(175 days)
No
The device description and performance studies focus on a quantitative chemical assay and its calibration, with no mention of AI or ML algorithms for data analysis or interpretation.
No
This device is an in vitro diagnostic assay used for the quantitative determination of creatine kinase activity, which aids in diagnosis and treatment, rather than directly providing therapy.
Yes
The "Intended Use / Indications for Use" section explicitly states that the ADVIA Chemistry® Creatine Kinase (CK_L) assay "is for in vitro diagnostic use" and "can be used to aid in the diagnosis and treatment of myocardial infarction and muscle diseases." This clearly indicates its role in diagnosis.
No
The device description clearly states it is a "ready-to-use liquid reagent" and a "liquid frozen human serum albumin based product," indicating it is a chemical assay and calibrator, not a software-only device.
Yes, both the ADVIA Chemistry® Creatine Kinase (CK_L) Assay and the ADVIA Chemistry® Enzyme 3 Calibrator are IVDs (In Vitro Diagnostics).
Here's why:
- Intended Use / Indications for Use: Both descriptions explicitly state "for in vitro diagnostic use". The CK_L assay is used to quantitatively determine creatine kinase activity in human samples (plasma or serum) to aid in the diagnosis and treatment of specific medical conditions (myocardial infarction and muscle diseases). The Enzyme 3 Calibrator is used to calibrate the CK_L assay, which is a necessary step for accurate diagnostic results.
- Device Description: Both devices are described as reagents or products used in a laboratory setting to perform tests on biological samples. The CK_L assay is a liquid reagent that reacts with components in the sample, and the Enzyme 3 Calibrator is a human serum albumin-based product used to standardize the assay.
- Performance Studies: The document includes performance studies (Method Comparison, Precision, Linearity, Detection Capability, Interference Testing, Matrix Comparison) which are typical for demonstrating the analytical performance of an IVD.
- Predicate Device(s): The mention of predicate devices (K991576 and K083579) further indicates that these devices are being compared to previously cleared IVDs.
Therefore, based on the provided information, both the ADVIA Chemistry® Creatine Kinase (CK_L) Assay and the ADVIA Chemistry® Enzyme 3 Calibrator clearly fall under the definition of In Vitro Diagnostic devices.
N/A
Intended Use / Indications for Use
ADVIA Chemistry® Creatine Kinase (CK_L) assay: The ADVIA Chemistry® Creatine Kinase (CK L) assay is for in vitro diagnostic use in the quantitative determination of creatine kinase activity in human plasma (lithium heparin) or serum on ADVIA Chemistry systems. The assay can be used to aid in the diagnosis and treatment of myocardial infarction and muscle diseases, such as Duchenne progressive muscular dystrophy.
ADVIA Chemistry® Enzyme 3 Calibrator: ADVIA Chemistry® Enzyme 3 Calibrator is intended for in vitro diagnostic use in the calibration of the ADVIA Chemistry Creatine Kinase (CK L) assay on the ADVIA Chemistry systems.
Product codes (comma separated list FDA assigned to the subject device)
CGS, JIT
Device Description
ADVIA Chemistry Creatine Kinase Assay: ADVIA Chemistry Creatine Kinase (CK L) assay is a ready-to-use liquid reagent packaged for use on the automated ADVIA Chemistry systems. Creatine Kinase reacts with creatine phosphate and ADP to form adenosine triphosphate (ATP), which is coupled to the hexokinase-G6PD reaction, generating NADPH. The concentration of NADPH is measured by the increase in absorbance at 340/596 nm.
ADVIA Chemistry ENZ 3 CAL: ENZ 3 CAL is a liquid frozen human serum albumin based product containing creatine kinase MM from human heart. Enzyme 3 Calibrator kit consists of six vials of the same calibrator which is ready for use (no preparation is required).
Mentions image processing
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Mentions AI, DNN, or ML
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Indicated Patient Age Range
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison: A split sample method comparison between the ADVIA Chemistry CK_L assay versus the predicate ADVIA Chemistry CKNAC (K991576) assay was performed with 116 native de-identified human serum samples across the assay range (15 to 1300 U/L) on the ADVIA Chemistry 1800 system. Analysis of the results using Deming (Orthogonal) regression yielded a slope of 1.01 (95% CI: 1.00 to 1.02), intercept of -1.8 U/L (95% CI: -3.3 to -0.3), and a correlation coefficient (R) of 1.00.
