The Ccpheid Smart GBS Assay performed on the Cepheid SmartCycler Dx System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from vaginal/rcctal swab specimens and Lim broth cultures. The test utilizes real-time polymerase chain reaction (PCR) for a unique gene-specific sequence amplification of Streptococcus 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 intrapartum women.

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 Smart GBS assay does not provide susceptibility results. Culture isolates are . needed for performing susceptibility testing as recommended for penicillin-allergic women.

Device Description

The Cepheid Smart GBS Assay is a rapid, DNA test for detecting GBS DNA from vaginal/rectal swab specimens from pregnant women. The assay is performed on the automated Cephcid SmartCycler Dx System. The SmartCycler Dx System is a rapid, realtime thermal cycler used for identifying DNA or RNA from prepared biological samples. Each instrument contains 16 independently programmable modules that can perform fourcolor, real-time fluorometric detection. Samples are amplified and measured in the SmartCycler's proprietary, scalable reaction tubes that are designed to optimize rapid thermal transfer and optical sensitivity.
The four channel optics in the SmartCycler Dx System enables the simultancous detection of four targets within a single sample (multiplex assays) by employing multiplex PCR techniques and real-time fluorescent technologies such as Molecular Beacons and TaqMan" probes, Amplifluor" and Scorpion® primers, and intercalating dyes.
The Smart GBS Assay includes an internal control (IC) to monitor the presence of inhibitors in the Polymerase Chain Reaction (PCR). The GBS primers and probe detect a unique region of the S. agalactiae chromosome.
A vaginal/rectal swab is collected and transported to the laboratory. Swab processing then proceeds by one of two methods (direct method or an optional enriched Lim broth method). The Smart GBS Assay includes the reagents required for sample processing (except for the Lims Broth) and the detection of the target GBS DNA. Once sample processing is completed, an aliquot is added to the reconstituted assay reagents. The resulting mixture is placed into the SmartTube, and then loaded into the SmartCycler Dx System for real-time PCR. For quality control, an external positive and negative run control are provided in the Smart GBS Assay for each run.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study information for the Cepheid Smart GBS™ Assay, based on the provided text:

Acceptance Criteria and Device Performance

The document does not explicitly state pre-defined acceptance criteria in terms of specific sensitivity, specificity, or accuracy thresholds that the device had to meet. Instead, it presents the device's performance characteristics as determined from clinical studies and compares them to those of a predicate device, as well as emphasizing the overall safety, effectiveness, and substantial equivalence to the predicate. The "Performance Characteristics as determined in the Cepheid Clinical Studies (Protocols 105 and 108) as determined relative to culture" from Table 5-1 could be considered the reported device performance.

Table of Reported Device Performance:

Protocol/Method	Performance Metric	Smart GBS™ Assay Performance
Protocol 105: Direct Method (Overall)	Sensitivity	81.6% (95% CI = 75.3% - 86.9%)
	Specificity	96.4% (95% CI = 94.6% - 97.8%)
	Accuracy	92.9% (95% CI = 90.9% - 94.6%)
	Prevalence	23.9% (95% CI = 20.9% - 27.07%)
Protocol 105: Direct Method (Intrapartum)	Sensitivity	84.9% (95% CI = 76.0% - 91.5%)
	Specificity	97.2% (95% CI = 94.7% - 98.7%)
	Accuracy	94.4% (95% CI = 91.7% - 96.4%)
	Prevalence	22.7% (95% CI = 18.8% - 27.1%)
Protocol 105: Direct Method (Antepartum)	Sensitivity	78.3% (95% CI = 68.44% - 86.2%)
	Specificity	95.6% (95% CI = 92.5% - 97.7%)
	Accuracy	91.2% (95% CI = 87.9% - 93.9%)
	Prevalence	25.2% (95% CI = 20.8% - 30.0%)
Protocol 108: Enriched Method (Antepartum Only)	Sensitivity	98.7% (95% CI = 92.8% - 100.0%)
	Specificity	90.5% (95% CI = 85.9% - 93.9%)
	Accuracy	92.5% (95% CI = 88.9% - 95.2%)
	Prevalence	24.5% (95% CI = 19.8% - 29.7%)
Reproducibility: Negative	Total % Agreement	98.9%
Reproducibility: Weak Positive	Total % Agreement	98.9%
Reproducibility: Positive	Total % Agreement	100%
Reproducibility: Strong Positive	Total % Agreement	100%
Reproducibility: Overall	Total % Agreement	99.4%

