(460 days)
Ortho-mune OK-COMBO CD3-FITC/CD4-PE is intended for use in identification and enumeration of CD3+ and CD4+ human T lymphocytes in whole blood by flow cytometry. The intended use is the same as the intended use of the predicate device, Simultest CD3/CD4 (Leu-4/3a) commercially distributed by Becton Dickinson Immunocytometry Systems.
Ortho-mune OK-COMBO CD3-FITC/CD4-PE (OKT3/OKT4A) Monoclonal Antibody (Murine) is a blend of the individual purified monoclonal antibodies OKT3 and OKT4A conjugated to the fluorochromes fluorescein isothiocyanate and phycoerythrin respectively.
The provided text describes a 510(k) summary for the Ortho-mune OK-COMBO CD3-FITC/CD4-PE (OKT3/OKT4A) Monoclonal Antibody (Murine) device, which is intended for the identification and enumeration of CD3+ and CD4+ human T lymphocytes in whole blood by flow cytometry. The study aims to demonstrate substantial equivalence to a predicate device, Simultest™ CD3/CD4 Ortho-mune™ OK-COMBO (Leu™-4 / 3a) CD3-FITC/CD4-PE (OKT™3 /OKT4A) Monoclonal Antibody (Murine).
Here's a breakdown of the requested information based on the provided text:
Acceptance Criteria and Reported Device Performance
The acceptance criteria are implicitly defined by achieving a statistically significant correlation between the performance of the new device (Ortho-mune OK-COMBO CD3-FITC/CD4-PE) and the predicate device (Simultest CD3/CD4), as well as between different flow cytometers used with the new device. The benchmark for significance is a p-value (SL) of 0.0001, indicating a very high probability of correlation. The Pearson Product Moment Correlation Coefficient is the metric used to assess this.
Table 1: Acceptance Criteria and Reported Device Performance
| Performance Metric | Acceptance Criteria (Implicit) | Reported Device Performance (Correlation Coefficient) |
|---|---|---|
| Normal Donors (N=202) | Pearson Correlation significantly high (e.g., SL < 0.0001) for comparison vs. predicate | |
| OKT3+ vs LEU4+ | 0.88 (SL: 0.0001) | |
| OKT4A+ vs LEU3a+ | 0.93 (SL: 0.0001) | |
| OKT3+T4A+ vs LEU4+3a+ | 0.93 (SL: 0.0001) | |
| AIDS/ARC Patients (N=86) | Pearson Correlation significantly high (e.g., SL < 0.0001) for comparison vs. predicate | |
| OKT3+ vs LEU4+ | 0.90 (SL: 0.0001) | |
| OKT4A+ vs LEU3a+ | 0.96 (SL: 0.0001) | |
| OKT3+T4A+ vs LEU4+3a+ | 0.97 (SL: 0.0001) | |
| Cytometer Comparison (N=17 Normal Donors) | Pearson Correlation significantly high (e.g., SL < 0.0001) for Ortho-mune on FACScan vs. CytoronAbsolute | |
| OKT3+ | 0.82 (SL: 0.0001) | |
| OKT4A+ | 0.89 (SL: 0.0001) | |
| OKT3+T4A+ | 0.89 (SL: 0.0001) | |
| Ortho-mune vs. Predicate on FACScan (N=17 Normal Donors) | Pearson Correlation significantly high (e.g., SL < 0.0001) | |
| OKT3+ vs LEU4+ | 0.85 (SL: 0.0001) | |
| OKT4A+ vs LEU3a+ | 0.92 (SL: 0.0001) | |
| OKT3+T4A+ vs LEU4+3a+ | 0.91 (SL: 0.0001) |
Additional Information:
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Sample size used for the test set and the data provenance:
- Primary Test Set: 202 normal donors and 86 AIDS/ARC patients.
- Secondary Test Set (Cytometer Comparison): 17 normal donors.
- Data Provenance: The text does not explicitly state the country of origin. It indicates "Whole blood specimens" were collected, implying prospective collection for the purpose of the study. It does not mention retrospective data.
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Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This device is a diagnostic reagent for flow cytometry, which measures cell populations directly. The "ground truth" is established by the flow cytometer itself detecting the stained cells. There is no mention of human experts interpreting images or signals to establish a ground truth; rather, the "truth" is the quantitative measurement of stained cells.
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Adjudication method for the test set:
- Not applicable. The study compares the performance of two different monoclonal antibody reagents and two different flow cytometers by measuring the percentage of positive stained cells. This is a direct quantitative comparison, not one that requires adjudication by human readers.
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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:
- No. This is a direct comparison of diagnostic reagents and flow cytometers, not an AI-based system involving human readers interpreting outputs.
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If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, in essence. The comparison is between the performance of two different reagents in identifying and enumerating cell populations using flow cytometry, which is an automated process of cell counting and characterization. The performance is measured directly by the instrument, without human interpretation of subjective data.
