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K Number
DEN130010
Device Name
VYSIS EGR1 FISH PROBE KIT - SC (SPECIMEN CHARACTERIZATION)
Manufacturer
ABBOTT MOLECULAR, INC.
Date Cleared
2013-07-29

(111 days)

Product Code
PDO
Regulation Number
864.1870
Type
Post-NSE
Panel
PA
Reference & Predicate Devices
N/A
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

The Vysis EGR1 FISH Probe Kit - SC detects the LSI EGR1 probe target on chromosome 5q in bone marrow specimens. The Vysis EGR1 FISH Probe Kit -SC assay results characterize bone marrow specimens from patients with acute myeloid leukemia or myelodysplastic syndrome. The assay results are intended to be interpreted by a qualified pathologist or cytogeneticist. This device is not intended for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening. The use of this product for diagnosis, monitoring or risk assessment has not been established.

Device Description

The Vysis EGR1 FISH Probe Kit - Specimen Characterization uses fluorescence in situ hybridization (FISH) DNA probe technology to detect probe target LSI EGR1 (containing early growth response 1 gene; location chromosome 5g31). The LSI D5S23, D5S721 probe (location chromosome 5p15.2) serves as a control.

The Vysis EGR1 FISH Probe Kit – SC (List No. 04N37-001) consists of the following components which are sufficient to process 20 assays:

  1. Vysis LSI EGR1 SpectrumOrange/D5S23, D5S721 Spectrum Green Probes
  2. Vysis LSI/WCP Hybridization Buffer
  3. DAPI II Counterstain
  4. NP-40
  5. 20X SSC Salt

Items 2 through 5 above are general purposes reagents.

DNA Probes: Vysis LSI EGR1 SpectrumOrange/ D5S23, D5S721 SpectrumGreen.

a. The SpectrumOrange-labeled LSI EGR1 probe, approximately 209 kb in length (chr5:137654208-137862738; February 2009 Assembly; UCSC Human Genome Browser) is located at 5g31 and contains the complete EGR1 gene.
b. The SpectrumGreen-labeled LSI D5S23, D5S721 probe, approximately 561 kb in length (chr5:9397109-9958407; February 2009 Assembly; UCSC Human Genome Browser) is located at 5p15.2.

AI/ML Overview

Here's a summary of the acceptance criteria and the studies performed for the Vysis EGR1 FISH Probe Kit - SC, based on the provided text:

Acceptance Criteria and Device Performance for Vysis EGR1 FISH Probe Kit - SC

1. Table of Acceptance Criteria and Reported Device Performance:

Study CategoryStudy TypeAcceptance CriteriaReported Device Performance
Analytical Performance
Precision/ReproducibilityIntra-Day and Inter-DayAgreement with the expected result of greater than or equal to 90% for the high positive specimen category for each site and 90% for the negative specimen category across all sites with no more than 3 discordant results occurring at one site.Acceptance criteria met
Reproducibility: Inter-SiteSame as above.Acceptance criteria met
Lot to Lot ReproducibilitySame as above.Acceptance criteria met
StabilityReal-Time StabilityAcceptable quality of all attributes (signal intensity, target background, cross-hybridization, specificity, overall readability) for all samples tested.Acceptance criteria met for 12-month stability
In-Use Freeze-Thaw StabilitySame as above.Acceptance criteria met throughout and at the end of 20 freeze-thaw cycles
Transport and Temperature Extreme StabilitySame as above.Acceptance criteria met
Post-Hybridization Signal StabilitySame as above.Acceptance criteria met for Post-hybridization stability of 3 weeks
Probe PhotostabilitySame as above.Acceptance criteria met for Photo-stability of 48 hours
Detection LimitAnalytical SensitivityNot explicitly stated as a pre-specified acceptance criterion but implied to be high for "expected 2 red/2 green signal pattern".99.6% (95% CI: 99.4, 99.7) of nuclei showed expected signal pattern
Analytical SpecificityAnalytical SpecificityNot explicitly stated as a pre-specified acceptance criterion but implied to be high for correct locus hybridization.100% (95% CI: 98, 100) for both D5S23, D5S721 and EGR1 probes
Reference RangeUpper Reference LimitThe assay identifies 1R2G patterns at or below 6% or 12 1R2G patterns per 200 scoreable interphase nuclei in karyotypically normal or deletion-free specimens.None of the 25 normal specimens produced 1R2G signals at or above the 6% upper reference limit.

