Afinion™ AS100 Analyzer System, consisting of the Afinion™ AS100 Analyzer Afinion™ Test Cartridges and Afinion™ Controls is for in-vitro diagnostic use only. Afinion™ AS100 Analyzer is a compact multi-assay analyzer for point-of -care testing, designed to analyze the Afinion™ Test Cartridges. The Afinion™ Analyzer System is easy to use, rapid and gives reliable and accurate results.

Afinion™ HbA Ic is an in-vitro test for quantitative determination of glycated hemoglobin in human blood. The measurement of % HbA1c is recommended as a marker of long-term metabolic control in persons with diabetes mellitus.

Afinion™ HbA1c Controls have been designed for use with the Afinion™ AS100 Analyzer System. Quality control using the Afinion™ HbA 1c Control should be done to confirm that the Afinion™ AS100 Analyzer System is working properly and provides reliable results.

Device Description

Instrument read, single usc in-vitro test for quantitative determination of glycated hemoglobin in human whole blood.

Afinion™ AS100 Analyzer utilizes a digital camera and Light Emitting Diodes to perform two kinds of measurements; reflection mcasurement (amount of light rcflected from a membrane) and transmission measurement (amount of light propagating through a liquid). The analyzer is self-calibrated and no calibration by user is needed.

AI/ML Overview

This looks like a 510(k) summary for a medical device called Afinion™ HbA1c, Afinion™ HbA1c Control, and Afinion™ AS100 Analyzer. I will extract the requested information based on the provided text.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are generally inferred from the "acceptable agreement" statements and specific thresholds mentioned for CV, linearity, and interference.

Study Type	Acceptance Criteria (Inferred/Stated)	Reported Device Performance
Method Comparison (Internal)	Acceptable agreement (implied by predicate equivalence)	Bias: -0.3 % HbA1c; 95% Limit of Agreement: -1.0 to 0.4 % HbA1c (vs. Bayer DCA 2000®)
Method Comparison (External)	Acceptable agreement (implied by predicate equivalence)	Slope: 0.91; y-intercept: 0.2 % HbA1c; r²: 0.96 (vs. Bayer DCA 2000®)
Method Comparison (vs. ERL Ref Method)	Excellent agreement (implied by predicate equivalence)	Bias: 0.0 % HbA1c; 95% Limit of Agreement: -0.3 to 0.3 % HbA1c (vs. Primus CLC385)
Capillary vs. Venous Blood	Excellent agreement	Bias: 0.0 %; 95% Limit of Agreement: -3.5 to 3.6 %; Slope: 0.99; y-intercept: 0.1 % HbA1c; r²: 0.99
Precision (Internal)	Within-run CV < 1.0%; Total CV ≤ 1.4% (for individual analytes)	Within-run CV: <1.0%; Total CV: ≤1.4% for both blood samples and controls
Precision (Internal, Multi-Analyzer)	CV ≤ 5%	CV: 2.1% and 2.8% on two blood samples
Precision (External)	Total CV < 2.5% (for EDTA samples)	Total CV: < 2.5% for all three EDTA samples (A, B, C)
Dilution Linearity	Meet all criteria for linearity (implied r² close to 1, slope close to 1, y-intercept close to 0)	Correlation coefficient r² = 1.00; Slope = 1.01; Y-intercept = 0.07 % HbA1c (analytical range 4-18% HbA1c)
Hb-Variant Interference	No interference (implied, by meeting ERL certification)	HbAC, HbAE, HbAD, HbAJ, HbAS, HbF, and carbamylated Hb do not interfere
Preglycated Hb Interference	≤ 5% interference	≤ 5% interference with the % HbA1c results for samples with up to 22% preglycated hemoglobin
Endogenous Interfering Substances	≤ 2% interference	Bilirubin (0.2 mg/mL), glucose (5.0 mg/mL), lipids (triglycerides; 15.7 mmol/L and cholesterol; 9.1 mmol/L) or fructosamine (680 umol/L) gave ≤ 2% interference
Exogenous Interfering Substances (Drugs)	≤ 3% interference	Glyburide (3.9 umol/L), metformin (310 umol/L), acetaminophen (1.7 mmol/L), ibuprofen (1.8 mmol/L), acetylsalicylic acid (3.3 mmol/L) and salicylic acid (4.3 mmol/L) gave ≤ 3% interference
Hemolysis Interference	Negligible interference (<4%) for low degree; Error code for high degree	For low degree of hemolysis (below 6%), <4% interference observed. For above 6% hemolysis, information code 204 (Hemolysed blood sample) displayed, and no result occurred.
Anticoagulant Comparison	No difference in results; Recoveries 98-103%; Average recoveries 100-101% compared to EDTA	No difference between capillary and venous blood with different anticoagulants (EDTA, Heparin, Na-citrate, NaF). Recoveries between 98-103% for each donor and anticoagulant; average recoveries 100-101% compared to EDTA.
Fail-safe System	Functioning satisfactorily (device aborts assay and ejects cartridge on error)	51 error messages observed during external study, all leading to assay abortion and cartridge ejection, with no result displayed.

