(56 days)
Ortho-mune OKB19A PE Conjugate is intended for use in identification and enumeration of CD19+ human B lymphocytes in whole blood by flow cytometry.
Ortho-mune OKB19A Monoclonal Antibody (Murine) Phycoerythrin (PE) Conjugate contains the purified monoclonal antibody OKB19A conjugated to the fluorochrome phycoerythrin.
The provided document describes the performance characteristics of the Ortho-mune™ OKB™19A (CD19) Monoclonal Antibody (Murine) Phycoerythrin Conjugate, a diagnostic device for identifying and enumerating CD19+ human B lymphocytes.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance:
The document doesn't explicitly state numerical acceptance criteria in a formal table. Instead, the acceptance is based on demonstrating "substantial equivalence" to a predicate device (Monoclonal Antibody Test for B Cells [Anti-Leu-12 (CD19) PE (Phycoerythrin)]). The performance is assessed through various studies. Below is a table summarizing the reported device performance and implicitly derived acceptance criteria based on equivalence:
| Performance Metric | Acceptance Criteria (Implicit, based on equivalence to predicate) | Reported Device Performance (Ortho-mune OKB19A) |
|---|---|---|
| Comparative Performance (Normal Donors) | Mean % CD19+ and Range % CD19+ should be comparable to the predicate device. | Mean % CD19+: 13.3, Range % CD19+: 1.3 - 31.1 |
| Comparative Performance (AIDS/ARC Patients) | Mean % CD19+ and Range % CD19+ should be comparable to the predicate device. | Mean % CD19+: 10.2, Range % CD19+: 0.4 - 41.9 |
| Linear Regression (Relative to Predicate) | High correlation (R value close to 1) and a slope close to 1, indicating similar measurements. | R = 0.909, Equation: Y = 0.711 + 0.88(X) (for combined data) |
| Within-Laboratory Reproducibility (Normal) | Coefficient of Variation (CV) should be acceptable for flow cytometry assays, similar to predicate performance (not explicitly stated, but assumed to be low). | Mean % Positive: 15.330, Site A CV: 5.082, Site B CV: 4.635, Site C CV: 4.545 |
| Within-Laboratory Reproducibility (Low) | CV should be acceptable. | Mean % Positive: 1.134, Site A CV: 24.182, Site B CV: 20.793, Site C CV: 22.106 |
| Within-Laboratory Reproducibility (High) | CV should be acceptable. | Mean % Positive: 26.760, Site A CV: 3.438, Site B CV: 3.401, Site C CV: 3.447 |
| Between-Laboratory Reproducibility (Normal) | Low CV across sites. | Overall Across Site CV: 0.976 |
| Between-Laboratory Reproducibility (Low) | Low CV across sites. | Overall Across Site CV: 1.466 |
| Between-Laboratory Reproducibility (High) | Low CV across sites. | Overall Across Site CV: 0.782 |
| Linearity (across lymphocyte count range) | Slopes indistinguishable from 1 and R values close to 1.000. | Slopes between 1.001 and 1.004, R values of 1.000 (for each donor and all combined) |
2. Sample Sizes Used for the Test Set and Data Provenance:
- Comparative Performance Study (against predicate):
- Sample Size: 205 normal donors and 87 AIDS/ARC patients.
- Data Provenance: The study was conducted at "three external, geographically distinct sites." The specific countries are not mentioned, but the distributed nature suggests a multi-center study. The data is prospective as specimens were stained and analyzed during the study.
- Reproducibility Studies:
- Sample Size: 10 normal donors for each of the three independent laboratories.
- Data Provenance: Three independent laboratories (suggesting different locations, likely within the same country as the submitter, USA, but not explicitly stated). The data is prospective as samples were processed and stained for the study.
- Linearity Study:
- Sample Size: Four normal donors.
- Data Provenance: Not explicitly stated where the donors or testing took place, but implied as part of the overall development and testing by the submitter. The data is prospective.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and the Qualifications of Those Experts:
This information is not applicable to this device. The device is a diagnostic reagent for flow cytometry, which measures cell populations based on antibody binding. The "ground truth" for the comparative study is the measurement obtained by the predicate device and the clinical classification of the patients (normal donor vs. AIDS/ARC). For reproducibility and linearity, the ground truth is statistical consistency and expected values determined by dilutions and other analytical methods, not expert consensus on an image or clinical case.
4. Adjudication Method for the Test Set:
This information is not applicable. Adjudication methods (like 2+1, 3+1) are typically used in studies where human readers are making subjective diagnoses or classifications from images/data, and discrepancies need to be resolved. This study involves objective measurements from a flow cytometer.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study:
No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. MRMC studies are associated with evaluating the effectiveness of diagnostic tools where multiple human readers interpret cases. This study is comparing a new reagent's performance to an existing reagent using instrumental measurements.
6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study:
Yes, the studies described are essentially a standalone performance evaluation of the Ortho-mune OKB19A reagent. The flow cytometer analyzes the stained cells, and the resulting data (percentage of CD19+ cells) is the output of the "algorithm" (the staining and detection process). Human involvement is in sample preparation, running the instrument, and data analysis, but the core measurement itself is automated and doesn't involve human interpretation of complex patterns in the way an AI algorithm for image analysis would. The performance is assessed purely on the device's ability to accurately identify and enumerate the target cells, comparing its output to a predicate device's output.
7. Type of Ground Truth Used:
- Comparative Performance: The ground truth was effectively the measurement obtained by the predicate device (Monoclonal Antibody Test for B Cells [Anti-Leu-12 (CD19) PE (Phycoerythrin)]) on the same samples. The clinical categorisation of "normal donor" and "AIDS/ARC patient" also serves as a clinical context for evaluating performance.
- Reproducibility Studies: The ground truth was based on the statistical expectation of consistent measurements when the same samples are tested multiple times (within-laboratory) and across different laboratories (between-laboratory). The "true" value for the percentage of CD19+ cells in the prepared samples was the reference point.
- Linearity Study: The ground truth was the expected values calculated by multiplying serial dilutions by the hematology analyzer-derived buffy coat lymphocyte count and the CYTORONABSOLUTE-derived lymphocyte subset percent positive.
8. Sample Size for the Training Set:
This information is not applicable as this is not an AI/Machine Learning device that requires a training set. The device is a monoclonal antibody conjugate; its performance is based on its biochemical properties and interaction with target cells.
9. How the Ground Truth for the Training Set Was Established:
This information is not applicable for the reason stated above.
§ 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.”