(135 days)
The Bayer Advia IMS C-Reactive Protein (CRP) assay is an in vitro diagnostic device into ded to measure C-Reactive Protein in human serum. Measurements of CRP are used in the evaluation and treatment on injuries to body tissues and in monitoring the progress of traumatic injuries, rheumatic fever and rheumatoid arthritis.
This in vitro method is intended to quantitatively measure C-reactive protein (CRP) in serum on the Bayer ADVIA IMS systems.
Here's an analysis of the provided text, outlining the acceptance criteria and study details for the ADVIA IMS High Sensitivity C-Reactive Protein (CRP) Method based on the 510(k) summary:
Acceptance Criteria and Device Performance for ADVIA IMS High Sensitivity C-Reactive Protein (CRP) Method
This device intends to quantitatively measure C-reactive protein (CRP) in serum, primarily for evaluating and treating tissue injuries and monitoring traumatic injuries, rheumatic fever, and rheumatoid arthritis. The study compares the performance of the ADVIA IMS CRP assay against a predicate device, the Dade/Behring N High Sensitivity CRP (K991385).
1. Acceptance Criteria and Reported Device Performance
The acceptance criteria for this diagnostic device are typically established by demonstrating substantial equivalence to a legally marketed predicate device, focusing on analytical performance characteristics such as imprecision, correlation, and interference.
| Performance Characteristic | Acceptance Criteria (Implied by Predicate Performance) | Reported Device Performance (ADVIA IMS CRP) |
|---|---|---|
| Imprecision (Normal Range) | ||
| Level 1 (16.5 mg/L) | Total CV < 5.7% (for 10 mg/L) | 2.9% |
| Level 2 (31.7 mg/L) | Total CV < 5.7% (for 25 mg/L) | 2.1% |
| Level 3 (47.5 mg/L) | Total CV < 5.7% (for 60 mg/L) | 3.1% |
| Imprecision (High Sensitivity Range) | ||
| Level 1 (0.25 mg/L) | No direct predicate comparison provided | 11.2% |
| Level 2 (0.52 mg/L) | Total CV < 2.5% (for 0.5 mg/L) | 5.3% |
| Level 3 (1.21 mg/L) | Total CV < 3.8% (for 1.3 mg/L) | 2.5% |
| Correlation (Normal Range) | R-value close to 1, Syx low, slope ~1, intercept ~0 (vs BN100) | Y=0.97X - 0.04; Syx=2.41 mg/L; R=0.998 |
| Correlation (High Sensitivity Range) | R-value close to 1, Syx low, slope ~1, intercept ~0 (vs BN100) | Y=0.90X - 0.08; Syx=0.11 mg/L; R=0.997 |
| Interfering Substances (Normal Range - % Change within acceptable limits) | Bilirubin (unconjugated): < target impact | +6% (5.0 mg/L CRP, 20 mg/dL Bil) |
| Bilirubin (conjugated): < target impact | +6% (5.3 mg/L CRP, 20 mg/dL Bil) | |
| Hemoglobin: < target impact | +4% (5.4 mg/L CRP, 500 mg/dL Hemoglobin) | |
| Lipids (Triglycerides): < target impact | +2% (5.2 mg/L CRP, 1000 mg/dL Lipids) | |
| Interfering Substances (High Sensitivity Range - % Change within acceptable limits) | Bilirubin (unconjugated): < target impact | -7% (1.79 mg/L CRP, 25 mg/dL Bil) |
| Bilirubin (conjugated): < target impact | +1% (1.95 mg/L CRP, 25 mg/dL Bil) | |
| Hemoglobin: < target impact | 0% (1.94 mg/L CRP, 500 mg/dL Hemoglobin) | |
| Lipids (Triglycerides): < target impact | -6% (1.82 mg/L CRP, 500 mg/dL Lipids) |
Note: The acceptance criteria are implicitly derived from the performance shown by the predicate device (Dade/Behring BN100) and the general expectations for analytical performance in diagnostic assays (e.g., high R-values for correlation, low CVs for imprecision, minimal interference). Specific numerical acceptance thresholds were not explicitly stated as "acceptance criteria" but are demonstrated by the presented data's favorable comparison to the predicate.
