(117 days)
Immunoturbidometric assay for the in vitro quantitative determination of CRP in human serum and plasma on Roche automated clinical chemistry analyzers.
Measurement of c-reactive protein aids in the evaluation of the amount of injury to body tissues.
The C-Reactive Protein Gen 3 assay is a particle enhanced turbidimetric assay. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The precipitate is determined turbidimetrically at 570 nm.
Here's a breakdown of the acceptance criteria and study information for the Tina-Quant C-Reactive Protein Gen. 3 device, based on the provided text:
Acceptance Criteria and Device Performance
The provided document describes modifications to an existing device (Tina-Quant C-Reactive Protein Gen 3) and claims substantial equivalence to its predicate device (Tina-Quant C-Reactive Protein (Latex), K032336). Therefore, the acceptance criteria are implicitly defined by demonstrating comparable core performance characteristics to the predicate device. The information below presents the modified device's performance alongside the predicate's performance for comparison, which serves as the "acceptance criteria" through the lens of substantial equivalence.
Table of Acceptance Criteria (Predicate Performance) and Reported Device Performance (Modified Device)
| Feature | Acceptance Criteria (Predicate Device Performance - K032336) | Reported Device Performance (Modified Device - K082444) |
|---|---|---|
| Measuring Range | Roche/Hitachi 902: 1-265 mg/LRoche/Hitachi 717/Modular D: 1-265 mg/L, 1-398 mg/L with rerunRoche/Hitachi 904/911/912: 1-260 mg/L, 1-520 mg/L with rerunRoche/Hitachi 917/Modular P: 1-280 mg/L, 1-560 mg/L with rerun | Roche/Hitachi 901/912/917/Modular P/Modular D analyzers: 0.3-350 mg/L. Dilution of samples via the rerun function is a 1:2 dilution. |
| Precision (Within Run) | Control 1: Mean (mg/L) 3.36, SD (mg/L) 0.09, %CV 2.76Control 2: Mean (mg/L) 22.17, SD (mg/L) 0.44, %CV 1.96Control 3: Mean (mg/L) 51.12, SD (mg/L) 0.90, %CV 1.77H Pool 1: Mean (mg/L) 5.76, SD (mg/L) 0.14, %CV 2.50H Pool 2: Mean (mg/L) 150.15, SD (mg/L) 1.14, %CV 0.76 | Control 1: Mean (mg/L) 3.6, SD (mg/L) 0.03, %CV 0.85Control 2: Mean (mg/L) 42.2, SD (mg/L) 0.26, %CV 0.61H Pool 1: Mean (mg/L) 0.9, SD (mg/L) 0.03, %CV 4.00H Pool 2: Mean (mg/L) 1.6, SD (mg/L) 0.02, %CV 1.02H Pool 3: Mean (mg/L) 18.4, SD (mg/L) 0.09, %CV 0.48 |
| Precision (Between Run) | Control 1: Mean (mg/L) 3.51, SD (mg/L) 0.16, %CV 4.61Control 2: Mean (mg/L) 22.01, SD (mg/L) 0.62, %CV 2.81Control 3: Mean (mg/L) 50.41, SD (mg/L) 0.94, %CV 1.86H Pool 1: Mean (mg/L) 5.99, SD (mg/L) 0.15, %CV 2.53H Pool 2: Mean (mg/L) 146.31, SD (mg/L) 2.63, %CV 1.80 | Control 1: Mean (mg/L) 3.1, SD (mg/L) 0.08, %CV 2.7Control 2: Mean (mg/L) 41.4, SD (mg/L) 0.86, %CV 2.1H Pool 1: Mean (mg/L) 0.5, SD (mg/L) 0.03, %CV 6.2H Pool 2: Mean (mg/L) 1.5, SD (mg/L) 0.05, %CV 3.3H Pool 3: Mean (mg/L) 39.1, SD (mg/L) 0.73, %CV 1.9 |
| Analytical Sensitivity | Functional Sensitivity: 0.88 mg/LLower Detection Limit: 0.425 mg/L | Limit of Quantitation (Functional Sensitivity): 0.6 mg/LLoB: 0.2 mg/LLoD: 0.3 mg/L |
| Interferences | Icterus: No significant interference up to 60 mg/dLHemolysis: No significant interference up to 950 mg/dLLipemia: No significant interference up to L index of 1700Rheumatoid Factor: No interference up to 1200 IU/mLHigh dose hook effect: No false results up to CRP concentrations of 1200 mg/L | Icterus: same (implicitly up to 60 mg/dL)Hemolysis: No significant interference up to 1000 mg/dLLipemia: No significant interference up to L index of 1000Rheumatoid Factor: same (implicitly up to 1200 IU/mL)High dose hook effect: same (implicitly up to 1200 mg/L) |
| Method Comparison | Slope (Passing Bablok): 1.020Intercept: 0.000Coefficients of correlation (r): 1.000 | Comparison was performed against Tina-Quant C-Reactive Protein (latex) on Hitachi 917. Specific numerical results (slope, intercept, correlation coefficient) for the modified device against the predicate are not provided in this section, but the predicate's values are listed as the reference, implying the modified device aims to match these. |
Study Information
The provided document describes a Special 510(k): Device Modification submission for the Tina-Quant C-Reactive Protein Gen 3 assay. The core of the "study" is a comparison of the modified device's performance characteristics against its predicate device (Tina-Quant C-Reactive Protein (Latex), K032336), to demonstrate substantial equivalence.
