The SERADYN OMS™ DIGOXIN assay is used for the quantitation of digoxin in human serum or plasma on the Abbott AEROSET® System.
Digoxin is a potent cardiac glycoside widely prescribed for the treatment of patients suffering from congestive heart failure, as well as some types of cardiac arrhythmias. Digoxin intoxication is a common and serious problem in the clinical setting. This is, in part, a result of the fact that cardiac glycosides have a low therapeutic ratio (a very small difference between therapeutic and tissue toxic levels). Coupled with the narrow therapeutic range is a marked patient variability in response to the same dosage of drug, often resulting in unpredictable serum drug levels. Intoxication symptoms are often indistinguishable from the original condition for which the drug was prescribed. It may not be immediately apparent whether the patient has been under or overdosed.
Monitoring serum digoxin levels combined with other clinical data can provide the physician with useful information to aid in adjusting patient dosage and achieving optimal therapeutic effect while avoiding useless sub-therapeutic or harmful toxic dosage levels.

Device Description

The Seradyn QMS™ Digoxin Assay is a homogeneous Particle Enhanced Turbidimetric Immunoassay used for the quantitation of digoxin in serum or plasma. The assay is intended for use on the Abbott AEROSET® System, using the Seradyn QMS Digoxin Calibrators (previously cleared as Digoxin Immunoassay K983323.
The reagent system components are 1) digoxin coated microparticle reagent, and 2) the antibody reagent which consists of a mouse monoclonal antibody specific for digoxin.
The technology is based on competition between the digoxin in the sample and digoxin coated onto the microparticles, for the antibody-binding sites of the anti-digoxin antibody reagent. In the absence of digoxin in the sample, the specific antibody in the antibody reagent binds the digoxin on the particle, and results in rapid agglutination of the microparticles. In the presence of digoxin in the sample, the digoxin in the sample competes for antibody binding sites of the specific antibody in the antibody reagent, and partially inhibits the agglutination of the microparticles. The rate of agglutination (turbidity) is directly proportional to the rate in absorbance change of incident light and is measured spectrophotometrically by the Abbott AEROSET® System at a wavelength of 700 nm.
A six level Seradyn QMS™ Digoxin Calibrator set, with known digoxin concentrations is used to quantitate the assay. An internal concentration-dependent calibration curve is generated by the AEROSET® System, by measuring the rate of absorbance change of each calibrator level. Maximum absorbance rate is at the lowest digoxin concentration and the lowest absorbance rate at the highest digoxin concentration.
By monitoring the change in rate of a specimen with unknown digoxin concentration, and comparing to the internal calibration curve, a sample's concentration can readily be obtained and reported as digoxin concentration in either ng/ml or nmol/L.

AI/ML Overview

Here's an analysis of the Seradyn QMS™ Digoxin assay's acceptance criteria and the studies performed, based on the provided text:

Acceptance Criteria and Device Performance for Seradyn QMS™ Digoxin on the Abbott AEROSET® System

1. Table of Acceptance Criteria and Reported Device Performance

Study Parameter	Acceptance Criteria	Reported Device Performance
Specificity	Comparable to predicate device (Roche Tina-quant Digoxin)	Similar % Cross-Reactivity for tested compounds (Digitoxigenin, Digitoxin, Digoxigenin, Digoxigenin bis-digitoxoside, Digoxigenin mono-digitoxoside, Spironolactone, Canrenone).
Accuracy by Recovery	100 ± 10% of theoretical value	94% - 102% recovery across four tested concentrations (1.21 - 4.85 ng/mL).
Sensitivity	Comparable to predicate (explicit criterion not stated but implied by comparison)	0.05 ng/mL (lower than predicate's 0.15 ng/mL)
Accuracy & Linearity by Dilution	100 ± 10% of theoretical value (recovery); Acceptable linearity	98% - 105% recovery across five dilutions (1.00 - 5.00 ng/mL); R² = 0.9955 (linear regression)
Precision	No explicit acceptance criteria stated, implied good precision from comparison to predicate.	Within Run CV(%): 0.98% - 2.17%; Between Day CV(%): 0.28% - 0.80%; Total Run CV(%): 0.91% - 2.31%
Method Comparison	No explicit acceptance criteria stated, implied good correlation to predicate.	Correlation Coefficient: 0.99346 (vs. Tina-quant on Hitachi 717)
Interfering Substances	100 ± 12% for hemoglobin; 100 ± 10% for bilirubin; 100 ± 20% for lipids (Note: Discrepancy in bilirubin and hemoglobin acceptance values in text)	99% for Bilirubin (20 mg/dL); 110% for Hemoglobin (1,000 mg/dL); 106% for Intralipid (2,000 mg/dL)
HAMA Interference	100 ± 10% recovery of control serum	101% for HAMA 1; 107% for HAMA 2
Instrument On-board Stability	Acceptable control recoveries, no re-calibration required	Demonstrated stability for 70 days, claimed on-board stability of at least 60 days.
Instrument Calibration Stability	No re-calibration required during the period under study	Claimed 60 days of stability based on on-board stability data.

