ELECSYS CK-MB STAT IMMUNOASSAY, ELECSYS CK-MB IMMUNOASSAY

• K Number: K132571
• Device Name: ELECSYS CK-MB STAT IMMUNOASSAY, ELECSYS CK-MB IMMUNOASSAY
• Manufacturer: Roche Diagnostics
• Date Cleared: 2013-10-18 ( 64 days)
• Product Code: JHY
• Regulation Number: 862.1215

Intended Use

Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma. Measurements of the MB isoenzyme of creatinine kinase are used as an aid in the diagnosis of myocardial infarction. The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers.

Device Description

The CK-MB STAT Assay and the CK-MB Assay are two-step sandwich immunoassays with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve (5-point-calibration) provided with the reagent bar code. The CK-MB STAT application is identical to the CK-MB assay, with the only difference being the length of incubation (9 minutes vs. 18 minutes).

Predicate Devices

K022654

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The summary describes a standard immunoassay technology and does not mention any AI or ML components in the device description, performance studies, or key metrics. The "Mentions AI, DNN, or ML" section is explicitly marked as "Not Found".

Therapeutic

No.

This device is an in vitro diagnostic (IVD) immunoassay that quantitatively determines the MB isoenzyme of creatine kinase. It is used as an aid in diagnosing myocardial infarction by providing measurement results, not by directly treating or mitigating a disease or condition.

Diagnostic

Yes.

The "Intended Use / Indications for Use" section explicitly states that "Measurements of the MB isoenzyme of creatinine kinase are used as an aid in the diagnosis of myocardial infarction." This is a clear diagnostic claim.

SaMD (Software as a Medical Device)

No

The device is an immunoassay reagent kit intended for use on specific immunoassay analyzers, which are hardware devices. The description details the chemical and physical components of the assay, not just software.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

Here's why:

• Intended Use: The "Intended Use / Indications for Use" section explicitly states "Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma." The phrase "in vitro" is a key indicator of an IVD.
• Sample Type: The assay is performed on human serum and plasma, which are biological samples taken from the body but tested outside of it.
• Purpose: The measurement is used as an aid in the diagnosis of myocardial infarction, which is a medical condition. IVDs are used to provide information for the diagnosis, monitoring, or treatment of diseases or conditions.
• Device Description: The description details an immunoassay process using reagents and an analyzer, which is typical of IVD devices used in clinical laboratories.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

Immunoassay for the in vitro quantitative determination of the MB isoenzyme of creatine kinase in human serum and plasma. Measurements of the MB isoenzyme of creatinine kinase are used as an aid in the diagnosis of myocardial infarction.

The electrochemiluminescence immunoassay "ECLIA" is intended for use on the indicated Elecsys and cobas e immunoassay analyzers.

Product codes (comma separated list FDA assigned to the subject device)

JHY

Device Description

The CK-MB STAT Assay and the CK-MB Assay are two-step sandwich immunoassays with streptavidin microparticles and electrochemiluminescence detection. Results are determined using a calibration curve that is generated specifically on each instrument by a 2-point calibration and a master curve (5-point-calibration) provided with the reagent bar code. The CK-MB STAT application is identical to the CK-MB assay, with the only difference being the length of incubation (9 minutes vs. 18 minutes).

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

For prescription use only

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Method Comparison performed on Serum Samples
n = 165
Min = 1.08 ng/ml
Max = 283 ng/ml
Passing/Bablok
Slope: 1.053
Intercept: -0.525
Tau/r: 0.982
Linear Regression
Slope: 1.067
Intercept: -0.740
Tau/r: 0.999

Clinical Study/ Reference Range Study
N: Women 760, Men 628
Median: 0.97 (Women), 1.35 (Men)
97.5th percentile (ng/mL): 2.88 (Women), 4.94 (Men)
99th percentile (ng/mL): 3.77 (Women), 6.73 (Men)
All Subjects (99th percentile): 5.34
Subjects with no Self-reported risk factors (99th percentile): 10.36
Gender: Female 523 (99th percentile: 4.30), Male 568 (99th percentile: 7.70)
Subjects represented "apparently heart healthy" population with exclusion of subjects with known poor cardiac health

Matrix Comparison (Serum vs. various plasma types):
Na-heparin: P/B: y = 0.994x + (-0.0100), r = 0.9997
Li-heparin: P/B: y = 0.9960x + (0.0045), r = 0.9996
K₂-EDTA: P/B: y = 1.020x + (-0.0082), r = 0.9999
K₃-EDTA: P/B: y = 0.988x + (-0.0115), r = 0.9998
All data passed criteria: Slope: 0.9-1.1; Coefficient of correlation: Pearson r > 0.95; Intercept: ≤± 0.15; For single sample pairs: 100% ±20% based on reference.

