(177 days)
Not Found
No
The description focuses on automated real-time PCR technology and does not mention AI or ML.
No.
The device is described as a "rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes ... as an aid in the diagnosis of Group A Streptococcal pharyngitis." Its purpose is to detect a pathogen, not to treat a condition.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is a "rapid, qualitative in vitro diagnostic test" and "can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis."
No
The device is an in vitro diagnostic test that utilizes a hardware system (GeneXpert Xpress System) and disposable cartridges to perform PCR and detect DNA. It is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
The "Intended Use / Indications for Use" section explicitly states: "The Xpert Xpress Strep A test... is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes..."
The "Device Description" section also reiterates: "The Xpert Xpress Strep A test is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of Streptococcus pyogenes..."
These statements clearly identify the device as an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Xpert Xpress Strep A test, performed on the GeneXpert Xpress System, is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A B-hemolytic Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Xpert Xpress Strep A test can be used as an aid in the diagnosis of Group A Streptococcal pharvngitis. The assay is not intended to monitor treatment for Group A Streptococus infections.
The Xpert Xpress Strep A test utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA.
Product codes (comma separated list FDA assigned to the subject device)
PGX, OOI
Device Description
The Xpert Xpress Strep A test is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of Streptococcus pyogenes from throat swab specimens from patients with signs and symptoms of pharyngitis.
The Xpert Xpress Strep A test is performed on the Cepheid GeneXpert® Xpress System. The GeneXpert Xpress System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Xpress System requires the use of single-use, disposable cartridges (the Xpert Xpress Strep A cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
The Xpress Strep A test includes primers and probes for the detection of a targeted sequence of the S. pyogenes genome allowing detection of Strep A directly from throat swab specimens collected from patients with signs and symptoms of pharyngitis. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Xpress System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The Probe Check Control verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of genomic DNA S. pyogenes in ~24 minutes or less. The GeneXpert Xpress System, comprised of the GeneXpert Xpress II and GeneXpert Xpress IV, is capable of performing separate sample preparation and realtime PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
Throat swab specimens are collected using the ESwab collection device and transported to the GeneXpert area and prepared according to package insert instructions. After mixing the specimen, the liquid sample is transferred to the Xpert Xpress Strep A cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert Xpress instrument platform, which performs hands-off real-time, multiplex PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Throat swab specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
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
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-Clinical Studies:
Analytical Sensitivity (Limit of Detection): Studies were performed to determine the analytical sensitivity or Limit of Detection (LoD) of the Xpert Xpress Strep A using the ESwab collection kit. The LoD is the lowest concentration of sample (reported as CFU/mL in ESwab transport medium or CFU/test) that can be reproducibly distinguished from negative samples 95% of the time, or the lowest concentration of organisms at which 19 of 20 replicates were positive. This study determined the lowest concentration of Streptococcus pyogenes cells diluted into pooled clinical throat swab matrix that can be detected using the Xpert Xpress Strep A. The analytical sensitivity was performed using two lots of reagents tested across three testing days with two Streptococcus pyogenes strains: ATCC BAA-946 and ATCC 19615. The claimed LoD for ATCC BAA-946 was 9 CFU/mL (3 CFU/test) and for ATCC 19615 was 18 CFU/mL (6 CFU/test).
Analytical Reactivity (Inclusivity): Twenty-four Streptococcus pyogenes strains were tested at 3X LoD using the Xpert Xpress Strep A in replicates of three. All 24 strains were correctly reported as Strep A DETECTED.
Analytical Specificity (Exclusivity): The analytical specificity of the Xpert Xpress Strep A was evaluated by testing a panel of 70 potentially cross-reactive microorganisms. All three replicates of all 70 organisms were reported as Strep A NOT DETECTED. The analytical specificity was 100%.
Microbial Interference: An interfering microorganism study was performed to assess the inhibitory effects of commensal microorganisms in throat swab samples on the performance of the Xpert Xpress Strep A. Twenty-seven microorganisms were tested for potential interference with Strep A detection, in the presence of Strep A at 3X LoD concentration. The results showed that the presence of the tested microorganisms did not interfere with the detection of Strep A target DNA.
Potentially Interfering Substances Study: Ten potentially interfering substances were evaluated for their potential to interfere with the performance of the Xpert Xpress Strep A. Medically and/or physiologically relevant concentrations were tested in simulated throat swab matrix in the presence and absence of Strep A at 3X LoD. There was no assay interference in the presence of the substances at the concentrations tested.
