(203 days)
Not Found
No
The summary describes a standard immunoturbidimetric assay for measuring CRP, which relies on chemical reactions and optical detection, not AI/ML algorithms. There are no mentions of AI, ML, or related concepts in the document.
No
This device is an in vitro diagnostic (IVD) assay designed to quantitatively determine C-reactive protein in human serum and plasma, which aids in evaluating tissue injury, rather than providing direct therapy or treatment.
Yes
This device is an immunoturbidimetric assay for the quantitative determination of C-Reactive Protein (CRP) in human serum and plasma. The "Intended Use / Indications for Use" section explicitly states that "Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues," which is a diagnostic purpose.
No
The device is a reagent kit for an in vitro diagnostic test, consisting of liquid components and latex particles. It is not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The description explicitly states "for the in vitro quantitative determination of CRP in human serum and plasma". "In vitro" means "in glass" or "outside the body," which is a key characteristic of IVDs. It also specifies the sample type (human serum and plasma) and the analyte being measured (C-Reactive Protein).
- Device Description: The description details the reagents used to perform the test on biological samples (serum and plasma).
- Performance Studies: The document describes various performance evaluations conducted on the device using biological samples (human serum). These studies are typical for demonstrating the analytical performance of an IVD.
- Predicate Device: The mention of a "Predicate Device" with a K number (K083444) indicates that this device is being compared to a previously cleared IVD.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Tina-quant® C-Reactive Protein IV is an immunoturbidimetric assay for the in vitro quantitative determination of CRP in human serum and plasma on cobas c systems.
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 plasma. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.
Product codes (comma separated list FDA assigned to the subject device)
DCN
Device Description
The Tina-quant® C-Reactive Protein IV reagent will be a liquid ready to use 2 component particle enhanced immunoturbidimetric assay.
Reagents - working solutions
R1: TRIS* buffer with bovine serum albumin; preservatives
R2 Latex particles coated with anti-CRP (mouse) in glycine buffer; immunoglobulins (mouse); preservative
- TRIS= Tris(hydroxymethyl)-aminomethane
The Tina-quant® C-Reactive Protein IV assay will be based on the DUREL technology (dual radius enhanced latex - technology) which is also used in C-Reactive Protein Gen.3 predicate method. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The aggregates are determined turbidimetrically.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision: Repeatability and Intermediate Precision (CLSI EP05-A3)
The Tina-quant® C-Reactive Protein IV reagent was evaluated on a single cobas c 501 analyzer. The protocol consisted of 4 human serum samples along with 2 controls (Precinorm Protein and Precipath Protein) which were analyzed in 2 parts for 21 days. Two aliquots of each sample were randomized and then analyzed on 3 lots of reagents. One operator performed all analysis along with utilizing 1 calibration throughout the 21-day study period.
- Key Results:
- Repeatability (Mean (mg/L), SD (mg/L), CV %):
- Precinorm Protein: 9.69, 0.128, 1.3
- Precipath Protein: 55.2, 0.859, 1.6
- Serum 2: 4.55, 0.0702, 1.5
- Serum 3: 10.6, 0.167, 1.6
- Serum 4: 82.4, 1.82, 2.2
- Serum 5: 186, 3.76, 2.0
- Serum 6: 331, 4.40, 1.3
- Intermediate/Within Lab Precision (Mean (mg/L), SD (mg/L), CV %):
- Precinorm Protein: 9.69, 0.142, 1.5
- Precipath Protein: 55.2, 1.04, 1.9
- Serum 2: 4.55, 0.0735, 1.6
- Serum 3: 10.6, 0.206, 1.9
- Serum 4: 82.4, 1.97, 2.4
- Serum 5: 186, 4.39, 2.4
- Serum 6: 331, 5.80, 1.8
- Repeatability (Mean (mg/L), SD (mg/L), CV %):
Analytical Sensitivity (CLSI EP17-A2)
- Limit of Blank (LoB): Tested on 3 reagent lots. Ten aliquots of analyte free saline were analyzed on 1 Roche cobas c 501 analyzer in 6 runs over 3 days, for a total of N=60 determinations per lot.