Note on Interfering Substances: The document states "Acceptance criteria are recoveries of 100±12% for hemoglobin, 100±10% for hemoglobin、100 ±20% for lipids". There appears to be a typo, possibly intending 100±10% for bilirubin and 100±12% for hemoglobin, or vice-versa, given the reported values. I have used the written acceptance criteria as provided.

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

Specificity (Cross-reactivity): Not explicitly stated, samples were "spiked" with specific compounds. Data provenance: Not explicitly stated, but implies laboratory-prepared samples.
Accuracy by Recovery: Not explicitly stated how many samples were used, but "human serum" was spiked at four different concentrations. Data provenance: Not explicitly stated, but implies laboratory-prepared human serum.
Sensitivity: Not explicitly stated how many samples or what method, only the "lowest Digoxin concentration that can be distinguished from zero with 95% confidence."
Accuracy & Linearity by Dilution: The 5.0 ng/mL Digoxin Calibrator was diluted at 80%, 60%, 40%, and 20%. The "diluted samples, as well as the 5.0 ng/mL calibrator" were analyzed. Data provenance: Laboratory-prepared dilutions from a calibrator.
Precision: "A tri-level human serum based commercial control containing digoxin was assayed in duplicate twice a day for twenty days." This means n=80 (3 levels * 2 replicates/day * 20 days) for each level presented in the table. Data provenance: Laboratory testing using commercial control.
Method Comparison: "55" clinical specimens. Data provenance: Not explicitly stated, but "clinical specimens" suggests patient samples.
Interfering Substances: "Abnormal bilirubin levels were prepared by adding to human serum pool... Abnormal hemoglobin levels were prepared by addition of red blood cell lysate... Abnormal lipid levels were prepared by addition of Intralipid®". N=2 for each tested interfering substance. Data provenance: Laboratory-prepared human serum pools.
HAMA Interference: "A normal human serum pool (control), and HAMA type 1 and HAMA type 2 samples were spiked with the same amounts of digoxin." Each of these was assayed "in duplicate". Data provenance: Laboratory-prepared human serum and HAMA samples.
Instrument On-board Stability: Controls were assayed "twice weekly for a period of 60 days". Specific 'n' not given, but implies multiple measurements over time. Data provenance: Laboratory testing.
Instrument Calibration Stability: Data from on-board stability study was used.

In summary, the test set primarily consists of laboratory-prepared samples (spiked human serum, diluted calibrators, commercial controls, prepared interfering substance samples), with one study (Method Comparison) using "clinical specimens." The country of origin is not specified but is likely the US, given the submission to the FDA. All studies appear to be prospective experimental studies conducted by the manufacturer.

3. Number of Experts and Qualifications for Ground Truth

None stated. The studies described are analytical performance studies focused on the intrinsic characteristics and measurement accuracy of the device. They do not involve human interpretation or diagnostic decision-making that would typically require expert ground truth establishment. The ground truth for these studies is based on theoretical concentrations (for recovery, linearity, spiking) or established reference methods (for method comparison).

