The Cepheid Xpert GBS LB Assay, performed on the GeneXpert® Instrument Systems, is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens, using fully automated real-time polymerase chain reaction (PCR) with fluorogenic detection of the amplified DNA. Xpert GBS LB Assay testing is indicated as an aid in determining GBS colonization status in antepartum women.

The Xpert GBS LB Assay is used for antepartum testing on enriched Lim broth cultures of vaginal/rectal swabs after 18-24 hours of incubation.
The Xpert GBS LB assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

Device Description

The Cepheid Xpert GBS LB Assay is an automated in vitro diagnostic DNA test for the qualitative detection of Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens, using fully automated real-time polymerase chain reaction (PCR) with fluorogenic detection of the amplified DNA. Xpert GBS LB Assay testing is indicated for identification of antepartum GBS colonization with vaginal/rectal swab specimens prepared using an enrichment method in LB broth and then tested in the Xpert GBS LB Assay. The assay is performed on the Cepheid GeneXpert® Instrument Systems.

The GeneXpert Instrument Systems automate and integrate sample lysis, nucleic acid purification and amplification, and detection of the target sequence in complex samples using real-time PCR (Polymerase chain reaction) assays. The GeneXpert Instrument System family comprises a GeneXpert Dx instrument (GX-I, GX-IV, GX-XVI), the GeneXpert Dx XVI available with 4, 8, 12, or 16 modules; a GeneXpert Infinity-48. available with 16, 24, 32, 40 or 48 modules, or a GeneXpert Infinity-80 available with 16, 24, 32, 40, 48, 56, 64, 72, or 80 modules. The modules are identical for all instrument systems. The instrument systems also contain a computer, and preloaded software for running tests and viewing the results. The GeneXpert Infinity Systems contain robotic features for cartridge handling. Each module contains a syringe drive for dispensing fluids, an ultrasonic horn for lysing cells or spores, a valve drive for sample movement, and I-CORE® thermocycler for performing real-time PCR and detection.

The Xpert GBS LB Assay includes reagents pre-loaded in the Xpert GBS LB cartridge for the simultaneous detection of the target GBS DNA. A Sample Processing Control (SPC), an Internal Control (IC) and a Probe Check Control (PCC) are also included in the cartridge. The SPC is present to control for adequate processing of the target DNA; the IC is present to monitor the presence of inhibitors in the PCR reaction. The PCC verifies reagent rehydration, PCR-tube filling in the cartridge, probe integrity, and dye stability. The GBS primers and probe detect a target within a 3' DNA region adjacent to the cfb gene of S. agalactiae.

After collecting and transporting a swab sample to the laboratory, the swab is placed in Lim broth for enrichment overnight, after which a clean swab (Cepheid part number SDPS-120) dipped into the enrichment broth specimen is transferred to the designated chamber of the cartridge. The GeneXpert Instrument System performs sample preparation by eluting the specimen material from the swab, mixing the sample with the SPC (Bacillus globigii) in the form of a bead within the cartridge) and treatment reagent, capturing cellular material on a filter, lysing the cells, and eluting the DNA. The DNA solution is then mixed with dry PCR reagents and transferred into the integrated reaction tube for real-time PCR and detection. The results are interpolated by the GeneXpert Instrument Systems from measured fluorescent signals and embedded calculation algorithms. Results may be viewed and printed. The test process takes approximately 55 minutes. Sample preparation, amplification, and real-time detection are all fullyautomated and completely integrated.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert GBS LB Assay, based on the provided text:

