← Product Code [DKJ](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DKJ) · K093939

# ADVIA CHEMISTRY SALICYLATE REAGENT (K093939)

_Siemens Healthcare Diagnostics · DKJ · May 19, 2010 · Clinical Toxicology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKJ/K093939

## Device Facts

- **Applicant:** Siemens Healthcare Diagnostics
- **Product Code:** [DKJ](/submissions/TX/subpart-d%E2%80%94clinical-toxicology-test-systems/DKJ.md)
- **Decision Date:** May 19, 2010
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.3830
- **Device Class:** Class 2
- **Review Panel:** Clinical Toxicology

## Indications for Use

For in vitro diagnostic use in the quantitative determination of salicylate in human serum and plasma (lithium heparin) on the ADVIA 1650 Chemistry systems. Such measurements are used in the diagnosis of salicylate toxicity and overdose.

## Device Story

In vitro diagnostic reagent system for quantitative salicylate measurement in human serum/plasma; used on ADVIA 1650 Chemistry systems. Principle: salicylate hydroxylase catalyzes conversion of salicylate and NADH to catechol and NAD+ in presence of oxygen; decrease in absorbance at 340/410 nm proportional to salicylate concentration. Operated by laboratory personnel in clinical settings. Output: salicylate concentration (mg/dL). Auto-rerun mechanism extends range up to 400 mg/dL. Results assist clinicians in diagnosing salicylate toxicity/overdose.

## Clinical Evidence

No clinical data provided; bench testing only.

## Technological Characteristics

In vitro diagnostic reagent for quantitative salicylate determination. Designed for use on ADVIA 1650 Chemistry systems. Utilizes automated chemical analysis principles for serum and plasma (lithium heparin) samples.

## Regulatory Identification

A salicylate test system is a device intended to measure salicylates, a class of analgesic, antipyretic and anti-inflammatory drugs that includes aspirin, in human specimens. Measurements obtained by this device are used in diagnosis and treatment of salicylate overdose and in monitoring salicylate levels to ensure appropriate therapy.

## Submission Summary (Full Text)

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>
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY ONLY TEMPLATE

A. 510(k) Number:
k093939

B. Purpose for Submission:
New device

C. Measurand:
Salicylate

D. Type of Test:
Quantitative, enzymatic

E. Applicant:
Siemens Healthcare Diagnostics

F. Proprietary and Established Names:
ADVIA Chemistry Salicylate Reagent

G. Regulatory Information:
1. Regulation section:
21 CFR § 862.3830 Salicylate test system
2. Classification:
Class II
3. Product codes:
DKJ
4. Panel:
Toxicology (91)

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2

H. Intended Use:

1. Intended use(s):
See indication(s) for use below.

2. Indication(s) for use:
For *in vitro* diagnostic use in the quantitative determination of salicylate in human serum and plasma (lithium heparin) on the ADVIA 1650 Chemistry systems. Such measurements are used in the diagnosis of salicylate toxicity and overdose.

3. Special conditions for use statement(s):
For prescription use only

4. Special instrument requirements:
For use on the ADVIA 1650 Chemistry system only

I. Device Description:

The device consists of two liquid reagents R1 and R2, which have the following components:

|  Reagent | Component | Concentration  |
| --- | --- | --- |
|  Salicylate Reagent 1 | Buffer, pH 10.4 |   |
|   | NADH | 1.2 mmol/L  |
|  Salicylate Reagent 2 | Buffer, pH 7.6 |   |
|   | Salicylate hydroxylase (bacterial) | ≥ 770 U/L  |
|   | Sodium azide | 0.1%  |

J. Substantial Equivalence Information:

1. Predicate device name(s):
Genzyme Diagnostics (formerly DCL) Salicylate assay

2. Predicate 510(k) number(s):
k042329

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3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | New Device | Predicate Device  |
|  Indications for Use | For the in vitro quantitative measurement of salicylate concentration in serum and plasma. Such measurements are used in the diagnosis of salicylate toxicity and overdose | Same  |
|  Sample Matrix | Serum, Plasma (Li Heparin) | Same  |
|  Test Principle | Salicylate hydroxylase catalyzes the conversion of salicylate and NADH to catechol and NAD in the presence of oxygen. | Same  |
|  Reference range | Toxic Range >30 mg/dL | Same  |
|  Reportable range | 3.0 – 100 mg/dL | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | New Device | Predicate Device  |
|  Calibrator | Siemens Healthcare Diagnostics
ToxAmmonia Calibrator | Genzyme Diagnostics
Salicylate calibrator  |

K. Standard/Guidance Document Referenced (if applicable):

CLSI EP05-A2: Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline-Second Edition

L. Test Principle:

The Salicylate (SAL) method is based on the reaction of salicylate hydroxylase with salicylate and NADH. Salicylate hydroxylase catalyzes the conversion of salicylate and NADH to catechol and NAD⁺ in the presence of oxygen. The resulting decrease in absorbance at 340/410 nm, due to the conversion of NADH to NAD⁺, is directly proportional to the concentration of salicylate in the sample.