Study Details

Sample sizes used for the test set and the data provenance:
- Direct Method Study (Test Set): 783 maternity subjects (363 antepartum, 420 intrapartum).
- Enriched Culture Study (Test Set): 306 antepartum maternity subjects.
- Data Provenance: Prospective investigational studies conducted at multiple institutions (six for direct method, three for enriched method) with maternity services in the United States.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing the ground truth. It refers to the "CDC-recommended culture technique" being performed in clinical laboratories.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- The document does not describe a formal adjudication method involving multiple readers. The ground truth was established by the CDC-recommended culture technique which is a laboratory method, not typically adjudicated by multiple human experts in this context.
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 done. This device is an in vitro diagnostic (IVD) assay that provides automated detection of GBS DNA; it is not an AI system that assists human readers in interpreting images or other data.
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, the performance presented is for the device in a standalone capacity ("algorithm only" in the context of an IVD assay where the "algorithm" is the real-time PCR detection and interpretation by the SmartCycler Dx System). The results are generated by the automated instrument, and while laboratory personnel perform sample preparation and load the device, the interpretation of the GBS detection itself is automated.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- The ground truth used was the CDC-recommended culture technique. This involves microbiological culture in selective broth medium (Lim broth), overnight incubation, subculture onto solid blood agar medium, and specific identification of GBS colonies with slide agglutination tests.
The sample size for the training set:
- The document describes prospective investigational studies whose results are presented as the device's performance. It does not explicitly mention a separate "training set" for the purpose of machine learning or algorithm development. The analytical studies (analytical sensitivity, specificity) likely served for initial assay development and optimization, but a distinct pre-defined "training set" as understood in machine learning is not detailed.
How the ground truth for the training set was established:
- As no distinct "training set" is described in the context of machine learning, this question is not fully applicable. However, for the analytical studies that would have informed the assay's development, the ground truth for detecting GBS strains (analytical sensitivity) was established using quantitated cultures of known Streptococcus agalactiae strains. For analytical specificity, known bacterial and yeast strains, and human DNA, were tested.

Summary

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K062948

DEC = 8 2006

Confidential

5.0 510(k) Summary or 510(k) Statement

As required by 21 CFR Section 807.92(c).

Submitted by:	Cepheid904 Caribbean DriveSunnyvale, CA 94089Phone number: (408) 400-8230Fax number: (408) 541-6439
Contact:	Russel K. Enns, Ph.D.
Date of Preparation:	September 27, 2006
Device:
Trade name:	Cepheid Smart GBST™ Assay
Common name:	Group B Strep Assay
Classification name:	Nucleic Acid Amplification Assay System, Group B Streptococcus, Direct Specimen Tes
Regulation number:	866.3740
Procode:	NJR
Classification Advisory Committee	Microbiology
Predicate Device:	IDI-Strep B Assay[510(k) no. K022504]

Device Description:

The four channel optics in the SmartCycler Dx System enables the simultancous detection of four targets within a single sample (multiplex assays) by employing multiplex PCR techniques and real-time fluorescent technologies such as Molecular Beacons and TaqMan" probes, Amplifluor" and Scorpion® primers, and intercalating dyes.

The Smart GBS Assay includes an internal control (IC) to monitor the presence of inhibitors in the Polymerase Chain Reaction (PCR). The GBS primers and probe detect a unique region of the S. agalactiae chromosome.

A vaginal/rectal swab is collected and transported to the laboratory. Swab processing then proceeds by one of two methods (direct method or an optional enriched Lim broth method). The Smart GBS Assay includes the reagents required for sample processing (except for the Lims Broth) and the detection of the target GBS DNA. Once sample processing is completed, an aliquot is added to the reconstituted assay reagents. The resulting mixture is

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placed into the SmartTube, and then loaded into the SmartCycler Dx System for real-time PCR. For quality control, an external positive and negative run control are provided in the Smart GBS Assay for each run.