Method Comparison completed using Serum Samples (4th Generation STAT vs. 4th Generation 18-minute):
n = 115
Min = 1.44 ng/ml
Max = 283 ng/ml
Passing/Bablok
Slope: 1.003
Intercept: -0.005
Tau/r: 0.985
Linear Regression
Slope: 1.006
Intercept: 0.071
Tau/r: 0.999

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Measuring Range (4th Generation CK-MB STAT Assay): 1-300 ng/mL
Measuring Range (4th Generation CK-MB 18-minute assay): same

Precision (4th Generation CK-MB STAT Assay, cobas e 411):
Within-run (Repeatability): 1.2% CV @ 5.46 ng/mL, 1.3% CV @ 29.5 ng/mL, 1.3% CV @ 93.5 ng/mL, 1.5% CV @ 301 ng/mL, 0.06 SDPC1@ 4.44 ng/mL, 1.4% CVPC2 @ 57.9 ng/mL
Total (Intermediate): 2.5% CV @ 5.46 ng/mL, 4.2% CV @ 29.5 ng/mL, 4.1% CV @ 93.5 ng/mL, 3.3% CV @ 301 ng/mL, 0.12 SDPC1@ 4.44 ng/mL, 3.0% CVPC2 @ 57.9 ng/mL

Precision (4th Generation CK-MB 18-minute assay, cobas e 411):
Within-run (Repeatability): 1.3% CV @ 5.27 ng/mL, 1.4% CV @ 28.4 ng/mL, 1.2% CV @ 91.2 ng/mL, 1.3% CV @ 297 ng/mL, 0.06 SDPC1 @ 4.25 ng/mL, 1.2% CVPC2 @ 54.7 ng/mL
Total (Intermediate): 2.0% CV @ 5.27 ng/mL, 2.4% CV @ 28.4 ng/mL, 2.6% CV @ 91.2 ng/mL, 2.0% CV @ 297 ng/mL, 0.10 SDPC1 @ 4.25 ng/mL, 2.3% CVPC2 @ 54.7 ng/mL

Analytical Sensitivity (4th Generation CK-MB STAT Assay):
Limit of Blank (LoB): ≤ 0.1 ng/ml
Limit of Detection (LoD): ≤ 0.3 ng/ml
Limit of Quantitation (LoQ): ≤ 1 ng/ml

Analytical Sensitivity (4th Generation CK-MB 18-minute assay): Same as above.

Analytical Specificity:
Analyte: CK-MM, Reactivity: None (for both assays)
Analyte: CK-BB, Reactivity: 0.10% (for both assays)

Hook Effect: There is no high-dose hook effect at CK-MB concentrations up to 5000 ng/mL (for both assays).

Limitations/Interferences (4th Generation CK-MB STAT Assay):
The assay is unaffected by:
Hemoglobin ≤1000 mg/dL.
Bilirubin ≤ 34 mg/dL
Intralipid ≤ 1.500 mg/dL
Biotin ≤ 30 ng/mL
Rheumatoid factors ≤ 1,500 IU/mL
IgG ≤ 7 g/dl
IgM ≤ 1 g/dl
IgA ≤ 1.6 g/dl
Serum Albumin ≤ 20 g/dl
In vitro tests were performed on 51 commonly used pharmaceuticals. No interference with the assay was found.
In rare cases, interference due to extremely high titers of antibodies to analyte-specific antibodies, streptavidin or ruthenium can occur. These effects are minimized by suitable test design.
For diagnostic purposes, the results should always be assessed in conjunction with the patient`s medical history, clinical examination and other findings.

Limitations/Interferences (4th Generation CK-MB 18-minute assay): Same as above.

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K022654

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 862.1215 Creatine phosphokinase/creatine kinase or isoenzymes test system.

(a)
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.(b)
Classification. Class II.

Summary

0

K B257/

510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays

Date prepared:	October 17, 2013
Purpose of submission	Roche Diagnostics hereby submits this 510(k) to provide FDA with notification of intent to market a new device named Elecsys CK-MB Gen.4 reagent. All data in this submission was generated using the CK-MB STAT assay on the cobas e 411 analyzer as indicated. Method comparison data is included for the CK-MB STAT and CK-MB (18-minute) assay, as well as CK-MB STAT and Predicate device.