Precision: Testing was performed over twenty (20) days, two (2) runs per day, a single test from two (2) independent cups were analyzed for each test material using the ADVIA Chemistry CK L assay on the ADVIA Chemistry 1800 System. Analysis of variance (ANOVA) was used to evaluate the data. Repeatability and within-lab results for various QC materials and plasma/serum pools are summarized with mean, SD, and %CV values. For example, for BIORAD QC 1 (Mean 75 U/L), repeatability SD was 1.3 and %CV was 1.7, while within-lab SD was 1.9 and %CV was 2.6.
Linearity: Linearity across the assay range was confirmed according to CLSI EP06-A, by testing a sample with a high concentration of creatine kinase on the ADVIA Chemistry CK_L assay and diluting it with low serum sample. Data were analyzed using weighted linear regression analysis. A 200 - and 36 -order polynomial regressions of the mean observed analyte values vs. expected concentrations were generated. These data support the measuring range of 15 to 1300 U/L. The linear regression equation was Y=1.00X+0.5 with a regression constant of 0.5 and R of 1.00. % Bias from the Predicted ranged from -6% to 8%.
Detection Capability: The LoB for the ADVIA Chemistry CK_L assay is 3 U/L. The LoD for the ADVIA Chemistry CK L assay is 6 U/L. The LoQ for the ADVIA Chemistry CK_L assay is 15 U/L. These values were determined with proportions of false positives (α) less than 5% and false negatives (β) less than 5%, based on 450 determinations with 225 blank and 225 low-level sample replicates.
Interference Testing: Interference testing was performed according to CLSI/NCCLS EP07-A2 to determine the effect of various endogenous and exogenous substances on the ADVIA Chemistry CK_L assay. The percent bias was determined by testing a control sample without the interferent and comparing it to the value obtained from a test sample to which the potential interferent had been added. Interferents were tested at two levels of creatine kinase. % Difference was generally low for tested interferents (Hemolysate, Bilirubin Conjugated, Bilirubin Unconjugated, Lipemia, Ascorbid Acid, Sulfasalazine, Sulfapyridine).
Method Comparison versus IFCC Reference Method: A split sample method comparison between the ADVIA Chemistry CK_L assay on the ADVIA Chemistry 1800 system versus the IFCC certified reference method on the Konelab 30i analyzer (Thermo Fisher Scientific) was performed with 100 native de-identified human serum samples across the assay range (15 to 1300 U/L). Analysis of the results yielded a slope of 1.05 (95% CI: 1.03 to 1.07), intercept of -6.9 U/L (95% CI: -8.8 to -4.9), and a correlation coefficient (R) of 1.00.
Matrix Comparison: The performance of the ADVIA Chemistry CK L assay was compared for serum and lithium heparin plasma samples using 55 matched samples. The study resulted in a slope of 1.01, intercept of -0.6 U/L, and a correlation coefficient (R) of 1.00, confirming equivalency of sample types.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Linearity: % Bias from the Predicted ranged from -6% to 8%.
Detection Capability: LoB = 3 U/L, LoD = 6 U/L, LoQ = 15 U/L.
Interference Testing: % Difference for interferents was generally low (e.g., Hemolysate 1-7%, Bilirubin 1-2%, Lipemia 0-5%, Ascorbic Acid 1-4%, Sulfasalazine 0-2%, Sulfapyridine 1-2%).
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.
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.
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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).
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§ 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.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
SIEMENS HEALTHCARE DIAGNOSTICS, INC. KATHLEEN DRAY-LYONS REGULATORY AND CLINICAL AFFAIRS SPECIALIST 500 GBC DRIVE NEWARK DE 19714
September 7, 2016
Re: K160724
Trade/Device Name: ADVIA Chemistry® Creatine Kinase (CK L) Assay. ADVIA Chemistry® Enzyme 3 Calibrator Regulation Number: 21 CFR 862.1215 Regulation Name: Creatine phosphokinase/creatine kinase or isoenzymes test system Regulatory Class: II Product Code: CGS, JIT Dated: August 2, 2016 Received: August 3, 2016
Dear Kathleen Dray-Lyons:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
1
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely yours,
Katherine Serrano -S
For : Courtney H. Lias, Ph.D. Director Division of Chemistry and Toxicology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K160724
Device Name ADVIA Chemistry® Creatine Kinase (CK L) Assay ADVIA Chemistry® Enzyme 3 Calibrator
Indications for Use (Describe)
ADVIA Chemistry® Creatine Kinase (CK L) Assay:
The ADVIA Chemistry® Creatine Kinase (CK_L) assay is for in vitro diagnostic use in the quantitative determination of creatine kinase activity in human plasma (lithium heparin) or serum on ADVIA Chemistry systems. The assay can be used to aid in the diagnosis and treatment of myocardial infarction and muscle diseases, such as Duchenne progressive muscular dystrophy.
