NEPHROCHECK Test System

K171482 · Astute Medical, Inc. · PIG · Nov 16, 2017 · Clinical Chemistry

Device Facts

• Record ID: K171482
• Device Name: NEPHROCHECK Test System
• Applicant: Astute Medical, Inc.
• Product Code: PIG · Clinical Chemistry
• Decision Date: Nov 16, 2017
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1220
• Device Class: Class 2

Intended Use

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 Story

The NEPHROCHECK® Test System is a bench-top diagnostic tool used by trained medical professionals in central laboratories. It utilizes a single-use cartridge containing two immunoassays to detect protein biomarkers IGFBP7 and TIMP-2 in urine samples. The operator mixes a urine sample with a fluorescent conjugate, applies it to the cartridge, and inserts it into the ASTUTE140® Meter. The meter performs incubation, calculates the AKIRISK® Score based on biomarker concentrations, and displays the result on an LCD screen. Internal procedural controls monitor cartridge function; errors prevent result reporting. The system includes liquid controls and calibration verification kits for quality assurance. By providing an AKIRISK® Score, the device aids clinicians in assessing the risk of moderate or severe AKI, facilitating timely clinical decision-making for critically ill patients.

Clinical Evidence

Bench testing only. Verification activities included ASTUTE140® Electronic Quality Control (EQC) shelf-life and performance, test kit shelf-life extension, and ASTUTE140® meter testing (LCD compatibility, cleaning, climate, electrostatic discharge, optics board electrical/optical/mechanical performance, noise, temperature coefficient, vibration, and drop testing). All components met specifications.

Technological Characteristics

Sandwich fluorescent immunoassay. Components: single-use cartridge with membrane containing capture antibodies for TIMP-2 and IGFBP-7; ASTUTE 140 Meter (bench-top analyzer). Meter uses internal optics to measure fluorescent intensity. Calibration via factory settings, EQC cartridge, and liquid verifiers. Connectivity: RFID card for lot-specific calibration data. Sterilization: N/A. Software: Embedded firmware for signal processing and AKIRisk score calculation.

Indications for Use

Indicated for ICU patients aged 21+ with recent (within 24 hours) acute cardiovascular or respiratory compromise to assess risk of moderate/severe acute kidney injury (AKI) within 12 hours. Not for standalone use; for prescription, central laboratory use only.

Regulatory Classification

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.

Special Controls

Acute kidney injury test systems must comply with the following special controls: 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 failure to correctly interpret 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 (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.

*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 820.10(c) design and development activities, you must document the appropriate end user device training program provided in your premarket notification submission to satisfy the special control in paragraph (b)(1) of this section 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.

Predicate Devices

• NEPHROCHECK® Test System (K153165)

Submission Summary (Full Text)

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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 ([e-mail]) or phone [phone] 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)

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.

| Type of Use (Select one or both, as applicable) | |
|-------------------------------------------------------------------------------------|------------------------------------------------------------------------------------|
| <span style="font-size: 10pt;"></span> Prescription Use (Part 21 CFR 801 Subpart D) | <span style="font-size: 10pt;"></span> 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

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

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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.

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.

## 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.