(88 days)
No
The device uses a linear combination of gene expression levels to generate a score, which is a deterministic algorithm, not AI/ML. The performance studies describe logistic regression modeling for analysis, but this is used to evaluate the SeptiSCORE™'s utility, not as part of the device's core function.
No
This device is an in vitro diagnostic test that aids in differentiating infection-positive from infection-negative systemic inflammation in patients suspected of sepsis. It does not provide therapy or treatment.
Yes
The device aids in differentiating infection-positive (sepsis) from infection-negative systemic inflammation, generates a score for interpretation, and is used in conjunction with clinical assessments and other laboratory findings, all of which align with the function of a diagnostic device.
No
The device description explicitly states it is an "in vitro diagnostic test" and a "kit" that uses "reverse transcription quantitative polymerase chain reaction (RT-gPCR)" and is developed for a specific "Real-Time PCR System." While it includes "SeptiCyte™ Analysis software" to process the data, the core of the device is a physical assay kit and requires specific hardware (the PCR system) to function.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The description explicitly states, "SeptiCyte™ LAB is in-vitro diagnostic use." It also describes its use in quantifying gene expression levels from whole blood to aid in differentiating infection-positive from infection-negative systemic inflammation in patients suspected of sepsis. This is a classic description of an in vitro diagnostic test.
- Device Description: The description further reinforces this by stating, "SeptiCyte™ LAB is an in vitro diagnostic test..." and details how it analyzes biological samples (whole blood) to provide information about a patient's condition.
- Anatomical Site: The test uses "whole blood collected from peripheral venous blood," which is a biological sample.
- Intended User/Care Setting: It is intended for use by "trained professional, and used in conjunction with clinical assessments and other laboratory findings to aid in managing patients with, and suspected of, sepsis. professional settings such as central hospital laboratories." This indicates it's used in a clinical laboratory setting for diagnostic purposes.
All these points align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
SeptiCyte™ LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene™ Blood RNA Tube. SeptiCyte™ LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic in patients suspected of sepsis on their first day of ICU admission. The test generates a score (SeptiSCORE™) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. SeptiCyte™ LAB is in-vitro diagnostic use.
Product codes
PRE
Device Description
SeptiCyte™ LAB is an in vitro diagnostic test to be used when prescribed by a clinician in professional settings such as central hospital laboratories. SeptiCyte™ LAB is a reverse transcription quantitative polymerase chain reaction (RT-gPCR)-based laboratory test that quantifies the relative expression levels of four host response genes (CEACAM4, LAMP1, PLA2G7, PLAC8) using RNA extracted from the whole blood of critically ill patients suspected of sepsis. It is a kit developed specifically for the Applied Biosystems® 7500 Fast Dx Real-Time PCR System. SeptiCyte™ LAB serves as an indicator of the host response to infection in systemically inflamed patients by measuring the expression of specific genes with roles in immune function, and infection. More specifically it aids in differentiating infection-positive systemic inflammation (IPSI) from infection-negative systemic inflammation (INSI).
SeptiCyte™ LAB measures the relative expression levels of the four genes by threshold cycle (Ct) in RT-qPCR. Ct values are linearly combined in a SeptiSCORE™ ranging from 0 to 10 by SeptiCyte™ Analysis software. The higher the SeptiSCORE™ value, the greater the likelihood of IPSI; the lower the SeptiSCORE™, the less likely the condition is caused by infection (INSI).
Performing SeptiCyte™ LAB includes:
a) Isolation of total (unfractionated) RNA from whole blood collected from peripheral venous blood (using PAXgene™ Blood RNA System, K042613, manual or QlAcube® automated procedure)
b) Reverse transcription of RNA to cDNA
c) Amplification of specific regions of cDNAs corresponding to CEACAM4, LAMP1, PLA2G7, PLAC8 mRNAs, with acquisition of real time gene expression detected by fluorescent quantification using Applied Biosystems® 7500 Fast Dx Real-Time PCR Instrument (K082562), and
d) Incorporation of information from the raw RT-qPCR gene expression data into the calculation of a single numerical SeptiSCORE™ by the SeptiCyte™ Analysis software.