2. Sample Sizes and Data Provenance
| Test Type | Sample Size (Test Set) | Data Provenance |
|---|---|---|
| Imprecision | Not explicitly stated | Implied prospective testing in a laboratory setting, likely in the US, as part of device development and validation. |
| The levels (e.g., 16.5, 31.7, 47.5 mg/L for normal range; 0.25, 0.52, 1.21 mg/L for high sensitivity) suggest prepared control materials or pooled patient samples. | ||
| Correlation | 165 (Normal Range) | Clinical serum samples. Provenance (e.g., country of origin, retrospective/prospective) is not explicitly stated, but typically these are prospective clinical samples collected for method comparison. |
| 25 (High Sensitivity) | Clinical serum samples. Provenance (e.g., country of origin, retrospective/prospective) is not explicitly stated. | |
| Interference | Not explicitly stated | Implied prospective testing using prepared samples spiked with interfering substances and CRP. Likely laboratory-based. |
3. Number of Experts and Qualifications for Ground Truth
This type of submission for an in vitro diagnostic device assessing an analyte (CRP) does not typically involve human experts establishing ground truth in the way image-based diagnostics might. The "ground truth" for the performance studies described here (imprecision, correlation, interference) is established by:
- Reference Methods: For correlation studies, the predicate device (Dade/Behring BN100) serves as the reference or comparison system against which the new device's measurements are correlated. The output of the predicate device is considered the "ground truth" for comparison.
- Known Concentrations: For imprecision and interference studies, the "ground truth" refers to the known concentrations of CRP in control materials or spiked samples.
Therefore, no external clinical experts (like radiologists) are involved in establishing ground truth for these analytical performance studies.
4. Adjudication Method for the Test Set
Not applicable. Diagnostic assays measuring an analyte like CRP do not typically employ adjudication methods for their test sets in the same way clinical trials or image-based AI studies do. The readings are quantitative measurements, and accuracy is determined by comparison to reference methods or known concentrations, not by consensus among human interpreters.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No. A MRMC comparative effectiveness study is not relevant or typically performed for this type of in vitro diagnostic device (analyte measurement). These studies are primarily for devices that rely on human interpretation of complex medical data (e.g., images) and aim to assess the impact of AI assistance on human reader performance.
6. Standalone (Algorithm Only) Performance
Yes, the studies presented are all standalone performance evaluations of the ADVIA IMS CRP assay. The device directly measures CRP concentrations in serum samples. There is no human-in-the-loop performance component in these specific analytical validation studies, as they assess the direct output of the instrument.
7. Type of Ground Truth Used
The ground truth used for these analytical studies is primarily:
- Reference Device/Method Data: For correlation, the measurements obtained from the predicate device (Dade/Behring BN100) are used as the comparative "ground truth."
- Known Concentrations/Values: For imprecision and interference studies, the ground truth is based on the known or assigned concentrations of CRP in control materials or samples spiked with specific amounts of CRP and interfering substances.
8. Sample Size for the Training Set
Not applicable. The ADVIA IMS CRP method is an immunoassay, not a machine learning or AI-based algorithm that requires a "training set" in the conventional sense. Its performance is based on chemical and optical measurements, with calibration determining its quantitative output.
9. How Ground Truth for the Training Set Was Established
Not applicable, as there is no "training set" in the context of an immunoassay. The device is calibrated using materials with known CRP concentrations, and this calibration process is distinct from the machine learning concept of training data. The "ground truth" for calibration materials would be established by highly accurate reference methods or certified reference materials.
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510(k) SUMMARY OF SAFETY AND EFFECTIVENESS High Sensitivity C-Reactive Protein (CRP) Method for ADVIA® IMS™
This summary of 510(k) safety and effectiveness information is being submitted in Fills Summary of 51 (1) Sales July 1998) and the Safe Medical Device Act of 1990 and 21 CFR 807.92.
The assigned 510(k) number is: K012337
1. Intended Use
This in vitro method is intended to quantitatively measure C-reactive protein (CRP) in serum on the Bayer ADVIA IMS systems. Measurements of CRP are used in the evaluation and treatment of injuries to body tissues and in monitoring the progress of traumatic injuries, rheumatic fever and rheumatoid arthritis.
Predicate Device 2.
| Product Name | Reagent Part # | Calibrator Part # |
|---|---|---|
| Dade/Behring N HighSensitivity CRP,K991385 | OQIY 21 | OQIK |
Device / Method 3.
