(269 days)
The ADVIA Centaur® Erythropoietin (EPO) assay is for in the quantitative measurement of exythropoitin in pediatric and adult human serum or plasma (K2-EDTA, lithium heparin) using the ADVIA Centaur XP system. Measurement of erythropoietin is used as an aid in the diagnosis of anemias and polycythemias.
The ADVIA Centaur EPO assay is a fully automated, one-step sandwich immunoassay using direct chemiluminescent technology. The assay utilizes an acridinium-ester-labeled monoclonal mouse anti-EPO antibody in the Lite Reagent. The Solid Phase consists of mouse anti-EPO monoclonal antibody-coated paramagnetic microparticles.
Here's an analysis of the provided text to extract the acceptance criteria and study details for the ADVIA Centaur Erythropoietin (EPO) assay:
1. Table of Acceptance Criteria and Reported Device Performance
This table compiles information primarily from the "Summary of Non-Clinical Performance" and "Summary of Clinical Performance" sections.
| Acceptance Criterion (Implicit) | Reported Device Performance (ADVIA Centaur EPO assay) |
|---|---|
| Linearity (range over which results are proportional to actual concentration) | Linear from 0.83–750.00 mIU/mL. |
| Dilution Recovery (accuracy after dilution) | Observed percent recovery for individual samples ranged from 76 - 111% when diluted 1:10. |
| Measuring Interval (reportable range) | 0.83 - 750.00 mIU/mL. |
| Limit of Blank (LoB) | 0.46 mIU/mL. |
| Limit of Detection (LoD) (lowest concentration detectable with 95% probability) | 0.75 mIU/mL. |
| Limit of Quantitation (LoQ) (lowest concentration detectable at total error of 30%) | 0.83 mIU/mL. (Results below LoQ should be reported as 18 mg/dL caused >10% change at 4-6 mIU/mL EPO; Albumin >6.8 g/dL caused >10% change at 4-6 mIU/mL EPO; EPO soluble receptor >31.25 ng/dL caused >10% change at 4-6 mIU/mL EPO; Human gamma globulins (IgG) 6.7 g/dL caused >10% change at 25-35 mIU/mL EPO). |
| Precision (reproducibility and repeatability) | Coefficients of Variation (CV%) for Repeatability (Within-Run) ranged from 1.6% to 4.8%. CV% for Within-Lab (Total) ranged from 2.6% to 8.4% across 7 samples with EPO concentrations from 1.69 to 579.41 mIU/mL. |
| Specimen Collection Comparison (equivalence across different tube types) | Correlation coefficient (r) ≥ 0.95, a slope of 0.90-1.10, and an intercept ± 1.00 mIU/mL for alternate tube types (y) versus human serum (x). Demonstrated r values of 0.99-1.00, slopes of 0.97-1.02 and intercepts of -0.33 to -0.20 for K2-EDTA, Lithium Heparin, Sodium Heparin, Plasma Separator Tube, and Serum Separator Tube compared to human serum. |
| Method Comparison (Agreement with a legally marketed predicate device) | Passing-Bablok regression: ADVIA Centaur EPO (y) = 0.99 (x) + 0.81 mIU/mL (intercept), r = 0.99 (1st study). |
| ADVIA Centaur EPO (y) = 1.07 (x) + 0.00 mIU/mL (intercept), r = 1.00 (2nd study). | |
| ADVIA Centaur EPO (y) = 1.01 (x) + 0.36 mIU/mL (intercept), r = 0.99 (3rd multi-site study). | |
| Expected Values (establishment of reference ranges for adult and pediatric populations) | Established 95% Reference Range for combined adult male and female: 5.44 - 26.25 mIU/mL. |
| Established pediatric ranges for Male Child (2-12): 4.13-25.52 mIU/mL; Male Adolescent (13-21): 4.15-26.15 mIU/mL; Female Child (2-12): 4.94-24.47 mIU/mL; Female Adolescent (13-21): 4.07-40.30 mIU/mL. | |
| Standardization (traceability to international standards) | Traceable to WHO 2nd International Reference Preparation for Erythropoietin (human, urinary derived); NIBSC code: 67/343, and WHO 3rd International Standard for Erythropoietin, recombinant, for bioassay; NIBSC code: 11/170. |
| Substantial Equivalence (Overall conclusion based on studies showing similar performance to predicate) | The ADVIA Centaur EPO assay demonstrated substantially equivalent performance to the Beckman Coulter Access EPO assay. |
2. Sample Size Used for the Test Set and Data Provenance
- Linearity: Not specified, but involved three high EPO samples mixed with low EPO human serum.
- Dilution Recovery: 10 samples (containing high EPO levels: 618.63-986.07 mIU/mL).
- Detection Capability (LoD): 323 determinations using 10 low-level samples.
- Cross-reactivity: Not explicitly stated as a "sample size," but involved numerous cross-reactants (e.g., various plasma proteins, epoetin alfa, darbepoetin alfa).
- Interference: Not explicitly stated as a specific "sample size" for each interferent, but involved various substances tested at different concentrations.
- Precision: 7 pooled serum samples. For each sample, there were 80 observations (replicates of 2, in 2 runs/day, over 20 days).
- Specimen Collection Comparison: 65 samples (serum EPO values ranging from 4.39 - 707.81 mIU/mL).
- Method Comparison:
- Study 1: 216 human serum samples (range: 3.29 – 691.60 mIU/mL).
- Study 2: 100 human serum samples from US population (range: 4.45 - 407.74 mIU/mL).
- Study 3 (Multi-site): 327 human serum samples (range: 3.55 - 596.81 mIU/mL), with ≥ 100 samples per site.
- Expected Values (Adult): 251 apparently healthy subjects (128 males, 123 females), older than 21 years of age.
- Expected Values (Pediatric): 266 apparently healthy children (2 to
§ 864.7250 Erythropoietin assay.
(a)
Identification. A erythropoietin assay is a device that measures the concentration of erythropoietin (an enzyme that regulates the production of red blood cells) in serum or urine. This assay provides diagnostic information for the evaluation of erythrocytosis (increased total red cell mass) and anemia.(b)
Classification. Class II. The special control for this device is FDA's “Document for Special Controls for Erythropoietin Assay Premarket Notification (510(k)s).”