ADVIA CHEMISTRY C-REACTIVE PROTEIN_2, (CRP_2) AND CALIBRATORS
Device Facts
| Record ID | K072658 |
|---|---|
| Device Name | ADVIA CHEMISTRY C-REACTIVE PROTEIN_2, (CRP_2) AND CALIBRATORS |
| Applicant | Siemens Medical Solutions Diagnostics |
| Product Code | DCN · Immunology |
| Decision Date | Apr 1, 2008 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5270 |
| Device Class | Class 2 |
Indications for Use
The ADVIA™ Chemistry C-Reactive Protein_2 assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin) on the ADVIA Chemistry systems. Such measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation. The ADVIA Chemistry C-Reactive Protein_2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the C-Reactive Protein_2 (CRP-2) method.
Device Story
ADVIA Chemistry C-Reactive Protein_2 (CRP_2) assay is an in vitro diagnostic test for human serum and plasma; utilizes latex turbidimetric immunoassay principle. Input: patient serum/plasma sample mixed with rabbit anti-CRP antibody-coated polystyrene latex particles. Reaction produces agglutination, increasing turbidity measured at 571 nm. Output: quantitative CRP concentration derived from a 6-point calibration curve. Used in clinical laboratories on ADVIA Chemistry systems (1200/1650/1800/2400). Results assist clinicians in evaluating infection, tissue injury, and inflammatory disorders. Benefits include rapid, automated quantitative assessment of inflammatory markers to support clinical decision-making.
Clinical Evidence
No clinical data provided. Performance established via bench testing, including precision (CLSI EP5-A2), linearity (CLSI EP17-A), analytical specificity (interference/prozone), and method comparison against the predicate device (n=35, R=0.99). Matrix equivalence between serum and lithium-heparin plasma confirmed (n=56, R=0.999).
Technological Characteristics
Latex-enhanced turbidimetric immunoassay. Reagents: glycine buffer and rabbit anti-CRP antibody-coated polystyrene latex particles. Read wavelength: 571 nm. Analytical range: 4 to 336 mg/L (extendable via auto-dilution). Standardization: CRM-470. Calibration: 6-point. Storage: 2-8°C. Compatible with ADVIA Chemistry systems (1200/1650/1800/2400).
Indications for Use
Indicated for quantitative determination of C-Reactive Protein (CRP) in human serum and plasma to aid in evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. For prescription use.
Regulatory Classification
Identification
A C-reactive protein immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the C-reactive protein in serum and other body fluids. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.
Predicate Devices
- ADVIA® Chemistry Systems C-Reactive Protein (k992662)
- ADVIA Chemistry wrCRP Calibrators (K022682)
Related Devices
- K030545 — CRP-LATEX (II)X2 SEIKEN ASSAY KIT · Denka Seiken Co., Ltd. · Jun 2, 2003
- K103557 — DIAZYME HS CRP ASSAY KIT / CALIBRATOR SET / CONTROL SET · Diazyme Laboratories · Apr 27, 2011
- K023269 — HEMOSIL C-REACTIVE PROTEIN - HIGH SENSITIVITY AND HIGH SENSITIVITY CONTROLS · Instrumentation Laboratory CO · Dec 23, 2002
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
k072658
B. Purpose for Submission:
New Device
C. Measurand:
C-Reactive Protein (CRP)
D. Type of Test:
Latex-enhanced turbidimetric immunoassay, quantitative
E. Applicant:
Seimens Medical Solutions Diagnostics
F. Proprietary and Established Names:
ADVIA™ Chemistry C-Reactive Protein_2 (CRP_2) Assay
ADVIA™ Chemistry C-Reactive Protein_2 Calibrators
G. Regulatory Information:
1. Regulation section:
866.5270 C-reactive protein immunological test system
862.1150 Calibrator
2. Classification:
Class II
3. Product code:
DCN System, test, c - reactive protein
JIX Calibrator, multi-analyte mixture
4. Panel:
Immunology
Clinical Chemistry
H. Intended Use:
1. Intended use(s):
The ADVIA™ Chemistry C-Reactive Protein_2 assay is for in vitro diagnostic use in the quantitative determination of the concentration of C-Reactive Protein (CRP) in human serum and plasma (lithium heparin) on the ADVIA Chemistry systems. Such measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation.
The ADVIA Chemistry C-Reactive Protein_2 Calibrators are for in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the C-Reactive Protein_2 (CRP-2) method.
2. Indication(s) for use:
Same as above
3. Special conditions for use statement(s):
Prescription use
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4. Special instrument requirements: ADVIA Chemistry system (1200/1650/1800/2400)
I. Device Description:
The ADVIA™ Chemistry C-Reactive Protein_2 assay consists of two liquid, ready-to-use components: Reagent 1 is a glycine buffer solution; Reagent 2 is a suspension of uniform polystyrene latex particles coated with rabbit anti-CRP antibody.
