The DIGXN method is an in vitro diagnostic test for the quantitative measurement of digoxin in human serum and plasma on the Dimension Vista® System. Measurements of digoxin are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to help ensure appropriate therapy.

The DRUG 4 CAL is an in vitro diagnostic product for the calibration of the LOCI Digoxin (DIGXN) method on the Dimension Vista® System.

Device Description

Method: The DIGXN method is a homogeneous, sequential, chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated F(ab')2 fragment of an anti-Digoxin mouse monoclonal antibody. The first bead reagent (Chemibeads) is coated with ouabain, a weaker binding analog of digoxin, and contains a photosensitizer dye. In a first step, sample is incubated with biotinylated F(ab')> which allows digoxin from the sample to saturate a fraction of the biotinylated F(ab')2 that is directly related to the digoxin concentration. In a second step, ouabain chemibeads are added and form bead/biotinylated F(ab')> immunocomplexes with the non-saturated fraction of the biotinylated F(ab')>. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemilyminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the digoxin concentration in the sample.

Calibrator: The DRUG 4 Calibrator is a 5 level, liquid calibrator. It is packaged as a kit of ten vials, two vials per level (A, B, C, D and E), 2.5 mL per vial. The product matrix is human serum.

AI/ML Overview

Here's a summary of the acceptance criteria and study details for the Dimension Vista® LOCI Digoxin Flex® Reagent Cartridge (K6435) and Dimension Vista® DRUG 4 Calibrator (KC460), based on the provided text:

Acceptance Criteria and Device Performance

Feature	Acceptance Criteria (Implied by Predicate Equivalence)	Reported Device Performance (DIGXN vs. Predicate DGNA)
Method Comparison
Slope	Close to 1.00	1.02
Intercept	Close to 0 ng/mL	-0.04 ng/mL
Correlation Coeff. (r)	High, close to 1.0	0.98
Reproducibility	(Based on CLSI EP5-A2 guidance and typical precision for similar assays. Specific numerical targets not explicitly stated as "acceptance criteria" but demonstrated through performance.)
Repeatability %CV	Low, indicating good precision	Level 1 QC: 1.5%Level 2 QC: 1.2%Level 3 QC: 1.4%Level 1 serum pool: 1.5%Level 2 serum pool: 1.3%
Within Lab %CV	Low, indicating good precision	Level 1 QC: 1.7%Level 2 QC: 1.4%Level 3 QC: 1.5%Level 1 serum pool: 1.7%Level 2 serum pool: 1.4%
Measuring Range	<0.06 - 5.00 ng/mL (Matches predicate)	<0.06 - 5.00 ng/mL

Study Details

Sample size used for the test set and the data provenance:
- Test Set Sample Size: 116 samples for the method comparison study.
- Data Provenance: Not specified in the provided text (e.g., country of origin, retrospective or prospective).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is a diagnostic device for measuring a chemical analyte (digoxin concentration). The "ground truth" for the test set refers to the values obtained from the predicate device. Therefore, human experts are not directly establishing a subjective ground truth, but rather running the predicate device. The qualifications of the technicians or operators running these instruments are not specified.
Adjudication method for the test set:
- Not applicable. The comparison is between two quantitative assays (the new device and the predicate device), not involving human interpretation requiring adjudication.
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. This is an in vitro diagnostic device for measuring an analyte, not an AI-assisted diagnostic imaging or interpretation tool for human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance stated is for the device (DIGXN method) operating in a standalone capacity, producing quantitative measurements of digoxin concentration. The results were then compared to those of the predicate device.
The type of ground truth used:
- The "ground truth" for the method comparison was the quantitative results obtained from the predicate device (Dimension® Digoxin Flex® reagent cartridge, DGNA). For reproducibility, the "ground truth" is inherent to the statistical analysis of repetitive measurements, aiming to quantify the device's inherent variability around a mean value for known control materials and serum pools.
The sample size for the training set:
- Not applicable as this is not an AI/machine learning device that requires a training set in that sense. The device's calibration and validation would involve various samples, but they are not referred to as a "training set" in the context of this traditional analytical device. The calibration for the DIGXN method uses the DRUG 4 Calibrator, which has five levels.
How the ground truth for the training set was established:
- Not applicable as there is no "training set" in the context of AI. For the calibrator, the "ground truth" (assigned values for each of the five levels) would have been established during its manufacturing and validation process, ensuring accuracy and traceability, likely against reference methods or materials, though this detail is not provided in the summary.

Summary

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510(k) Summary of Safety and Effectiveness for the Dimension Vista® LOCI Digoxin Flex® Reagent Cartridge (K6435) and Dimension Vista® DRUG 4 Calibrator (KC460)

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.