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The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth is established by the quantitative measurement of cells positively stained by the predicate device's reagents (Simultest CD3/CD4). The study then evaluates if the new device's reagents produce statistically equivalent measurements. In the cytometer comparison, the ground truth for comparing the CytoronAbsolute to the FACScan is also the measurement performed by the predicate device on the FACScan. The underlying biological "ground truth" is the actual percentage of CD3+ and CD4+ T lymphocytes present in the whole blood samples, as identified by specific antibody binding.
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The sample size for the training set:
- Training sets are not mentioned. This type of study validates a specific reagent's performance against a legally marketed predicate device rather than training a machine learning model. The study evaluates the performance of the reagent on a test set (normal donors and AIDS/ARC patients).
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How the ground truth for the training set was established:
- Not applicable, as there is no mention of a training set in the context of machine learning. The study focuses on comparing the new device's performance to a predicate device.
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950568
510 (k) SUMMARY
MAY 1 3 1996
Ortho Diagnostic Systems Inc. SUBMITTER: 1001 U.S. Hwy 202 Raritan, NJ 08869-0606
CONTACT : Joanne Harris Tel.: (908) 218-8404 Fax.: (908) 218-8168
PREDICATE: Simultest™ CD3/CD4 Ortho-mune™ OK-COMBO DEVICE NAME: (Leu™-4 / 3a) CD3-FITC/CD4-PE (OKT™3 /OKT4A) Monoclonal Antibody (Murine)
DATE: February 3, 1995
DEVICE DESCRIPTION:
Ortho-mune OK-COMBO CD3-FITC/CD4-PE (OKT3/OKT4A) Monoclonal Antibody (Murine) is a blend of the individual purified monoclonal antibodies OKT3 and OKT4A conjugated to the fluorochromes fluorescein isothiocyanate and >hycoerythrin respectively.
INTENDED USE:
Ortho-mune OK-COMBO CD3-FITC/CD4-PE is intended for use in identification and enumeration of CD3+ and CD4+ human T lymphocytes in whole blood by flow The intended use is the same as the intended use of the cytometry. predicate device, Simultest CD3/CD4 (Leu-4/3a) commercially distributed by Becton Dickinson Immunocytometry Systems.
TECHNOLOGICAL CHARACTERISTICS:
Both Ortho-mune OK-COMBO CD3-FITC/CD4-PE (OKT3/OKT4A) Monoclonal Antibody (Murine) and Simultest CD3/CD4 (Leu-4/3a) utilize monoclonal antibodies specific for human T cells (OKT3/Leu-4) and human helper/inducer T cells (OKT4A/Leu-3a) respectively, conjugated to the same fluorochromes, fluorescein isothiocyanate and phycoerythrin.
Ortho Diagnostic Systems Inc. Ortho-mune™ OK-COMBO CD3-FITC/CD4-PE (OKT 3/OKT4) Sonoclonal Antibody (Murine) age 118
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PERFORMANCE DATA:
Performance of the two color reagent Ortho-mune OK-COMBO CD3-FITC/CD4-PE roKT3/OKT4A) Monoclonal Antibody (Murine) was compared with that of Simultest CD3/CD4(Leu-4/3a). Whole blood specimens from 202 normal donors, and 86 AIDS/ARC_patients were stained and analyzed using the and oo Arborake particular , Ortho Diagnostic Systems Inc.
For each specimen, the percentage of gated cells which showed positive staining by each marker was compared. The comparison was done by scalling by each marker was complex of positive stained cells for each marker. The Pearson product moment correlation was the statistical method used to compare the reagents. These data are shown in Table A for mechod about on orable B for the AIDS/ARC population. OK-COMBO che normal pope and Simultest CD3/CD4 reagents gave equivalent results for the CD3 and CD4 markers when used to stain whole blood from normal donors and AIDS/ARC patients.
| TABLE A: N=202PEARSON PRODUCT MOMENT CORRELATIONPERCENT POSITIVE STAINED CELLS IN NORMAL DONORS DETECTED BY OKT3/OKT4AAND LEU4/3a ASSAYED ON THE CYTORONABSOLUTE | |||||||
|---|---|---|---|---|---|---|---|
| Ortho-MuneReagent | Mean% | Range% | BDReagent | Mean% | Range% | Correlation | SL1 |
| OKT3+ | 75.8 | 58.3-89.1 | LEU4+ | 74.2 | 57.0-87.7 | 0.88 | 0.0001 |
| OKT4A+ | 46.2 | 13.5-69.0 | LEU3a+ | 45.3 | 14.5-64.1 | 0.93 | 0.0001 |
| OKT3+T4A+ | 45.6 | 13.3-69.0 | LEU4+3a+ | 44.9 | 14.3-63.7 | 0.93 | 0.0001 |
i. SL Is The Significance Level, e.g., An SL Of 0.0500 Would Mean That There Is A 95% Probability That The Ortho-Mune And The BD Reagent Are Significantly Correlated.