Carry-Over Contamination: A study was conducted to demonstrate that single-use, self-contained GeneXpert cartridges prevent specimen and amplicon carry-over contamination from very high titer positive samples into successively run negative samples. The study consisted of a negative sample processed immediately after a very high titer positive sample (≥ 1 X 10^6 CFU/mL). The testing scheme was repeated 40 times between 2 GeneXpert instruments. All 42 negative samples were correctly reported as Strep A NOT DETECTED, and all 40 positive samples were correctly reported as Strep A DETECTED.
Linearity: Not applicable, as the Xpert Xpress Strep A test is a qualitative assay.
Clinical Studies:
Clinical Performance: A prospective, multi-center investigational study was conducted to evaluate the clinical performance of the Xpert Xpress Strep A. An initial throat swab was collected for the standard of care method and a second throat swab was collected from consented subjects for testing by the Xpert Xpress Strep A and reference method (culture and latex agglutination for Strep A typing). 666 specimens were initially enrolled, with 623 included in the analysis. 94.7% (590/623) were successful on the initial test and 99.2% (618/623) upon retest. Discordant results were investigated using an alternative PCR/bidirectional sequencing assay. On initial testing, 33/623 specimens (5.3%) produced indeterminate results; 31/33 were retested, with 28 producing valid results for a final indeterminate rate of 0.8%.
Reproducibility Study: A four member reproducibility panel with varying concentrations of Streptococcus pyogenes was tested two times per day on five different days by three different operators at three sites (4 specimens x 2 times/day x 5 days x 3 operators x 3 sites), using three lots of Xpert Xpress Strep A cartridges. The samples were prepared in simulated throat swab matrix.
Key results are summarized in tables 8-9 and 8-10.
For the "Strep A High Neg" sample, overall agreement by sample was 91% (82/90).
For the "Strep A Low Pos" sample, overall agreement by sample was 97% (87/90).
For "Neg" and "Strep A Mod Pos" samples, overall agreement was 100% (90/90).
Mean Ct values and coefficients of variation for between-site, between-lot, between-day, between-operator, and within-assay were provided. For example, for Strep A Low Pos, the total CV was 3.5% with a mean Ct of 38.6.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity: 99.4% (95%CI: 96.5-99.9)
Specificity: 94.1% (95%CI: 91.6-95.9)
PPV: 85.3% (95%CI: 79.5-89.7)
NPV: 99.8% (95%CI: 98.7-100.0)
Accuracy: 95.5% (95%CI: 93.5-96.8)
Prevalence: 25.6% (95% CI: 22.3-29.1)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
IQuum Roche Liat™ Strep A Assay [510(k) #K141338]
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.2680
Streptococcus spp. nucleic acid-based assay.(a)
Identification. AStreptococcus spp. nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify variousStreptococcus spp. nucleic acids extracted directly from clinical specimens. The device detects specific nucleic acid sequences for organism identification. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate.
(6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.
(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.
(8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.
0
Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The FDA logo is composed of two parts: the Department of Health & Human Services logo on the left and the FDA acronym along with the full name of the agency on the right. The Department of Health & Human Services logo features a stylized depiction of a human figure, while the FDA part includes the acronym "FDA" in a blue square and the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.
April 26, 2018
Cepheid Jim Kelly Executive Director, Regulatory Affairs 904 Caribbean Drive Sunnyvale, California 94089
Re: K173398
Trade/Device Name: Xpert Xpress Strep A Regulation Number: 21 CFR 866.2680 Regulation Name: Streptococcus spp. nucleic acid-based assay Regulatory Class: Class II Product Code: PGX, OOI Dated: October 28, 2017 Received: October 31, 2017
Dear Jim Kelly:
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 comply with all the Act's 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR
1
Part 820); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Ribhi Shawar -S
For
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
2
Indications for Use
510(k) Number (if known) K173398
Device Name
Xpert Xpress Strep A
Indications for Use (Describe)
The Xpert Xpress Strep A test, performed on the GeneXpert Xpress System, is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A B-hemolytic Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Xpert Xpress Strep A test can be used as an aid in the diagnosis of Group A Streptococcal pharvngitis. The assay is not intended to monitor treatment for Group A Streptococus infections.
The Xpert Xpress Strep A test utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA.