- Observed LoB: 0.0700 mg/L (Claimed: 0.2 mg/L)
- Limit of Detection (LoD): Tested on 3 reagent lots. Five samples of low analyte level human serum were analyzed, each with 2 aliquots, on 1 Roche cobas c 501 analyzer, in 6 runs, over 3 days, for a total of N=60 determinations per lot.
- Observed LoD: 0.137 mg/L (Claimed: 0.3 mg/L)
- Limit of Quantitation (LoQ): Tested on 3 reagent lots. Nine low concentration human serum samples (in the range from LoB up to approximately 2 times the specified LoQ) were analyzed on 1 Roche cobas c 501 analyzer, in 5 runs, with 5 aliquots of each sample for a total of N=25 determinations per sample per lot.
- Observed LoQ: 0.313 mg/L (Claimed: 3 mg/L)
Linearity/Assay Reportable Range (CLSI EP06-A)
The dilution series was prepared from native unmodified human serum sample pools and then analyzed on using Tina-quant® C-Reactive Protein IV reagent. The dilution series was prepared resulting in 15 levels (including the high and low concentration pools). The diluted samples spanned the measuring range including a non-zero sample below the low end of measuring range and a sample over the high end of measuring range. Each dilution level was measured in triplicate (n ≥ 3).
- Key Results:
- Linear Regression: y=1.002x-0.0169
- Pearson correlation coefficient (R): 0.9994
- Claimed Measuring Range: 3 to 350 mg/L
Endogenous Interference
- L, H, and I Indices: Effect determined at 2 levels (5-10 mg/L and 35-100 mg/L c-reactive protein) utilizing a dilution set of the added interfering substances. Eleven level serial dilution sets were prepared. Each of the 11 interferent levels were measured in triplicate.
- No interference up to: Lipemia 1000 L Index, Hemolysis 1000 H Index, Bilirubin 60 I Index, Ditauro Bilirubin 60 I Index.
- Albumin, Immunoglobulin (IgG) and Rheumatoid Factors Interference: Effect determined at 2 levels (5-10 mg/L and 35-100 mg/L c-reactive protein) utilizing a dilution set of the added interfering substances. Eleven level serial dilution sets were prepared. Each of the eleven interferent levels were measured in triplicate.
- No interference up to: Albumin 60 g/L, IgG 50 g/L, RF Factor 1200 IU/mL.
Exogenous Interferences - Drugs
Effect determined at 2 levels (5-10 mg/L and 35-100 mg/L c-reactive protein). One portion of each pool was spiked with the respective amount of drug and the other portion with solvent. Mean % Recovery calculated comparing drug spiked portions to baseline.
- Key Results: Tested Up To With No Interference (mg/L): N-Acetylcysteine 1660, Ampicillin-Na 1000, Ascorbic acid 300, Cefoxitin 6600, Heparin 5000 IU/L, Levodopa 20, Methyldopa + 1.5 22.5, Metronidazole 200, Doxycyclin 50, Acetylsalicylic acid 1000, Rifampicin 60, Ticarcillin 225, Penicillamin 24, Phenylbutazone 400, Cyclosporine 5, Acetaminophen 200, Theophylline 100.
Sample Matrix Comparison
The effect on quantitation of c-reactive protein in the presence of anticoagulants was determined on the cobas c 501 analyzer by comparing values obtained from native samples (single donors) drawn into serum, Li-Heparin, K2- and K3-EDTA plasma primary tubes.
- Key Results:
- Serum vs. Li-Heparin: y = 1.029x - 0.192, r = 0.999 (Range Tested: 3.34 to 344 mg/L)
- Serum vs. K2-EDTA: y = 1.024x - 0.201, r = 0.999 (Range Tested: 3.34 to 344 mg/L)
- Serum vs. K3-EDTA: y = 1.024x - 0.258, r = 0.999 (Range Tested: 3.34 to 344 mg/L)
Method Comparison to Predicate
A method comparison of the Tina-quant® C-Reactive Protein IV on the cobas c 501 analyzer versus the predicate device, Roche Diagnostics C-Reactive Protein Gen.3 was completed. One hundred ten native, unaltered serum samples, were tested in 1 run on 1 cobas c 501 analyzer in singlet using 1 lot of reagent.