All steps within the SeptiCyte™ LAB protocol are performed in a 96-well plate based assay format according to the Instructions for Use. Each SeptiCyte™ LAB kit includes reagents sufficient for up to 12 patient samples. Up to three patient samples can be run together on the same plate.
Components including master-mixes and individual reagents (i.e., oligonucleotide primers, probe sets, reverse transcriptase (RT), random hexamers, polymerase, and controls) are added to the assay according to the Instructions for Use.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult patients
Intended User / Care Setting
Clinician in professional settings such as central hospital laboratories. Intended for prescription use, to be performed only by a trained professional.
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
Clinical performance was evaluated in observational, prospective clinical trials conducted across eight clinical sites in the US and Europe. The evaluation recruited 447 adult patients admitted to the ICU with two or more signs of systemic inflammation (≥ 2 SIRS criteria). The SeptiSCORE™ was compared to a non-reference method (termed Retrospective Physician Diagnosis or RPD) based on independent clinical case review by a panel of three medical experts after the patient was discharged from the hospital and other information available at discharge. The medical experts remained blinded to SeptiCyte™ LAB test results. The medical experts based their diagnosis on data and had no direct contact with patients.
Two Diagnostic Methods were followed:
- Consensus RPD: Subjects were stratified by diagnosis SIRS, Sepsis or Indeterminate according to the majority opinion of three medical experts (RPD panel). Indeterminate cases (n=37) were those for which a definitive diagnosis could not be reached by expert review and were not included in the analysis.
- Forced RPD: Subjects were stratified by diagnosis SIRS or sepsis according to the majority opinion of three expert reviewers. The Indeterminate category was not allowed, so all patients were forced into either the SIRS or sepsis categories, with no exclusions.
Summary of Performance Studies
Clinical Study:
Sample Size: 447 adult patients
Study type: Observational, prospective clinical trials.
Key results:
Primary Endpoint: Demonstration that SeptiSCORE™ correlates with probability of sepsis: The clinical data exhibited a direct relationship between SeptiSCORE™ and the probability of sepsis across each SeptiSCORE™ Interpretation Band. Non-adjacent SeptiSCORE™ Interpretation Bands displayed non-overlapping 80% confidence intervals (Cls) with respect to sepsis probability.
Secondary Endpoint: Demonstration that SeptiSCORE™ is a significant component of a logistic regression model of sepsis diagnosis:
Models were constructed including or excluding PCT using a backwards-elimination variable selection procedure combined with a logistic regression rule. The backwards-elimination was used to determine which clinical variables best discriminate IPSI (sepsis) from INSI (SIRS). Area Under Receiver Operating Characteristic Curve (AUC) was used as the metric for assessing model performance for each analysis. Regardless of whether PCT was available as a variable, the SeptiSCORE™ was always a significant component of the logistic regression models built to classify IPSI (sepsis) and INSI (SIRS) patients. SeptiSCORE™ was also the top-ranked variable in all sepsis diagnosis backward-elimination models indicating it contained the most clinical value irrespective of what other clinical variables were used during modeling.
No adverse events were reported during the Clinical Study.
Bench Studies:
Precision and Reproducibility:
Intermediate Precision: SD
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002
IMMUNEXPRESS, INC. VICTORIA ROTHWELL REGUALTORY AND SCIENTIFIC SPECIALIST 425 PONTIUS AVE. NORTH SEATTLE WA 98109
April 6, 2017
Re: K163260 Trade/Device Name: SeptiCyte™ LAB Regulation Number: 21 CFR 866.3215 Regulation Name: Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis. Regulatory Class: II Product Code: PRE Dated: November 17, 2016 Received: November 21, 2016
Dear Dr. Rothwell.
This letter corrects our substantially equivalent letter of February 17, 2017.
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 may, therefore, market the device, subject to the general controls provisions of the Act. 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
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comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. 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
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm
You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address
http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.