4. Adjudication Method for the Test Set

None applicable. As stated above, these are analytical performance studies, not studies involving human interpretation or subjective assessments that would require adjudication.

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

No, an MRMC comparative effectiveness study was not done. The studies are analytical performance assessments of the assay itself, comparing its measurements to known values or a predicate device. There is no human reader component to this type of device (an in-vitro diagnostic assay).

6. Standalone Performance Study (Algorithm only without human-in-the-loop)

Yes, all reported studies are standalone performance studies. The Seradyn QMS™ Digoxin assay is a fully automated immunoturbidimetric assay on the Abbott AEROSET® System. Its performance characteristics (specificity, accuracy, precision, etc.) are measured directly from the output of the instrument, without human intervention in the measurement process itself, beyond sample preparation and loading. The results are numerical concentrations.

7. Type of Ground Truth Used

The ground truth used varies by study:

Specificity (Cross-reactivity): Theoretical concentration of spiked cross-reactants.
Accuracy by Recovery: Theoretical concentrations of digoxin spiked into human serum.
Sensitivity: Defined statistically as the lowest concentration distinguishable from zero with 95% confidence.
Accuracy & Linearity by Dilution: Theoretical concentrations based on serial dilutions of a known calibrator.
Precision: Mean concentrations of commercial controls.
Method Comparison: Results from the predicate device (Roche Tina-quant assay on the Hitachi 717) using clinical specimens.
Interfering Substances: Theoretical concentrations of spiked interfering substances.
HAMA Interference: Mean concentration of the control normal human serum.
Instrument On-board Stability & Calibration Stability: Reference measurements at Day 0, against which subsequent measurements are compared.

8. Sample Size for the Training Set

Not applicable / Not explicitly stated. This device is an in-vitro diagnostic assay rather than an AI/ML algorithm that undergoes a distinct "training phase." Calibration for such assays involves using a multi-level calibrator set to establish a standard curve. The document mentions a "six level Seradyn QMS™ Digoxin Calibrator set" used to generate an "internal concentration-dependent calibration curve." This calibrator set essentially serves the function of "training" the instrument to interpret absorbance changes into digoxin concentrations.

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

For calibration: The ground truth for the "training set" (the six-level calibrator set) is established by the known digoxin concentrations assigned to each calibrator level. These concentrations are determined by the manufacturer (Seradyn, Inc.) through a rigorous process, typically involving reference methods (e.g., mass spectrometry) or traceability to international reference materials. While not detailed in this 510(k) summary, the previous clearance of "Digoxin Immunoassay K983323" for the QMS Digoxin Calibrators suggests their concentrations were already established and accepted by the FDA.

Summary

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OCT 2 4 2002

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: K023058

1. Company/contact person:

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

Establishment registration No: 1836010

Lisa Brown Director of Quality Telephone: (317) 610-3821 Fax: (317) 610-0018 e-mail: lbrown@seradyn.com

1. Prepared:
  September 12, 2002

3. Device Name:

a. Proprietary Name:	QMS™ Digoxin on the Abbott AEROSET® System
b. Common Name:	Digoxin Particle Enhanced Immunoturbimetric Assay
c. Classification Name:	862.3320 Enzyme Immunoassay, Digoxin

4. Legally marketed devices to which equivalency is claimed:

Seradyn QMS™ Digoxin on the Abbott AEROSET® System is substantially equivalent to the Roche Tina-quant Digoxin cleared under K953239.

5. Description of Device:

The reagent system components are 1) digoxin coated microparticle reagent, and 2) the antibody reagent which consists of a mouse monoclonal antibody specific for digoxin.

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The technology is based on competition between the digoxin in the sample and digoxin coated onto the microparticles, for the antibody-binding sites of the anti-digoxin antibody reagent. In the absence of digoxin in the sample, the specific antibody in the antibody reagent binds the digoxin on the particle, and results in rapid agglutination of the microparticles. In the presence of digoxin in the sample, the digoxin in the sample competes for antibody binding sites of the specific antibody in the antibody reagent, and partially inhibits the agglutination of the microparticles. The rate of agglutination (turbidity) is directly proportional to the rate in absorbance change of incident light and is measured spectrophotometrically by the Abbott AEROSET® System at a wavelength of 700 nm.

