Xpert® Xpress SARS-CoV-2

Instructions for Use

For Use Under an Emergency Use Authorization (EUA) Only

XPRSARS-COV2-10

For Use with GeneXpert Dx or GeneXpert Infinity Systems

For use under an Emergency Use

Authorization (EUA) Only 302-3562, Rev. G April 2022

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Trademark, Patents and Copyright Statements

Cepheid®, the Cepheid logo, GeneXpert® and Xpert® are trademarks of Cepheid.
AccuPlex™ is a trademark of SeraCare Life Sciences.
Windows® is a trademark of Microsoft Corporation.

THE PURCHASE OF THIS PRODUCT CONVEYS TO THE BUYER THE NON-

TRANSFERABLE RIGHT TO USE IT IN ACCORDANCE WITH THIS INSTRUCTIONS FOR
USE. NO OTHER RIGHTS ARE CONVEYED EXPRESSLY, BY IMPLICATION OR BY
ESTOPPEL. FURTHERMORE, NO RIGHTS FOR RESALE ARE CONFERRED WITH THE
PURCHASE OF THIS PRODUCT.

Copyright © 2021 Cepheid. All rights reserved.

Cepheid
904 Caribbean Drive
Sunnyvale, CA 94089 USA
Phone: +1 408 541 4191
Fax: +1 408 541 4192

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Xpert Xpress SARS-CoV-2

For use under the Emergency Use Authorization (EUA) only.

1 Proprietary Name
Xpert® Xpress SARS-CoV-2

2 Common or Usual Name

Xpert Xpress SARS-CoV-2

3 Intended Use
The Xpert Xpress SARS-CoV-2 test is a rapid, real-time RT-PCR test intended for the
qualitative detection of nucleic acid from the SARS-CoV-2 in upper respiratory specimens
(i.e., nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab or nasal wash/ aspirate)
collected from individuals suspected of COVID-19 by their healthcare provider.
Testing of nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab or nasal
wash/aspirate specimens using the Xpert Xpress SARS-CoV-2 test run on the GeneXpert
Dx and GeneXpert Infinity systems is limited to laboratories certified under the Clinical
Laboratory Improvement Amendments of 1988 (CLIA), 42 U.S.C. § 263a, that meet
requirements to perform high or moderate complexity tests.
Testing of nasopharyngeal, nasal, or mid-turbinate swab specimens using the Xpert Xpress
SARS-CoV-2 test run on the GeneXpert Xpress System (Tablet and Hub Configurations)
is limited to laboratories certified under CLIA that meet requirements to perform high,
moderate, or waived complexity tests. Testing of these specimens is authorized for use at
the Point of Care (POC), i.e., in patient care settings operating under a CLIA Certificate of
Waiver, Certificate of Compliance, or Certificate of Accreditation.
Results are for the detection of SARS-CoV-2 RNA. The SARS-CoV-2 RNA is generally
detectable in upper respiratory specimens during the acute phase of infection. Positive
results are indicative of active infection with SARS-CoV-2; clinical correlation with
patient history and other diagnostic information is necessary to determine patient infection
status. Positive results do not rule out bacterial infection or co-infection with other
viruses. The agent detected may not be the definite cause of disease. Laboratories within
the United States and its territories are required to report all results to the appropriate
public health authorities.
Negative results do not preclude SARS-CoV-2 infection and should not be used as the sole
basis for treatment or other patient management decisions. Negative results must be
combined with clinical observations, patient history, and epidemiological information.
Testing with the Xpert Xpress SARS-CoV-2 test is intended for use by trained operators
who are proficient in performing tests using either GeneXpert Dx, GeneXpert Infinity
and/or GeneXpert Xpress systems. The Xpert Xpress SARS-CoV-2 test is only for use
under the Food and Drug Administration’s Emergency Use Authorization.

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4 Summary and Explanation

An outbreak of respiratory illness of unknown etiology in Wuhan City, Hubei Province,
China was initially reported to the World Health Organization (WHO) on December 31,
2019.1 Chinese authorities identified a novel coronavirus (2019-nCoV), which has
resulted in thousands of confirmed human infections in multiple provinces throughout
China and exported cases in several Southeast Asian countries and more recently the
United States. Cases of severe illness and some deaths have been reported. The
International Committee for Taxonomy of Viruses (ICTV) renamed the virus SARS-
CoV-2.2
The Xpert Xpress SARS-CoV-2 test is a molecular in vitro diagnostic test that aids in the
detection and diagnosis SARS-CoV-2 and is based on widely used nucleic acid
amplification technology. The Xpert Xpress SARS-CoV-2 test contains primers and probes
and internal controls used in RT-PCR for the in vitro qualitative detection of SARS-CoV-2
RNA in upper respiratory specimens.
5 Principle of the Procedure
The Xpert Xpress SARS-CoV-2 test is an automated in vitro diagnostic test for qualitative
detection of nucleic acid from SARS-CoV-2. The Xpert Xpress SARS-CoV-2 test is
performed on GeneXpert Instrument Systems.
The GeneXpert Instrument Systems automate and integrate sample preparation, nucleic
acid extraction and amplification, and detection of the target sequences in simple or
complex samples using real-time PCR assays. The systems consist of an instrument,
computer, and preloaded software for running tests and viewing the results. The systems
require the use of single-use disposable cartridges that hold the RT-PCR reagents and host
the RT-PCR process. Because the cartridges are self-contained, cross-contamination
between samples is minimized. For a full description of the systems, see the GeneXpert Dx
System Operator Manual or the GeneXpert Infinity System Operator Manual.
The Xpert Xpress SARS-CoV-2 test includes reagents for the detection of RNA from
SARS-CoV-2 in nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab and/or nasal
wash/aspirate specimens. A Sample Processing Control (SPC) and a Probe Check Control
(PCC) are also included in the cartridge utilized by the GeneXpert instrument. The SPC is
present to control for adequate processing of the sample and to monitor for the presence of
potential inhibitor(s) in the RT-PCR reaction. The SPC also ensures that the RT-PCR
reaction conditions (temperature and time) are appropriate for the amplification reaction
and that the RT-PCR reagents are functional. The PCC verifies reagent rehydration, PCR
tube filling, and confirms that all reaction components are present in the cartridge
including monitoring for probe integrity and dye stability.
The nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab specimen and/or nasal
wash/aspirate specimen is collected and placed into a viral transport tube containing 3 mL
transport medium or 3 mL of saline. The specimen is briefly mixed by rapidly inverting
the collection tube 5 times. Using the supplied transfer pipette, the sample is transferred to
the sample chamber of the Xpert Xpress SARS-CoV-2 cartridge. The GeneXpert cartridge
is loaded onto the GeneXpert Instrument System platform, which performs hands-off,