Acceptance Criteria and Device Performance

Acceptance Criterion	Reported Device Performance
Clinical Performance (Enriched Method):	Xpert GBS LB Assay:
Sensitivity	99.0% (95% CI: 96.3-99.9)
Specificity	92.4% (95% CI: 90.1-94.4)
Positive Predictive Value (PPV)	79.7% (95% CI: 74.1-84.7)
Negative Predictive Value (NPV)	99.7% (95% CI: 98.8-100)
Analytical Sensitivity (LoD)	Overall LoD for the assay: 333 CFU/mL (lowest concentration reproducibly distinguished from negative samples with 95% confidence, or 19/20 replicates positive). Specific LoDs for 11 GBS strains ranged from 67 CFU/mL to 333 CFU/mL.
Analytical Specificity (Exclusivity)	100% (No false positives with 100 strains including 24 Streptococci, 76 other species, microflora, and human DNA at high concentrations).
Interfering Substances	None of the tested endogenous/exogenous substances (e.g., amniotic fluid, blood, urine, fecal sample, various medications, lubricants) had a statistically significant effect on assay performance. All positive samples reported correctly as GBS Positive, and all negative samples reported correctly as GBS Negative.
Carry-Over Contamination	100% prevention of carry-over. All 48 negative samples processed immediately after very high GBS positive samples (1x10^6 CFU/swab) were correctly reported as GBS negative.
Reproducibility	Overall Agreement: - GBS strain 1 moderate positive: 100.0%- GBS strain 1 low positive: 98.9%- GBS strain 1 high negative: 72.2%- GBS strain 2 moderate positive: 100.0%- GBS strain 2 low positive: 100.0%- GBS strain 2 high negative: 80.0%- Negative: 100.0% (Except one instance due to retesting mistake)
Instrument Precision	Total Agreement by Sample (GeneXpert Dx & Infinity-80):- GBS strain 1 moderate positive: 100.0%- GBS strain 1 low positive: 100.0%- GBS strain 1 high negative: 76.6%- GBS strain 2 moderate positive: 100.0%- GBS strain 2 low positive: 98.4%- GBS strain 2 high negative: 83.9%- Negative: 100.0%
Linearity	The assay responds linearly over four to five logs, ranging from 1x10^8 CFU/swab to 10 CFU/swab, depending on the GBS serotype.

Study Details

Clinical Performance Study

Sample size used for the test set and the data provenance:
- Sample Size: 826 specimens were tested in the clinical performance study.
- Data Provenance: The study was a "prospective multi-center study at three sites." The text does not specify the country of origin but implies it was conducted in the U.S., as it references "three institutions in the U.S."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the clinical performance study was established by reference culture. The text does not mention the number or qualifications of experts for interpreting these cultures or establishing a ground truth based on expert consensus. It refers to "culture" as the standard of care without detailing expert involvement for that specific ground truth method.
- However, for the specific cases where the Xpert GBS LB Assay results disagreed with the culture (48 false positives, 2 false negatives), sequencing was used for further investigation. The text doesn't specify if experts were involved in sequencing interpretation, but it is a laboratory technique rather than expert clinical judgment for the primary ground truth.
Adjudication method for the test set:
- The primary comparison was against "reference culture." For discrepant results between the Xpert GBS LB Assay and the reference culture, sequencing was used to resolve discrepancies.
  - 47 of 48 Xpert GBS positive / Culture negative specimens were sequenced. Of these, 42 were GBS positive by sequencing, and 5 were GBS negative by sequencing. One Lim broth was not sequenced.
  - Both of the 2 Xpert GBS negative / Culture positive specimens were sequenced and both were GBS negative by sequencing.
- This suggests a form of tiered adjudication where culture was the initial ground truth, and sequencing was used to investigate discrepancies.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No, a multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly mentioned or presented in the provided text. This device is an automated in vitro diagnostic (IVD) test (a lab test), not an AI-assisted diagnostic imaging or interpretation tool for human readers. Therefore, the concept of human readers improving with AI assistance is not applicable here.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the Cepheid Xpert GBS LB Assay is explicitly described as a standalone algorithm. It is "fully automated real-time polymerase chain reaction (PCR) with fluorogenic detection" and "The GeneXpert Instrument System performs sample preparation by eluting the specimen material... The results are interpolated by the GeneXpert Instrument Systems from measured fluorescent signals and embedded calculation algorithms." This indicates a fully automated, standalone performance.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The primary ground truth used for the clinical performance study was reference culture. For discrepant samples, sequencing was used as a confirmatory method.
The sample size for the training set:
- The document describes a clinical performance study using 826 specimens, which serves as the test set. It does not explicitly mention a separate "training set" for the clinical performance characteristics. For an IVD like this, the "training" (development and optimization) of the embedded algorithms typically happens during the assay development phase, using internal validation samples, rather than a separate, formally documented "training set" comparable to machine learning models. The document focuses on the validation of the device against established methods.
How the ground truth for the training set was established:
- As a formal "training set" for the clinical performance study is not described, the method for establishing its ground truth is not applicable or detailed in this document. The assay's internal algorithms and parameters were likely developed and refined using laboratory-controlled samples and reference strains (e.g., those used for analytical sensitivity, specificity, and linearity studies) during the product development process.

