(60 days)
For In Vitro Diagnostic Use
Mouse Anti-Human T-cell, CD2/FITC, MT910 + Mouse Anti-Human B-cell, CD19/RPE, HD37 (DAKO Anti-CD2/FITC and Anti-CD19/RPE) has been developed for use in flow cytometry for the analysis of CD2+ T-cells and CD19+ B-cells. This reagent allows simultaneous detection and quantification of T- and B-cells in normal and pathological conditions such as immunodeficiency disorders. It is one component of the suggested monoclonal antibody (MAb) combinations for routine immunophenotyping of lymphocytes in peripheral blood using flow cytometry.
Purified mouse anti-human CD2, Clone MT910, conjugated with fluorescein isothiocyanate, isomer 1 (FITC) + purified mouse anti-human CD19, Clone HD37, conjugated with R-phycoerythrin, present in 0.05M Tris-HCl buffer, pH 7.2, 15 mM NaN3, 0.1M NaCl, stabilized with 1% carrier protein.
Subpopulations of lymphocytes may be stained with fluorochrome-conjugated antibody and evaluated in peripheral blood specimens when contaminating red blood cells (RBC's) are lysed prior to flow cytometric analysis. A subpopulation of WBC's are selected for assessment based upon cell morphology.
Here's an analysis of the provided text regarding the acceptance criteria and study for the DAKO Mouse Anti-Human T-cell, CD2/FITC, MT910 + Mouse Anti-Human B-cell, CD19/RPE, HD37 device.
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria (Stated or Implied) | Reported Device Performance |
|---|---|
| Correlation with Predicate Device (CD2+ Cells) | Correlation > 0.99 for measurement of CD2+ T-cells (new device vs. DAKO CD2/FITC predicate). The statement "approached a direct 1:1 comparison" further supports this. |
| Correlation with Predicate Device (CD19+ Cells) | Correlation > 0.99 for measurement of CD19+ T-cells (new device vs. DAKO CD19/RPE predicate). The statement "approached a direct 1:1 comparison" further supports this. |
| Linearity of CD2/FITC | Linear equation: y = -0.02 + 0.997x; r = 0.9965 (using JM cells). The high 'r' value indicates good linearity. |
| Linearity of CD19/RPE | Linear equation: y = -0.49 + 0.99x; r = 0.999 (using Raji cells). The high 'r' value indicates good linearity. |
| Reproducibility | "Reproducibility of DAKO reagents using replicates (from peripheral blood) run on two different flow cytometers was measured at three concentrations of each antigen." (No specific quantitative acceptance criteria or results are provided, only that it was measured). |
| Cross-reactivity | "Cross-reactivity of Anti-CD2/FITC, plus Anti-CD19/RPE with peripheral blood cells (red blood cells, monocytes, granulocytes, lymphocytes, and platelets) was measured." (No specific quantitative acceptance criteria or results are provided, only that it was measured). |
| Performance "as well as" Predicate | Concluded that the new reagent performs "as well as" the predicate devices for detecting and enumerating CD2 and CD19 lymphocytes. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: Not explicitly stated as a numerical count. The text mentions "peripheral blood samples obtained from apparently healthy adults" and "peripheral blood samples from normal and ill patients." It also refers to "replicates (from peripheral blood)" for reproducibility testing. Without a specific number, it's impossible to determine the precise sample size.
- Data Provenance: The data appears to be from a general population of "apparently healthy adults" and "normal and ill patients." The country of origin is not specified. It is a retrospective study, as it's a comparison of a newly combined reagent against existing, previously cleared predicate devices.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
- Number of Experts: Not applicable in the context of this device. The "ground truth" for the comparison study is the performance of the predicate devices themselves, which are well-established for flow cytometry.
- Qualifications of Experts: Not applicable.
4. Adjudication Method for the Test Set
- Adjudication Method: Not applicable. The "ground truth" is the measurement obtained from the predicate devices, not an expert consensus requiring adjudication.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- MRMC Study: No, an MRMC study was not done. This device is a reagent for flow cytometry, not an imaging or diagnostic AI tool that involves human readers interpreting results. The comparison is between two reagents.
- Effect Size of Human Readers: Not applicable.
6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done
- Standalone Performance: Yes, in a sense, the study describes the standalone performance of the new combined reagent compared to the standalone performance of the individual predicate reagents. Flow cytometry itself is an automated process, and the "performance" here refers to the quantitative measurements made by the instrument using the reagent. There is no "human-in-the-loop" performance in the traditional AI context.
7. The Type of Ground Truth Used
- Type of Ground Truth: The ground truth for this validation study is the performance of the predicate devices (DAKO Monoclonal Mouse Anti-Human T-cell, CD2/FITC, MT910 and DAKO Monoclonal Mouse Anti-Human B-cell, CD19/RPE, HD37). The goal was to show that the new combined reagent performed equivalently to the established individual reagents. Additionally, the clustering of the antibody clones (MT910 and HD37) at the Second Leukocyte Typing Workshop serves as a form of expert consensus and scientific validation of their specificity.
8. The Sample Size for the Training Set
- Sample Size for Training Set: Not explicitly mentioned. For reagents like this, there isn't a "training set" in the machine learning sense. The development of the individual antibodies (CD2, CD19) involves initial screening and selection. The manufacturing and formulation process optimization would involve various internal testing batches, but these are not typically quantified as a "training set" in regulatory summaries for this type of device.
9. How the Ground Truth for the Training Set Was Established
- Ground Truth for Training Set: As there's no traditional "training set" for an AI algorithm here, this question isn't directly applicable. However, the specificity and efficacy of the individual antibody clones (MT910 and HD37) that form the basis of this reagent were established through extensive research and validation, including their clustering at the Second Leukocyte Typing Workshop, Boston, 1984. This workshop functions as a multi-center expert consensus and standardization effort, effectively establishing the "ground truth" for the characteristics of these specific CD markers and their corresponding antibodies.
§ 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.”