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automated sample processing, and real-time RT-PCR for detection of viral RNA.
6 Reagents and Instruments
6.1 Materials Provided
The Xpert Xpress SARS-CoV-2 kit contains sufficient reagents to process 10 specimens
or quality control samples. The kit contains the following:

Xpert Xpress SARS-CoV-2 Cartridges

with Integrated Reaction Tubes 10
• Bead 1, Bead 2, and Bead 3 (freeze-dried) 1 of each per cartridge
• Lysis Reagent 1.5 mL per cartridge
• Binding Reagent 1.5 mL per cartridge
• Elution Reagent 3.0 mL per cartridge
Disposable Transfer Pipettes 10-12 per kit
CD 1 per kit
• Assay Definition File (ADF)
• Instructions to import ADF into GeneXpert software

Flyer 1 per kit

• Directions to locate the Product Insert on www.cepheid.com

Note Safety Data Sheets (SDS) are available at www.cepheid.com or

www.cepheidinternational.com under the SUPPORT tab.

Note The bovine serum albumin (BSA) in the beads within this product was produced
and manufactured exclusively from bovine plasma sourced in the United States.
No ruminant protein or other animal protein was fed to the animals; the animals
passed ante- and post-mortem testing. During processing, there was no mixing of
the material with other animal materials.

7 Storage and Handling

• Store the Xpert Xpress SARS-CoV-2 cartridges at 2-28°C.
• Do not open a cartridge lid until you are ready to perform testing.
• Do not use a cartridge that is wet or has leaked.

8 Materials Required but Not Provided

• GeneXpert Dx or GeneXpert Infinity systems (catalog number varies by
configuration): GeneXpert instrument, computer, barcode scanner,
operator manual.
For GeneXpert Dx System: GeneXpert Dx software version 4.7b or higher
For GeneXpert Infinity-80 and Infinity-48s systems: Xpertise software
version 6.4b or higher

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9 Materials Available but Not Provided

SeraCare AccuPlex™ Reference Material Kit, catalog number 0505-0126 (Order Code
CEPHEID)

10 Warnings and Precautions

10.1 General
• For in vitro diagnostic use.
• For emergency use only.
• This product has not been FDA cleared or approved, but has been authorized by
FDA under an EUA for use by authorized laboratories.
• This product has been authorized only for the detection of nucleic acid from
SARS-CoV-2, not for any other virus or pathogens.
• This product is only authorized for the duration of the declaration that circumstances
exist justifying the authorization of emergency use of in vitro diagnostics for detection
and/or diagnosis of COVID-19 under Section 564(b)(1) of the Act, 21 U.S.C. § 360bbb-
3(b)(1), unless the declaration is terminated or authorization is revoked sooner.
• Positive results are indicative of presence of SARS-CoV-2-RNA.
• Laboratories within the United States and its territories are required to report all results
to the appropriate public health authorities.
• Performance characteristics of this test have only been established with nasopharyngeal
swab specimens. The performance of this assay with other specimen types or samples
has not been evaluated.
• Treat all biological specimens, including used cartridges, as if capable of
transmitting infectious agents. Because it is often impossible to know which
might be infectious, all biological specimens should be handled using standard
precautions. Guidelines for specimen handling are available from the U.S.
Centers for Disease Control and Prevention3 and the Clinical and Laboratory
Standards Institute.4
• Follow safety procedures set by your institution for working with chemicals and
handling biological specimens.
• Consult your institution’s environmental waste personnel on proper disposal of
used cartridges, which may contain amplified material. This material may
exhibit characteristics of federal EPA Resource Conservation and Recovery Act
(RCRA) hazardous waste requiring specific disposal requirements. Check state
and local regulations as they may differ from federal disposal regulations.
Institutions should check the hazardous waste disposal requirements within their
respective countries.
10.2 Specimens
• Maintain proper storage conditions during specimen transport to ensure the
integrity of the specimen (see Section 12, Specimen Collection, Transport, and
Storage). Specimen stability under shipping conditions other than those
recommended has not been evaluated.