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

Method Comparison (Internal): 40 venous EDTA blood samples. Provenance: Not explicitly stated, but "analyzed internally" suggests within the manufacturer's lab. Retrospective or prospective is not specified.
Method Comparison (External): 75 venous EDTA blood samples. Provenance: Three external study sites. Retrospective or prospective is not specified.
Method Comparison (vs. European Reference Laboratory): 39 venous EDTA blood samples. Provenance: European Reference Laboratory for glycohemoglobin (ERL). Retrospective or prospective is not specified.
Capillary vs. Venous Blood: 74 donors. Provenance: "analyzed externally." Retrospective or prospective is not specified.
Precision (Internal): Two levels of blood samples and two controls. Numbers of replicates/runs not explicitly given for total samples, but for multi-analyzer test, two blood samples were used.
Precision (External): Three EDTA blood samples (A, B, C). Provenance: Three external study sites.
Dilution Linearity: One high HbA1c sample mixed with a low HbA sample to create seven intermediate concentrations.
Hb-Variant Interference: Not explicitly specified, but "studies performed according to the ERL Manufacturer Check Up Certification procedure."
Preglycated Hb Interference: Not explicitly specified, but "Blood samples with up to 22 % preglycated hemoglobin."
Endogenous Interfering Substances: EDTA blood samples (number not specified).
Exogenous Interfering Substances (Drugs): EDTA blood samples (number not specified).
Hemolysis Interference: Samples with varying degrees of hemolysis.
Anticoagulant Comparison: 10 donors.

General Data Provenance: The studies were conducted by Axis-Shield PoC AS (Norway) and external study sites, including the European Reference Laboratory (ERL). The data is likely a mix of internally and externally generated data from Europe/US. The text does not explicitly state if the studies were retrospective or prospective, but the phrasing suggests prospective testing for most assays.

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

The document does not explicitly state the number or qualifications of experts used to establish a ground truth in the sense of a subjective expert reading/diagnosis. Instead, the ground truth for this device (an HbA1c assay) is established by:

Reference Methods: The predicate device (Bayer DCA 2000® Hemoglobin A1c assay) and the ERL reference method (Primus CLC385), which are themselves considered established and validated laboratory methods for HbA1c. These methods have inherent analytical capabilities, not dependent on expert interpretation for individual results.
IFCC Traceability: The device's results are traceable to the International Federation of Clinical Chemistry (IFCC) Reference Method and reported at DCCT-level via the NGSP Master Equation. This standardization provides the "true" value.

4. Adjudication Method (e.g. 2+1, 3+1, none) for the Test Set

Not applicable. This is an in-vitro diagnostic device that provides quantitative numerical results, not subjective interpretations requiring human adjudication. The "ground truth" is established by comparison to other analytical methods or reference standards, not by consensus among human readers.

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

Not applicable. This device is an automated assay for quantitative determination of HbA1c, not an AI system designed to assist human readers in interpreting images or data. There is no human reading component or AI assistance involved.