ADVIA Chemistry® Enzyme 3 Calibrator:
ADVIA Chemistry® Enzyme 3 Calibrator is intended for in vitro diagnostic use in the calibration of the ADVIA Chemistry Creatine Kinase (CK L) assay on the ADVIA Chemistry systems.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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3
510(k) Summary
This summary of 510(k) safety and effectiveness information is submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.
The assigned 510(k) number is: K160724
-
- Manufacturer's Name, Address, Telephone, and Contact Person, Date of Preparation
| Applicant: | |
|---|---|
| ------------ | -- |
Contact Information:
Siemens Healthcare Diagnostics Inc. 500 GBC Drive Newark, DE 19714
Siemens Healthcare Diagnostics Inc. P.O. Box 6101 Newark, DE 19714 Attn: Kathleen Dray-Lyons Tel: 781-826-4551 Email: kathleen.a.dray-lyons@siemens.com
Date of Preparation:
September 6, 2016
2. Device Names:
- ADVIA Chemistry® Creatine Kinase (CK_L) Assay
ADVIA Chemistry® Enzyme 3 Calibrator
Classification:
- 21 CFR §862.1215; Creatine phosphokinase/creatine kinase or O isoenzymes test system, Class II
- 21 CFR §862.1150; Calibrator Secondary, Class II O
Product Code:
- o CGS
- o JIT
Panel:
- o Clinical Chemistry
- Clinical Chemistry o
3. Identification of the Predicate Devices:
ADVIA Chemistry Creatine Kinase (CKNAC) Assay - K991576 Dimension Vista ENZ 6 CAL - K083579
4
4. Device Description:
ADVIA Chemistry Creatine Kinase Assay:
ADVIA Chemistry Creatine Kinase (CK L) assay is a ready-to-use liquid reagent packaged for use on the automated ADVIA Chemistry systems. Creatine Kinase reacts with creatine phosphate and ADP to form adenosine triphosphate (ATP), which is coupled to the hexokinase-G6PD reaction, generating NADPH. The concentration of NADPH is measured by the increase in absorbance at 340/596 nm.
ADVIA Chemistry ENZ 3 CAL:
ENZ 3 CAL is a liquid frozen human serum albumin based product containing creatine kinase MM from human heart. Enzyme 3 Calibrator kit consists of six vials of the same calibrator which is ready for use (no preparation is required).
5. Device Intended Use:
ADVIA Chemistry Creatine® Kinase (CK_L) Assay:
The ADVIA Chemistry® Creatine Kinase (CK L) assay is for in vitro diagnostic use in the quantitative determination of creatine kinase activity in human plasma (lithium heparin) or serum on ADVIA Chemistry systems. The assay can be used to aid in the diagnosis and treatment of myocardial infarction and muscle diseases, such as Duchenne progressive muscular dystrophy.
ADVIA Chemistry ENZ 3 CAL:
ADVIA Chemistry® Enzyme 3 Calibrator is intended for in vitro diagnostic use in the calibration of the ADVIA Chemistry Creatine Kinase (CK L) assay on the ADVIA Chemistry systems.
6. Medical device to which equivalence is claimed:
ADVIA Chemistry Creatine® Kinase (CK L) Assay:
The modified ADVIA Chemistry CK L assay is substantially equivalent in intended use and technology to the predicate ADVIA Chemistry Creatine Kinase (CKNAC) assay cleared under K991576. Both assays utilize creatine kinase, which reacts with creatine phosphate and ADP to form ATP that is coupled to the hexokinase-G6PD reaction, generating NADPH. The concentration of NADPH is measured by the increase in absorbance. A comparison of the similarities and differences between the currently marketed ADVIA Chemistry CKNAC (predicate) versus the proposed modified ADVIA Chemistry CK L assay is provided in the table below.
