(417 days)
The Access EPO assay is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of erythropoietin levels in human serum and plasma (heparin) using the Access Immunoassay Systems. This assay is intended as an aid in the diagnosis of anemias and polycythemias. With the advent of the administration of recombinant erythropoietin as a biologic therapy to increase red blood cell mass, an erythropoietin assay may be used also to aid in the prediction and monitoring of response to recombinant erythropoietin treatment in persons with anemias.
The Access EPO calibrators are intended to calibrate the Access EPO assay for the quantitative determination of EPO levels in human serum and plasma (heparin) using the Access Immunoassay Systems.
The Access® EPO assay consists of the reagent pack and calibrators. Other items needed to perform the assay include the Access substrate and wash buffers.
Here's a breakdown of the acceptance criteria and study information for the Access® EPO Assay based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance:
| Performance Metric | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision | Total precision of ≤ 10% CV at EPO concentrations > 3 mIU/mL | Internal Data: |
- Precision tested at concentrations from approximately 9 to 475 mIU/mL.
- Within-run imprecision ranged from 1.8% CV to 8.7% CV.
- Total imprecision ranged from 2.6% CV to 8.7% CV.
Conclusion: Meets the criterion; total precision values are all ≤ 10% CV. |
| Analytical Sensitivity | Lowest detectable level of EPO distinguishable from zero (Access EPO Calibrator S0) is ≤0.6 mIU/mL | Internal Data: - Reported as ≤0.6 mIU/mL. |
| Dilution Recovery (Linearity) | Sample mean recovery values for all serum and plasma samples were within the range of 100 ± 15%. | Internal Data: - Dilution recovery studies performed by diluting multiple human serum and plasma (heparin) samples at various levels with Access EPO Calibrator S0.
- Sample mean recovery values were within the range of 100 ± 15%. |
| Methods Comparison | Acceptable agreement with predicate device (RDS Quantikine ELISA assays). | Internal Site Study: - Slope of 1.0511, intercept of -1.3595, and correlation coefficient (r) of 0.988.
- N=103 with EPO concentration range of approximately 3 to 182 mIU/mL.
External Site Study: - Slope of 1.1216, intercept of -2.4168, and correlation coefficient (r) of 0.995.
- N=113 with EPO concentration range of approximately 3 to 193 mIU/mL. |
| Analytical Specificity | No significant interference from therapeutic drugs, similar compounds, or potential sample contaminants (total protein, bilirubin, hemoglobin, and triglycerides). | Internal Data: - No significant interference from therapeutic drugs or similar compounds.
- No significant interference from potential sample contaminants (total protein, bilirubin, hemoglobin, and triglycerides). |
| Stability | EPO reagents stable for 28 days after opening; calibrators stable for 90 days after opening; calibration curve stable for 28 days. | Internal Data: - EPO reagents are stable for 28 days after opening.
- Calibrators are stable for 90 days after opening.
- The calibration curve is stable for 28 days. |
2. Sample Sizes Used for the Test Set and the Data Provenance:
- Precision: Not explicitly stated as a separate "test set" in the context of clinical samples, but the study was performed on samples with EPO concentrations ranging from 9 to 475 mIU/mL.
- Dilution Recovery (Linearity): "Multiple human serum and plasma (heparin) samples." The exact number is not provided.
- Methods Comparison:
- Internal Site Study: N=103
- External Site Study: N=113
- Analytical Specificity: Not explicitly stated as a numerical sample size, but indicates testing for interference from "therapeutic drugs or similar compounds" and "potential sample contaminants."
- Data Provenance: The studies are described as "Internal Site Study" and "External Site Study," suggesting the data comes from within Beckman Coulter's testing facilities and at least one other external laboratory. The samples were "human serum and plasma (heparin)." The country of origin is not explicitly stated, but the submission is to the FDA (USA). The studies appear to be prospective in nature, as they involve testing the performance of the new Access® EPO assay.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
This information is not provided in the document. For an immunoassay, the "ground truth" for the test set is typically established by comparing the device's results to a well-established, often reference, method. In this case, the predicate device (RDS Quantikine ELISA) served as the reference for method comparison. The document does not describe expert adjudication for these numerical results.
4. Adjudication Method for the Test Set:
This is not applicable in the context of an immunoassay performance study focused on quantitative measurements. Adjudication methods (like 2+1, 3+1) are typically used in imaging or diagnostic accuracy studies where expert consensus is required to establish a qualitative or subjective ground truth. Here, the comparison is against an established quantitative predicate method.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. without AI Assistance:
This information is not applicable to this device. The Access® EPO Assay is an in vitro diagnostic (IVD) immunoassay, not an AI-powered diagnostic imaging device or an AI human-in-the-loop system. Therefore, MRMC studies examining human reader performance with or without AI assistance are not relevant here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done:
Yes, the studies presented represent the standalone performance of the Access® EPO Assay. This is an automated immunoassay system; its performance metrics (precision, sensitivity, linearity, methods comparison, specificity, stability) characterize the algorithm and instrument's ability to quantitatively determine EPO levels without direct human interpretation of the assay's core output.
7. The Type of Ground Truth Used:
For the quantitative performance studies, particularly the "Methods Comparison," the ground truth was effectively the results obtained from established predicate devices, specifically the R&D Systems Quantikine IVD Erythropoietin ELISA Kit. These predicate devices are themselves validated diagnostic assays.
8. The Sample Size for the Training Set:
This information is not provided in the document. For an immunoassay, a "training set" in the context of machine learning isn't directly applicable in the same way it would be for an AI algorithm. Instead, "training" for such a system typically involves:
- Assay development and optimization using numerous samples.
- Establishing calibration curves using specific calibrator materials.
- Method validation experiments that might involve hundreds or thousands of samples over time.
The document refers to "Summary of Performance Studies" as direct validation of the assay's performance attributes rather than detailing a distinct "training set."
9. How the Ground Truth for the Training Set Was Established:
As mentioned above, the concept of a "training set" with an explicitly established ground truth (like expert consensus or pathology for AI) is not directly applicable to this type of IVD immunoassay. The development and calibration of the assay would rely on:
- Reference materials/standards: The assay is standardized against the "WHO 2nd IRP 67/343" (International Reference Preparation). This serves as a fundamental "ground truth" for the quantitative measurement of EPO.
- Known concentrations: During assay development, samples with known EPO concentrations (often characterized by reference methods or gravimetric methods for primary standards) would be used to build and validate the assay's response curve.
- Cross-validation with existing methods: Early in development, comparison with established methods would help refine the assay's performance.
§ 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).”