(486 days)
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No
The summary describes a DNA probe for FISH analysis and its performance characteristics. There is no mention of image processing, AI, DNN, or ML. The analysis relies on manual interpretation of fluorescent signals.
No
This device is an in vitro diagnostic (IVD) assay designed for detection and quantification of chromosome 8, which is used for diagnostic purposes, not for treating a condition.
Yes
Explanation: The device is described as an "assay" designed for "detection and quantification of chromosome 8" using FISH, which is inherently a method for identifying the presence and amount of specific biological markers, indicating its use for diagnosis. The performance studies also include sensitivity and specificity relative to standard cytogenetic analysis for classifying trisomy 8, further confirming its diagnostic purpose.
No
The device description explicitly states it is a "SpectrumOrange fluorescent labeled DNA probe," which is a physical reagent, not software. The summary describes performance studies related to the probe's analytical characteristics and its use in a laboratory setting, further indicating it is a hardware/reagent-based device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states that the assay is designed for the "detection and quantification of chromosome 8 in both interphase nuclei and metaphase spreads by fluorescence in situ hybridization (FISH)." This is a diagnostic purpose, aiming to identify and measure a specific biological marker (chromosome 8) in human samples (bone marrow).
- Device Description: The device is a "fluorescent labeled DNA probe specific for the centromeric region of chromosome 8." This is a reagent used in a laboratory setting to perform a diagnostic test.
- Anatomical Site: The test is performed on "Bone marrow," which is a human specimen.
- Performance Studies: The document details performance studies, including analytical sensitivity, specificity, reproducibility, and methods comparison with standard cytogenetic analysis using clinical specimens. This is characteristic of the validation required for an IVD.
- Key Metrics: The document provides key metrics like relative sensitivity and specificity, which are crucial for evaluating the performance of a diagnostic test.
The core function of the device is to provide information about a patient's biological state (the presence and quantity of chromosome 8) using a test performed on a sample taken from the patient. This aligns directly with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The CEP 8 SpectrumOrange DNA Probe is a SpectrumOrange fluorescent labeled DNA probe specific for the centromeric region of chromosome 8. This assay is designed to provide a method for the detection and quantification of chromosome 8 in both interphase nuclei and metaphase spreads by fluorescence in situ hybridization (FISH).
Product codes (comma separated list FDA assigned to the subject device)
OYU, KIR
Device Description
The CEP 8 SpectrumOrange DNA Probe is a SpectrumOrange fluorescent labeled DNA probe specific for the centromeric region of chromosome 8.
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
bone marrow
Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
The document describes several studies:
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Analytical Sensitivity and Specificity
- Hybridization Efficiency: In a pilot study, 35 bone marrow (BM) specimens showed an average of 0.22% cells with no hybridization signal. In a pivotal study, 60 BM specimens showed an average of 0.11% cells with no hybridization signal.
- Analytical Sensitivity: The 0% specimen was estimated with a mean of 0.95% (s.d. 0.51%) tri-signaled nuclei. The 5% specimen was estimated at 5.37% (s.d. = 0.98%). The limit of detection for CEP 8 in interphase cells is estimated to be 4.0%.
- Analytical Specificity: 62 metaphase spreads were examined. No cross-hybridization to other chromosome loci was observed; hybridization was limited to the centromere region of chromosome 8.
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Reproducibility
- Pilot study (inter-site, inter-day, inter-observer): One normal bone marrow specimen was evaluated for %tri-signaled cells. Statistically significant site-to-site and observer-to-observer variations were observed. Classification of slides as positive or negative for trisomy 8 (using a cutoff of 2.2%) was 96% correct (1 of 24 had 2.4% tri-signaled nuclei). Overall variation for %tri-signaled nuclei: N=24, mean=0.99%, SD=0.57%, CV=58%.
- Pivotal study (inter-site, inter-lot, inter-day, inter-observer): One low level (approximately 7%) trisomy 8 bone marrow specimen was evaluated. Statistically significant site-to-site and observer variations were observed. Classification of slides as positive or negative for trisomy 8 (using a cutoff of 2.2%) was 100% correct. Overall variation for %trisignaled nuclei: N=24, mean=7.70%, SD=1.45%, CV=19%.
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Methods Comparison; Clinical Specimens
- Study Type: Multi-center, blinded, controlled, comparative study to determine sensitivity and specificity relative to standard cytogenetic analysis.
- Sample Size: 368 archived bone marrow specimens from 4 laboratories assayed at 3 investigation sites. Of these, 151 were positive for trisomy 8, 201 negative, and 16 ambiguous by standard cytogenetic analysis. Specimen diagnoses included AML (102), MPD (44), MDS (80), CML (72), and HIDNOS (70). Some specimens from one site failed to produce informative FISH results due to improper storage.
