The MULTIGENT™ Hb A1c assay is used in clinical laboratories for the quantitative in vitro measurement of percent Hb Alc (hemoglobin fraction) in human whole blood on the AEROSET® System and ARCHITECT® c8000™ System. The Hb A1c assay is intended to aid in the monitoring of long-term blood glucose control and compliance in individuals with diabetes mellitus. The MULTIGENT™ Hb A1c assay is not intended for use in diagnosing diabetes mellitus.

The MULTIGENT™ Ho A1c Calibrators are intended for in vitro diagnostic use with the AEROSET® System and the ARCHITECT® c8000™ System for the calibration of the assays in the MULTIGENT™ Hb Alc Reagent Kit.

The MULTIGENT™ Ho Alc Controls are intended for in vitro diagnostic use with the AEROSET® System and the ARCHITECT® c8000™ System for quality control of the assays in the MULTIGENTTM Hb A1c Reagent Kit.

Device Description

The Device consists of the MULTIGENT™ Hemoglobin A 1 c Reagents, MULTIGENT™ Hemoglobin Alc Calibrators , and MULTIGENT™ Hemoglobin A 1 c Controls, intended for use on AEROSET® System and ARCHITECT® c8000™ System for determination of stable % HbAlc.

The assay consists of two separate concentration measurements, the stable form of glycated hemoglobin (Hb A 1 c) and the total hemoglobin (THb), which are used only to determine the percent Hb Alc. and must not be used individually for diagnostic purposes.

The whole blood specimen is pre-treated to lyse the erythrocytes. The hemoglobin is degraded by the proteolytic enzyme, pepsin, to form a hemolysate. Both the THb and the Hb A1c concentrations are determined from the same hemolysate.

The concentration of total hemoglobin is determined colorimetrically using a wavelength of 604 mm. The sample's measured absorbance is compared to a two-point calibration curve for total hemoglobin.

The concentration of stable Hb Alc is measured immunoturbidimetrically using a microparticle agglutination inhibition method. The Hb A1c antibody reagent (R1) contains specific anti-Hb A 1c mouse monoclonal antibodies coupled to microparticles. The Hb A1c agglutinator reagent (R2) contains several copies of the immunoreactive portion of Hb A1c (hapten), covalently bound to a polymer.

In the absence of Hb Alc in the sample, the hapten in the R2 reagent binds with the antibodycoated microparticles in the R1 antibody reagent and results in an increase in the rate of agglutination and results in an increase in measured absorbance. In the presence of HD A Ic in the sample, the Hb Alc competes with the hapten in the R2 reagent for binding sites on the antibody-coated microparticles in the R1 antibody reagent and will slow the rate of agglutination as it competes with the Hb Alc agglutinator for antibody binding sites.

The increase in concentration of Hb Alc in the sample is inversely proportional to the rate of agglutination and the measured absorbance. The absorbance is measured using a wavelength of 700 nm. The measured absorbance of the sample is compared to the measured absorbance of known Hb Alc concentrations (g/dL) of a six-level calibration curve, and the concentration of the sample is interpolated. The percent Hb A1c is the Hb A1c /THb ratio, calculated automatically by the AEROSET® System and ARCHITECT® c8000™ System, using a conversion factor to correlate the result with an NGSP-certified method.