This candidate device is a new reagent that was developed by Roche Diagnostics. The previous generation of reagent, CK-MB STAT, was cleared in 510(k) K022654 and serves as the predicate device. The candidate and predicate devices use the same calibrator and controls. Only the reagents differ. This submission presents data to support clearance of this new reagent.

Measurand	CK-MB
Type of test	Quantitative colorimetric method; Cpk or Isoenzymes
Applicant	Kelli Turner
Roche Diagnostics
9115 Hague Road
Indianapolis, IN 46250
Telephone: [phone]
Fax: [phone]
Email: [e-mail]

OCT 1 8 2013

| Candidate device names | Proprietary name:
(1) Elecsys CK-MB STAT Immunoassay
(2) Elecsys CK-MB Immunoassay
Common name:
(1) CK-MB STAT Immunoassay
(2) CK-MB Immunoassay |

------------------------	-----------------------------------------------------------------------------------------------------------------------------------------------------------------

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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued

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Regulatory information

Product Code	Classification	Regulation	Panel
JHY	Class II	21 CFR 862.1215
(Creatine
phosphokinase/creatine
kinase or isoenzymes test
system)	Clinical
Chemistry

Continued on next page

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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------

Intended use	CK-MB STAT Reagent and CK-MB Reagent have the same intended uses:
	Immunoassay for the in vitro quantitative determination of the MB isoenzyme
of creatine kinase in human serum and plasma. Measurements of the MB
isoenzyme of creatinine kinase are used as an aid in the diagnosis of
myocardial infarction.
	The electrochemiluminescence immunoassay "ECLIA" is intended for use on
the indicated Elecsys and cobas e immunoassay analyzers.
Indications for
use	Immunoassay for the in vitro quantitative determination of the MB isoenzyme
of creatine kinase in human serum and plasma. Measurements of the MB
isoenzyme of creatinine kinase are used as an aid in the diagnosis of
myocardial infarction.
	The electrochemiluminescence immunoassay "ECLIA" is intended for use on
the indicated Elecsys and cobas e immunoassay analyzers.
Special
conditions for
use	For prescription use only
Special
instrument
requirements	The electrochemiluminescence immunoassay "ECLIA" is intended for use on
the indicated Elecsys and cobas e immunoassay analyzers.
Candidate
device
description	The CK-MB STAT Assay and the CK-MB Assay are two-step sandwich
immunoassays with streptavidin microparticles and
electrochemiluminescence detection. Results are determined using a
calibration curve that is generated specifically on each instrument by a 2-
point calibration and a master curve (5-point-calibration) provided with the
reagent bar code.
	The CK-MB STAT application is identical to the CK-MB assay, with the
only difference being the length of incubation (9 minutes vs. 18 minutes).
	Continued on next page

:

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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued

and the control control control control control controllers and consideration of the consideration of the consideration of the consideration of the consideration of the consi

Predicate Roche Diagnostics claims substantial equivalence to CK-MB, 3rd generation, device immunoassay, cleared in K022654.

。

Page 4 of 21

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510(k) Summary for Elecsys CK-MB STAT and Elecsys CK-MB Immunoassays, Continued

| Substantial

equivalence -	There are two tables in this summary:
similarities	The first table compares the CK-MB STAT generation 4 immunoassay
(Master Assay) with the predicate device.
	The second table exhibits the comparison between CK-MB STAT generation
4 immunoassay to the CK-MB 18-minute generation 4 immunoassay.
	Continued on next page

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Comparison of Assays, Similarities and Differences

Table 1 CK-MB STAT 3td Generation vs. CK-MB STAT 4th Generation

Assay Comparison
Feature	Predicate Device: Elecsys 3rd
Generation CK-MB STAT Assay
(K022654)	4th Generation CK-MB STAT Assay
(modified)
General Assay Features
Intended
Use/
Indications
for Use	Immunoassay for the in vitro
quantitative determination of MB
isoenzyme of creatine kinase in human
serum and plasma. Measurements of
the MB isoenzyme of creatine kinase
are used as an aid in the diagnosis of
myocardial infarction.	Same
Assay
Protocol	Two-step Sandwich assay using
biotinylated and ruthenium labeled
antibodies and streptavidin
microparticles	Same
Detection
Protocol	Electrochemiluminescent
Immunoassay	Same
Applications	STAT application (noted as CK-MB
STAT in the labeling) and 18-minute
application (noted as CK-MB in the
labeling).	STAT application (noted as CK-MB
STAT in the labeling)