- Key Results:
- Passing/Bablok Regression: Slope 0.985, Intercept +0.278, Correlation (Pearson) 0.999
- Weighted Deming Regression: Slope 0.979, Intercept +0.296, Correlation (Pearson) 0.999
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Roche Diagnostics C-Reactive Protein Gen.3 K083444
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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).
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" followed by the words "U.S. FOOD & DRUG ADMINISTRATION" stacked on top of each other.
February 21, 2020
Roche Diagnostics Operations (RDO) Barbara McWhorter Regulatory Affairs Program Manager 9115 Hague Road Indianapolis, Indiana 46250
Re: K192072
Trade/Device Name: Tina-quant C-Reactive Protein IV Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: August 20, 2019 Received: August 22, 2019
Dear Barbara McWhorter:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 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.
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
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Carolina Kagan Acting Chief, IMFB Division of Immunology and Hematology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K192072
Device Name Tina-quant® C-Reactive Protein IV
Indications for Use (Describe)
Tina-quant® C-Reactive Protein IV is an immunoturbidimetric assay for the in vitro quantitative determination of CRP in human serum and plasma on cobas c systems.
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 plasma. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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Tina-quant® C-Reactive Protein IV 510(k) Summary
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
In accordance with 21 CFR 807.87, Roche Diagnostics hereby submits official notification as required by Section 510(k) of the Federal Food, Drug and Cosmetics Act of our intention to market the device described in this Premarket Notification 510(k).
The purpose of this Traditional 510(k) Premarket Notification is to obtain FDA review and clearance for the Tina-quant® C-Reactive Protein IV.
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| Submitter Name | Roche Diagnostics |
|---|---|
| Address | 9115 Hague Road |
| P.O. Box 50416 | |
| Indianapolis, IN 46250-0457 | |
| Contact | Barbara Ann McWhorter |
| Phone: (317) 521-2336 | |
| FAX: (317) 521-2324 | |
| Email: barbara.mcwhorter@roche.com | |
| Date Prepared | January 10, 2020 |
| Proprietary Name | Tina-quant® C-Reactive Protein IV |
| Common Name | C-Reactive Protein |
| Classification Name | C-reactive protein immunological test system |
| Product Codes, | |
| Regulation Numbers | DCN, 21 CFR § 866.5270 |
| Predicate Devices | Roche Diagnostics C-Reactive Protein Gen.3 |
| Establishment Registration | Roche Diagnostics GmbH Mannheim, Germany: 9610126 |
| Roche Diagnostics GmbH in Penzberg, Germany: 9610529 | |
| Roche Diagnostics Indianapolis IN, United States: 1823260 |
5
1. DEVICE DESCRIPTION
The Tina-quant® C-Reactive Protein IV reagent will be a liquid ready to use 2 component particle enhanced immunoturbidimetric assay.
Reagents - working solutions
R1: TRIS* buffer with bovine serum albumin; preservatives
R2 Latex particles coated with anti-CRP (mouse) in glycine buffer; immunoglobulins (mouse); preservative
- TRIS= Tris(hydroxymethyl)-aminomethane
The Tina-quant® C-Reactive Protein IV assay will be based on the DUREL technology (dual radius enhanced latex - technology) which is also used in C-Reactive Protein Gen.3 predicate method. Human CRP agglutinates with latex particles coated with monoclonal anti-CRP antibodies. The aggregates are determined turbidimetrically.
2. INDICATIONS FOR USE
Tina-quant® C-Reactive Protein IV is an immunoturbidimetric assay for the in vitro quantitative determination of CRP in human serum and plasma on cobas c systems.
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 plasma. Measurement of C-reactive protein aids in evaluation of the amount of injury to body tissues.
