The AxSYM Digoxin III assay is a microparticle enzyme immunoassay (MEIA) for the quantitative measurement of digoxin, a cardiovascular drug, in serum or plasma. The measurements obtained are used in the treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.

Device Description

The AxSYM Digoxin III Reagent Pack is composed of the following reagent components: • Digoxin: Alkaline Phosphatase Conjugate • Anti-digoxin (Rabbit) Coated Microparticles • MEIA Buffer • Digoxin III Probe Wash Solution
The AxSYM Digoxin III Calibrators contain six bottles of accurately measured amounts of digoxin prepared in recalcified human plasma, nonreactive for HBsAg, HIV-1 RNA or HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2.
The AxSYM Digoxin III Controls contain three bottles of accurately measured amounts of digoxin prepared in recalcified human plasma, nonreactive for HBsAg, HIV-1 RNA or HIV-1 Ag, anti-HCV, and anti-HIV-1/HIV-2.

AI/ML Overview

Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance:

The document primarily focuses on demonstrating substantial equivalence to a predicate device by comparing attributes and performance characteristics. While explicit "acceptance criteria" in a traditional sense (e.g., specific thresholds for accuracy, precision) are not fully detailed as a separate section, the comparison points serve as acceptance criteria for demonstrating equivalence.

Acceptance Criterion (Attribute)	Predicate Device Performance (AxSYM Digoxin II)	Modified Device Performance (AxSYM Digoxin III)	Met/Not Met (Based on comparison)
Analyte Measured	Digoxin	Same	Met
Assay Principle	MEIA technology, competitive format	Same	Met
Instrumentation	Abbott AxSYM Analyzer	Same	Met
Sample Type	Serum or plasma	Same	Met
Sample Volume	150 µL (Routine), 131 µL (STAT)	194 µL (Routine and STAT)	Met (Change noted, but acceptable)
Sample Pretreatment	No	No	Met
Assay Type	Quantitative	Same	Met
Dynamic Range	0.0 to 4.0 ng/mL (0.00 to 5.12 nmol/L)	Same	Met
Calibrator Values	0.0, 0.5, 1.0, 2.0, 3.0, and 4.0 ng/mL	Same	Met
Control Values	0.9, 1.9, and 3.2 ng/mL	Same	Met
Sensitivity	0.3 ng/mL (0.38 nmol/L)	Same	Met
Immunoassay Format	2-step	1-step	Met (Change noted, but acceptable)
Saponin (%) in Conjugate Diluent	0.13	0.3	Met (Change noted, but acceptable)
Antibody	Rabbit Polyclonal	Same	Met
Conjugate	Digoxin: Alkaline Phosphatase	Same	Met
Bilirubin Interference at 20 mg/dL	Less than 10%	Less than 20%	Met (Within acceptable range)
Drug Compound Interference (Aldosterone inhibitors and other steroids)	-33% to -3%	-2% to 2%	Met (Showed improvement)
Probe Wash Solution Ingredients	2 M sodium chloride 0.1% sodium azide	2 M sodium chloride 0.1% sodium azide 0.5% Triton X-100 0.05% antifoam	Met (Change noted, but acceptable)
Medium Control Range (Target: 1.9 ng/mL)	1.50 to 2.30 ng/mL	1.43 to 2.38 ng/mL	Met (Similar range)
High Control Range (Target: 3.2 ng/mL)	2.60 to 3.80 ng/mL	2.50 to 3.90 ng/mL	Met (Similar range)

The overall conclusion is: "Results of laboratory testing demonstrate that the performance of the Abbott AxSYM Digoxin III assay is acceptable and comparable to the performance of the predicate device, when used according to its intended use." This statement confirms all criteria were met to achieve substantial equivalence.

2. Sample size used for the test set and the data provenance:

The document does not explicitly state the sample size used for the test set or the data provenance (e.g., country of origin, retrospective/prospective). It only mentions "Results of laboratory testing."

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

This information is not provided in the document. For an in vitro diagnostic device like this, the "ground truth" would likely be established through reference methods or highly accurate comparative assays rather than expert interpretation.

4. Adjudication method for the test set:

This information is not provided.

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 an in vitro diagnostic device (IVD) for quantitative measurement of a drug in serum/plasma. It is not an AI-assisted diagnostic imaging device or one that involves human "readers" in the context of interpretation. Therefore, an MRMC comparative effectiveness study involving human readers and AI assistance is not applicable and was not performed.

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

The AxSYM Digoxin III assay is an automated in vitro diagnostic device. The performance data presented (e.g., interference, control ranges) represent the standalone performance of the assay system itself, without direct human intervention in the interpretive process of the result once generated by the instrument.

7. The type of ground truth used:

While not explicitly detailed, for an IVD test measuring drug levels, the "ground truth" would typically be established by:

Reference Methods: Highly accurate and validated analytical techniques (e.g., mass spectrometry) to determine the true concentration of digoxin in samples.
Known Concentrations: Use of samples with precisely known concentrations of digoxin (e.g., spiked samples, certified reference materials).

