The Cytovale IntelliSep test is a semi-quantitative test that assesses cellular host response via deformability cytometry of leukocyte biophysical properties and is intended for use in conjunction with clinical assessments and laboratory findings to aid in the early detection of sepsis with organ dysfunction manifesting within the first 3 days after testing. It is indicated for use in adult patients with signs and symptoms of infection who present to the Emergency Department. The test is performed on an EDTA anticoagulated whole blood sample.

The IntelliSep test generates an IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis with organ dysfunction manifesting within the first three days after testing. The IntelliSep test represents the probability of the clinical syndrome of sepsis and is intended to be used alongside other clinical information and clinical judgement. It does not identify the causative agent of infection and should not be used as the sole basis to determine the presence of sepsis. The IntelliSep test is intended for in vitro diagnostic use.

Device Description

The Cytovale IntelliSep test is a short turn-around time (STAT) test, producing results in 10 minutes or less, to aid in the early detection of sepsis with organ dysfunction manifesting within the first 3 days after testing. It assesses the state of immune activation in patients with signs and symptoms of infection who present in the Emergency Department (ED).

The IntelliSep test is run on the Cytovale System, a laboratory benchtop analyzer depicted in Figure 1 and Figure 2.

To run a test, the laboratory operator transfers 100 uL of whole blood into the sample preparation tube which is then placed into the Cytovale System. The system automatically lyses red blood cells, and washes the purified leukocytes in a diluent, producing a total volume of approximately 1mL of prepared sample, which the operator then transfers to the IntelliSep cartridge for analysis on the Cytovale System. A microfluidic deformability cytometry technique is used to measure the biophysical properties of thousands of individual leukocytes in rapid succession. These properties have been shown to differ in quiescent white blood cell populations when compared to those in septic patients, enabling rapid assessment of the host response and the likelihood of having sepsis with organ dysfunction manifesting within the first 3 days after testing.

Based on these measurements, the test provides a single score, the IntelliSep Index (ISI), ranging from 0.1-10.0, stratified into three discrete interpretation bands (Band 2, Band 3) of increasing sepsis likelihood.

AI/ML Overview

The provided document, K250513, focuses on a Special 510(k) submission for modifications to an already cleared device, the Cytovale IntelliSep test (K220991). As such, it does not detail a full clinical study with specific acceptance criteria and performance metrics for initial device clearance. Instead, it aims to demonstrate that the modifications made do not negatively impact the previously established performance of the device.

Therefore, the response below will describe the approach taken to prove the modifications meet the underlying performance requirements, rather than a new standalone clinical study with fresh acceptance criteria.

Key takeaway: The study proves that the modified device maintains identical analytical and clinical performance to the previously cleared device (K220991). The acceptance criteria, in this context, are implicitly tied to the performance claims and limitations established in the original K220991 clearance.

Acceptance Criteria and Study Proving Device Meets Criteria (for Modified Device)

Given that K250513 is a Special 510(k) for device modifications, the "acceptance criteria" here refer to demonstrating that the modified device performs identically to the original cleared device (K220991). The study's goal was to show non-inferiority and preservation of performance.

1. Table of Acceptance Criteria (Implicit) and Reported Device Performance

Acceptance Criteria (based on K220991 performance)	Reported Device Performance (K250513)
Maintain identical analytical performance.	No performance differences observed compared to K220991 for Within Laboratory Precision, Reproducibility, and Healthy Reference Range.
Maintain identical clinical performance.	No performance differences observed compared to K220991 when re-processing data from the IntelliSep Clinical Validation Study (CV-CLN-007).
No new risks identified.	No new risks identified following risk assessment of modifications; successful software V&V, cybersecurity testing, and electrical safety/EMI/EMC testing.
No changes to labeled performance claims or limitations.	Confirmed. All performance claims and limitations remain as per K220991.
Accurate and valid internal quality control metrics.	Modifications to internal QC metrics refine clog detection and discern assay failures, without changing the core result calculation. Demonstrated to not impact performance.
Data integrity for remote log export function.	Confirmed data integrity between Cytovale System and external network location.
Robust cybersecurity for network connection.	Independent penetration testing demonstrated controls against physical and digital cyberattacks.
Electrical safety, EMC, EMI compliance.	Successfully demonstrated per IEC 60601-1-2:2014/AMD1:2020 and applicable IEC 61010-1:2010, AMD1:2016.

