(31 days)
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No
The device description and performance studies focus on a standard turbidimetric assay and do not mention any AI or ML components.
No
This device is an in vitro diagnostic (IVD) assay designed to quantitatively determine cystatin C levels in human serum and plasma. The results aid in the diagnosis and treatment of renal disease, but the device itself does not directly treat or prevent a disease in a patient, which is the definition of a therapeutic device.
Yes
The device is explicitly stated to be for "in vitro diagnostic use" and aids in the "diagnosis and treatment of renal disease" through quantitative determination of cystatin C in human samples.
No
The device is an in vitro diagnostic kit containing reagents and is used on an ADVIA Chemistry System, indicating it is a hardware-based system with associated reagents, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: Explicitly states "for the in vitro diagnostic use".
- Device Description: Describes the kit as an "in vitro diagnostics kit".
- Function: The device is used to quantitatively determine cystatin C in human serum and plasma, which are biological samples tested in vitro (outside the body).
- Purpose: The measurement of cystatin C aids in the diagnosis and treatment of renal disease, which is a clinical application of the test results.
N/A
Intended Use / Indications for Use
The ADVIA® Chemistry Cystatin C 2 (CYSC 2) assay is for the in vitro diagnostic use in the quantitative determination of cystatin C in human serum and plasma (lithium heparin, potassium EDTA) on ADVIA Chemistry systems. Measurement of cystatin C aids in the diagnosis and treatment of renal disease.
Product codes
NDY
Device Description
The ADVIA Cystatin C_2 assay (CYSC_2) is an in vitro diagnostics kit containing reagents for the quantitative determination of cystatin C in human serum and plasma by means of particle-enhanced turbidimetry using the ADVIA Chemistry Systems. Used in conjunction with other clinical and laboratory findings, ADVIA Chemistry Cystatin C 2 measurements are used as an aid in the diagnosis and treatment of renal diseases.
The ADVIA Chemistry Cystatin C 2 latex reagent is a suspension of uniform latex particles coated with anti-cystatin-C antibody. When serum or plasma containing cystatin C is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 and 805 nm. The cystatin C concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.
Mentions image processing
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Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
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Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
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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
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Method Comparison versus the Predicate:
Study Type: Method comparison
Sample Size: One hundred and fifty-eight (158) frozen human serum samples
Data Source: Not specified
Annotation Protocol: Not specified
Key Results:
Passing-Bablok regression analysis:
Methods: ADVIA CYCS_2 versus N Latex Cystatin C
n: 158
N Latex Sample Range Analyzed (mg/L): 0.44 to 8.07
Slope (95% CI): 1.008 (0.998 to 1.022)
Intercept mg/L (95% CI): 0.101 (0.086 to 0.113)
r-Value: 1.000
Weighted Least Square Linear regression:
Methods: ADVIA CYCS_2 versus N Latex Cystatin C
n: 158
N Latex Sample Range Analyzed (mg/L): 0.44 to 8.07
Slope (95% CI): 1.021 (1.006 to 1.037)
Intercept mg/L (95% CI): 0.079 (0.063 to 0.96)
r-Value: 1.000
Repeatability and Within Lab Precision:
Study Type: Precision testing
Sample Size: 80 replicates/sample
Data Source: Not specified
Annotation Protocol: Not specified
Key Results:
Multiqual 1 Control (Mean: 0.52 mg/L): Repeatability SD: 0.01, %CV: 2.0; Within-Lab Precision SD: 0.02, %CV: 3.7
Randox 2 Control (Mean: 0.85 mg/L): Repeatability SD: 0.01, %CV: 1.1; Within-Lab Precision SD: 0.01, %CV: 1.5
Randox 3 Control (Mean: 3.91 mg/L): Repeatability SD: 0.04, %CV: 1.1; Within-Lab Precision SD: 0.07, %CV: 1.9
Serum Pool 1 (Mean: 1.09 mg/L): Repeatability SD: 0.01, %CV: 0.9; Within-Lab Precision SD: 0.01, %CV: 1.2
Serum Pool 2 (Mean: 8.92 mg/L): Repeatability SD: 0.12, %CV: 1.4; Within-Lab Precision SD: 0.21, %CV: 2.4
Linearity:
Study Type: Linearity
Sample Size: 11
Data Source: Not specified
Annotation Protocol: Not specified
Key Results: Linearity demonstrated by linear fit deviation of 2.50 mg/L and linear fit deviation of ≤ 0.25 mg/L for samples ≤ 2.50 mg/L.