Device Intended Use:

The Cepheid Smart GBS Assay performed on the Cepheid SmartCycler Dx System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens and Lim broth cultures. The test utilizes real-time polymerase chain reaction (PCR) for a unique gene-specific sequence amplification of Streptococcus 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 intrapartum women.

. The use of the Smart GBS for intrapartum screening should not preclude the use of other strategies (e.g., antepartum testing). Intrapartum Smart GBS rcsults are useful to identify candidates for intrapartum antibiotic prophylaxis when administration of intravenous antibiotics is not delayed pending results.
. The Smart GBS assay docs not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

Substantial Equivalence:

The Cepheid Smart GBS Assay is substantially equivalent to the Infectio Diagnostic Inc. IDI-Strep B assay. Both assays detect Group B Streptococcus; both assays use the Cepheid SmartCycler Dx System to determine the presence of GBS through real-time PCR amplification and fluorogenic target-specific hybridization detection; both assays recommend the use of Copan Collection and Transport Liquid Stuarts medium for specimen collection.

The Smart GBS performed on the SmartCycler Dx System also has the same intended use and many of the same technological characteristics, and reagent and instrument components as the Ccpheid Xpert GBS and the GeneXpert Dx System. (For example both assays have the same primers and probe that detect the same unique DNA region of of S. agalactiae. Both assays utilize the I-CORF. thermal cycling module for amplification and detection. The Xpert GBS Assay [510(k) No. K0605401 was cleared on July 25, 2006.

Table 5-1 shows the similaritics and differences between the Smart GBS and the predicate device.