6

Comparison of Assays-Similarities and Differences, continued

Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4th Generation, continued

Assay Comparison
Feature	Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654)	4th Generation CK-MB STAT Assay (modified)
General Assay Features
Instrument Platform	Roche Elecsys 2010	Roche cobas e 411
Sample Volume	15 µL	Same
Sample Type	Human serum and plasma treated with K3-EDTA, lithium heparin, sodium heparin and Na-citrate plasma.	Human serum and plasma treated with K2-EDTA, K3-EDTA, lithium heparin and sodium heparin plasma.
Reagents	Sandwich principle. Total duration of assay: 9 minutes.
• 1st incubation: 15 µL of sample, a biotinylated monoclonal anti-CK-MB antibody, and a monoclonal CK-MB-specific antibody labeled with a ruthenium complex react to form a sandwich complex.
• 2nd incubation: After addition of streptavidin-coated microparticles, the complex becomes bound to the solid phase via interaction of biotin and streptavidin.	Same
Calibrator	CK-MB STAT CalSet (CK-MB Calset for 18-minute assay)	Same

7

Assay Comparison
Feature	Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654)	4th Generation CK-MB STAT Assay (modified)
	General Assay Features
Calibration Interval	Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows:
Elecsys 2010 analyzers:
After 1 month (28 days) when using the same reagent lot. After 7 days (when using the same reagent kit on the analyzer). As required: e.g. quality control findings outside the specified limits	Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows:
cobas e 411 analyzers:
After 1 month (28 days) when using the same reagent lot. After 7 days (when using the same reagent kit on the analyzer). As required: e.g. quality control findings outside the specified limits
Controls	Elecsys PreciControl Cardiac II	Same

Comparison of Assays-Similarities and Differences, continued

Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4" Generation, continued

8

Feature	Assay Comparison
	Predicate Device: Elecsys 3rd Generation CK-MB STAT Assay (K022654)	4th Generation CK-MB STAT Assay (modified)
General assay features
Traceability /
Standardization	The linearity of the CK-MB STAT assay was improved by using human recombinant CK-MB from Seradyn. The test was standardized against the previous Elecsys CK-MB STAT assay in the range of 0-20.0 ng/mL; this leads to up to a 30% reduction of the test results in the range of 20-500 ng/mL.	The CK-MB STAT assay is traceable to the Abbott IMx CK-MB assay and linearized using human recombinant CK-MB from Seradyn.
Reagent Stability	Unopened:
2-8°C - Up to the stated expiration date
Opened 2-8°C - 12 weeks
On Analyzers – 8 weeks	Unopened:
2-8°C - Up to the stated expiration date
Opened 2-8°C - 12 weeks
On Analyzers – 6 weeks

Comparison of Assays-Similarities and Differences, continued

Table 1 CK-MB STAT 3rd Generation vs. CK-MB STAT 4th Generation, continued

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Table 1 CK-MB STAT 3" Generation vs. CK-MB STAT 4" Generation, continued
Assay Comparison
	Predicate Device: Elecsys 3rd	40 Generation CK-MB STAT
Feature	Generation CK-MB STAT Assay	Assay (modified)
	(K022654)
21 8 8 7 1 2 3
Labeled Performance Characteristics -----
Measuring	0.1-500 ng/mL	1-300 ng/mL
Range
Precision	Elecsys 2010:	cobas e 411:
Within-run (will be labeled Repeatability)
5.77 ng/mL
1.5% CV @
12.4 ng/ml.
2.1% CV (a),
39.7 ng/mlL
1.8% CV (a),
1.9% CVKI @
5.86 ng/mL
1.9% CVPC2 @
53.1 ng/mL
Total (will be labeled Intermediate)
2.3% CV (a),
5.77 ng/mL
12.4 ng/mL
2.6% CV (1)
2.3% CV (a)
39.7 ng/mL		Within-run (will be labeled Repeatability)
1.2% CV @
5.46 ng/ml
29.5 ng/ml
1.3% CV @
93.5 ng/mL
1.3% CV (a),
301 ng/mL
1.5% CV @
0.06 SDPC1 @
4.44 ng/ml
1.4% CVPC2
57.9 ng/mL
Total (will be labeled Intermediate)
2.5% CV (1),
5.46 ng/mL
29.5 ng/mL
4.2% CV (a)
93.5 ng/mL
4.1% CV (0),
	2.4% CVPCI @
5.86 ng/ml_
2.7% CVPC2 (a),
53.1 ng/mL	3.3% CV (0)
301 ng/mL
0.12 SD"Cl @
4.44 ng/ml
3.0% CVPC2
57.9 חייוון 57.9
Precision testing was completed over 21
days, according to CLSI EP5-A2, utilizing
human serum samples and PreciControl
Cardiac II.
Analytical
Sensitivity	Lower Detection Limit : 0.95 .