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10.3 Assay/Reagent
• Do not open the Xpert Xpress SARS-CoV-2 cartridge lid except when adding
specimen.
• Do not use a cartridge that has been dropped after removing it from the packaging.
• Do not shake the cartridge. Shaking or dropping the cartridge after opening the
cartridge lid may yield non-determinate results.
• Do not place the sample ID label on the cartridge lid or on the barcode label on the
cartridge.
• Do not use a cartridge with a damaged barcode label.
• Do not use a cartridge that has a damaged reaction tube.
• Each single-use Xpert Xpress SARS-CoV-2 cartridge is used to process one test. Do
not reuse processed cartridges.
• Each single-use disposable pipette is used to transfer one specimen. Do not reuse
disposable pipettes.
• Do not use a cartridge if it appears wet or if the lid seal appears to have been broken.
• Wear clean lab coats and gloves. Change gloves between the handling of each
specimen.
• In the event of a spill of specimens or controls, wear gloves and absorb the spill with
paper towels. Then, thoroughly clean the contaminated area with a 10% freshly
prepared household chlorine bleach. Allow a minimum of two minutes of contact
time. Ensure the work area is dry before using 70% denatured ethanol to remove
bleach residue. Allow surface to dry completely before proceeding. Or, follow your
institution’s standard procedures for a contamination or spill event. For equipment,
follow the manufacturer’s recommendations for decontamination of equipment.
• Biological specimens, transfer devices, and used cartridges should be considered
capable of transmitting infectious agents requiring standard precautions. Follow your
institution’s environmental waste procedures for proper disposal of used cartridges and
unused reagents. These materials may exhibit characteristics of chemical hazardous
waste requiring specific disposal. If country or regional regulations do not provide
clear direction on proper disposal, biological specimens and used cartridges should be
disposed per WHO [World Health Organization] medical waste handling and disposal
guidelines.

11 Chemical Hazards5,6
• Signal Word: Warning
• UN GHS Hazard Statements
• Harmful if swallowed.
• May be harmful in contact with skin.
• Causes eye irritation.

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• UN GHS Precautionary Statements

• Prevention
• Wash hands thoroughly after handling.
• Response
• Call a POISON CENTER or doctor/physician if you feel unwell.
• If skin irritation occurs: Get medical advice/attention.
• IF IN EYES: Rinse cautiously with water for several minutes. Remove
contact lenses, if present and easy to do. Continue rinsing.
• If eye irritation persists: Get medical advice/attention.

12 Specimen Collection, Transport, and Storage

Proper specimen collection, storage, and transport are critical to the performance of this
test. Inadequate specimen collection, improper specimen handling and/or transport may
yield a false result. See Section 12.1 for nasopharyngeal swab collection procedure,
Section 12.2 for oropharyngeal swab collection procedure, Section 12.3 for nasal swab
collection procedure, and Section 12.4 for mid-turbinate swab collection procedure, and
Section 12.5 for nasal wash/aspirate procedure. Nasopharyngeal, nasal, and mid-
turbinate swabs and nasal wash/aspirate specimens can be stored at room temperature
(15–30 °C) for up to 8 hours and refrigerated (2–8 °C) up to seven days until testing is
performed on the GeneXpert Instrument Systems. For oropharyngeal swab specimen
transport and storage requirements and additional information, refer to the CDC Interim
Guidelines for Collecting, Handling, and Testing Clinical Specimens from Persons Under
Investigation (PUIs) for Coronavirus Disease 2019 (COVID-19) using the link provided
below.
https://www.cdc.gov/coronavirus/2019-nCoV/lab/guidelines-clinical-specimens.html.
12.1 Nasopharyngeal Swab Collection Procedure
Insert the swab into either nostril, passing it into the posterior nasopharynx (see Figure 1).
Rotate swab by firmly brushing against the nasopharynx several times. Remove and place
the swab into the tube containing 3 mL of viral transport medium or 3 mL of saline. Break
swab at the indicated break line and cap the specimen collection tube tightly.

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Figure 1. Nasopharyngeal Swab Collection

12.2 Oropharyngeal Swab Collection Procedure

1. Swab the posterior pharynx, tonsils, and other inflamed areas. Avoid touching the
tongue, cheeks, and teeth with the swab when collecting specimens.
2. Remove and place the swab into the tube containing 3 mL of viral transport medium or
3 mL of saline. Break swab at the indicated break line and cap the specimen collection
tube tightly.
12.3 Nasal Swab Collection Procedure
1. Insert a nasal swab 1 to 1.5 cm into a nostril. Rotate the swab against the inside of the
nostril for 3 seconds while applying pressure with a finger to the outside of the nostril
(see Figure 2).

Figure 2. Nasal Swab Collection for First Nostril

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2. Repeat on the other nostril with the same swab, using external pressure on the outside
of the other nostril (see Figure 3). To avoid specimen contamination, do not touch the
swab tip to anything other than the inside of the nostril.

Figure 3. Nasal Swab Collection for Second Nostril

3. Remove and place the swab into the tube containing 3 mL of viral transport medium or
3 mL of saline. Break swab at the indicated break line and cap the specimen collection
tube tightly.

12.4 Mid-Turbinate Swab Collection Procedure

1. Insert the mid-turbinate swab into either nostril, passing it into the mid-turbinate area
(see Figure 4). Rotate swab by firmly brushing against the mid-turbinate area several
times.
2. Remove and place the swab into the tube containing 3 mL of viral transport medium or
3 mL of saline. Break swab at the indicated break line and cap the specimen collection
tube tightly.

