Tina-quant Cardiac high sensitivity CRP III
Device Facts
| Record ID | K260026 |
|---|---|
| Device Name | Tina-quant Cardiac high sensitivity CRP III |
| Applicant | Roche Diagnostics |
| Product Code | NQD · Immunology |
| Decision Date | Apr 2, 2026 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.5270 |
| Device Class | Class 2 |
Indications for Use
The Tina-quant Cardiac high sensitivity CRP III application is an in vitro test for the quantitative determination of C-reactive protein (CRP) in human serum and plasma on cobas c systems. Cardiac high sensitive measurement of CRP may be used as an aid in the assessment of the risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation methods of acute coronary syndromes, it may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome.
Device Story
Tina-quant Cardiac high sensitivity CRP III is a particle-enhanced immunoturbidimetric assay for use on Roche cobas c 503 analyzers. The device measures C-reactive protein (CRP) in human serum or plasma samples. Input samples are mixed with latex particles coated with monoclonal anti-CRP antibodies; CRP in the sample causes agglutination of the latex particles. The resulting precipitate is measured turbidimetrically. The assay provides a quantitative result (0.150–10.0 mg/L) used by clinicians to assess cardiovascular disease risk and prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome. The device is intended for professional use in clinical laboratory settings.
Clinical Evidence
Bench testing only. Analytical performance validated per CLSI guidelines (EP05-A3, EP17-A2, EP06-Ed2). Precision studies (N=84) showed CVs < 2.5%. Linearity confirmed across 0.150–10.0 mg/L range. Interference testing evaluated endogenous substances and common cardiovascular drugs; no significant interference observed. Method comparison (N=104) against predicate showed high correlation (r=0.999). No clinical studies were required.
Technological Characteristics
Particle-enhanced immunoturbidimetric assay. Reagents: TRIS buffer, bovine serum albumin, latex particles coated with mouse anti-CRP antibodies. Measuring range: 0.150–10.0 mg/L. Traceability: ERM-DA474/IFCC. Instrument: Roche cobas c 503. Software: Embedded firmware on analyzer. Sterilization: Not applicable (reagent kit).
Indications for Use
Indicated for quantitative determination of CRP in human serum and plasma to assess risk for future cardiovascular disease and as a prognostic marker for recurrent events in patients with stable coronary disease or acute coronary syndrome.
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
- C-reactive Protein (Latex) High Sensitive Test System For Cobas Integra Instruments (K053603)
Submission Summary (Full Text)
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FDA
U.S. FOOD & DRUG
ADMINISTRATION
# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
ASSAY ONLY
## I Background Information:
A 510(k) Number
K260026
B Applicant
Roche Diagnostics
C Proprietary and Established Names
Tina-quant Cardiac high sensitivity CRP III
D Regulatory Information
| Product Code(s) | Classification | Regulation Section | Panel |
| --- | --- | --- | --- |
| NQD | Class II | 21 CFR 866.5270 - C-Reactive Protein Immunological Test System | IM - Immunology |
## II Submission/Device Overview:
A Purpose for Submission:
Modification of a previously cleared device
B Measurand:
C-Reactive Protein (cardiac)
C Type of Test:
Quantitative Immunoturbidimetric
Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov
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## III Intended Use/Indications for Use:
### A Intended Use(s):
See Indications for Use below.
### B Indication(s) for Use:
The Tina-quant Cardiac high sensitivity CRP III application is an in vitro test for the quantitative determination of C-reactive protein (CRP) in human serum and plasma on cobas c systems. Cardiac high sensitive measurement of CRP may be used as an aid in the assessment of the risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation methods of acute coronary syndromes, it may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome.
### C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
### D Special Instrument Requirements:
Roche cobas c 503 analyzer, K191899.
## IV Device/System Characteristics:
### A Device Description:
The Tina-quant Cardiac high sensitivity CRP III assay is a particle enhanced immunoturbidimetric assay. The device is supplied ready for use.
