STRATUS CS ACUTE CARE MB ISOENZYME OF CREATINE KINASE (CKMB) TEST PAK; STRATUS CS ACUTE CARE CKMB TESTPAK.

K051650 · Dade Behring, Inc. · JHX · Sep 8, 2005 · Clinical Chemistry

Device Facts

• Record ID: K051650
• Device Name: STRATUS CS ACUTE CARE MB ISOENZYME OF CREATINE KINASE (CKMB) TEST PAK; STRATUS CS ACUTE CARE CKMB TESTPAK.
• Applicant: Dade Behring, Inc.
• Product Code: JHX · Clinical Chemistry
• Decision Date: Sep 8, 2005
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 862.1215
• Device Class: Class 2

Indications for Use

The Stratus® CS Acute Care™ CKMB method is an in vitro diagnostic test for the measurement of the MB isoenzyme of creatine kinase (ATP:Creatine N-Phosphostransferase, E.C. No. 2.7.3.2) in heparinized plasma. Measurements of CKMB are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings. The Stratus® CS Acute Care™ CKMB Calibrator (CKMB CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ CKMB method. The Stratus® CS Acute Care™ CKMB Dilution Pak (CKMB DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CKMB TestPak for the measurement of samples with elevated levels of CKMB. The Stratus® CS Acute Care™ Troponin I method (cTnI) is an in vitro diagnostic assay for the measurement of cardiac troponin I in heparinized plasma. Cardiac troponin I measurements can be used as an aid in the diagnosis of acute myocardial infarction (AMI). Cardiac troponin I can also be used as an aid in the risk stratification of patients with acute coronary syndromes (ACS) with respect to their relative risk of mortality. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings. The Stratus® CS Acute Care™ Troponin I Calibrator (cTnI CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ Troponin I method. The Stratus® CS Acute Care™ Troponin I Dilution Pak (cTnI DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ cTnI TestPak for the measurement of samples with elevated levels of cardiac troponin I. The Stratus® CS Acute Care™ Myoglobin method (MYO) is an in vitro diagnostic assay for the measurement of myoglobin in heparinized plasma. Measurements of myoglobin aid in the rapid diagnosis of renal or heart disease, e.g. myocardial infarction. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings. The Stratus® CS Acute Care™ Myoglobin Calibrator (MYO CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ myoglobin method. The Stratus® CS Acute Care™ Myoglobin Dilution Pak (MYO DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ MYO TestPak for the measurement of samples with elevated Myoglobin levels.

Device Story

The Stratus® CS Acute Care™ system performs in vitro diagnostic immunoassays for CKMB, cTnI, and Myoglobin. The device uses solid-phase Radial Partition Immunoassay (RPIA) technology. Input samples (heparinized plasma) are applied to glass fiber paper containing immobilized antibodies. After incubation, enzyme-labeled monoclonal antibodies are added to form an antibody-antigen-labeled antibody sandwich. A substrate wash solution elutes unbound labeled antibody and initiates enzyme activity. An optical system monitors the reaction rate via front surface fluorescence. A microprocessor performs all data analysis. The device is intended for use by trained healthcare professionals in clinical laboratories and point-of-care (POC) settings. Results assist clinicians in diagnosing myocardial infarction, muscular dystrophy, and risk-stratifying acute coronary syndrome patients. The system includes specific TestPaks, CalPaks (calibrators), and DilPaks (diluents) for each analyte.

Clinical Evidence

Bench testing only. Method comparison and precision analysis were performed at three locations (clinical laboratory, Emergency Department, and Cardiac Care Unit) across two sites. Data demonstrated that precision and accuracy generated by non-laboratory personnel are comparable to those generated by laboratory personnel, supporting the expansion of the intended use to point-of-care settings.

Technological Characteristics

Two-site sandwich Radial Partition Immunoassay (RPIA). Reagents: alkaline phosphatase-conjugated Fab fragments, dendrimer-linked monoclonal antibodies, 4-methylumbelliferyl phosphate substrate. Form factor: TestPak cartridges for use on Stratus® CS STAT Fluorometric Analyzer. Energy: front-surface fluorescence optical detection. Connectivity: microprocessor-controlled analyzer. Sterilization: N/A (reagents).

Indications for Use

Indicated for trained healthcare professionals in clinical laboratory and POC settings to measure CKMB (myocardial infarction, muscular dystrophy), cardiac troponin I (AMI diagnosis, ACS risk stratification), and myoglobin (renal or heart disease, myocardial infarction) in heparinized plasma.

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.