Figure 4. Mid-turbinate Swab Specimen Collection

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12.5 Nasal Wash/Aspirate Procedure

Using a clean transfer pipette, transfer 600 µL of the sample into the tube containing 3 mL
of viral transport medium or 3 mL of saline and then cap the tube.

13 Procedure
13.1 Preparing the Cartridge
Important: Start the test within 30 minutes of adding the sample to the cartridge.
1. Remove a cartridge from the package.
2. Check the specimen transport tube is closed.
3. Mix specimen by rapidly inverting the specimen transport tube 5 times. Open cap on the
specimen transport tube.
4. Open the cartridge lid.
5. Remove the transfer pipette from the wrapper.
6. Squeeze the top bulb of the transfer pipette completely and then place the pipette
tip in the specimen transport tube (see Figure 5).

Figure 5. Transfer Pipette

7. Release the top bulb of the pipette to fill the pipette before removing from the
tube. After filling pipette, excess sample will be seen in the overflow reservoir
bulb of the pipette (see Figure 5). Check that the pipette does not contain bubbles.
8. To transfer the sample to the cartridge, squeeze the top bulb of the transfer pipette
completely again to empty the contents of the pipette (300 µL) into the large
opening (Sample Chamber) in the cartridge shown in Figure 6. Dispose of the
used pipette.

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Sample Chamber
(Large Opening)

Figure 6. Xpert Xpress SARS-CoV-2 Cartridge (Top View)

Note Take care to dispense the entire volume of liquid into the Sample Chamber. False
negative results may occur if insufficient sample is added to the cartridge.

9. Close the cartridge lid.

13.2 External Controls

External controls described in Section 9 are available but not provided and may be used in
accordance with local, state, and federal accrediting organizations, as applicable.
To run a control using the Xpert Xpress SARS-CoV-2 test, perform the following steps:
1. Mix control by rapidly inverting the external control tube 5 times. Open cap on
external control tube.
2. Open the cartridge lid.
3. Using a clean transfer pipette, transfer one draw of the external control sample (300 µL)
into the large opening (Sample Chamber) in the cartridge shown in Figure 6.
4. Close cartridge lid.

13.3 Starting the Test

Note Before you start the test, make sure that the system contains modules with
GeneXpert Dx software version 4.7b or higher or Infinity Xpertise software 6.4b or
higher, and that the Xpert Xpress SARS-CoV-2 Assay Definition File is imported
into the software.
This section lists the default steps to operate the GeneXpert Instrument System.
For detailed instructions, see the GeneXpert Dx System Operator Manual or the
GeneXpert Infinity System Operator Manual, depending on the model that is being
used.
Note The steps you follow may be different if the system administrator has changed the
default workflow of the system.

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1. Turn on the GeneXpert Instrument System:

• GeneXpert Dx:
If using the GeneXpert Dx instrument, first turn on the instrument and then
turn on the computer. Log into the Windows operating system. The
GeneXpert software may launch automatically or may require double-
clicking on the GeneXpert Dx shortcut icon on the Windows® desktop.
or
• GeneXpert Infinity System:
If using the GeneXpert Infinity instrument, power up the instrument by
turning the power switch clockwise to the ON position. On the Windows
desktop, double-click the Xpertise Software shortcut icon to launch the
software.
2. Log on to the System software. The login screen appears. Type your user name
and password.
3. In the GeneXpert System window, click Create Test (GeneXpert Dx) or
Orders followed by Order Test (Infinity).
4. Scan or type in the Patient ID (optional). If typing the Patient ID, make sure the
Patient ID is typed correctly. The Patient ID is shown on the left side of the View
Results window and is associated with the test result.
5. Scan or type in the Sample ID. If typing the Sample ID, make sure the Sample
ID is typed correctly. The Sample ID is shown on the left side of the View
Results window and is associated with the test result.
6. Scan the barcode on the Xpert Xpress SARS-CoV-2 cartridge. Using the
barcode information, the software automatically fills the boxes for the
following fields: Reagent Lot ID, Cartridge SN, Expiration Date and Selected
Assay.
Note If the barcode on the Xpert Xpress SARS-CoV-2 cartridge does not scan, then
repeat the test with a new cartridge.
7. Click Start Test (GeneXpert Dx) or Submit (Infinity) if Auto-Submit is not
enabled. In the dialog box that appears, type your password, if required.
For the GeneXpert Dx Instrument
A. Locate the module with the blinking green light, open the instrument
module door and load the cartridge.
B. Close the door. The test starts and the green light stops blinking. When the
test is finished, the light turns off and the door will unlock. Remove the
cartridge.
C. Dispose of used cartridges in the appropriate sample waste containers
according to your institution's standard practices.
or

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For the GeneXpert Infinity System

A. After clicking Submit, you will be asked to place the cartridge on the
conveyor belt. After placing the cartridge, click OK to continue. The
cartridge will be automatically loaded, the test will run and the used
cartridge will be placed onto the waste shelf for disposal.
B. When all samples are loaded, click on the End Order Test icon.

Note Do not turn off or unplug the instruments while a test is in progress. Turning
off or unplugging the GeneXpert instrument or computer will stop the test.

14 Viewing and Printing Results

For detailed instructions on how to view and print the results, see the GeneXpert
Dx System Operator Manual or the GeneXpert Infinity System Operator Manual.