6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done

Yes, this entire submission describes standalone performance. The Afinion™ AS100 Analyzer System is a fully automated assay system ("algorithm only") that quantifies HbA1c in human whole blood. The performance studies evaluate the device's ability to accurately and precisely measure HbA1c without human intervention in the result generation, beyond sample loading and initiation.

7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)

The ground truth used is primarily comparison to established reference methods and predicate devices.

Predicate Device: Bayer DCA 2000® Hemoglobin A1c assay (K951361).
Reference Method: Primus CLC385 as used by the European Reference Laboratory for glycohemoglobin (ERL).
International Standardization: Traceability to the IFCC Reference Method and reporting at DCCT-level via the NGSP Master Equation.
Analytical Verification: For aspects like precision, linearity, and interference, the ground truth is against defined analytical standards and expected behaviors of known samples.

8. The Sample Size for the Training Set

The document does not refer to a "training set" in the context of machine learning or AI. This is a traditional IVD device. The development and calibration of such a device would involve numerous samples, but it's not a "training set" in the AI sense. The text mentions the analyzer is "self-calibrated and no calibration by user is needed," implying built-in calibration mechanisms developed during the device's engineering, not through an explicit "training set" as with AI algorithms.

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

As there is no "training set" in the AI sense, this question is not applicable. The device's internal calibration and algorithms were likely established through engineering and analytical validation using a wide range of known HbA1c concentrations and blood samples, traceable to international standards during its development phase.

Summary

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First response to K050574 Afinion™; HbA1c, Control & Analyzer; Appendix 5 Page 1 of 5 Axis-Shield PoC AS

510(k) Summary

Afinion™ HbA1c, Afinion™ HbA1c Control &

Afinion™ AS100 Analyzer

1. Introduction

According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for determination of substantial equivalence.

2. Submitter

Manufacturer/Owner Axis-Shield PoC AS Marstrandgata 6 P.O. Box 5863 Rodelokka N-0504 Oslo Norway Tel: +47 22 042 000 Fax: +47 22 042 001 Contact person: Jorunn Grevle Lolland Title: Manager Quality Assurance and Regulatory Affairs E-mail: JGL(@no.axis-shicld.com

Date prepared: March 3rd 2005

3. Device name

Trade name: Afinion™ HbA1c Common name: Glycated Hemoglobin Assay Classification name: Glycosylated Hemoglobin assay Regulation Number: 21 CFR § 864.7470

4. Predicate Device

Predicate device name: DCA2000® Hemoglobin A1c Reagent kit

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5. Device Description

Instrument read, single usc in-vitro test for quantitative determination of glycated hemoglobin in human whole blood.

6. Intended Use

Afinion™ HbA1c is an in-vitro test for quantitative determination of glycated hemoglobin in human blood. The measurement of % HbA1c is recommended as a marker of long-term metabolic control in persons with diabetes mellitus.

Afinion™ HbA1c Controls have been designed for use with the Afinion™ AS100 Analyzer System. Quality control using the Afinion™ HbA1c Control should be done to confirm that the Afinion™ AS100 Analyzer System is working properly and provides reliable results.

7. Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

The formation of glycohemoglobins is principally a function of the concentration of glucose to which the erythrocytes are exposed. Glycated hemoglobin is a clinically useful index of mean glycemia during the preceding 6-8 weeks. Chronic elevated blood sugar level of persons with diabetes mellitus will over time cause damage to the small vessels of the body. The damages develop slowly over years and are known to cause late complications. Depending on the assay method, HbA1c is approximately 3-6 % in non-diabetics, 6-8 % in controlled diabetics and can be as much as 18 % or higher in poorly controlled diabetics.

The Afinion™ HbA1c is a fully automated assay for the determination of the percentage of HbA1c in human whole blood, by use of Afinion™ AS100 Analyzer.

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Several fail-safe functions are provided to ensure the quality of assay results, to ensure that no erroneous results are presented to the user and to prevent mechanical damage to the analyzer itself. If an error should occur, an information code described in the User Manual is displayed.

Verification of the Afinion™ AS100 Analyzer has been performed and the results demonstrate compliance with specifications.

