(240 days)
No reference devices were used in this submission.
No
The summary describes a standard next-generation sequencing workflow and data analysis pipeline for identifying genetic alterations and tumor mutational burden. There is no mention of AI or ML in the device description, intended use, or performance studies. The software verification and validation testing is described as per FDA guidance for a "MODERATE" level of concern, which is typical for this type of diagnostic assay and does not inherently indicate the use of AI/ML.
No
The device is described as a qualitative in vitro diagnostic test that provides information (e.g., point mutations, tumor mutational burden) for use by healthcare professionals. It explicitly states that it "is not conclusive or prescriptive for labeled use of any specific therapeutic product." This indicates its purpose is diagnostic, not therapeutic.
Yes
The "Intended Use / Indications for Use" states that the Omics Core assay is a "qualitative in vitro diagnostic test." It also notes that the test is intended to "provide informations (point mutations and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals," which are characteristics of a diagnostic device.
No
The device description clearly outlines a complex process involving physical sample preparation (DNA extraction, shearing, ligation, capture), sequencing on an Illumina NovaSeq 6000 (hardware), and subsequent bioinformatics analysis. While software is used for data analysis, it is an integral part of a larger system that includes significant hardware and laboratory procedures.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The very first sentence explicitly states: "The Omics Core assay is a qualitative in vitro diagnostic test..." This is the most direct indicator.
- Device Description: The description details the process of analyzing biological samples (tumor tissue and normal specimens) outside of the body ("in vitro") to detect specific genetic alterations. This is the core function of an IVD.
- Anatomical Site: The samples are taken from the body (tumor tissue and normal specimens), but the analysis is performed on these samples in a laboratory setting.
- Intended User/Care Setting: The test is intended for use by "qualified health care professionals," which is typical for IVDs used in clinical decision-making. The fact that it's a "single-site assay performed at NantHealth, Inc." indicates a laboratory setting where IVD testing is conducted.
- Performance Studies: The document includes detailed performance studies (Precision, Analytical Sensitivity, Accuracy) which are standard requirements for demonstrating the reliability and validity of an IVD.
- Predicate Device(s): The mention of a predicate device (MSK-IMPACT) which is also a Next Generation Sequencing Assay used for cancer profiling further supports its classification as an IVD, as predicate devices are typically other legally marketed IVDs.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Omics Core assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffin-embedded tumor tissue matched with normal specimens with solid malignant neoplasms to detect tumor gene alterations in a broad multi gene panel. The test is intended to provide informations (point mutations (point mutations and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals in accordance with professional guidelines, and is not conclusive or prescriptive for labeled use of any specific therapeutic product. Omics Core is a single-site assay performed at NantHealth, Inc.
Product codes
PZM
Device Description
The NantHealth Omics Core assay is a custom targeted whole exome sequencing platform, utilizing solution-phase exon capture and sequencing, to report somatic alterations (point mutations, small insertions and deletions) in 468 genes and sequencing of 19,396 protein-coding genes (whole exome) to determine overall tumor mutation burden in tumor specimens.
Genomic DNA is extracted from both a tumor and a patient-matched normal control sample. Sequence libraries are prepared through a series of enzymatic steps including shearing of double-stranded DNA, end repair, A-base addition, ligation of barcoded sequence adaptors, and low cycle PCR amplification. Single barcoded sequence libraries are captured using the biotinylated probes. Captured DNA fragments are then pooled and sequenced on an Illumina NovaSeq 6000 as paired-end reads. Sequence reads are then aligned to the reference human genome. Somatic alterations are identified in the tumor DNA by direct comparison to the matched normal DNA.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Formalin-fixed paraffin-embedded tumor tissue
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Qualified health care professionals; single-site assay performed at NantHealth, Inc.
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Precision was assessed using 12 FFPE clinical tumor samples and 1 commercial cell line. A total of 530 variants were identified in the samples that included 483 SNVs, 32 deletions, and 15 insertions.
Accuracy was assessed by comparing Omics Core results to results obtained from the orthogonal method in a total of 401 FFPE tumor samples representing mutations covering 2,634 SNVs, 125 small insertions and 313 small deletions.