15 Quality Control
15.1 Internal Controls
Each cartridge includes a Sample Processing Control (SPC) and Probe Check Control
(PCC).
Sample Processing Control (SPC) – Ensures that the sample was processed correctly.
The SPC verifies that sample processing is adequate. Additionally, this control detects
sample-associated inhibition of the real-time PCR assay, ensures that the PCR reaction
conditions (temperature and time) are appropriate for the amplification reaction, and that
the PCR reagents are functional. The SPC should be positive in a negative sample and can
be negative or positive in a positive sample. The SPC passes if it meets the validated
acceptance criteria.
Probe Check Control (PCC) – Before the start of the PCR reaction, the GeneXpert
System measures the fluorescence signal from the probes to monitor bead rehydration,
reaction tube filling, probe integrity, and dye stability. The PCC passes if it meets the
validated acceptance criteria.
15.2 External Controls
External controls should be used in accordance with local, state, and federal accrediting
organizations as applicable.
16 Interpretation of Results
The results are interpreted automatically by the GeneXpert System and are clearly shown
in the View Results window. The Xpert Xpress SARS-CoV-2 test provides test results
based on the detection of two gene targets according to the algorithms shown in Table 1.

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Table 1. Xpert Xpress SARS-CoV-2 Possible Results

Result Text N2 E SPC
SARS-CoV-2 POSITIVE + +/- +/-
SARS-CoV-2 PRESUMPTIVE POS - + +/-
SARS-CoV-2 NEGATIVE - - +
INVALID - - -

See Table 2 to interpret test result statements for the Xpert Xpress SARS-CoV-2
test.

Table 2. Xpert Xpress SARS-CoV-2 Results and Interpretation

Result Interpretation
The 2019 novel coronavirus (SARS-CoV-2) target nucleic acids are
detected.
• The SARS-CoV-2 signal for the N2 nucleic acid target or signals
SARS-CoV-2
for both nucleic acid targets (N2 and E) have a Ct within the valid
POSITIVE
range and endpoint above the minimum setting
• SPC: NA; SPC is ignored because coronavirus target amplification
occurred
• Probe Check: PASS; all probe check results pass
The 2019 novel coronavirus (SARS-CoV-2) nucleic acids may be
present.
Sample should be retested according to the Retest Procedure in
Section 17.2. For samples with a repeated presumptive positive
SARS-CoV-2 result, additional confirmatory testing may be conducted, if it is
PRESUMPTIVE necessary to differentiate between SARS-CoV-2 and SARS-CoV-1 or
POS other Sarbecovirus currently unknown to infect humans, for
epidemiological purposes or clinical management.
• The SARS-CoV-2 signal for only the E nucleic acid target has a
Ct within the valid range and endpoint above the minimum setting
• SPC: NA; SPC is ignored because a target amplification has
occurred.
• Probe Check: PASS; all probe check results pass
The 2019 novel coronavirus (SARS-CoV-2) target nucleic acids are not
detected.
SARS-CoV-2 • The SARS-CoV-2 signals for two nucleic acid targets (N2 and E)
NEGATIVE do not have a Ct within the valid range and endpoint above the
minimum setting
• SPC: PASS; SPC has a Ct within the valid range and endpoint
above the minimum setting
• Probe Check: PASS; all probe check results pass

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Result Interpretation
SPC does not meet acceptance criteria. Presence or absence of the
2019 novel coronavirus (SARS-CoV-2) nucleic acids cannot be
INVALID determined. Repeat test according to the Retest Procedure in Section
17.2.
• SPC: FAIL; SPC and SARS-CoV-2 signals do not have a Ct
within valid range and endpoint below minimum setting
• Probe Check – PASS; all probe check results pass
Presence or absence of the 2019 novel coronavirus (SARS-CoV-2)
nucleic acids cannot be determined. Repeat test according to the Retest
Procedure in Section 17.2.
• SARS-CoV-2: NO RESULT
ERROR • SPC: NO RESULT
• Probe Check: FAIL1 ; all or one of the probe check results fail
1 If the probe check passes, the error is caused by the maximum

pressure limit exceeding the acceptable range, no sample added, or by a

system component failure.
Presence or absence of the 2019 novel coronavirus (SARS-CoV-2)
nucleic acids cannot be determined. Repeat test according to the Retest
Procedure in Section 17.2. A NO RESULT indicates that insufficient
data were collected. For example, the operator stopped a test that was
NO RESULT
in progress.
• SARS-CoV-2: NO RESULT
• SPC: NO RESULT
• Probe Check: NA (not applicable)

The Xpert Xpress SARS-CoV-2 test includes an Early Assay Termination (EAT) function which will
provide earlier time to results in high titer specimens if the signal from the target nucleic acid reaches a
predetermined threshold before the full 45 PCR cycles have been completed. When SARS-CoV-2 titers
are high enough to initiate the EAT function, the SPC amplification curve may not be seen and its
results may not be reported.

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17 Retests
17.1 Reasons to Repeat the Assay
If any of the test results mentioned below occur, repeat the test once according to
instructions in Section 17.2, Retest Procedure.
• A PRESUMPTIVE POS result indicates the 2019 novel coronavirus (SARS-CoV-2)
nucleic acids may be present. Only one of the SARS-CoV-2 nucleic acid target was
detected (E gene) while the other SARS-CoV-2 nucleic acid target (N2 gene) was not
detected.
• An INVALID result indicates that the control SPC failed. The sample was not
properly processed, PCR is inhibited, or the sample was not properly collected.
• An ERROR result could be due to, but not limited to, Probe Check Control
failure, system component failure, no sample added, or the maximum pressure
limits were exceeded.
• A NO RESULT indicates that insufficient data were collected. For example,
cartridge failed integrity test, the operator stopped a test that was in progress, or
a power failure occurred.
If an External Control fails to perform as expected, repeat external control test
and/or contact Cepheid for assistance.