The calibrators are supplied in liquid form and are ready to use without pretreatment. The controls are supplied in lyophilized form and are to be reconstituted with the supplied reconstitution fluid.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study details for the Seradyn MULTIGENT™ Hemoglobin A1c device, based on the provided 510(k) summary:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Acceptance Criteria (from Predicate Device Label Claims)	Reported Device Performance (MULTIGENT™ HbA1c Assay)
Linearity (% HbA1c)	4.2% to 20.8%	2% to 20%
Specificity/Interfering Substances
Bilirubin	Difference of ≤ 1% Hb A1c (for MULTIGENT) / ± 10% of untreated sample (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 50 mg/dL
Triglyceride	Difference of ≤ 1% Hb A1c (for MULTIGENT) / ± 10% of untreated sample (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 1600 mg/dL
Rheumatoid Factor	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 3100 U/mL
Acetyl Salicylate	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 50.8 mg/dL
Sodium Cyanate	Difference of ≤ 1% Hb A1c (for MULTIGENT) / ± 10% of untreated sample (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 50 mg/dL
Ascorbic Acid	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 50 mg/dL
Urea (Carbamyl GHb)	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 667 mg/dL
Gamma Globulin	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 5 g/dL
HAMA Type 1	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 100% replaced plasma
HAMA Type 2	None reported for Tosoh	No interference (≤ 1% Hb A1c difference from untreated sample) at 100% replaced plasma
Labile Hb A1c	Separates LA1c (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 14 mg/mL of glucose
Ala	Chromatographically Separates out Ala (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 2.85%
Alb	Chromatographically Separates out Alb (for Tosoh)	No interference (≤ 1% Hb A1c difference from untreated sample) at 1.25%
Precision (Mean ~5.0% HbA1c)
- Within Run CV	0.90 %CV	1.17 %CV
- Between Run CV	0.40 %CV	0.40 %CV
- Total CV	1.12 %CV	1.46 %CV
Precision (Mean ~10.5% HbA1c)
- Within Run CV	0.53 %CV (for 10.9% HbA1c)	1.07 %CV
- Between Run CV	0.46 %CV (for 10.9% HbA1c)	0.73 %CV
- Total CV	0.71 %CV (for 10.9% HbA1c)	1.31 %CV
Method Comparison (Correlation)	Implied high correlation (predicate is marketed)	Multiple R (Correlation Coef.): 0.993 (Aeroset) & 0.994 (c8000)

Study Details

Sample Size Used for the Test Set and Data Provenance:
- Specificity and Interfering Substances: Specific concentrations of various interfering substances were used. The number of samples tested per substance is not explicitly stated, but the tests were performed "with the MULTIGENT™ Hb A1c assay." The provenance is not specified but is implicitly from laboratory testing.
- Precision: "Whole blood samples" were used. The sample size for precision studies was n=80 (following NCCLS EP5-A protocol) for each of two concentration levels on both the AEROSET® System and ARCHITECT® c8000™ System. Data provenance is implicitly from laboratory testing, most likely in the USA where Seradyn Inc. is located.
- Method Comparison: 117 "whole blood patient samples" were used. The provenance is not specified but is implicitly from laboratory testing, most likely in the USA.
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This is a submission for an in-vitro diagnostic device (reagents and controls), not an imaging or diagnostic algorithm that relies on expert interpretation. Therefore, the concept of "experts establishing ground truth" in the traditional sense of clinical interpretations (e.g., radiologists) is not directly applicable.
- The "ground truth" for the comparative studies is established by the predicate device, the Tosoh Medics Inc., G7 Automated HPLC Analyzer: HbA1c Variant Analysis Mode. This predicate device is a legally marketed device and its results are considered the reference for comparison.
Adjudication Method for the Test Set:
- Not applicable. The study is a comparative analysis between the new device and a predicate device, and laboratory performance metrics. Human adjudication of results is not described or relevant for this type of device submission.
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:
- No, an MRMC comparative effectiveness study was not done. This type of study is relevant for diagnostic imaging or interpretation by human readers, where AI might assist in improving their performance. This submission is for an in-vitro diagnostic instrument system, which automates the measurement process.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, the performance data presented (linearity, specificity, precision, method comparison) reflects the standalone performance of the MULTIGENT™ Hb A1c assay on the AEROSET® System and ARCHITECT® c8000™ System. While human operators are involved in running the assay and handling samples, the measurement itself is automated by the device, and the reported performance characteristics are inherent to the assay and instrument.
The type of ground truth used:
- For the comparative analysis, the results obtained from the legally marketed predicate device (Tosoh G7 Automated HPLC - Hb A1c Variant Analysis Mode) served as the ground truth or "reference method" for demonstrating substantial equivalence.
- For other performance characteristics like linearity and precision, the ground truth is established through internal scientific validation against known standards and established protocols (e.g., NCCLS EP5-A).
The sample size for the training set:
- The document does not explicitly mention a "training set" in the context of machine learning. For an in-vitro diagnostic device of this nature, calibration curves are established using known concentrations of HbA1c calibrators, and internal validation is performed. The number of samples for developing these internal parameters is not specified, but the calibrators themselves are a "six-level calibration curve" (page 2).
How the ground truth for the training set was established:
- Again, a "training set" in the AI/ML sense is not directly applicable. The "ground truth" for establishing the calibration and internal performance characteristics is based on:
  - Known concentrations of stable HbA1c in the MULTIGENT™ Hb A1c Calibrators. These calibrators are provided in liquid form and are used to create the six-level calibration curve for the assay.
  - Standardized protocols and materials for internal validation studies, such as the NCCLS EP5-A protocol for precision.