**Reagents**
- R1: TRIS(A) buffer with bovine serum albumin, pH 7.6; preservative (A)TRIS = Tris(hydroxymethyl)-aminomethane
- R3: Latex particles (0.31 % w/w) coated with anti-CRP (mouse) in glycine buffer; immunoglobulins (mouse, 0.0075 % w/w), pH 8.0; preservative
**Materials required but not provided:**
- Calibrator f.a.s. Proteins (5 × 1 mL)
- CRP T Control N (5 × 0.5 mL)
- PreciControl ClinChem Multi 1 (4 × 5 mL)
- Diluent NaCl 9% (123 mL)
The following modifications have been implemented in the candidate Tina-quant Cardiac high sensitivity CRP III assay in comparison to the predicate:
- Reagent formulation change
- Less sample volume
- Traceability change to ERM-DA474/IFCC certified reference material
- Different measuring range (0.150-10.0 mg/L)
- Differences in clinical indications
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B Principle of Operation:
The Tina-quant Cardiac high sensitivity CRP III assay is a particle enhanced immunoturbidimetric assay. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically.
V Substantial Equivalence Information:
A Predicate Device Name(s):
C-reactive Protein (Latex) High Sensitive Test System For Cobas Integra Instruments
B Predicate 510(k) Number(s):
K053603
C Comparison with Predicate(s):
| Device & Predicate Device(s): | K260026 | K053603 |
| --- | --- | --- |
| Device Trade Name | Tina-quant Cardiac high sensitivity CRP III | C-Reactive Protein (Latex) High Sensitive Test System For Cobas Integra Instruments |
| General Device Characteristic Similarities | | |
| Intended Use/Indications For Use | For the quantitative determination of C-reactive protein (CRP) in human serum and plasma. Cardiac high sensitive measurement of CRP may be used as an aid in the assessment of the risk for future cardiovascular disease. When used in conjunction with traditional clinical laboratory evaluation methods of acute coronary syndromes, it may be useful as an independent marker of prognosis for recurrent events in patients with stable coronary disease or acute coronary syndrome | Same |
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| Assay Principle | Particle-enhanced immunoturbidimetric assay | Same |
| --- | --- | --- |
| Calibration Method | Non-linear | Same |
| Sample Type/ Matrix | Human serum and plasma | Same |
| General Device Characteristic Differences | | |
| Traceability/ Standardization | This method has been standardized against the certified reference material in human serum of the IRMM (Institute for Reference Materials and Measurements) ERM-DA474/IFCC, which is directly traceable to ERM-DA470 (formerly named CRM470). | This method has been standardized against the reference preparation of the IRMM (Institute for Reference Materials and Measurements) BCR470/CRM470 (RPPHS - Reference Preparation for Proteins in Human Serum) |
| Assay Range / Measuring Interval | 0.150-10.0 mg/L | 0-20 mg/L |
| Clinical Indications | Not intended for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. | For the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. |
VI Standards/Guidance Documents Referenced:
CLSI EP05-A3, Evaluation of Precision of Quantitative Measurement Procedures; Approved Guideline - Third Edition.
CLSI EP17-A2, Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline-2nd Edition.
CLSI EP06 -ED2:2020, Evaluation of Linearity of Quantitative Measurement Procedures, 2nd Edition.
