The Astute Medical NEPHROCHECK® Test System is intended to be used in conjunction with clinical evaluation in patients who currently have or have had within the past 24 hours acute cardiovascular and or respiratory compromise and are ICU patients as an aid in the risk assessment for moderate or severe acute kidney injury (AKI) within 12 hours of patient assessment. The NEPHROCHECK® Test System is intended to be used in patients 21 years of age or older.

Device Description

The Astute NEPHROCHECK® Test System is comprised of the NEPHROCHECK® Test Kit, the ASTUTE140® Meter Kit, NEPHROCHECK® Liquid Controls Kit and the NEPHROCHECK® Calibration Verification (Cal Vers) Kit. The system is designed to be used by trained medical professionals in the central laboratory.

The NEPHROCHECK® Test Kit, includes the NEPHROCHECK® Test which is a single-use cartridge comprised of two immunoassays for the protein biomarkers, insulin-like growth factor-binding protein (IGFBP7) and tissue-inhibitor of metalloproteinases 2 (TIMP-2) on a membrane test strip enclosed in a plastic housing. The concentrations of the TIMP-2 and IGFBP-7 proteins are used to derive an AKIRISK® Score. The test procedure involves the operator applying a clinical urine sample mixed with labeled fluorescent conjugate to the NEPHROCHECK® Test cartridge, and then inserting the Test cartridge into the ASTUTE140® Meter for incubation, result calculation and result display. Internal positive and negative procedural controls in each NEPHROCHECK® Test cartridge monitor the function of each test cartridge. If the automatic check of these procedural controls shows that the control value results are not within pre-defined limits, the ASTUTE140® Meter will display an error message and the Test result will not be reported.

Included in the NEPHROCHECK® Test is test buffer and the NEPHROCHECK® Test Conjugate Vial which contains murine monoclonal and goat polyclonal antibodies against TIMP-2 and IGFBP-7, fluorescent dye, stabilizers and excipients. Each Kit has the materials necessary to perform 25 tests. Each NEPHROCHECK® Test Kit also contains a lot-specific radio-frequency identification (RFID) card containing lot and calibration information. The RFID card information must be loaded prior to using a new Test kit lot.

The AsTUTE140® Meter is a bench-top analyzer that converts the fluorescent signal from each of the two immunoassays (TIMP-2 and IGFBP7) contained within the NEPHROCHECK® Test cartridge into the AKIRISK® Score. The NEPHROCHECK® Test result is displayed on the Meter LCD screen in approximately 20 minutes from the addition of the specimen. Only the AKIRISK® Score appears on the Meter display. The ASTUTE140® Meter contains an internal printer that can print the AKIRISK® Score.

The NEPHROCHECK® Low Liquid Control and NEPHROCHECK® High Liquid Control are bi-level, lyophilized control materials prepared from human urine containing human TIMP-2 and human IGFBP7 proteins with protein stabilizers. TIMP-2 and IGFBP-7 proteins have been added to the urine to achieve specified target concentration levels. Each NEPHROCHECK® Liquid Controls Kit also contains a high and low RFID encoded with the Liquid Control Kit lot number, expiration date, and the expected range of concentration values based on + two standard deviations in the measurement of each protein biomarker (TIMP-2 and IGFBP-7) in each Liquid Control level. Each NEPHROCHECK® Liquid Control Kit Vial is intended for single use only.

The NEPHROCHECK® Calibration Verification Kit includes five levels of Iyophilized material prepared from human urine, containing TIMP-2 and human IGFBP-7 to achieve specified target concentration levels that evenly span the reportable range of the AKIRISK® Score. The expected concentrations and standard deviations of the individual biomarkers are printed on an enclosed Values Card.

AI/ML Overview

This document describes a 510(k) premarket notification for a modified NEPHROCHECK® Test System. The submission claims substantial equivalence to a previously cleared device (K153165). Therefore, the "study that proves the device meets the acceptance criteria" in this context is primarily focused on demonstrating that the modifications do not negatively impact the device's performance characteristics or its intended use, rather than a de novo clinical trial establishing efficacy or accuracy.

Based on the provided text, here's a breakdown of the requested information:

1. A table of acceptance criteria and the reported device performance

The document does not explicitly present a table of acceptance criteria with corresponding performance data in a detailed quantitative manner for the modified device's clinical performance. Instead, it states that the modified components "met its specifications in this testing." The acceptance criteria for this 510(k) are implicitly focused on ensuring the new modifications do not degrade the performance previously established for the predicate device.