A six level Seradyn QMS™ Digoxin Calibrator set, with known digoxin concentrations is used to quantitate the assay. An internal concentration-dependent calibration curve is generated by the AEROSET® System, by measuring the rate of absorbance change of each calibrator level. Maximum absorbance rate is at the lowest digoxin concentration and the lowest absorbance rate at the highest digoxin concentration.

By monitoring the change in rate of a specimen with unknown digoxin concentration, and comparing to the internal calibration curve, a sample's concentration can readily be obtained and reported as digoxin concentration in either ng/ml or nmol/L.

6. Intended Use:

The SERADYN OMS™ DIGOXIN assay is used for the quantitation of digoxin in human serum or plasma.

	Device Name
	QMS™ Digoxin	Tina-quant® Digoxin
Indicationsfor Use	The Seradyn QMS™ Digoxin assay is usedfor the quantitation of digoxin in humanserum or plasma on the Abbott AEROSET®System.Digoxin is a potent cardiac glycoside widelyprescribed for the treatment of patientssuffering from congestive heart failure, aswell as some types of cardiac arrhythmias.Digoxin intoxication is a common and seriousproblem in the clinical setting.Monitoring serum digoxin levels combinedwith other clinical data can provide thephysician with useful information to aid inadjusting patient dosage, achieving optimaltherapeutic effect while avoiding uselesssubtherapeutic or harmful toxic dosage levels.	The Tina-quant Digoxin method is used forthe quantitative determination of digoxin, acardioactive drug, in human serum andplasma on the Hitachi® analyzers.Measurements are used in the diagnosis andtreatment of digoxin overdose and inmonitoring levels of digoxin to ensure propertherapy.
	Device Name
	QMS™ Digoxin	Tina-quant® Digoxin
ReagentComponents	Two (2) reagent systemAnti-digoxin Antibody reagent (R1)Digoxin coated Microparticle reagent(R2)	Two (2) reagent systemAnti-digoxin Antibody reagent (R1)Digoxin coated Microparticle reagent(R2)
Calibration	Seradyn QMS™ Digoxin Calibrators - Sixlevels	Preciset Digoxin Calibrators - Six levels
Assay Range	0.05 to 5.0 ng/mL(0.06 to 6.40 nmol/L)	0.15 to 7.5 ng/mL(0.19 to 9.6 nmol/L)
MethodPrinciples	The Seradyn QMS™ Digoxin Assay is ahomogeneous Particle EnhancedTurbidimetric Immunoassay based on theprinciple of spectrophotometricallymeasuring turbidity and changes in absorbedlight, which result when activatedmicrospheres agglutinate.The microspheres (R2) are coated withdigoxin, which in the presence of an anti-digoxin antibody (R1), rapidly agglutinate.The sample is incubated with the Antibodyreagent. The microparticles are added andallowed to incubate. In the absence of anydigoxin in the sample, rapid agglutinationoccurs, resulting in a turbid solution. When asample containing digoxin is introduced, theagglutination is partially inhibited, slowingdown the agglutination process. Thus theAbbott AEROSET® analyzer can measurethe resulting turbidity and generate a classicinhibition curve (calibration curve), withrespect to concentration, with maximum rateof agglutination at the lowest digoxinconcentration, and minimum rate ofagglutination at the highest digoxinconcentration. By monitoring the change inrate of specimen agglutination (absorbancerate), and comparing to the internalcalibration curve, a sample's concentrationcan readily be obtained and reported asdigoxin concentration in either ng/ml ornmol/L.	The Tina-quant® Digoxin is also ahomogeneous Particle EnhancedTurbidimetric Immunoassay with exactly thesame principles as the Seradyn QMS™Digoxin Assay. The only difference is thatthe turbidity (change in absorbance) ismeasured spectrophotometrically on theHitachi® analyzers. The digoxinconcentration can also be reported in ng/mlor nmol/L.

