(74 days)
For In Vitro Diagnostic Use
Mouse Anti-Human T-cell, CD4/FITC, MT310 + Mouse Anti-Human T-cell, CD8/RPE,DK25 (DAKO CD4/CD8) has been developed for use in flow cytometry for the analysis of T-helper/inducer cells and T-cytotoxic/suppressor cells. This reagent allows simultaneous detection and quantification of helper/inducer T-cells (CD4+ cells) and cytotoxic/supprossor T-cells (CD8+ cells) in peripheral blood of 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 CD4, CloneMT310, conjugated with fluorescein isothiocyanate, isomer 1 (FITC) + purified mouse anti-human CD8, Clone DK25, 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.
This is a 510(k) summary for a medical device, specifically, a dual-color flow cytometry reagent (DAKO CD4/CD8) for identifying T-helper/inducer (CD4+) and T-cytotoxic/suppressor (CD8+) cells in peripheral blood. The submission's purpose is to demonstrate substantial equivalence to a predicate device, not to establish new performance criteria. Therefore, the information provided focuses on comparative performance rather than setting and meeting independent acceptance criteria.
Here's an analysis based on the provided text, addressing your questions where applicable:
Acceptance Criteria and Reported Device Performance
The concept of "acceptance criteria" as distinct, pre-defined thresholds against which the device must perform is not explicitly stated in this 510(k) summary. Instead, the performance is demonstrated by comparison to a predicate device. The implied acceptance criterion is that the DAKO CD4/CD8 reagent should perform "as well as" or show "high correlation" with the predicate device (CytoStat/Coulter Clone T8-RD1/T4-FITC).
Table of Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implied) | Reported Device Performance (DAKO CD4/CD8 vs. Predicate) |
|---|---|---|
| CD4+ T-cell Measurement Correlation | Correlation "approached a direct 1:1 comparison" and "greater than 0.98" | Correlation greater than 0.98 (using whole blood method) |
| CD8+ T-cell Measurement Correlation | Correlation "approached a direct 1:1 comparison" and "greater than 0.98" | Correlation greater than 0.98 (using whole blood method) |
| CD4 Linearity (using CEM cells) | N/A (Predicte performance not given, but good linearity is desirable) | y = 4.26% + 0.93x; r = 0.999 |
| CD8 Linearity (using JM cells) | N/A (Predicate performance not given, but good linearity is desirable) | y = 0.06% + 1.01x; r = 0.999 |
| Reproducibility | N/A (Implied: acceptable consistency across replicates/flow cytometers) | Measured, but specific quantitative results not provided; described as "reproducibility... was measured" at three concentrations on two different flow cytometers. |
| Cross-reactivity | N/A (Implied: minimal/no significant cross-reactivity with other blood cells) | Measured with peripheral blood cells (RBCs, monocytes, granulocytes, lymphocytes, and platelets); specific results not provided. |
Study Details
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Sample Size used for the test set and the data provenance:
- The exact sample size for the test set is not explicitly stated. The text mentions "peripheral blood samples obtained from apparently healthy adults as well as ill patients" for the correlation studies.
- Data Provenance: Not specified (e.g., country of origin). The study involved "apparently healthy adults" and "ill patients," suggesting clinical samples. The linearity testing used CEM cells and JM cells, which are cell lines. The antibody clones were characterized at international workshops (Boston, USA and Oxford, England).
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- Not applicable in the conventional sense of expert review for image/diagnostic interpretation. This device is a flow cytometry reagent for cell enumeration. The "ground truth" for the comparison study would be the results obtained from the predicate device. The qualification of individuals operating the flow cytometer and performing the tests would be standard clinical laboratory personnel, but details are not provided. The Leukocyte Typing Workshops involved experts in immunology and cell surface markers, but their role was in characterizing the antibody clones, not in establishing ground truth for a specific patient test set in this 510(k) study.
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Adjudication method for the test set:
- Not applicable. This study involves quantitative measurements by two different reagents/methods rather than subjective interpretation requiring adjudication.
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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-assisted diagnostic device, nor does it involve human "readers" interpreting images or cases in the context of an MRMC study. It's a laboratory reagent.
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If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- The device itself is a reagent used in conjunction with a flow cytometer. The "standalone" performance in this context would refer to the reagent's inherent ability to bind to specific cell markers. The performance data (correlation, linearity, reproducibility) represents the algorithm only (i.e., the reagent's performance characteristics) as measured by the flow cytometer, without human subjective interpretation influencing the quantitative output of the cell counts. The human is "in-the-loop" for sample preparation, running the instrument, and interpreting the raw numerical output from the flow cytometer, but not in a way that introduces variability in the measurement itself between the two reagents being compared.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The "ground truth" for the comparative effectiveness study was the measurements obtained from the predicate device (CytoStat/Coulter Clone T8-RD1/T4-FITC), which had been previously cleared by FDA. This is a common approach for demonstrating substantial equivalence for new reagents/devices that perform an existing function.
- For the antibody clones themselves (MT310 for CD4, DK25 for CD8), their identity and specificity were established through international scientific consensus at the Leukocyte Typing Workshops, which relied on extensive experimental evidence and expert evaluation.
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The sample size for the training set:
- Not applicable. This device is a diagnostic reagent, not a machine learning or AI algorithm that requires a "training set" in the computational sense.
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How the ground truth for the training set was established:
- Not applicable. See point 7.
§ 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.”