8. The sample size for the training set:

The document does not provide information about a "training set" or its sample size. For an IVD assay like this, development typically involves method optimization and validation rather than machine learning training sets in the computational sense.

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

As no training set is discussed or implied, this information is not provided.

Summary

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K061249

JUN - 2 2006

Special 510(k) Summary

Summary of Safety and Effectiveness Information Supporting a Substantially Equivalent Determination

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

Submitter's Name and Address:	Abbott LaboratoriesDiagnostics Division100 Abbott Park RoadAbbott Park, Illinois 60064-3500Telephone: (847) 938-4807Fax: (847) 937-9616Contact: Kenton.Smith@abbott.com
Date Prepared:	May 2006
Device Proprietary Name:Device Common Name:Classification Number:	AxSYM® Digoxin IIIDigoxinToxicology, 21 CFR §862.3320
Predicate Device:	AxSYM Digoxin II510(k) Number: K953718
Device Description:	The AxSYM Digoxin III Reagent Pack iscomposed of the following reagent components:• Digoxin: Alkaline Phosphatase Conjugate• Anti-digoxin (Rabbit) Coated Microparticles• MEIA Buffer• Digoxin III Probe Wash Solution
	The AxSYM Digoxin III Calibrators contain sixbottles of accurately measured amounts ofdigoxin prepared in recalcified human plasma,nonreactive for HBsAg, HIV-1 RNA or HIV-1Ag, anti-HCV, and anti-HIV-1/HIV-2.
	The AxSYM Digoxin III Controls contain threebottles of accurately measured amounts ofdigoxin prepared in recalcified human plasma,nonreactive for HBsAg, HIV-1 RNA or HIV-1Ag, anti-HCV, and anti-HIV-1/HIV-2.

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Intended Use:

Comparison to Predicate Device:

Attribute	AxSYM Digoxin IIPredicate Device	AxSYM Digoxin IIIModified Device
Analyte Measured	Digoxin	Same
Assay Principle	MEIA technology,competitive format	Same
Instrumentation	Abbott AxSYM Analyzer	Same
Sample Type	Serum or plasma	Same
Sample Volume	150 µL (Routine)131 µL (STAT)	194 µL (Routine and STAT)
Sample Pretreatment	No	No
Assay Type	Quantitative	Same
Dynamic Range	0.0 to 4.0 ng/mL (0.00 to5.12 nmol/L)	Same
Calibrator Values	0.0, 0.5, 1.0, 2.0, 3.0, and 4.0ng/mL (0.00, 0.64, 1.28,2.56, 3.84, and 5.12 nmol/L)	Same
Control Values	0.9, 1.9, and 3.2 ng/mL(1.15, 2.43, and 4.10 nmol/L)	Same
Sensitivity	0.3 ng/mL (0.38 nmol/L)	Same
Immunoassay Format	2-step	1-step
Saponin (%) in ConjugateDiluent	0.13	0.3
Antibody	Rabbit Polyclonal	Same
Conjugate	Digoxin: AlkalinePhosphatase	Same

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Bilirubin Interference at20 mg/dL	Less than 10%	Less than 20%
Drug CompoundInterference (Aldosteroneinhibitors and othersteroids)	-33% to -3%	-2% to 2%
Probe Wash SolutionIngredients	2 M sodium chloride0.1% sodium azide	2 M sodium chloride0.1% sodium azide0.5% Triton X-1000.05% antifoam
Medium Control Range(Target: 1.9 ng/mL)	1.50 to 2.30 ng/mL	1.43 to 2.38 ng/mL
High Control Range(Target: 3.2 ng/mL)	2.60 to 3.80 ng/mL	2.50 to 3.90 ng/mL

Conclusion: Results of laboratory testing demonstrate that the performance of the Abbott AxSYM Digoxin III assay is acceptable and comparable to the performance of the predicate device, when used according to its intended use.

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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

Mr. Kenton L. Smith Senior Regulatory Affairs Specialist Abbott Laboratories Dept. 9VA, Bldg AP6C-2 100 Abbott Park Road Abbott Park, Illinois 60064-3500

JUN - 2 2006

Re: K061249

Trade/Device Name: AxSYM® Digoxin III Regulation Number: 21 CFR§ 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Code: KXT, JIT, JJT, JJX Dated: May 3, 2006 Received: May 4, 2006

Dear Mr. Smith:

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 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 (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 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/industry/support/index.html.

Sincerely yours,

Alberto Gutz

Alberto Gutierrez, Ph.D. 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

510(k) Number (if known): K061249

Device Name: AxSYM® Digoxin III

Indications For Use:

Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use (21 CFR 807 Subpart C)

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

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Carol C Benam
Division Sign-Off

Page 1 of 1

Office of In Vitro Diagnostic Device Evaluation and Safety

310(k) K061249

Regulation Number and Section

§ 862.3320 Digoxin test system.

(a)
Identification. A digoxin test system is a device intended to measure digoxin, a cardiovascular drug, in serum and plasma. Measurements obtained by this device are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to ensure appropriate therapy.(b)
Classification. Class II.