17.2 Retest Procedure

To retest a non-determinate result (INVALID, NO RESULT, or ERROR) or a
PRESUMPTIVE POS result, use a new cartridge.
Use the leftover sample from the original specimen transport medium tube or new external
control tube.
1. Put on a clean pair of gloves. Obtain a new Xpert Xpress SARS-CoV-2
cartridge and a new transfer pipette.
2. Check the specimen transport tube or external control tube is closed.
3. Mix the sample by rapidly invert the specimen transport medium tube or
external control tube 5 times. Open the cap on the specimen transport tube or
external control tube.
4. Open the cartridge lid.
5. Using a clean transfer pipette (supplied), transfer sample (one draw) to the
sample chamber with the large opening in the cartridge.
6. Close the cartridge lid.

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18 Limitations
• The performance of this test was established based on the evaluation of a limited
number of clinical specimens. Clinical performance has not been established with all
circulating variants but is anticipated to be reflective of the prevalent variants in
circulation at the time and location of the clinical evaluation. Performance at the time
of testing may vary depending on the variants circulating, including newly emerging
strains of SARS-CoV-2 and their prevalence, which change over time.
• Performance of the Xpert Xpress SARS-CoV-2 test has only been established in
nasopharyngeal swab specimens. Use of the Xpert Xpress SARS-CoV-2 test with
other specimen types has not been assessed and performance characteristics are
unknown.
• Oropharyngeal, nasal swabs and mid-turbinate swabs (self-collected under supervision
of or collected by a healthcare provider) as well as nasal wash/aspirate are considered
acceptable specimen types for use with the Xpert Xpress SARS-CoV-2 test but
performance with these specimen types has not been established.
• A false negative result may occur if a specimen is improperly collected, transported or
handled. False negative results may also occur if inadequate numbers of organisms are
present in the specimen.
• As with any molecular test, mutations within the target regions of Xpert Xpress SARS-
CoV-2 could affect primer and/or probe binding resulting in failure to detect the
presence of virus.
• This test cannot rule out diseases caused by other bacterial or viral pathogens.
• The performance of this device has not been assessed in a population vaccinated against
COVID-19.

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19 Conditions of Authorization for Laboratories

The Cepheid Xpert Xpress SARS-CoV-2 Letter of Authorization, along with the
authorized Fact Sheet for Healthcare Providers, the authorized Fact Sheet for Patients
and authorized labeling are available on the FDA website:
https://www.fda.gov/medical-devices/coronavirus-disease-2019-covid-19-emergency-
use-authorizations-medical-devices/in-vitro-diagnostics-euas
However, to assist clinical laboratories and/or Point of Care Settings using the Xpert
Xpress SARS-CoV-2 (referred to in the Letter of Authorization as “Your Product”), the
relevant Conditions of Authorization are listed below.
• Authorized laboratories1 using your product must include with test result reports all
authorized Fact Sheets. Under exigent circumstances, other appropriate methods for
disseminating these Fact Sheets may be used, which may include mass media.
• Authorized laboratories using your product must use your product as outlined in the
authorized labeling. Deviations from the authorized procedures, including the
authorized instruments, authorized extraction methods, authorized clinical specimen
types, authorized control materials, authorized other ancillary reagents and authorized
materials required to use your product are not permitted.
• Authorized laboratories that receive your product must notify the relevant public
health authorities of their intent to run your product prior to initiating testing.
• Authorized laboratories using your product must have a process in place for reporting
test results to healthcare providers and relevant public health authorities, as
appropriate.
• Authorized laboratories using your product must collect information on the
performance of your product and report to DMD/OHT7-OIR/OPEQ/CDRH (via
email: CDRH-EUA [email protected]) and Cepheid (+1 888 838 3222 or
[email protected] ) any suspected occurrence of false positive or false
negative results and significant deviations from the established performance
characteristics of the test of which they become aware.
• All operators using your product must be appropriately trained in performing and
interpreting the results of your product, use appropriate personal protective
equipment when handling this kit, and use your product in accordance with the
authorized labeling.
• You, authorized distributors, and authorized laboratories using your product
must ensure that any records associated with this EUA are maintained until
otherwise notified by FDA. Such records will be made available to FDA for
inspection upon request.

1 The letter of authorization refers to “authorized laboratories” as follows: “Testing of

nasopharyngeal, oropharyngeal, nasal, or mid-turbinate swab or nasal wash/aspirate specimens
using the Xpert Xpress SARS-CoV-2 test run on the GeneXpert Dx and GeneXpert Infinity Systems
is limited to laboratories certified under the Clinical Laboratory Improvement Amendments of 1988
(CLIA), 42 U.S.C. §263a, that meet requirements to perform high or moderate complexity tests.
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Testing of nasopharyngeal, nasal, or mid-turbinate swab specimens using the Xpert Xpress SARS-
CoV-2 test run on the GeneXpert Xpress System (Tablet and Hub Configurations) is limited to
laboratories certified under CLIA that meet requirements to perform high, moderate, or waived
complexity tests. Testing of these specimens is authorized for use at the Point of Care (POC), i.e., in
patient care settings operating under a CLIA Certificate of Waiver, Certificate of Compliance, or
Certificate of Accreditation.”

