(28 days)
VITROS Chemistry Products CRP Slides:
For in vitro diagnostic use only.
VITROS Chemistry Products CRP Slides quantitatively measure C-reactive protein (CRP) concentration in serum and plasma using VITROS 250/350/5.1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System.
C-reactive protein is synthesized by the liver and is one of the acute phase response, increased concentrations of a number of plasma proteins, including CRP, are observed. CRP concentration measurements are useful in the detection and evaluation of inflammatory disorders, tissue injury, and infections.
VITROS Chemistry Products Calibrator Kit 7:
For in vitro diagnostic use only.
VITROS Chemistry Products Calibrator Kit 7 is used to calibrate VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of CRP.
The VITROS CRP Slide method is performed using the VITROS CRP Slides and the VITROS Chemistry Products Calibrator Kit 7 on VITROS Chemistry and Integrated Systems.
The VITROS CRP Slide is a multilayered, analytical element coated on a polyester support. The immuno-rate format for CRP is based on an enzymatic heterogeneous, sandwich immunoassay format. In this format a derivative of phosphorylcholine (PC) is covalently bound to polystyrene polymer beads and in the presence of calcium serves as a capture agent. Monoclonal anti-CRP antibody conjugated to horseradish peroxidase (HRP) serves as a signal generator.
A drop of patient sample is deposited on the slide and is evenly distributed by the spreading layer to the underlying layers. CRP in the sample binds to PC-linked capture beads and anti-CRP antibody labeled with horseradish peroxidase to form an insoluble sandwich complex in Incubation 1. The subsequent addition of 12 microliters of VITROS Immuno-Wash Fluid to the slide removes unbound materials from the read area, while also providing the hydrogen peroxide required for the enzyme-mediated oxidation of leuco dye.
The reflection density of the dye is measured after the addition of VITROS Immuno-Wash Fluid at the end of Incubation 2. This reflection density is directly proportional to the concentration of CRP in the sample. To determine if an adequate wash has occurred, the wash detection dye is read at 540 nm immediately after Incubation 2.
The VITROS Calibrator Kit 7 is prepared from processed human serum to which purified human C-reactive protein, inorganic salts, and preservatives have been added.
The human blood products provided as components of VITROS Calibrator Kit 7 have been tested at the individual donor level and found nonreactive for hepatitis B surface antigen (HBsAg), antibody to HCV, and antibody to HIV using FDA approved methods.
1. Table of Acceptance Criteria and Reported Device Performance:
The document describes performance characteristics rather than explicit "acceptance criteria" with pass/fail thresholds in a formal table. However, we can infer the criteria from the studies conducted.
| Performance Characteristic | Acceptance Criteria (Inferred) | Reported Device Performance |
|---|---|---|
| Method Comparison | Close agreement with predicate device (VITROS Chemistry Products CRP assay traceable to ERM-DA472) as demonstrated by slope and y-intercept 95% Confidence Intervals (CI) embracing 1.0 and 0 respectively (or very near). | VITROS 350 Chemistry System: Slope: 1.009 (1.008 to 1.010); y-intercept: -4.819 (-4.886 to -4.751) VITROS 5,1 FS Chemistry System: Slope: 1.009 (1.007 to 1.011); y-intercept: -4.938 (-5.070 to -4.805) VITROS 4600 Chemistry System: Slope: 1.009 (1.006 to 1.012); y-intercept: -4.952 (-5.114 to -4.790) VITROS 5600 Chemistry System: Slope: 1.009 (1.006 to 1.011); y-intercept: -4.905 (-5.052 to -4.759) |
| Limits of Blank (LOB) | Low value, indicating minimal signal in the absence of analyte. | 2.03 mg/L |
| Limits of Detection (LOD) | Low value, indicating sensitivity to detect low concentrations. | 2.72 mg/L |
| Limits of Quantitation (LOQ) | Low value, indicating ability to quantify at low concentrations. | 4.80 mg/L |
| Linearity | Linear response across the measuring range with acceptable deviation from ideal linearity. | Linear range found to extend across the measuring range of 5 to 90 mg/L. |
| Analytical Range | Consistent and validated measuring range across different systems. | 5 to 90 mg/L (for VITROS 250/350, 5,1 FS, 4600 Chemistry System, and VITROS 5600 Integrated System) |
2. Sample Size Used for the Test Set and Data Provenance:
- Sample Size: 98 to 103 human serum samples were used for the method comparison study.
