← Product Code [NJR](/submissions/MI/subpart-d%E2%80%94serological-reagents/NJR) · K173250

# Solana GBS Assay (K173250)

_Quidel Corporation · NJR · Dec 21, 2017 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/NJR/K173250

## Device Facts

- **Applicant:** Quidel Corporation
- **Product Code:** [NJR](/submissions/MI/subpart-d%E2%80%94serological-reagents/NJR.md)
- **Decision Date:** Dec 21, 2017
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.3740
- **Device Class:** Class 1
- **Review Panel:** Microbiology

## Indications for Use

The Solana® GBS assay is a qualitative in vitro diagnostic test for detection of Group B Streptococcus in either LIM or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation. The Solana® GBS Assay utilizes helicase-dependent amplification (HDA) of the Thiolase (atoB) gene sequence. The Solana® GBS Assay is intended for use only with the Solana® Instrument. The Solana® GBS Assay does not provide susceptibility results. Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

## Device Story

Solana GBS Assay; qualitative in vitro diagnostic test; detects S. agalactiae DNA in enriched vaginal/rectal swab cultures. Input: 50µL of Lim or Carrot broth culture medium. Process: Heat lysis at 95°C for 5 minutes; Helicase-Dependent Amplification (HDA) of thiolase (atoB) gene; fluorescence-based detection of target nucleic acid and internal Process Control. Output: Automated result interpretation (Positive, Negative, Invalid) on Solana instrument screen. Used in laboratory settings; operated by lab personnel. Benefits: Rapid detection (38-42 minutes post-enrichment) to aid in determining GBS colonization status in antepartum women.

## Clinical Evidence

Prospective clinical study (n=753) at four U.S. sites. Compared Solana GBS Assay to conventional microbiological culture (blood agar, Gram stain, catalase, latex agglutination). Sensitivity 100% (95% CI: 98.0-100%); Specificity 95.9% (95% CI: 94.0-97.3%). Performance consistent across Lim and Carrot broth media.

## Technological Characteristics

Real-time DNA amplification (HDA) assay. Materials: Pre-filled Process Buffer tubes, lyophilized reagents in Reaction Tubes. Energy: Thermal lysis (95°C) and instrument-based incubation/fluorescence detection. Connectivity: Standalone Solana instrument. Software: Automated result interpretation based on fluorescence thresholds. Sterilization: Not specified.

## Regulatory 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 identify Streptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genus Streptococcus 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.

## Predicate Devices

- AmpliVue® GBS Assay ([K133503](/device/K133503.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY ASSAY AND INSTRUMENT COMBINATION TEMPLATE

A. 510(k) Number:
K173250

B. Purpose for Submission:
To obtain a substantial equivalence determination for the Solana GBS Assay

C. Measurand:
Conserved region of the *Streptococcus agalactiae* (Group B *Streptococcus*) atoB gene

D. Type of Test:
Qualitative real-time DNA amplification and detection assay

E. Applicant:
Quidel Corporation

F. Proprietary and Established Names:
Solana GBS Assay

G. Regulatory Information:
1. Regulation section:
21 CFR 866.3740: *Streptococcus* serological reagents
2. Classification:
Class I (non-exempt)
3. Product code:
NJR: Nucleic acid amplification assay system, Group B *Streptococcus*, direct specimen test

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4. Panel:

83-Microbiology

H. Intended Use:

1. Intended use(s):

The Solana GBS Assay is a qualitative *in vitro* diagnostic test for detection of Group B *Streptococcus* from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation.

The Solana GBS Assay utilizes helicase-dependent amplification (HDA) of the thiolase (*atoB*) gene sequence. The Solana GBS Assay is intended for use only with the Solana Instrument.

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

2. Indication(s) for use:

Same as Intended Use.

3. Special conditions for use statement(s):

For *in vitro* diagnostic use.

For prescription use only.

4. Special instrument requirements:

The Solana GBS Assay is for use only with the Solana instrument.

I. Device Description:

The Solana GBS Assay is an *in vitro* diagnostic, real-time DNA amplification test for the direct, qualitative detection of Group A *Streptococcus* DNA in vaginal/rectal swab specimens that have been incubated for 18-24 hours in enrichment broth.