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Table 5-1

Similarities and Differences Between the Smart GBS™ and the IDI-Strep BTM Assay

	Smart GBSTM	IDI-Strep BTM Assay
Regulation no./Procode	21 CFR 866.3740/ NJR	Same
DeviceClassificationName	Nucleic Acid Amplification AssaySystem, Group B Streptococcus, DirectSpecimen Test	Same
Intended Use	A qualitative in vitro diagnostic testdesigned to detect Group BStreptococcus (GBS) DNA fromvaginal/rectal swab specimens and Limbroth cultures. The test utilizes real-time polymerase chain reaction (PCR)for a unique gene-specific sequenceamplification of Streptococcusagalactiae recovered from clinicalsamples and fluorogenic target specifichybridization for the detection of theamplified DNA. Results from the SmartGBS Assay are intended for use as amethod for rapid detection of GBScolonization in antepartum andintrapartum women.• The use of the Smart GBS forintrapartum screening should notpreclude the use of other strategies(e.g., antepartum testing).Intrapartum Smart GBS results areuseful to identify candidates forintrapartum antibiotic prophylaxiswhen administration of intravenousantibiotics is not delayed pendingresults.• The Smart GBS assay does notprovide susceptibility results.Culture isolates are needed forperforming susceptibility testing asrecommended for penicillin-allergicwomen.	A qualitative in vitro diagnostic testfor the rapid detection of Group Bstreptococcus (GBS) invaginal/rectal specimens fromantepartum or intrapartum women.The test performed on theSmartCycler® automated analyzerutilizes polymerase chain reaction(PCR) for the amplification of a cfbgene sequence of GBS recoveredfrom clinical samples andfluorogenic target-specifichybridization for the detection ofthe amplified DNA.IDI-Strep BTM Assay can be used toestablish GBS colonization status ofantepartum and intrapartum women.
OrganismDetection	Group B streptococcus DNA	Same
	Smart GBSTM	IDI-Strep BTM Assay
Specimen Type	Vaginal/rectal swab	Same
Collection andTransport Medium	Copan with Liquid Stuart Medium	Same
Sample Preparation	All reagents are provided inindividually packaged tubes for manualsample preparation. The samplepreparation procedure requires manualpipetting, fluid transfers, vortexing andcentrifugation steps.	Same
Sample Processing	Direct Method: The vaginal/rectal swabis placed in Sample PreparationReagent and processed for real-timePCR amplification and detection.Enriched Method: The vaginal/rectalswab is placed into Lim broth andincubated overnight at 37°C, prior tobeing processed for real-time PCRamplification and detection.	Same as Direct Method.
Assay Platform	Cepheid SmartCycler Dx System	Same
Assay Format	Amplification: PCR with I-COREheating and cooling module.Detection: Fluorogenic target-specifichybridization	Same
Single use	Yes;single-use Smart GBS reagent beadssingle-use Smart GBS reagent liquidssingle-use Cepheid SmartTube™reaction tubes	Yes;single-use Cepheid SmartTube™reaction tubes
Automated assay	Yes; amplification, detection and resultinterpretation	Same
Time to result	Direct Method:Approximately 75 minutes, includingsample processing for the directmethod.Enriched Method: Optional overnightincubation; then same as direct method.	Direct Method:Approximately 45 minutes, plus 15minutes for sample processing forthe direct method.Enriched Method: not cleared forthis method.
External RunControls	External positive and negative runcontrols are required and provided foreach assay run	Same
	Smart GBS™	IDI-Strep B™ Assay
External SampleProcessingControls	Materials available commercially, butnot required	Materials available commercially,but not required
Internal Assay andSystem Controls	Internal Control;Probe Check (all optical channels)Failures result in single sample repeat.	Internal controlSite check (1 optical channel)Same
Criteria for Ctdetermination	Primary growth curve	2nd derivative analysis
Users	CLIA high complexity laboratories	Same
PerformanceCharacteristics asdetermined in theCepheid ClinicalStudies (Protocols105 and 108) asdetermined relativeto culture.	Protocol 105: Direct:Sensitivity: 81.62%Specificity: 96.43%Protocol 108: Enriched:Sensitivity: 98.67%Specificity: 90.48%	As determined in the CepheidClinical study using the samesubjects as tested with the Smart GBS™:Sensitivity: 81.52%Specificity: 95.51%
Probes	TaqMan® Probes	Molecular beacons

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Non-Clinical Studies:

Analytical Scnsitivity/Limit of Detection (LOD):

The analytical sensitivity was determined using 11 Streptococcus agalactiae strains representing nine known serotypes. Quantitated cultures were tested in four replicates. All 11 strains were detected by the Smart GBS Assay. The LOD was cvaluated in a separate study using groups of swabs (n=20) spiked with GBS Scrotype II (75 µL/swab) at 4 concentrations (100, 250, 500, and 750 CFU). The LOD was shown to be 750 CFU/swab (20/20 detected).

Analytical Specificity:

Analytical specificity was evaluated using 106 strains representing 28 Streptococci, 78 other species including strains phylogenctically related to Streptococcus agalactiae, other microflora (bactcria and yeasts) commonly found in vaginal and anal flora, and human DNA. Replicates of three were tested at 1.5 ng/25 uL reaction (~2c5 equivalent genome copics per reaction). Nonc of the 28 Streptococcal isolates (non-GBS) tested positive. Of the remaining 78 strains, four (Enterococcus gallinarium, Staphylococcus simulans, Micrococcus luteus, and Propionibacterium acnes) wcrc wcakly positive in one of six replicates at 1.5 ng/25 µL reaction.

Clinical Studies:

Performance characteristics of the Smart GBS Assay were determined in two multi-site prospective investigational studies. The first study evaluated the Smart GBS using the

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direct mcthod. The second study evaluated the Smart GBS using enriched culture method.

The direct method study (antepartum and intrapartum subjects) was performed at six institutions and the enriched culture study (antepartum subjects only) was performed at three institutions with maternity services in the United States. Each institution had a culturebased or nucleic acid test (NAT) based screening program. Testing was done in clinical laboratorics.

Study participants had to mect inclusion and exclusion criteria.