A. 510(k) Number: K093441

B. Date of Preparation: October 30, 2009

C. Proprietary and Established Names:

Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435) Dimension Vista® DRUG 4 Calibrator, DRUG 4 CAL (KC460)

D. Applicant:

Siemens Healthcare Diagnostics Inc., P.O. Box 6101, Newark, DE 19714-6101 Frances A. Dillon, Regulatory Affairs & Compliance Manager Office: (302) 631-6951 Fax: (302) 631-6299

E. Requlatory Information:

Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435)

1. Regulation section: 21 CFR § 862.3320 Digoxin test system
1. Classification: Class II
1. Product Code: KXT
1. Panel: Toxicology

Dimension Vista® DRUG 4 Calibrator, DRUG 4 CAL (KC460)

1. Requlation section: 21 CFR § 862.1150 calibrator, multi-analyte mixture
1. Classification: Class II
1. Product Code: JIX
1. Panel: Clinical Chemistry

F. Predicate Device:

Method

Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435), is substantially equivalent to the Dimension® Digoxin Flex® reagent cartridge, DGNA (DF35A), cleared under K94615.

Calibrator

Dimension Vista® DRUG 4 Calibrator, DRUG 4 CAL (KC460), is substantially equivalent to Dimension® Drug Calibrator, DRUG CAL (DC22B), cleared under K011035.

G. Device Description:

Method

The DIGXN method is a homogeneous, sequential, chemiluminescent immunoassay based on LOCI® technology. The LOCI® reagents include two synthetic bead reagents and a biotinylated F(ab')2 fragment of an anti-Digoxin mouse monoclonal antibody. The first bead reagent (Chemibeads) is coated with ouabain, a weaker binding analog of digoxin, and contains a photosensitizer dye. In a first step, sample

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is incubated with biotinylated F(ab')> which allows digoxin from the sample to saturate a fraction of the biotinylated F(ab')2 that is directly related to the digoxin concentration. In a second step, ouabain chemibeads are added and form bead/biotinylated F(ab')> immunocomplexes with the non-saturated fraction of the biotinylated F(ab')>. Sensibeads are then added and bind to the biotin to form bead pair immunocomplexes. Illumination of the complex at 680 nm generates singlet oxygen from Sensibeads which diffuses into the Chemibeads, triggering a chemilyminescent reaction. The resulting signal is measured at 612 nm and is an inverse function of the digoxin concentration in the sample.

Calibrator

The DRUG 4 Calibrator is a 5 level, liquid calibrator. It is packaged as a kit of ten vials, two vials per level (A, B, C, D and E), 2.5 mL per vial. The product matrix is human serum.

H. Intended Use:

Method

The DIGXN method is an in vitro diagnostic test for the quantitative measurement of digoxin in human serum and plasma on the Dimension Vista" System. Measurements of digoxin are used in the diagnosis and treatment of digoxin overdose and in monitoring levels of digoxin to help ensure appropriate therapy.

Calibrator

The DRUG 4 CAL is an in vitro diagnostic product for the calibration of the LOCI Digoxin (DIGXN) method on the Dimension Vista® System.

I. Substantial Equivalence Information:

The Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435) and the Dimension Vista® DRUG 4 Calibrator, DRUG 4 CAL (KC460) were compared to the respective predicate devices, Dimension® Digoxin Flex® reagent cartridge, DGNA (DF35A), cleared under K94615 and Dimension® Drug Calibrator, DRUG CAL (DC22B), cleared under K011035. A comparison of the important similarities and differences between the devices is provided in the following tables:

Method

Similarities

Feature	Dimension Vista® LOCI DIGXNFlex® reagent cartridge (K6435)	PredicateDimension® DGNA Flex®reagent cartridge (DF35A)
IntendedUse	The DIGXN method is an in vitrodiagnostic test for the quantitativemeasurement of digoxin in humanserum and plasma on theDimension Vista® System.Measurements of digoxin are usedin the diagnosis and treatment ofdigoxin overdose and in monitoringlevels of digoxin to help ensureappropriate therapy.	The DGNA method used on theDimension® clinical chemistrysystem is an in vitro diagnostictest intended to measure digoxin,a cardiovascular drug, in humanserum and plasma. DGNA testresults are used in the diagnosisand treatment of digoxinoverdose and in monitoring levelsof digoxin to ensure appropriatetherapy.

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SampleTypes	Serum and plasma	Serum and plasma
MeasuringRange	<0.06 - 5.00 ng/mL	<0.06 - 5.00 ng/mL
CalibrationInterval	30 days, same reagent lot	30 days, same reagent lot

Differences

Feature	Dimension Vista® LOCI DIGXNFlex® reagent cartridge (K6435)	PredicateDimension® DGNA Flex®reagent cartridge (DF35A)
AssayType	Chemiluminescent immunoassaybased on LOCI® technology	Affinity particle mediatedimmunoassay
Measure-ment	measurement at 612 nm	Bichromatic rate(577 and 700 nm)
Antibody	Monoclonal Mouse Antibody	Rabbit Antibody
SampleVolume	10 µL	30 µL