The assay kit comprises pre-filled tubes containing Process Buffer that are used for specimen processing, and separate Reaction Tubes that contain lyophilized reagents for Helicase-Dependent Amplification and fluorescence-based detection of the target nucleic acid and a Process Control.

After incubation of a vaginal/rectal swab specimen in Lim or Carrot broth, a portion of the

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culture medium is transferred to a Process Buffer tube that is heated at 95°C for 5 minutes to lyse the target organisms (if present). An aliquot of the lysate is then used to rehydrate the contents of a Reaction Tube which is placed in the Solana instrument for nucleic acid amplification, detection and automated result interpretation.

# J. Substantial Equivalence Information:

1. Predicate device name(s):

AmpliVue GBS Assay

2. Predicate 510(k) number(s):

K133503

3. Comparison with predicate:

|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device (K173250) Solana GBS Assay | Predicate (K133503) AmpliVue GBS Assay  |
|  Regulation | 21 CFR 866.3740: Streptococcus serological reagents | Same  |
|  Product Code | NJR: Nucleic acid amplification assay system, Group B Streptococcus, direct specimen test | Same  |
|  Classification | Class II | Same  |
|  Intended Use | The Solana GBS Assay is a qualitative in vitro diagnostic test for detection of Group B Streptococcus from either Lim or Carrot enrichment broth cultures of vaginal/rectal swabs from antepartum women following 18 to 24 hours of incubation.The Solana GBS Assay utilizes helicase-dependent amplification (HDA) of the Thiolase (atoB) gene sequence. The Solana GBS Assay is intended 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 [sic] 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  |

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|  Similarities  |   |   |
| --- | --- | --- |
|  Item | Device (K173250) Solana GBS Assay | Predicate (K133503) AmpliVue GBS Assay  |
|   | only with the Solana Instrument.The Solana GBS Assay does not provide susceptibility results.Culture isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women. | 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 far 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.  |
|  Specimen Type | Vaginal/rectal swab specimen following enrichment broth culture | Same  |
|  Measurand | Conserved region of the S. agalactiae atoB gene | Same  |
|  DNA Amplification Technology | Helicase-Dependent Amplification | Same  |
|  Differences  |   |   |
| --- | --- | --- |
|  Item | Device (K173250) Solana GBS Assay | Predicate (K133503) AmpliVue GBS Assay  |
|  Enrichment Broth | Lim or Carrot Broth | Lim Broth  |
|  Nucleic Acid Detection | Cleavage of fluorescently-labeled probes; automated interpretation of fluorescence values | Lateral flow sandwich assay; visual interpretation of lines on the detection strip  |
|  Instrument | Solana | None  |
|  Time-to-result (post enrichment) | 38-42 minutes | 75-90 minutes  |

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K. Standard/Guidance Document Referenced (if applicable):

Not applicable

L. Test Principle:

The Solana GBS Assay uses Helicase-Dependent Amplification with fluorescently-labeled probes to detect a conserved region of the *S. agalactiae* thiolase *atoB* gene in culture medium from vaginal/rectal swabs that are obtained from pregnant women.

Vaginal/rectal swab specimens are cultured for 18-24 hours in either Lim or Carrot broth, after which a sample of the culture medium is transferred to a tube containing Process Buffer. The tube is heated at 95°C for 5 minutes to lyse the target organisms, and an aliquot of the lysate is used to rehydrate Reaction Tubes that contain reagents for the amplification and detection of *S. agalactiae* target DNA and an internal Process Control. After rehydration, the test operator loads the Reaction Tubes into the Solana instrument for automated incubation, fluorescence detection and result interpretation. Results are reported on the instrument screen as “GBS Positive,” “GBS Negative” or “Invalid” (due to Process Control failure) and may be printed.