5
Similarities and Differences ADVIA Chemistry CK Assay (K991576) versus Modified ADVIA Chemistry CK_L Assay
| Feature | Predicate
ADVIA Chemistry CKNAC
K991576 | Proposed
ADVIA Chemistry CK_L
Modified Device |
|---------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use
Statement | For in vitro diagnostic use in the
quantitative determination of
creatine kinase activity in human
serum and plasma on the ADVIA
Chemistry systems. Such
measurements are used mainly
in the diagnosis and treatment of
myocardial infarction and muscle
diseases such as Duchenne
progressive muscular dystrophy. | The ADVIA Chemistry® Creatine
Kinase (CK_L) assay is for in
vitro diagnostic use in the
quantitative determination of
creatine kinase activity in human
plasma (lithium heparin) or
serum on ADVIA Chemistry
systems. The assay can be
used to aid in the diagnosis and
treatment of myocardial
infarction and muscle diseases,
such as Duchenne progressive
muscular dystrophy. |
| Principle | Creatine Kinase reacts with
creatine phosphate and ADP to
form ATP which is coupled to the
hexokinase-G6PD reaction,
generating NADPH. The
concentration of NADPH is
measured by the increase in
absorbance at 340/410 nm. | Creatine Kinase reacts with
creatine phosphate and ADP to
form ATP which is coupled to the
hexokinase-G6PD reaction,
generating NADPH. The
concentration of NADPH is
measured by the increase in
absorbance at 340/596 nm. |
| Kit Components | Reagent 1 - lyophilized
Reagent 1 mix - lyophilized | Reagent 1 - liquid
Reagent 2 - liquid |
| Calibrator | None - fixed calibrator value | ADVIA Enzyme 3 Calibrator |
| Sample Type | Serum and lithium heparin
plasma | Same |
| Analytical Range | 0 to 1300 U/L | 15 to 1300 U/L |
| Extended Range | 1300 to 7800 U/L | Same |
| Analyzers | ADVIA Chemistry 1650, 1200,
1800, 2400 and XPT Systems | ADVIA Chemistry 1800 System |
ADVIA Chemistry ENZ 3 CAL:
The ENZ 3 CAL is substantially equivalent in intended use to the predicate Dimension Vista ENZ 6 CAL (K083579). A comparison of the similarities and differences between the currently Dimension Vista ENZ 6 CAL versus the proposed ADVIA Chemistry ENZ 3 CAL is provided in the table below.
6
Similarities and Differences Dimension Vista ENZ 6 CAL (K083579) versus ADVIA Chemistry ENZ 3 CAL
| Feature | Predicate
Dimension Vista® ENZ 6 CAL | Proposed
ADVIA Chemistry® ENZ 3 CAL |
|-------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ENZ 6 CAL is an in vitro
diagnostic product for the calibration
of Creatine Kinase (CKI) and
Creatine Kinase MB (MBI) methods
on the Dimension Vista® System | ADVIA Chemistry® Enzyme 3
Calibrator is intended for in vitro
diagnostic use in the calibration of
ADVIA Chemistry Creatine Kinase
(CK_L) assay on the ADVIA
Chemistry® systems. |
| Traceable to: | IFCC Reference Method | Same |
| Composition | ENZ 6 CAL is a liquid frozen human
serum albumin based product
containing creatinine kinase BB from
porcine brain and creatine kinase
MM from human heart. | ADVIA Chemistry ENZ 3 CAL is a
liquid frozen human serum albumin
(5%) and preservatives with lot-
specific concentrations of creatine
kinase MM from human heart. |
| Packaging Content | 3 vials: Calibrator A, 2mL per vial | 6 vials of calibrator, 2mL per vial |
| Storage | -20 °C or below | -25 to -15°C |
7. Performance Characteristics
Method Comparison:
A split sample method comparison between the ADVIA Chemistry CK_L assay versus the predicate ADVIA Chemistry CKNAC (K991576) assay was performed with 116 native de-identified human serum samples across the assay range (15 to 1300 U/L) on the ADVIA Chemistry 1800 system. Analysis of the results using Deming (Orthogonal) regression yielded the following:
| Method | n | Predicate
Method
Sample
Range
U/L | Proposed
Method
Sample
Range
U/L | Slope
(95% CI) | Intercept
U/L
(95% CI) | Correlation
Coefficient
(R) |
|----------------------------------|-----|-----------------------------------------------|----------------------------------------------|---------------------------|------------------------------|-----------------------------------|
| ADVIA CKNAC
versus ADVIA CK_L | 116 | 23 to 1253 | 22 to 1280 | 1.01
(1.00 to
1.02) | -1.8
(-3.3 to -
0.3) | 1.00 |
Precision:
Testing was performed over twenty (20) days, two (2) runs per day, a single test from two (2) independent cups were analyzed for each test material using the ADVIA
7
Chemistry CK L assay on the ADVIA Chemistry 1800 System. Analysis of variance (ANOVA) was used to evaluate the data consistent with the recommendations of CLSI EP05-A2. Typical precision is summarized below.