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) |
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
3
510(k) Summary
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 90489
Phone number: (847) 228-3299
Fax number: (847) 890-6589 |
|--------------------------------------------|---------------------------------------------------------------------------------------------------------------------|
| Contact: | Jim Kelly, Ph.D. |
| Date of Preparation: | April 23, 2018 |
| Device: | |
| Trade name: | Xpert® Xpress Strep A |
| Common name: | Xpert Xpress Strep A |
| Type of Test: | Real-time PCR assay for qualitative detection of Group A
Streptococcus DNA in throat swab specimens. |
| Regulation number,
Classification name, | 21 CFR 866.2690, Streptococcus spp. nucleic acid based
assay, PGX |
| Product code: | 21 CFR 862.2570, Instrumentation for clinical multiplex test
systems, OOI |
| Classification
Advisory Panel | Microbiology (83) |
| Prescription Use | Yes |
| Predicate Device
Assay: | IQuum Roche Liat™ Strep A Assay
[510(k) #K1413381] |
Device Description:
The Xpert Xpress Strep A test is an automated real-time polymerase chain reaction (PCR) in vitro diagnostic test for qualitative detection of Streptococcus pyogenes from throat swab specimens from patients with signs and symptoms of pharyngitis.
The Xpert Xpress Strep A test is performed on the Cepheid GeneXpert® Xpress System. The GeneXpert Xpress System platform automates sample preparation, amplification and real-time detection.
The GeneXpert Xpress System requires the use of single-use, disposable cartridges (the Xpert Xpress Strep A cartridges) that hold the PCR reagents and host the PCR process. Because the cartridges are self-contained and specimens never come into contact with working parts of the instrument modules, cross-contamination between samples is minimized.
4
The Xpress Strep A test includes primers and probes for the detection of a targeted sequence of the S. pyogenes genome allowing detection of Strep A directly from throat swab specimens collected from patients with signs and symptoms of pharyngitis. A Sample Processing Control (SPC) and a Probe Check Control (PCC) are internal controls utilized by the GeneXpert Xpress System platform. The SPC is present to control for adequate processing of the target bacteria and to monitor for the presence of inhibitor(s) in the PCR assay to avoid false-negative results. The Probe Check Control verifies reagent rehydration, real-time PCR tube filling in the cartridge, probe integrity, and dye stability.
The single-use, multi-chambered fluidic cartridges are designed to complete sample preparation and real-time PCR for the detection of genomic DNA S. pyogenes in ~24 minutes or less. The GeneXpert Xpress System, comprised of the GeneXpert Xpress II and GeneXpert Xpress IV, is capable of performing separate sample preparation and realtime PCR and RT-PCR tests. Each module contains a syringe drive for dispensing fluids (i.e., the syringe drive activates the plunger that works in concert with the rotary valve in the cartridge to move fluids between chambers), an ultrasonic horn for lysing cells or spores, and a proprietary I-CORE® thermocycler for performing real-time PCR and RT-PCR and detection.
Throat swab specimens are collected using the ESwab collection device and transported to the GeneXpert area and prepared according to package insert instructions. After mixing the specimen, the liquid sample is transferred to the Xpert Xpress Strep A cartridge. The user initiates a test from the system user interface and places the cartridge into the GeneXpert Xpress instrument platform, which performs hands-off real-time, multiplex PCR for detection of DNA. The results are automatically generated at the end of the process in a report that can be viewed and printed.
Device Intended Use:
The Xpert® Xpress Strep A test, performed on the GeneXpert Xpress System, is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A ß-hemolytic Streptococcus, Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Xpert Xpress Strep A test can be used as an aid in the diagnosis of Group A Streptoccal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections.
The Xpert Xpress Strep A test utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA.
Substantial Equivalence:
The Xpert Xpress Strep A test is substantially equivalent to the Roche Liat Strep A Assay [510(k) # K141338]. The performance of the Xpert Xpress Strep A test was evaluated in a multi-site clinical study in which the performance of Xpert Xpress Strep A was determined relative to culture. The results of the study demonstrated that the performance of Xpert Xpress Strep A is substantially equivalent to the predicate device.