Guidance for Industry and Staff, Review Criteria for Assessment of C-Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assays. 2005
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VII Performance Characteristics (if/when applicable):
A Analytical Performance:
1. Precision/Reproducibility:
Precision measurements were conducted to evaluate repeatability (within-run precision) and the intermediate precision (within-laboratory precision) per recommendations in the CLSI EP05-A3 guideline. Repeatability and intermediate precision studies were performed using five human serum samples and two controls with concentrations spanning the measuring range. Samples were tested in duplicate using 2 runs per day over 21 days for a total of 84 replicates per sample on one cobas c 503 analyzer, using 3 reagent lots. Repeatability (within run precision), intermediate precision (within lab precision) and between day precision were calculated. Results from multiple lots were similar, with results from one representative lot shown below:
| Sample | N | Repeatability | | | Intermediate Precision | | | Between Day | | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | Mean mg/L | SD mg/L | CV (%) | Mean mg/L | SD mg/L | CV (%) | Mean mg/L | SD mg/L | CV (%) |
| QC1 | 84 | 4.14 | 0.0158 | 0.4 | 4.14 | 0.0216 | 0.5 | 4.14 | 0.00986 | 0.2 |
| QC2 | 84 | 6.40 | 0.0222 | 0.3 | 6.44 | 0.0643 | 1.0 | 6.40 | 0 | 0.0 |
| Serum 1 | 84 | 0.429 | 0.00795 | 1.9 | 0.429 | 0.00826 | 1.9 | 0.429 | 0.00139 | 0.3 |
| Serum 2 | 84 | 1.09 | 0.0184 | 1.7 | 1.09 | 0.0221 | 2.0 | 1.09 | 0.0124 | 1.1 |
| Serum 3 | 84 | 2.93 | 0.0159 | 0.5 | 2.93 | 0.0225 | 0.8 | 2.93 | 0.00359 | 0.1 |
| Serum 4 | 84 | 6.46 | 0.0340 | 0.5 | 6.46 | 0.0517 | 0.8 | 6.46 | 0.0162 | 0.3 |
| Serum 5 | 84 | 9.86 | 0.0432 | 0.4 | 9.86 | 0.0636 | 0.6 | 9.86 | 0.0387 | 0.4 |
A reproducibility study was conducted using five serum samples and two control levels. Samples were assayed using one cobas c 503 analyzer over seven days, two runs per day, 2 replicates per run and 3 reagent lots. The results are shown below:
| | | | Between Lot | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- |
| Sample | N | Mean (mg/L) | SD (mg/L) | CV (%) | SD (mg/L) | CV (%) |
| QC1 | 84 | 4.14 | 0.00000 | 0.0 | 0.0194 | 0.5 |
| QC2 | 84 | 6.42 | 0.0227 | 0.4 | 0.0619 | 1.0 |
| Serum 1 | 84 | 0.437 | 0.00779 | 1.8 | 0.0109 | 2.5 |
| Serum 2 | 84 | 1.08 | 0.0124 | 1.2 | 0.0235 | 2.2 |
| Serum 3 | 84 | 2.88 | 0.0398 | 1.4 | 0.0453 | 1.6 |
| Serum 4 | 84 | 6.36 | 0.1220 | 1.9 | 0.130 | 2.0 |
| Serum 5 | 84 | 9.72 | 0.1700 | 1.8 | 0.178 | 1.8 |
2. Linearity:
Linearity of the Tina-quant Cardiac high sensitivity CRP III (HSCRP) was assessed per recommendations in the CLSI EP06-Ed2 guideline on one cobas c 503 analyzer in 1 run using 3 reagent lots for serum, 1 reagent lot for plasma, and 4 replicates per sample. A human sample pool (sample High) with an analyte concentration above the upper limit of the
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measuring range and a human sample pool Low were mixed to prepare the dilution series. SD and CV were calculated for each 4-fold determination. For serum and plasma samples, the deviation from linearity for $>1.00\mathrm{mg / L}$ concentration was $< 4\%$ and absolute difference for $\leq 1.00\mathrm{mg / L}$ concentration was $< 0.03\mathrm{mg / L}$ . The linearity study results support that the assay is linear across the claimed reportable range from 0.150 to $10.0\mathrm{mg / L}$ .
