Afinion™ ACR is an in vitro diagnostic test for quantitative determination of albumin, creatinine and albumin/creatinine ratio (ACR) in human urine. The measurement of urine albumin, creatinine and albumin/creatinine ratio aids in the early diagnosis of nephropathy.

Afinion™ ACR Control is a assayed in vitro diagnostic quality control material used to confirm that the Afinion™ ACR and the Afinion™ AS100 Analyzer System is working properly and provides reliable results

Device Description

The Afinion™ ACR assay is an in vitro diagnostic test for quantitative determination of albumin, creatinine and albumin/creatinine ratio (ACR) in human urine using the Afinion™ AS100 Analyzer. The measure of urine albumin aids in the early diagnosis of nephropathy.

The Afinion™ ACR Control kit contains liquid preparations of albumin and creatinine in citrate buffer. The controls should be used to confirm that the Afinion™ AS100 Analyzer System is working properly and provides reliable results.

Afinion™ ACR is a fully automated assay for determination of albumin, creatinine and albumin/creatinine ratio (ACR) in human urine.

The Afinion™ ACR Test Cartridge contains all the reagents necessary for determining albumin, creatinine and ACR in a human urine sample. The sample material is sampled using the sampling device integrated into the Test Cartridge.

Albumin is quantified using a solid phase immunochemical assay. In the Afinion™ ACR Test Cartridge the sample is automatically diluted and aspirated through a membrane coated with antialbumin antibodies, which concentrates and immobilizes the albumin from the sample. A goldantibody conjugate then binds to the immobilized albumin resulting in a red-brown stained membrane. Excess gold-antibody conjugate is removed in a washing step. The Afinion™ AS100 Analyzer measures the color intensity of the membrane, which is proportional to the amount of albumin in the sample.

Creatinine is quantified using an enzymatic colorimetric test that involves four enzymatic steps. The test requires incubation with two distinct enzyme solutions. A colored end product is measured in one of the cartridge wells.

The concentration of albumin, the concentration of creatinine, and the calculated albumin/creatinine ratio are displayed on the Afinion™ AS100 Analyzer.

AI/ML Overview

Acceptance Criteria and Study Details for Afinion™ ACR

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Afinion™ ACR assay were implicitly established through its comparison to a legally marketed predicate device, the DCA 2000® Microalbumin/Creatinine assay (K963142). The goal was to demonstrate "substantial equivalence" in performance. While explicit numerical acceptance criteria were not provided in terms of thresholds for correlation coefficients or precision values, the reported device performance, demonstrating strong correlation and acceptable precision, was considered sufficient to meet the equivalence standard.

Performance Metric	Acceptance Criteria (Implicit)	Reported Device Performance (External Study)	Reported Device Performance (Internal Study)	Reported Device Performance (External Precision Study)
Method Comparison (Correlation with Predicate)	Substantial Equivalence to DCA 2000®
Albumin (mg/L)	High correlation (e.g., r > 0.95 or similar)	Y = 1.10x + 1.4, r = 0.99	Y = 0.92x + 2.1, r = 0.99	N/A
Creatinine (mg/dL)	High correlation (e.g., r > 0.95 or similar)	Y = 0.93x + 2.3, r = 0.99	Y = 1.00x - 3.2, r = 0.99	N/A
ACR (mg/g)	High correlation (e.g., r > 0.95 or similar)	Y = 1.16x + 1.0, r = 0.99	Y = 1.01x + 0.7, r = 0.99	N/A
Precision	Acceptable CV values for within-run and total precision	N/A	N/A
Within-run CV (all analytes)	≤ 8% (implicit)	N/A	N/A	≤ 8%
Total CV (all analytes)	≤ 9% (implicit)	N/A	N/A	≤ 9%
Control Precision (Afinion™ ACR Control)	Acceptable CV values for within-day, within-site, and between-site precision	N/A	N/A
Within-day CV (all analytes)	≤ 7% (implicit)	N/A	N/A	≤ 7%
Within-site CV (all analytes)	≤ 7% (implicit)	N/A	N/A	≤ 7%
Between-site CV (all analytes)	≤ 4% (implicit)	N/A	N/A	≤ 4%

2. Sample Size and Data Provenance

Test Set (Method Comparison - External Study):
- Sample Size: 169 urine samples
- Data Provenance: Studies were conducted at "four external study sites." The specific country of origin is not explicitly stated, but the submission is from Norway, hence it's likely European or international. The samples were retrospective, as they were "analyzed" with both devices.
Test Set (Method Comparison - Internal Study):
- Sample Size: 91 urine samples for Albumin and ACR, 95 urine samples for Creatinine.
- Data Provenance: "Internal method comparison study," implying the data originated from the manufacturer's own facilities. These were retrospective samples.
Test Set (Precision Study):
- Sample Size: Not explicitly stated as a number of unique patient samples for the clinical precision study. Instead, it refers to "two levels of urine samples" (Sample 1 and Sample 2) run multiple times. For the control precision, controls were run in "6 replicates each day over 5 operating days."
- Data Provenance: "External precision study" and "3 study sites" for controls.