The method of reference used was the culture tcchnique recommended by the Centers for Discase Control and Prevention (CDC): microbiological culture in selective broth medium (Lim broth, which is Todd-Hewitt broth supplemented with 15 µg/mL of nalidixic acid, and 10 ug/mL of colistin), followed by overnight incubation and subculture onto solid blood agar medium. Specific identification of colonies suggestive of GBS was done with slide agglutination tests.

The performance characteristics of the Smart GBS Assay were determined from the results of 783 maternity subjects in the direct study (363 antepartum and 420 intrapartum), and 306 antepartem maternity subjects in the enriched culture study.

Total Results:

Vaginal/rectal specimens were collected from cach subject using two sets of double-marked collection swabs. One of the swabs from the first set was used in the CDC-recommended culture technique; the other swab was used for Smart GBS. The second set of doublemarked swabs was divided: one swab was used in the Xpcrt GBS Assay on the GeneXpert Dx System, the other was used in the IDI Strep BTM Assay on the SmartCycler® System.

To minimize swab-to-swab variation, the swabs remaining from the Smart GBS Assay and the IDI Strep B Assay were both cultured. Sensitivity and specificity were calculated relative to the culture results.

Table 5-2 compares the overall results from the Smart GBS Assay run on the SmartCycler Dx System and the CDC-recommended culture technique. The sensitivity and specificity data are shown below the table.

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Confidential

Table 5-2

Direct Method Overall Results Comparison of Smart GBS Assay and the CDC culture technique.

		Culture
		Positive	Negative	Total
Smart GBS	Positive	151	21	172
	Negative	34	568	602
	Total	185	589	774

81.6% (95% CI = 75.3% - 86.9%) Sensitivity: Specificity: 96.4% (95% CI = 94.6% - 97.8%) Accuracy: 92.9% (95% CI = 90.9% - 94.6%) Prevalence: 23.9% (95% CI = 20.9% - 27.07%) Intrapartum Results:

Table 5-3 compares the intrapartum culture results from the Smart GBS Assay run on the SmartCycler Dx System and the CDC recommended culture technique. The sensitivity and specificity data are shown below the table.

Table 5-3

Direct Method Intrapartum Results Comparison of Smart GBS Assay and the CDC culture technique.

			Culture
			Positive	Negative	Total
Smart GBS	Positive	79	9	88
	Negative	14	307	321
	Total	93	316	409

84.9% (95% CI = 76.0% - 91.5%) Sensitivity: Specificity: 97.2% (95% CI = 94.7% - 98.7%) Accuracy: 94.4% (95% CI = 91.7% - 96.4%) Prevalence: 22.7% (95% CI = 18.8% - 27.1%)

Antepartum Results:

Table 5-4 compares the antepartum results from the Smart GBS Assay run on the SmartCycler Dx System relative to the CDC-rccommended culture technique. The sensitivity and specificity data are shown below the table.

Table 5-4

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			Culture
			Positive	Negative	Total
Smart GBS	Positive	72	12	84
	Negative	20	261	281
	Total	92	273	365

Direct Method Antepartum Results Comparison of Smart GBS Assay and the CDC culture technique

Sensitivity: 78.3% (95% CI = 68.44% - 86.2%) Specificity: 95.6% (95% CI = 92.5% - 97.7%) Accuracy: 91.2 % (95% CI = 87.9% - 93.9%) Prevalence: 25.2% (95% CI = 20.8% - 30.0%)

Enriched Method Smart GBS: Antepartum Results:

Table 5-5 compares the antepartum culture results from the cnriched culture method Smart GBS Assay run on the SmartCycler Dx System relative to the CDC-recommended culture technique. The sensitivity and specificity data are shown below the table.

Table 5-5

Enriched Method Overall Results: (Antepartum Only) Comparison of Smart GBS Assay and the CDC culture technique

	Culture
	Positive	Negative	Total
Smart GBS	Positive	74	22	96
	Negative	1	209	210
	Total	75	231	306

Sensitivity: 98.7% (95% CI = 92.8% - 100.0%) Specificity: 90.5% (95% CI = 85.9% - 93.9%) Accuracy: 92.5% (95% (95% CI = 88.9% - 95.2%%) Prevalence: 24.5% (95% CI = 19.8% - 29.7%)

Summary of Indeterminate Result Rates:

The number of indeterminate results obtained from using the Smart GBS Assay was compared to the number obtained from using the predicate device, IDI-Strep B Assay.