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Sample size used for the test set and the data provenance:
- Test Set Sample Size: The document does not explicitly state the specific number of samples used for each test (e.g., precision, interference, method comparison). For the "Method Comparison," it refers to a "Scatter plot showing correlation between two methods for measuring C-Reactive Protein," which implies a collection of patient or control samples were run on both methods. However, the exact count is not given.
- Data Provenance: Not explicitly stated. The studies were conducted by Roche Diagnostics, suggesting internal studies. The country of origin of the data is not mentioned, nor is whether the data was retrospective or prospective.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is an in vitro diagnostic (IVD) device for quantitative determination of CRP. For such devices, "ground truth" is typically established by reference methods or highly accurate analytical techniques, not by expert consensus on interpretations like with imaging. The document traces the device's standardization to CRM 470, which is a certified reference material for proteins. There is no mention of experts establishing a ground truth in the context of clinical interpretation, as this device provides a quantitative measurement.
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Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable. This is an IVD device for quantitative measurement. Adjudication methods like "2+1" typically apply to diagnostic tasks involving human interpretation or subjective assessments, where disagreements between experts need to be resolved.
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If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, an MRMC comparative effectiveness study was not done. This device is an automated in vitro diagnostic assay, not a device that assists human readers (like AI for image analysis). Therefore, comparisons of human reader performance with or without AI assistance are not relevant to this submission.
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If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, effectively, this is a standalone device performance evaluation. The device is an automated clinical chemistry analyzer that quantitatively measures CRP. The performance metrics reported (precision, analytical sensitivity, interference, method comparison) are intrinsic to the device's analytical function without direct human intervention in the result generation process, beyond sample loading and general operation.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Reference material standardization. The device claims traceability to CRM 470 for standardization. This implies that the "ground truth" for the quantitative CRP measurements is established against this internationally recognized reference material, rather than clinical outcomes, pathology, or expert consensus on a diagnostic interpretation.
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The sample size for the training set:
- Not applicable. This document is for a device modification of an in vitro diagnostic assay, not an AI/ML algorithm. Therefore, there isn't a "training set" in the sense of data used to train a machine learning model. The assay's parameters would have been developed and optimized through laboratory experiments, but the concept of a "training set" as commonly understood in AI/ML is not directly relevant here.
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How the ground truth for the training set was established:
- Not applicable. As explained above, there is no "training set" for an AI/ML algorithm. For the initial development and optimization of the assay reagents and methods, ground truth for measuring CRP would typically be established using highly characterized samples with known CRP concentrations (e.g., purified CRP, reference materials like CRM 470, or validated high-accuracy laboratory methods).
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· MAR I 8 2009
510(k) Summary – Tina-Quant C-Reactive Protein Gen. 3
| 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 46250(317) 521 - 3723Contact Person: Kathie J. GoodwinDate Prepared: November 17th, 2008 |
| Submission Purpose | Roche Diagnostics hereby submits this Special 510(k): Device Modification to provide notification of modifications to our Tina-Quant C-Reactive Protein Gen 3 assay. This assay was most recently cleared for use in K032336 on the Roche/Hitachi Clinical Chemistry analyzers. |
Since the K032336 filing, modifications to the CRPL3 assay on the Roche/Hitachi clinical chemistry analyzers include:
- The Interference section of the insert was modified regarding potential HAMA interference.
- The lower detection limit was added to the measuring range section in the package insert according to the product specification of <0.2 mg/L.
- Modification to the insert to clarify when calibration is required.
Modifications prompting this filing include:
- The reagent composition for R2 was modified.
- LOB and LOD values were determined and reported in the insert.
- The functional sensitivity was modified.