An analysis of 220 positive mutations and 12,612 wildtype calls demonstrated a PPA of 99.54% (97.48-99.99%) and NPA of 99.99% (99.99-100%).
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Precision Study:
Sample Size: 12 FFPE clinical tumor samples and 1 commercial cell line.
Key Results:
- Panel-Wide Reproducibility: The overall positive call rate for all variants analyzed was 98.4% (2607/2650).
- Per Specimen Precision: 100% concordance for 511 out of 530 unique mutations, or 96.4% (94.5%-97.8% CI).
- Well Characterized Reference Material: Achieved an overall positive call rate of 99.86% (99.75%-99.93% CI).
- TMB Precision: Per sample TMB analysis demonstrated repeatable and reproducible TMB rates with a %CV = 95%. SNVs called at 96.7% (82.8%-99.9% CI), insertions at 100% (83.2%-100.0% CI) and deletions at 100.0% (78.2%-100.0% CI).
LoD - TMB:
Sample Size: 10 FFPE tumor specimens.
Key Results: Demonstrated consistent repeatability and reproducibility as all samples evaluated had a %CV
§ 866.6080 Next generation sequencing based tumor profiling test.
(a)
Identification. A next generation sequencing (NGS) based tumor profiling test is a qualitative in vitro diagnostic test intended for NGS analysis of tissue specimens from malignant solid neoplasms to detect somatic mutations in a broad panel of targeted genes to aid in the management of previously diagnosed cancer patients by qualified health care professionals.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the following information:
(i) A detailed description of all somatic mutations that are intended to be detected by the test and that are adequately supported in accordance with paragraph (b)(1)(v) of this section and reported in the test results in accordance with paragraph (b)(2)(iv) of this section, including:
(A) A listing of mutations that are cancer mutations with evidence of clinical significance.
(B) As appropriate, a listing of mutations that are cancer mutations with potential clinical significance.
(ii) The indications for use must specify the following:
(A) The test is indicated for previously diagnosed cancer patients.
(B) The intended specimen type(s) and matrix (
e.g., formalin-fixed, paraffin-embedded tumor tissue).(C) The mutation types (
e.g., single nucleotide variant, insertion, deletion, copy number variation or gene rearrangement) for which validation data has been provided.(D) The name of the testing facility or facilities, as applicable.
(iii) A detailed device description including the following:
(A) A description of the test in terms of genomic coverage, as follows:
(
1 ) Tabulated summary of all mutations reported, grouped according to gene and target region within each gene, along with the specific cDNA and amino acid positions for each mutation.(
2 ) A description of any within-gene targeted regions that cannot be reported and the data behind such conclusion.(B) Specifications for specimen requirements including any specimen collection devices and preservatives, specimen volume, minimum tumor content, specimen handling, DNA extraction, and criteria for DNA quality and quantity metrics that are prerequisite to performing the assay.
(C) A detailed description of all test components, reagents, instrumentation, and software required. Detailed documentation of the device software including but not limited to, software applications and hardware-based devices that incorporate software.
(D) A detailed description of the methodology and protocols for each step of the test, including description of the quality metrics, thresholds, and filters at each step of the test that are implemented for final result reporting and a description of the metrics for run-failures, specimen-failures, invalids, as applicable.
(E) A list of links provided by the device to the user or accessed by the device for internal or external information (
e.g., decision rules or databases) supporting clinical significance of test results for the panel or its elements in accordance with paragraphs (b)(1)(v) and (b)(2)(vi) of this section.(F) A description of internal and external controls that are recommended or provided and control procedures. The description must identify those control elements that are incorporated into the testing procedure.
(iv) Information demonstrating analytical validity of the device according to analytical performance characteristics, evaluated either specifically for each gene/mutation or, when clinically and practically justified, using a representative approach based on other mutations of the same type, including:
(A) Data that adequately supports the intended specimen type (
e.g., formalin-fixed, paraffin-embedded tumor tissue), specimen handling protocol, and nucleic acid purification for specific tumor types or for a pan-tumor claim.(B) A summary of the empirical evidence obtained to demonstrate how the analytical quality metrics and thresholds were optimized.