5
Table 8-1 shows the similarities and differences between Xpert Xpress Strep A and the predicate device.
| Similarities | ||
|---|---|---|
| Item | Device | Predicate Device |
| Cepheid Xpert Xpress Strep A | IQuum Inc. (Roche) Liat Strep A Assay | |
| 510(k) Number | To be assigned | K141338 |
| Regulation | Same | 866.2680 |
| Product Code | Same | PGX |
| Device Class | Same | II |
| Intended Use | The Xpert® Xpress Strep A test, performed on the GeneXpert Xpress System, is a rapid, qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A β-hemolytic Streptococcus , Strep A) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Xpert Xpress Strep A test can be used as an aid in the diagnosis of Group A Streptococcal pharyngitis. The assay is not intended to monitor treatment for Group A Streptococcus infections. The Xpert Xpress Strep A test utilizes an automated real-time polymerase chain reaction (PCR) to detect Streptococcus pyogenes DNA. | The Liat™ Strep A Assay, performed on the Liat™ Analyzer, is a qualitative in vitro diagnostic test for the detection of Streptococcus pyogenes (Group A β-hemolytic Streptococcus ) in throat swab specimens from patients with signs and symptoms of pharyngitis. The Liat™ Strep A Assay utilizes nucleic acid purification and polymerase chain reaction (PCR) technology to detect Streptococcus pyogenes by targeting a segment of the Streptococcus pyogenes genome. |
| Assay Target | Same | Streptococcus A |
| Table 8-1: Comparison of Similarities and Differences | ||
|---|---|---|
| of Xpert Xpress Strep A with the Predicate Device |
6
| Similarities | ||
|---|---|---|
| Item | Device | |
| Cepheid Xpert Xpress Strep A | Predicate Device | |
| IQuum Inc. (Roche) Liat Strep A Assay | ||
| Specimen Type | Same | Throat swab |
| Assay Controls | Yes | Yes |
| Strep A Target | Same | Conserved sequence within the |
| genome of S. pyogenes | ||
| Assay Method | Same | PCR for detecting the presence / absence of bacterial DNA in |
| clinical specimens | ||
| Extraction Method | Same | Automated nucleic acid extraction and purification |
| Detection Technique | Same | Different reporter dyes for target and Internal Control |
| Assay Result | Same | Qualitative |
| Differences | ||
| Item | New Device | |
| Cepheid Xpert Xpress Strep A | Predicate Device | |
| IQuum Inc. (Roche) Liat Strep A Assay | ||
| Equipment Required | Cepheid GeneXpert® Dx, | |
| GeneXpert Infinity-48s, | ||
| GeneXpert Infinity-80, and | ||
| GeneXpert Xpress System | Liat™ Analyzer | |
| Early assay | ||
| termination function | Yes | |
| (for positive samples) | No | |
| Time-to-result | ~24 minutes without early | |
| assay termination; | ||
| ~18 minutes with early assay | ||
| termination for positive | ||
| samples | ~15 minutes |
The Xpert Xpress Strep A test has the same general intended use as the predicate device and has the same technological characteristics as the predicate device. The differences between Xpert Xpress Strep A and the predicate device do not raise different questions of safety and effectiveness. The clinical study demonstrates that the Xpert Xpress Strep A test is acceptable for its intended use with inexperienced lab users and is substantially equivalent to the predicate device described above.
7
Non-Clinical Studies:
Analytical Sensitivity (Limit of Detection)
Studies were performed to determine the analytical sensitivity or Limit of Detection (LoD) of the Xpert Xpress Strep A using the ESwab collection kit. The limit of detection is the lowest concentration of sample (reported as CFU/mL in ESwab transport medium or CFU/test) that can be reproducibly distinguished from negative samples 95% of the time, or the lowest concentration of organisms at which 19 of 20 replicates were positive. This study determined the lowest concentration of Streptococcus pyogenes cells diluted into pooled clinical throat swab matrix that can be detected using the Xpert Xpress Strep A.
The analytical sensitivity of the Xpert Xpress Strep A was performed using two lots of reagents tested across three testing days with two Streptococcus pyogenes strains: ATCC BAA-946 and ATCC 19615.
The claimed LoD for each Strep A strain tested is summarized in Table 8-2.
| Strep A Strain | emm type | LoD
(CFU/mL in ESwab
transport medium) | LoD
(CFU/test) |
|----------------|----------|----------------------------------------------|-------------------|
| ATCC BAA-946 | 6 | 9 | 3 |
| ATCC 19615 | 80 | 18 | 6 |
Table 8-2: Strep A LoD
Analytical Reactivity (Inclusivity)
Twenty-four Streptococcus pyogenes strains were tested at 3X LoD using the Xpert Xpress Strep A in replicates of three. The strains tested included representative isolates of emm types 1, 3, 4, 6, 11, 12, 18, 22, 25, 27, 38, 75, 77, 89, 94, 95. The list of strains tested in ESwab medium containing simulated throat swab matrix is shown in Table 8-3. All 24 strains were correctly reported as Strep A DETECTED with the Xpert Xpress Strep A.