7. Comparison of Technological Characteristics:

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Tina-quant® and Hitach® are registered trademarks of Roche Diagnostics Corp.

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8. Summary of Non-clinical Testing:

NONE

9. Summary of Clinical Testing:

The results of the clinical testing (Performance Characteristics) oof the Seradyn OMS Digoxin assay were compared to results of the studies reported in the Roche Tina-quant Digoxin Package Insert.

A. Specificity

Cross-reactivity was tested on the AEROSET using the Seradyn QMS Digoxin assay. The major digoxin active metabolites, digoxigenin bis-digitoxoside, digoxigenin monodigitoxoside, and digoxigenin, as well as digitoxin, another cardiac glycoside, and its common analogue, digitoxigenin, were tested.

Cross reactivity was calculated using the following formula:

(Equivalent digoxin conc of spiked sample – Dgoxin conc of sample without cross reactant) X 100% Conc of cross reactant

The % cross reactivity on the AEROSET was compared to the reported Roche Tina-quant cross reactivity.

	AEROSETConc. of		Tina-quant
	Cross-Reactant		Conc. of
	Spiked (ng/mL)	% Cross-Reactivity	Cross-ReactantSpiked (ng/mL)	% Cross-Reactivity
Compound
Digitoxigenin	500	0.5%	Not Reported	<1%
Digitoxin	50	3.1%	51	4.1%
Digoxigenin	50	4.0%	33	6.4%
Digoxigenin bis-digitoxoside	5	112%	1.75	120%
Digoxigenin mono-digitoxoside	5	78.2%	1.9	111%

Spironolactone and Canrenone

Aldosterone inhibitors, spironolactone and canrenone have been reported to interfere with digoxin recovery in other commercially available immonoassays. These compounds were tested on the Abbott AEROSET® System using the Seradyn OMS™ Digoxin assay. The effect of spironolactone and canrenone were assessed in both the presence and absence of digoxin in the sample.

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	AEROSET		Tina-quant
	Conc. of		Conc. of
	Interferent	% Cross-	Interferent	% Cross-
Compound	Spiked (ng/mL)	Reactivity	Spiked (ng/mL)	Reactivity
Spironolactone	800	0.0%	Not Reported	<1%
Canrenone	3,000	<0.002%	Not Reported	Not Reported

Percent cross reactivity was calculated and compared to the Tina-quant reported results.

B. Accuracy by Recovery

Accuracy by analyte spike recovery was determined by adding a concentrated digoxin solution to human serum at four different concentrations. Percent recoveries for each level were calculated using the following formula:

% Recovery = ("mean recovered concentration" divided by "theoretical concentration") x 100%

Data summary are shown below.

% AnalyteAdded	Added (Theoretical)Concentration(ng/mL)	MeanRecoveredConcentration(ng/mL)	Percent (%Recovery
100%	4.85	4.85	100%
75%	3.64	3.73	102%
50%	2.43	2.37	98%
25%	1.21	1.14	94%

Acceptable Recovery: 100±10% of theoretical value

The Roche Tina-quant package insert has no reported study of accuracy by recovery

C. Sensitivity

The least detectable dose, defined as the lowest Digoxin concentration that can be distinguished from zero with 95% confidence, is 0.05 ng/mL (0.064 nmol/L).

The Roche Tina-quant assay reports a lower detection limit of 0.15 ng/mL (0.19 nmol/L).

D. Accuracy & Linearity by Dilution

Accuracy and linearity by dilution was determined using a slightly modified procedure described in National Committee for Clinical Laboratory Standards (NCCLS) proposed guideline EP6-P. The 5.0 ng/mL Digoxin Calibrator was diluted with the 0.0 ng/mL Digoxin Calibrator at 80%, 60%, 40%, and 20%. The diluted samples, as well as the 5.0 ng/mL calibrator were analyzed on the AEROSET® using the Seradyn QMS™ Digoxin assay.

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Percent recoveries for each level were calculated using the following formula:

% Recovery = ("mean recovered concentration" divided by "theoretical concentration") x 100%

Representative data are shown below.

