(71 days)
No
The summary describes a real-time PCR assay and an automated thermal cycler system. There is no mention of AI or ML in the device description, intended use, or performance studies. The technology described is standard molecular diagnostics.
No.
This device is an in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA, not to provide therapy.
Yes
The "Intended Use / Indications for Use" states that it is a "qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA". It is used for "rapid detection of GBS colonization" which implies it aids in diagnosis.
No
The device description clearly states that the Cepheid Smart GBS Assay is performed on the automated Cepheid SmartCycler Dx System, which is a hardware device (real-time thermal cycler) with optical detection capabilities. The assay also includes reagents and requires sample processing, indicating it is not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The document explicitly states the device is a "qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from vaginal/rectal swab specimens and Lim broth cultures." This directly aligns with the definition of an in vitro diagnostic device, which is intended for use in the collection, preparation, and examination of specimens taken from the human body to obtain information for diagnostic purposes.
- Device Description: The description details how the device analyzes biological samples (vaginal/rectal swabs and Lim broth cultures) using real-time PCR to detect GBS DNA. This process is performed outside of the body (in vitro).
- Performance Studies: The document describes clinical studies where the device's performance (sensitivity, specificity, accuracy) was evaluated using human specimens against a reference method (culture). This is a standard requirement for demonstrating the performance of an IVD.
N/A
Intended Use / Indications for Use
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.
Product codes
NJR
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, real-time thermal cycler used for identifying DNA or RNA from prepared biological samples. Each instrument contains 16 independently programmable modules that can perform four-color, 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.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
vaginal/rectal swab specimens
Indicated Patient Age Range
antepartum and intrapartum women.
Intended User / Care Setting
CLIA high complexity laboratories
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
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 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.
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.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Non-Clinical Studies:
- Analytical Sensitivity/Limit of Detection (LOD):
- Evaluated using 11 Streptococcus agalactiae strains representing nine known serotypes. All 11 strains were detected.
- LOD evaluated with groups of swabs (n=20) spiked with GBS Scrotype II at 4 concentrations (100, 250, 500, and 750 CFU). The LOD was shown to be 750 CFU/swab (20/20 detected).
- Analytical Specificity:
- Evaluated using 106 strains representing 28 Streptococci, 78 other species (including phylogenctically related and common microflora), and human DNA.
- None of the 28 non-GBS Streptococcal isolates tested positive.
- Four of the other 78 strains (Enterococcus gallinarium, Staphylococcus simulans, Micrococcus luteus, and Propionibacterium acnes) were weakly positive in one of six replicates at 1.5 ng/25 µL reaction.
Clinical Studies:
- Study Type: Two multi-site prospective investigational studies (Direct Method Study and Enriched Culture Method Study).
- Reference Method: CDC-recommended culture technique (microbiological culture in selective broth medium (Lim broth), followed by overnight incubation and subculture onto solid blood agar medium. Specific identification with slide agglutination tests).
- Direct Method Overall Results (N=774):
- 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%)
- Direct Method Intrapartum Results (N=409):
- 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%)
- Direct Method Antepartum Results (N=365):
- 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 Overall Results (Antepartum Only) (N=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:
- Direct Study:
- Smart GBS Assay: 98.23% (779/793) successful, 91.17% (723/793) on first attempt. 51 retested due to failed internal control, 14 did not give result on second attempt. 4 invalid runs (33 tests) due to failed external controls.
- IDI-Strep B Assay (Predicate): 99.75% (791/793) successful, 95.08% (754/793) on first attempt. 12 retested due to failed internal control, 2 did not give result on second attempt. 4 invalid runs (29 tests) due to failed external controls.
- Enriched Method Study:
- Smart GBS Assay: 100% (306/306) successful, 98.36% (301/306) on first attempt. 1 invalid run (3 tests) due to failed external controls, 2 invalid specimens due to failed internal controls.
- IDI-Strep B assay (Predicate): 100% (306/306) successful, 96.73% (296/306) on first attempt. 3 invalid runs (9 tests) due to failed external controls, and one unresolved specimen due to computer loss power.
Reproducibility Study:
- Study Design: Panel of four simulated specimens (Negative, Weak Positive, Positive, Strong Positive) tested 3 times per day on 10 different days at each of three sites (4 specimens × 3 × 10 days × 3 sites), using one lot of reagent.