Linear Regression: 1.087
Intercept: -0.014
Correlation: 0.999
Percent Deviation: 10%
Absolute Deviation: 0.25 mg/L
Sample Range mg/L: 0.19 - 9.06
Detection Capability (LoB, LoD, LoQ):
Study Type: Detection Capability
Sample Size: N=480 replicates for LoB and LoD; Not specified for LoQ.
Data Source: Not specified
Annotation Protocol: Not specified
Key Results:
LoB: 0.10 mg/L
LoD: 0.25 mg/L
LoQ: 0.25 mg/L
Interference Testing:
Study Type: Interference testing
Sample Size: Not specified
Data Source: Not specified
Annotation Protocol: Performed according to CLSI EP07-A2: Approved Guideline Interference Testing in Clinical Chemistry.
Key Results: No significant interference (NSI) observed for:
Bilirubin (conjugated) at 60 mg/dL for Cystatin C concentrations 0.69 mg/L and 2.51 mg/L.
Bilirubin (unconjugated) at 60 mg/dL for Cystatin C concentrations 0.78 mg/L and 2.74 mg/L.
Lipemia (triglycerides from Intralipid) at 1000 mg/dL for Cystatin C concentrations 0.79 mg/L and 2.75 mg/L.
Hemolysis (hemoglobin) at 1000 mg/dL for Cystatin C concentrations 1.13 mg/L and 2.64 mg/L.
Rheumatoid Factor at 1200 IU/mL for Cystatin C concentrations 0.89 mg/L and 3.14 mg/L.
Expected Values:
Study Type: Normal Range Study
Sample Size: 208 apparently healthy samples
Data Source: Performed by Siemens.
Annotation Protocol: Following CLSI Procedure EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory.
Key Results:
Median: Not reported
2.5 Percentile: 0.64 mg/L
97.5 Percentile: 1.23 mg/L
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s)
Reference Device(s)
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 862.1225 Creatinine test system.
(a)
Identification. A creatinine test system is a device intended to measure creatinine levels in plasma and urine. Creatinine measurements are used in the diagnosis and treatment of renal diseases, in monitoring renal dialysis, and as a calculation basis for measuring other urine analytes.(b)
Classification. Class II.
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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
May 25, 2018
Siemens Healthcare Diagnostics, Inc. Kathleen Dray-Lyons Regulatory and Clinical Affairs Specialist 500 GBC Drive Newark, NJ 19714
Re: K181082
Trade/Device Name: ADVIA Chemistry Cystatin C 2 Assay (CYSC 2) Regulation Number: 21 CFR 862.1225 Regulation Name: Creatinine test system Regulatory Class: Class II Product Code: NDY Dated: April 23, 2018 Received: April 24, 2018
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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Kellie B. Kelm -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)
K181082
Device Name ADVIA® Chemistry Cystatin C 2 (CYSC 2) assay
Indications for Use (Describe)
The ADVIA® Chemistry Cystatin C 2 (CYSC 2) assay is for the in vitro diagnostic use in the quantitative determination of cystatin C in human serum and plasma (lithium heparin, potassium EDTA) on ADVIA Chemistry systems. Measurement of cystatin C aids in the diagnosis and treatment of renal disease.
Type of Use (Select one or both, as applicable)
X 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:
1. Submitter
| Company | Siemens Healthcare Diagnostics Inc. |
|---|---|
| Address | 500 GBC Drive |
| Newark, DE 19702 | |
| Contact | Kathleen Dray-Lyons |
| Telephone | 617-688-6117 |
| Date of Preparation | May 24, 2018 |
2. Trade Name:
ADVIA® Chemistry Cystatin C_2 Assay (CYSC_2)
Common Name:
Test, Cystatin C
Classification:
21 CFR § 862.1225; Class II
Product Code:
NDY
Panel:
Clinical Chemistry
3. Identification of the Predicate Devices:
N Latex Cystatin C (K171072)
The ADVIA Cystatin C_2 (CYSC_2) assay is substantially equivalent to the N Latex Cystatin C assay cleared under K171072.
4. Device Description:
The ADVIA Cystatin C_2 assay (CYSC_2) is an in vitro diagnostics kit containing reagents for the quantitative determination of cystatin C in human serum and plasma by means of particle-enhanced turbidimetry using the ADVIA Chemistry Systems. Used in
4
conjunction with other clinical and laboratory findings, ADVIA Chemistry Cystatin C 2 measurements are used as an aid in the diagnosis and treatment of renal diseases.