Implicit Acceptance Criteria (for modifications) and Reported Performance:

Acceptance Criteria (General)	Reported Device Performance (for modified components)
ASTUTE140® Electronic Quality Control (EQC) Device Shelf-Life and Ambient Shipping Performance	Met specifications.
ASTUTE140® Electronic Quality Control (EQC) Device - Verification of Performance	Met specifications.
NEPHROCHECK® Test Kit cartridge - Shelf-Life Extension Performance	Met specifications.
ASTUTE140® Meter Modified LCD Window Screen Compatibility with Standard Cleaning Process, Climate Testing, Electrostatic Discharge Testing Performance	Met specifications.
ASTUTE140® Meter Modified Optics Board Verification of Electrical, Optical, and Mechanical Performance; Noise Testing; Test Result Stability; Temperature Coefficient Reproducibility; Verification of Production; Climate Testing (Storage & Operating); Vibration and Drop Testing Performance	Met specifications.
No impact on previously established final release specifications	"The NEPHROCHECK® Test System final release specifications as cleared in K153165 are not impacted by these minor changes." and "None of these changes impact the indications, warnings or precautions for the device."

Note: The detailed acceptance criteria (e.g., specific ranges for shelf-life, noise levels, etc.) are not provided in this summary document. The document primarily focuses on demonstrating that modifications did not negatively affect performance, relying on previously established performance for the predicate device.

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

The document primarily describes engineering and stability testing for the modified components, as opposed to a clinical test set for diagnostic performance.

Sample Size for Test Set: Not explicitly stated in numerical terms for each tested parameter (e.g., how many cartridges were tested for shelf-life, how many meters for climate testing etc.). The context suggests sufficient samples were used for engineering verification and validation testing, but specific numbers are not disclosed.
Data Provenance: The nature of the studies (shelf-life, climate testing, electrical/optical performance, etc.) implies laboratory or manufacturing test data. No information on country of origin or whether it was retrospective/prospective is provided, as these are typically not human clinical studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g., radiologist with 10 years of experience)

This section is not applicable to the type of studies described. The document does not describe a clinical study where human experts establish ground truth for diagnostic performance. The tests are engineering and stability evaluations.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

This is not applicable. Adjudication methods are typically used in clinical studies where multiple human readers' interpretations need to be reconciled to establish a "ground truth" for a diagnosis. The studies described are hardware/software verification and shelf-life testing.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This is not applicable. The NEPHROCHECK® Test System measures biomarkers directly; it is not an AI-assisted diagnostic imaging device that human readers interpret. Therefore, an MRMC study is not relevant to this device.

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

The NEPHROCHECK® Test System is an in vitro diagnostic device that produces a quantitative result (AKIRISK® Score) from a biological sample (urine) using immunoassays. The "algorithm" for this device is the formula used to derive the AKIRISK® Score from the concentrations of TIMP-2 and IGFBP-7.

The device itself, the ASTUTE140® Meter, performs the measurement, calculation, and display of the AKIRISK® Score. Therefore, its performance in generating the AKIRISK® Score from a sample is its "standalone" performance. The document states: "The NEPHROCHECK® Test result is displayed on the Meter LCD screen in approximately 20 minutes from the addition of the specimen. Only the AKIRISK® Score appears on the Meter display."

The initial 510(k) for the predicate device (K153165) would have established the clinical and analytical performance of this standalone functionality. This current submission verifies that the modifications to the device components (e.g., optics board, LCD screen) do not negatively impact this standalone performance.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For the modifications described in this 510(k) summary, the "ground truth" refers to engineering specifications and established analytical performance. For example:

Shelf-life: Stability over time, confirming the device components maintain their specified performance characteristics (e.g., calibration, reagent integrity, mechanical function).
Climate Testing: Performance within specified temperature and humidity ranges.
Electrical/Optical Performance: Conformance to design specifications for signal detection, noise, and measurement accuracy.
Cleaning Compatibility: Verification that the device withstands specified cleaning agents without degradation.

For the original clearance of the predicate device (K153165), the ground truth for establishing the clinical aid in risk assessment for AKI would have involved patient outcomes data (e.g., acute kidney injury diagnosis within a certain timeframe based on clinical criteria and/or biomarker levels) correlated with the AKIRISK® Score. However, this 510(k) for a modified device does not present such clinical ground truth data anew.

8. The sample size for the training set

This information is not provided and is likely not relevant to this specific 510(k) submission, as it focuses on modifications to an already cleared device. The original development of the NEPHROCHECK® Test System (predicate device K153165) would have involved extensive data for biomarker correlation and algorithm development, which would conceptually be its "training set," but those details are not in this document.

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

As with point 8, this information pertains to the original development and clearance of the predicate device (K153165) and is not detailed in this document. For a diagnostic test like NEPHROCHECK®, the "ground truth" for its development would typically involve:

Clinical Diagnosis of AKI: Based on standard clinical criteria (e.g., KDIGO guidelines, serum creatinine changes, urine output) established by clinicians.
Correlation with Outcomes: Investigating the relationship between the biomarker levels/AKIRISK® Score and the subsequent development or severity of AKI in patient cohorts.

These studies would have been part of the clinical evidence submitted for the original 510(k) (K153165).

Summary

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November 16, 2017

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.