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M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Within run and within-lab (total) imprecision were evaluated by testing three serum pools spiked with salicylate, two levels of a serum-based control material and a calibrator. Concentrations ranged from a low of 6.40 mg/dL to a high of 88.66 mg/dL. The concentrations were chosen to test the upper and lower limits of the expected range of the assay, the medically significant cutoff level as well as various levels throughout the assay range.

Each sample was assayed 2 times per run and 2 runs per day for 10 days, for a total of 40 replicates per concentration. The study was run using one reagent lot on one ADVIA 1650 Chemistry system, and one operator performed the study.

Within-run and total run imprecision statistics were calculated and are presented below:

|   |  | Within Run |   | Among Run |   | Among Day |   | Total  |   |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
|  Sample | Mean | SD | CV% | SD | CV% | SD | CV% | SD | CV%  |
|  Control 1 | 6.40 | 0.29 | 4.6 | 0.29 | 4.5 | 0.37 | 5.8 | 0.56 | 8.7  |
|  Serum 1 | 13.23 | 0.47 | 3.5 | 0.21 | 1.6 | 0.18 | 1.4 | 0.55 | 4.1  |
|  Control 2 | 16.57 | 0.43 | 2.6 | 0.12 | 0.8 | 0.36 | 2.2 | 0.57 | 3.5  |
|  Calibrator | 26.55 | 0.50 | 1.9 | 0.00 | 0.0 | 0.43 | 1.6 | 0.66 | 2.5  |
|  Serum 2 | 74.83 | 0.40 | 0.5 | 0.29 | 0.4 | 0.88 | 1.2 | 1.00 | 1.3  |
|  Serum 3 | 88.66 | 0.21 | 0.2 | 0.18 | 0.2 | 1.01 | 1.1 | 1.05 | 1.2  |

b. Linearity/assay reportable range:

The claimed measuring range of the assay is 3 - 100 mg/dL

The low end of the assay range was calculated based on the Limit of Detection studies. The assay range is based on the linearity and method comparison studies.

To assess linearity, each of five (5) diluted serum samples was tested in triplicate using one reagent lot on one ADVIA 1650 Chemistry system.

Results are presented below.

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|  Level | Expected values | Observed result | Bias | % recovery  |
| --- | --- | --- | --- | --- |
|  1 | 3.02 | 3.03 | 0.01 | 100.33%  |
|  2 | 6.04 | 6.11 | 0.07 | 101.16%  |
|  3 | 12.08 | 11.91 | -0.17 | 98.59%  |
|  4 | 24.15 | 24.32 | 0.17 | 100.70%  |
|  5 | 48.31 | 48.13 | -0.18 | 99.63%  |
|  6 | 96.61 | 96.61 | 0 | 100%  |

Linear regression of the data produced the following:

$$
\text{slope} = 1.00
$$

$$
y\text{-intercept} = 0
$$

$$
r^2 = 1.00
$$

ADVIA Chemistry systems extend the salicylate assay measuring range by an auto-rerun mechanism. This mechanism is triggered by a result above the upper range of the assay. The highest reportable value using the auto-rerun feature is 400 mg/dL.

The sponsor tested the auto-run feature as follows: a sample spiked to approximately 400 mg/dL was analyzed using auto-rerun. The auto-rerun feature produced a value of 391.4 mg/dL, or 98% recovery of the expected value of 401.1 mg/dL.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

ADVIA Chemistry Salicylate assay is calibrated using ADVIA Chemistry ToxAmmonia single-level calibrator cleared previously under k031683 and available separately. Calibrator value assignment and stability were addressed in k031683.

The sponsor does not specify the control materials, but recommends the use of a commercially available control with at least three levels.

d. Detection limit:

The estimations of the Limit of Blank (LoB) and Limit of Detection (LoD) were performed by running 40 replicates of a blank (DI water) and 40 replicates of a low serum pool. The low serum pool was a serum based low

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control with an approximate concentration of 6 mg/dL of salicylate. The standard deviation calculated from the 40 replicates of the blank and 40 replicates of the low serum pool were then used to calculate the Limit of Blank and Limit of Detection below.

Testing was conducted over a period of 10 days, 2 runs per day using one ADVIA 1650 Chemistry system and one reagent lot. A total of 40 replicates of each sample were run. One trained operator performed the testing.

The formulas described in the CLSI guideline EP17-A were used to determine the LoB and LoD.

The LoB was calculated as 1.33 mg/dL using the formula:

$$
\mathrm{LoB} = \frac{\text{Mean}_{\text{blank}} + 1.645 \times \text{total std dev of the blank}}{\text{LoD}}
$$

The LoD was calculated as 2.24 mg/dL using the formula:

$$
\mathrm{LoD} = \frac{\text{LoB} + 1.645 \times \text{total std dev of the low sample concentration}}{\text{LoD}}
$$

The sponsor selected 3 mg/dL as the lowest reportable concentration for the assay.

e. Analytical specificity:

Analytical specificity for the salicylate method was evaluated with two serum pools spiked with salicylate to approximately 20 and 50 mg/dL. Each of these pools was further spiked with five different levels of hemoglobin, unconjugated and conjugated bilirubin, or triglycerides (in the form of Intralipid). Hemoglobin was added at concentrations up to 1000 mg/dL, unconjugated bilirubin and conjugated bilirubin at concentrations up to 25 mg/dL, and Intralipid at concentrations up to 1000 mg/dL.

