← Product Code [MYT](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/MYT) · K051433

# I-STAT CREATINE KINASE MB (CK-MB) (K051433)

_I-Stat Corporation · MYT · Dec 15, 2005 · Clinical Chemistry · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/MYT/K051433

## Device Facts

- **Applicant:** I-Stat Corporation
- **Product Code:** [MYT](/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/MYT.md)
- **Decision Date:** Dec 15, 2005
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 862.1215
- **Device Class:** Class 2
- **Review Panel:** Clinical Chemistry

## Indications for Use

The i-STAT CK-MB test is an in vitro diagnostic test for the quantitative measurement of creatinine kinase MB mass in whole blood or plasma samples. CK-MB measurements can be used as an aid in the diagnosis and treatment of myocardial infarction (MI).

## Device Story

i-STAT CK-MB and cTnI tests are single-use cartridges for point-of-care use. User scans barcode; applies ~16 microliters of fresh whole blood to cartridge; inserts into i-STAT 1 Analyzer. Analyzer performs automated analysis: sample incubation with enzyme-linked antibody conjugate; sample discard; substrate/wash solution application; amperometric signal measurement via alkaline phosphatase cleavage. Results displayed on analyzer; stored for transfer. System provides rapid quantitative measurement of cardiac markers to assist clinicians in diagnosing myocardial infarction and monitoring cardiac status. Benefits include rapid turnaround time compared to central lab testing, facilitating timely clinical decision-making in emergency departments, ICUs, and CCUs.

## Clinical Evidence

Clinical study compared i-STAT CK-MB to Abbott AxSYM plasma results in 263 patients presenting with chest pain. Deming regression analysis showed a slope of 1.01, intercept of -0.19, and correlation coefficient of 0.994 for all samples. For samples <20.0 ng/mL (n=234), slope was 0.993, intercept -0.05, and correlation 0.960. Non-clinical data established LLD of 0.6 ng/mL, insensitivity to hematocrit (0-70% PCV), and lack of significant interference from CK-BB or CK-MM isoforms.

## Technological Characteristics

Single-use test cartridge; two-site ELISA; electrochemical sensing principle using alkaline phosphatase enzyme label; resistive heating for temperature control; automated fluidics; quantitative measurement; compatible with i-STAT 1 Analyzer.

## Regulatory 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.

## Predicate Devices

- Triage Cardiac Panel (CK-MB test)

## Reference Devices

- i-STAT 1 Analyzer ([K001387](/device/K001387.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
K051433

B. Purpose for Submission:
New assay for I-STAT CREATINE KINASE MB (CK-MB) and change in indications for use for the i-STAT Cardiac Troponin I (cTnI) (k031739) to include use with whole blood instead of heparinized whole blood.

C. Measurand:
Creatine Kinase MB, Troponin I

D. Type of Test:
Quantitative/Electrochemical two site ELISA

E. Applicant:
I-STAT CORPORATION

F. Proprietary and Established Names:
I-STAT CREATINE KINASE MB (CK-MB)

G. Regulatory Information:
1. Regulation section:
21CFR Sec- 862.1215-Creatine phosphokinase/creatine kinase or isoenzymes test system.
2. Classification:
2
3. Product code:
MYT - BIOSENSOR, IMMUNOASSAY, CPK OR ISOENZYMES
MMI - IMMUNOASSAY METHOD, TROPONIN SUBUNIT
4. Panel:
Chemistry (75)

H. Intended Use:
1. Intended use(s):
See indications for use
2. Indication(s) for use:
The i-STAT CK-MB test is an in vitro diagnostic test for the quantitative measurement of creatine kinase MB mass in whole blood or plasma samples. CK-MB measurements can be used as an aid in the diagnosis of myocardial infarction (MI), re-infarction, and the sizing of infarction. CK-MB measurements can also be used in monitoring reperfusion during thrombolytic therapy and perioperative myocardial infarction (poMI) after cardiac surgery.

The i-STAT Cardiac Troponin I (cTnI) test is an in vitro diagnostic test for the quantitative measurement of cardiac troponin I in whole blood or plasma. Measurements of cardiac Troponin I are used in the diagnosis and treatment of myocardial infarction and as an aid in the risk stratification of patients with acute coronary syndromes with respect to their relative risk of mortality.