Summary

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1.0 510(k) Summary

As required by 21 CFR Section 807.92(c).

	NOV 2 2012
Submitted by:	Cepheid®904 Caribbean DriveSunnyvale, CA 90489Phone number: (408) 400-8460Fax number: (408) 541-6439kerry.flom@cepheid.com
Contact:	Russel K. Enns, Ph.D.
Date of Preparation:	May 23, 2012
Device:
Trade name:	Xpert® GBS LB
Common name:	Group B Strep Lim broth assay or Xpert GBS LB Assay
Type of Test:	Nucleic Acid Amplification System, Group B Streptococcuswith enriched broth method
Classification:	Class I (not exempt)
Classification name:	Streptococcus species serological reagents
Regulation number:	866.3740
Product code:	NJR
ClassificationAdvisoryCommittee:	Microbiology (83)

171539

Predicate Devices: Cepheid Smart GBS Assay [510(k) #K062948]

Device Description:

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Device Intended Use:

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The Xpert GBS LB Assay is used for antepartum testing on enriched Lim . broth cultures of vaginal/rectal swabs after 18-24 hours of incubation.
The Xpert GBS LB assay does not provide susceptibility results. Culture isolates . are needed for performing susceptibility testing as recommended for penicillinallergic women.

Substantial Equivalence:

The Xpert GBS LB Assay is substantially equivalent to Cepheid's Smart GBS Assay [510(k) #K062948]. Both assays detect Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens. Both assays determine the presence of the target organisms through real-time PCR amplification and fluorogenic target-specific hybridization detection and utilize the same Cepheid I-CORE instrumentation format. Table 5.1 shows the similarities and differences between the Xpert GBS LB Assay and the predicate device.

A prospective multi-center study at three sites was conducted on 719 patients to determine the performance characteristics of the device on the GeneXpert Instrument Systems for detection of GBS colonization in antepartum women from vaginal/rectal swab specimens with Lim broth enrichment. Sensitivity and specificity of the Assay relative to reference culture were compared to the sensitivity and specificity of the predicate device, the Cepheid Smart GBS Assay, relative to reference culture. The test results showed the Xpert GBS LB Assay to be substantially equivalent to the Smart GBS predicate device and the reference culture, the current standard of care,