20 Performance Characteristics
20.1 Clinical Evaluation
The performance of the Xpert Xpress SARS-CoV-2 test was evaluated using archived
clinical nasopharyngeal (NP) swab specimens in viral transport medium. A total of 45
SARS-CoV-2 positive and 45 SARS-CoV-2 negative NP swab specimens were tested with
Xpert Xpress SARS-CoV-2 in a randomized and blinded fashion.
All the 45 SARS-CoV-2 positive specimens and 30 of the 45 SARS-CoV-2 negative
specimens were collected during COVID-19 pandemic in the US and had previously been
characterized as positive or negative for SARS-CoV-2 by an EUA RT-PCR test. Fifteen of
the 45 SARS-CoV-2 negative NP swab specimens were collected before December 2019
and are expected to be negative for SARS-CoV-2.
Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) were
determined by comparing the results of the Xpert Xpress SARS-CoV-2 test relative to the
expected results. Results of these 90 archived clinical NP swab specimens are shown in
Table 3. The PPA was 97.8% (95% CI: 88.4% - 99.6%) and the NPA was 95.6% (95% CI:
85.2% - 98.8%).

Table 3. Xpert Xpress SARS-CoV-2 Performance Results

Expected Results

Positive Negative Total

Positive 44 a 2b 46
Xpert Xpress SARS-CoV-2
Negative 1 43 44

Total 45 45 90

PPA 97.8% (95% CI: 88.4% - 99.6%)

NPA 95.6% (95% CI: 85.2% - 98.8%)

a. One specimen was reported as “SARS-CoV-2 Presumptive Pos” in initial testing and yielded a
“SARS-CoV-2 Positive” test result upon retesting.
b. The two false positive specimens were collected during the COVID-19 pandemic.

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21 Analytical Performance
21.1 Analytical Sensitivity (Limit of Detection) – Live SARS-CoV-2 Virus
Studies were performed to determine the analytical limit of detection (LoD) of the Xpert
Xpress SARS-CoV-2. The LoD of Xpert Xpress SARS-CoV-2 was established using one
lot of reagent and limiting dilutions of live SARS-CoV-2 virus (USA_WA1/2020 strain)
prepared in viral transport medium and NP swab clinical matrix. The concentration level
with observed hit rates greater than or equal to 95% in the LoD determination study were
0.0050 and 0.0200 PFU/mL for the N2 target and E target, respectively (Table 4).
Verification of the estimated LoD claim was performed on one reagent lot in replicates of
20 prepared in pooled NP swab clinical matrix. The LoD is the lowest concentration
(reported as PFU/mL) of live SARS-CoV-2 virus samples that can be reproducibly
distinguished from negative samples ≥ 95% of the time with 95% confidence. The claimed
LoD is 0.0200 PFU/mL (Table 4).

Table 4. LoD Determination using USA-WA1/2020 Strain

Hit Hit
Total Rate Rate Mean Ct Mean Ct
Concentration
Strain Valid (%) (%)
(PFU/mL)
Results N2 E N2 E
Target Target Target Target
0.0200 20 100 95.0 38.3 36.4
0.0050 22 95.5 68.2 40.5 39.1
0.0025 22 90.9 36.4 41.5 39.6

SARS-CoV-2 virus 0.0010 22 50.0 18.2 42.0 42.0

(USA_WA1/2020) 0.0005 22 45.5 18.2 41.7 41.5
0.0003 22 18.2 4.5 42.1 44.9
0.0001 22 9.1 0 42.9 N/A
0 0 0 0 N/A N/A

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21.2 Analytical Reactivity (Inclusivity)

The inclusivity of Xpert Xpress SARS-CoV-2 was evaluated using in silico analysis of the
assay primers and probes in relation to 110,206 SARS-CoV-2 sequences available (as of
October 21, 2020) in the GISAID gene database for two targets, E and N2.
For the E target, 214 matching sequences were excluded due to ambiguity codes, which
reduced the total to 109,992 sequences. Xpert Xpress SARS-CoV-2 had 99.14% match to
the sequences with the exception of 926 sequences that had a single mismatch and 21
sequences with additional mismatches. The 21 sequences with additional mismatches
were:
• One sequence contained one mismatch in the forward primer region and a second
mismatch between oligos;
• One sequence contained one mismatch in the probe binding region and a second
mismatch between oligos;
• One sequence contained two mismatches in the probe binding region,
• One sequence contained a 3-nucleotide deletion and multiple mismatches at the 3’-end
of the probe region;
• Two sequences contained two mismatches in the forward primer region;
• Three sequences contained a 6-nucleotide deletion in the probe binding region with
multiple mismatches at the 3’ end of the amplicon; and
• Twelve sequences contained a ‘AA’ dinucleotide but this lies between the
oligonucleotides used in the assay.
None of these mismatches are predicted to have a negative impact on the performance of
the assay.

For the N2 target, 211 matching sequences were excluded due to ambiguity codes, which
reduced the total to 109,995 sequences. Xpert Xpress SARS-CoV-2 had 97.29% match to
the sequences with the exception of 2,919 sequences that had a single mismatch and sixty-
three sequences with two or more mismatches. The 63 sequences with additional
mismatches were:
• One sequence contained two mismatches in the probe binding region and a third
mismatch between oligos;
• Two sequences contained one mismatch in the forward primer region and a second
mismatch in the reverse primer region;
• Six sequences contained one mismatch in the forward primer region and a second
mismatch between oligos;
• Twenty-seven sequences contained one mismatch in the probe binding region and a
second mismatch in the reverse primer region; and
• Twenty-seven sequences contained one mismatch in the forward primer region and a
second mismatch in the probe binding region.
None of these mismatches are predicted to have a negative impact on the performance of
the assay.

