OLYMPUS CREATINE KINASE REAGENT OSR6179/OSR6279

K043202 · Olympus America, Inc. · CGS · Dec 23, 2004 · Clinical Chemistry

Device Facts

• Record ID: K043202
• Device Name: OLYMPUS CREATINE KINASE REAGENT OSR6179/OSR6279
• Applicant: Olympus America, Inc.
• Product Code: CGS · Clinical Chemistry
• Decision Date: Dec 23, 2004
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Indications for Use

The Olympus Creatine Kinase reagent is intended for use in Olympus automated clinical chemistry analyzers for the quantitative determination of creatine kinase activity in human serum and plasma. Measurements of creatine kinase are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Device Story

Olympus Creatine Kinase Reagent; 3-part liquid reagent kit for use on Olympus automated clinical chemistry analyzers (AU400/AU400e, AU600/AU640/AU640e, AU2700/AU5400). Input: human serum or plasma samples. Principle: enzymatic colorimetric assay; creatine kinase catalyzes conversion of creatine phosphate and ADP to ATP; subsequent hexokinase and G-6-P-dehydrogenase reactions produce NADPH. Output: rate of increase in absorbance at 340/660 nm, proportional to creatine kinase activity (U/L). Used in clinical laboratories by professional staff. Results assist clinicians in diagnosing/monitoring myocardial infarction and muscle disorders. Reagent format modification from 2-part to 3-part liquid reagents to improve stability.

Clinical Evidence

No clinical data provided; substantial equivalence is based on performance characteristics of the reagent for quantitative determination of creatine kinase activity in human serum and plasma.

Technological Characteristics

Quantitative enzymatic colorimetric assay. Reagents: 3-part liquid (buffers, preservatives, stabilizers, enzymes). Analyzers: Olympus AU series (automated). Detection: spectrophotometric (340/660 nm). Standards: NCCLS EP5-A (precision), EP6-P (linearity), EP7-P (interference), EP9-A (method comparison).

Indications for Use

Indicated for quantitative determination of creatine kinase activity in human serum and plasma to aid in diagnosis and treatment of myocardial infarction and muscle diseases, including progressive Duchenne-type muscular dystrophy.

Regulatory Classification

Identification

A creatine phosphokinase/creatine kinase or isoenzymes test system is a device intended to measure the activity of the enzyme creatine phosphokinase or its isoenzymes (a group of enzymes with similar biological activity) in plasma and serum. Measurements of creatine phosphokinase and its isoenzymes are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

Submission Summary (Full Text)

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

A. 510(k) Number:
k043202

B. Purpose for Submission:
Clearance of new reagent format (to lengthen stability claim) and addition of a new matrix (plasma)

C. Measurand:
Creatine kinase

D. Type of Test:
Quantitative enzymatic colorimetric assay

E. Applicant:
Olympus America, Inc.

F. Proprietary and Established Names:
Olympus Creatine Kinase Reagent

G. Regulatory Information:
1. Regulation section:
21 CFR §862.1215, Creatine phosphokinase/creatine kinase or isoenzymes test system
2. Classification:
Class II
3. Product code:
CGS - NAD reduction/NADH oxidation, CPK or isoenzymes
4. Panel:
Clinical Chemistry (75)

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H. Intended Use:

1. Intended use(s):

The Olympus Creatine Kinase reagent is intended for use in Olympus automated clinical chemistry analyzers for the quantitative determination of creatine kinase activity in human serum and plasma.

Measurements of creatine kinase are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy.

2. Indication(s) for use:

See intended use above

3. Special conditions for use statement(s):

For professional use only

4. Special instrument requirements:

Olympus AU400/AU400e, AU600/AU640/AU640e, or AU2700/AU5400 analyzers

I. Device Description:

The Olympus Creatine Kinase reagent consists of 3 ready-to-use liquid reagents to be used on the Olympus family of analyzers. The reagents contain buffers, preservatives, stabilizers, and the reactive compounds and enzymes listed in Test Principle section below.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Olympus Creatine Kinase Reagent

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

k994189

3. Comparison with predicate:

This device is a second generation device with additional matrix claims and slight modifications to the way reagents are supplied.