The ADVIA Chemistry C- Reactive Protein_2 Calibrators consist of six (6) levels of protein stabilized matrices containing varying concentrations of recombinant human CRO. The Calibrators have targeted expected values (lot specific) of 0, 5, 20, 40, 160 and 320 mg/L. The Calibrators (1 mL/vial) are liquid and ready to use. Storage is at 2-8°C.
J. Substantial Equivalence Information:
1. Predicate device name(s): ADVIA Chemistry C-Reactive Protein_2 Wide Range Calibrators ADVIA Chemistry C-Reactive Protein (CRP)
2. Predicate K number(s): k022682 k992662
3. Comparison with predicate:
ADVIA Chemistry C-reactive Protein_2
| Similarities | | |
| --- | --- | --- |
| Item | New Device | Predicate |
| Intended Use | For in vitro diagnostic use in the quantitative determination of C-reactive Protein. measurements are used in the evaluation of infection, tissue injury, inflammatory disorders, and associated diseases. Increases in CRP values are non-specific for many disease processes and should not be interpreted without a complete clinical evaluation. | Same |
| Expected Values | < 10 mg/L | Same |
| Reagent matrix | Two liquid, ready-to use | Same |
| Capture Antibody | Rabbit anti-CRP | Same |
| Storage | 2-8°C | Same |
| Standardization | CRM-470 | Same |
| Calibration | 6-point | Same |
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| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Specimen Type | Serum or plasma (lithium heparin) | Serum |
| Assay Principle | Latex turbidimetric immunoassay | Polyethylene glycol assisted turbidimetric immunoassay |
| Read wavelength | 571 nm | 340/694 nm |
| Analytical range | 4 to 336 mg/L | 5-205 mg/L |
| On-board stability | 60 days | 30 days |
## ADVIA Chemistry C-Reactive Protein_2 Calibrators
| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | For in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the CRP_2 method. | For in vitro diagnostic use in the calibration of ADVIA Chemistry systems for the wrCRP method. |
| Measurand | Recombinant human CRP | Same |
| Levels | 6 point calibration; 1 mL each | Same |
| Matrix | Liquid, Ready-to-use | Same |
| Traceability | CRM470 | Same |
| Shelf life | 18 months at 2-8°C | Same |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Expected Values | 0, 5, 20, 40, 160, and 320 mg/L; lot specific | 0, 2.5, 10, 20, 80, and 160 mg/L; lot specific |
| Open-vial stability | 60 days at 2-8°C | 28 days at 2-8°C |
## K. Standard/Guidance Document referenced (if applicable):
CLSI document EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline. CLSI EP17-A, Protocols for Determination of Limits of Detection and Limits of Quantitation; Approved Guideline.
## L. Test Principle:
Sample is diluted by the instrument and then 40 µL of diluted sample is incubated with a buffer (Reagent 1). Reagent 2, a CRP_2 latex reagent, which is a suspension of uniform polystyrene latex particles coated with rabbit anti-CRP antibody, is added 10 minutes later. When serum or plasma containing CRP is mixed with the latex
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reagent, agglutination takes place resulting in an increase in the turbidity. This turbidity is measured at 571 nm. The CRP concentration in serum or plasma is determined from a calibration curve that is generated with the CRP_2 calibrators.
## M. Performance Characteristics (if/when applicable):
### 1. Analytical performance:
#### a. Precision/Reproducibility:
Within-run and total precision were evaluated by testing three serum pools and 3 control levels on the ADVIA 1650. Samples were evaluated in duplicate in 2 runs per day for 10 days. Precision was evaluated using calculation methods in CLSI EP-5A2. Acceptance criteria (described below) were met.
| Sample | Level mg/L | Within-run | | Total | |
| --- | --- | --- | --- | --- | --- |
| | | SD | CV(%) | SD | CV(%) |
| Control 1 | 31 | 0.33 | 1.1 | 0.38 | 1.3 |
| Control 2 | 56 | 0.51 | 0.9 | 0.61 | 1.1 |
| Control 3 | 83 | 1.11 | 1.3 | 1.27 | 1.5 |
| Serum Pool 1* | 12.8 | 0.50 | 3.9 | 0.50 | 3.9 |
| Serum Pool 2 | 221 | 2.48 | 1.1 | 3.24 | 1.5 |
| Serum Pool 3* | 310.7 | 22.86 | 7.4 | 22.86 | 7.4 |
*5-day protocol
The acceptance criteria for precision performance are as follows:
| C-RP concentration | Acceptance Criteria | |
| --- | --- | --- |
| | Within-run CV | Total CV |
| Lower range (~10 mg/L) | 5% | 8% |
| Upper range | ≤ 10% | 12% |
Additionally, CRP_2 Control recoveries on each platform must be within ± 5% of the ADVIA 1650.