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21.3 Analytical Specificity (Exclusivity)

An in silico analysis for possible cross-reactions with all the organisms listed in Table 5
was conducted by mapping primers and probes in the Xpert Xpress SARS-CoV-2 test
individually to the sequences downloaded from the GISAID database (as of March 13,
2020). E primers and probes are not specific for SARS-CoV-2 and will detect Human and
Bat SARS-coronavirus. No potential unintended cross reactivity with other organisms
listed in Table 5 is expected based on the in silico analysis.

Table 5. Xpert Xpress SARS-CoV-2 Analytical Specificity Microorganisms

Microorganisms from the Same High Priority Organisms
Genetic Family
Human coronavirus 229E Adenovirus (e.g. C1 Ad. 71)
Human coronavirus OC43 Human Metapneumovirus (hMPV)
Human coronavirus HKU1 Parainfluenza virus 1-4
Human coronavirus NL63 Influenza A
SARS-coronavirus Influenza B
MERS-coronavirus Influenza C
Bat coronavirus Enterovirus (e.g. EV68)
Respiratory syncytial virus
Rhinovirus
Chlamydia pneumoniae
Haemophilus influenzae
Legionella pneumophila
Mycobacterium tuberculosis
Streptococcus pneumoniae
Streptococcus pyogenes
Bordetella pertussis
Mycoplasma pneumoniae
Pneumocystis jirovecii (PJP)
Parechovirus
Candida albicans
Corynebacterium diphtheriae
Legionella non-pneumophila
Bacillus anthracis (Anthrax)
Moraxella catarrhalis
Neisseria elongate and meningitidis
Pseudomonas aeruginosa
Staphylococcus epidermidis
Staphylococcus salivarius
Leptospira
Chlamydia psittaci
Coxiella burnetii (Q-Fever)
Staphylococcus aureus

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21.4 FDA SARS-CoV-2 Reference Panel Testing

The evaluation of sensitivity and MERS-CoV cross-reactivity was performed using
reference material (T1), blinded samples and a standard protocol provided by the FDA.
The study included a range finding study and a confirmatory study for LoD. Blinded
sample testing was used to establish specificity and to confirm the LoD. The samples were
tested using the GeneXpert Dx System. The results are summarized in Table 6.

Table 6. Summary of LoD Confirmation Result Using the

FDA SARS-CoV-2 Reference Panel
Reference Materials Provided Specimen Product LoD Cross-Reactivity
by FDA Type (NDU/mL)
SARS-CoV-2 5.4x10 3 N/A
NP Swab
MERS-CoV N/A ND
NDU/mL = RNA NAAT detectable units/mL
N/A: Not applicable
ND: Not detected

22 References
1. Centers for Disease Control and Prevention. https://www.cdc.gov/coronavirus/2019-
ncov/index.html. Accessed February 9, 2020.
2. bioRxiv. (https://www.biorxiv.org/content/10.1101/2020.02.07.937862v1). Accessed
March 3, 2020.
3. Centers for Disease Control and Prevention. Biosafety in Microbiological and
Biomedical laboratories (refer to latest edition).
http://www.cdc.gov/biosafety/publications/
4. Clinical and Laboratory Standards Institute. Protection of Laboratory Workers from
Occupationally Acquired Infections; Approved Guideline. Document M29 (refer to
latest edition).
5. REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF
THE COUNCIL of 16 December 2008 on the classification labeling and packaging of
substances and mixtures amending and repealing, List of Precautionary Statements,
Directives 67/548/EEC and 1999/45/EC (amending Regulation (EC) No 1907/2007).
6. Occupational Safety and Health Standards, Hazard Communication, Toxic and Hazard
Substances (March 26, 2012) (29 C.F.R., pt. 1910, subpt. Z).

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23 Cepheid Headquarters Locations

Corporate Headquarters European Headquarters
Cepheid Cepheid Europe SAS
904 Caribbean Drive Vira Solelh
Sunnyvale, CA 94089 81470 Maurens-Scopont
USA France
Telephone: +1 408 541 4191 Telephone: +33 563 825 300
Fax: +1 408 541 4192 Fax: +33 563 825 301
www.cepheid.com www.cepheidinternational.com

24 Technical Assistance
Before contacting Cepheid Technical Support, collect the following information:
• Product name
• Lot number
• Serial number of the instrument
• Error messages (if any)
• Software version and, if applicable, Computer Service Tag number

Region Telephone Email

US + 1 888 838 3222 [email protected]
France + 33 563 825 319 [email protected]
Australia 1800 130 821
[email protected]
New Zealand 0800 001 028
Contact information for all Cepheid Technical Support offices is available on our website:
www.cepheid.com/en_US/support/contact-us.

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25 Table of Symbols
Symbol Meaning

Catalog number

In vitro diagnostic medical device

Do not re-use

Batch code

Consult instructions for use

Caution

Manufacturer

Country of manufacture

Contains sufficient for <n> tests

Control

Expiration date

Temperature limitation

Biological risks

For prescription use only

Cepheid
904 Caribbean Drive
Sunnyvale, CA 94089 USA
Phone: +1 408 541 4191
Fax: +1 408 541 4192
For use under Emergency Use Authorization (EUA) Only

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