Sincerely,
Uwe Scherf -S
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K163260
Device Name SeptiCyte™ LAB
Indications for Use (Describe)
SeptiCyte™ LAB is a gene expression assay using reverse transcription polymerase chain reaction to quantify the relative expression levels of host response genes isolated from whole blood collected in the PAXgene™ Blood RNA Tube. SeptiCyte™ LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic in patients suspected of sepsis on their first day of ICU admission. The test generates a score (SeptiSCORE™) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. SeptiCyte™ LAB is in-vitro diagnostic use.
| 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) |
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Image /page/3/Picture/0 description: The image shows the logo for "Immuneexpress". The logo consists of a blue abstract symbol on the left, followed by the word "Immune" in blue and "express" in gray. The symbol is made up of several intersecting lines.
the signature diagnostics for sepsis
510(k) Summary - SeptiCyte™ LAB
1. OWNER:
Immunexpress, Inc. 425 Pontius Ave. North Seattle, WA 98109 Telephone: 206-858-6436
Contact Person: Victoria Rothwell, Ph.D. Email: victoria.r@Immunexpress.com Telephone: 206-858-6436
February 16, 2017
2. DEVICE
Name of Device: SeptiCyte™ LAB Common or Usual Name: Infection Biomarker Classification Name: Non-microbial human analyte(s) which are meant to aid in the assessment of patients with suspected sepsis (21 CFR 866.3215). Regulatory Class: II
3. PREDICATE DEVICE
B.R.A.H.M.S.PCT sensitive KRYPTOR® (DEN150009)
4. DEVICE DESCRIPTION
SeptiCyte™ LAB is an in vitro diagnostic test to be used when prescribed by a clinician in professional settings such as central hospital laboratories. SeptiCyte™ LAB is a reverse transcription quantitative polymerase chain reaction (RT-gPCR)-based laboratory test that quantifies the relative expression levels of four host response genes (CEACAM4, LAMP1, PLA2G7, PLAC8) using RNA extracted from the whole blood of critically ill patients suspected of sepsis. It is a kit developed specifically for the Applied Biosystems® 7500 Fast Dx Real-Time PCR System. SeptiCyte™ LAB serves as an indicator of the host response to infection in systemically inflamed
Image /page/3/Picture/13 description: The image contains the logo for Immunexpress. The logo consists of a blue symbol resembling interwoven strands, followed by the word "Immunexpress" in a combination of blue and gray. The word "Immune" is in blue, while "xpress" is in gray.
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patients by measuring the expression of specific genes with roles in immune function, and infection. More specifically it aids in differentiating infection-positive systemic inflammation (IPSI) from infection-negative systemic inflammation (INSI).
SeptiCyte™ LAB measures the relative expression levels of the four genes by threshold cycle (Ct) in RT-qPCR. Ct values are linearly combined in a SeptiSCORE™ ranging from 0 to 10 by SeptiCyte™ Analysis software. The higher the SeptiSCORE™ value, the greater the likelihood of IPSI; the lower the SeptiSCORE™, the less likely the condition is caused by infection (INSI).
| Description | Volume
(12 Determinations) | Storage Temperature |
|----------------------------------------------|-------------------------------|---------------------|
| SeptiCyte™ LAB Reagents
Kit Box 1 of 2 | | |
| Diluent | 1000 μL | -15 to -30 °C |
| RT Buffer | 250 μL | -15 to -30 °C |
| RT Enzyme Mix | 115 μL | -15 to -30 °C |
| qPCR Buffer | 1500 μL | -15 to -30 °C |
| Primer/Probe Mix A | 3 x75 μL | -15 to -30 °C |
| Primer/Probe Mix B | 3 x 75 μL | -15 to -30 °C |
| qPCR Enzyme Mix | 85 μL | -15 to -30 °C |
| SeptiCyte™ Lab Control Set
Kit Box 2 of 2 | | |
| High Positive Control | 3 x 55 μL | -15 to -30 °C |
| Low Positive Control | 3 x 55 μL | -15 to -30 °C |
| Negative Control | 3 x 55 μL | -15 to -30 °C |
Contents of SeptiCyte™ LAB Test Kits
Performing SeptiCyte™ LAB includes:
- a) Isolation of total (unfractionated) RNA from whole blood collected from peripheral venous blood (using PAXgene™ Blood RNA System, K042613, manual or QlAcube® automated procedure)
- b) Reverse transcription of RNA to cDNA
- c) Amplification of specific regions of cDNAs corresponding to CEACAM4, LAMP1, PLA2G7, PLAC8 mRNAs, with acquisition of real time gene expression detected by fluorescent quantification using Applied Biosystems® 7500 Fast Dx Real-Time PCR Instrument (K082562), and
- d) Incorporation of information from the raw RT-qPCR gene expression data into the calculation of a single numerical SeptiSCORE™ by the SeptiCyte™ Analysis software.