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

4. Special instrument requirements:
i-STAT 1 Analyzer

I. Device Description:
The i-STAT CK-MB and cTnI tests are contained in single cartridges. In use, the user scans a bar-code and then places approximately 16 microliters of fresh whole blood in the cartridge. The cartridge is inserted into the thermally controlled i-STAT Analyzer, and all analytical steps are performed automatically. Patient and user information may be entered into the analyzer via a keypad during the automated analysis cycle. The CK-MB and cTnI test cartridges are assembled from plastic components that provide the conduits for fluid handling and house the sensor chips and heating elements necessary for temperature control and signal measurement.

Upon insertion of the cartridge into the analyzer, it performs several quality checks. The sample and enzyme-linked antibody conjugate are incubated for a predetermined period of time under temperature control. The sample is discarded and the substrate/wash solution is brought over the alkaline phosphatase captured on the CK-MB or cTnI sensor. The enzyme cleaves the substrate giving rise to an amperometric signal which the analyzer measures. The result is displayed and stored in memory for possible transfer via infra red to a printer or to electronic databases.

J. Substantial Equivalence Information:

1. Predicate device name(s):
Biosite, Triage Cardiac Panel, i-STAT Cardiac Troponin I (cTnI)

2. Predicate 510(k) number(s):
k030286, k031739

3. Comparison with predicate:

|  Characteristic | Triage CK-MB | i-STAT CK-MB  |
| --- | --- | --- |
|  Assay methodology | Two-site ELISA | Two-site ELISA  |
|  Capture site | Heterogeneous | Heterogeneous  |
|  Capture antibodies | Monoclonal | Monoclonal  |
|  Enzyme label antibody | Polyclonal | Monoclonal  |
|  Enzyme label | Fluorescent dye | Alkaline phosphatase  |
|  Analysis sequence | Simultaneous capture/label | Simultaneous capture/label  |
|  Analysis time | 16 minutes | 5 minutes  |
|  Sample type | Whole blood or plasma | Whole blood or plasma  |
|  Enzyme detection | Fluorescent | Electrochemical  |
|   | i-STAT cTnI (k031739) | New i-STAT cTnI  |
|  Assay characteristics | Same | Same  |
|  Sample type | Heparinized whole blood or plasma | Whole blood or plasma  |

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K. Standard/Guidance Document Referenced (if applicable):
CLSI – EP09-A2: Method Comparison and Bias Estimation Using Patient Samples
CLSI – EP05-A2: Evaluation of Precision Performance of Clinical Chemistry
Devices CLSI – EP07-A: Interference Testing in Clinical Chemistry
IEC – 61326: 2002 Electrical equipment for measurement, control and laboratory use-EMC requirements

L. Test Principle:
The i-STAT CK-MB test is an enzyme-linked immunosorbent assay (ELISA) with amperometric detection of the alkaline phosphatase enzyme signal, similar in principle to the i-STAT cTnI cartridge.

Antibodies specific to an epitope unique to the MB subunit, that therefore do not bind to CK-MM nor CK-BB, are patterned on the gold sensor via partial drop microprinitng of a carboxylated polystyrene latex microsphere suspension. The CK-MB capture antibodies are covalently bound to the microspheres prior to their deposition on the spheres. The gold sensor is situated on a silicon chip positioned in the microfluidic channel of the cartridge.

An alkaline phosphatase-CK-BB Fab conjugate is also printed on the silicon chip. This conjugate is formulated with antibody fragments that are specific to an epitope on the B subunit of creatine kinase, in a matrix of materials which aid in the stabilization of enzyme conjugate and aid in decreasing immunological interferences during the CK-MB assay. The specificity of the conjugate antibody to the B subunit allows this conjugate to recognize CK-MB and CK-BB but not CK-MM.

i-STAT cTnI Two Site Elisa. The analyte, cardiac Troponin I is captured by a probe impregnated with a monoclonal anti-cTnI antibody. The sample is discarded. The probe is treated with a second reagent composed of anti-cTnI polyclonal antibodies which are tagged with Alkaline Phosphatase. After washing, the sandwich complex is treated with a substrate which upon being cleaved by the captured alkaline phosphatase produces and electronic signal which is read by the i-STAT analyzer.

M. Performance Characteristics (if/when applicable):
i-STAT Cardiac Troponin I (cTnI) - subject of k031739 except for matrix studies below
1. Analytical performance:
a. Precision/Reproducibility:
An imprecision study involving twenty test events, three lots of i-STAT CK-MB test cartridges, seven i-STAT 1 analyzers and a single lot of control fluids was performed by hospital personnel at the clinical site. A second imprecision study was performed at i-STAT Canada Limited, Ottawa, by i-STAT personnel. Six different i-STAT 1 analyzers and the same cardiac marker control fluid lot were used in this study. In each event of these precision studies, different vials of three levels of controls were run in duplicate in each of three sub-lots of i-STAT CK-MB test cartridges. The hospital imprecision data was collected over a 23-day period while the study at i-STAT ran for 20 days.