2. Sample sizes used for the test set and the data provenance:

  • Precision/Reproducibility (Intra-Day, Inter-Day, Inter-Site, Lot-to-Lot):
    • Test Set Sample Size: 6 bone marrow specimens (2 high positive, 2 low positive, 2 negative).
    • Nuclei evaluated: 200 nuclei per panel member (100 by each of 2 technologists) for a total of 1200 nuclei per study type (e.g., Intra-day, Inter-day, etc.).
    • Data Provenance: Not explicitly stated (e.g., country of origin). Appears to be prospective analytical testing conducted by the manufacturer.
  • Analytical Sensitivity:
    • Test Set Sample Size: 25 bone marrow specimens (karyotypically normal or 5p15 and 5q31 deletion-free).
    • Nuclei evaluated: 200 nuclei per specimen (100 by each of 2 technologists) for a total of 5000 scoreable nuclei.
    • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
  • Analytical Specificity:
    • Test Set Sample Size: Metaphase chromosomes prepared from peripheral blood cultures of five karyotypically normal males (pooled).
    • Nuclei evaluated: 100 consecutive metaphase nuclei by one technologist, for a total of 200 target loci (100 for each probe).
    • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
  • Reference Range Validation:
    • Test Set Sample Size: 25 bone marrow specimens (karyotypically normal or 5p15.2 and 5q31 deletion-free).
    • Nuclei evaluated: 200 nuclei per specimen (100 by each of 2 technologists).
    • Data Provenance: Not explicitly stated. Appears to be prospective analytical testing.
  • Clinical Supportive Data (Clinical Validity):
    • Test Set Sample Size:
      • Data Source 1 (Sun et al.): 320 bone marrow specimens
      • Data Source 2 (Galvan et al.): 28 bone marrow specimens
      • Data Source 3 (Vance et al.): 181 bone marrow specimens
    • Data Provenance: Retrospective, derived from peer-reviewed published literature (implicitly based on patient data from the respective study locations, not specified).

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:

  • Analytical Performance Studies (Precision, Sensitivity, Specificity, Reference Range):
    • "Two technologists" or "one technologist" were involved in evaluating nuclei. Their specific qualifications (e.g., "cytogeneticist with X years of experience") are not explicitly stated, beyond being referred to as "technologists."
    • The overall interpretation is intended for a "qualified pathologist or cytogeneticist."
  • Clinical Supportive Data:
    • Ground truth for the clinical studies would have been established by the methods described in those published papers, likely involving consensus diagnostics by pathologists and/or cytogeneticists based on conventional cytogenetics and clinical information. The number and qualifications of these experts are not detailed in this summary document.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set:

  • For the analytical performance studies where two technologists evaluated slides (e.g., Precision, Analytical Sensitivity, Reference Range Validation), the text states "each technologist evaluated 100 nuclei per panel member" or "100 nuclei per specimen." It does not explicitly describe an adjudication method (e.g., 2+1, 3+1) if their readings disagreed. It simply reports aggregated results.

5. 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, an MRMC comparative effectiveness study was not done.
  • This device is described as an assay (FISH probe kit) intended to be interpreted by a qualified pathologist or cytogeneticist, not an automated system or AI-assisted diagnostic tool. The text explicitly states: "These devices do not include automated systems that directly report results without review and interpretation by a qualified pathologist or cytogeneticist." Therefore, the concept of human readers improving with AI assistance is not applicable to this submission.

6. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:

  • No, a standalone (algorithm only) performance study was not done.
  • As noted above, this is a FISH probe kit, which is a laboratory assay requiring manual interpretation by human experts. It is not an algorithm that performs standalone analysis.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

  • Analytical Performance Studies:
    • Expected signal pattern: This serves as the ground truth for parameters like precision and sensitivity. It's based on the known genetic characteristics of the specimens (e.g., high positive, low positive, negative, normal karyotype).
    • Known chromosomal location: For analytical specificity, the ground truth is the established chromosomal location of the gene targets.
  • Clinical Supportive Data:
    • The ground truth for the clinical studies (validation of clinical utility) was likely established through a combination of pathology reports, conventional cytogenetics, and clinical diagnoses of AML or MDS as carried out in the respective peer-reviewed studies. The "percentage of cells with 1R2G signal pattern" would have been correlated with these clinical states.

8. The sample size for the training set:

  • Not applicable. The Vysis EGR1 FISH Probe Kit is a diagnostic assay (chemical reagents and probes), not a machine learning algorithm. Therefore, there is no "training set" in the context of AI/ML. All samples discussed are for analytical or clinical validation/support.

9. How the ground truth for the training set was established:

  • Not applicable, as there is no "training set" for this type of device.

§ 864.1870 Early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization.

(a)
Identification. An early growth response 1 (EGR1) gene fluorescence in-situ hybridization (FISH) test system for specimen characterization is a device intended to detect the EGR1 probe target on chromosome 5q in bone marrow specimens from patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist. These devices do not include automated systems that directly report results without review and interpretation by a qualified pathologist or cytogeneticist. These devices also do not include any device intended for use to select patient therapy, predict patient response to therapy, or to screen for disease as well as any device with a claim for a particular diagnosis, prognosis, monitoring, or risk assessment.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must also include the following information:
(i) A detailed description of all probes included in the kit;
(ii) Purpose of each probe;
(iii) Probe molecular specificity;
(iv) Probe specificity;
(v) Probe limits;
(vi) Probe sensitivity;
(vii) Specification of required ancillary reagents, instrumentation, and equipment;
(viii) Specification of the specimen collection, processing, storage and slide preparation methods;
(ix) Specification of the assay procedure;
(x) Specification of control elements that are incorporated into the recommended testing procedures;
(xi) Specification of risk mitigation elements: Description of all additional procedures, methods, and practices incorporated into the directions for use that mitigate risks associated with testing;
(xii) Specification of the criteria for test result interpretation and reporting;
(xiii) Device analytical sensitivity data;
(xiv) Device analytical specificity data;
(xv) Device reference limit data;
(xvi) Device precision/reproducibility data;
(xvii) Device stability data to include:
(A) Real-time stability,
(B) Freeze-thaw stability,
(C) Transport and temperature stability,
(D) Post-hybridization signal stability,
(E) Photostability of probe, and
(xviii) Documentation that demonstrates the clinical validity of the device. The documentation must include data from clinical studies, a minimum of two peer-reviewed published literature references using the specific device seeking marketing clearance, or both. Documentation for the clinical studies and peer-reviewed published literature references cited must include the following elements:
(A) Documentation that the sponsor's probe was used in the literature reference,
(B) Number and type of specimens,
(C) Target population studied,
(D) Upper reference limit, and
(E) Range of positive probe results.
(2) Your § 809.10(b)(12) of this chapter compliant labeling must include a statement summarizing the data identified in paragraphs (b)(1)(xiii) through (xviii) of this section and a description of the studies supporting the information, including the pre-specified acceptance criteria for these performance studies, justification for the pre-specified acceptance criteria, and whether the pre-specified acceptance criteria were met.
(3) Your § 809.10 of this chapter compliant labeling must include:
(i) A warning that reads “The assay results are intended to be interpreted only by a qualified pathologist or cytogeneticist.”
(ii) A warning that reads “This device is not for high-risk uses such as selecting therapy, predicting therapeutic response or disease screening.”
(iii) A warning that reads “The use of this device for diagnosis, monitoring or risk assessment has not been established.”