(C) Device precision data using clinical samples to adequately evaluate intra-run, inter-run, and total variability. The samples must cover all mutation types tested (both positive and negative samples) and include samples near the limit of detection of the device. Precision must be assessed by agreement within replicates on the assay final result for each representative mutation, as applicable, and also supported by sequencing quality metrics for targeted regions across the panel.
(D) Description of the protocols and/or data adequately demonstrating the interchangeability of reagent lots and multiplexing barcodes.
(E) A description of the nucleic acid assay input concentration range and the evidence to adequately support the range.
(F) A description of the data adequately supporting the limit of detection of the device.
(G) A description of the data to adequately support device accuracy using clinical specimens representing the intended specimen type and range of tumor types, as applicable.
(
1 ) Clinical specimens tested to support device accuracy must adequately represent the list of cancer mutations with evidence of clinical significance to be detected by the device.(
2 ) For mutations that are designated as cancer mutations with evidence of clinical significance and that are based on evidence established in the intended specimen type (e.g., tumor tissues) but for a different analyte type (e.g., protein, RNA) and/or a measurement (e.g., incorporating a score or copy number) and/or with an alternative technology (e.g., IHC, RT-qPCR, FISH), evidence of accuracy must include clinically adequate concordance between results for the mutation and the medically established biomarker test (e.g., evidence generated from an appropriately sized method comparison study using clinical specimens from the target population).(
3 ) For qualitative DNA mutations not described in paragraph (b)(1)(iv)(G)(2 ) of this section, accuracy studies must include both mutation-positive and wild-type results.(H) Adequate device stability information.
(v) Information that adequately supports the clinical significance of the panel must include:
(A) Criteria established on what types and levels of evidence will clinically validate a mutation as a cancer mutation with evidence of clinical significance versus a cancer mutation with potential clinical significance.
(B) For representative mutations of those designated as cancer mutations with evidence of clinical significance, a description of the clinical evidence associated with such mutations, such as clinical evidence presented in professional guidelines, as appropriate, with method comparison performance data as described in paragraph (b)(1)(iv)(G) of this section.
(C) For all other mutations designated as cancer mutations with potential clinical significance, a description of the rationale for reporting.
(2) The 21 CFR 809.10 compliant labeling and any product information and test report generated, must include the following, as applicable:
(i) The intended use statement must specify the following:
(A) The test is indicated for previously diagnosed cancer patients.
(B) The intended specimen type(s) and matrix (
e.g., formalin-fixed, paraffin-embedded tumor tissue).(C) The mutation types (
e.g., single nucleotide variant, insertion, deletion, copy number variation or gene rearrangement) for which validation data has been provided.(D) The name of the testing facility or facilities, as applicable.
(ii) A description of the device and summary of the results of the performance studies performed in accordance with paragraphs (b)(1)(iii), (b)(1)(iv), and (b)(1)(v) of this section.
(iii) A description of applicable test limitations, including, for device specific mutations validated with method comparison data to a medically established test in the same intended specimen type, appropriate description of the level of evidence and/or the differences between next generation sequencing results and results from the medically established test (
e.g., as described in professional guidelines).(iv) A listing of all somatic mutations that are intended to be detected by the device and that are reported in the test results under the following two categories or equivalent designations, as appropriate: “cancer mutations panel with evidence of clinical significance” or “cancer mutations panel with potential clinical significance.”
(v) For mutations reported under the category of “cancer mutations panel with potential clinical significance,” a limiting statement that states “For the mutations listed in [cancer mutations panel with potential clinical significance or equivalent designation], the clinical significance has not been demonstrated [with adequate clinical evidence (
e.g., by professional guidelines) in accordance with paragraph (b)(1)(v) of this section] or with this test.”(vi) For mutations under the category of “cancer mutations panel with evidence of clinical significance,” or equivalent designation, link(s) for physicians to access internal or external information concerning decision rules or conclusions about the level of evidence for clinical significance that is associated with the marker in accordance with paragraph (b)(1)(v) of this section.