Each test sample was assayed in duplicate using one reagent lot on one ADVIA 1650 Chemistry system. Calculations were performed by comparing observed salicylate concentration at each level of interferent vs. observed salicylate concentration of control (no interferent), expressed in %.

Results of the study were as follows:

|  Potential Interferent Concentration | Salicylate concentration (mg/dL) | Recovery (%)  |
| --- | --- | --- |
|  Hb conc.(mg/dL)  |   |   |
|  0 | 21.5 | 0.0  |
|  250 | 21.2 | -1.4  |

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|  Potential Interferent Concentration | Salicylate concentration (mg/dL) | Recovery (%)  |
| --- | --- | --- |
|  500 | 21.3 | -0.9  |
|  750 | 21.0 | -2.3  |
|  1000 | 21.3 | -0.9  |
|  0 | 53.2 | 0.0  |
|  250 | 52.4 | -1.5  |
|  500 | 52.2 | -1.9  |
|  750 | 51.6 | -3.0  |
|  1000 | 51.6 | -3.0  |
|  Bilirubin (unconjugated) (mg/dL)  |   |   |
| --- | --- | --- |
|  0 | 22.1 | 0.0  |
|  6.25 | 22.5 | 1.8  |
|  12.5 | 21.5 | -2.7  |
|  18.75 | 21.4 | -3.2  |
|  25 | 21.0 | -5.0  |
|  0 | 54.9 | 0.0  |
|  6.25 | 54.6 | -0.5  |
|  12.5 | 54.3 | -1.1  |
|  18.75 | 54.2 | -1.3  |
|  25 | 53.6 | -2.4  |
|  Bilirubin (conjugated) (mg/dL)  |   |   |
|  0 | 21.7 | 0.0  |
|  6.25 | 21.2 | -2.3  |
|  12.5 | 19.9 | -8.3  |
|  18.75 | 19.5 | -10.1  |
|  25 | 18.8 | -13.4  |
|  0 | 54.6 | 0.0  |
|  6.25 | 54.2 | -0.7  |
|  12.5 | 53.1 | -2.7  |
|  18.75 | 52.5 | -3.8  |
|  25 | 51.4 | -5.9  |

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|  Potential Interferent Concentration | Salicylate concentration (mg/dL) | Recovery (%)  |
| --- | --- | --- |
|  TRIG (Intralipid) (mg/dL)  |   |   |
|  0 | 20.3 | 0.0  |
|  250 | 20.2 | -0.5  |
|  500 | 19.7 | -3.0  |
|  750 | 19.2 | -5.4  |
|  1000 | 19.0 | -6.4  |
|  0 | 50.4 | 0.0  |
|  250 | 49.6 | -1.6  |
|  500 | 49.6 | -1.6  |
|  750 | 49.2 | -2.4  |
|  1000 | 49.5 | -1.8  |

Interference at high concentrations of conjugated bilirubin is noted in the labeling.

f. Assay cut-off:

Not applicable

2. Comparison studies:

a. Method comparison with predicate device:

The sponsor analyzed a total of 104 samples on the ADVIA Chemistry 1650 system using the ADVIA Chemistry Salicylate method and on the predicate method. Both spiked and unaltered clinical samples were analyzed.

The samples analyzed span the proposed measuring range of the assay (3.0 - 100 mg/dL).

Linear regression produced the following:

slope = 0.989 (95% confidence interval 0.975 – 1.003)
y-intercept = -0.455 (95% confidence interval -1.174 – 0.264)
r² = 0.995

b. Matrix comparison:

Serum / plasma equivalency studies were performed to characterize the correlation between serum and lithium heparin plasma samples.

Twenty matched serum and plasma (Li-heparin) samples were collected in-house. The paired serum and plasma samples were collected and spiked with

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identical levels of purified sodium salicylate to achieve concentrations of salicylate from 3.7 to 91.1 mg/dL across the range of the assay. They were analyzed with the ADVIA Chemistry Salicylate method on one ADVIA 1650 Chemistry system using one lot of reagent, in single replicates.

Linear regression produced the following:

$$
\text{Plasma (Li-Heparin)} = 0.991 \times \text{Serum} + 0.798
$$

3. Clinical studies:

a. Clinical Sensitivity:

Not applicable

b. Clinical specificity:

Not applicable

c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off:

Not applicable

5. Expected values/Reference range*:

The toxic range stated by the sponsor is > 30 mg/dL.

*Henry JB. Clinical Diagnosis and Management by Laboratory Methods. 19th ed. Philadelphia, PA: W.B. Saunders; 1996:1454.

N. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

O. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

---

**Source:** [https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKJ/K093939](https://fda.innolitics.com/submissions/CH/subpart-d%E2%80%94clinical-toxicology-test-systems/DKJ/K093939)

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