Calibrator

Similarities

Feature	Dimension Vista® DRUG 4Calibrator, DRUG 4 CAL (KC460)	PredicateDimension® Drug Calibrator,DRUG CAL (DC22B)
IntendedUse	The DRUG 4 CAL is an in vitrodiagnostic product for thecalibration of the LOCI Digoxin(DIGXN) method on the DimensionVista® System.	The Drug Calibrator is an in vitrodiagnostic product to be used tocalibrate the Digoxin (DGNA),Lithium (LI), Phenobarbital(PHNO), Phenytoin (PTN), andTheophylline (THEO) methods onthe Dimension® clinical chemistrysystem. The Drug Calibrator wasdesigned to meet the needs ofusers to assure accurate resultsover the assay range of thesemethods.
Matrix	Human serum based	Human serum based
Form	Liquid stored at 2 - 8°C	Liquid stored at 2 - 8°C

Differences

Feature	Dimension Vista® DRUG 4Calibrator, DRUG 4 CAL (KC460)	PredicateDimension® Drug Calibrator,DRUG CAL (DC22B)
Analytes	digoxin	digoxin, lithium, phenobarbital.phenytoin, and theophylline
Volume	2.5 mL per vial.	3.0 mL per vial.
TypicalLevels	Five Levels, (0.00, 0.60, 1.25, 2.50,and 5.30 ng/mL)	Five levels, (0.00, 0.60, 1.20,2.50 and 5.00 ng/mL)

J. Method Performance Summary

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Split sample method comparisons demonstrated equivalence between the Dimension Vista® DIGXN Flex® reagent cartridge assay and the Dimension® DGNA Flex® reagent cartridge assay as shown with the following correlation statistics:

DimensionVista®	Predicate	Slope	Intercept	CorrelationCoefficient (r)	n
DIGXN	Dimension®DGNA	1.02	- 0.04 ng/mL	0.98	116

Reproducibility testing was done in accordance with CLSI Guideline EP5-A2: Evaluation of Precision Performance of Clinical Chemistry Devices. For each test level, single tests from two independent cups were analyzed twice a day, for 20 days. The repeatability and within lab precision standard deviations (SD) and percent coefficient of variation (% CV) were calculated by the analysis of variance method. Typical precision for the Dimension Vista® LOCI DIGXN method is summarized below:

Material	Mean(ng/mL)	RepeatabilitySD	Repeatability%CV	Within LabSD	Within Lab%CV
Level 1 QC	0.67	0.01	1.5	0.01	1.7
Level 2 QC	1.63	0.02	1.2	0.02	1.4
Level 3 QC	3.31	0.05	1.4	0.05	1.5
Level 1 serumpool	0.92	0.01	1.5	0.02	1.7
Level 2 serumpool	2.44	0.03	1.3	0.03	1.4

K. Conclusion:

The Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435) and the Dimension® Digoxin Flex® reagent cartridge, DGNA (DF35A) are substantially equivalent based on their intended use and performance characteristics as described above.

The calibrator products, the Dimension Vista® DRUG 4 Calibrator (KC460) and Dimension® Drug Calibrator, DRUG CAL (DC22B) are substantially equivalent in design and intended use with their respective assay systems.

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Image /page/4/Picture/0 description: The image shows the logo for the Department of Health & Human Services USA. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" written around the perimeter. Inside the circle is an abstract image of an eagle.

Food and Drug Administration 10903 New Hampshire Avenue Document Mail Center - WO66-0609 Silver Spring, MD 20993-0002

Siemens Healthcare Diagnostics Inc. c/o Frances Dillon Regulatory Affairs and Compliance Manager P.O. Box 6101, Mailstop 514 Newark, DE, 19714-6101

APR 0 7 2010

Re: K093441

Trade Name: Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435) and Dimension Vista® Drug 4 Calibrator, DRUG 4 CAL (KC460) Regulation Number: 21 CFR 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Codes: KXT. DLJ Dated: February 18, 2010 Received: February 22, 2010

Dear Ms. Dillon:

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); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2 -

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (301) 796-5760. 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/ReportalProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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 ) 796-5680 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours.

Courtney C. Harper, 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): K093441

Device Name:

Dimension Vista® LOCI Digoxin Flex® reagent cartridge, DIGXN (K6435)

Indications for Use:

Prescription Use and/or (Part 21 CFR 801 Subpart D)

Over-the-counter Use (21 CFR 801 Subpart C)

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

d===========================================================================================================================================================================

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

Carol Benson
Division Sign Off

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

510(k) K093441

Page 1 of_2

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Indications For Use

510(k) Number: K093441

Device Name:

Dimension Vista® Drug 4 Calibrator, DRUG 4 CAL (KC460)

Indications for Use:

The DRUG 4 CAL is an in vitro diagnostic product for the calibration of the LOCI Digoxin (DIGXN) method on the Dimension Vista® System.

Prescription Use ج and/or (Part 21 CFR 801 Subpart D)

Over-the-counter Use (21 CFR 801 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. Benson

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

510(k) K093441

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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.