	Xpert GBS LB(Proposed Device)	Predicate:Smart GBS (K062948)
Regulation no./Product code	21 CFR 866.3740 /NJR	Same
DeviceClassificationName	Nucleic Acid AmplificationAssay System, Group BStreptococcus, enriched brothmethod	Nucleic Acid Amplification AssaySystem, Group B Streptococcus,Direct Specimen Test and enrichedbroth method
Intended Use	The Cepheid Xpert GBS LBAssay, performed on theGeneXpert® InstrumentSystems, is a qualitative in vitrodiagnostic test designed to detectGroup B Streptococcus (GBS)DNA from enrichedvaginal/rectal swab specimens,using fully automated real-time	The Cepheid Smart GBS performedon the Cepheid SmartCycler DxSystem is a qualitative in vitrodiagnostic test designed to detectGroup B Streptococcus (GBS) DNAfrom vaginal/rectal specimens andLim broth cultures. The test utilizesreal-time polymerase chain reaction(PCR) for a unique gene specific
	Xpert GBS LB(Proposed Device)	Predicate:Smart GBS (K062948)
	polymerase chain reaction (PCR) with fluorogenic detection of the amplified DNA. Xpert GBS LB Assay testing is indicated as an aid in determining GBS colonization status in antepartum women.	sequence amplification ofStreptococcus agalactiae recovered from clinical samples and fluorogenic target-specific hybridization for the detection of the amplified DNA.Results from the Smart GBS Assay are intended for use as a method for rapid detection of GBS colonization in antepartum and intraparatum women.
	• The Xpert GBS LB Assay is used for antepartum testing on enriched Lim broth cultures of vaginal/rectal swabs after 18-24 hours of incubation.	• The use of the Smart GBS for intrapartum screening should not preclude the use of other strategies (e.g., antepartum testing). Intrapartum Smart GBS results are useful to identify candidates for intrapartum antibiotic prophylaxis when administration of intravenous antibiotics is not delayed pending results.
	• The Xpert GBS LB assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.	• The Smart GBS assay does not provide antibiotic susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.
Organism Detection	Group B Streptococcus DNA	Same
Specimen Type	From 18-24 hour Lim broth cultures of Vaginal/rectal swab	Direct from Vaginal/rectal swab or from 18-24 hour Lim broth cultures
Collection and Transport Medium	Cepheid Collection Device or swab in a non- nutritive transport medium	Same
Assay Platform	Cepheid GeneXpert Dx System,GeneXpert Infinity-48 System,	Cepheid SmartCycler System
	Xpert GBS LB(Proposed Device)	Predicate:Smart GBS (K062948)
Assay Format	Amplification: PCR with I-CORE heating and cooling module.Detection: Fluorogenic target-specific hybridization	Same
DNA TargetSequence	3' untranslated region of the cfb gene	Same
Probes	TaqMan®	Same
Self-containedsystem assay	Yes	Yes, after sample preparation which is off-line.
Single use	Yes; single-use Cepheid cartridge includes integrated reaction tube	Yes; single-use reaction tubes.
Samplepreparation	Automated Sample Preparation after swab specimen is placed in Lim broth for 18-24 hours at 35°-37° C.	Manual sample preparation With enriched option, swab specimen is placed in Lim broth overnight at 37° C.
Automatedamplification /detection andresultinterpretation	Yes	Same
Time to result	≤ 55 minutes total after sample addition to cartridge.	~ 75 minutes total including sample preparation and addition to reaction tube.
Built in Lysiscontrol	Yes	N/A, the negative and positive controls do not go through sample preparation steps.
External AssayControls	Materials available, but not required.	Materials available and required.
SampleProcessingControl	Sample Processing Control;Failures result in single sample repeat.	Uses external controls for sample Processing Control
Internal AssayControls	Sample Processing Control;Internal control;Probe Check (all optical channels)Failures result in single sample repeat.	Internal Control
Fluidics	Self-contained	Manual sample preparation
Criteria for Ct	Primary growth curve	Same
	Xpert GBS LB(Proposed Device)	Predicate:Smart GBS (K062948)
PerformanceCharacteristic*	Enriched methodSensitivity: 99.0%Specificity: 92.4%	Enriched methodSensitivity: 98.8%Specificity: 95.3%

Table 5.1

Similarities and Differences Between the Xpert GBS LB and the Predicate Device

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、

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as determined in the Cepheid Clinical Study Comparing Xpert and Smart GBS Sensitivity and Specificity relative to culture.

Non-Clinical Studies:

Analytical Sensitivity (Limit of Detection)

Studies were performed to determine the analytical limit of detection (LoD) of 11 GBS strains representing nine known serotypes. All GBS strains used were procured from ATCC or CDC. The LoD is defined as the lowest concentration per sample that can be reproducibly distinguished from negative samples with 95% confidence or the lowest concentration at which 19 of 20 replicates were positive. Each strain was tested in replicates of 20 per concentration of bacteria.

The LoD was determined empirically as the lowest concentration that had 19/20 or 20/20 positive results. The LoD point estimates for each strain tested are summarized in Table 5.2. The overall LoD for the assay is 333 CFU/mL.