- FISH Interphase Analysis versus Standard Cytogenetics: Based on a 2.2% cutoff:
- Relative sensitivity: 96.03% (145/151) [95% C.I. 92.55 -99.51%]
- Relative specificity: 98.01% (197/201) [95% C.I. 96.08 -99.94%]
- Correlation coefficient of trisomy 8 between standard cytogenetic metaphase analysis and CEP 8 interphase analysis: 0.91.
- Regression coefficient of CEP 8 assay on cytogenetic analysis: 0.71.
- Equation: y = 1.2944 + 0.7112x (x = percent metaphase spreads with trisomy 8 by standard cytogenetics, y = percent tri-signaled interphase nuclei by CEP 8 analysis).
- FISH Metaphase Analysis versus Standard Cytogenetics:
- Sample Size: 348 cases (20 cases excluded due to insufficient metaphase spreads).
- Using a cutoff of ≥ 2 tri-signaled metaphases:
- Relative sensitivity: 89.19% (132/148) [95% C.I. 84.19 - 94.19%]
- Relative specificity: 91.30% (168/184) [95% C.I. 87.22 - 95.37%]
- Correlation coefficient of trisomy 8 between cytogenetic metaphase analysis and CEP 8 metaphase analysis: 0.91.
- Regression coefficient of CEP 8 assay on cytogenetic analysis: 0.83.
- Equation: y = 1.6979 + 0.8325x (x = percent metaphase spreads with trisomy 8 by standard cytogenetics, y = percent tri-signaled metaphase spreads by CEP 8 analysis).
- FISH Interphase Analysis versus FISH Metaphase Analysis:
- Sample Size: 348 clinical specimens.
- Concordance: 90.8% [(133+183)/348].
- Correlation coefficient of trisomy 8 between CEP 8 interphase analysis and CEP 8 metaphase analyses: 0.95.
- Regression coefficient of CEP 8 metaphase analysis on interphase analysis: 0.81.
- Equation: y = 1.0942 + 0.8119x (x = percent tri-signaled interphase cells by CEP 8 analysis, y = percent tri-signaled metaphase spreads by CEP 8 analysis).
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Analytical Sensitivity: 4.0% (limit of detection for interphase cells)
- Analytical Specificity: 100% (No cross-hybridization to other chromosome loci)
- Relative Sensitivity (FISH Interphase vs Standard Cytogenetics): 96.03% (145/151) [95% C.I. 92.55 -99.51%]
- Relative Specificity (FISH Interphase vs Standard Cytogenetics): 98.01% (197/201) [95% C.I. 96.08 -99.94%]
- Relative Sensitivity (FISH Metaphase vs Standard Cytogenetics): 89.19% (132/148) [95% C.I. 84.19 - 94.19%]
- Relative Specificity (FISH Metaphase vs Standard Cytogenetics): 91.30% (168/184) [95% C.I. 87.22 - 95.37%]
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
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Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 866.4700 Automated fluorescence
in situ hybridization (FISH) enumeration systems.(a)
Identification. An automated FISH enumeration system is a device that consists of an automated scanning microscope, image analysis system, and customized software applications for FISH assays. This device is intended for in vitro diagnostic use with FISH assays as an aid in the detection, counting and classification of cells based on recognition of cellular color, size, and shape, and in the detection and enumeration of FISH signals in interphase nuclei of formalin-fixed, paraffin-embedded human tissue specimens.(b)
Classification. Class II (special controls). The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Automated Fluorescencein situ Hybridization (FISH) Enumeration Systems.” See § 866.1(e) for the availability of this guidance document.
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SAFETY AND EFFECTIVENESS INFORMATION SUMMARY: FOR CEP 8 SpectrumOrange DNA Probe Kit
The CEP 8 SpectrumOrange DNA Probe is a SpectrumOrange fluorescent labeled DNA probe specific for the centromeric region of chromosome 8. This assay is designed to provide a method for the detection and quantification of chromosome 8 in both interphase nuclei and metaphase spreads by fluorescence in situ hybridization (FISH).
Standard cytogenetic analysis detects cytogenetic abnormalities such as trisomy 8 by karyotyping metaphase spreads after staining the chromosomes with a dye in cultured tissue cells.
Safety and effectiveness issues relevant to FISH CEP 8 assay may include cross-reactivity, poor sensitivity, poor specificity, or poor reproducibility. The following summarize the specific performance characteristics of CEP 8 assay:
Analytical Sensitivity and Specificity
Hybridization Efficiency
In a pilot study, the average percentage of cells with no hybridization signal was 0.22% (s.d. 0.20%) on 35 bone marrow (BM) specimens. In a pivotal study, the average percentage of cells with no hybridization signal was 0.11% (s.d .- 0.21%) on 60 BM specimens. Thus,