3. TECHNOLOGICAL CHARACTERISTICS
| Table 1: Tina-quant® C-Reactive Protein IV Technical Characteristics | ||||
|---|---|---|---|---|
| -- | -- | --------------------------------------------------------------------------- | -- | -- |
| Feature | Predicate C-Reactive Protein
Gen.3
K083444 | Candidate Device
Tina-quant® C-Reactive Protein
IV K192072 |
|------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | Immunoturbidometric assay for the in
vitro quantitative determination of CRP
in human serum and plasma on Roche
automated clinical chemistry analyzers. | Tina-quant® C-Reactive Protein IV is an
immunoturbidimetric assay for the in vitro
quantitative determination of CRP in
human serum and plasma on cobas c
systems. |
| Feature | Predicate C-Reactive Protein
Gen.3
K083444 | Candidate Device
Tina-quant® C-Reactive Protein
IV K192072 |
| Indications for Use | Measurement of C-reactive protein aids
in evaluation of the amount of injury to
body tissues. | 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 plasma.
Measurement of C-reactive protein aids in
evaluation of the amount of injury to body
tissues. |
| Assay Method | Particle enhanced immunoturbidimetric
assay | Same |
| Detection Method | turbidimetric | Same |
| Instrument Platform | Roche automated clinical chemistry
analyzers | cobas c 501 analyzer |
| Sample Type/Matrix | Serum
Plasma: K2- or K3-EDTA, lithium
heparin | Same |
| Calibrator | Calibrator f.a.s. Proteins | Same |
| Calibration Method | 6-point spline | Same |
| Calibration Interval | After reagent lot change
As required following quality control
procedures | - after reagent lot change
- after 3 weeks on-board the analyzer
- after 6 months when using a single
reagent lot - as required following quality control
procedures |
| Controls | Precinorm Protein
Precipath Protein
PreciControl ClinChem Multi 1
PreciControl ClinChem Multi 2 | Precinorm Protein
Precipath Protein
PreciControl ClinChem Multi 1
PreciControl ClinChem Multi 2 |
| Traceability/Standardization | Standardized against an internal method
traceable to CRM 470 (RPPHS -
Reference Preparation for Proteins in
Human Serum). | Standardized against the certified
reference material in human serum of the
IRMM (Institute for Reference Materials
and Measurements) ERM-DA474/IFCC. |
| Reagent Stability | Shelf life at 2-8 °C: See expiration date
on cobas c pack label.
On-board in use and refrigerated on the
analyzer: 12 weeks | Same |
| Measuring Range | 0.3 to 350 mg/L | 3 to 350 mg/L |
6
7
| Feature | Predicate C-Reactive Protein
Gen.3
K083444 | | | Candidate Device
Tina-quant® C-Reactive Protein
IV K192072 | | | | |
|-----------|--------------------------------------------------|----------------|--------------|------------------------------------------------------------------|------------------------|--------------|--------|-----|
| | Repeatability | | | Repeatability | | | | |
| | | Mean
(mg/L) | SD
(mg/L) | CV% | Mean
(mg/L) | SD
(mg/L) | CV% | |
| | CRP T
Control N | 3.35 | 0.04 | 1.2 | Precinorm
Protein | 9.69 | 0.128 | 1.3 |
| | Precipath
Protein | 44.4 | 0.6 | 1.3 | Precipath
Protein | 55.2 | 0.859 | 1.6 |
| | Human
Serum 1 | 0.57 | 0.02 | 3.6 | Human
Serum 2 | 4.55 | 0.0702 | 1.5 |
| | Human
Serum 2 | 1.56 | 0.03 | 1.6 | Human
Serum 3 | 10.6 | 0.167 | 1.6 |
| | Human
Serum 3 | 43.2 | 0.5 | 1.2 | Human
Serum 4 | 82.4 | 1.82 | 2.2 |
| | | | | | Human
Serum 5 | 186 | 3.76 | 2.0 |
| Precision | | | | | Human
Serum 6 | 331 | 4.40 | 1.3 |