- Total % Agreement: 99.4% (358/360)
- Negative: 98.9% (89/90)
- Weak Positive: 98.9% (89/90)
- Positive: 100% (90/90)
- Strong Positive: 100% (90/90)
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Direct Method Overall Results:
- 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%)
Direct Method Intrapartum Results:
- 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%)
Direct Method Antepartum Results:
- 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 Overall Results: (Antepartum Only)
- 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%)
Reproducibility:
- Total % Agreement: 99.4%
Predicate Device(s)
IDI-Strep B Assay [510(k) no. K022504]
Reference Device(s)
Ccpheid Xpert GBS and the GeneXpert Dx System. (The Xpert GBS Assay [510(k) No. K0605401 was cleared on July 25, 2006.
Predetermined Change Control Plan (PCCP) - All Relevant Information
Not Found
§ 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.
0
DEC = 8 2006
Confidential
5.0 510(k) Summary or 510(k) Statement
As required by 21 CFR Section 807.92(c).
| Submitted by: | Cepheid
904 Caribbean Drive
Sunnyvale, CA 94089
Phone number: (408) 400-8230
Fax 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 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
1
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.
2
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 | |
| Device | ||
| Classification | ||
| Name | Nucleic Acid Amplification Assay | |
| System, Group B Streptococcus, Direct | ||
| Specimen Test | Same | |
| Intended Use | 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 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. | A qualitative in vitro diagnostic test | |
| for the rapid detection of Group B | ||
| streptococcus (GBS) in | ||
| vaginal/rectal specimens from | ||
| antepartum or intrapartum women. | ||
| The test performed on the | ||
| SmartCycler® automated analyzer | ||
| utilizes polymerase chain reaction | ||
| (PCR) for the amplification of a cfb | ||
| gene sequence of GBS recovered | ||
| from clinical samples and | ||
| fluorogenic target-specific | ||
| hybridization for the detection of | ||
| the amplified DNA. | ||
| IDI-Strep BTM Assay can be used to | ||
| establish GBS colonization status of | ||
| antepartum and intrapartum women. | ||
| Organism | ||
| Detection | Group B streptococcus DNA | Same |
| Smart GBSTM | IDI-Strep BTM Assay | |
| Specimen Type | Vaginal/rectal swab | Same |
| Collection and | ||
| Transport Medium | Copan with Liquid Stuart Medium | Same |
| Sample Preparation | All reagents are provided in | |
| individually packaged tubes for manual | ||
| sample preparation. The sample | ||
| preparation procedure requires manual | ||
| pipetting, fluid transfers, vortexing and | ||
| centrifugation steps. | Same | |
| Sample Processing | Direct Method: The vaginal/rectal swab | |
| is placed in Sample Preparation | ||
| Reagent and processed for real-time | ||
| PCR amplification and detection. |
Enriched Method: The vaginal/rectal
swab is placed into Lim broth and
incubated overnight at 37°C, prior to
being processed for real-time PCR
amplification and detection. | Same as Direct Method. |
| Assay Platform | Cepheid SmartCycler Dx System | Same |
| Assay Format | Amplification: PCR with I-CORE
heating and cooling module.
Detection: Fluorogenic target-specific
hybridization | Same |
| Single use | Yes;
single-use Smart GBS reagent beads
single-use Smart GBS reagent liquids
single-use Cepheid SmartTube™
reaction tubes | Yes;
single-use Cepheid SmartTube™
reaction tubes |
| Automated assay | Yes; amplification, detection and result
interpretation | Same |
| Time to result | Direct Method:
Approximately 75 minutes, including
sample processing for the direct
method.
Enriched Method: Optional overnight
incubation; then same as direct method. | Direct Method:
Approximately 45 minutes, plus 15
minutes for sample processing for
the direct method.
Enriched Method: not cleared for
this method. |
| External Run
Controls | External positive and negative run
controls are required and provided for
each assay run | Same |
| | Smart GBS™ | IDI-Strep B™ Assay |
| External Sample
Processing
Controls | Materials available commercially, but
not required | Materials available commercially,
but not required |
| Internal Assay and
System Controls | Internal Control;
Probe Check (all optical channels)
Failures result in single sample repeat. | Internal control
Site check (1 optical channel)
Same |
| Criteria for Ct
determination | Primary growth curve | 2nd derivative analysis |
| Users | CLIA high complexity laboratories | Same |
| Performance
Characteristics as
determined in the
Cepheid Clinical
Studies (Protocols
105 and 108) as
determined relative
to culture. | Protocol 105: Direct:
Sensitivity: 81.62%
Specificity: 96.43%
Protocol 108: Enriched:
Sensitivity: 98.67%
Specificity: 90.48% | As determined in the Cepheid
Clinical study using the same
subjects as tested with the Smart GBS™:
Sensitivity: 81.52%
Specificity: 95.51% |
| Probes | TaqMan® Probes | Molecular beacons |
3
4
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
5
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.
6
| 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
7
| 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
8
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 | Total | |
| Agreement | 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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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 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.
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