M. Performance Characteristics (if/when applicable):

1. Analytical performance:

Analytical studies to characterize the performance of the Solana GBS Assay were conducted using Lim or Carrot broth that was inoculated with clinical vaginal/rectal swab matrix, incubated for 18-24 hours at 37°C, screened as GBS-negative using the Solana GBS Assay, pooled and stored frozen at ≤-20°C. Samples for testing were prepared by mixing an aliquot of the vaginal/rectal swab culture medium with enumerated stock suspensions of *S. agalactiae*, Solana GBS Assay Process Buffer and other components appropriate to the conditions under investigation.

a. Precision/Reproducibility:

Reproducibility

The reproducibility of the Solana GBS Assay between laboratories was evaluated in a study performed by two operators at each of three sites over a period of five non-consecutive days. The Solana GBS Assay exhibited similar analytical sensitivity with Lim and Carrot broth samples and therefore the Reproducibility Study was performed with a panel of contrived positive and negative Lim broth samples as the representative sample type (refer to Sections M(1)(d) and M(2)(b)). The positive samples were prepared using two strains of GBS at three different target levels based on the limit of detection of the assay. On each day, each operator tested three negative samples and one or two replicates of each *S. agalactiae* positive panel member (3 sites × 2 operators × 5 days × 2-4 samples per target level per day = 90 replicates per target level). The results of the study are summarized in Table 1.

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Table 1. Summary of results from the Solana GBS Assay Reproducibility Study

|  Target Level | Strain of GBS | CFU/mL | Positive/Number Tested (%)  |   |   |   |   |
| --- | --- | --- | --- | --- | --- | --- | --- |
|   |   |   |  Site 1 | Site 2 | Site 3 | All Sites | Overall  |
|  Moderate Positive (3X LoD) | SS617 | 2.4 x 10^6 | 16/16 (100) | 16/16 (100) | 16/16 (100) | 48/48 (100) | 90/90 (100)  |
|   |  SS618 | 2.1 x 10^6 | 14/14 (100) | 14/14 (100) | 14/14 (100) | 42/42 (100)  |   |
|  Low Positive (1X LoD) | SS617 | 8.0 x 10^5 | 16/16 (100) | 16/16 (100) | 16/16 (100) | 48/48 (100) | 90/90 (100)  |
|   |  SS618 | 7.1 x 10^5 | 14/14 (100) | 14/14 (100) | 14/14 (100) | 42/42 (100)  |   |
|  High Negative (0.01X LoD) | SS617 | 8.0 x 10^3 | 5/16 (31.3) | 7/16 (43.8) | 8/16 (50.0) | 20/48 (41.7) | 50/90 (55.6)  |
|   |  SS618 | 7.1 x 10^3 | 12/14 (85.7) | 8/14 (57.1) | 10/14 (71.4) | 30/42 (71.4)  |   |
|  Negative | NA | 0 | 0/30 (0.0) | 0/30 (0.0) | 0/30 (0.0) | 0/90 (0.0)  |   |

NA: Not applicable; LoD: Limit of Detection

In addition to testing the reproducibility panel members, on each day of the study, the operators each tested three Positive and three Negative External Controls (3 sites x 2 operators x 3 replicates x 5 days = 90 replicates per control). The controls were prepared using the Quidel Molecular GBS Control Set. In all cases the Positive and Negative External Controls produced the expected results (90/90 = 100%).

The results of this study demonstrated acceptable reproducibility from site-to-site at target levels close to the limit of detection (LoD) of the Solana GBS assay.

## Repeatability

The within-laboratory repeatability of the Solana GBS Assay was evaluated by testing a panel of contrived positive and negative Lim broth samples over a period of 15 non-consecutive days. The positive samples were prepared using two strains of GBS at three different target levels. On each day, six negative samples and either two or four replicates of each positive panel member were tested (15 days x 2 strains x 2-4 replicates per panel member = 90 replicates per target level). The results of the study are summarized in Table 2.

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Table 2. Summary of results from the Solana GBS Assay Repeatability Study

|  Target Level | Strain of GBS | CFU/mL | Positive/Number Tested (%)  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  By Strain | Overall  |
|  Moderate Positive (3X LoD) | SS617 | 2.4 x 10^6 | 48/48 (100) | 90/90 (100)  |
|   |  SS618 | 2.1 x 10^6 | 42/42 (100)  |   |
|  Low Positive (1X LoD) | SS617 | 8.0 x 10^5 | 48/48 (100) | 90/90 (100)  |
|   |  SS618 | 7.1 x 10^5 | 42/42 (100)  |   |
|  High Negative (0.01X LoD) | SS617 | 8.0 x 10^3 | 22/48 (45.8) | 50/90 (55.6)  |
|   |  SS618 | 7.1 x 10^3 | 29/42 (69.0)  |   |
|  Negative | NA | 0 | 0/90 (0.0)  |   |

NA: Not applicable; LoD: Limit of Detection

In addition to testing the panel members, on each day of the Repeatability Study, six Positive and six Negative External Controls were also tested (6 replicates x 15 days = 90 replicates per control). The controls were prepared using the Quidel Molecular GBS Control Set. In all cases the Positive and Negative Controls produced the expected results (90/90 = 100%).