| | Intermediate Precision | | | | Intermediate Precision | | | |
| | | Mean
(mg/L) | SD
(mg/L) | CV% | Mean
(mg/L) | SD
(mg/L) | CV% | |
| | CRP T
Control N | 3.06 | 0.09 | 2.9 | Precinorm
Protein | 9.69 | 0.142 | 1.5 |
| | Precipath
Protein | 43.6 | 0.8 | 1.9 | Precipath
Protein | 55.2 | 1.04 | 1.9 |
| | Human
Serum 1 | 0.51 | 0.06 | 11.1 | Human
Serum 2 | 4.55 | 0.0735 | 1.6 |
| | Human
Serum 2 | 1.44 | 0.06 | 3.9 | Human
Serum 3 | 10.6 | 0.206 | 1.9 |
| | Human
Serum 3 | 41.3 | 0.7 | 1.7 | Human
Serum 4 | 82.4 | 1.97 | 2.4 |
| | | | | | Human
Serum 5 | 186 | 4.39 | 2.4 |
| | | | | | Human
Serum 6 | 331 | 5.80 | 1.8 |
| LoB | 0.2 mg/L | | | Same | | | | |
| LoD | 0.3 mg/L | | | Same | | | | |
| LoQ | 0.6 mg/L | | | 3 mg/L | | | | |
8
| Feature | Predicate C-Reactive Protein
Gen.3
K083444 | Candidate Device
Tina-quant® C-Reactive Protein
IV K192072 |
|----------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------|
| Method Comparison:
Predicate vs Candidate | Passing Bablok: | |
| | $Y=0.985x+0.278$ | |
| | $R=0.999$ | |
| | N=110
Min=3.06/Max=347 mg/L | |
| Interferences: | Serum Index:
I=60 mg/dL
H=1000 mg/dL
L=1000
RH: no interference up to 1200 IU/mL
Immunoglobulins: no interference up to
50 g/L | Same |
4. NON-CLINICAL PERFORMANCE EVALUATION
The following performance data were provided in support of the substantial equivalence determination:
Precision according to CLSI EP5-A3
Detection Limit: LoB, LoD and LoQ according to CLSI EP17-A2
Linearity according to CLSI EP6-A
Interferences- L, H and I Indices
Interferences – Albumin, Immunoglobulin (IgG) and Rheumatoid Factors
Interference - Drugs
Matrix Comparison - Anticoagulants
Method Comparison to Predicate
All performance specifications were met.
4.1. Precision: Repeatability and Intermediate Precision (CLSI EP05-A3)
Precision measurements were conducted to evaluate repeatability (within-run precision) and the intermediate precision (within-laboratory precision) according the CLSI guideline EP05-A3.
9
The Tina-quant® C-Reactive Protein IV reagent was evaluated on a single cobas c 501 analyzer according to CLSI guideline EP05-A3. The protocol consisted of 4 human serum samples along with 2 controls (Precinorm Protein and Precipath Protein) which were analyzed in 2 parts for 21 days. Two aliquots of each sample were randomized and then analyzed on 3 lots of reagents. One operator performed all analysis along with utilizing 1 calibration throughout the 21-day study period.
| Specimen | Mean (mg/L) | SD (mg/L) | CV % |
|---|---|---|---|
| Precinorm Protein | 9.69 | 0.128 | 1.3 |
| Precipath Protein | 55.2 | 0.859 | 1.6 |
| Serum 2 | 4.55 | 0.0702 | 1.5 |
| Serum 3 | 10.6 | 0.167 | 1.6 |
| Serum 4 | 82.4 | 1.82 | 2.2 |
| Serum 5 | 186 | 3.76 | 2.0 |
| Serum 6 | 331 | 4.40 | 1.3 |
Table 2: Repeatability Summary
Table 3: Intermediate/Within Lab Precision Summary
| Specimen | Mean (mg/L) | SD (mg/L) | CV % |
|---|---|---|---|
| Precinorm Protein | 9.69 | 0.142 | 1.5 |
| Precipath Protein | 55.2 | 1.04 | 1.9 |
| Serum 2 | 4.55 | 0.0735 | 1.6 |
| Serum 3 | 10.6 | 0.206 | 1.9 |
| Serum 4 | 82.4 | 1.97 | 2.4 |
| Serum 5 | 186 | 4.39 | 2.4 |
| Serum 6 | 331 | 5.80 | 1.8 |
4.2. Analytical Sensitivity (CLSI EP17-A2)
4.2.1. Limit of Blank (LoB)
LoB of the Tina-quant® C-Reactive Protein IV assay was tested on 3 reagent lots. Ten aliquots of analyte free saline were analyzed on 1 Roche cobas c 501 analyzer in 6 runs over 3 days, for a total of N=60 determinations per lot.