0
November 18. 2019
Image /page/0/Picture/1 description: The image shows the logos of the Department of Health and Human Services and the Food and Drug Administration (FDA). The Department of Health and Human Services logo is on the left, and the FDA logo is on the right. The FDA logo includes the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
NantHealth, Inc. Aleece Nolasco Vice President, Regulatory Affairs 9920 Jefferson Blvd Culver City, CA 90232
Re: K190661
Trade/Device Name: Omics Core Regulation Number: 21 CFR 866.6080 Regulation Name: Next generation sequencing based tumor profiling test Regulatory Class: Class II Product Code: PZM Dated: September 26, 2019 Received: September 27, 2019
Dear Aleece Nolasco:
This letter corrects our substantially equivalent letter of November 9, 2019.
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You mav, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration. listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's
1
requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Donna M. Roscoe -S
Donna Roscoe, Ph.D. Chief. Molecular Genetics Branch Division of Molecular Genetics and Pathology OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K190661
Device Name
Omics Core
Indications for Use (Describe)
The Omics Core assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffinembedded tumor tissue matched with normal specimens with solid malignant neoplasms to detect tumor gene alterations in a broad multi gene panel. The test is intended to provide informations (point mutations (point mutations and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals in accordance with professional guidelines, and is not conclusive or prescriptive for labeled use of any specific therapeutic product. Omics Core is a single-site assay performed at NantHealth, Inc.
| Type of Use (Select one or both, as applicable) | Prescription Use (Part 21 CFR 801 Subpart D) Over-The-Counter Use (21 CFR 801 Subpart C) | Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
|---|---|---|---|
| Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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TABLE OF CONTENTS
| 510(K) SUMMARY | ||
|---|---|---|
| 1. | SUBMITTER | |
| 2. | DEVICE | |
| 3. | PREDICATE DEVICE | |
| 4. | DEVICE DESCRIPTION | |
| 4.1. | Test Principle | |
| 4.2. | Equipment, Supplies and Reagents | |
| 4.3. | Omics Core Workflow | |
| 4.4. | Indications For Use | |
| ર્ . | COMPARISON OF TECHNOLOGICAL CHARACTERISTICS | |
| WITH THE PREDICATE DEVICE | ||
| 6. | PERFORMANCE DATA | |
| 7. | SUMMARY |
4
LIST OF TABLES
| Table 1: Equipment Supplies, Reagents, and Software | 5 |
|---|---|
| Table 2: Comparison of Omics Core with Predicate Device | 9 |
| Table 3: Omics Core Performance Specifications | 11 |
5
LIST OF FIGURES
| Figure 1: Laboratory Workflow |
|---|
| Figure 2: Bioinformatics Workflow |
6
510(K) SUMMARY
This summary of 510(k) safety and effectiveness information is being submitted in accordance with the requirements of 21 CFR 807.92.
1. SUBMITTER
NantHealth, Inc. 9920 Jefferson Blvd. Culver City, CA 90232
Contact Person: Aleece Nolasco Vice President, Regulatory Affairs Phone: 310-405-7549 Email: Aleece.Nolasco@NantHealth.com
Date prepared: October 21, 2019
2. DEVICE
| Name of Device | Omics Core |
|---|---|
| Common Name | Next Generation Sequencing Tumor Profiling Test |
| Classification Name | Next Generation Sequencing Based Tumor Profiling Test |
| (21CFR 866.6080) | |
| Regulatory Class | II |
| Product Code | PZM |
PREDICATE DEVICE 3.
MSK-IMPACT (Integrated Mutation Profiling Of Actionable Cancer Targets): A Hybridization-Capture Based Next Generation Sequencing Assay, DEN170058
This predicate device has not been subject to a design-related recall.
No reference devices were used in this submission.
7
DEVICE DESCRIPTION 4.
Test Principle 4.1.
The NantHealth Omics Core assay is a custom targeted whole exome sequencing platform, utilizing solution-phase exon capture and sequencing, to report somatic alterations (point mutations, small insertions and deletions) in 468 genes and sequencing of 19,396 protein-coding genes (whole exome) to determine overall tumor mutation burden in tumor specimens.