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

The document explicitly states that "raw assay videos from the following performance studies were processed on both the modified device (K250513) and the baseline device (K220991)." This indicates that existing previously collected data from these studies served as the test set.

Test Set Data Provenance:
- IntelliSep Clinical Validation Study (CV-CLN-007): The original source of clinical data from K220991 clearance. The document does not specify the country of origin, but generally, clinical validation studies for FDA clearance are conducted in the United States or include diverse sites if international. It was a prospective study for the original clearance.
- Within Laboratory Precision (CLSI EP05-A3): Data from analytical precision studies.
- Reproducibility (CLSI EP05-A3): Data from analytical reproducibility studies.
- Healthy Reference Range (CLSI EP28-A3C): Data for establishing a healthy population reference.
- Sequestered Data Set: Processed on both devices for comparison. This implies a previously collected, retrospective dataset or a subset of data held separate from training/development.
Sample Size for Test Set: The document does not specify the sample sizes for these re-analyzed datasets. It refers to the Decision Summary for K220991 for detailed performance claims and limitations, implying sample sizes for these studies would be found there. For a Special 510(k), the key is comparative performance on existing data, not necessarily new, large-scale clinical trials.

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

The document does not explicitly state the number or qualifications of experts used to establish ground truth for the test set in the context of this Special 510(k) re-analysis.

However, for the original K220991 clinical validation study (CV-CLN-007), the ground truth for sepsis with organ dysfunction would have been established by clinical experts based on:

Standard clinical definitions (e.g., Sepsis-3 criteria).
Review of electronic health records, lab findings, clinical assessments, and patient outcomes by qualified physicians (likely intensivists, emergency medicine physicians, or infectious disease specialists).
This process would have involved their clinical judgment and interpretation of a comprehensive patient profile.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test set used in this Special 510(k). This is because the study re-ran previously established data (raw assay videos) through the modified and unmodified systems and compared the device's output directly. The focus was on whether the device's results changed, not on re-evaluating the ground truth diagnoses.

For the original clinical validation study that established the ground truth (CV-CLN-007), it is highly likely that an adjudication process (e.g., by expert clinicians, 2+1 or 3+1 consensus on patient outcomes/diagnosis) was used to establish the gold standard for sepsis with organ dysfunction. However, this is not detailed in the K250513 document.

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

No MRMC study was done or is described in this document. The IntelliSep test is an in vitro diagnostic (IVD) device that provides a quantitative index (IntelliSep Index) and an interpretation band. It is not an imaging AI system that aids human readers in interpretations. Its output is a score, not an image for human reading or analysis. Therefore, an MRMC study is not applicable to this type of device.

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

Yes, the primary evaluation for this device is standalone performance. The IntelliSep test is designed to generate an IntelliSep Index value and associated interpretation bands based on the biophysical properties of leukocytes. It's an automated measurement. For K250513, the core comparison was whether the modified algorithm/hardware produced the same ISI values and interpretation bands as the original algorithm/hardware when given the same raw data. The document explicitly states: "Raw assay videos from the following performance studies were processed on both the modified device (K250513) and the baseline device (K220991). The results were then directly compared to each other..." This confirms a standalone-like comparison of the device's output.

7. The Type of Ground Truth Used

For the foundational clinical performance validation (referenced from CV-CLN-007, originally for K220991), the ground truth for "sepsis with organ dysfunction manifesting within the first 3 days after testing" would have been established using expert consensus based on clinical assessments, laboratory findings, and patient outcomes data. This would align with standard clinical definitions of sepsis (e.g., Sepsis-3 criteria) and involved careful retrospective review of patient charts/records by clinicians and/or adjudication committees to determine the presence or absence of sepsis with organ dysfunction.

For the purpose of this Special 510(k), the "ground truth" was effectively the performance of the predicate device (K220991) on the re-analyzed data. The goal was to show that the modified device produced inputs/outputs identical to that ground truth.

8. The Sample Size for the Training Set

The document does not specify the sample size for the training set.