- Data Provenance: The document states "Human serum samples were tested." The country of origin is not specified, but the context implies it was likely from a clinical setting. It is a retrospective dataset as it involves testing existing samples.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
This information is not explicitly provided. The "ground truth" for the test set is established by comparing the new device's readings against a "predicate method" (VITROS Chemistry Products CRP assay traceable to ERM-DA472). The document describes this predicate as generating the reference measurements, not a panel of experts.
4. Adjudication Method for the Test Set:
Not applicable. The study compares the new device's measurements to a predicate device's measurements, not to expert consensus.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
Not applicable. This device is an in vitro diagnostic (IVD) assay for quantitative measurement, not an AI or imaging device requiring human reader interpretation or assistance.
6. Standalone Performance:
Yes, the studies described (Method Comparison, Limits of Blank, Detection, and Quantitation, Linearity, Analytical Range) directly assess the standalone performance of the VITROS Chemistry Products CRP Slides without human-in-the-loop performance. The results are generated solely by the device and its associated systems.
7. Type of Ground Truth Used:
The ground truth used for performance evaluation is comparative measurement against a legally marketed predicate device (VITROS Chemistry Products CRP assay traceable to ERM-DA472), which itself has established performance characteristics and traceability to a recognized international reference material (ERM-DA472). In essence, it's a reference measurement from an established method.
8. Sample Size for the Training Set:
The document does not mention a "training set." This type of in vitro diagnostic device typically undergoes analytical validation studies (as described) rather than machine learning model training.
9. How the Ground Truth for the Training Set Was Established:
Not applicable, as there is no training set for this device as described. Its performance is evaluated through direct analytical studies.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
ORTHO-CLINICAL DIAGNOSTICS, INC. MS. JESSICA MILLER SENIOR REGULATORY AFFAIRS ASSOCIATE 100 INDIGO CREEK DRIVE ROCHESTER, NEW YORK 14626
Re: K152433
Trade/Device Name: VITROS Chemistry Products CRP Slides VITROS Chemistry Products Calibrator Kit 7 Regulation Number: 21 CFR 866.5270 Regulation Name: C-Reactive Protein immunological test system Regulatory Class: II Product Code: DCK, JIT Dated: August 26, 2015 Received: August 27, 2015
Dear Ms. Miller:
September 24, 2015
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 vour 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
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807): labeling (21 CFR Parts 801 and 809); medical device reporting of medical devicerelated adverse events) (21 CFR 803); 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.
If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR 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.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevicesforYou/Industry/default.htm.
Sincerely yours,
Kelly Oliner -S
FOR
Leonthena Carrington, MS, MBA, MT (ASCP) Director Division of Immunology and Hematology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K152433
Device Name
VITROS Chemistry Products CRP Slides and VITROS Chemistry Products Calibrator Kit 7
Indications for Use (Describe)
VITROS Chemistry Products CRP Slides:
For in vitro diagnostic use only.
VITROS Chemistry Products CRP Slides quantitatively measure C-reactive protein (CRP) concentration in serum and plasma using VITROS 250/350/5.1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System.
C-reactive protein is synthesized by the liver and is one of the acute phase response, increased concentrations of a number of plasma proteins, including CRP, are observed. CRP concentration measurements are useful in the detection and evaluation of inflammatory disorders, tissue injury, and infections.
VITROS Chemistry Products Calibrator Kit 7:
For in vitro diagnostic use only.
VITROS Chemistry Products Calibrator Kit 7 is used to calibrate VITROS 250/350/5,1 FS and 4600 Chemistry Systems and the VITROS 5600 Integrated System for the quantitative measurement of CRP.
| 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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510(k) Summary VITROS Chemistry Products CRP Slides, Calibrator Kit 7
A summary of 510(k) safety and effectiveness information in accordance with the requirements of 21 CFR 807.92.