Predicate Devices

• Stratus® CS CKMB TestPak and DilPak (k984067, k981099)
• Stratus® CS CKMB CalPak (k981097)
• Stratus® CS cTnI Acute Care™ TestPak and DilPak (k033487, k984093, k981098)
• Stratus® CS cTnI CalPak (k012233, k983722)
• Stratus® CS MYO TestPak and DilPak (k981102, k984056)
• Stratus® CS MYO CalPak (k981101)

Submission Summary (Full Text)

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

A. 510(k) Number:
k051650

B. Purpose for Submission:
Modification to Indications for Use and Intended Use of Dade Behring Stratus® CS CKMB, troponin I and myoglobin assays to add: This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings. CKMB and myoglobin assays renamed to Acute Care™ CKMB and Acute Care™ MYO.

C. Measurand:
MB isozyme of Creatine Kinase (CKMB)
Troponin I
Myoglobin

D. Type of Test:
Two-site sandwich immunoassay

E. Applicant:
Dade Behring Inc.

F. Proprietary and Established Names:
Stratus® CS Acute Care™ MB isoenzyme of creatine kinase (CKMB) TestPak
Stratus® CS Acute Care™ CKMB CalPak
Stratus® CS Acute Care™ CKMB DilPak
Stratus® CS Acute Care™ Troponin I (cTnI) TestPak
Stratus® CS Acute Care™ cTnI CalPak
Stratus® CS Acute Care™ cTnI DilPak

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Stratus® CS Acute Care™ Myoglobin (MYO) TestPak

Stratus® CS Acute Care™ MYO CalPak

Stratus® CS Acute Care™ MYO DilPak

## G. Regulatory Information:

1. Regulation section:
- 21 CFR 862.1215, Creatine phosphokinase/creatine kinase or isoenzymes test system
- 21 CFR 866.5680, Myoglobin immunological test system
- 21 CFR 862.1150, Calibrator

2. Classification:
- Class II

3. Product code:
- JHX, Fluorometric method, CPK or isoenzymes
- MMI, Immunoassay Method, Troponin Subunit
- DDR, Myoglobin, antigen, antiserum, control
- JIT, Calibrator, Secondary

4. Panel:
- Chemistry (75)
- Immunology (82)

## H. Intended Use:

1. Intended use(s):
- See Indications for Use

2. Indication(s) for use:
- CKMB

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The Stratus® CS Acute Care™ CKMB method is an in vitro diagnostic test for the measurement of the MB isoenzyme of creatine kinase (ATP:Creatine N-Phosphostransferase, E.C. No. 2.7.3.2) in heparinized plasma. Measurements of CKMB are used in the diagnosis and treatment of myocardial infarction and muscle diseases such as progressive, Duchenne-type muscular dystrophy. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

The Stratus® CS Acute Care™ CKMB Calibrator (CKMB CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ CKMB method.

The Stratus® CS Acute Care™ CKMB Dilution Pak (CKMB DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ CKMB TestPak for the measurement of samples with elevated levels of CKMB.

## Troponin I

The Stratus® CS Acute Care™ Troponin I method (cTnI) is an in vitro diagnostic assay for the measurement of cardiac troponin I in heparinized plasma. Cardiac troponin I measurements can be used as an aid in the diagnosis of acute myocardial infarction (AMI). Cardiac troponin I can also be used as an aid in the risk stratification of patients with acute coronary syndromes (ACS) with respect to their relative risk of mortality. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

The Stratus® CS Acute Care™ Troponin I Calibrator (cTnI CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ Troponin I method.

The Stratus® CS Acute Care™ Troponin I Dilution Pak (cTnI DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ cTnI TestPak for the measurement of samples with elevated levels of cardiac troponin I.

## Myoglobin

The Stratus® CS Acute Care™ Myoglobin method (MYO) is an in vitro diagnostic assay for the measurement of myoglobin in heparinized plasma. Measurements of myoglobin aid in the rapid diagnosis of renal or heart disease, e.g. myocardial infarction. This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings.

The Stratus® CS Acute Care™ Myoglobin Calibrator (MYO CalPak) is an in vitro diagnostic product intended to be used for calibration of the Stratus® CS Acute Care™ myoglobin method.

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The Stratus® CS Acute Care™ Myoglobin Dilution Pak (MYO DilPak) is an in vitro diagnostic product intended to be used in conjunction with the Acute Care™ MYO TestPak for the measurement of samples with elevated Myoglobin levels.

3. Special conditions for use statement(s):

Professional use only

4. Special instrument requirements:

Stratus® CS STAT Fluorometric Analyzer

I. Device Description:

Stratus® CS Acute Care™ MB isoenzyme of creatine kinase (CKMB) TestPak kit contains 100 TestPaks composed of the following reagents: Alkaline phosphatase (calf intestine enzyme) conjugated to anti-CKBB Fab (mouse monoclonal antibody), ACES buffer, sodium azide < 0.1 %, dendrimer linked CKMB antibody (mouse IgG monoclonal), 4-methylumbelliferyl phosphate, diethanolamine buffer.