The ADVIA Chemistry Cystatin C 2 latex reagent is a suspension of uniform latex particles coated with anti-cystatin-C antibody. When serum or plasma containing cystatin C is mixed with the latex reagent, agglutination takes place resulting in an increase in turbidity. This turbidity is measured at 571 and 805 nm. The cystatin C concentration in serum or plasma is determined from a calibration curve that is generated with the calibrators.
5. Device Intended Use:
The ADVIA Chemistry Cystatin C 2 (CYSC 2) assay is for the in vitro diagnostic use in the quantitative determination of cystatin C in human serum and plasma (lithium heparin, potassium EDTA) on ADVIA Chemistry systems. Measurement of cystatin C aids in the diagnosis and treatment of renal disease.
6. Technical Characteristics:
Similarities and Differences to the predicate:
A comparison of the similarities and differences between the proposed ADVIA Chemistry Cystatin C 2 assay versus the N Latex Cystatin C assay (predicate) is provided in the table below.
| Attributes | Proposed
ADVIA Cystatin C_2 Assay | Predicate
N Latex Cystatin C
(K171072) |
|--------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | The ADVIA® Chemistry Cystatin
C_2 (CYSC_2) assay is for the in vitro diagnostic use in the
quantitative determination of
cystatin C in human serum and
plasma (lithium heparin,
potassium EDTA) on ADVIA
Chemistry systems.
Measurement of cystatin C aids
in the diagnosis and treatment of
renal disease. | N Latex Cystatin C is an in vitro
diagnostics kit containing
reagents for the quantitative
determination of cystatin C in
human serum and lithium-
heparinized plasma by means of
particle enhanced
immunonephelometry using the
BN Systems. Cystatin C
measurements are used in the
diagnosis and treatment of renal
diseases. |
| Assay format | Turbidimetry | Immunonephelometry |
| Antibody | Rabbit | Same |
| Traceability | The assay calibrator is traceable
to the IFCC European Reference
Material ERM-DA471/IFCC | Same |
ADVIA Cystatin C 2 Assay versus N Latex Cystatin C
5
| | certified for cystatin C
measurements | |
|--------------------|--------------------------------------------------------|---------------------------------------|
| Analyzers | ADVIA Chemistry Systems | BN Systems |
| Sample type | Serum and Plasma (lithium
heparin, potassium EDTA) | Serum and Plasma (lithium
heparin) |
| Units | mg/L | Same |
| Measuring
Range | 0.25 to 8.93 mg/L
0.25 to 26.79 mg/L (1:3 dilution) | 0.27 – 9.4 mg/L |
| Calibrators | 5 levels | One level |
7. Non-Clinical Performance Evaluation:
Method Comparison versus the Predicate:
The ADVIA Chemistry Cystatin C_2 assay on the ADVIA 1800 system was compared to the predicate N Latex Cystatin C assay (K171072) on the BN ProSpec system in accordance with CLSI EP09-A3: Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline Third Edition. One hundred and fifty-eight (158) frozen human serum samples were assayed in singlicate across the assay range of 0.25 - 8.93 mg/L. Analysis of the results using weighted linear regression, standard Passing-Bablok regression and Least Squares was calculated. The correlation coefficient (r) was obtained by linear regression.
Passing-Bablok regression analysis vielded the following:
| Methods | n | N Latex
Sample
Range
Analyzed
(mg/L) | Slope
(95% CI) | Intercept
mg/L
(95% CI) | r-
Value* |
|-------------------------------------------------|-----|--------------------------------------------------|------------------------------|-------------------------------|--------------|
| ADVIA CYCS_2
versus
N Latex
Cystatin C | 158 | 0.44 to 8.07 | 1.008
(0.998 to
1.022) | 0.101
(0.086 to
0.113) | 1.000 |
Weighted Least Square Linear regression yielded the following:
| Methods | n | N Latex
Sample
Range
Analyzed
(mg/L) | Slope
(95% CI) | Intercept
mg/L
(95% CI) | r-
Value* |
|------------------|---|--------------------------------------------------|-------------------|-------------------------------|--------------|
| ADVIA CYCS_2 158 | | | 1.021 | 0.079 | 1.000 |
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| versus
N Latex
Cystatin C | 0.44 to 8.07 | (1.006 to
1.037) | (0.063 to
0.96) |
| --------------------------------- | -------------- | --------------------- | -------------------- |
|---|
- Correlation coefficient (r) was obtained from ordinary least squares regression.