3. Number of Experts and Qualifications for Ground Truth

The study relies on comparing the performance of the new device against a predicate device (DCA 2000® Microalbumin/Creatinine assay). Therefore, the "ground truth" for the test set is effectively the result obtained from the predicate device. No human experts were used to establish a separate, independent ground truth for the test samples in this specific type of comparison study. The predicate device itself acts as the reference standard.

4. Adjudication Method

Not applicable. Since the ground truth for comparison was the result from a predicate device, and the study focused on quantitative correlation and precision, there was no need for expert adjudication of results.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This submission is for an in vitro diagnostic (IVD) device, specifically an automated assay for quantitative measurement. This type of study is more common for imaging devices or those requiring human interpretation of results. The study design focuses on the analytical performance (accuracy, precision) of the device itself compared to a predicate device, not on how human readers' diagnostic performance might improve with or without AI assistance.

6. Standalone (Algorithm Only) Performance

Yes, the study describes the standalone performance of the Afinion™ ACR assay. It is an "automated assay" that "quantifies" albumin and creatinine, and "calculates" the ACR. The performance metrics (correlation coefficients, precision) presented are solely based on the device's measurements from urine samples, without human intervention in the result generation or interpretation to modify the output.

7. Type of Ground Truth Used

The "ground truth" used for evaluating the Afinion™ ACR assay was the results obtained from a legally marketed predicate device, the DCA 2000® Microalbumin/Creatinine assay (K963142). This is a common approach for demonstrating substantial equivalence for in vitro diagnostic devices. It relies on the established accuracy and reliability of the predicate.

8. Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its sample size in the context of device development. For IVD assays, development often involves extensive internal testing, calibration, and optimization using various samples, but this is usually distinct from the formal "training set" concept seen in AI/machine learning development.

9. How Ground Truth for the Training Set was Established

Given that this is an in vitro diagnostic assay and not a machine learning algorithm in the typical sense, there isn't a "training set" with ground truth established in the way one would for an AI model.

The "standardization" section states that:

Albumin is calibrated against the ERM®-DA470 reference preparation.
Creatinine is calibrated against SRM 914a.

These reference materials serve as the foundational "ground truth" for the device's calibration, ensuring that its measurements are traceable to recognized international standards. This calibration process, along with extensive internal testing and optimization (which would involve numerous samples with known values, likely determined through reference methods or predicate devices), forms the basis of the device's accuracy.

Summary

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K072409

FEB 1 2 2008

510(k) SAFETY AND EFFECTIVENESS SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of CFR.

Ms Jorunn Grevle Lolland Director Quality Assurance & Regulatory Affairs Axis-Shield PoC Marstrandgata 6 N-0566 Norway Tel: +47 22 04 20 00 Fax: +47 22 04 20 01

Submission Date: 2007-08-17

Device Name: Afinion™ ACR

Reagents:

Classification Name:	1) Albumin, Antigen, Antiserum, Control2) Enzymatic Method, Creatinine
Trade Name:	AfinionTM ACR
Common Name:	1) Test for albumin in urine2) Test for creatinine in urine
Governing Regulation:	1) 866.50402) 862.1225
Device Classification:	Class II
Classification panel:	1) Immunology2) Clinical Chemistry
Product Code:	1) DCF2) JFY

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Controls:Classification Name:	Multi-Analyte Controls, All Kinds (Assayed and Unassayed)
Trade Name:	Afinion™ ACR Control
Common Name:	Control
Governing Regulation:	862.1660
Device Classification:	Class I
Classification panel:	Clinical Chemistry
Product Code:	JJY

Substantial Equivalence:

Afinion™ ACR is substantial equivalent to the DCA 2000® Microalbumin/Creatinine assay (K963142). These assays yield similar Performance Characteristics.

Intended use

Test Description

Albumin is a small protein present in high concentrations in plasma. Normally only small amounts of albumin are excreted in urine. Sustained elevations of urinary albumin concentrations are known as microalbuminuria. Microalbuminuria is also defined as a urinary excretion rate (AER) between 20-200ug/min in at least two of three urine samples within a six month period.

Creatinine is a degradation product of the muscle tissue protein creatine. All creatinine crosses the glomerular basement membrane and is excreted with the urine. As muscle degradation is a continuous process, creatinine is filtered at a constant rate. Measurements of creatinine in urine will thus correct for varying diuresis and calculating the albumin/creatinine ratio will give a more accurate result of the albumin excretion rate.

Microalbuminuria is connected to several late complications of diabetes such as retinopathy and neuropathy, as well as essential hypertension, preeclampsia, cardiovascular diseases, inflammatory conditions and mortality. Today ACR is a predictive marker of great importance in the early detection of kidney disease and identification of patients at risk for complications of diabetes or hypertension.

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Principle of the device

Afinion™ ACR is a fully automated assay for determination of albumin, creatinine and albumin/creatinine ratio (ACR) in human urine.

