(46 days)
The Tina-quant® CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
The Tina-quant® CRP (latex) HS Test System is a latex particle-enhanced immunoturbidimetric test for the measurement of C-reactive protein in human serum or plasma.
The provided submission describes an in vitro diagnostic device (IVD) for measuring C-reactive protein (CRP), the "Tina-Quant® CRP (Latex) HS Test System." This is a Class II device and the submission seeks substantial equivalence to existing devices. Therefore, the information provided focuses on comparing the new device's specifications and performance to its predicates, rather than presenting a novel clinical study with independent acceptance criteria for a new type of device.
Here's an analysis based on the provided text, addressing your points:
1. Table of Acceptance Criteria and Reported Device Performance
The submission does not explicitly state "acceptance criteria" in the traditional sense of a specified threshold that the device needed to meet in a new clinical study. Instead, it demonstrates substantial equivalence by comparing the performance characteristics of the new device against its predicate devices. The implicit acceptance criterion is that the performance characteristics of the new device should be comparable or equivalent to the predicate devices.
| Characteristic | Tina-Quant® CRP (Latex) HS (modified intended use) | Predicate Device Tina-Quant® CRP (Latex) HS (K003400) | Predicate Device Dade-Behring N High Sensitivity CRP (K033908) |
|---|---|---|---|
| Intended Use | Extended to include assessment of CAD risk and recurrent event prognosis in ACS/stable CAD. | Quantitative determination of CRP in human serum/plasma for inflammatory disorders. | Quantitative determination of CRP in human serum/plasma for inflammatory disorders, CAD risk, and recurrent event prognosis in ACS/stable CAD. |
| Assay Principle | Same as K003400 (Latex particle-enhanced immunoturbidimetric test) | Latex particle-enhanced immunoturbidimetric test | Particle-enhanced agglutination with nephelometric detection |
| Instrument | Same as K003400 (Roche/Hitachi family of analyzers) | Roche/Hitachi family of analyzers | Dade-Behring BN Systems (nephelometric systems) |
| Reagent Stability | Same as K003400 (Unopened: up to stated expiration date at 2-8°C; On board: 90 days) | Unopened: up to stated expiration date at 2-8°C; On board: 90 days | Unopened: up to stated expiration date at 2-8°C; Opened: 4 weeks |
| Sample Type | Same as K003400 (Human serum and plasma) | Human serum and plasma | Human serum, and heparin and EDTA plasma |
| Traceability/Standardization | Same as both predicates (IFCC/BCR/CAP reference preparation CRM 470) | IFCC/BCR/CAP reference preparation CRM 470 | IFCC/BCR/CAP reference preparation CRM 470 |
| Measuring Range | Same as K003400 (0.1 – 20 mg/L without dilution, 0.1 - 300 mg/L with dilution) | 0.1 – 20 mg/L without dilution, 0.1 - 300 mg/L with dilution | 0.175 – 1100 mg/L with dilution |
| Lower Detection Limit | Same as K003400 (0.03 mg/L) | 0.03 mg/L | 0.175 mg/L |
| Within-run precision (%CV) | Same as K003400 | Control: 0.43% (4.27 mg/L), 0.41% (11.62 mg/L); Human serum: 1.34% (0.55 mg/L), 0.28% (12.36 mg/L) | 2.5% (0.5 mg/L), 3.8% (1.3 mg/L), 2.1% (2.1 mg/L), etc. |
| Between-run precision (%CV) | Same as K003400 | Control: 2.70% (4.34 mg/L), 3.45% (11.90 mg/L); Human serum: 5.70% (0.52 mg/L), 2.51% (10.98 mg/L) | 3.1% (0.5 mg/L), 3.8% (1.1 mg/L), 3.4% (2.1 mg/L), etc. |
| Functional Sensitivity (CV < 10%) | Same as K003400 (0.11 mg/L) | 0.11 mg/L | Not available |
| Limitations/Interferences | Same as K003400 (No interference from high bilirubin, hemoglobin, triglycerides; specific L index values) | No interference from Bilirubin up to 230 mg/L, Hemoglobin up to 36 g/L, Triglycerides up to 7.4 g/L; Highly lipemic samples must not be tested. | No significant interference up to I index of 60, H index of 1000, L index of 1000 (at CRP > 5mg/L); RF < 1200 IU/mL; No high dose hook effect up to 1000 mg/L. |
2. Sample Size Used for the Test Set and Data Provenance
The document does not detail specific "test set" sample sizes or data provenance (country of origin, retrospective/prospective) in the context of a new clinical performance study for the modified device. Instead, it refers to the performance characteristics being "Same as K003400" or derived from studies supporting the predicate devices. The data presented for precision (within-run, between-run) are typically derived from internal laboratory studies using control materials and human serum/plasma, rather than a broad patient test set for the intended use claims.