The IntelliSep test's underlying algorithm (ISI calculation) and the deformability cytometry technique "remain unchanged from K220991." This suggests the core model was trained for the original K220991 submission.
The modifications described in K250513 relate to software refinements (internal QC metrics, remote log export) and hardware changes (new IAM variant). These modifications would likely involve internal testing and verification/validation using previously established data or internal engineering samples, rather than a new "training set" in the machine learning sense, as the core algorithm itself was not re-trained.
The comparison against a "sequestered data set" for internal quality control metrics indicates good machine learning practice, suggesting that if any internal model within the QC process was re-trained (which is not explicitly stated), this set would have been held out from that specific training.

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

Since the K250513 document does not describe new training, it relies on the previous K220991 submission. For the original development of the IntelliSep test (prior to K220991), the ground truth for training the algorithm would have been established through a similar process as the clinical test set: expert consensus based on clinical assessments, laboratory findings, and patient outcomes data according to established sepsis criteria. This clinical information would have been associated with the biophysical property measurements from the Cytovale system to enable the algorithm to learn the correlation between leukocyte deformability and sepsis severity/likelihood.

Summary

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March 21, 2025

Image /page/0/Picture/1 description: The image shows 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.

Cytovale, Inc. Sarah Esterquest Director, Regulatory Affairs 2 Tower Place, 18th Floor South San Francisco, California 94404

Re: K250513

Trade/Device Name: IntelliSep Test (CV-ICG-048) Regulation Number: 21 CFR 866.3215 Regulation Name: Device To Detect And Measure Non-Microbial Analyte(S) In Human Clinical Specimens To Aid In Assessment Of Patients With Suspected Sepsis Regulatory Class: Class II Product Code: OUT Dated: January 29, 2025 Received: February 21, 2025

Dear Sarah Esterquest:

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.

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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).

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 QS 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 and Part 809); 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-safetyreporting-combination-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.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-device-advicecomprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

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 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-regulatory

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assistance/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,

Noel J. Gerald -S

Noel J. Gerald, Ph. D. Deputy Division Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics 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) K250513

Device Name IntelliSep Test

Indications for Use (Describe)

The IntelliSep test generates an IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis with organ dysfunction manifesting within the first three days after test represents the probability of the clinical syndrome of sepsis and is intended to be used alongside other clinical information and clinical judgement. It does not identify the causative agent of infection and should not be used as to determine the presence of sepsis. The IntelliSep test is intended for in vitro diagnostic 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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1. 510(k) Owner/Submitter Information

Name:	Cytovale, Inc.
Address:	2 Tower Place, 18th Floor, South San Francisco, CA 94080
Telephone:	1-415-417-2188
Contact Person:	Sarah Esterquest
Email Address:	sarah.esterquest@cytovale.com

2. Date Summary Was Prepared

March 19, 2025

3. Device Name and Classification

Trade Name:	IntelliSep test
Instrument Name:	Cytovale System
Classification:	Class II (Special Controls)
Classification Name:	Device to detect and measure non-microbial analyte(s) in human
	clinical specimens to aid in assessment of patients with suspected sepsis
	(21 CFR 866.3215)
Product Code:	QUT
Panel:	DMD – Division of Microbiology Devices
Submission Type:	Special

4. Predicate Device Information

Predicate Product	510(k)Number	Date of Clearance	Classification	Regulation	ClassificationProduct Code
IntelliSep test	K220991	December 20, 2022	Class II(Special Controls)	866.3215	QUT

Table 1: Predicate device information

This Special 510(k) (K250513) describes modifications made to the IntelliSep test software and Cytovale System hardware. These modifications are described in Section 8.

5. Device Description

The IntelliSep test is run on the Cytovale System, a laboratory benchtop analyzer depicted in Figure 1 and Figure 2.

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Image /page/5/Figure/2 description: The image shows the Cytovale system, which is a platform for cell analysis. The system consists of several modules, including the Sample Preparation Module (SPM), the Cell Imaging Module (CIM), and the Imaging Analysis Module (IAM). The image also shows Cytovale reagents and a printer and barcode scanner. The Cytovale system is used for a variety of applications, including drug discovery, diagnostics, and basic research.

Figure 1: The Cytorale System is a closed system benchtop andyzer, comprised of three modules: Sample Preparation Module, Cell Imaging Module, and Imaging Andysis Module. The original K22099 I Imaging Analysis Module is shown in this figure. Also included are the Cytovale System Reagents (Cytovale Reagent Kit, Cytovale Cleanse), Barcode Scanner and Printer (not shown: IntelliSep Quality Controls, IntelliSep Cartridge, Sample Preparation Tube).