Genomic DNA is extracted from both a tumor and a patient-matched normal control sample. Sequence libraries are prepared through a series of enzymatic steps including shearing of double-stranded DNA, end repair, A-base addition, ligation of barcoded sequence adaptors, and low cycle PCR amplification. Single barcoded sequence libraries are captured using the biotinylated probes. Captured DNA fragments are then pooled and sequenced on an Illumina NovaSeq 6000 as paired-end reads. Sequence reads are then aligned to the reference human genome. Somatic alterations are identified in the tumor DNA by direct comparison to the matched normal DNA.
4.2. Equipment, Supplies and Reagents
Table 1 summarizes some of the main equipment, supplies, reagents, and software used by the Omics Core assay.
All reagents, materials and equipment needed to perform the assay are qualified by NantHealth.
| Library Prep | Kapa Hyper Prep Kit |
|---|---|
| Hybridization | IDT xGen® Exome Research Panel v1.0 |
| Sequencer Chemistry | 2-Channel SBS Chemistry |
| Sequencer | Illumina NovaSeq 6000 |
| Bioinformatics | Omics Core software |
Table 1: Equipment Supplies, Reagents, and Software
Omics Core Workflow 4.3.
The following figures provide an illustrated overview of the flow of the Omics Core testing process from sample receipt, through testing, to the report. Detailed descriptions of each aspect of the assay are provided in subsequent sections.
The laboratory workflow for Omics Core is illustrated in Figure 1.
The bioinformatics workflow for Omics Core is illustrated in Figure 2.
8
Image /page/8/Figure/2 description: The image shows the title of a figure. The title is "Figure 1: Laboratory Workflow". The words are written in a bold, sans-serif font.
Image /page/8/Figure/3 description: This image shows a laboratory workflow. The workflow starts with specimen preparation, which includes FFPE tumor tissue (5-20 x 10 μm) and whole blood (2 x 2.5 mL). The next step is library preparation, which includes fragmentation, adapters added, and library amplification. The final step is sequencing, which includes sequencing ready targeted libraries and sequencing using Illumina NovaSeq 6000 and PhiX Control v3.
9
Bioinformatics Workflow Figure 2:
Image /page/9/Figure/3 description: This image is a flowchart that describes the process of sequencing data. The process starts with sequencing data, which is then used to generate tumor and normal FASTQ files. These files are then used to align the tumor and normal DNA, which is followed by variant calling. The variants are then classified, interpreted, and evaluated for TMB. Finally, a report is finalized and released, and the report is made available to the physician.
10
Indications For Use 4.4.
The Omics Core assay is a qualitative in vitro diagnostic test that uses targeted next generation sequencing of formalin-fixed paraffin-embedded tumor tissue matched with normal specimens from patients with solid malignant neoplasms to detect tumor gene alterations in a broad multi gene panel. The test is intended to provide information on somatic mutations (point mutations and small insertions and deletions) and tumor mutational burden (TMB) for use by qualified health care professionals in accordance with professional guidelines, and is not conclusive or prescriptive for labeled use of any specific therapeutic product. Omics Core is a single-site assay performed at NantHealth, Inc.
The Indications For Use statement for Omics Core is not identical to the predicate device. Omics Core is intended to provide information on tumor mutational burden (TMB) and not intended to provide information on microsatellite instability. Omics Core reports TMB as additional information on the tumor tissue. TMB is reported via two metrics: (1) total number of somatic non-synonymous exonic variants within the 19,396 genes (whole exome) surveyed and (2) a calculation of mutation rate by counting all somatic, synonymous and non-synonymous variants detected in gene coding regions and dividing by the approximate size of the exome (33.7 Mb). TMB is reported as mutations per megabase (mut/Mb) unit. Mutations included in the calculation of TMB must be present at 5% allele frequency or greater after direct comparison between tumor and matched normal DNA. TMB is reported as rate (not as High/Low) and as a mutation within the category of "Cancer Mutations with Potential Clinical Significance" to be signed off by the Medical Director. This difference does not constitute a new Indications For Use nor raises different issues of safety and effectiveness.
COMPARISON OF TECHNOLOGICAL ട. CHARACTERISTICS WITH THE PREDICATE DEVICE
The primary technological characteristics and indications for use of the Omics Core assay are substantially equivalent to MSK-IMPACT. A substantial equivalence table comparing overall similarities and differences between Omics Core and MSK-IMPACT is provided in Table 2.