The Solana GBS Assay demonstrated acceptable repeatability between days.

b. Linearity/assay reportable range:

Not applicable.

c. Traceability, Stability, Expected values (controls, calibrators, or methods):

Sample Stability

Studies were conducted to evaluate the stability of samples of vaginal/rectal swab culture matrix prior to addition to the Process Buffer. Testing was performed using Lim and Carrot broth vaginal/rectal swab culture matrix that was seeded with S. agalactiae strain ATCC BAA-611 at 2X LoD (Section M(1)(d)). Enrichment cultures in both Lim and Carrot broth were shown to be stable for up to 48 hours at  $20 - 25^{\circ}\mathrm{C}$  or 7 days at  $2 - 8^{\circ}\mathrm{C}$ . Following addition to Process Buffer, samples stored at  $2 - 8^{\circ}\mathrm{C}$  were found to be stable for up to 72 hours prior to or after heat lysis.

Process Control

The Solana GBS Assay Process Buffer Tube contains a Process Control that is designed to monitor sample processing and the presence of substances that are inhibitory to DNA amplification, as well as reagent or instrument failure. Specimens that are negative for S. agalactiae by the Solana GBS Assay and in which the Process Control is also not detected are reported as "Invalid" and should be retested from the processed sample. If an Invalid result is obtained upon retesting, another aliquot of

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the same broth culture should be processed or a new enrichment culture should be prepared.

## External Controls

External Controls should be tested according to guidelines or requirements of local, provincial and/or federal regulations or accreditation organizations. External Positive and Negative Controls should be processed in the same manner as patient specimens to monitor for substantial reagent or instrument failure.

Positive and Negative External Controls from the Quidel Molecular GBS Control Set were tested on each day that patient specimens were evaluated during the prospective Clinical Study described in Section M(3)(a). A total of 52 pairs of Positive and Negative Controls were tested during the study, all of which (100%) produced the expected results.

Additional Positive and Negative External Controls were also tested during the Reproducibility and Repeatability Studies and in all cases produced the expected results (refer to Section M(1)(a)).

## d. Detection Limit:

### Limit of Detection

The LoD of the Solana GBS Assay was determined for six strains of *S. agalactiae* using contrived Lim broth-enriched vaginal/rectal samples that were seeded with *S. agalactiae* cells at different concentrations. Initial testing was performed with a single lot of Solana GBS Assay reagents. The preliminary LoD for each strain was defined as the lowest concentration at which ≥19/20 replicates produced a positive result. The preliminary LoD was confirmed by testing two additional lots of Solana GBS Assay reagents at the estimated LoD target level. For the LoD for each strain to be confirmed ≥19/20 replicates with each reagent lot had to produce positive results. The results of the study are summarized in Table 3.

The highest LoD among the six strains of *S. agalactiae* tested was for strain ATCC 12403 at 2.6 × 10⁶ CFU/mL. The LoD for this strain was shown to be the same in the presence of contrived Lim and Carrot broth-enriched vaginal/rectal swab matrices, demonstrating that the analytical sensitivity of the Solana GBS Assay is independent of the type of broth culture medium used.