# 3. Analytical Specificity/Interference:
Potential interference from endogenous substances was evaluated per CLSI EP07 Ed 03. For each potential interferent, samples with CRP concentration at around 1.0 and $3.0\mathrm{mg / L}$ were measured in the presence of interferent at 11 interferent concentrations. Percent recovery at each concentration was calculated as the mean value of 5 replicates at that concentration compared to the control sample. The results are summarized in the table below:
| Interferent Substance | Highest Concentration Tested Without Significant Interference |
| --- | --- |
| Albumin | 70.7 g/L |
| Conjugated Bilirubin | 62 mg/dL |
| Hemolysis | 700 mg/dL |
| Immunoglobulin G | 79.2 g/L |
| Lipemia (Intralipid) | 2000 mg/dL |
| Triglycerides | 539 mg/dL |
| Unconjugated Bilirubin | 62 mg/dL |
| Rheumatoid Factor | 520 IU/mL |
The effect on quantitation of the Tina-quant Cardiac high sensitivity CRP III in the presence of potentially interfering drugs was determined at 2 CRP concentrations. Two human serum sample pools containing CRP concentration levels were divided into 2 portions. One portion of each pool was spiked with the respective amount of drug, and the other portion of the pool with solvent used to dissolve the drug, which was used for the baseline reference CRP concentration. The CRP mean concentration of both portions was determined in $N = 5$ results. The mean % Recovery and absolute deviation were calculated when comparing the drug spiked portions to the CRP baseline reference mean concentration. At the following concentrations, the percent difference between the results of the spiked samples compared to the results of the control samples was less than $\pm 8.1\%$ . The results are summarized in the table below:
| Interferent Substance | Highest Concentration Tested Without Significant Interference (mg/dL) |
| --- | --- |
| Atorvastatin | 0.75 |
| Lisinopril | 0.25 |
| Metoprolol succinate | 1.5 |
| Warfarin | 75 |
| Repaglinide | 1.15 |
| Hydrochlorothiazide | 1.13 |
| Clonidine | 0.0195 |
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| Interferent Substance | Highest Concentration Tested Without Significant Interference (mg/dL) |
| --- | --- |
| Apixaban | 6 |
| Ezetimibe | 0.0213 |
| Fenofibrate | 45 |
| Valsartan | 11.7 |
| Spironolactone | 0.56 |
| Clopidogrel | 45 |
| Glimepiride | 1.64 |
| Empagliflozin | 10.5 |
| Liraglutide | 0.17 |
| Amlodipine | 0.075 |
| N-Acetylcysteine | 150 |
| Acetylsalicylic acid | 30 |
| Ampicillin-Na | 75 |
| Ascorbic acid | 52.5 |
| Cefoxitin | 750 |
| Doxycyclin | 18 |
| Heparin | 3300 IU/L |
| Levodopa | 7.5 |
| Methyldopa | 22.5 |
| Metronidazole | 123 |
| Rifampicin | 48 |
| Evolocumab | 6 |
| Icosapent ethyl | 2400 |
| Metformin | 12 |
| Sitagliptin | 60 |
| Hydralazine | 14.4 |
| Prazosin | 3 |
| Cyclosporine | 1.8 |
| Phenylbutazone | 321 |
| Acetaminophen | 156 |
| Ibuprofen | 219 |
| Theophylline | 60 |
A study was conducted to confirm that no false results will be reported due to high-dose hook effect using the Tina-quant Cardiac high sensitivity CRP III. Two human serum samples were made by spiking a serum pool with CRP. The two high pools were diluted with a serum pool containing a low CRP concentration to create 15 levels each (including high pools). Each level was measured in triplicate on 1 analyzer using 3 reagent lots. The data supports the claim that no false result occurs up to a CRP concentration of 1000 mg/L due to hook effect.
The labeling states: HAMA - Although measures were taken to minimize interference caused by human anti-mouse antibodies, erroneous findings may be obtained from samples taken
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from patients who have been treated with monoclonal mouse antibodies or have received them for diagnostic purposes.
4. Assay Reportable Range:
Measuring range of 0.150 – 10.0 mg/L.
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
Traceability: This method has been standardized against the certified reference material in human serum of the IRMM (Institute for Reference Materials and Measurements) ERM-DA474/IFCC.
Sample stability
A study was conducted to verify sample stability with the candidate device. The results support the sponsor’s sample stability claims as reported in the labeling:
Stability in serum and Li-heparin plasma:
14 days at 15-25 °C
28 days at 2-8 °C
12 months at -20 °C (±5 °C)
Stability in K2 EDTA plasma:
2 days at 15-25 °C
28 days at 2-8 °C
12 months at -20 °C (±5 °C)
Studies show that specimens can be frozen and thawed up to 4 times.
6. Detection Limit:
Detection limits were determined per recommendations in CLSI EP17-A2 guideline.