11
| Characteristics | Predicate Device:
MSK-IMPACT (DEN170058) | Subject Device:
Omics Core |
|-----------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Similarities | | |
| Indications For
Use | The MSK-IMPACT assay is a
qualitative in vitro diagnostic test
that uses targeted next generation
sequencing of formalin-fixed
paraffin-embedded tumor tissue
matched with normal specimens
from patients with solid malignant
neoplasms to detect tumor gene
alterations in a broad multi gene
panel. The test is intended to
provide information on somatic
mutations (point mutations and
small insertions and deletions) and
microsatellite instability for use by
qualified health care professionals
in accordance with professional
guidelines, and is not conclusive
or prescriptive for labeled use of
any specific therapeutic product.
MSK-IMPACT is a single-site
assay performed at Memorial
Sloan Kettering Cancer Center. | The Omics Core assay is a
qualitative in vitro diagnostic test
that uses targeted next generation
sequencing of formalin-fixed
paraffin-embedded tumor tissue
matched with normal specimens
from patients with solid malignant
neoplasms to detect tumor gene
alterations in a broad multi gene
panel. The test is intended to
provide information on somatic
mutations (point mutations and
small insertions and deletions) and
tumor mutational burden (TMB)
for use by qualified health care
professionals in accordance with
professional guidelines, and is not
conclusive or prescriptive for
labeled use of any specific
therapeutic product. Omics Core is
a single-site assay performed at
NantHealth, Inc. |
| Technology | Hybrid Capture | Same |
| Specimen Types | Formalin-fixed, paraffin-
embedded (FFPE) tumor tissue
matched with normal specimens
from patients with solid malignant
neoplasms | Same |
| Target Population | Patients with solid malignant
neoplasms | Same |
| Genes on Panel for
Reporting SNVs
and Indels | 468 | Same |
| Test Environment | Single-site assay (performed at
Memorial Sloan Kettering Cancer
Center) | Same. Single-site assay
(performed at NantHealth, Inc.) |
| Controls | Matched normal Positive control Negative control No template control (NTC) | Omics Core uses the same types of
controls. |
| Characteristic | Predicate Device:
MSK-IMPACT (DEN170058) | Subject Device:
Omics Core |
| Differences | | |
| Black List | 73 exons | 203 exons |
| Variant types | Intended to provide information
on somatic mutations (point
mutations and small insertions
and deletions), and
microsatellite instability | Same except Omics Core provides
information on tumor mutational
burden (TMB) and not
microsatellite instability (MSI). |
| Instrument | Illumina HiSeq® 2500
Sequencing System | Illumina NovaSeq™ 6000
Sequencing System |
| Determination of
Pipeline Thresholds | Based on >200X target coverage 100X for ≥ 98% target exons hotspot mutation calling threshold (mutation coverage (DP) ≥ 20, mutant reads (AD) ≥ 8, mutation frequency (VF) ≥ 2%, and non-hotspot mutation threshold (DP ≥ 20, AD ≥ 10, VF ≥ 5%)). | Based on ≥ 500X target coverage ≥ 100X for 95% of target exons, and a mutation calling threshold of allele frequency (AF) ≥ 2% with Conf > 15 and heuristic filters The minimum read depth for variants in the Omics Core assay are allele depth (AD) ≥ 2 and overall depth (DP) ≥ 4. |
| Assay cut-off | MSK-IMPACT does not report
mutations below 2% for known
hotspot mutations and 5% for
non-hotspot mutations. | Omics Core does not report
mutations below 2% for all
mutations. |
| Clinical Evidence
Curation
Oncopanel results are
reported under one of
these two categories: | Classification criteria were
developed by MSK using the
in-house OncoKB database.
OncoKB undergoes periodic
updates through the review of
new information by a panel of
experts | Classification criteria weredeveloped by NantHealth, Inc.