Stratus® CS Acute Care™ CKMB CalPak is a refrigerated liquid product containing human heart CKMB in a buffered bovine protein matrix with stabilizers and preservative. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.

Stratus® CS Acute Care™ CKMB DilPak is a refrigerated liquid product containing buffered human protein matrix with stabilizers and 0.2 % sodium azide. The kit consists of 5 DilPaks with diluent in one well.

Stratus® CS Acute Care™ Troponin I (cTnI) TestPak kit contains 100 TestPaks composed of the following reagents: Alkaline phosphatase conjugated (calf intestine enzyme) conjugated to anti-cardiac troponin I Fab (mouse monoclonal antibody), buffer, sodium azide < 0.1 %, dendrimer linked cardiac troponin I antibody (mouse IgG monoclonal), 4-methylumbelliferyl phosphate, diethanolamine buffer.

Stratus® CS Acute Care™ cTnI CalPak is a frozen liquid product containing native human troponin complex in a human serum base with < 0.1 % sodium azide. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.

Stratus® CS Acute Care™ cTnI DilPak is a refrigerated liquid product containing phosphate buffer with preservatives including < 0.1 % sodium azide. The kit consists of 5 DilPaks with diluent in one well.

Stratus® CS Acute Care™ Myoglobin (MYO) TestPak kit contains 100 TestPaks composed of the following reagents: Alkaline phosphatase (calf intestine enzyme)

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conjugated to anti-MYO Fab (mouse monoclonal antibody), ACES buffer, sodium azide < 0.1 %, dendrimer linked (mouse IgG monoclonal) MYO antibody, 4-methylumbelliferyl phosphate, diethanolamine buffer.

Stratus® CS Acute Care™ MYO CalPak is a refrigerated liquid product containing human heart myoglobin in a bovine albumin matrix with stabilizers and < 0.1 % sodium azide. The kit consists of five CalPaks at a single calibrator level. Each CalPak contains calibrator reagent in three wells.

Stratus® CS Acute Care™ MYO DilPak is a refrigerated liquid product containing buffered bovine protein matrix with stabilizers and 0.2 % sodium azide. The kit consists of 5 DilPaks with diluent in one well.

Human source material was tested and found to be negative/non-reactive for antibodies to HIV-1/2, HBsAg, and HCV.

J. Substantial Equivalence Information:

1. Predicate device name(s):

Stratus® CS CKMB TestPak and DilPak

Stratus® CS CKMB CalPak

Stratus® CS cTnI Acute Care™ TestPak and DilPak

Stratus® CS cTnI CalPak

Stratus® CS MYO TestPak and DilPak

Stratus® CS MYO CalPak

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

Stratus® CS CKMB TestPak and DilPak k984067

k981099

Stratus® CS CKMB CalPak k981097

Stratus® CS cTnI Acute Care™ TestPak and DilPak k033487

k984093

k981098

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Stratus® CS cTnI CalPak
k012233
k983722
k012233

Stratus® CS MYO TestPak and DilPak
k981102
k984056

Stratus® CS MYO CalPak
k981101

3. Comparison with predicate:

| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Test principle for CKMB, cTnI and MYO assays | Same | Same |
| Performance characteristics for CKMB, cTnI and MYO assays | Same | Same |
| Composition and traceability of CKMB, cTnI and MYO calibrators | Same | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| CKMB, cTnI and MYO calibrators | Addition of Stratus® CS Acute Care to name | Not applicable |
| CKMB and MYO assays. | Addition of Stratus® CS Acute Care to name (Acute Care was added to cTnI assay name in k033487) | Not applicable |
| Indications for Use for CKMB, cTnI and MYO assays | Addition of: This method is for use by trained health care professionals in the clinical laboratory and point of care (POC) settings. | Not applicable |
| Reproducibility | Addition of reproducibility data from ED, CCU and Central Laboratory to labeling | Not applicable |

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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Correlation | Addition of POC data subset regression statistics to labeling | Not applicable |

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

CLSI EP5-T2

## L. Test Principle:

### CKMB

The Stratus® CS Acute Care™ CKMB method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. Dendrimer linked monoclonal CKMB antibody is added to the center portion of a square piece of glass fiber paper in the CKMB TestPak. Sample is then added onto the paper where it reacts with the immobilized anti-CKMB antibody. After a short incubation, a conjugate consisting of enzyme labeled monoclonal antibody directed against a distinct antigenic site on the B subunit of the CKMB molecule is pipetted onto the reaction zone of the paper. During the second incubation period, enzyme-labeled antibody reacts with the bound CKMB, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of CKMB in the sample. The reaction rate is measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