In the Direct Study, the Smart GBS Assay was successful on 98.23% (779/793) of all cligible patients, and 91.17% (723/793) gave a result on the first attempt. There were 51

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specimens retested due to failed internal control and of these 14 specimens that did not give a result on the second attempt. There were a total of 4 invalid runs (33 tests) due to failed external controls.

The IDI-Strep B Assay was succssful on 99.75% (791/793) of all eligible patients, and 95.08% (754/793) gave a result on the first attempt. There were 12 specimens retested due to failed internal control, and of these 2 specimens did not give a result on the second attempt. There were a total of 4 invalid runs (29 tests) due to failed external controls.

In the Enriched Method Study, the Smart GBS Assay was successful on 100% (306/306) of all eligible patients, and 98.36% (301/306) give a result on the first attempt. There was a total of 1 invalid run (3 tests) due to failed external controls and 2 invalid specimens due to failed internal controls.

The IDI-Strep B assay was successful on 100% (306/306) of all cligible patients, and 96.73% (296/306) gave a result on the first attempt. There were a total of 3 invalid runs (9 tests) due to failed external controls and onc unresolved specimen due to computer loss power.

Reproducibility:

A pancl of four simulated specimens with varying concentrations of GBS were tested 3 times per day on 10 different days at cach of the three sites (4 specimens × 3 × 10 days × 3 sites). One lot of reagent was used for the study.

Summary of Reproducibility Results
Specimen ID	Site 1	Site 2	Site 3	TotalAgreement	Total %Agreement
Negative	30/30	30/30	29/30	89/90	98.9%
Weak Positive	29/30	30/30	30/30	89/90	98.9%
Positive	30/30	30/30	30/30	90/90	100%
Strong Positive	30/30	30/30	30/30	90/90	100%
Total Agreement	119/120	120/120	119/120	358/360	99.4%
% Agreement	99.2%	100%	99.2%	99.4%	99.4%

Table 5-6

Conclusions:

The results of the nonclinical and clinical studies discussed above demonstrate that the device is as safe, as effective, and performs as well or better than the predicate device and the reference method, and is substantially equivalent to the Predicate device, IDI-Strep B Assay.

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Image /page/9/Picture/10 description: The image shows the seal of the Department of Health and Human Services (HHS). The seal features an eagle with outstretched wings, symbolizing protection and service. The words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" are arranged in a circular pattern around the eagle. The seal is simple and monochromatic.

Public Health Service

DEC - 8 2006

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

Russel K. Enns, Ph.D. Senior Vice President Regulatory & Clinical Affairs, Quality System and Reimbursement Cepheid. Inc. 904 Caribbean Drive Sunnyvale, CA 94089

Re: K062948 Trade/Device Name: Smart GBSTM Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus Spp. Serological Reagents Regulatory Class: Class II Product Code: NJR Dated: September 27, 2006 Received: September 28, 2006

Dear Dr. Enns:

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 such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 Parts 801 and 809); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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This letter will allow you to begin marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific information about the application of labeling requirements to your device, 11 you don't op the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (240)276-0450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). Other general information on your responsibilities under the Act may be obtained from the Oilvision of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Sally, attorn

Sally A. Hoivat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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4.0 Indications for Use Statement

510(k) Number (if known): K062948

Device Name: Smart GBSTM

Indications for Use:

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 Smart GBS assay does not provide susceptibility results. Culture isolates are . needed for performing susceptibility testing as recommended for penicillin-allergic women.

Prescription Use X (Part 21 CFR 801 Subpart D)

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

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

Eueddei a. Poole
Division Sign-Off

Cepheid Smart GBS Assay 510(k) Notifical of In Vitro Diagnostic Device Device of Volume I, Page 22 of 274 Evaluation and Safety September 27, 2006

K062948

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.