For precision, the numbers of samples/replicates are not specified, but typically these studies use multiple replicates of control materials and patient samples across several runs to establish these coefficients of variation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
Given this is an IVD for quantitative measurement of a biomarker, "ground truth" is typically established by reference methods or validated laboratory measurements rather than expert consensus on diagnostic images or clinical assessments. The submission refers to "IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619)" for traceability/standardization, which is the ground truth for calibration and accuracy. There is no mention of human experts defining ground truth for performance evaluation in this type of submission.
4. Adjudication Method for the Test Set
Not applicable as this is an IVD measuring a biomarker. Adjudication methods are typically used in clinical trials or imaging studies where subjective interpretation or complex clinical outcomes require consensus.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Improvement with AI vs. Without AI Assistance
Not applicable. This device is not an AI-assisted diagnostic tool or an imaging device requiring human reader interpretation. It is a laboratory assay.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study Was Done
Not applicable. This is a laboratory diagnostic assay, not an algorithm or AI system. The performance presented is inherently "standalone" in the sense that it measures the device's analytical performance on its own.
7. The Type of Ground Truth Used
The ground truth for the quantitative measurement of CRP is established by reference materials and standardization protocols, specifically "IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619)". This ensures that the CRP measurements are accurate and comparable across different laboratories and devices, aligning with established scientific standards for the analyte.
8. The Sample Size for the Training Set
Not applicable in the context of this device. A "training set" is relevant for machine learning algorithms or AI models. For an IVD like the Tina-Quant CRP assay, performance is established through analytical validation studies (e.g., precision, accuracy, linearity, detection limits, interference) using a variety of human samples (serum, plasma) and control materials. The number of samples used for these analytical studies is not explicitly quantified as a "training set" in the provided K042485 summary.
9. How the Ground Truth for the Training Set Was Established
Not applicable for a non-AI IVD. The calibration and analytical accuracy are established against the aforementioned international reference standard (IFCC/BCR/CAP reference preparation CRM 470).
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OCT 2 9 2004
| Introduction | According to the requirements of 21 CFR 807.92, the following information provides sufficient detail to understand the basis for a determination of substantial equivalence. |
|---|---|
| Submitter name, address, contact | Roche Diagnostics9115 Hague RoadIndianapolis, IN 46250317-521-3723 |
| Contact Person: Theresa M. Ambrose | |
| Date Prepared: September 9, 2004 | |
| Device Name | Proprietary name: Tina-Quant CRP (Latex) HS Test System (C-reactive protein (latex) high sensitive) |
| Common name: hsCRP test system | |
| Classification name: Cardiac C-reactive Protein, Antigen, Antiserum, and Control | |
| Predicate device | The Tina-quant® CRP (latex) HS Test System is substantially equivalent to the currently marketed Roche Tina-quant® CRP (latex) HS Test System cleared under K003400. For purposes of the extended intended use, we claim equivalence to the currently marketed Dade Behring N High Sensitivity CRP (K033908) |
| Device Description | The Tina-quant® CRP (latex) HS Test System is a latex particle-enhanced immunoturbidimetric test for the measurement of C-reactive protein in human serum or plasma. |
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510(k) Summary, Continued
Intended use The Tina-quant® CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome. The below table compares Tina-Quant® CRP (Latex) HS with the predicate Comparison to
predicate device
devices, Tina-Quant® CRP (Latex) HS (K003400), and Dade-Behring N High Sensitivity CRP (K033908).