Astute Medical, Inc. Karin A. Hughes Vice President Clinical and Regulatory Strategy 3550 General Atomics Ct., Building 2, R 432 San Diego, CA 92121

Re: K171482

Trade/Device Name: NEPHROCHECK Test System Regulation Number: 21 CFR 862.1220 Regulation Name: Acute kidney injury test system Regulatory Class: Class II Product Code: PIG Dated: October 10, 2017 Received: October 10, 2017

Dear Karin Hughes:

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. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR

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Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Kellie B. Kelm -S

for Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K171482

Device Name NEPHROCHECK® Test System

Indications for Use (Describe)

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

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K171482 510(k) SUMMARY

Astute Medical Inc.'s Modified NEPHROCHECK® Test System

Submitter's Name, Address, Telephone Number, Contact Person and Date Prepared

Astute Medical, Inc.

3550 General Atomics Ct.

Building 2

San Diego, CA 92121

Phone:	+1.858.500.7044
--------	-----------------

Facsimile: +1.858.882.0449

Contact Person: Karin A. Hughes, Ph.D.

Date Prepared: October 10, 2017

Name of Device:

NEPHROCHECK® Test System

Common or Usual Name:

NEPHROCHECK® Test System

Classification Name:

Acute Kidney Injury Test System (21 C.F.R. 862.1220, Product Code PIG)

Panel:

Clinical Chemistry

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Device Classification:

Class II

Predicate Device:

Name: NEPHROCHECK® Test System

Device Company: Astute Medical, Inc.

510(k) Number: K153165

Intended Use / Indications for Use

Device Description:

The AsTUTE140® Meter is a bench-top analyzer that converts the fluorescent signal from each of the two immunoassays (TIMP-2 and IGFBP7) contained within the NEPHROCHECK® Test cartridge into

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the AKIRISK® Score. The NEPHROCHECK® Test result is displayed on the Meter LCD screen in approximately 20 minutes from the addition of the specimen. Only the AKIRISK® Score appears on the Meter display. The ASTUTE140® Meter contains an internal printer that can print the AKIRISK® Score.

Technological Characteristics:

The modified NEPHROCHECK® Test System has the same technological characteristics as the previously cleared NEPHROCHECK® Test System, to which it is a modification. There have been no changes to the technological features between the modified NEPHROCHECK® Test System and the previously cleared NEPHROCHECK® Test System. The NEPHROCHECK® Test System final release specifications as cleared in K153165 are not impacted by these minor changes. The only modification that is being implemented for the modified device is minor updates to the NEPHROCHECK® Test System's end user training program.

Performance Data

The modified NEPHROCHECK® Test Kit System components were tested to verify their performance for the following parameters:

ASTUTE140® Electronic Quality Control (EQC) Device Shelf-Life and Ambient Shipping 0
o ASTUTE140® Electronic Quality Control (EQC) Device - Verification of Performance
NEPHROCHECK® Test Kit cartridge - Shelf-Life Extension
ASTUTE140® Meter Modified LCD Window Screen Compatibility with Standard Cleaning . Process, Climate Testing, Electrostatic Discharge Testing
ASTUTE140® Meter Modified Optics Board Verification of Electrical, Optical, and . Mechanical Performance; Noise Testing; Test Result Stability; Temperature Coefficient Reproducibility; Verification of Production; Climate Testing (Storage & Operating); Vibration and Drop Testing

The NEPHROCHECK® Test Kit System met its specifications in this testing.

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Substantial Equivalence

The company's modified NEPHROCHECK® Test System is a modification to the previously cleared NEPHROCHECK® Test System (K153165), which was cleared in May 2016. The modified NEPHROCHECK® Test System has the same intended use and indications for use, same principles of operation, and same technological characteristics as the previously cleared predicate NEPHROCHECK® Test System.

Changes in this submission include shelf life extensions for the NEPHROCHECK® Test Kit cartridges and ASTUTE140® Electronic Quality Control (EQC) device; minor engineering changes to ASTUTE140® Meter optic board (dimensions, cabling and layout); and minor changes to the labeling for compliance to the FDA final rules related to "Use of Symbols in Labeling" and "Unique Device Identification System". None of these changes impact the indications, warnings or precautions for the device. Thus, the modified NEPHROCHECK® Test System is substantially equivalent to its predicate.

Conclusions

The modified NEPHROCHECK® Test System is substantially equivalent to the predicate NEPHROCHECK® Test System.

Regulation Number and Section

§ 862.1220 Acute kidney injury test system.

(a)
Identification. An acute kidney injury test system is a device that is intended to measure one or more analytes in human samples as an aid in the assessment of a patient's risk for developing acute kidney injury. Test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including confirmation by alternative methods.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must detail an appropriate end user device training program that will be offered while marketing the device as part of your efforts to mitigate the risk of incorrect interpretation of test results.
(2) As part of the risk management activities performed as part of your 21 CFR 820.30 design controls, you must document the appropriate end user device training program provided in your premarket notification submission to satisfy special control 21 CFR 862.1220(b)(1) that will be offered while marketing the device as part of your efforts to mitigate the risk of incorrect interpretation of test results.
(3) Robust clinical data demonstrating the positive predictive value, negative predictive value, sensitivity and specificity of the test in the intended use population must be submitted as part of the premarket notification submission.