The results from the Afinion™ HbAlc assay are traceable to the International Federation of Clinical Chemistry (IFCC) Reference Method for measurement of HbA1c in human blood. NGSP (National Glycohemoglobin Standardization Program, US) recommends that HbA1c values are reported at DCCT-level (Diabetes Control and Complications Trial, US). The IFCC Working Group on Standardization of HbA1c has established a Master Equation for the Designated Comparison Method (the method used in the DCCT study, referred to as the NGSP Master Equation by the Working Group). This master equation (NGSP = 0.9148 IFCC + 2.152) is implemented in the Afinion™ AS100 Analyzer software and the Analyzer displays values at DCCT level.

The substantial equivalence, safety and efficacy of the Axis-Shield PoC Afinion™ HbA1c assay to Bayer DCA 2000® Hemoglobin A1c assay (K951361), 510(k) cleared 05/05/1995, CLIA Waived 11/12/1997, was evaluated internally and externally at three study sites.

Forty (40) venous EDTA blood samples were analyzed internally on both Afinion™ AS100 Analyzer and Bayer DCA 2000 . The Bland-Altman method comparison showed acceptable agreement with a bias of -0.3 % HbA1c and 95 % limit of agreement from -1.0 to 0.4 % HbA1c.

At three external study sites 75 venous EDTA blood samples were analyzed on both Afinion™ AS100 Analyzer and Bayer DCA 2000". The linear regression comparison method showed acceptable agreement with; slope = 0.91, y-intercept = 0.2 % HbA1c and r2 = 0.96.

39 venous EDTA blood samples from the European Reference Laboratory for glycohemoglobin (ERL) wcre analyzed internally by the Afinion™ HbA1c assay and by ERL with their reference method Primus CLC385. The Bland-Altman method comparison showed excellent agreement with a bias of 0.0 % HbA 1 c and 95 % limit of agreement from -0.3 to 0.3 % HbA1c.

Capillary and venous blood samples from 74 donors were analyzed externally with the Afinion™ HbA1c assay. The Bland-Altman comparison showed excellent agreement with a bias of 0.0 % and 95 % limit of agreement from -3.5 to 3.6 %. Linear regression; slope = 0.99, y-interccpt = 0.1 % HbA1c and r2 = 0.99.

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Precision studies were performed according to Clinical and Laboratory Standards NCCLS guideline EP5-A by using two levels of blood samples (5,6 and 10,0 % HbAlc) and two Afinion™ HbA1c Controls (6,5 and 9,1 % HbA1c). The withinrun CV was <1.0 % and the total CV was ≤1.4 % for both samples and controls.

The total precision of the Afinion™ HbA1c assay for two blood samples tested on ten Afinion™ AS100 Analyzers showed a CV of 2.1 % and 2.8 %. which is well within the acceptance criterion of CV ≤ 5 %.

Intended users at three external study sites performed external precision studies on three Afinion™ AS100 Analyzers. Two lots of Afinion™ HbA1c and three EDTA blood samples (A, B and C), analyzed for 10 operating days with six replicates of each sample, were used. The total precision showed a CV of < 2.5 % for all three EDTA samples.

Dilution linearity within the analytical range of 4-18 % HbA1c was demonstrated to meet all criteria for linearity. Dilution of high HbA1c sample by mixing with a sample with low HbA into seven intermediate concentrations showed a correlation coefficient r2 = 1.00, slope = 1.01 and y-intercept = 0.07 % HbA1c,

Studies performed according to the ERL Manufacturer Check Up Certification procedure by ERL technical staff showed that the Hb-variants HbAC. HbAE. HbAD, HbAJ, HbAS, HbF and the derivate carbamylated Hb do not interfere with analyzes of % HbA1c on Afinion™ AS100 Analyzer.

Blood samples with up to 22 % preglycated hemoglobin (labile form) showed ≤ 5 % interference with the % HbA1c results when analyzed with the Afinion™ HbA1c assay.