NantHealth periodically updates
Omics Core through the review of
new information available. |
| "Cancer Mutations with Evidence of Clinical Significance" or "Cancer Mutations with Potential Clinical Significance." | | |
Comparison of Omics Core with Predicate Device Table 2:
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13
PERFORMANCE DATA 6.
Table 3 summarizes the performance data that are provided in support of the substantial equivalence determination. Performance specifications were established following special controls outlined for next generation sequencing based tumor profiling test (21 CFR 866.6080).
| Characteristic | Performance Specifications |
|---|---|
| Specimens | The specimens accepted for testing are formalin-fixed, paraffin- |
| embedded (FFPE) tumor tissue blocks and two vials of whole | |
| blood for the normal comparator. If a tumor block is not available, | |
| slides containing tumor sections are acceptable. The FFPE blocks | |
| and slides are prepared per industry standards by the requesting | |
| medical facility. | |
| Tumor sample requirements are 5-20 unstained sections, | |
| 10 microns thick. Tumor sections must have more than 10% of | |
| tumor cells; however, sections containing >20% viable tumor are | |
| preferred for testing. | |
| Pre-Analytical | DNA samples are normalized to yield 50-300ng input in 60μl |
| prior to shearing. | |
| Characteristic | Performance Specifications |
| Precision | Precision was assessed using 12 FFPE clinical tumor samples and |
| 1 commercial cell line. A total of 530 variants were identified in | |
| the samples that included 483 SNVs, 32 deletions, and | |
| 15 insertions. | |
| Precision – Panel-Wide Reproducibility: | |
| The overall positive call rate for all variants analyzed across the | |
| 12 FFPE clinical samples and one commercial cell line was | |
| 2607/2650, or 98.4% (97.8-98.8% CI). Three-hundred and ninety- | |
| eight (398) of 521 (76%) mutations in the clinical specimens had | |
| %CV ≤ 10%; 91 of 521 (17%) were between 10 and 20%; and | |
| 32 of 521 (6%) were > 20%. | |
| Precision – Per Specimen: | |
| Per specimen variant analysis for 12 clinical specimens and a | |
| commercial cell line demonstrated consistent repeatability and | |
| reproducibility by showing 100% concordance for 511 out of | |
| 530 unique mutations, or 96.4% (94.5%-97.8% CI). | |
| Precision - Well Characterized Reference Material: | |
| Analysis of the well characterized sample demonstrated consistent | |
| repeatability and reproducibility by achieving an overall positive | |
| call rate of 99.86% (99.75%-99.93% CI). | |
| Precision - TMB: | |
| TMB precision analysis was based on 12 clinical samples and | |
| 1 commercial cell line. The tumor purity for these samples ranged | |
| from 25% to 90%. The per sample TMB analysis demonstrated | |
| repeatable and reproducible TMB rates with a %CV 2,000 samples support that any interference from any challenging tissues is minimized. | |
| Assay Cut-Off | Omics Core does not report mutations below 2% MAF. Mutations included in the calculation of TMB must be present at 5% allele frequency or greater. |
| Characteristic | Performance Specifications |
| Clinical Performance | The genes in the panel include those that play a role in cancer |
| pathogenesis and tumor suppression, or for clinical or mechanistic | |
| information of relevance in the management of cancer patients. | |
| The assay reports mutations under two categories: "Cancer | |
| Mutations with Evidence of Clinical Significance" and "Cancer | |
| Mutations with Potential Clinical Significance" consistent with the | |
| intended use clinical settings. Mutations with evidence of clinical | |
| significance are represented in professional guidelines as | |
| established by consensus opinion of experts in the healthcare | |
| community. | |
| Software Verification and | |
| Validation Testing | Software level of concern: MODERATE |
| Verification and validation testing conducted as per FDA's | |
| Guidance for Industry and FDA Staff, "Guidance for the Content | |
| of Premarket Submissions for Software Contained in Medical | |
| Devices" and "Content of Premarket Submissions for | |
| Management of Cybersecurity in Medical Devices" |
Table 3: Omics Core Performance Specifications
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7. SUMMARY
The submitted information in this 510(k) notification supports the Indications For Use for Omics Core and demonstrates that the Omics Core assay is as safe and effective as the predicate device and therefore supports a substantial equivalence conclusion.