Image /page/5/Figure/4 description: The image shows a Cytovale system, which is a device used for cell imaging and analysis. The system consists of several modules, including the Sample Preparation Module (SPM), the Cell Imaging Module (CIM), and the Imaging Analysis Module (IAM). The image also shows Cytovale reagents, as well as a printer and barcode scanner. The modules are arranged in a row, with the SPM on the left, followed by the CIM, and then the IAM, with the printer and barcode scanner on the right.

Figure 2: The modified Cytovale System, including an additional Imaging Analysis Module hardware configuration (K250513, described in Section 8). All other Cytovale System materials remain identical to those described in Figure 1 and Table 2.

The IntelliSep test requires use of the materials described in Table 2.

IntelliSep Test Materials & Equipment	Description
Cytovale System:(Required and supplied)Sample Preparation Module (SPM) Cell Imaging Module (CIM) Imaging Analysis Module (IAM)	A closed system benchtop analyzer as shown in Figure 1 andFigure 2. It is comprised of three modules: SamplePreparation Module, Cell Imaging Module, and ImagingAnalysis Module.
Barcode scanner(Optional and supplied)	Scanner used to automatically enter sample and materialidentifiers.

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IntelliSep Test Materials & Equipment	Description
Printer(Optional and supplied)	Printer used to print a hard copy of results.
Sample Preparation Tube(Required and supplied)	A single-use, commercial off-the-shelf test tube used forsample preparation.
IntelliSep Cartridge(Required and supplied)	Closed system test cartridge which presents the sample fortesting in the Cell Imaging Module.
Cytovale Reagent Kit(Required and supplied)	Nonbiological salt solutions (Reagent A Lysis and Reagent BQuench), for use with the Sample Preparation Module to lysered blood cells and quench the lysis reaction.
Cytovale Diluent and Cleanse Reagents(Required and supplied)	The Diluent solution is used in the Sample PreparationModule to suspend white blood cells for analysis. TheCleanse is a rinsing solution for the SPM.
IntelliSep Quality Control Kit(Quality controls are required but not supplied)	A two-level Quality Control set, derived from stabilizedwhole blood.Note: Per 42 CFR 493.1256, quality controls are required for theIntelliSep test; however, at their discretion, laboratory directors maydevelop their own quality control materials or order the IntelliSepQuality Control Kit.

Table 2: Materials and equipment required for the IntelliSep test

6. Intended Use

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symptoms of infection who present to the Emergency Department. The test is performed on an EDTA anticoagulated whole blood sample.

7. Indications for Use

See "Intended Use".

8. Overall Comparison Between Subject Device and Predicate

This Special 510(k) (K250513) describes modifications made to the IntelliSep test software and Cytovale System hardware. There were no changes to the intended use or indications for use for the IntelliSep test, nor were there any changes to the underlying technological characteristics or principles of operation of the Cytovale System.

The modifications are described below.

8.1. Implementation of Optional Remote Log Export Function

The original Cytovale System (K220991) did not include an external network connection, i.e., an internet connection. The modified Cytovale System (K250513) includes an external network connection utilized to export System logs for purposes of remote troubleshooting. This remote log export is unidirectional; the Cytovale System does not accept any incoming data. There is no patient protected health information (PHI) included in the exported System logs.

This external network connection is optional and can be enabled following appropriate assessment by a customer laboratory's Information Technology (IT) department.

8.2. Refinement of Internal Quality Control Metrics

The original IntelliSep test software (K220991) included internal quality control metrics to ensure the validity of IntelliSep test results. The Cytovale System will only report a test result if these internal quality control metrics are met. Otherwise, a test error is reported.

The modified IntelliSep test software (K250513) incorporates modifications to certain internal quality control metrics to refine clog detection within the IntelliSep Cartridge's microfluidic junction and to further discern any assay failures. The modifications also establish new metrics to achieve this same goal.

The modifications are limited to the System's evaluation of the in-process assay results and determination of assay validity. The cell deformability cytometry technique and IntelliSep result calculation process remain unchanged from K220991.