For determination of Limit of Blank (LoB), one analyte-free saline (0.9% NaCl) sample was measured with three reagent lots in 6 runs, each run with 10-fold determination, distributed over 3 days, on one cobas c 503 analyzer. Data analysis is based on determination of the 95th percentile of the 60 measured values. The 95th percentile is the average of the 57th and 58th value.
The Limit of Detection (LoD) is the lowest concentration of CRP that can be detected with a probability of 95%. Five different human serum samples containing low levels of CRP were diluted with analyte-free saline (0.9% NaCl) to be within the range of LoB up to approximately 4X the specified LoB. The 5 samples were measured on three lots with 2-fold determination per run. Six runs distributed over 3 days on one instrument were performed. Data analysis was based on determination of the 60 measured values of the five low analyte samples.
The Limit of Quantitation (LoQ) is the lowest concentration of analyte which can be quantified with a CV of no more than 20.0%. Five different native human serum samples containing CRP within the range of LoB up to approximately 2x the specified LoQ were used for testing. The 5 samples were measured on three reagent lots with 5-fold determination per
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run. Six runs distributed over 5 days on one instrument were performed. The results of the studies are reported below:
LoB = 0.100 mg/L
LoD = 0.150 mg/L
LoQ = 0.150 mg/L
7. Assay Cut-Off:
Not applicable.
B Comparison Studies:
1. Method Comparison with Predicate Device:
A method comparison of the Tina-quant Cardiac high sensitivity CRP III on one cobas c 503 analyzer versus the predicate device was performed. One-hundred four unaltered native serum samples were tested in 1 run in singlet using 1 lot of reagent. The method comparison study was evaluated by Passing-Bablok regression analysis and is summarized below:
| N | Slope | Intercept | r | Test Range (mg/L) | Claimed Measuring Range (mg/L) |
| --- | --- | --- | --- | --- | --- |
| 104 | 1.068 | 0.0302 | 0.999 | 0.395 – 8.59 | 0.150 – 10.0 |
| MDL | Predicted Bias [%] | Lower Limit 95% CI | Upper Limit 95% CI |
| --- | --- | --- | --- |
| 1 mg/L | 3.8 | 2.1 | 5.4 |
| 3 mg/L | 5.8 | 4.9 | 6.5 |
The sponsor provided information to support that the comparison and the predicted biases at each medical decision level (MDL) between the candidate device and the device cleared in K033908 are similar to the comparison and the predicted biases between the candidate and predicate device reported above.
2. Matrix Comparison:
A matrix comparison study was performed to demonstrate the equivalence between serum and plasma samples when measuring CRP using the candidate device. Matched native human serum and plasma (K2 EDTA and Lithium Heparin) samples were tested in singlicate. Seventy samples were tested across the assay range. The results were analyzed using Passing-Bablok regression and are shown below.
| Specimen Type | N | Slope | Intercept | r | Test Range (mg/L) |
| --- | --- | --- | --- | --- | --- |
| K2EDTA plasma | 70 | 1.023 | -0.029 | 0.999 | 0.185 – 9.23 |
| Lithium Heparin plasma | 70 | 1.028 | -0.027 | 1.000 | |
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C Clinical Studies:
1. Clinical Sensitivity:
Not applicable.
2. Clinical Specificity:
Not applicable.
3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.
D Clinical Cut-Off:
Not applicable.
E Expected Values/Reference Range:
A statement of the CDC/AHA from 2003 recommended the following hsCRP cut-off points (tertiles) for CVD risk assessment for adults $^{1,2}$
| HsCRP level (mg/L) | Relative risk |
| --- | --- |
| < 1.00 | Low |
| 1.00-3.00 | Average |
| > 3.00 | High |
$^{1}$ Pearson TA, Mensah GA, Alexander RW, et al. Markers of Inflammation and Cardiovascular Disease. Application to Clinical and Public Health Practice. A Statement for Healthcare Professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 2003;107:499-511.
$^{2}$ Ridker PM. Clinical Application of C-Reactive Protein for Cardiovascular Disease Detection and Prevention. Circulation 2003;107:363-369.
VIII Proposed Labeling:
The labeling supports the finding of substantial equivalence for this device.
IX Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