Strain ID	ConfirmedLoD(CFU/swab)[at least 19/20positive]	Confirmed LoD(CFU/mL of LimBroth)[at least 19/20 positive]	LoD Estimate (Logistic Regression)(CFU/swab)
			Lower95% CI	LoDEstimate	Upper95% CI
Serotype Ia	13 (20/20)	173	8.0	10.0	14.2
Serotype Ib	25 (20/20)	333	8.7	11.1	15.7
Serotype II	25 (20/20)	333	10.4	13.3	20.1
Serotype II	25 (20/20)	333	20.1	23.6	32.1
Serotype III	25 (19/20)	333	16.3	21	35.4
Serotype IV	25 (20/20)	333	10.7	14.4	23.7
Serotype IVc	5 (20/20)	67	2.4	3.1	4.8
Serotype V	25 (20/20)	333	14.2	18.2	26.1
Serotype VI	25 (20/20)	333	7.6	10.4	17.8
Serotype VII	25 (20/20)	333	10.2	13.4	20.7
Serotype VIII	10 (20/20)	133	4.3	5.6	8.4

Table 5.2: Confirmed LoD - GBS Serotynes

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Analytical Specificity (Exclusivity)

The analytical specificity of the Xpert GBS LB Assay was evaluated by testing a panel of 100 strains representing 24 Streptococci, 76 other species including strains phylogenetically related to S. agalactiae, other microflora (bacteria and yeasts) commonly found in vaginal/anal flora, and human DNA. Replicates of three were tested at concentrations of 4.5 to 9.5x108 CFU/mL or 1.7 - 3.2 McFarland units in Lim broth. The analytical specificity was 100%.

Interfering Substances Study

In a non-clinical study, potentially interfering substances that may be present in vaginal/rectal specimens were evaluated directly relative to the performance of the Xpert GBS LB Assay. Potentially interfering endogenous and exogenous substances include, but are not limited to: human amniotic fluid, meconium, serum, urine, fecal material, human blood, lubricating gel, vaginal anti-itch medications, vaginal antifungal medications, anti-diarrheal medications, laxatives, stool softeners, topical hemorrhoid ointments, body oil, body powder, deodorant sprays, enema solutions, and spermicidal foam . Substances were tested at concentrations close to saturation. These substances are listed in Table 5.3 with active ingredients. None of the substances tested had a statistically significant effect on the assay performance. All positive samples were correctly reported as GBS Positive, and all negative samples were correctly reported as GBS Negative.

Category	Substance/Supplier	Final Concentration
Lim broth (Control)	Becton, Dickinson and Company	-
Human Amniotic Fluid	New England Life Sciences	2.0% (v/v)
Human Whole Blood (EDTA)	Stanford Blood Center	2.0% (v/v)
Human Whole Blood (NaCitrate)	Stanford Blood Center	2.0% (v/v)
Human Serum	Stanford Blood Center	2.0% (v/v)
Human Urine sample	In-house	2.0% (v/v)
Human Fecal sample	In-house	0.47% (w/v)
Human Meconium sample	LEE BioSolutions	1.75% (w/v)
Personal Lubricant	K-Y® Jelly Personal Lubricant(Personal Products Company,Skillman, NJ)	1.22% (w/v)
Lubricating Gel	AquaGel® Lubricating Gel(Parker Laboratories, Inc.,Fairfield, NJ)	0.57% (w/v)
Vaginal Anti-itch Medication	Vagisil Cream	0.41% (w/v)
Vaginal Antifungal Medication	Monistat Cream	0.29% (w/v)
	Yeast Gard (Douche)	1.89% (w/v)
Topical Hemorrhoid Ointments	Preparation H Cream	0.26% (w/v)
Anti-Diarrheal Medications	Pepto BismolKaopectate	1.00% (w/v)1.33% (w/v)
Deodorant Powder	Vagisil Powder	0.31% (w/v)