The concentration of albumin, the concentration of creatinine, and the calculated albumin/creatinine ratio are displayed on the Afinion™ AS100 Analyzer.

Comparison of technological characteristics

Afinion™ ACR has different technological characteristics compared to the DCA 2000 Microalbumin/Creatinine assay.

In the Afinion™ ACR assay, albumin is quantified based on an immunometric membrane flowthrough principle, where the color intensity of the membrane is measured by reflection. In the DCA 2000 Microalbumin/Creatinine assay, a specific antibody binds with albumin in the presence of polyethylene glycol. The albumin-antibody complexes that are formed cause increased turbidity which is measured as absorbance.

In the Afinion™ ACR assay, creatinine is quantified in an enzymatic colorimetric test where the creatinine concentration is measured by transmission. In the DCA 2000® Microalbumin/Creatinine assay, the creatinine assay is based on the Benedict/Behre chemistry (non enzymatic) and the creatinine concentration is quantified by absorbance.

Standardization

Albumin is calibrated against the ERM®-DA470 reference preparation. Creatinine is calibrated against SRM 914a.

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Summary of Non-Clinical Performance

The Afinion™ ACR assay is substantially equivalent to the DCA 2000® Microalbumin/Creatinine assay as demonstrated by non-clinical performance data in this 510(k) submission.

Summary of Clinical Performance

The Afinion™ ACR assay demonstrated substantially equivalent performance to the DCA 2000 Microalbumin/Creatinine assay as indicated by method comparison and precision tests.

Method Comparison:

At four external study sites 169 urine samples were analyzed with the Afmion™ ACR assay and the DCA 2000 Microalbumin/Creatinine assay. The correlation data (Passing-Bablok analysis) are summarized in Table 1.

Table 1. Method comparison, external study sites. Afinion™ ACR (y) vs. DCA 2000® Microalbumin/Creatinine assay.

Analyte	N	Regression line	Correlation coefficient
Albumin (mg/L)	169	$Y = 1.10x + 1.4$	0.99
Creatinine (mg/dL)	169	$Y = 0.93x + 2.3$	0.99
ACR (mg/g)	169	$Y = 1.16x + 1.0$	0.99

Linear regression analysis data, N = number of samples, r = correlation coefficient

In an internal method comparison study, 91 - 95 urine samples were analyzed with the Afinion™ ACR assay and the DCA 2000 Microalbumin/Creatinine assay. The correlation data (Passing-Bablok analysis) are summarized in Table 2.

Table 2. Method comparison, internal study. Afinion™ ACR (y) vs. DCA 2000® Microalbumin/Creatinine assay.

Analyte	N	Regression line	Correlationcoefficient
Albumin (mg/L)	91	Y=0.92x + 2.1	0.99
Creatinine (mg/dL)	95	Y=1.00x - 3.2	0.99
ACR (mg/g)	91	Y=1.01x + 0.7	0.99

Linear regression analysis data, N = number of samples, r = correlation coefficient

Precision:

An external precision study was performed in accordance with CLSI EPS-A protocol using two levels of urine samples (Sample1: albumin: < 20 mg/L and creatinine: 110-170 mg/dL, Sample 2: albumin: > 100 mg/L and creatinine > 170 mg/dL). The within-run CV was ≤ 8 % and the total CV was ≤ 9 % for all three analytes with both samples.

Afinion™ ACR Control:

An external precision study for Afinion™ ACR Control C I and C II was performed at 3 study sites. The Afinion™ ACR Controls were run in 6 replicates each day over 5 operating days. The

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within-day CV was ≤ 7 %, the within-site CV was ≤ 7 % and the between-site CV was ≤ 4 % for all three analytes with both control levels.

Conclusion

The Afinion™ ACR assay is substantially equivalent to the DCA 2000® Microalbumin/Creatinine assay (K963142) as demonstrated.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/5/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB 1 2 2008

Axis-Shield POC As c/o Mr. Jorunn Grevie Lolland Director of Quality Assurance & Regulatory Affair Marstrandgata 6, PO Box 6863 Rodelokka, Oslo, Norway N-0504

K072409 Re:

Trade/Device Name: Afinion™ ACR and Afinion™ ACR Control Regulation Number: 21 CFR §862.1225 Regulation Name: Creatinine test system. Regulatory Class: Class II Product Code: JFY, JIR, JJY Dated: February 4, 2008 Received: February 7, 2008

Dear Mr. Lolland:

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.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to legally marketed predicate device results in a classification for your device and thus, perroits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240) 276-0490. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its tollefire no (800) 638-2041 or (240) 276-3150 or at its Internet address at http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours.

Jean M. Cooper, M.S., D.v.M.

Yéan M. Cooper, M.S., D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Indication for Use

510(k) Number (if known): K072409

Device Name: Afinion™ ACR and Afinion™ ACR Control

Indication For Use:

Prescription Use _ (21 CFR Part 801 Subpart D)

And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

· Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

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Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K072409

Regulation Number and Section

§ 862.1225 Creatinine test system.

(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.