- The measuring range for the Roche/Hitachi clinical chemistry analyzers was harmonized to 0.3-350 mg/L.
- The Interference with Hemolysis and Lipemia were modified.
- Only standard anticoagulants were tested and claimed; Na-heparin and Na2 EDTA were not mentioned in the insert.
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| SubmissionHistory | The Tina-Quant C-Reactive Protein assay was originally cleared inK003400. In K032336, the following device modifications werecleared:Broadening the measuring range of the assay Increasing the R1 buffer concentration Deleting citrated plasma and adding K2-EDTA as acceptable specimen types Changing the name of the assay to TQ CRP (latex) |
|---|---|
| Device Name | Proprietary name: Tina-Quant C-Reactive Protein Gen 3 |
| And | Common name: CRPL3 |
| Classification | Classification name: C-Reactive Protein Immunological Test SystemProduct code: DCNRegulation Citation: 866.5270Panel: 82 ImmunologyClass II |
| EstablishmentRegistration | The establishment registration number for Roche Diagnostics GmbHPenzberg is 9610126. |
| DeviceDescription | The C-Reactive Protein Gen 3 assay is a particle enhancedturbidimetric assay. Human CRP agglutinates with latex particlescoated with monoclonal anti-CRP antibodies. The precipitate isdetermined turbidimetrically at 570 nm. |
| Intended use | Immunoturbidometric assay for the in vitro quantitative determination of CRPin human serum and plasma on Roche automated clinical chemistryanalyzers. |
| Substantialequivalence | The Roche Tina-Quant C-Reactive Protein Gen. 3 is substantially equivalentto the Roche Tina-Quant C-Reactive Protein (Latex) (CRPLX) cleared inK032336. |
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Substantial equivalence –
| Feature | Modified Device : Tina-Quant C-Reactive Protein Gen 3 | Predicate Device: Tina-Quant C-Reactive Protein (Latex) (K032336) |
|---|---|---|
| Intended Use | Immunoturbidimetric assay for thein vitro quantitative determinationof CRP in human serum and plasmaon Roche automated clinicalchemistry analyzers. | Immunoturbidimetric assay for the invitro quantitative determination ofCRP in human serum and plasma onautomated clinical chemistry analyzers. |
| Sample Type | SerumPlasma: Li-heparin, K2-/K3-EDTAplasma | SerumPlasma: Li-/Na-heparin, Na-/K3-EDTA, citrate plasma |
| InstrumentPlatform | Roche/Hitachi family includingH902, H912, H917, Mod P and ModD.(See section 4 (Other SupportiveInformation) for additionalinformation on application to thecobas c501 and c311 clinicalchemistry analyzers.) | Roche/Hitachi family including H902,H911, H912, H917, Mod P and ModD. |
| Calibrator | Same | PresiSet Serum Proteins and CFASProteins |
| Calibrationfrequency | After entering new calibrator values,after reagent lot change and asrequired following quality controlprocedures | After reagent lot change and asrequired following quality controlprocedures |
| Controls | Same | CRP T Control N, Precinorm Protein,Precipath Protein |
| Traceability | Same | Standardized against CRM 470 |
| ReagentStability | Same | • Up to expiration at 2-8 deg C• R1/R2: 84 days opened andrefrigerated on the analyzer |
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| Measuring Range | Roche/Hitachi 901/912/917/Modular P/Modular D analyzers:0.3-350 mg/L Dilution of samples via the rerun function is a 1:2 dilution. | Roche/Hitachi 902: 1-265 mg/L Roche/Hitachi 717/Modular D: 1-265 mg/L, 1-398 mg/L with rerun Roche/Hitachi 904/911/912: 1-260 mg/L, 1-520 mg/L with rerun Roche/Hitachi 917/Modular P: 1-280 mg/L, 1-560 mg/L with rerun | ||||||
|---|---|---|---|---|---|---|---|---|
| Precision | Within Run: | Within Run: | ||||||
| Sample | Mean (mg.L) | SD (mg/L) | %CV | Sample | Mean (mg.L) | SD (mg/L) | %CV | |
| Control 1 | 3.6 | 0.03 | 0.85 | Control 1 | 3.36 | 0.09 | 2.76 | |
| Control 2 | 42.2 | 0.26 | 0.61 | Control 2 | 22.17 | 0.44 | 1.96 | |
| H Pool 1 | 0.9 | 0.03 | 4.00 | Control 3 | 51.12 | 0.90 | 1.77 | |
| H Pool 2 | 1.6 | 0.02 | 1.02 | H Pool 1 | 5.76 | 0.14 | 2.50 | |
| H Pool 3 | 18.4 | 0.09 | 0.48 | H Pool 2 | 150.15 | 1.14 | 0.76 | |
| Between Run: | Between Run: | |||||||
| Sample | Mean (mg.L) | SD (mg/L) | %CV | Sample | Mean (mg.L) | SD (mg/L) | %CV | |
| Control 1 | 3.1 | 0.08 | 2.7 | Control 1 | 3.51 | 0.16 | 4.61 | |
| Control 2 | 41.4 | 0.86 | 2.1 | Control 2 | 22.01 | 0.62 | 2.81 | |
| H Pool 1 | 0.5 | 0.03 | 6.2 | Control 3 | 50.41 | 0.94 | 1.86 | |
| H Pool 2 | 1.5 | 0.05 | 3.3 | H Pool 1 | 5.99 | 0.15 | 2.53 | |