Summary

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Suite 1000 Indianapolis, IN 46268

510K SUMMARY

This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.

The assigned 510(k) number is: K0336

1. COMPANY/CONTACT PERSON:

Seradyn, Inc 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268

Establishment registration No: 1836010

Les Padilla Technical Product Manager Telephone: (317) 610-3823 Fax: (317) 610-0018 e-mail: lpadilla@seradyn.com

2. DATE PREPARED:

November 18, 2003

3. DEVICE NAME:

a. Proprietary Name:	MULTIGENTTM Hemoglobin A1c ReagentsMULTIGENTTM Hb A1c CalibratorsMULTIGENTTM Hb A1c Controls
b. Common Name:	Hemoglobin A1c (Hb A1c); Glycated / GlycosylatedHemoglobin
c. Classification Name:	Class II, LCP, 21 CFR 864.7470 GlycosylatedHemoglobin assay

4. LEGALLY MARKETED DEVICES TO WHICH EQUIVALENCY IS CLAIMED:

Tosoh Medics Inc., G7 Automated HPLC Analyzer: HbA1c Variant Analysis Mode, cleared under K011434.

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5. DESCRIPTION OF DEVICE:

The concentration of total hemoglobin is determined colorimetrically using a wavelength of 604 mm. The sample's measured absorbance is compared to a two-point calibration curve for total hemoglobin.

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6. INTENDED USE:

The MULTIGENT™ Hb A1c assay is used in clinical laboratories for the quantitative in vitro measurement of percent Hb Alc (hemoglobin fraction) in human whole blood on the AEROSET® System and ARCHITECT® c8000™ System. The Hb A 1 c assay is intended to aid in the monitoring of long-term blood glucose control and compliance in individuals with diabetes mellitus. The MULTIGENT™ Hb A1c assay is not intended for use in diagnosing diabetes mellitus.

The MULTIGENT™ Hb A1c Calibrators are intended for in vitro diagnostic use with the AEROSET® System and the ARCHITECT® c8000™ System for the calibration of the assays in the MULTIGENTTM Hb A1c Reagent Kit.

The MULTIGENT™ Hb Alc Controls are intended for in vitro diagnostic use with the AEROSET® System and the ARCHITECT® c8000™ System for quality control of the assays in the MULTIGENTTM Hb A1c Reagent Kit.

7. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS:

The MULTIGENT™ Hemoglobin A1c system for measuring % Hb A1c is based on an immunoturbidimetrically microparticle agglutination inhibition method that is specific for stable Hb Alc and is used in conjunction with a colorimetric method to determine the Total Hemoglobin.

The Predicate device, Tosoh Medics Inc., G7 Automated HPLC Analyzer: Hb A1c Vanant Analysis Mode, uses an automated High Performance Liquid Chromatography (HPLC) system, a cation exchange column and gradient elution buffers which separates the stable Hb A1c from other hemoglobin components

Although the MULTIGENT™ Hemoglobin A1c system has technological differences from the predicate device, the intended use are similar and the results from performance characteristics data from non-clinical studies supports a claim of substantial equivalence to the predicate device.

The performance data is summarized below.

8. SUMMARY OF NON-CLINICAL TESTING (COMPARATIVE ANALYSIS TO PREDICATE DEVICE LABEL CLAIMS:

Linearity (% HbA1c) and Limit of Detection

Linearity of the MULTIGENT™ HbA1c assay for the reportable % Hb A1c is from 2% to 20%. The label claim for the predicate device is 4.2% to 20.8%

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Specificity and Interfering Substances:

The MULTIGENT™ Hb A1c assay has no interference as defined by acceptance criteria of difference of ≤ 1% Hb Alc when compared to an untreated sample. Below is a summary of the concentrations tested with the MULTIGENT™ HbA1c assay and the predicate device. Tosoh acceptance criteria is ± 10% of the untreated sample.