	TheoreticalConcentration(ng/mL)	MeanRecoveredConcentration(ng/mL)	Percent (%)Recovery
Dilution
Neat	5.00	4.92	98%
80%	4.00	4.2	105%
60%	3.00	3.14	105%
40%	2.00	2.05	103%
20%	1.00	1.05	105%

Acceptable Recovery: 100 ± 10% of theoretical value.

Linearity was assessed by performing linear regression analysis using the least squares method. The expected values were plotted on the x-axis against the observed values on the y-axis. Linear regression statistics yielded: y = 1.0066x - 0.0923; R2 = 0.9955

The Roche Tina-quant assay reported "acceptable linearity" when serially diluting a with a digoxin concentration of 6.8 ng/mL with Digoxin Calibrator 1. It is acknowledged that concentration levels this high are extremely rare.

E. Precision

Precision was determined as described in National Committee for Clinical Laboratory Standards (NCCLS) protocol EP5 (including an additional estimate of between dav precision). A tri-level human serum based commercial control containing digoxin was was assayed in duplicate twice a day for twenty days. The between run, within run, and total sd and %CVs were calculated.

The following are representative results from pooled data:

Sample	n	Mean(ng/mL)	Within RunSD	Within RunCV(%)	Between DaySD	Between DayCV(%)	Total RunSD	Total RunCV(%)
1	80	0.59	0.0128	2.17%	0.0047	0.80%	0.0137	2.31%
2	80	1.48	0.0145	0.98%	0.0042	0.28%	0.0151	1.02%
3	80	4.81	0.0372	0.77%	0.0227	0.47%	0.0436	0.91%

The Roche Tina-quant assay reports the following imprecision, using an internal protocol:

Sample	N	Within Run			Between Day
		Mean(ng/mL)	SD	CV(%)	Mean(ng/mL)	SD	CV(%)
Control	63	1.17	0.06	5.1	1.81	0.07	3.6
Control	63	2.09	0.05	2.3	4.85	0.13	2.7
Human Serum	63	---	---	---	1.9	0.09	4.5

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F. Method Comparison

Correlation Studies were performed using NCCLS Protocol EP9-A. Results from the Seradyn QMS™ Digoxin assay on the AEROSET® System were compared to the Tinaquant® assay on the Hitachi® 717. The clinical specimens ranged from 0.33 ng/mL (0.42 nmol/L) to 3.06 ng/mL (3.92 nmol/L). Results of the specimen testing are shown below.

	Hitachi
y-intercept	1.06
Slope	-0.13
CorrelationCoefficient	0.99346
Number of Samples	55

G. Interfering Substances

Digoxin assay on the Abbott AEROSET® System at the concentrations indicated. Interference studies were conducted using NCCLS protocol EP7-P as a guideline document.

Abnormal bilirubin levels were prepared by adding to human serum pool containing approximately 0.8 ng/mL of digoxin. Abnormal hemoglobin levels were prepared by addition of red blood cell lysate to the same human serum pool. Abnormal lipid levels were prepared by addition of Intralipid® to the same human serum pool.

Results showed no interference at the following levels:

InterferingSubstance	Interferent Concentration	N	Target(no Interferent)(ng/mL)	MeanRecovery(ng/mL)	Observed(% ofTarget)
Bilirubin	20 mg/dL(342 umol/L)	2	0.84	0.83	99%
Hemoglobin	1,000 mg/dL(10 g/L)	2	0.80	0.88	110%
Intralipid	2,000 mg/dL(22.6 mmol/L)	2	0.84	0.89	106%

Acceptance criteria are recoveries of 100±12% for hemoglobin, 100±10% for hemoglobin、100 ±20% for lipids

The Roche Tina-quant package insert reports "no significant interference" up approximately 60 mg/dL of bilirubin, approximately 1,000 mg/dL of hemoglobin, and approximately 1700 mg/dL of triglyceride.