• Intercept: ≤± 0.15 ●
• For single sample pairs: 100% ±20% based on reference .

| Anticoagulant | Sample Concentration
Range Tested (ng/mL) | Claimed Measuring Range
(ng/mL) |
|---------------|----------------------------------------------|------------------------------------|
| Na-heparin | 1.46-297.83 | 1.00 – 300 ng/mL |
| Li-heparin | 1.39-244.83 | |
| K2-EDTA | 1.58-299.65 | |
| K3-EDTA | 1.56-291.89 | |

In addition, method comparisons with plasma vs. serum were calculated with the following results:

Serum vs. Na-heparin Plasma :	P/B: y = 0.994x + (-0.0100), r = 0.9997
Serum vs. Li-heparin Plasma:	P/B: y = 0.9960x + (0.0045), r = 0.9996
Serum vs. K₂-EDTA Plasma:	P/B: y = 1.020x + (-0.0082), r = 0.9999
Serum vs. K₃-EDTA Plasma:	P/B: y = 0.988x + (-0.0115), r = 0.9998

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Table 2 4th Generation STAT vs. 4th Generation 18-Minute
Assay Comparison
Feature	4th Generation CK-MB STAT Assay	4th Generation CK-MB 18-Minute
assay
(modified)
	General Assay Features
Intended
Use/
Indications
for Use	Immunoassay for the in vitro
quantitative determination of MB
isoenzyme of creatine kinase in human
serum and plasma. Measurements of
the MB isoenzyme of creatine kinase
are used as an aid in the diagnosis of
myocardial infarction.	Same
Assay
Protocol	Two step Sandwich assay using
biotinylated and ruthenium labeled
antibodies and streptavidin
microparticles	Same
Detection
Protocol	Electrochemiluminescent
Immunoassay	Same
Applications	STAT application (noted as CK-MB
STAT in the labeling)	18-minute application (noted as CK-
MB in the labeling).

Table 2 4th Generation STAT vs. 4th Generation 18-Minute

14

| Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

Assay Comparison
Feature	4th Generation CK-MB STAT Assay	4th Generation CK-MB 18-minute assay
(modified)
	General Assay Features
Instrument
Platform	Roche cobas e 411	Same
Sample
Volume	15 µL	Same
Sample
Type	Human serum and plasma treated with
K2-EDTA, K3-EDTA, lithium heparin
and sodium heparin plasma.	Same.
Reagents	Sandwich principle. Total duration of
assay: 9 minutes.
• 1st incubation: 15 µL of sample, a
biotinylated monoclonal anti-CK-MB
antibody, and a monoclonal CK-MB-
specific antibody labeled with a
ruthenium complex react to form a
sandwich complex.
• 2nd incubation: After addition of
streptavidin-coated microparticles,
the complex becomes bound to the
solid phase via interaction
of biotin and streptavidin	Sandwich principle. Total duration of
assay: 18 minutes.
• 1st incubation: 15 µL of sample, a
biotinylated monoclonal anti-CK-MB
antibody, and a monoclonal CK-MB-
specific antibody labeled with a
ruthenium complex react to form a
sandwich complex.
• 2nd incubation: After addition of
streptavidin-coated microparticles,
the complex becomes bound to the
solid phase via interaction
of biotin and streptavidin
Calibrator	CK-MB STAT CalSet	CK-MB CalSet

Comparison of Assays—Similarities and Differences, continued

Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

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Comparison of Assays-Similarities and Differences, continued

Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

Feature	4th Generation CK-MB STAT Assay	4th Generation CK-MB 18-minute assay (modified)
General Assay Features
Calibration Interval	Calibration must be performed once per reagent lot using fresh reagent (i.e. not more than 24 hours since the reagent kit was registered on the analyzer). Renewed calibration is recommended as follows:
cobas e 411 analyzers:
• After 1 month (28 days) when using the same reagent lot.
• After 7 days (when using the same reagent kit on the analyzer).
• As required: e.g. quality control findings outside the specified limits	Same
Controls	Elecsys PreciControl Cardiac II	Same