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Table 4: LoB
| Claimed LoB [mg/L] | Observed LoB [mg/L] |
|---|---|
| 0.2 | 0.0700 |
4.2.2. Limit of Detection (LoD)
LoD of the Tina-quant® C-Reactive Protein IV assay was tested on 3 reagent lots. Five samples of low analyte level human serum were analyzed, each with 2 aliquots, on 1 Roche cobas c 501 analyzer, in 6 runs, over 3 days, for a total of N=60 determinations per lot.
Table 5: LoD
| Claimed LoD [mg/L] | Observed LoD [mg/L] |
|---|---|
| 0.3 | 0.137 |
Limit of Quantitation (LoQ) 4.2.3.
The LoQ of Tina-quant® C-Reactive Protein IV assay was tested on 3 reagent lots. Nine low concentration human serum samples (in the range from LoB up to approximately 2 times the specified LoQ) were analyzed on 1 Roche cobas c 501 analyzer, in 5 runs, with 5 aliquots of each sample for a total of N=25 determinations per sample per lot.
Table 6: LoQ
| Claimed LoQ [mg/L] | Observed LoQ [mg/L] |
|---|---|
| 3 | 0.313 |
Linearity/Assay Reportable Range (CLSI EP06-A) 4.3.
The dilution series was prepared from native unmodified human serum sample pools and then analyzed on using Tina-quant® C-Reactive Protein IV reagent. The dilution series was prepared resulting in 15 levels (including the high and low concentration pools). The diluted samples spanned the measuring range including a non-zero sample below the low end of measuring range and a sample over the high end of measuring range. Each dilution level was measured in triplicate (n ≥ 3).
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Table 7: Linearity
| Sample type / | Linear Regression | Claimed Measuring Range |
|---|---|---|
| Serum | y=1.002x-0.0169 | |
| Pearson correlation coefficient | ||
| (R)=0.9994 | 3 to 350 mg/L |
4.4. Endogenous Interference
4.4.1. L, H, and I Indices
The effect on quantitation of Tina-quant® C-Reactive Protein IV in the presence of lipemia, hemolysis and bilirubin were determined at 2 levels, 5-10 mg/L and 35-100 mg/L c-reactive protein, utilizing a dilution set of the added interfering substances. Eleven level serial dilution sets were prepared. Each of the 11 interferent levels were measured in triplicate from low to high concentration. All dilution levels for each interferent were measured in 1 run. The mean concentration of the 3 replicates at each level was used to calculate recovery to the known creactive protein concentration.
Table 8: Interference - L, H and I Indices
| Interferent | Claim
No interference up to |
|-------------------|--------------------------------|
| Lipemia | 1000 L Index |
| Hemolysis | 1000 H Index |
| Bilirubin | 60 I Index |
| Ditauro Bilirubin | 60 I Index |
Albumin, Immunoglobulin (IgG) and Rheumatoid Factors Interference 4.4.2.
The effect on quantitation of Tina-quant® C-Reactive Protein IV in the presence of albumin, IgG and rheumatoid factors were determined at 2 levels, 5-10 mg/L and 35-100 mg/L c-reactive protein, utilizing a dilution set of the added interfering substances. Eleven level serial dilution sets were prepared. Each of the eleven interferent levels were measured in triplicate from low to high concentration. All dilution levels for each interferent were measured in 1 run. The median
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concentration of the 3 replicates at each level was used to calculate recovery to the known creactive protein concentration.