#### b. Linearity/assay reportable range:
Linearity was evaluated by making equally spaced dilutions of a high serum pool with a low serum pool and comparing the expected vs. observed CRP concentration. Difference in recovery was ≤ 3.5%. Linear regression statistics demonstrated that the slope (and 95% CI) was 1.01 (0.987 to 1.034), y-intercept -0.10 (-4.35 to 4.14); r= 1.0.
| ADVIA 1650 CRP_2 (mg/L) | | | |
| --- | --- | --- | --- |
| Sample | Expected | Observed | Recovery (%) |
| P1 | 0 | | NA |
| P2 | 38 | 38 | 100.6% |
| P3 | 76 | 75 | 98.7% |
| P4 | 114 | 115 | 100.5% |
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| ADVIA 1650 CRP 2 (mg/L) | | | |
| --- | --- | --- | --- |
| Sample | Expected | Observed | Recovery (%) |
| P5 | 152 | 156 | 102.3% |
| P6 | 190 | 189 | 99.4% |
| P7 | 228 | 236 | 103.5% |
| P8 | 267 | 270 | 101.1% |
| P9 | 305 | 305 | 100.0% |
The ADVIA Chemistry system has an 'auto-dilution' option to extend the measuring range above CRP concentrations of $304\mathrm{mg / L}$ (highest level calibrator). Samples above this are automatically diluted 3-fold by the system. The extended linearity of the ADVIA 1650 assay was evaluated by making equally spaced dilutions of two serum pools and comparing expected vs. observed CRP concentrations. Difference in recovery was $\leq 8.3\%$ . Linear regression statistics for the entire assay range (0 to $1071\mathrm{mg / L}$ ) demonstrated that the slope (and $95\%$ CI) was 1.033 (1.001 to 1.064), intercept was 2.04 (-12.85 to 16.94), $r = 0.999$ .
| ADVIA 1650 CRP 2 (mg/L) | | | |
| --- | --- | --- | --- |
| Sample | Expected | Observed | Recovery (%) |
| P1 | 337 | 337 | 100.0% |
| P2 | 521 | 542 | 104.1% |
| P3 | 704 | 763 | 108.3% |
| P4 | 888 | 942 | 106.2% |
| P5 | 1071 | 1071 | 100.0% |
c. Traceability, Stability, Expected values (controls, calibrators, or methods): Traceable to CRM-470.
Data and testing methodology were provided to support the open and closed stability claims in the labeling. Closed stability: 18 months at $2 - 8^{\circ}\mathrm{C}$ ; Onboard stability 60 days. Calibrator stability 60 days $2 - 8^{\circ}\mathrm{C}$ .
d. Detection limit:
The Limit of detection (LoD) was obtained using the mean and SD of a blank and a low sample containing CRP ( $\sim 3\mathrm{mg / L}$ ); and computed according to CLSI EP-17A protocol and determined to be $0.2\mathrm{mg / L}$ , $n = 40$ . The data support the low end claim for the analytical range as $4\mathrm{mg / L}$ .
e. Analytical specificity:
Interference was evaluated by spiking human serum pools with hemoglobin (max $1000\mathrm{mg / dL}$ ), unconjugated and conjugated bilirubin (max $60\mathrm{mg / dL}$ ), Intralipid and avian triglycerides (max $1000\mathrm{mg / dL}$ ), and rheumatoid factor $(200\mathrm{IU / mL})$ . Multiple levels up to the maximum concentration listed of each of the interfering substances were tested at CRP concentration of $\sim 5\mathrm{mg / L}$ . Interference was also tested on samples containing $10\mathrm{mg / L}$ CRP using a single concentration of interferent (highest evaluated). All results passed the acceptance criteria for interference of $\leq 10\%$ .
Prozone: No hook effect demonstrated up to $1000\mathrm{mg / L}$ of CRP.
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Cross-reactivity: cross-reactivity to other substances was not evaluated.
f. Assay cut-off:
Not applicable.
2. Comparison studies:
a. Method comparison with predicate device:
The CRP_2 method on the ADVIA 1650 was compared to the ADVIA Chemistry CRP method on the same analyzer using the 35 samples that spanned the assay range. The mean of duplicate measurements were analyzed by Passing-Bablock regression analysis yielding the following results:
| Comparison Method (x) | N | Slope (95% C.I.) | Intercept (95% C.I.) | R | Sample Range |
| --- | --- | --- | --- | --- | --- |
| ADVIA Chemistry CRP | 35 | 0.970 (0.938 to 1.00) | 0.71 (-1.48 to 2.56) | 0.99 | 6.5 to 192.3 mg/L |
b. Matrix comparison:
A matrix comparison study was performed using matched serum and lithium-heparin plasma samples spanning the range of the assay. The results demonstrated equivalence between the matrices. Least square regression demonstrated the results:
| N | Slope (95% C.I.) | Intercept (95% C.I.) | R | Sample Range |
| --- | --- | --- | --- | --- |
| 56 | 0.999 (0.987 – 1.011) | -0.01 (-1.61 – 1.60) | 0.999 | 6- 246 mg/L |
3. Clinical studies:
a. Clinical Sensitivity:
Not available.
b. Clinical specificity:
Not available.
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable
4. Clinical cut-off:
Not available.
5. Expected values/Reference range:
<10 mg/L (according to Tietz Clinical Guide to Laboratory Tests, 4th edition)
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.
