(462 days)
Ortho-mune OK-COMBO CD3-FITC/CD8-PE is intended for use in identification and enumeration of CD3+ and CD8+ human T lymphocytes in whole blood by flow cvtometry. The intended use is the same as the intended use of the predicate device(s), Ortho-mune OKT3 Monoclonal Antibody (Murine) FITC Conjugate, and Ortho-mune OKT8 Monoclonal Antibody (Murine) Phycoerythrin conjugate.
Ortho-mune OK-COMBO CD3-FITC/CD8-PE (OKT3/OKT8) Monoclonal Antibody (Murine) is a blend of the individual purified monoclonal antibodies OKT3 and OKT8 conjugated to the fluorochromes fluorescein isothiccyanate and phycoerythrin respectively.
This document describes the performance characteristics of the Ortho-mune™ OK-COMBO CD3-FITC/CD8-PE (OKT3/OKT8) Monoclonal Antibody (Murine) and its equivalence to predicate single-color reagents. Note: This document is from 1996 and uses terminology and study designs common for that era. There are no explicitly stated "acceptance criteria" in the format of pass/fail thresholds in this summary. Instead, the study aims to demonstrate "equivalence" through statistical comparisons and reproducibility. The document also does not describe an AI/algorithm-based device but rather a new diagnostic reagent. Therefore, sections related to AI-specific criteria (e.g., human-in-the-loop, AI vs. without AI assistance, training data) are not applicable.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
As mentioned, explicit, quantitative acceptance criteria with pass/fail thresholds are not stated. Instead, the studies aimed to demonstrate equivalence to predicate devices and acceptable reproducibility and linearity. The reported device performance is presented as statistical comparisons and descriptive statistics.
| Study Type | Performance Metric | Stated Goal (Implicit Acceptance Criteria) | Reported Device Performance and Conclusion |
|---|---|---|---|
| Equivalence to Predicate Dual-color vs. Single-color Reagents | Mean % & Range % for CD3+ and CD8+ cells | Equivalence in percentage detection to predicate single-color reagents. | Normal Donors (N=199): |
- CD3+: Dual Color Mean % = 74.5 (Range 45.9-87.4) vs. Single Color Mean % = 75.9 (Range 58.4-90.1)
- CD8+: Dual Color Mean % = 31.2 (Range 15.0-74.9) vs. Single Color Mean % = 29.2 (Range 13.2-75.5)
AIDS/ARC Patients (N=77):
- CD3+: Dual Color Mean % = 73.5 (Range 27.5-90.7) vs. Single Color Mean % = 77.7 (Range 35.6-96.4)
- CD8+: Dual Color Mean % = 59.1 (Range 25.6-89.8) vs. Single Color Mean % = 60.3 (Range 18.1-92.1)
Combined Population (Normal & AIDS/ARC):
- CD3+: Linear regression: Y = -0.359 + 0.976(X), R = 0.928
- CD8+: Linear regression: Y = 5.547 + 0.882(X), R = 0.969
Conclusion: Performance is "equivalent" to single-color reagents. |
| Equivalence to Other Flow Cytometers | Linear regression (Correlation R-value) | Equivalence of ORTHO CYTORONABSOLUTE with recognized flow cytometers (FACScan and EPICS). | CYTORONABSOLUTE vs. FACScan (CD3+CD8+): Y = -0.3519 + 1.03999(x), R = 0.9955
CYTORONABSOLUTE vs. COULTER EPICS (CD3+CD8+): Y = 2.707 + 0.981(X), R = 0.983
Conclusion: Demonstrates "equivalent performance" of the ORTHO CYTORONABSOLUTE flow cytometer to Becton Dickinson FACScan and COULTER EPICS. |
| Within-Laboratory Reproducibility | Coefficient of Variation (CV) | Acceptable within-laboratory reproducibility for various cell percentages (low, normal, high). | TOTAL CD3+ Low/Normal/High: CVs from 1.539% to 3.488% across 3 sites.
CD3+CD8+ Low/Normal/High: CVs from 2.904% to 11.214% across 3 sites.
Conclusion: Acceptable within-laboratory reproducibility. |
| Between-Laboratory Reproducibility | Coefficient of Variation (CV) | Acceptable between-laboratory reproducibility for various cell percentages. | TOTAL CD3+ Low/Normal/High: Across Site CVs from 1.139% to 2.899%.
CD3+CD8+ Low/Normal/High: Across Site CVs from 1.837% to 12.309%.