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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Reagents | Identical in final reaction mixture | Identical in final reaction mixture |
| Open vial stability | 30 days | 30 days |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Matrix | Serum and plasma | serum |
| Reagent format | 3 liquid reagents | 2 liquid reagents |

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

NCCLS Guideline EP5-A – Evaluation of Precision Performance of Clinical Chemistry Devices

NCCLS Guideline EP6-P – Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach

NCCLS Guideline EP7-P – Interference testing in Clinical Chemistry

NCCLS Guideline EP9-A – Method comparison and Bias Estimation using Patient Samples

# L. Test Principle:

The Olympus creatine kinase reagent measures creatine kinase activity in the sample via the following mechanism:

Creatine kinase (from sample)

Creatine phosphate + ADP → creatine + ATP

Hexokinase, Mg²⁺

ATP + glucose → ADP + glucose-6-phosphate (G-6-P)

G-6-P-dehydrogenase

G-6-P + NADP⁺ → 6-phosphogluconate + NADPH + H⁺

The rate of increase in absorbance at 340/660 nm from NADPH production is directly proportional to the activity of creatine kinase in the sample.

# M. Performance Characteristics (if/when applicable):

1. Analytical performance:

a. Precision/Reproducibility:

Assay imprecision was evaluated by testing 3 serum-based control pools in duplicate twice a day for 20 days (total n per sample = 80) on each of three analyzer systems. Results are summarized below (units = U/L):

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AU400:

| Mean | Within Run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV |
| 101.91 | 2.08 | 2.04 % | 5.55 | 5.44 % |
| 278.03 | 2.63 | 0.95 % | 8.89 | 3.20 % |
| 836.08 | 5.11 | 0.61 % | 29.60 | 3.54 % |

AU600/AU640e:

| Mean | Within Run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV |
| 104.16 | 2.22 | 2.13 % | 5.46 | 5.25 % |
| 284.10 | 3.32 | 1.17 % | 9.93 | 3.50 % |
| 853.97 | 3.61 | 0.42 % | 30.06 | 3.52 % |

AU2700/AU5400:

| Mean | Within Run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | %CV | SD | %CV |
| 99.00 | 2.35 | 2.37 % | 4.51 | 4.55 % |
| 270.16 | 2.70 | 1.00 % | 8.64 | 3.20 % |
| 810.43 | 5.22 | 0.64 % | 26.59 | 3.28 % |

A second set of precision data was generated using 4 samples for inclusion in the package insert. Samples were tested in duplicate twice a day for 20 days (total n per sample = 80) on each of three analyzer systems. Results are summarized below (units = U/L):

AU400/AU400e:

| Mean (U/L) | Within run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | CV% | SD | CV% |
| 115 | 0.68 | 0.60 | 1.18 | 1.00 |
| 137 | 0.73 | 0.50 | 1.65 | 1.20 |
| 455 | 1.88 | 0.40 | 4.38 | 1.00 |
| 510 | 2.02 | 0.40 | 3.92 | 0.80 |

AU600/AU640/AU640e:

| Mean (U/L) | Within run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | CV% | SD | CV% |
| 117 | 1.22 | 1.00 | 1.77 | 1.50 |
| 135 | 2.04 | 1.50 | 3.83 | 2.80 |
| 452 | 4.85 | 1.10 | 11.47 | 2.50 |
| 498 | 5.44 | 1.10 | 9.94 | 2.00 |

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AU2700/AU5400:

| Mean (U/L) | Within run | | Total | |
| --- | --- | --- | --- | --- |
| | SD | CV% | SD | CV% |
| 118 | 0.99 | 0.80 | 2.34 | 2.00 |
| 138 | 1.30 | 0.90 | 1.93 | 1.40 |
| 465 | 3.07 | 0.70 | 5.37 | 1.20 |
| 500 | 4.46 | 0.90 | 9.54 | 1.90 |

# b. Linearity/assay reportable range:

The linearity of the assay was evaluated by testing a commercially available linearity set that covers the useable range. Each level was assayed in quadruplicate, and the mean results were plotted against the expected results. The regression statistics for testing on each analyzer are as follows:

AU400: slope $= 0.977$ intercept $= -0.496$

AU640: slope $= 0.988$ intercept $= -0.816$

AU2700: slope $= 0.933$ intercept $= -1.2305$

The data support the package insert claim that the assay is linear from 10-2000 U/L.