Table 8-3: Analytical Reactivity (Inclusivity) of Xpert Xpress Strep A
| Strep A Strain ID | emm type | Strain |
|---|---|---|
| ATCC 12202 | 1 | NCTC 8370 |
| ATCC 12344 | 1 | T1 |
| ATCC 700294 | 1 | SF370 |
| ATCC 12383 | 3 | D58X |
| ATCC 12384 | 3 | C203 |
| ATCC 12385 | 4 | J17A4 |
| ATCC 12203 | 6 | NCTC 8709 |
8
| Strep A Strain ID | emm type | Strain |
|---|---|---|
| ATCC 12352 | 11 | T11 |
| ATCC BAA-1065 | 12 | MGAS 2096 |
| ATCC BAA-1315 | 12 | MGAS9429 |
| ATCC 12357 | 18 | J17C |
| ATCC 10403 | 22 | T22 |
| ATCC 12204 | 25 | A25 |
| ATCC 8135 | 27 | T27 |
| ATCC 12365 | 38 | C107 |
| ATCC 12370 | 38 | C94 |
| ATCC 700497 | 75 | CDC-SS-1147 |
| ATCC 700499 | 77 | CDC-SS-1149 |
| ATCC 700949 | 89 | CDC-SS-1397 |
| ATCC BAA-355 | 94 | N/A |
| ATCC BAA-356 | 95 | N/A |
| ATCC 14289 | M protein-deficient S. | |
| pyogenes | C203 S | |
| ATCC 49399 | emm type not available | QC A62 |
| ATCC 51339 | emm type not available | 1805 |
Analytical Specificity (Exclusivity)
The analytical specificity of the Xpert Xpress Strep A was evaluated by testing a panel of 70 potentially cross-reactive microorganisms, including species that are phylogenetically related to Streptococcus pyogenes and members of the throat commensal microflora (e.g., other bacteria, viruses, and yeast). The 70 organisms tested were identified as either Gram-positive (27), Gram-negative (33), or Gram-indeterminate (3), yeast (1), and viruses (6). Streptococcus Group B, Streptococcus Group C, and Streptococcus Group G strains were also included in this study. All strains were tested in triplicate in ESwab transport medium containing simulated throat swab matrix at ≥10 CFU/mL for bacteria and yeast and ≥10 TCID The reproducibility of the Xpert Xpress Strep A was also evaluated in terms of the fluorescence signal expressed in Ct values for each target detected. The mean, standard deviation (SD), and coefficient of variation (CV) between-sites, between-lots, betweendays, between-operators and within-assay for each panel member are presented in Table 8-10.
| | Assay
Channel
(Analyte) | Nᵃ | Mean
Ct | Between-
Site | | Between-
Lot | | Between-
Day | | Between-
Operator | | Within-
Assay | | Total | |
|------------------|-------------------------------|----|------------|------------------|-----|-----------------|-----|-----------------|-----|----------------------|-----|------------------|-----|-------|-----|
| Sample | | | | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV | SD | CV |
| Neg | SPC | 90 | 33.5 | 0.3 | 0.9 | 1.0 | 3.0 | 0.3 | 0.9 | 0 | 0 | 1.5 | 4.5 | 1.9 | 5.5 |
| Strep A High Neg | SPC | 82 | 33.6 | 0.4 | 1.2 | 1.1 | 3.2 | 0 | 0 | 0 | 0 | 1.3 | 3.9 | 1.7 | 5.2 |
| Strep A Low Pos | SAᵇ | 87 | 38.6 | 0 | 0 | 0.4 | 0.9 | 0 | 0 | 0 | 0 | 1.3 | 3.4 | 1.3 | 3.5 |
| Strep A Mod Pos | SAᵇ | 90 | 37.2 | 0 | 0 | 0.1 | 0.3 | 0.2 | 0.5 | 0.2 | 0.5 | 0.9 | 2.4 | 1.0 | 2.6 |
Table 8-10: Summary of Reproducibility Data
a. Results with non-zero Ct values out of 90.
b. SA = Strep A
Conclusions
The results of the nonclinical analytical and clinical performance studies summarized above demonstrate that the Xpert Xpress Strep A test is substantially equivalent to the predicate device.