Table 5.3: Potentially Interfering Substances in Xpert GBS LB Assay

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Category	Substance/Supplier	FinalConcentration
Deodorant Suppositories	Norforms Suppositories	0.30% (w/v)
Deodorant Spray	FDS Deodorant Spray	0.53% (w/v)
Body Powder	Gold Bond Powder	0.40% (w/v)
Body Oil	Neutrogena Body Oil	1.41% (w/v)
Spermicidal Foam	Delfen Contraceptive Foam	0.59% (w/v)
Oral Laxatives	Metamucil Fiber SupplementExlax (Chocolate Pieces)Phillips Milk of Magnesia	0.33% (w/v)0.60% (w/v)1.78% (w/v)
Stool Softener	Dulcolax Suppositories	0.25% (w/v)
Enema Solution	Fleet Enema	1.93% (w/v)

Carry-Over Contamination Study

A study was conducted to demonstrate that single-use, self-contained Xpert GBS LB Assay cartridges prevent carry-over contamination in negative samples run following very high positive samples in the same GeneXpert module. The study consisted of a negative sample processed in the same GeneXpert module immediately following a very high GBS positive sample (roughly 1x106 CFU/swab) Lim broth consisting of GBS serotype II or GBS serotype IV cells. This testing scheme was repeated 20 times on four GeneXpert modules for a total of 88 runs resulting in 40 positive and 48 negative specimens. All 40 positive samples were correctly reported as GBS. All 48 negative samples were correctly reported as GBS negative.

Reproducibility

A panel of seven specimens with varying concentrations of 2 different GBS strains were tested by 2 operators each in triplicate on 5 different days at three sites (7 specimens x 2 operators x 3 times/ day x 5 days x 3 sites). One lot of Xpert GBS LB Assay was used at each of the 3 testing sites. The three levels were moderate positive (~3-4X LOD), low positive (~1X LOD) and high negative (below LOD). Xpert GBS LB Assays were performed on the GeneXpert Instrument Systems according to the Xpert GBS LB Assay procedure. Results are summarized in Table 5.4.

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Specimen ID	Site 1(Infinity-48)	Site 2(GeneXpert Dx)	Site 3(Infinity-80)	% TotalAgreementby Sample
GBS strain 1	100.0%	100.0%	100.0%	100.0%
moderate positive	(30/30)	(30/30)	(30/30)	(90/90)
GBS strain 1	100.0%	96.7%	100.0%	98.9%
low positive	(30/30)	(29/30)	(30/30)	(89/90)
GBS strain 1	73.3%	80.0%	63.3%	72.2%
high negative	(22/30)	(24/30)	(19/30)	(65/90)
GBS strain 2	100.0%	100.0%	100.0%	100.0%
moderate positive	(30/30)	(30/30)	(30/30)	(90/90)
GBS strain 2	100.0%	100.0%	100.0%	100.0%
low positive	(30/30)	(30/30)	(30/30)	(90/90)
GBS strain2	80.0%	83.3%	76.7%	80.0%
high negative	(24/30)	(25/30)	(23/30)	(72/90)
Negative	100.0%	100.0%	100.0%	100.0%
	(30/30)	(29/29) a	(30/30)	(89/89) a

Table 5.4: Summary of Reproducibility Results

ªOne negative sample had indeterminate result on initial test but was not retested by mistake.

Instrument System Precision

An in-house precision study was conducted to compare the performance of the GeneXpert Dx and the Infinity-80 instrument systems. A panel of seven specimens with varying concentrations of two different GBS strains was tested on 12 different days by two operators. Each operator conducted four runs of each panel specimen per day on each of the two instrument systems (7 specimens x 4 times/ day x 12 days x 2 operators x 2 instrument systems). One lot of Xpert GBS LB Assay was used for the study. Xpert GBS LB assays were performed according to the Xpert GBS LB Assay procedure. Results are summarized in Table 5.5.