| H Pool 3 | 39.1 | 0.73 | 1.9 | H Pool 2 | 146.31 | 2.63 | 1.80 | |
| Analytical Sensitivity | Limit of Quantitation (Functional Sensitivity): 0.6 mg/LLoB: 0.2 mg/LLoD: 0.3 mg/L | Functional Sensitivity: 0.88 mg/L | ||||||
| Analytical Specificity | Not Claimed | Lower Detection Limit: 0.425 mg/L |
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| Interferences | ||
|---|---|---|
| Icterus: same | Icterus: No significant interference up to 60 mg/dL | |
| Hemolysis: No significant interference up to 1000 mg/dL | Hemolysis: No significant interference up to 950 mg/dL | |
| Lipemia: No significant interference up to L index of 1000 | Lipemia: No significant interference up to L index of 1700 | |
| Rheumatoid Factor: same | Rheumatoid Factor: No interference up to 1200 IU/mL | |
| High does hook effect: same | High does hook effect: No false results up to CRP concentrations of 1200 mg/L | |
| Expected Values | same | <5.0 mg/L |
| Method Comparison | Tina-Quant C-Reactive Protein Gen 3 on Hitachi 917 compared to Tina-Quant C-Reactive Protein (latex) on Hitachi 917 | |
| Slope (Passing Bablok): 1.020 | ||
| Intercept: 0.000 | ||
| Coefficients of correlation (r): 1.000 | ||
| Image: Scatter plot showing correlation between two methods for measuring C-Reactive Protein. |
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/5/Picture/1 description: The image contains the words "Public Health Service" in a simple, sans-serif font. The text is arranged on a single line, with each word clearly legible. The overall impression is clean and straightforward, suggesting an official or institutional context.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
MAR 1 8 2009
Roche Diagnostics Corp. c/o Ms. Kathie J. Goodwin Regulatory Affairs Consultant 9115 Hague Rd., P.O. Box 50416 Indianapolis, Indiana 46250-0416
Re: K083444
Trade/Device Name: Tina-Quant C-Reactive Protein (Latex) Gen. 3 Regulation Number: 21 CFR 866.5270 Regulation Name: C- reactive protein immunological test system Regulatory Class: II Product Code: DCN Dated: January 26, 2009 Received: February 2, 2009
Dear Ms. Goodwin:
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 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). You may, therefore, market the device, subject to the general controls provisions of the Act. However, you are responsible to determine that the medical devices you use as components in the [kit/tray] have either been determined as substantially equivalent under the premarket notification process (Section 510(k) of the act), or were legally on the market prior to May 28, 1976, the enactment date of the Medical Device Amendments. Please note: If you purchase your device components in bulk (i.e., unfinished) and further process (e.g., sterilize) you must submit a new 510(k) before including these components in your kit/tray. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, and 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 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.
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Page 2- Ms. Goodwin
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); 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.
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 advice for your device on the labeling regulation, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at 240- 276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For question regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at 240-276-3474. For questions regarding the reporting of device adverse events (Medical Device Reporting (MDR), please contact the Division of Surveillance Systems at 240-276-3464. You many obtain other general information on your responsibilities under the Act from the Division of Small Manufactuers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (240) 276-3150 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Maria M. Chan
Maria M. Chan, Ph.D. Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostic Device Evaluation and Safety
Center for Devices and Radiological Health
Enclosure
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Indication for Use
510(k) Number (if known):
Device Name: Tina-Quant C-Reactive Protein (Latex) Gen. 3
Indication For Use:
Measurement of c-reactive protein aids in the evaluation of the amount of injury to body tissues.
× Prescription Use _ (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)
Division Signoff
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K083444
§ 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).