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Table 3. Limits of Detection for the Solana GBS Assay

|  Culture Medium | Strain | Serotype | Confirmed LoD  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  CFU/mL1 | CFU/Assay2  |
|  Lim Broth | ATCC BAA-611 | V | 5.9 x 105 | 1.4 x 103  |
|   |  SS617 | Ia | 8.0 x 105 | 1.9 x 103  |
|   |  SS618 | Ib | 7.1 x 105 | 1.7 x 103  |
|   |  SS619 | II | 7.6 x 105 | 1.8 x 103  |
|   |  ATCC 12403 | III | 2.6 x 106 | 6.3 x 103  |
|   |  SS700 | Ic | 4.9 x 105 | 1.2 x 103  |
|  Carrot Broth | ATCC 12403 | III | 2.6 x 106 | 6.3 x 103  |

ATCC: American Type Culture Collection
CFU/mL of vaginal/rectal swab culture medium
2 Number of CFU per amplification reaction

# Inclusivity (Analytical Reactivity)

The inclusivity of the Solana GBS Assay was evaluated by testing 14 different strains of S. agalactiae in addition to those included in the LoD Study (Table 4). Each strain was tested in triplicate in Lim broth cultured vaginal/rectal swab matrix at the claimed LoD target level  $(2.6 \times 10^{6} \mathrm{CFU} / \mathrm{mL}$  of culture medium). All the replicates of each of strain produced positive results. These results are acceptable.

Table 4. Strains of S. agalactiae evaluated in the Inclusivity Study for the Solana GBS Assay

|  Strain | Serotype | Strain | Serotype  |
| --- | --- | --- | --- |
|  ATCC 12973 | II | ATCC 4768 | Not typed  |
|  CCUG 28551 | IV | ATCC 7077  |   |
|  CCUG 29785 | VI | ATCC 9925  |   |
|  CNCTC 6609 | VII | ATCC 12927  |   |
|  ATCC BAA-2669 | VIII | ATCC 27956  |   |
|  ATCC BAA-2668 | IX | ATCC 55191  |   |
|  ATCC 49449 | X | ATCC 55194  |   |

ATCC: American Type Culture Collection

# Bioinformatic Analysis

The inclusivity of the Solana GBS Assay primers and probes for the detection of GBS was analyzed in silico using the Basic Local Alignment Search Tool (BLAST).

Overall, the region was shown to be highly conserved. One strain of S. agalactiae was found to have a single mismatch near the middle of the reverse primer, although this is not predicted to have an adverse effect of amplification/detection. These results are acceptable.

# e. Analytical specificity:

# Cross-reactivity Study

The analytical specificity of the Solana GBS Assay was evaluated by testing a panel of 97 organisms and viruses that may be found in vaginal/rectal specimens, as well as human DNA (Table 5). Three replicates of each potentially cross-reactive organism

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or virus were prepared using Lim broth vaginal/rectal swab culture matrix. Bacteria and yeast species were tested at  $10^{6}$  CFU/mL of vaginal/rectal swab culture medium, while viruses were tested at  $10^{5}$  TCID $_{50}$ /mL. No false positive or Invalid results were obtained. These results are acceptable.

Table 5. Organisms and viruses evaluated for potential cross-reaction and/or interference in the Solana GBS Assay

|  Gram Negative (43) | Gram Positive (36)  |
| --- | --- |
|  Acinetobacter baumanii | Abiotrophia defectiva  |
|  Aeromonas hydrophila (2 strains) | Bacillus cereus  |
|  Alcaligenes faecalis subsp. faecalis | Bacillus subtilis (2 strains)  |
|  Bacteroides fragilis (2 strains) | Bifidobacterium adolescentis (2 strains)  |
|  Campylobacter fetus | Clostridium bifermentans  |
|  Campylobacter hyointestinalis | Clostridium butyricum  |
|  Campylobacter jejuni (2 strains) | Clostridium difficile  |
|  Citrobacter freundii | Clostridium haemolyticum  |
|  Edwardsiella tarda | Clostridium novyi  |
|  Enterobacter aerogenes | Clostridium orbiscindens  |
|  Enterobacter cloacae | Clostridium perfringens  |
|  Escherichia coli | Clostridium septicum  |
|  Escherichia fergusonii | Clostridium sordellii  |
|  Helicobacter pylori | Clostridium sporogenes  |
|  Klebsiella oxytoca | Enterococcus faecalis  |
|  Klebsiella pneumoniae | Enterococcus faecium  |
|  Legionella pneumophila | Lactobacillus acidophilus  |
|  Mobiluncus mulieris | Listeria monocytogenes  |
|  Moraxella cartarrhalis | Peptostreptococcus anaerobius  |
|  Morganella morganii | Staphylococcus aureus  |
|  Neisseria gonorrhoeae | Staphylococcus epidermidis  |
|  Pleisiomonas shigelloides | Streptococcus Group C  |
|  Porphyromonas asaccharolytica | Streptococcus mutans  |
|  Prevotella melaninogenica | Streptococcus pyogenes  |
|  Proteus mirabilis | Streptococcus bovis  |
|  Providencia alcalifaciens | Streptococcus dysgalactiae  |
|  Pseudomonas aeruginosa | Streptococcus gordonii  |
|  Pseudomonas fluorescens | Streptococcus intermedius  |
|  Salmonella choleraesius (typhimurium) | Streptococcus mitis  |
|  Salmonella enterica arizonae | Streptococcus oralis  |
|  Salmonella enterica enterica serovar typhimurium | Streptococcus pneumoniae  |
|  Salmonella enterica indica | Streptococcus salivarius  |
|  Serratia liquefaciens | Streptococcus suis  |
|  Serratia marcescens | Streptococcus uberis  |
|  Shigella boydii |   |