| Submitter Information | |
|---|---|
| Name | Ortho-Clinical Diagnostics, Inc. |
| Address | 100 Indigo Creek DriveRochester, New York 14626 |
| Phone number | 908-218-8173 |
| Fax number | 908-218-8168 |
| Establishment Registration Number | 1319681 |
| Name of contact person | Jessica Miller |
| Date prepared | August 26, 2015 |
| Name of devices | |
| Trade or proprietary name | VITROS Chemistry Products CRP SlidesVITROS Chemistry Products Calibrator Kit 7 |
| Common or usual name | C-reactive protein immunological test system |
| Classification name | C-reactive protein, antigen, antiserum, and control |
| Classification panel | Immunology |
| Regulation | 21 CFR 866.5270: C-Reactive Protein immunological testsystem21 CFR 862.1150: CalibratorClassification: Class II |
| Product Code(s) | DCK, JIT |
| Legally marketeddevice(s) to whichequivalence isclaimed | The VITROS Chemistry Products CRP Slides and VITROSChemistry Products Calibrator Kit 7 (modified) is substantiallyequivalent to the VITROS Chemistry Products CRP Slides andVITROS Chemistry Products Calibrator Kit 7 (current),cleared March, 2003 (K030626). |
| Device description | The VITROS CRP Slide method is performed using theVITROS CRP Slides and the VITROS Chemistry ProductsCalibrator Kit 7 on VITROS Chemistry and IntegratedSystems.The VITROS CRP Slide is a multilayered, analytical elementcoated on a polyester support. The immuno-rate format forCRP is based on an enzymatic heterogeneous, sandwichimmunoassay format. In this format a derivative ofphosphorylcholine (PC) is covalently bound to polystyrenepolymer beads and in the presence of calcium serves as acapture agent. Monoclonal anti-CRP antibody conjugated tohorseradish peroxidase (HRP) serves as a signal generator.A drop of patient sample is deposited on the slide and is evenlydistributed by the spreading layer to the underlying layers.CRP in the sample binds to PC-linked capture beads and anti-CRP antibody labeled with horseradish peroxidase to form aninsoluble sandwich complex in Incubation 1. The subsequentaddition of 12 $ \mu $ L of VITROS Immuno-Wash Fluid to the slideremoves unbound materials from the read area, while alsoproviding the hydrogen peroxide required for the enzyme-mediated oxidation of leuco dye.The reflection density of the dye is measured after the additionof VITROS Immuno-Wash Fluid at the end of Incubation 2.This reflection density is directly proportional to theconcentration of CRP in the sample. To determine if anadequate wash has occurred, the wash detection dye is read at540 nm immediately after Incubation 2.The VITROS Calibrator Kit 7 is prepared from processedhuman serum to which purified human C-reactive protein,inorganic salts, and preservatives have been added.The human blood products provided as components ofVITROS Calibrator Kit 7 have been tested at the individualdonor level and found nonreactive for hepatitis B surfaceantigen (HBsAg), antibody to HCV, and antibody to HIVusing FDA approved methods. |
| IntendedUse/Indications for Use | CRP Slide:For in vitro diagnostic use only.VITROS Chemistry Products CRP Slides quantitativelymeasure C-reactive protein (CRP) concentration in serum andplasma using VITROS 250/350/5,1 FS and 4600 ChemistrySystems and the VITROS 5600 Integrated System |
| C-reactive protein is synthesized by the liver and is one of theacute phase proteins. In the acute phase response, increased | |
| concentrations of a number of plasma proteins, including CRP, | |
| are observed. CRP concentration measurements are useful in | |
| the detection and evaluation of inflammatory disorders, tissue | |
| injury, and infections. | |
| Calibrator Kit 7: | |
| For in vitro diagnostic use only. | |
| VITROS Chemistry Products Calibrator Kit 7 is used to | |
| calibrate VITROS 250/350/5,1 FS and 4600 Chemistry | |
| Systems and the VITROS 5600 Integrated System for the | |
| quantitative measurement of CRP. |
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Comparison with Predicate Devices:
Table 1: VITROS Chemistry Products CRP Slides
| Characteristic | Predicate [VITROS CRP Slides(Current), K030626] | New Device [VITROS CRPSlides (Modified)] |
|---|---|---|
| Intended Use | For in vitro diagnostic use only.VITROS Chemistry Products CRPSlides quantitatively measure C-reactive protein (CRP) concentrationin serum and plasma using VITROS250/350/950/5,1 FS and 4600Chemistry Systems and the VITROS5600 Integrated System. | For in vitro diagnostic use only.VITROS Chemistry Products CRPSlides quantitatively measure C-reactive protein (CRP)concentration in serum and plasmausing VITROS 250/350/5,1 FS and4600 Chemistry Systems and theVITROS 5600 Integrated System. |
| Basic Principle | Fixed-point immuno-rate | No Change |
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| Characteristic | Predicate [VITROS CRP Slides (Current), K030626] | New Device [VITROS CRP Slides (Modified)] |
