(237 days)
The ADVIA Centaur® anti-CCP IgG (aCCP) assay is for in vitro diagnostic use in the semi-quantitative determination of the IgG class of autoantibodies specific to cyclic citrullinated peptide (CCP) in human serum or plasma (K2-EDTA and lithium heparin) using the ADVIA Centaur XP system. Detection of anti-CCP antibodies is used as an aid in the diagnosis of Rheumatoid Arthritis (RA) and should be used in conjunction with other clinical information. Autoantibody levels represent one parameter in a multi-criteria diagnostic process, encompassing both clinical and laboratory-based assessments.
Quality Control:
The ADVIA Centaur® Anti-CCP IgG (aCCP) quality control material is for in vitro diagnostic use to monitor the precision and accuracy of the ADVIA Centaur aCCP assay using the ADVIA Centaur systems.
Master Curve Material (MCM):
The ADVIA Centaur® Anti-CCP IgG (aCCP) Master Curve Material (MCM) is for in vitro diagnostic use in the verification of calibration and reportable range of the ADVIA Centaur aCCP assay.
The ADVIA Centaur aCCP assay is a fully automated, two-step immunoassay using chemiluminescent technology. The assay utilizes an acridinium ester-labeled anti-human lgG as the Lite Reagent. The Solid Phase consists of biotinylated CCP coupled to streptavidin which is then coated onto magnetic latex microparticles.
Here's an analysis of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Device Name: ADVIA Centaur® Anti-CCP IgG (aCCP) Assay
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state "acceptance criteria" as a separate, quantitative table derived from a pre-defined standard (like a predicate device's performance). Instead, it compares the performance of the new device (ADVIA Centaur aCCP assay) to a predicate device (ARCHITECT Anti-CCP Assay) for several characteristics and implies that similar performance constitutes meeting the criteria for substantial equivalence. I will reconstruct a table showing the implied acceptance criteria (based on the predicate's performance or general expectations for such an assay) and the reported performance.
| Performance Metric | Implied Acceptance Criteria (Based on Predicate or General Assay Expectations) | Reported Device Performance (ADVIA Centaur aCCP Assay) |
|---|---|---|
| Intended Use | Semi-quantitative determination of IgG class anti-CCP antibodies, aid in RA diagnosis, used with other clinical info. | Matches: Semi-quantitative determination of IgG class anti-CCP antibodies, aid in RA diagnosis, used with other clinical info. |
| Assay Technology | Automated, Chemiluminescent Microparticle Immunoassay (CMIA) | Matches: Automated, Chemiluminescent Microparticle Immunoassay (CMIA) |
| Specimen Type | Human serum, serum separator tubes, human plasma (lithium heparin, potassium EDTA) | Matches: Human serum, serum separator tubes, human plasma (lithium heparin, potassium EDTA) |
| Capture Antibody | Cyclic citrullinated peptide (CCP), second generation | Matches: Cyclic citrullinated peptide (CCP), second generation |
| Conjugate Antibody | Mouse anti-human IgG: acridinium-labeled | Matches: Mouse anti-human IgG: acridinium-labeled |
| Storage Conditions | Intended Storage of 2-8 °C | Matches: Intended Storage of 2-8 °C |
| Calibrator Range | 0.0-200.0 U/mL | Matches: 0.0-200.0 U/mL |
| Suggested Cut-Off | 5.0 U/mL | Matches: 5.0 U/mL |
| Interference (Total Protein) | No interference from Total Protein (12 g/dL) | Matches: No interference from Total Protein (12 g/dL) |
| Interference (Rheumatoid Factor) | No interference from Rheumatoid Factor (200 IU/mL) | Matches: No interference from Rheumatoid Factor (200 IU/mL) |
| Cross-Reactivity (General) | No significant cross-reactivity with specified autoantibodies (e.g., SSA, SSB, Sm, RNP, Scl-70, TPO, Jo-1, ds-DNA, Ribosomal P) | Matches: No significant cross-reactivity with specified autoantibodies (SSA, SSB, Sm, RNP, Scl-70, TPO, Jo-1, ds-DNA, Ribosomal P). Also M2, Chromatin. |
| Sample Stability | Specimens stable for up to 7 days at 2-8ºC or 22 hours at 30ºC, avoid > 3 freeze/thaw cycles. | Separated specimens stable for up to 22 hours at room temp or up to 7 days at 2-8 ºC. Avoid > 2 freeze-thaw cycles. (Slight difference in freeze/thaw cycle recommendation, but generally comparable). |
| Imprecision (Within-Lab %CV) | Predicate: Within-run CV of 2.0% to 4.7% and total CV of 2.8 to 7.7% (2.7 to 195.3 U/mL). | |
| New device design spec: 50 U/mL. | Meets Design Spec: Ranged from 3.0 to 4.3% (2.37 to 111.53 U/mL). | |
| Sensitivity (Limit of Detection) | ≤ 0.5 U/mL | Better: 0.40 U/mL (design goal was ≤ 1.50 U/mL) |
| Measurable Range | 0.5 - 200.0 U/mL | Comparable/Slightly Wider: 0.40 – 200.0 U/mL |
| On-board Reagent Stability | Max 30 days | Better: Max 60 days |
| High Dose Hook | Not explicitly stated but assumed desirable to avoid. | Patient samples up to 3000.00 U/mL will assay > 200.00 U/mL (no high-dose hook effect within this range). |
| Interference (General) | No significant effects from hemolyzed, icteric, lipemic samples within specified limits. | Hemolyzed (1000 mg/dL Hb), Icteric (40 mg/dL unconj/conj bilirubin), Lipemic (1500 mg/dL Intralipid, 2450 mg/dL triglycerides). Biotin (500 ng/dL), Caprine IgG (6 g/dL). |