16

Comparison of Assays-Similarities and Differences, continued

Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

| Feature | Assay Comparison | 4th Generation CK-MB STAT Assay | 4th Generation CK-MB 18-Minute
Assay
(modified) |
|-----------------------------------|-------------------------------------------------------------------------------------------------------------------------------------|---------------------------------|-------------------------------------------------------|
| General assay features | | | |
| Traceability /
Standardization | The CK-MB STAT assay is traceable
to the Abbott IMx CK-MB assay and
linearized using human recombinant
CK-MB from Seradyn. | Same | |
| Reagent Stability | Unopened:
2-8°C - Up to the stated expiration
date
Opened 2-8°C - 12 weeks
On Analyzers – 6 weeks | Same | |

17

| Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

Assay Comparison
Feature	4th Generation CK-MB STAT Assay	4th Generation CK-MB 18-minute assay (modified)
Labeled Performance Characteristics
Measuring Range	1-300 ng/mL	same
Precision according to CLSI EP5-A2	cobas e 411:
Within-run (will be labeled Repeatability)
1.2% CV @ 5.46 ng/mL
1.3% CV @ 29.5 ng/mL
1.3% CV @ 93.5 ng/mL
1.5% CV @ 301 ng/mL
0.06 SDPC1@ 4.44 ng/mL
1.4% CVPC2 @ 57.9 ng/mL

Total (will be labeled Intermediate)
2.5% CV @ 5.46 ng/mL
4.2% CV @ 29.5 ng/mL
4.1% CV @ 93.5 ng/mL
3.3% CV @ 301 ng/mL
0.12 SDPC1@ 4.44 ng/mL
3.0% CVPC2 @ 57.9 ng/mL

Precision testing was completed over 21 days, according to CLSI EP5-A2, utilizing human serum samples and PreciControl Cardiac II. | cobas e 411:
Within-run (will be labeled Repeatability)
1.3% CV @ 5.27 ng/mL
1.4% CV @ 28.4 ng/mL
1.2% CV @ 91.2 ng/mL
1.3% CV @ 297 ng/mL
0.06 SDPC1 @ 4.25 ng/mL
1.2% CVPC2 @ 54.7 ng/mL

Total (will be labeled Intermediate)
2.0% CV @ 5.27 ng/mL
2.4% CV @ 28.4 ng/mL
2.6% CV @ 91.2 ng/mL
2.0% CV @ 297 ng/mL
0.10 SDPC1 @ 4.25 ng/mL
2.3% CVPC2 @ 54.7 ng/mL

Precision testing was completed over 21 days, according to CLSI EP5-A2, utilizing human serum samples and PreciControl Cardiac II. |
| Analytical Sensitivity1 according to CLSI EP17-A | Limit of Blank (LoB): = 0.1 ng/ml
Limit of Detection (LoD): = 0.3 ng/ml
Limit of Quantitation (LoQ): = 1 ng/ml | Same |

Comparison of Assays-Similarities and Differences, continued

Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued

PC1=PreciControl Cardiac 1

PC2=PreciControl Cardiac 2

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Table 2 4th Generation STAT vs. 4th Generation 18-Minute, continued Assay Comparison . 4th Generation CK-MB 18-minute Feature . . 4th Generation CK-MB STAT Assay assav · (modificd) Labeled Performance Characteristics Analytical Analyte Reactivity Same CK-MM Specificity none CK-BB 0.10% There is no high-dose hook effect at Hook Effect Same CK-MB concentrations up to 5000 ng/ml_ The assay is unaffected by: Limitations Same. Hemoglobin ≤1000 mg/dL. . . Bilirubin The Limit of Blank is the 95th percentile value from n ≥ 60 measurements of analyte-free samples over several independent series. The Limit of Blank corresponds to the concentration below which analyte-free samples are found with a probability of 95 %.

The Limit of Detection is determined based on the Limit of Blank and the standard deviation of low concentration samples. The Limit of Detection corresponds to the lowest analyte concentration which can be detected (value above the Limit of Blank with a probability of 95 %).

The Limit of Quantitation is defined as the lowest amount of analyte in a sample that can be accurately quantitated with a total allowable error of