| Repeatability | Within-Lab | ||||
|---|---|---|---|---|---|
| Product | Mean U/L | SD | %CV | SD | %CV |
| BIORAD QC 1 | 75 | 1.3 | 1.7 | 1.9 | 2.6 |
| BIORAD QC 2 | 232 | 1.5 | 0.6 | 3.1 | 1.4 |
| BIORAD QC 3 | 639 | 2.6 | 0.4 | 8.1 | 1.3 |
| PLASMA POOL 1 | 1202 | 4.7 | 0.4 | 6.3 | 0.5 |
| SERUM POOL 1 | 85 | 1.7 | 2.0 | 2.9 | 3.4 |
| SERUM POOL 2 | 194 | 3.0 | 1.5 | 3.2 | 1.7 |
| SERUM POOL 3 | 938 | 5.2 | 0.6 | 5.6 | 0.6 |
Repeatability and Within-Lab Results ADVIA CK_L on the ADVIA 1800
Linearity
Linearity across the assay range was confirmed according to CLSI EP06-A, Evaluation of the Linearity of Quantitative Measurement, by testing a sample with a high concentration of creatine kinase on the ADVIA Chemistry CK_L assay and diluting it with low serum sample. Data were analyzed using weighted linear regression analysis [x-axis: theoretical concentration versus y-axis: measured concentration]. A 200 - and 36 -order polynomial regressions of the mean observed analyte values vs. expected concentrations were generated. These data support the measuring range of 15 to 1300 U/L. A summary of the linearity data is presented below.
| Range of
Samples | | Linear
Regression
Equation | Regression
Constant | R | P-Value | | |
|---------------------|------|----------------------------------|------------------------|------|--------------|----------|----------|
| Low | High | | | | Quadratic X2 | Cubic X2 | Cubic X3 |
| 1 | 1372 | Y=1.00X+0.5 | 0.5 | 1.00 | 0.2346 | 0.1962 | 0.2610 |
| | Expected | Observed Results (U/L) | | | | | | Linear | % Bias from the
Predicted | |
|------------------|------------------|------------------------|----------|----------|----------------|-----|------|--------------------|------------------------------|---------------|
| Sample
Number | Results
(U/L) | Result 1 | Result 2 | Result 3 | Mean
Values | SD | CV | Predicted
(U/L) | % Bias | Bias
(U/L) |
| 1 | 1 | 0 | 1 | 1 | 1 | 0.6 | 86.6 | 1 | N/A | 0 |
| 2 | 172 | 177 | 175 | 180 | 177 | 2.5 | 1.4 | 172 | 3 | 6 |
| 3 | 344 | 346 | 347 | 343 | 345 | 2.1 | 0.6 | 343 | 1 | 2 |
| 4 | 516 | 513 | 516 | 518 | 516 | 2.5 | 0.5 | 514 | 0 | 1 |
| 5 | 687 | 686 | 689 | 682 | 686 | 3.5 | 0.5 | 685 | 0 | 1 |
| 6 | 859 | 861 | 865 | 867 | 864 | 3.1 | 0.4 | 856 | 1 | 8 |
| 7 | 1031 | 1025 | 1023 | 1014 | 1021 | 5.9 | 0.6 | 1027 | -1 | -6 |
8
| Sample
Number | Expected
Results
(U/L) | Observed Results (U/L) | | | Mean
Values | SD | CV | Linear
Predicted
(U/L) | % Bias from the
Predicted | |
|------------------|------------------------------|------------------------|----------|----------|----------------|-----|-----|------------------------------|------------------------------|---------------|
| | | Result 1 | Result 2 | Result 3 | | | | | % Bias | Bias
(U/L) |
| 8 | 1202 | 1195 | 1196 | 1197 | 1196 | 1.0 | 0.1 | 1197 | 0 | -1 |
| 9 | 1374 | 1371 | 1370 | 1375 | 1372 | 2.6 | 0.2 | 1369 | 0 | 3 |
Detection Capability
The LoB and LoD values are determined with proportions of false positives (α) less than 5% and false negatives (β) less than 5%, based on 450 determinations with 225 blank and 225 low-level sample replicates.