Conclusion: Acceptable between-laboratory reproducibility. |
| Linearity Study | Slope and R-value of linear regression (Observed vs. Expected) | Linear performance across a wide range of lymphocyte counts. | TOTAL CD3+ (All donors): Slope = 0.999 (CI 0.001), R = 1.000
CD3+CD8+ (All donors): Slope = 1.000 (CI 0.002), R = 1.000
Conclusion: Demonstrated linear performance for both subsets across 20 to 18,676 cells/ul with slopes "indistinguishable from 1" and R values of 1.000. (Note: An R-value of exactly 1.000 is highly unusual in biological systems and may suggest data smoothing or specific analytical methods). |
2. Sample sizes used for the test set and the data provenance
Equivalence to Predicate Reagents Study:
- Sample Size: 199 normal donors and 77 AIDS/ARC patients. Total N=276.
- Data Provenance: Not explicitly stated, but likely from a US-based clinical setting as it's a 510(k) submission to the FDA. The data is prospective, collected for the purpose of this study.
Equivalence to Other Flow Cytometers Study:
- Sample Size: Ten normal donors (whole blood, EDTA).
- Data Provenance: Not explicitly stated, but likely from a US-based clinical setting, prospective.
Reproducibility Studies:
- Sample Size: Eleven normal donors (whole blood, EDTA).
- Data Provenance: Not explicitly stated, but likely from a US-based clinical setting, prospective. Conducted at three independent laboratories.
Linearity Study:
- Sample Size: Four normal donors (whole blood, EDTA).
- Data Provenance: Not explicitly stated, but likely from a US-based clinical setting, prospective.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This device is a reagent for flow cytometry, which directly identifies and enumerates cell populations. The "ground truth" for the test set is established by the measurements from the predicate devices (single-color reagents) which are considered the established method. There are no human experts "establishing ground truth" in the sense of image interpretation or diagnostic classification. The measurements are quantitative outputs from flow cytometers.
4. Adjudication method for the test set
Not applicable. This device provides quantitative measurements from a flow cytometer. The "ground truth" is derived from a comparative measurement against established methods (predicate reagents) or from internal consistency (reproducibility, linearity). There is no subjective human assessment requiring adjudication.
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
Not applicable. This is not an AI/algorithm-based diagnostic device where human readers interact with AI. It is a laboratory reagent.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This is not an AI algorithm. Its performance is evaluated in a standalone manner against predicate reagents and for its intrinsic measurement characteristics (reproducibility, linearity) when used with a flow cytometer.
7. The type of ground truth used
The ground truth used for assessing the new dual-color reagent (Ortho-mune OK-COMBO CD3-FITC/CD8-PE) was primarily:
- Comparative Measurements: Measurements obtained from the predicate single-color reagents (Ortho-mune OKT3 Monoclonal Antibody FITC Conjugate and Ortho-mune OKT8 Monoclonal Antibody Phycoerythrin conjugate) for CD3+ and CD8+ cell percentages.
- Internal Consistency: For reproducibility and linearity studies, the ground truth is the expected statistical behavior (e.g., low coefficient of variation for reproducibility, R-value near 1 and slope near 1 for linearity with serially diluted samples or known concentrations).
- Comparison to other established flow cytometers: For the instrument comparison part of the study, the measurements from the Becton Dickinson FACScan and COULTER EPICS flow cytometers were used as a comparative benchmark for the ORTHO CYTORONABSOLUTE.
There is no pathology, expert consensus on subjective findings, or outcomes data used as ground truth in this submission for this specific device.
8. The sample size for the training set
Not applicable. This is not an AI/machine learning algorithm. There is no concept of a "training set" for this type of diagnostic reagent.
9. How the ground truth for the training set was established
Not applicable. As this is not an AI/machine learning algorithm, there is no training set or ground truth established for it in that context.
§ 864.5220 Automated differential cell counter.
(a)
Identification. An automated differential cell counter is a device used to identify one or more of the formed elements of the blood. The device may also have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood, bone marrow, or other body fluids. These devices may combine an electronic particle counting method, optical method, or a flow cytometric method utilizing monoclonal CD (cluster designation) markers. The device includes accessory CD markers.(b)
Classification. Class II (special controls). The special control for this device is the FDA document entitled “Class II Special Controls Guidance Document: Premarket Notifications for Automated Differential Cell Counters for Immature or Abnormal Blood Cells; Final Guidance for Industry and FDA.”