HAMA Interference

As with any assay employing mouse antibodies, the possibility exists for interference by human anti-mouse antibodies (HAMA) in the sample, which could cause falsely elevated results. A normal human serum pool (control), and HAMA type 1 and HAMA type 2

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samples were spiked with the same amounts of digoxin. Each of the samples were assayed in duplicate on the Abbott AEROSET® System using the Seradyn OMS™ Digoxin assay. The means of each duplicate HAMA sample were compared to the mean of the control normal human serum. Acceptance criteria is a recovery of 100 ±10% of the control serum.

Results are as follows:

	Rep 1	Rep 2	Mean	%Recovery
Control	0.83	0.81	0.82	100
HAMA 1	0.83	0.83	0.83	101
HAMA 2	0.88	0.88	0.88	107

The Roche Tina-quant package insert reports no HAMA interference study.

H. Reagent Stability Data

Real Time Stability

The long-term stability is on going. Two months real time stability is collected so far.

Instrument on-board stabilitv

The reagents were left uncapped on-board and controls were assayed twice weekly for a period of 60 days. Control recoveries at subsequent time points were compared to Day 0 recovery. Data showed that the control recoveries to be acceptable, demonstrating reagents on board stability for 70 days. Based on this data, an on-board stability claim of at least 60 days is made. No re-calibration was required during the study.

Roche Tina-quant reports an instrument on-board stability of 90 days for their reagents.

I. Instrument Calibration Stability:

Data used in the on-board stability is used to claim instrument calibration stability of 60 days, since no re-calibration was required during the period under study.

Roche Tina-quant reports no calibration stability claim.

10. Conclusions:

The results of clinical testing demonstrate that the performance and effectiveness of the Seradyn QMS™ Digoxin Assay are substantially equivalent to those of the Roche Diagnostic Systems Tina-quant® Digoxin assay.

Refer to the Roche Diagnostic Systems Tina-quant® Digoxin Package Insert for Specific Performance data.

11. Other Information:

None

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/8/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is circular and contains the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. In the center of the logo is an abstract symbol that resembles an eagle or bird in flight. The symbol is composed of three curved lines that form the head, body, and tail of the bird.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Ms. Lisa Brown Director of Quality Seradyn. Inc. 7998 Georgetown Road, Suite 1000 Indianapolis, IN 46268

K023058 Trade/Device Name: Seradyn QMS™ Digoxin on the Abbott Aeroset® System Regulation Number: 21 CFR 862.3320 Regulation Name: Digoxin test system Regulatory Class: Class II Product Code: KXT: DLJ Dated: September 12, 2002 Received: September 13, 2002

Dear Ms. Brown:

Re:

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 the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 Part 801); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 -

This letter will allow you to begin marketing your device as described in your 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 advice for your device on our labeling regulation (21 CFR Part 801 and 1 additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained 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/cdrl/dsma/dsmamain.html".

Sincerely yours,

Steven Butman

Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Rev 1 9/12/02

INDICATIONS FOR USE FORM K023058

510(k) Number (if known): -

SERADYN QMS™ DIGOXIN ON THE ABBOTT AEROSET® SYSTEM Device Name:

Indications For Use:

The SERADYN OMS™ DIGOXIN assay is used for the quantitation of digoxin in human serum or plasma on the Abbott AEROSET® System.

Digoxin is a potent cardiac glycoside widely prescribed for the treatment of patients suffering from congestive heart failure, as well as some types of cardiac arrhythmias. Digoxin intoxication is a common and serious problem in the clinical setting. This is, in part, a result of the fact that cardiac glycosides have a low therapeutic ratio (a very small difference between therapeutic and tissue toxic levels). Coupled with the narrow therapeutic range is a marked patient variability in response to the same dosage of drug, often resulting in unpredictable serum drug levels. Intoxication symptoms are often indistinguishable from the original condition for which the drug was prescribed. It may not be immediately apparent whether the patient has been under or overdosed.

Monitoring serum digoxin levels combined with other clinical data can provide the physician with useful information to aid in adjusting patient dosage and achieving optimal therapeutic effect while avoiding useless sub-therapeutic or harmful toxic dosage levels.

(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)

Over-The-Counter Use

tan tan

(Division Sign-Off) Division of Clinical Laboratory Devices 510(k) Number _

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.