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The results of these studies are summarized below. The arithmetic mean of the total imprecision across all studies/sites is 10.5%, 10.4%, and 9.9% for level 1, 2 and 3 controls respectively.

## Imprecision Estimated from 20-Event Control Fluid Studies

|  Site | Control Level | CK-MB mean ng/mL | Within Run %CV | Total within lot %CV | Total %CV  |
| --- | --- | --- | --- | --- | --- |
|  i-STAT Canada Limited, Ottawa Ontario | 1 | 5.9 | 9.5 | 10.9 | 11.9  |
|   |  2 | 25.8 | 9.4 | 9.4 | 10.4  |
|   |  3 | 90.1 | 8.3 | 8.8 | 10.0  |
|  Utah Valley Regional Medical Center Provo, Utah | 1 | 5.3 | 8.8 | 9.1 | 9.1  |
|   |  2 | 22.2 | 8.2 | 10.2 | 10.3  |
|   |  3 | 68.0 | 8.0 | 9.8 | 9.8  |

b. Linearity/assay reportable range: up to 150 ng/mL

c. Traceability, Stability, Expected values (controls, calibrators, or methods): The calibration process in the factory is traceable to internal standards prepared using the recombinant CK-MB material recommended by the American Association of Clinical Chemists (AACC) for the standardization of creatine kinase mass assays. The applicant uses a 6 level calibrator set in the factory with approximate values at: 0, 7, 20, 60, 125, 175 ng/mL

d. Detection limit: lower limit of detection of 0.6 ng/mL.

e. Analytical specificity: Tested for common medications and those commonly prescribed to patients with cardiovascular conditions. The levels of the potential interferents were set using the CLSI guideline EP7-A: Interference Testing in Clinical Chemistry, Approved Guideline.

|  Generic Name | Test Level uMol/L | Control (ng/ml) | CK-MB ng/ml | % change  |
| --- | --- | --- | --- | --- |
|  Acetominophen | 1660 | 14.1 | 15.1 | 6.6%  |
|  Acetylsalicylic Acid | 3333 | 12.4 | 13.3 | 7.0%  |
|  Allopurinol | 294 | 14.8 | 15.7 | 6.0%  |
|  Ampicillin | 152 | 12.4 | 12.7 | 2.1%  |
|  Ascorbic Acid | 227 | 14.8 | 15.8 | 6.8%  |
|  Atenolol | 37.6 | 14.8 | 15.8 | 6.8%  |
|  Caffeine | 308 | 15.0 | 15.7 | 4.3%  |
|  Captopril | 23 | 12.4 | 12.7 | 2.6%  |
|  Chloramphenicol | 155 | 14.8 | 15.9 | 7.2%  |
|  Diclofenac | 169 | 14.8 | 15.9 | 7.4%  |

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|  Generic Name | Test Level uMol/L | Control (ng/ml) | CK-MB ng/ml | % change  |
| --- | --- | --- | --- | --- |
|  Digoxin | 6.15 | 14.8 | 15.5 | 4.9%  |
|  Dopamine | 5.87 | 14.1 | 13.9 | -1.5%  |
|  Enalaprilat | 0.86 | 14.8 | 15.9 | 7.6%  |
|  Erythromycin | 81.6 | 15.0 | 14.6 | -2.8%  |
|  Furosemide | 181 | 15.0 | 15.4 | 2.5%  |
|  Ibuprofen | 2425 | 15.0 | 15.0 | -0.3%  |
|  Isorbide Dinitrate | 636 | 12.4 | 12.5 | 0.8%  |
|  Methyldopa | 71 | 15.0 | 16.2 | 8.2%  |
|  Nicotine | 6.2 | 12.4 | 13.6 | 9.5%  |
|  Nifedipine | 1156 | 12.4 | 13.0 | 4.5%  |
|  Phenytoin | 198 | 15.0 | 15.4 | 2.5%  |
|  Propranolol | 7.71 | 15.0 | 15.0 | -0.1%  |
|  Salicylic Acid | 4.34 | 12.4 | 12.7 | 1.9%  |
|  Sodium Heparin | 90 U/mL | 12.4 | 11.9 | -4.0%  |
|  Theophylline | 222 | 15.0 | 14.0 | -6.8%  |
|  Verapamil | 4.4 | 15.0 | 15.6 | 3.9%  |
|  Warfarin | 64.9 | 15.0 | 15.0 | 0.1%  |

