K Number

Device Name

AMPLIVUE GBS ASSAY

Manufacturer

QUIDEL CORPORATION

Date Cleared

2013-12-20

(36 days)

Product Code

NJR

Regulation Number

866.3740

Intended Use

The AmpliVue® GBS Assay is a qualitative in vitro diagnostic test for the rapid detection of Group B Streptococcus from vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation in an LIM enrichment broth culture. The AmpliVue" GBS Assay utilizes helicase-dependent amplification (HDA) of the thiolase (atoB) gene sequence and a self-contained disposable amplification detection device that allows for manual evaluation of assay results. Results can be used as an aid in determining the colonization status of antepartum women. The AmpliVue GBS Assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women. The AmpliVue® GBS Assay is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

Device Description

The AmpliVue® GBS Assay combines simple sample processing, an isothermal amplification technology named helicase-dependent amplification (HDA), and a selfcontained disposable amplicon detection device, for the detection of Group B Streptococcus from vaginal /rectal swabs following 18 to 24 hours incubation in Lim enrichment broth culture. A small amount of cultured specimen is transferred into a dilution tube. The diluted sample culture is then transferred into a lysis tube, and the cells are lysed by simple heat treatment. After heat treatment, an aliquot of the lysed sample is added to a reaction tube containing a lyophilized mix of HDA reagents including primers specific for the amplification of the thiolase (atoB) gene. The rationale behind the selection of this particular target sequence were: 1) a BLAST search of this gene resulted in no thiolase with significant homology in species other than those belonging to S. agalactiae; 2) the gene is conserved in GBS based on the recent GBS Genome project. The assay also includes a process control that monitors sample processing, confirms the integrity of the assay reagents and cassette detection, and assays for HDA-inhibitors that may be present within a broth culture. After completion of the HDA reaction, the reaction tube is transferred to a cassette for rapid detection with test result displayed as test and/or control lines in the window of the cassette.

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Type

Center

Panel

Date Received

Product Code

Subsequent Product Codes

Applicant Name (Manufacturer)

Device Name

Decision

Street 1

Street 2

City

State

Country Code

ZIP

Postal Code

Class Advise Committee

SSP Indicator

Third Party Reviewed

Expedited Review

Predicate Devices

K112125

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description focuses on biological and chemical processes (HDA, gene amplification, heat lysis) and manual evaluation of results via a cassette. There is no mention of AI or ML in the text.

Therapeutic

No.
Explanation: The device is a qualitative in vitro diagnostic test for the rapid detection of Group B Streptococcus, not a therapeutic device. It helps in determining colonization status and does not provide treatment or therapy.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that "The AmpliVue® GBS Assay is a qualitative in vitro diagnostic test."

SaMD (Software as a Medical Device)

The device description explicitly mentions a "self-contained disposable amplification detection device" and a "cassette for rapid detection," indicating physical hardware components are integral to the device's function.

IVD (In Vitro Diagnostic)

Yes, this device is an IVD (In Vitro Diagnostic).

The document explicitly states in the "Intended Use / Indications for Use" section: "The AmpliVue® GBS Assay is a qualitative in vitro diagnostic test for the rapid detection of Group B Streptococcus..."

This statement directly identifies the device as an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The AmpliVue GBS Assay is a qualitative in vitro diagnostic test for the rapid detection of Group B Streptococcus from vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation in an LIM enrichment broth culture. The AmpliVue GBS Assay utilizes helicase-dependent amplification (HDA) of the thiolase (atoB) gene sequence and a self-contained disposable amplification detection device that allows for manual evaluation of assay results. Results can be used as an aid in determining the colonization status of antepartum women.

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

The AmpliVue® GBS Assay is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

Product codes

NJR

Device Description

A small amount of cultured specimen is transferred into a dilution tube. The diluted sample culture is then transferred into a lysis tube, and the cells are lysed by simple heat treatment. After heat treatment, an aliquot of the lysed sample is added to a reaction tube containing a lyophilized mix of HDA reagents including primers specific for the amplification of the thiolase (atoB) gene. The rationale behind the selection of this particular target sequence were: 1) a BLAST search of this gene resulted in no thiolase with significant homology in species other than those belonging to S. agalactiae; 2) the gene is conserved in GBS based on the recent GBS Genome project. The assay also includes a process control that monitors sample processing, confirms the integrity of the assay reagents and cassette detection, and assays for HDA-inhibitors that may be present within a broth culture. After completion of the HDA reaction, the reaction tube is transferred to a cassette for rapid detection with test result displayed as test and/or control lines in the window of the cassette.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

vaginal/rectal

Indicated Patient Age Range

The age range for these women i.e. antepartum women was between 15 to 44 years old.