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510(k) Summary, Continue
Substantial equivalence, comparison table.
| Substantial equivalence: comparison tableCharacteristic | Tina-Quant® CRP (Latex) HS(modified intended use) | Predicate deviceTina-Quant® CRP (Latex) HS(K003400) | Predicate deviceDade-Behring N High SensitivityCRP (K033908) | |
|---|---|---|---|---|
| Intended Use | The Tina-quant® CRP (Latex) HighSensitive Immmunoturbidimetricassay is for the in vitro quantitativedetermination of C-reactive protein(CRP) in human serum and plasmaon Roche automated clinicalchemistry analyzers. Highly sensitivemeasurement of CRP is of use for thedetection and evaluation ofinflammatory disorders andassociated diseases, infection andtissue injury. Measurement of CRPmay also be used as an aid in theassessment of the risk of futurecoronary heart disease. When used asan adjunct to other laboratoryevaluation methods of acute coronarysyndromes, it may also be anadditional independent indicator ofrecurrent event prognosis in patientswith stable coronary disease or acutecoronary syndrome. | Immunoturbidimetric assay for the invitro quantitative determination ofCRP in human serum and plasma onautomated clinical chemistry analyzers. | N High Sensitivity CRP is an in vitrodiagnostic reagent for the quantitativedetermination of C-reactive protein(CRP) in human serum, and heparinand EDTA plasma by means ofparticle-enhancedimmunonephelometry using BNSystems. In acute phase response,increased levels of a number of plasmaproteins, including C-reactive protein,are observed. Measurement of CRP isuseful for the detection and evaluationof infection, tissue injury,inflammatory disorders, and associateddiseases. Measurements may also beused as an aid in the identification ofindividuals at risk for futurecardiovascular disease. High sensitivityCRP (hsCRP) measurements, whenused in conjunction with traditionalclinical laboratory evaluation of acutecoronary syndromes, may be useful asan independent marker of prognosis forrecurrent events, in patients with stablecoronary disease or acute coronarysyndromes | |
| Characteristic | Indications for Use | Predicate deviceTina-Quant® CRP (Latex) HS(modified intended use) | Predicate deviceTina-Quant® CRP (Latex) HS(K003400) | Predicate deviceDade-Behring N High SensitivityCRP (K033908) |
| Indications forUse | Measurement of CRP is of use forthe detection and evaluation ofinflammatory disorders andassociated diseases, infection andtissue injury. Highly sensitivemeasurement of CRP may also beused as an aid in the assessment ofthe risk of coronary heart disease.When used as an adjunct to otherlaboratory evaluation methods ofacute coronary syndromes, it may bean additional independent indicatorof recurrent event prognosis inpatients with stable coronary diseaseor acute coronary syndrome. | For the quantitative determination ofC-reactive protein in human serum andplasma. In acute phase response,increased levels of a number of plasmaproteins, including C-reactive protein,are observed. Measurement of CRP isuseful for the detection and evaluationof infection, tissue injury,inflammatory disorders, and associateddiseases. | In acute phase response, increasedlevels of a number of plasma proteins,including C-reactive protein, areobserved. Measurement of CRP isuseful for the detection and evaluationof infection, tissue injury,inflammatory disorders, and associateddiseases. Measurements may also beused as an aid in the identification ofindividuals at risk for futurecardiovascular disease. High sensitivityCRP (hsCRP) measurements, whenused in conjunction with traditionalclinical laboratory evaluation of acutecoronary syndromes, may be useful asan independent marker of prognosis forrecurrent events, in patients with stablecoronary disease or acute coronarysyndromes | |
| Assay principle | Same as K003400 | Latex particle-enhancedimmunoturbidimetric test | Particle-enhanced agglutinationwith nephelometric detection | |
| Instrument | Same as K003400 | Roche/Hitachi family of analyzers | Dade-Behring BN Systems(nepholometric systems) | |
| ReagentStability | ||||
| Same as K003400 | Unopened kit: up to the stated expiration date at 2-8 °C On board the analyzer (opened and refrigerated): 90 days | Unopened kit: up to the stated expiration date at 2-8 °C Opened: 4 weeks at stored in closed vial. Do not freeze | ||
| Sample type | Same as K003400 | Human serum and plasma | Human serum, and heparin and EDTA plasma | |
| Traceability/standardization | Same as both predicates | IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) | IFCC/BCR/CAP reference preparation CRM 470 (RPPHS 91/0619) | |
| Measuringrange | Same as K003400 | 0.1 – 20 mg/l without dilution0.1 -300 mg/l extended range with dilution and rerun | 0.175 – 1100 mg/L with dilution | |