InterferingSubstance	Concentrations of InterferentTested by MULTIGENT™Hb A1c Assay with	Concentrations of Interferent TestedBy TOSOH G7 Automated HPLC
Bilirubin	50 mg/dL	20 mg/dL
Triglyceride	1600 mg/dL	2000 mg/dL
Rheumatoid Factor	3100 U/mL	None reported
Acetyl Salicylate	50.8 mg/dL	None reported
Sodium Cyanate	50 mg/dL	20 mg/dL
Ascorbic Acid	50 mg/dL	None reported
Urea (Carbamyl GHb)	667 mg/dL	None reported
Gamma Globulin	5 g/dL	None reported
HAMA Type 1	Plasma 100% replaced	None reported
HAMA Type 2	Plasma 100% replaced	None reported
Labile Hb Alc	14 mg/mL of glucose	Separates LA1c
Ala	2.85 %	Chromatographically Separates out Ala
Alb	1.25%	Chromatographically Separates out Alb

Precision

Precision studies for the MULTIGENT™ Hemoglobin A1c assay was performed on both the AEROSET® System and ARCHITECT® c8000™ System using the NCCLS EP5-A protocol (n=80). The studies demonstrated that a whole blood sample with a mean of approximately 5.0% HbA1c, a within run precision of 1.17 % CV, a between run precision of 0.40 %CV, and a total precision of 1.46 %CV was achieved. For a whole blood sample with approximately 10.5% HbAlc, a within run precision of 1.07 % CV, a between run precision of 0.73 %CV, and a total precision of 1.31 %CV was achieved.

The predicate device precision labeling claims are: within run precision of 0.90 %CV, between run precision of 0.40%CV, and a total precision of 1.12 %CV for a whole blood sample with a mean of 5.8% HbA1c. A whole blood sample with a mean of 10.9% HbA1c had a within run precision of 0.53 %CV, between run precision of 0.46%CV, and a total precision of 0.71 %CV

The precision of the MULTIGENT " Hemoglobin A1c assay, performed on either the AEROSET® System and ARCHITECT® c8000™ System are within acceptable limits. None of the raw data values differed from a MIN/MAX of >1% Hb A1c.

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Method Comparison

Correlation studies were performed by assaying whole blood patient samples on the Abbott AEROSET® System and the Abbott c8000 system using the MULTIGENT™ Hb A1c assay and the Tosoh G7 Automated HPLC - Hb A1c Variant Analysis Mode. The data was subjected to linear regression statistics (least squares method) and yielded the following results:

Regression Statistics
Independent Variable	Tosoh	Tosoh
Dependent Variable	Aeroset	c8000
Multiple R (Corr. Coef.)	0.993	0.994
Observations (n)	117	117
y-Intercept	0.240	0.141
Slope	0.976	0.998

9. CONCLUSIONS:

The results of non-clinical testing demonstrate that the performance and safety and effectiveness of the MULTIGENT™ Hb A1c assay on the Abbott AEROSET® System and the Abbott ARCHITECT® c8000 system are substantially equivalent to that of the Tosoh G7 Automated HPLC - Hb A1c Variant Analysis Mode.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

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Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

FEB - 9 2004

Mr. Les Padilla Technical Product Manager Seradyn, Inc. 7998 Georgetown Road - Suite 1000 Indianapolis, IN 46268-5620

Re: K033674

Trade/Device Name: Multigent™ Hemoglobin A1c on the Abbott Aeroset® System and the Abbott Architect® c8000TM System Regulation Number: 21 CFR 864.7470 Regulation Name: Glycosylated hemoglobin assay Regulatory Class: Class II Product Code: LCP; GGM; KRZ Dated: November 19, 2003 Received: November 24, 2003

Dear Mr. Padilla:

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. Iisting 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 a legally marketed predicate device results 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, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. 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 toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours.

Jean M. Cooper, MS, DVM.

Yean M. Cooper, MS, 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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7998 Georgetown Rd
Suite 1000
Indianapolis, IN 46268

INDICATIONS FOR USE STATEMENT

510(k) Number (if known): K033 (g 74

MULTIGENT™ HEMOGLOBIN A1c ON THE ABBOTT AEROSET® Device Name: SYSTEM AND THE ABBOTT ARCHITECT® c8000™ SYSTEM

Indications For Use:

The MULTIGENT™ Ho Alc assay is used in clinical laboratories for the quantitative in vitro measurement of percent Hb A1c (hemoglobin fraction) in human whole blood on the AEROSET® System and ARCHITECT® c8000™ System. The Hb A1c assay is intended to aid in the monitoring of long-term blood glucose control and compliance in individuals with diabetes mellitus. The MULTIGENT™ Hb A1c assay is not intended for use in diagnosing diabetes mellitus.

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

Concurrence of CDRH, Office of Device Evaluation (ODE)

Prescription Use (Per 21 CFR 801.109)
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Over-The-Counter Use (Optional Format 1-2-96)
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Carol C Benson
Division Sign-Off

Office of In Vitro Diagnostic Device Evaluation and Safety510(k) K03 3674

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).