Intended User / Care Setting

hospital, reference or state laboratory settings.

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

1. Analytical Performance:
a. Precision/Reproducibility: A blinded and randomized study panel containing Streptococcus agalactiae negative and positive samples were tested at three test sites (one in-house laboratory and two clinical sites). Each site tested a reproducibility panel and Assay Controls for five days in triplicate. Testing was done by two operators at each site. Each operator ran the panel once a day using one lot of AmpliVue® GBS Assay. A total of 540 specimens were tested (including controls).
Key Results: The results suggest that there are no significant differences between different users, different sites and different lots in different days.
d. Detection Limit (LoD): The analytical sensitivity (limit of detection or LoD) of the AmpliVue® GBS Assay was determined using quantified (CFU/mL) cultures of six Streptococcus agalactiae strains serially diluted in a Lim broth. Each test dilution was run as 20 replicates in the AmpliVue® assay and plated on 20 TSA + 5% blood plates.
Key Results: The LoD for the six strains tested ranged from 1.24 x 10^5 to 1.39 x 10^6 CFU/mL. The reported LoD for the AmpliVue® GBS Assay is the highest value of the six strains: 1.39 x 10^6 CFU/mL.
e. Analytical Specificity (Cross Reactivity and Interference):
* Cross Reactivity: A study was conducted using two strains of Streptococcus agalactiae (BAA-611 and SS617) tested near LoD to evaluate the AmpliVue® GBS Assay for potential interference using a panel of 91 organisms (76 bacteria, three yeast, 11 viruses and a parasite) potentially found in vaginal/rectal samples. Human genomic DNA was also evaluated. The microorganisms were tested above clinically relevant levels (bacteria >= 1 x 10^6 CFU/mL, viruses >= 1 x 10^5 TCID50/mL).
Key Results: None of the organisms or viruses tested cross-reacts with the performance of the AmpliVue® GBS Assay. Human genomic DNA also does not interfere.
* Interference: A study was conducted using two strains of Streptococcus agalactiae (BAA-611 and SS617) tested near LoD to evaluate the AmpliVue GBS Assay for potential interference using a panel consisting of 34 substances found in vaginal/rectal specimens. Substances were introduced into the assay dilution tubes at concentrations which were medically relevant.
Key Results: None of the substances tested were found to interfere with the AmpliVue® GBS Assay.
Analytical Reactivity (Inclusivity): The reactivity of the AmpliVue® GBS Assay was evaluated against an additional twelve strains of Streptococcus agalactiae. The testing was performed near the level of detection for the assay (1x LoD). Each strain was tested as three replicates.
Key Results: All twelve strains were detected by the AmpliVue® GBS Assay in this study at a LoD of 1084 CFU/assay (1.39 x 10^6 CFU/mL).

3. Clinical studies:
a. Clinical Sensitivity: Performance characteristics of the AmpliVue® GBS Assay were established during a prospective study conducted from July to November 2013. Nine hundred eleven specimens used for this study were collected from antepartum women between 35 to 37 weeks' gestation at four distinct geographical sites across the United States. Nine hundred eleven specimens were tested by both the AmpliVue® GBS Assay and bacterial culture. Three specimens (0.3%) were invalid in the AmpliVue® GBS Assay when initially tested and remained invalid upon repeat testing. The data presented below is for the remaining nine hundred eight specimens.
Key Results:
* AmpliVue® GBS Assay POS, Bacterial Culture POS: 196
* AmpliVue® GBS Assay POS, Bacterial Culture NEG: 52* (39 of these were positive for GBS with FDA-cleared molecular device, 13 were negative)
* AmpliVue® GBS Assay NEG, Bacterial Culture POS: 1** (was negative with FDA-cleared molecular device)
* AmpliVue® GBS Assay NEG, Bacterial Culture NEG: 659

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Sensitivity: Not explicitly stated, but based on the table, it would be 196 / 197 = 99.5%.
Specificity: 92.7% (95% CI: 90.5% - 94.3%)

Predicate Device(s)

K112125

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

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.