| Dilution Linearity (Recovery) | Not explicitly stated but assumed desirable to be within an acceptable range (e.g., 80-120%). | Sample 1 (140.63 U/mL) diluted 1:10 showed 107.87% recovery. Sample 2 (180.08 U/mL) diluted 1:10 showed 105.62% recovery. |
| Clinical Concordance (Overall % Agreement) | "Substantially equivalent performance" to predicate. Implicitly, high agreement. | 96.84% (CI 93.89 - 98.39%) with ARCHITECT Anti-CCP. |
| Clinical Sensitivity (RA diagnosis) | "Substantially equivalent performance." Implicitly, acceptable sensitivity for RA. | 68.08% (CI 62.5-73.3%) |
| Clinical Specificity (Non-RA population) | "Substantially equivalent performance." Implicitly, acceptable specificity for RA. | 97.17% (CI 95.22-98.49%) |
2. Sample Sizes and Data Provenance:
- Test Set (Clinical Performance):
- Method Comparison Study: 253 samples (143 confirmed positive for RA, and 110 samples where other auto-antibodies may be present). Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective), but it is a clinical study.
- Clinical Sensitivity and Specificity Study: 767 patient samples.
- 307 confirmed-positive RA subjects.
- 460 non-RA subjects with potentially cross-reacting conditions (22 subgroups).
- Data provenance not explicitly stated (e.g., country of origin, retrospective/prospective).
- Training Set: Not explicitly mentioned for this type of in vitro diagnostic assay. Immunoassays are generally calibrated and validated, not "trained" in the machine learning sense. The "training" in this context would likely refer to the development and optimization of the assay reagents and parameters.
3. Number of Experts and Qualifications for Ground Truth (Test Set):
- For RA Confirmation: "307 confirmed-positive RA subjects that were classified according to the American College of Rheumatology criteria." This implies expert clinical diagnosis based on established criteria, but the specific number and qualifications of individuals making these diagnoses are not provided.
- For Non-RA Subjects: "22 subgroups of non-RA subjects (n=460) with potentially cross-reacting conditions." This also implies clinical diagnosis by experts, but details are not provided.
- For Autoantibody Presence (Method Comparison): "110 samples where other auto-antibodies may be present." This suggests expert determination of autoantibody status, but details are not given.
4. Adjudication Method for the Test Set:
Not applicable or explicitly stated as this is an immunoassay, not an imaging device requiring expert adjudication of reader interpretations. The ground truth for clinical sensitivity and specificity is based on clinical diagnosis (American College of Rheumatology criteria for RA).
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, an MRMC comparative effectiveness study was not done. This type of study is typically performed for imaging devices or AI tools that assist human readers in interpretation. The ADVIA Centaur anti-CCP IgG assay is a standalone diagnostic laboratory test.
6. Standalone Performance:
Yes, standalone performance was done. The entire document describes the standalone performance of the ADVIA Centaur aCCP assay in various analytical and clinical studies (linearity, dilution linearity, detection capability, high dose hook, cross-reactivity, interference, precision, specimen collection comparison, clinical concordance with a predicate, and clinical sensitivity/specificity against clinical diagnosis). The results presented are solely the performance of the algorithm/assay without human intervention in the result determination.
7. Type of Ground Truth Used:
- Analytical Performance: Based on reference materials, spiked samples with known concentrations, or established analytical methods.
- Clinical Performance (Sensitivity/Specificity):
- RA Diagnosis: American College of Rheumatology criteria (clinical diagnosis) for RA.
- Non-RA Status: Clinical diagnosis of various conditions (22 subgroups).
- Method Comparison: The predicate device (ARCHITECT Anti-CCP Assay) results were used as a reference point for agreement.
8. Sample Size for the Training Set:
Not applicable in the machine learning sense. For an immunoassay, "training" is typically assay development, which involves optimizing reagents and parameters. The document doesn't specify sample sizes used during the development phase.
9. How the Ground Truth for the Training Set Was Established:
Not applicable. For an immunoassay, ground truth during development would involve well-characterized samples (e.g., confirmed positive/negative for CCP antibodies, known concentrations) to optimize the assay's performance characteristics. Specific details on this are not provided in the summary.
§ 866.5775 Rheumatoid factor immunological test system.
(a)
Identification. A rheumatoid factor immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the rheumatoid factor (antibodies to immunoglobulins) in serum, other body fluids, and tissues. Measurement of rheumatoid factor may aid in the diagnosis of rheumatoid arthritis.(b)
Classification. Class II (performance standards).