### Troponin I (cTnI)

The Stratus® CS Acute Care™ Troponin I method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. Dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the cTnI TestPak. This antibody recognizes a distinct antigenic site on the cardiac troponin I molecule. Sample is then added onto the paper where it reacts with the immobilized antibody. After a short incubation, a conjugate consisting of enzyme labeled monoclonal antibody directed against a second distinct antigenic site on the cardiac troponin I molecule is pipetted onto the reaction zone of the paper. During the second incubation period, enzyme-labeled antibody reacts with the bound cardiac troponin I, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By

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including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of cardiac troponin I in the sample. The reaction rate is measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

## Myoglobin (MYO)

The Stratus® CS Acute Care™ MYO method is a two-site sandwich assay based upon solid phase Radial Partition Immunoassay (RPIA) technology. Dendrimer linked monoclonal antibody is added to the center portion of a square piece of glass fiber paper in the MYO TestPak. This antibody recognizes a distinct antigenic site on the myoglobin molecule. Sample is then added onto the paper where it reacts with the immobilized anti-myoglobin antibody. After a short incubation, a conjugate consisting of enzyme labeled monoclonal antibody directed against a second distinct antigenic site on the myoglobin molecule is pipetted onto the reaction zone of the paper. During the second incubation period, enzyme-labeled antibody reacts with the bound myoglobin, forming an antibody-antigen-labeled antibody sandwich. The unbound labeled antibody is later eluted from the field of view of the Stratus® CS analyzer by applying a substrate wash solution to the center of the reaction zone. By including substrate for the enzyme within the wash solution, initiation of enzyme activity occurs simultaneously with the wash. The enzymatic rate of the bound fraction increases directly with the concentration of myoglobin in the sample. The reaction rate is measured by an optical system that monitors the reaction rate via front surface fluorescence. All data analysis functions are performed by the microprocessor within the analyzer.

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

### 1. Analytical performance:

a. Precision/Reproducibility:

Previously established for predicate devices

b. Linearity/assay reportable range:

Previously established for predicate devices

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

Previously established for predicate calibrators. The calibrators (Stratus® CS Acute Care™ CKMB CalPak, Stratus® CS Acute Care™ cTnI CalPak, and Stratus® CS Acute Care™ MYO CalPak) are identical to the predicate calibrators. Labeling changes reflect the name change in addition to minor

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format changes.

d. Detection limit:
Previously established for predicate devices

e. Analytical specificity:
Previously established for predicate devices

f. Assay cut-off:
Previously established for predicate devices

2. Comparison studies:
a. Method comparison with predicate device:
Previously established for predicate devices
b. Matrix comparison:
Previously established for predicate devices

3. Clinical studies:
a. Clinical Sensitivity:
Previously established for predicate devices
b. Clinical specificity:
Previously established for predicate devices
c. Other clinical supportive data (when a. and b. are not applicable):

**POC Studies**

Method comparison and precision analyses were performed at two external evaluation sites: York Hospital in York, Pennsylvania and Western Pennsylvania Hospital in Pittsburgh, Pennsylvania. At each of the two sites, three Stratus® CS analyzers were installed, one in each of these three different locations: clinical laboratory (LAB), Emergency Department (ED) and Cardiac Care (CCU). The data supports use of these products by trained health professionals in the clinical laboratory and point of care (POC) settings. The following table represents the comparison between the POC sites vs. the

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LAB site.

| | n | Slope | Intercept | r | Range of samples |
| --- | --- | --- | --- | --- | --- |
| CKMB | 147 | 0.95 | 0.56 | 0.990 | 0.3–123.9 ng/mL |
| cTnI | 149 | 0.99 | -0.04 | 0.990 | 0.0-43.3 ng/mL |
| MYO | 146 | 1.01 | 4.0 | 0.987 | 15-829 ng/mL |

The following table represents the $\%$ CV for total imprecision for the POC sites vs. the LAB site for CKMB. Specimens at each level were analyzed in quadruplicate for 5 runs.

| | LAB % CV | CCU | ED |
| --- | --- | --- | --- |
| Control Level 1 | 3.4 | 6.0 | 3.5 |
| Control Level 2 | 4.1 | 4.8 | 3.5 |

The following table represents the $\%$ CV for total imprecision for the POC sites vs. the LAB site for cTnI. Specimens at each level were analyzed in quadruplicate for 5 runs.

| | LAB % CV | CCU | ED |
| --- | --- | --- | --- |
| Control Level 1 | 4.1 | 4.5 | 3.6 |
| Control Level 2 | 3.7 | 4.2 | 3.4 |

The following table represents the $\%$ CV for total imprecision for the POC sites vs. the LAB site for MYO. Specimens at each level were analyzed in quadruplicate for 5 runs.

| | LAB % CV | CCU | ED |
| --- | --- | --- | --- |
| Control Level 1 | 4.2 | 6.9 | 5.6 |
| Control Level 2 | 4.6 | 5.2 | 4.8 |

# 4. Clinical cut-off:

Previously established for predicate devices

# 5. Expected values/Reference range:

Previously established for predicate devices

# 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.