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8.3. Additional Imaging Analysis Module Hardware Variant

The additional Imaging Analysis Module (IAM) configuration presented in K250513 was based on the original K220991 IAM configuration, with the same functional and performance requirements applied to both IAM variants.

The original hardware from the K220991 configuration was planned to be obsolesced by the workstation manufacturer, necessitating replacement of the central and graphics processing units with units of equivalent processing capabilities. Due to incidental improvements in component energy efficiency, the number of power supplies was also reduced from two (K220991) to one (K250513).

The IAM is responsible for receiving and processing data from the Cell Imaging Module (CIM) and providing assay results back to the CIM for display; no changes were made to either data interface.

9. Non-Clinical and/or Clinical Tests Summary & Conclusions

Verification and validation testing was successfully performed following risk assessment of the device modifications. This testing included the components listed below. No changes to assay performance or device function were observed, and no new risks were identified.

9.1. Cytovale System Software Verification and Validation

9.1.1.Holistic Assessment of All Modifications

Software supporting all three Cytovale System modules successfully completed software verification and validation. This included both verification and validation of the device modifications, and confirmation of continued System function and assay performance in alignment with final guidance Content of Premarket Submissions for Device Software Functions (June 2023).

9.1.2.Specific Activities for Remote Log Export Function

Specific verifications and validations were performed in acknowledgement of the new external network connection. These activities included confirmation of data integrity between the Cytovale System and the external network location, and performance of independent penetration testing to demonstrate controls against physical (kinetic) and digital cyberattacks. All activities were performed in alignment with final guidance Cybersecurity in Medical Devices: Ouality System Considerations and Content of Premarket Submissions (September 2023).

9.2. Internal Quality Control Metrics: Comparison of Clinical and Analytical Performance Results

In accordance with the applicable special controls listed in 21 CFR 866.3215, Cytovale confirmed that the modified device maintained identical and clinical performance to the cleared K220991 device. This comparison was of special concern due to the modifications to the internal quality control metrics used to determine result validity.

Raw assay videos from the following performance studies were processed on both the modified device (K250513) and the baseline device (K220991). The results were then directly compared to each other and to the original design requirements.

IntelliSep Clinical Validation Study (CV-CLN-007) .

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Within Laboratory Precision (CLSI EP05-A3) .
. Reproducibility (CLSI EP05-A3)
Healthy Reference Range (CLSI EP28-A3C) ●

No performance differences were observed for these data sets; there are no changes to labeled performance claims or limitations when compared to K220991. All performance claims and limitations may be found in the Decision Summary for K2209911.

9.3. Internal Quality Control Metrics: Comparison of Sequestered Data Set

A comparison of results from a sequestered data set was also evaluated in conformance with Good Machine Learning Practice for Medical Development (October 2021) as established by the US FDA. Health Canada, and MHRA, specifically "Training Data Sets Are Independent of Test Sets". Raw assay videos from the sequestered data set were processed on both the modified device (K250513) and the baseline device (K220991). The results were then directly compared to each other

No performance differences were observed for the sequestered data set, indicating that the device modifications will not impact future, new assay results or overall assay performance.

9.4. Additional Imaging Analysis Module Hardware Variant: Electrical Safety/EMI/EMC Testing

The additional IAM hardware configuration underwent electrical safety, electromagnetic compatibility (EMC), and electromagnetic interference (EMI) testing per IEC 60601-1-2:2014/AMD1:2020, and applicable portions of IEC 61010-1:2010, AMD1:2016 at an ASCA-certified test site (Intertek in Menlo Park, CA, USA). Continued ETL certification and authorization to mark was obtained through this testing.

In alignment with final guidance Electromagnetic Compatibility (EMC) of Medical Devices (June 2022), IEC TS 60601-4-2 was successfully employed to assess the immunity of the performance associated with the device's intended use.

10. Proposed Labeling

The labeling is sufficient and meets the requirements of 21 CFR Parts 801 and 809, as applicable, and meets the special controls for this device under 21 CFR 866.3215.

11. Conclusions

The submitted information in this Special 510(k) notification is complete and supports a substantial equivalence determination.

1 Available at < https://www.accessdata.fda.gov/cdrh docs/reviews/K220991.pdf>

Regulation Number and Section

§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.

(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.