| Ortho-MuneReagent | Mean% | Range% | BDReagent | Mean% | Range% | Correlation | SL1 |
|---|---|---|---|---|---|---|---|
| OKT3+ | 76.7 | 26.0-94.0 | LEU4+ | 76.5 | 39.8-95.3 | 0.90 | 0.0001 |
| OKT4A+ | 16.7 | 0.5-47.7 | LEU3a+ | 16.6 | 0.6-51.5 | 0.96 | 0.0001 |
| OKT3+T4A+ | 16.2 | 0.4-47.5 | LEU4+3a+ | 16.3 | 0.5-51.3 | 0.97 | 0.0001 |
- SL Is The Significance Level, e.g. An SL Of 0.0500 Would Mean That There Is A 95% Probability That The Ortho-Mune And The BD Reagent Are Significantly Correlated.
Ortho Diagnostic Systems Inc. (ORT' 3 / OKT. 4 ) Ortho-mune™ OK-COMBO CD3-FITC/CD4-PE Wonoclonal Antibody (Murine) age 119
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Studies were also performed using the Becton Dickinson FACScan™ flow cytometer. Whole blood samples were collected from 17 normal donors. These samples were tested as collected to provide normal range cell counts, nd were also concentrated 5-fold and diluted 5-fold to yield high range and low range cell counts. Samples were stained using Ortho-mune OX-COMBO CD3-FITC/CD4 PE and Simultest CD3/CD4 (Lev-4/3A) reagent. The samples stained with the OK-COMBO reagent were analyzed on both the CytoronAbsolute flow cytometer and the FACScan flow cytometer. The same samples stained with Simultest reagent were analyzed on the FACScan flow cytometer.
The mean percentage and range of positive stained cells for each marker and for the double positive stained cells were correlated using Pearson product The results with Ortho-mune OK-COMBO reagent analyzed moment correlation. on both the CytoronAbsolute flow cytometer and the FACScan flow cytometer are provided in Table F. The results comparing the OK-COMBO reagent with the Simultest reagent analyzed on the FACScan flow cytometer are provided in Table G.
The data demonstrate equivalent performance of Ortho-mune OK-COMBO CD3-FITC/CD4-PE reagent using both the CytoronAbsolute and FACScan flow cytometers, and equivalent performance of Ortho-mune OK-COMBO CD3-FITC/CD4-PE reagent to the Simultest CD3/CD4 (Leu-4/3a) reagent when analyzed on the FACScan flow cytometer.
| Ortho-MuneReagent | FACScan | Cytoron | FACScan Vs Cytoron | |||
|---|---|---|---|---|---|---|
| Mean% | Range | Mean% | Range | Correlation | SL1 | |
| OKT3+ | 72.7 | 53.0-92.0 | 72.3 | 51.9-84.9 | 0.82 | 0.0001 |
| OKT4A+ | 52.6 | 39.0-65.0 | 49.2 | 34.7-62.7 | 0.89 | 0.0001 |
| OKT3+T4A+ | 49.0 | 35.0-68.0 | 48.4 | 34.0-62.4 | 0.89 | 0.0001 |
- SL Is The Significance Level, e.g. SL Of 0.0500 Would Mean That There Is A 95% Probability That The Ortho-Mune Reagent, Assayed On Both Instruments, Are significantly Correlated.
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49.0
| Ortho-MuneReagent | FACScan | BDReagent | FACScan | Ortho Vs BD Reagent | |||
|---|---|---|---|---|---|---|---|
| Mean% | Range | Mean% | Range | Correlation | SL1 | ||
| OKT3+ | 72.7 | 53.0-92.0 | LEU4+ | 71.8 | 52.0-88.0 | 0.85 | 0.0001 |
| OKT4A+ | 52.6 | 39.0-65.0 | LEU3a+ | 51.8 | 36.0-65.0 | 0.92 | 0.0001 |
| OKT3+T4A+ | 49.0 | 35.0-68.0 | LEU4+3a+ | 47.5 | 33.0-62.0 | 0.91 | 0.0001 |
47.5
- SL Is The Significance Level, e.g. SL Of 0.0500 Would Mean That There Is A 95% Probability That The Ortho-Mune And BD Reagents, Assayed On The FACScan, Are Significantly Correlated.
LEU4 3a
35.0-68.0
CONCLUSIONS :
OKT3 T4A
Performance of the two color reagent Ortho-mune OK-COMBO CD3-FITC/CD4PE 1. (OKT3/OKT4A) Monoclonal Antibody (Murine) is substantially equivalent to Simultest CD3/CD4 (Leu-4/3a) reagent in identification and enumeration of CD3+ and CD4+ human lymphocytes in whole blood by flow cytometry.
0.91
33.0-62.0 |
§ 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.”