All steps within the SeptiCyte™ LAB protocol are performed in a 96-well plate based assay format according to the Instructions for Use. Each SeptiCyte™ LAB kit includes reagents sufficient for up to 12 patient samples. Up to three patient samples can be run together on the same plate.
5
Components including master-mixes and individual reagents (i.e., oligonucleotide primers, probe sets, reverse transcriptase (RT), random hexamers, polymerase, and controls) are added to the assay according to the Instructions for Use.
5. INDICATIONS FOR USE
SeptiCyte™ LAB is a gene expression assay using RT-qPCR to quantify relative expression levels of four host response genes isolated from whole blood collected in the PAXgene™ Blood RNA Tube. SeptiCyte™ LAB is used in conjunction with clinical assessments and other laboratory findings as an aid to differentiate infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission. The test generates a score (SeptiSCORE™) that falls within one of four discrete Interpretation Bands based on the increasing likelihood of infection-positive systemic inflammation. SeptiCyte™ LAB is intended for invitro diagnostic use.
SeptiCyte™ LAB is a test for non-microbial human analyte(s) with the general purpose of aiding in the assessment of critically ill patients suspected of sepsic. SeptiCyte™ LAB is intended for prescription use, to be performed only by a trained professional, and used in conjunction with clinical assessments and other laboratory findings to aid in managing patients with, and suspected of, sepsis.
The BRAHMS PCT Sensitive KRYPTOR® predicate device aids in the risk assessment of progression from severe sepsis to septic shock. In addition, PCT aids in the prediction of 28-dav mortality in sepsis patients. Unlike PCT, SeptiCyte™ LAB does not aid in risk assessment or prediction, but aids in differentiating infection-positive (sepsis) from infection-negative systemic inflammation in patients suspected of sepsis on their first day of ICU admission.
6. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS WITH THE PREDICATE DEVICE
The predicate device B.R.A.H.M.S PCT Sensitive KRYPTOR® is a homogeneous sandwich immunoassay for detection and quantitation of the circulating protein Procalcitonin (PCT) in human serum or plasma. The measuring principle is based on Time-Resolved Amplified Cryptate Emission (TRACE®) technology, which measures the signal emitted from an immuno-complex with time delay. SeptiCvte™ LAB is a whole blood quantitative gene expression assay for four genes (CEACAM4, LAMP1, PLA2G7, PLAC8) with roles in immune function, inflammation, and infection. The assay is based on real-time generation of fluorescence from hydrolysis of dye-quencher hydrolysis probes during cycles of PCR amplification of nucleic acid templates using the Applied Biosystems® 7500 Fast Dx Real-Time PCR System (Applied Biosystems®, Foster City, CA, catalogue number 440685; K082562). Relative expression levels of the four genes, as represented by Ct values in RT-qPCR, are processed by an algorithm and a SeptiSCORE™ ranging from 1 to 10 is generated as the report output.
Image /page/5/Picture/7 description: The image contains the logo for Immunexpress. The logo consists of a blue symbol resembling interwoven strands, followed by the word "Immunexpress". The word "Immun" is in blue, while "express" is in gray.
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7. PERFORMANCE DATA
A. Bench Studies
Precision and Reproducibility:
Intermediate Precision was assessed at Ct level. The standard deviation (SD) was