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Specimen ID	GeneXpert Dx	Infinity-80	% TotalAgreementby Sample
GBS strain 1moderate positive	100.0%(96/96)	100.0%(96/96)	100.0%(192/192)
GBS strain 1low positive	100.0%(96/96)	100.0%(96/96)	100.0%(192/192)
GBS strain 1high negative	77.1%(74/96)	76.0%(73/96)	76.6%(147/192)
GBS strain 2moderate positive	100.0%(96/96)	100.0%(96/96)	100.0%(192/192)
GBS strain 2low positive	99.0%(95/96)	97.9%(94/96)	98.4%(189/192)
GBS strain2high negative	85.4%(82/96)	82.3%(79/96)	83.9%(161/192)
Negative	100.0%(96/96)	100.0%(96/96)	100.0%(192/192)

Table 5.5: Summary of Instrument Precision Results

Linearity

A study was conducted to define the reportable range of the Xpert GBS LB Assay and demonstrate a linear relationship between target input and assay output. Linearity was evaluated using ten (10) GBS strains representing the nine (9) known serotypes that ranged in concentration from 1x10° CFU/swab to 10 CFU/swab depending on the serotype. Replicates of 4 were tested at each concentration. Positive and negative controls for Xpert GBS LB were included in the study. The Xpert GBS LB Assay responds linearly over four to five logs ranging from 1x108 CFU/swab to 10 CFU/swab depending on the GBS serotype.

Clinical Performance Characteristics

Clinical Performance

Performance characteristics of the Xpert GBS LB Assay were evaluated at three institutions in the U.S. Subjects included individuals whose routine care called for collection of vaginal/rectal swab specimens for GBS testing. For eligible subjects. aliquots of leftover Lim broth sample were obtained for testing with the Xpert GBS LB Assay and reference culture testing, and patient management continued at the site per the standard practice. The Xpert GBS LB Assay performance was compared to culture.

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Overall Results

A total of 826 specimens were tested for GBS by the Xpert GBS LB Assay, and culture. The Xpert GBS LB Assay demonstrated a sensitivity and specificity for detection GBS colonization of 99.0% and 92.4%, respectively, relative to culture (Table 5.6).

	Culture
	Pos	Neg	Total
Xpert GBS	Pos	189	48a	237
	Neg	2b	587	589
	Total	191	635	826
Sensitivity: 99.0% (95% CI: 96.3-99.9)
Specificity: 92.4% (95% CI: 90.1-94.4)
PPV: 79.7% (95% CI: 74.1-84.7)
NPV: 99.7% (95% CI: 98.8-100)

Table 5.6: Xpert GBS LB Assay Performance vs. Culture

4Testing result by sequencing: 47 of 48 GBS specimens were sequenced, 42 were GBS positive, 5 were GBS negative and one Lim broth was not sequenced.

bTesting result by sequencing: 2 of 2 GBS specimens were sequenced, both were GBS negative.

Xpert GBS LB Assays for 98.1% (810/826) of eligible specimens were successful on the first attempt. The indeterminate cases included twelve ERROR results, two INVALID results, and two NO RESULT outcomes. All of the 16 indeterminate cases were retested and yielded valid results upon repeat assay. The overall rate of assay success was 100% (826/826).

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Image /page/11/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo consists of a stylized eagle with three tail feathers, enclosed within a circle. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged around the upper portion of the circle.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002

Cepheid®

c/o Kerry J. Flom, Ph.D. Senior Vice President, Clinical Affairs and Regulatory Submissions 904 Caribbean Drive Sunnyvale, CA 94089

2 2012 NOV

Re: K121539

Trade/Device Name: Xpert® GBS LB Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcal spp. serological reagents Regulatory Class: Class I Product Code: NJR, OOI Dated: October 3, 2012 Received: October 4, 2012

Dear Dr. Flom:

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.

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); medical device reporting (reporting of medical

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Page 2 – Dr. Kerry Flom

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 regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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/ReportalProblem/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 Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

Sally A. Hojvat

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

{13}------------------------------------------------

Indications for Use Form 4.0

510(k) Number (if known): _ K121539

Device Name: Xpert® GBS LB

Indications for Use:

The Xpert GBS LB Assay is used for antepartum testing on enriched Lim broth . cultures of vaginal/rectal swabs after 18-24 hours of incubation.
The Xpert GBS LB assay does not provide susceptibility results. Culture isolates are ● needed for performing susceptibility testing as recommended for penicillin-allergic women.

Prescription Use	AN
(Part 21 CFR 801 Subpart D)	X

ND/OR	Over-The-Counter Use
	(21 CFR 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)

Hayas

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

K:21539. 510(k)

Page 1 of 1

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. 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 I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.