An important property of a CK-MB assay is its selectivity for the MB isoform of the creatine kinase enzyme. To demonstrate this selectivity, a plasma sample containing a low CK-MB level was measured pairwise using three different lots of CK-MB assay cartridges in the presence and absence of the other major isoforms of the CK enzyme.

|  CK isoform | Number of runs per condition | Mean CK-MB (ng/mL) With interferent | Mean CK-MB (ng/mL) without interferent  |
| --- | --- | --- | --- |
|  CK-BB 100 ng/mL | 6 | 6.7 (0.6)* | 7.1 (0.8)*  |
|  CK-MM 10000 ng/mL | 6 | 7.3 (0.7)* | 7.1 (0.6)*  |

* The number in parentheses is the standard deviation of the 6 cartridge results.

f. Assay cut-off:
Whole blood and plasma samples from 161 apparently healthy donors were assayed in duplicate using 3 different lots of i-STAT CK-MB cartridges. The 0 to 95% range of results spanned 0.0 ng/mL (μg/L) to 3.5 ng/mL (μg/L).

2. Comparison studies:
a. Method comparison with predicate device:
The test population at all three sites was comprised of patients in any hospital department (e.g., emergency department [ED], ICU, CCU, general ward) who presented with acute, severe, and prolonged chest pain. Testing was

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performed by end-user level personnel. Operators included nurses, physicians, research technicians, and medical technologists. Analysis of the method comparison data was undertaken in accordance with recommendations set forth in the CLSI guideline EP9-A2: Method Comparison and Bias Estimation Using Patient Samples.

Method comparison data for i-STAT whole blood and plasma results versus AxSYM plasma result:
N - 263, slope = 1.01, intercept = -0.224, r = 0.993

Method comparison data for i-STAT whole blood and plasma results versus AxSYM plasma result for which [CK-MB] &lt;20 ng/mL:
N = 234, slope = .0995, intercept = -0.053, r = 0.960

b. Matrix comparison:
Four 10 mL whole blood samples were drawn from 11 separate donors into untreated plastic vacutainers. Each sample was spiked with a concentrate containing both cTnI and CKMB. The 44 resulting samples were mixed and separated into a Li Heparin 5 mL vacutainer and an untreated 5 mL plastic vacutainer. These samples were allowed to incubate for 5 minutes. After the incubation, the 88 samples were run pairwise on a single lot of cTnI and CKMB assay cartridges using the i-STAT portable blood analyzer

Heparinized vs. Un-Heparinized CKMB:
y = 0.9385x + 3.7104, r²=0.975

Heparinized vs. Un-Heparinized cTnI:
y = 1.0341x + 0.1338, r²=0.9962

3. Clinical studies:
a. Clinical Sensitivity:
Not performed
b. Clinical specificity:
Not performed
c. Other clinical supportive data (when a. and b. are not applicable):

4. Clinical cut-off:
Not performed

5. Expected values/Reference range:
Whole blood and plasma samples from 161 apparently healthy donors were assayed in duplicate using 3 different lots of i-STAT CK-MB cartridges. The 0 to 95% range of results spanned 0.0 ng/mL (μg/L) to 3.5 ng/mL (μg/L).

N. Instrument Name:
i STAT 1 Analyzer - K001387

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O. System Descriptions:

1. Modes of Operation:
Single use cartridge

2. Software:
FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:
Yes ☐ X or No ☐

3. Specimen Identification:
Bar code reader is incorporated into the system.

4. Specimen Sampling and Handling:
Whole blood samples are applied directly into the sample well of the cartridge.

5. Calibration:
Factory set

6. Quality Control:
Quality control is material available. The reliability of the result is maintained through a combination of user testing and instrument self-checks. The self-checks occur with every cartridge run and verify performance of the analyzer and cartridge sub-systems. This includes checks on the individual sensor’s performance, the integrity of the calibrant fluid, the response of the pressure and thermal transducers, and the flow of calibrant and sample within the cartridge. Any values that are statistically deviant from the factory-established expectation values would cause the test results to be suppressed.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The “Performance Characteristics” Section above:

Q. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.

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

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**Source:** [https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/MYT/K051433](https://fda.innolitics.com/submissions/CH/subpart-b%E2%80%94clinical-chemistry-test-systems/MYT/K051433)

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