|---|---|---|
| ReagentComposition | Reactive Ingredients:Immobilized phosphorylcholine;mouse anti-CRPantibody labeled with horseradishperoxidase; calciumchloride; and 2-(3,5-dimethoxy-4-hydroxyphenyl)-4,5-bis(4-dimethylaminophenyl)imidazole (leuco dye)Other Ingredients:Binders, buffer, surfactants, cross-linking agent, polymer beads,proteins, stabilizers and washdetection dye. | No Change |
| Sample volume | 11 μL | No Change |
| Sample type | Serum, plasma | No Change |
| Assay RangeSerum, Plasma | 5 - 90 mg/L | No Change |
| Incubation timeand temperature | 7.5 minutes at 37°C | No Change |
| CalibrationTraceability ofValues (VITROSChemistryProductsCalibrator Kit 7) | IRMM Reference Material ERM-DA472 | IRMM Reference Material ERM-DA474/IFCC |
Table 1: VITROS Chemistry Products CRP Slides
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| Characteristic | Predicate [VITROS Calibrator Kit 7(Current), K030626] | New Device[VITROS Calibrator Kit 7(Modified)] |
|---|---|---|
| Intended Use | For in vitro diagnostic use only.VITROS Chemistry Products CalibratorKit 7 is used to calibrate VITROS250/350/950/5,1 FS and 4600 ChemistrySystems and the VITROS 5600 IntegratedSystem for the quantitative measurementof CRP. | For in vitro diagnostic useonly.VITROS Chemistry ProductsCalibrator Kit 7 is used tocalibrate VITROS250/350/5,1 FS and 4600Chemistry Systems and theVITROS 5600 IntegratedSystem for the quantitativemeasurement of CRP. |
| Matrix/Ingredients | Liquid; processed human serum to whichpurified human C-reactive protein,inorganic salts, and preservatives havebeen added. | No Change |
| Traceability ofValues | IRMM Reference Material ERM-DA472 | IRMM Reference MaterialERM-DA474/IFCC |
| Nominal Valuesfor CRP | Vial 1: 7 mg/LVial 2: 25 mg/LVial 3: 100 mg/L | No Change |
Table 2: VITROS Chemistry Products Calibrator Kit 7
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Performance Summary:
Substantial Equivalence was demonstrated by testing several performance characteristics including method comparison, linearity and detection (analytical range).
Method Comparison:
Method Comparison testing followed CLSI Protocol EP09-A3, Measurement Procedure Comparison and Bias Estimation Using Patient Samples. Human serum samples were tested with the VITROS Chemistry Products CRP assay traceable to ERM-DA474 and the obtained results were compared to the predicate method (VITROS Chemistry Products CRP assay traceable to ERM-DA472). 98 to103 samples ranging from 5 to 90 mg/L were tested with both assays. The correlation between the assays on each VITROS System is summarized below.
| Analyzer | Parameter | Result |
|---|---|---|
| VITROS 350 ChemistrySystem | Slope (95% CI) | 1.009 (1.008 to1.010) |
| y-intercept (95% CI) | -4.819 (4.886 to -4.751) | |
| VITROS 5,1 FS ChemistrySystem | Slope (95% CI) | 1.009 (1.007 to 1.011) |
| y-intercept (95% CI) | -4.938 (-5.070 to -4.805) | |
| VITROS 4600 ChemistrySystem | Slope (95% CI) | 1.009 (1.006 to 1.012) |
| y-intercept (95% CI) | -4.952 (-5.114 to -4.790) | |
| VITROS 5600 ChemistrySystem | Slope (95% CI) | 1.009 (1.006 to 1.011) |
| y-intercept (95% CI) | -4.905 (-5.052 to -4.759) |
Limits of blank, detection, and quantitation:
The Limit of Blank (LOB), Limit of Detection (LOD), and Limit of Quantitation (LOQ) of the VITROS CRP assay were determined according to CLSI EP17-A2: Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures. The following limits were determined:
LOB: 2.03 mg/L LOD: 2.72 mg/L LOO: 4.80 mg/L
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Linearity:
Linearity was determined following CLSI EP6-A: Evaluation of the Linearity of Quantitative Measurement Procedures: a Statistical Approach: Approved Guideline. A high CRP serum pool was intermixed with a low serum pool to generate 14 concentration levels each tested in six replicate determinations. Linear results were compared to 2nd and 3rd order polynomial fits against a pre-specified allowable error. The linearity range was found to extend across the measuring range of 5 to 90 mg/L.
Analytical Range (Serum/Plasma):
Results from linearity and detection studies support the analytical measuring range of the VITROS Chemistry Products Slides on the VITROS Systems as seen below.
| Analyzers | VITROS Chemistry Products CRP Assay |
|---|---|
| VITROS 250/350, 5,1 FS, and 4600Chemistry System, VITROS 5600Integrated System | 5 to 90 mg/L |
Conclusion:
The conclusions drawn from the nonclinical tests (discussed above) demonstrate the modified VITROS Chemistry Products CRP Slides and VITROS Chemistry Products Calibrator Kit 7 are as safe and effective as the predicate devices. The information submitted in the premarket notification is complete and supports a substantial equivalence decision.
§ 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).