Effect on quantification by endogenous interfering substances was tested. Bilirubin (0.2 mg/mL), glucose (5.0 mg/mL), lipids (triglycerides; 15.7 mmol/L and cholesterol; 9.1 mmol/L) or fructosamine (680 umol/L) in EDTA blood samples gave ≤ 2 % interference when analyzed for % HbA1c on the Afinion™ AS100 Analyzer.

The possible interference from the prescription drugs glyburide and metformin and the over-the-counter (OTC) drugs acetaminophen, ibuprofen, acetylsalicylic acid and its active metabolite salicylic acid has been tested according to Clinical and Laboratory Standards NCCLS guideline EP7-A. Glyburide (3.9 umol/L), metformin (310 umol/L), acetaminophen (1.7 mmol/L), ibuprofen (1.8 mmol/L), acetylsalicylic acid (3.3 mmol/L) and salicylic acid (4.3 mmol/L) in EDTA blood samples gave ≤ 3 % interference when analyzed for % HbA1c on the Afinion™ AS100 Analyzer.

Hemolysed samples cannot be analyzed by the Afinion™ HbA1c assay. Samples with a degrec of hemolysis above 6 % will result in information code 204 (Hemolysed blood sample) displayed on the Afinion™ AS100 Analyzer and no

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result will occur. In samples with a low degree of hemolysis (below 6 %) a negligible interference (<4 %) was observed when analyzed with Afinion™ HbAlc.

Capillary samples and EDTA, Heparin, Na-citrate and NaF blood samples were collected from 10 donors. The results show no difference between the capillary and venous blood with different anticoagulants. The recoveries, compared to EDTA, varied between 98-103 % for each donor and anticoagulant. The average recoveries for each anticoagulant were 100-101 % compared to EDTA.

In total 51 error messages were observed during the external study period. All messages lead to an abortion of the assay followed by an ejection of cartridge. That no results were displayed in these cases shows that the fail-safe system is functioning satisfactory.

When considering the comparison studies between Afinion™ HbA1c and Bayer DCA 2000® Hemoglobin Alc and the additional documentation supporting the Afinion™ HbA1c, it can be concluded that the Axis-Shield PoC Afinion™ HbA1c when tested on the Afinion™ AS100 Analyzer is substantially equivalent to Bayer DCA 2000® Hemoglobin A1c assay (K951361).

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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 features a stylized caduceus symbol, which is often associated with medicine and healthcare. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol. The logo is simple and recognizable, representing the department's role in promoting health and well-being in the United States.

JUL 2 2 2005

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Axis- Shield PoC AS c/o Ronald G. Leonardi, Ph.D. President R&R Registrations P.O. Box 262069 San Diego, CA 92196-2069

K050574 Re:

Trade/Device Name: Afinion™ HbA1c Afinion™ HbA1c Controls Afinion™ AS100 Analyzer Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP, JJX, JQT Dated: June 28, 2005 Received: July 5, 2005

Dear Dr. Leonardi:

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) This letter will and in your is of substantial equivalence of your device to a legally premaired notined.com "The sults in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, rr you desire sportion and advertising of your device, please contact the Office of In of questions on the promotion and Safety at (240) 276-0484. 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 I ou may ootain other generational and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Carol C. Benam

Carol C. Benson, M.A. Acting 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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INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K050574

Device Name: Afinion™ HbA1c, Afinion™ HbA1c Control and Afinion™ AS100 Analyzer

Indications For Use:

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

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Prescription Use (Per 21 CFR 801.109) OR

Over-The-Counter Use

(Optional Format 1-2-96)

Albert Seatz

Division Sign-Off

Office of In Vitro Diagnostic
Device Evaluation and Safety

S1014 K050574

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Regulation Number and Section

§ 864.7470 Glycosylated hemoglobin assay.

(a)
Identification. A glycosylated hemoglobin assay is a device used to measure the glycosylated hemoglobins (A1a , A1b , and A1c ) in a patient's blood by a column chromatographic procedure. Measurement of glycosylated hemoglobin is used to assess the level of control of a patient's diabetes and to determine the proper insulin dosage for a patient. Elevated levels of glycosylated hemoglobin indicate uncontrolled diabetes in a patient.(b)
Classification. Class II (performance standards).