The LoB is the highest measurement result that is likely to be observed on a blank sample. The LoB for the ADVIA Chemistry CK_L assay is 3 U/L.
The LoD is the smallest amount that this assay can reliably detect to determine presence or absence of an analyte. The LoD for the ADVIA Chemistry CK L assay is 6 U/L.
The LoQ is the lowest amount of creatine kinase that can be determined quantitatively within a defined total error. The LoQ for the ADVIA Chemistry CK_L assay is 15 U/L.
Interference Testing
Interference testing was performed according to CLSI/NCCLS EP07-A2: Approved Guideline Interference Testing in Clinical Chemistry to determine the effect of various endogenous and exogenous substances on the ADVIA Chemistry CK_L assay. For all interferents, the percent bias was determined by testing a control sample without the interferent and comparing it to the value obtained from a test sample to which the potential interferent had been added. Interferents were tested at two levels of creatine kinase, 95 ± 14 U/L and 265 ± 40 U/L. For each spiked sample, the % recovery was determined. A summary of the non-interfering substance data is presented below.
| Interferent | Interferent Test
Concentration | CK Test Level
(U/L) | % Difference |
|---------------------------|-----------------------------------|------------------------|--------------|
| Hemolysate | 125 (mg/dL) | 100 | 7% |
| | 125 (mg/dL) | 284 | 1% |
| Bilirubin
Conjugated | 60 (mg/dL) | 93 | 1% |
| | 60 (mg/dL) | 256 | 2% |
| Bilirubin
Unconjugated | 60 (mg/dL) | 94 | 2% |
| | 60 (mg/dL) | 264 | 2% |
| Lipemia
(Intralipid) | 1000 (mg/dL) | 94 | 5% |
| | 1000 (mg/dL) | 276 | 0% |
| Ascorbid Acid | 6 (mg/dL) | 91 | 4% |
Interference Testing CK L on the ADVIA 1800
9
| Interferent | Interferent Test
Concentration | CK Test Level
(U/L) | % Difference |
|---------------|-----------------------------------|------------------------|--------------|
| | 6 (mg/dL) | 271 | 1% |
| Sulfasalazine | 300 (mg/L) | 94 | 0% |
| | 300 (mg/L) | 264 | 2% |
| Sulfapyridine | 300 (mg/L) | 93 | 1% |
| | 300 (mg/L) | 263 | 2% |
Method Comparison versus IFCC Reference Method
A split sample method comparison between the ADVIA Chemistry CK_L assay on the ADVIA Chemistry 1800 system versus the IFCC certified reference method on the Konelab 30i analyzer (Thermo Fisher Scientific) was performed with 100 native de-identified human serum samples across the assay range (15 to 1300 U/L). Analysis of the results yielded the following:
| Method | n | Predicate
Method
Sample
Range
U/L | Proposed
Method
Sample
Range
U/L | Slope
(95% CI) | Intercept
U/L
(95% CI) | Correlation
Coefficient
(R) |
|--------------------------------------------|-----|-----------------------------------------------|----------------------------------------------|---------------------------|------------------------------|-----------------------------------|
| ADVIA CK_L versus
IFCC Reference Method | 100 | 21 to 1178 | 16 to 1245 | 1.05
(1.03 to
1.07) | -6.9
(-8.8 to -
4.9) | 1.00 |
Matrix Comparison
To confirm the equivalency of sample types, the performance of the ADVIA Chemistry CK L assay was compared for serum and lithium heparin plasma samples. Testing was performed using one lot of reagents and a single replicate from a matched set of serum and plasma samples in accordance with CLSI EP09-A3.
| Specimen
Type | n | Serum
Sample
Range
U/L | Plasma
(Lithium
heparin)
Sample
Range
U/L | Slope | Intercept
U/L | Correlation
Coefficient
(R) |
|------------------------|----|---------------------------------|----------------------------------------------------------|-------|------------------|-----------------------------------|
| Serum versus
Plasma | 55 | 37–1282 | 39 to 1284 | 1.01 | -0.6 | 1.00 |
8. Conclusion:
The proposed modified ADVIA Chemistry CK_L assay is substantially equivalent to the current legally marketed device based on intended use, principle and the performance characteristics above.