| Interferent | Claim
No interference up to |
|-------------|--------------------------------|
| Albumin | 60 g/L |
| IgG | 50 g/L |
| RF Factor | 1200 IU/mL |
| Table 9: Interference - Albumin, Immunoglobulin (IgG) and Rheumatoid Factors | |||||
|---|---|---|---|---|---|
| ------------------------------------------------------------------------------ | -- | -- | -- | -- | -- |
4.5. Exogenous Interferences - Drugs
The effect on quantitation of Tina-quant® C-Reactive Protein IV in the presence of potentially interfering drugs were determined at 2 levels, 5-10 mg/L and 35-100 mg/L c-reactive protein. 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 creactive protein concentration. The c-reactive protein mean concentration of both portions was determined in N=5 results. The mean % Recovery was calculated when comparing the drug spiked portions to the c-reactive protein baseline reference mean concentration.
| Drug | Tested Up To With No
Interference (mg/L) |
|----------------------|---------------------------------------------|
| N-Acetylcysteine | 1660 |
| Ampicillin-Na | 1000 |
| Ascorbic acid | 300 |
| Cefoxitin | 6600 |
| Heparin | 5000 IU/L |
| Levodopa | 20 |
| Methyldopa + 1.5 | 22.5 |
| Metronidazole | 200 |
| Doxycyclin | 50 |
| Acetylsalicylic acid | 1000 |
| Rifampicin | 60 |
| Ticarcillin | 225 |
| Penicillamin | 24 |
| Table 10: Exogenous Interference - Drugs | |||
|---|---|---|---|
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| Phenylbutazone | 400 |
|---|---|
| Cyclosporine | 5 |
| Acetaminophen | 200 |
| Ibuprofen | 500 |
| Theophylline | 100 |
Sample Matrix Comparison 4.6.
The effect on quantitation of c-reactive protein in the presence of anticoagulants with the Tinaquant® C-Reactive Protein IV reagent was determined on the cobas c 501 analyzer by comparing values obtained from native samples (single donors) drawn into serum, Li-Heparin, K2- and K3-EDTA plasma primary tubes.
Table 11: Sample Matrix Comparison
| Anticoagulant | Linear Regression | Range Tested [mg/L] |
|---|---|---|
| Serum vs. Li-Heparin | $y = 1.029x - 0.192, r = 0.999$ | 3.34 to 344 |
| Serum vs. K2-EDTA | $y = 1.024x - 0.201, r = 0.999$ | 3.34 to 344 |
| Serum vs. K3-EDTA | $y = 1.024x - 0.258, r = 0.999$ | 3.34 to 344 |
Method Comparison to Predicate 4.7.
A method comparison of the Tina-quant® C-Reactive Protein IV on the cobas c 501 analyzer versus the predicate device, Roche Diagnostics C-Reactive Protein Gen.3 was completed. One hundred ten native, unaltered serum samples, were tested in 1 run on 1 cobas c 501 analyzer in singlet using 1 lot of reagent. All samples were also testing for icteric, lipemic and hemolytic interference via analyzer serum indices. Statistics were created using Passing/Bablok and weighted Deming regression analysis.
| | Passing/Bablok
Regression | Weighted Deming
Regression |
|-----------------------|------------------------------|-------------------------------|
| Slope | 0.985 | 0.979 |
| Intercept | +0.278 | +0.296 |
| Correlation (Pearson) | 0.999 | 0.999 |
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4.8. Stability
The stability studies and acceptance criteria have been reviewed and found to be acceptable. The stability data supports Roche Diagnostic's claims as reported on the package labeling.
5. FDA GUIDANCE
FDA Guidance for Industry and FDA Staff: Review Criteria for Assessment of C-Reactive Protein (CRP), High Sensitivity C-Reactive Protein (hsCRP) and Cardiac C-Reactive Protein (cCRP) Assays was followed in this 510(k) submission.
6. ADDITIONAL INFORMATION
Other Devices Required But Not Provided:
- Calibrator f.a.s Proteins, K133330 ●
- . Precinorm Protein, K133330
- . Precipath Protein, K133330
- . PreciControl ClinChem Multi 1, K133330
- . PreciControl ClinChem Multi 2, K133330
There have been no changes to these items marketed with the new Tina-quant® C-Reactive Protein IV.