Summary

K133503

Quidel Corporation

AmpliVue® GBS Assay Page 1 of 15

510(k) Summary

Applicant:

DEC 2 0 2013

Quidel Corporation 10165 McKellar Court San Diego, California 92121 Telephone: 858-552-7910 Fax: 858-646-8045

Contact Information:

Ronald H. Lollar, Senior Director Clinical and Quality Affairs 1055 East State Street Suite 100 Athens, Ohio 45701 740-589-3300 - Corporate number 740-589-3373 – Desk phone 740-593-8437 - Fax lollar@dhiusa.com

Date of preparation of 510(k) summary:

December 19, 2013

A. 510(k) Number:

K133503

B. Purpose for Submission:

To obtain substantial equivalence for the AmpliVue® GBS Assay

C. Measurand:

Thiolase (atoB) gene of S. agalactiae (Group B Streptococcus)

D. Type of Test:

Helicase-dependent amplification (HDA)

E. Applicant:

Quidel Corporation

F. Proprietary and Established Names:

AmpliVue® GBS Assay

G. Regulatory Information:

| NJR - Nucleic Acid
Amplification Assay
System, Group B
Streptococcus,
Direct Specimen | Class I (Non-
exempt) | 21 CFR 866.3740 - Streptococcus spp.
Serological Reagents | Microbiology (83) |
|---------------------------------------------------------------------------------------------------|--------------------------|--------------------------------------------------------------|-------------------|

H. Intended Use:

1. Intended Use(s):

The AmpliVue GBS Assay is a qualitative in vitro diagnostic test for the rapid detection of Group B Streptococcus from vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation in an LIM enrichment broth culture. The AmpliVue" GBS Assay utilizes helicase-dependent amplification (HDA) of the thiolase (atoB) gene sequence and a self-contained disposable amplification detection device that allows for manual evaluation of assay results. Results can be used as an aid in determining the colonization status of antepartum women.

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

The AmpliVue® GBS Assay is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

2. Indication(s) for Use:

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

The AmpliVue® GBS Assay is intended for use in hospital, reference or state laboratory settings. The device is not intended for point-of-care use.

3. Special conditions for use statement(s):

For in vitro diagnostic use only .
For prescription use only .

4. Special instrument requirements:

None

Device Description: I.

Materials Provided:

· 16 Tests per Kit

Symbol	Component	Quantity	Storage
1	Detection Cassettes	16/kit	2° to 30°C
2	Dilution Buffer	16 tubes/kit 0.35 mL	2° to 8°C
3	Lysis Buffer	16 tubes/kit 0.35 mL	2° to 8°C
4	Reaction Tubes	16 tubes/kit	2° to 8°C
5	Amplicon Cartridge	16/kit	2° to 30°C

Materials required but not provided:

External controls for Group B Streptococcus (e.g. AmpliVue® GBS Control Set, . which contains positive and negative controls, serves as an external processing and extraction control)
Sterile DNAse-free filter-blocked or positive displacement micropipettor tips .
. Micropipettor
Stopwatch or timer .
. Scissors or a blade
Micro tube tray .
Heat block capable of 95° C ± 2° C temperature .
Heat block with heated lid capable of 64° ± 2° C temperature .
. Thermometer

J. Substantial Equivalence Information:

1. Predicate device name(s):
  illumigene® GBS Assay, external control kit (Meridian Bioscience, Inc.)
1. Predicate 510(k) number(s):
  K112125

and the same of the same of the same of the same of the same of the same of the states of the states of the states of the states of the states of the states of the states of

510(k) Summary

Comparison with predicate: 3.

Similarities
Item	Device (K133503)	Predicate (K112125)
Intended Use	Qualitative in vitro diagnostic test
for the rapid detection of Group B
Streptococcus from vaginal/rectal
swabs from antepartum women
following 18 to 24 hours of
incubation in enriched Lim broth
culture	Same
Sample Types	Enriched Lim broth cultures of
Vaginal/Rectal swab specimens	Same
Sample Heat Lysis	Manual	Same
Self-Contained System Assay
after sample preparation	Yes	Same

Differences
Item	Device (K133503)	Predicate (K112125)
Sample Type Enrichment
Culture	Lim broth cultures, only	Trans Vag and Lim broth
DNA Amplification Technology
(HDA)	Helicase-dependent amplification
(HDA)	Loop-mediated isothermal DNA
amplification (LAMP)
Target Sequence Detected	Thiolase (atoB) gene	213 base pair (bp) sequence
residing in the 593-805 bp region
of S. agalactiae genome
Segment 3
Detection Technique	Manual	Automated
Instrument	None	illumipro-10
Testing Time	75 - 90 minutes	60 minutes
Clinical Sensitivity	99.5% (95% CI: 96.9-100%)	97.4% (95% CI: 91.9 - 99.0%)

	Differences
A
.

.
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.

175 1575 31 64 3 2 5 2 4 6 5 8 5 4 5 4 5 4 5 4 1 6 6 4 7 4 4 4 5 4 1 6 6
.
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