#### Clinical Performance Evaluations

For the performance evaluation of the autoSCORE spike detection device, the study was conducted to measure outputs of autoSCORE against the assessments from independent human experts as well as the spike detection from the predicate devices – encevis and Persyst 13.

Further, for the autoSCORE performance evaluation of additional technological features (not in the predicate device), the study was conducted to measure autoSCORE results of nonepileptiform abnormalities detection and categorization of abnormalities against Human Experts (HE).

The clinical validation study was carried out in five parts to compare the performance of autoSCORE with the human experts as well as with the predicate devices:

- 1. Performance evaluation against human experts (single-Center): A single-center dataset of 4,850 EEGs assessed by 9 human experts assessing more than 1% of the EEGs each.
- 2. Performance evaluation against human experts (multi-center): A multi-center dataset of 100 EEGs were assessed by 11 independent human experts.

## 3. Direct comparison against primary predicate device (encevis): The same dataset of 100 EEGs used in Part 2 were used to evaluate performance against the primary predicate device, encevis.

### 4. Benchmarking against primary and secondary predicate device (encevis and Persyst 13):

A dataset of 58 EEGs was used to benchmark performance of both the primary predicate device encevis, the predicate device Persyst 13, and autoSCORE against human expert consensus.

- 5. Performance evaluation against human experts (two centers):
A hold-out dataset of 1315 EEGs not used for training of the Al model acquired from two centers were assessed by 15 human experts assessing more than 1% of the EEGs each.

The validation study was performed across five separate datasets with the following characteristics:

| Validation Parts | Number of sites | Sample size | Number of reviewers | Patient gender | EEG Duration min-max | Patient age min-max (median) | Pediatric (P) vs Adult (A)* |
|------------------|-----------------|-------------|---------------------|----------------|----------------------|------------------------------|-----------------------------|
|------------------|-----------------|-------------|--------------------…