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

No traceability was provided.

On-board stability of the reagents was evaluated. Protocols and acceptance criteria were reviewed and found to be acceptable. The studies support an on-board stability claim of 30 days.

# d. Detection limit:

The analytical sensitivity of the assay, calculated adding three standard deviations to the mean of 20 replicates of an analyte-free sample, was determined to be $2 - 3\mathrm{U} / \mathrm{L}$ , which is below the stated claim of $10\mathrm{U} / \mathrm{L}, + / - 5\mathrm{U} / \mathrm{L}$ .

The sponsor states in the package insert that the typical change in absorbance per minute for $1\mathrm{U} / \mathrm{L}$ of CK is $0.12\mathrm{m}$ Absorbance for all members of the Olympus family of chemistry analyzers.

# e. Analytical specificity:

Potential interferences were evaluated by testing samples spiked with increasing concentrations of bilirubin (AU640), hemoglobin (AU400), or Intralipid (AU2700- to test for interference by lipemia). Results are summarized below:

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| Bilirubin added (mg/dL) | % Recovery |
| --- | --- |
| 0 | 100.0 |
| 4 | 100.8 |
| 8 | 101.6 |
| 12 | 101.4 |
| 16 | 100.2 |
| 20 | 102.2 |
| 24 | 103.6 |
| 28 | 101.9 |
| 32 | 103.7 |
| 36 | 102.1 |
| 40 | 101.8 |
| Hemolysate added (mg/dL) | % Recovery |
| --- | --- |
| 0 | 100.0 |
| 50 | 101.5 |
| 100 | 103.2 |
| 150 | 104.0 |
| 200 | 103.9 |
| 250 | 104.5 |
| 300 | 103.5 |
| 350 | 105.3 |
| 400 | 104.8 |
| 450 | 105.6 |
| 500 | 105.8 |
| Intralipid added (mg/dL) | % Recovery |
| --- | --- |
| 0 | 100.0 |
| 100 | 98.7 |
| 200 | 98.8 |
| 300 | 97.8 |
| 400 | 98.8 |
| 500 | 98.4 |
| 600 | 98.5 |
| 700 | 97.6 |
| 800 | 97.7 |
| 900 | 99.1 |
| 1000 | 98.3 |

f. Assay cut-off: Not applicable

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2. Comparison studies:

a. Method comparison with predicate device:

Both serum and plasma samples were run using both the predicate reagent (current version of the reagent) and the new reagent (device). Least squares regression statistics are summarized below :

Serum :
$$ \text{Device} = 0.992(\text{Predicate}) + 0.026 $$
Correlation coefficient = 1.000
Range = 21.73 – 1903.13

Plasma :
$$ \text{Device} = 0.990(\text{Predicate}) + 0.872 $$
Correlation coefficient = 1.000
Range = 18.00 – 1967.00

Samples run with the AU640 analyzer (Validated in separate experiments versus the predicate - see above) was compared to the same samples run on the AU400 and AU2700/AU5400 analyzers. Least squares regression statistics are summarized below :

AU400 :
$$ \text{AU400} = 1.040(\text{AU640}) - 2.089 $$
Correlation coefficient = 0.999
Range = 17.70 – 1879.78

AU2700/AU5400 :
$$ \text{AU2700/AU5400} = 0.999(\text{AU640}) - 1.763 $$
Correlation coefficient = 1.000
Range = 17.70 – 1879.78

b. Matrix comparison:

The sponsor performed accuracy testing on both serum and plasma samples (see above).

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):
Not applicable

4. Clinical cut-off:
Not applicable

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5. Expected values/Reference range:

This information is the same as for the predicate device (k994189). The expected values in an adult population are 30-223 U/L creatine kinase. The applicant states that this range is based on data collected from 200 blood donors in North Texas.

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.

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