| LowerDetection Limit | Same as K003400 | 0.03 mg/L | 0.175 mg/L | |
| Within-runprecision(%CV) | Same as K003400 | Control material 0.43% at 4.27 mg/L 0.41% at 11.62 mg/L Human serum 1.34% at 0.55 mg/L 0.28% at 12.36 mg/L | 2.5% at 0.5 mg/L 3.8% at 1.3 mg/L 2.1% at 2.1 mg/L 2.6% at 14 mg/L 3.9% at 24 mg/L 5.7% at 56 mg/L | |
| Between-runprecision(%CV) | Same as K003400 | Control material 2.70% at 4.34 mg/L 3.45% at 11.90 mg/L Human serum 5.70% at 0.52 mg/L 2.51% at 10.98 mg/L | 3.1% at 0.5 mg/L 3.8% at 1.1 mg/L 3.4% at 2.1 mg/L 4.0% at 15 mg/L 2.3% at 26 mg/L 4.4% at 62 mg/L | |
| FunctionalSensitivity(CV < 10%) | Same as K003400 | 0.11 mg/L | Not available. | |
| Limitations:interferences | Limitations:ResultInterpretation | Expected values | ||
| Same as K003400 | No interference from Bilirubin up to 230 mg/L Hemoglobin up to 36 g/L Triglycerides up to 7.4 g/L Highly lipemic samples that cannotbe clarified by centrifugation (10min at 15000 X G) must not betested. | Same as K003400 | Same as both predicates (both sets ofinformation are provided) | |
| No significant interference up to I index of 60 (60 mg/dL bilirubin) H index of 1000 (1000 mg/dLhemoglobin) L index of 1000 at CRP > 5mg/L(lipemia; intralipid) L index of 800 at CRP > 4mg/L L index of 500 at CRP > 2 mg/L Rheumatoid factors < 1200 IU/mL | Particles that are formed inincompletely clotted serum orplasma or due to proteindenaturation must be removed bycentrifugation prior to testing. | Increases in CRP values are non-specific and should not be interpretedwithout a complete clinical history.When using CRP to assess the risk ofcoronary heart disease results shouldbe compared to previous values. Fordiagnostic purposes, results shouldalways be assessed in conjunction withthe patient's medical history and otherfindings. | Adults: < 5.0 mg/LNeonates 0-3 weeks: 0.1 – 4.1 mg/LChildren (2 months-15 years) 0.1 – 2.8mg/L | |
| No high dose hook effect up to 1000mg/LIn rare cases, gammopathy, inparticular IgM Waldenstrom'smacroglobinemia may causeunreliable results | Relative risk/average hsCRP:Low < 1 mg/LAverage 1.0-3.0 mg/LHigh >3.0 mg/L |
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510(k) Summary, Continued
Predicate device (continued
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/6/Picture/1 description: The image shows the logo for the Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with two snakes coiled around it. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the caduceus symbol. The logo is black and white.
Public Health Service
OCT 2 9 2004
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
Theresa M. Ambrose, Ph.D., DABCC, FACB, RAC Regulatory Principal Roche Diagnostics 9115 Hague Road Indianapolis, IN 46250
Re: K042485
Trade/Device Name: Tina-Ouant® CRP (Latex) HS Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: NQD Dated: September 10, 2004 Received: September 13, 2004
Dear Dr. Ambrose:
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.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA). it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).
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Page 2
This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.
If you desire specific information about the application of labeling requirements to your device. or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.
Sincerely yours,
Jean M. Cooper, US, DVM.
Jean M. Cooper, MS, D.V.M. Director Division of Chemistry and Toxicology Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): N/A K042485
510(k) Number (if known): N/A
Device Name: Tina-Quant® CRP (Latex) HS
Indications For Use:
The Tina-quant® CRP (Latex) High Sensitive Immmunoturbidimetric assay is for the in vitro quantitative determination of C-reactive protein (CRP) in human serum and plasma on Roche automated clinical chemistry analyzers. Measurement of CRP is of use for the detection and evaluation of inflammatory disorders and associated diseases, infection and tissue injury. Highly sensitive measurement of CRP may also be used as an aid in the assessment of the risk of future coronary heart disease. When used as an adjunct to other laboratory evaluation methods of acute coronary syndromes, it may also be an additional independent indicator of recurrent event prognosis in patients with stable coronary disease or acute coronary syndrome.
Prescription Use X (Part 21 CFR 801 Subpart D) AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD) Page 1 of
Carol Benson
Division Sign-Off
of in Vitro Diaar
510(k). K02485
24
§ 866.5270 C-reactive protein immunological test system.
(a)
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.(b)
Classification. Class II (performance standards).