| Product Name | Reagent BAN | CalibratorBAN |
|---|---|---|
| ADVIA IMS CRP | 03987289 (100 test)02136137 (250 test) | 02537697 |
A. Imprecision (normal range)
| ADVIA IMS | |
|---|---|
| Level (mg/L) | Total CV (%) |
| 16.5 | 2.9 |
| 31.7 | 2.1 |
| 47.5 | 3.1 |
| Dade/Behring | |
|---|---|
| BN100 | |
| Level(mg/L) | TotalCV(%) |
| 10 | <5.7 |
| 25 | <5.7 |
| 60 | <5.7 |
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Imprecision (high sensitivity range)
| ADVIA IMS | Dade/BehringBN100 | ||
|---|---|---|---|
| Level(mg/L) | TotalCV (%) | Level(mg/L) | TotalCV(%) |
| 0.25 | 11.2 | ||
| 0.52 | 5.3 | 0.5 | 2.5 |
| 1.21 | 2.5 | 1.3 | 3.8 |
B. Correlation (Y=ADVIA IMS, X=Comparison system) for Normal and High Sensitivity Ranges
| Specimen type | ComparisonSystem (X) | N | RegressionEquation | Syx(mg/L) | R | SampleRange(mg/L) |
|---|---|---|---|---|---|---|
| Serum | BN100 | 165 | Y=0.97X - 0.04 | 2.41 | 0.998 | 1.0 - 179.0 |
| Serum | BN100 | 25 | Y=0.90X - 0.08 | 0.11 | 0.997 | 0.2-5.1 |
C. Interfering Substances (normal range)
| InterferingSubstance | Interfering Sub.Conc. (mg/dL) | CRP Conc.(mg/L) | Effect(% change) |
|---|---|---|---|
| Bilirubin(unconjugated) | 20 | 5.0 | +6 |
| Bilirubin(conjugated) | 20 | 5.3 | +6 |
| Hemoglobin | 500 | 5.4 | +4 |
| Lipids(Triglycerides) | 1000 | 5.2 | +2 |
Interfering Substances (high sensitivity range)
| InterferingSubstance | Interfering Sub.Conc. (mg/dL) | CRP Conc.(mg/L) | Effect(% change) |
|---|---|---|---|
| Bilirubin(unconjugated) | 25 | 1.79 | -7 |
| Bilirubin(conjugated) | 25 | 1.95 | +1 |
| Hemoglobin | 500 | 1.94 | 0 |
| Lipids(Triglycerides) | 500 | 1.82 | -6 |
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Image /page/2/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines forming its body and wings. The eagle is enclosed in a circle with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. The text is in all capital letters and is evenly spaced around the circle.
Food and Drug `Administration 2098 Gaither Road Rockville MD 20850
DEC 0 6 2001
Kenneth T. Edds, Ph. D. Regulatory Affairs Bayer Corporation Diagnostics Division 511 Benedict Avenue Tarrytown, NY 10591-5097
K012337 Re:
K012537
Trade/Device Name: ADVIA IMS High Sensitivity C-Reactive Protein Assay Regulation Number: 21 CFR 866.5270 Regulation Name: C-reactive protein immunological test system Regulatory Class: Class II Product Code: DCN Dated: October 12, 2001 Received: October 16, 2001
Dear Dr. Edds:
We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becally b r (c) fee device is substantially equivalent (for the indications felerenced above and nave acterimes ally marketed predicate devices marketed in interstate for use stated in the choosars) to regard) the enactment date of the Medical Device Americans, or to Commerce pror to May 20, 1978, the canomance with the provisions of the Federal Food, Drug, devices mat have been recuire approval of a premarket approval application (PMA). and Cosment Act (Act) that ao not required to the general controls provisions of the Act. The T ou may, merciolo, market the act include requirements for annual registration, listing of general controls provisions of vactice, 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 If your device is classified (soc above) and existing major regulations affecting your device can
may be subject to such additional controls. Existing major regulation Fift thay be subject to suen additional seculations, Title 21, Parts 800 to 898. In addition, FDA may be found in the Oouv cements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean r rease oc advised that I Dri 3 issualites or our device complies with other requirements of the Act mall I DA has made a determinations administered by other Federal agencies. You must of any I coural statutes and registments, including, but not limited to: registration and listing (21 comply with an the 110 CFR Part 801); good manufacturing practice requirements as set CI K Fart 6077, adoling (21 (QS) regulation (21 CFR Part 820); and if applicable, the electronic form in the quality bystems (Sections 531-542 of the Act); 21 CFR 1000-1050.
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This letter will allow you to begin marketing your device as described in your 510(k) premarket I his lotter will and in your your substantial equivalence of your device to a legally marketed nouthoution. "The 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 our labeling regulation (21 CFR Part 801 and 1 If you desire specific as in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, (201) 594-1566. Tradiation f Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small information on 90 in 100pal and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Putman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory-Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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510(k) Number: K012337
Device Name: ADVIA IMS High Sensitivity C-Reactive Protein Assay
Indications for Use:
The Bayer Advia IMS C-Reactive Protein (CRP) assay is an in vitro diagnostic device into ded to measure C-Reactive Protein in human serum. Measurements of CRP are used in the evaluation and treatment on injuries to body tissues and in monitoring the progress of traumatic injuries, rheumatic fever and rheumatoid arthritis.
(Division Sign-Off)
Division of Clinical Laboratory Devices
510(k) Number K012337
(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use
(Per 21 CFR 801.109)
OR
Over-The-CounterUse
(Optional Format 1-2-96)
§ 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).