Repeatability and Within Lab Precision:
Testing was performed over twenty (20) days, two (2) runs per day, two (2) times per run for a total 80 replicates/sample. Analysis of variance (ANOVA) was used to calculate the Repeatability and Within-Lab imprecision. Typical precision observed on the ADVIA Cystatin C 2 assay is summarized below.
| Material | N | Mean | Repeatability | | Within-Lab
Precision | |
|---------------------|----|------|---------------|-----|-------------------------|-----|
| | | mg/L | SD | %CV | SD | %CV |
| Multiqual 1 Control | 80 | 0.52 | 0.01 | 2.0 | 0.02 | 3.7 |
| Randox 2 Control | 80 | 0.85 | 0.01 | 1.1 | 0.01 | 1.5 |
| Randox 3 Control | 80 | 3.91 | 0.04 | 1.1 | 0.07 | 1.9 |
| Serum Pool 1 | 80 | 1.09 | 0.01 | 0.9 | 0.01 | 1.2 |
| Serum Pool 2 | 80 | 8.92 | 0.12 | 1.4 | 0.21 | 2.4 |
Repeatability and Within-Lab Results
Linearity
Linearity across the assay range (0.25 to 8.93 mg/L) was confirmed in accordance with CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: A Statistical Approach, by testing a high concentration of cystatin C on the ADVIA Chemistry 1800 system using one lot of reagent and calibrators. This high concentration sample was serially diluted with a low concentration sample (serum) with equally spaced dilution levels ranging from 0.19 to 9.06 mg/L. Linearity was demonstrated by linear fit deviation of 2.50 mg/L and linear fit deviation of ≤ 0.25 mg/L for samples ≤ 2.50 mg/L. Samples above 2.5 mg/L were found to deviate no more than 10%, while samples below or equal to 2.5 mg/L did not demonstrate a bias greater than 0.03.
| ADVIA
System | Linear Regression | | | Percent
Deviation | Absolute
Deviation | n | Sample
Range
mg/L |
|-----------------|-------------------|--------|-------|----------------------|-----------------------|----|-------------------------|
| 1800 | 1.087 | -0.014 | 0.999 | 10% | 0.25 mg/L | 11 | 0.19 - 9.06 |
ADVIA Cystatin C_2 Assay
7
Detection Capability
LoB: Four (4) blank samples were prepared at a concentration of 0 mg/L. All four samples were tested in replicates of twenty (20) on the ADVIA 1800 system over three (3) days using two (2) reagent lots for a total of N=480 replicates. The LoB for the ADVIA Chemistry CYSC 2 assay is 0.10 mg/L.
LoD: Four (4) samples were prepared at a concentration of approximately 0.1 mg/L. All four samples were tested in replicates of twenty (20) on the ADVIA 1800 system over three (3) days using two (2) reagent lots for a total of N=480 replicates. The LoD for the ADVIA Chemistry CYSC_2 assay is 0.25 mg/L.
LoQ: Four (4) serum samples were prepared at a concentration of approximately 0.1 mg/L. All four samples were tested in replicates of twenty (20) on the ADVIA 1800 system over three (3) days using two (2) reagent lots. The LoQ for the ADVIA Chemistry CYSC_2 assay is 0.25 mg/L.
LoB and LoD values were calculated non-parametrically with proportions of false positives (α) less than 5% and false negatives (β) less than 5%, based on 480. LoQ is the lowest amount of cystatin C that can be determined quantitatively at 10% is considered a significant interference.
8
Expected Values:
The expected values for healthy individuals are from 0.64-1.23 mg/L. These are the 2.5 and the 97.5 percentile values from the results of a normal range study, following CLSI Procedure EP28-A3c Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory with 208 apparently healthy samples, performed by Siemens.
| ADVIA Cystatin C_2 | |
|---|---|
| Median | |
| 2.5 Percentile | 0.64 mg/L |
| 97.5 Percentile | 1.23 mg/L |
Calibrator Traceability:
The assay is standardized using calibrators, which are traceable to the IFCC European Reference Material ERM-DA471/IFCC, certified for Cystatin C measurements.
8. Conclusion:
The ADVIA Chemistry Cystatin C_2 assay is substantially equivalent to the predicate devices based on intended use, principle and the performance characteristics above.