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|  Gram Negative (43) | Gram Positive (36)  |
| --- | --- |
|  Shigella flexneri |   |
|  Shigella sonnei |   |
|  Stenotrophomonas maltophilia |   |
|  Vibrio parahaemolyticus |   |
|  Yersinia enterocolitica |   |
|  Other (8)  |   |
|  Candida albicans | Gardnerella vaginalis  |
|  Candida glabrata | Trichomonas vaginalis2  |
|  Candida parapsilosis | Ureaplasma urealyticum3  |
|  Chlamydia trachomatis1 | Human Genomic DNA3  |
|  Viruses (11)  |   |
|  Adenovirus | Herpes Simplex Virus 1 (Macintyre)  |
|  Cytomegalovirus | Herpes Simplex Virus 2 (G)  |
|  Coxsackie virus | Norovirus  |
|  Echovirus | Rotavirus  |
|  Enterovirus | Varicella Zoster Virus  |
|  Human Papillomavirus 164 |   |

Tested at  $10^{6}$  IFU (Inclusion Forming Units)/mL
2 Tested at  $10^{6}$  trichomonads/mL
3 Tested at  $10^{6}$  copies/mL
4 Tested at  $10^{5}$  copies/mL

# Bioinformatic Analysis

In silico analysis using the Basic Local Alignment Search Tool (BLAST) was performed to evaluate the potential for cross-reaction of the Solana GBS Assay primers and probes with non-target organisms. No significant similarity was observed between the Solana atoB amplicon, primers or probes and sequences from other species. These results are acceptable.

# Contamination Study

The potential for false-positive results with the Solana GBS Assay due to within run or between run cross-contamination was evaluated by testing an alternating series of S. agalactiae "high positive" and negative samples in successive instrument runs, in addition to Positive and Negative External Controls. The high positive samples contained S. agalactiae at a concentration of  $1.8 \times 10^{8}$  CFU/mL of Lim broth vaginal/rectal matrix. Negative samples comprised simulated throat swab matrix alone. The expected results were obtained for all S. agalactiae positive and negative samples (50/50 each). Each of the Positive and Negative External Controls also produced the expected results (10/10 each). These results are acceptable.

# f. Assay cut-off:

The algorithm parameters for the Solana GBS Assay were established through analysis of fluorescence amplification curves obtained from testing known GBS positive and negative samples on the Solana Instrument. The cut-offs were chosen to

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optimize sensitivity for detection of GBS and minimize Invalid test results due to failure of the Process Control.

g. Assay interference:

Potentially Interfering Substances

The potential for interference with the Solana GBS Assay was evaluated with endogenous and exogenous substances that may be present in vaginal/rectal swab specimens (Table 6). Each substance was tested in triplicate in the presence and absence of S. agalactiae at 2X LoD (5.2 x 10⁶ CFU/mL) using samples prepared with Lim broth-enriched vaginal/rectal matrix. No false positive, false negative or Invalid test results were observed under any of the conditions tested. These results are acceptable.

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Table 6. Substances evaluated for potential interference with the Solana GBS Assay

|  Substance | Test Concentration1  |
| --- | --- |
|  Amniotic Fluid | 2% (v/v)  |
|  Baby Powder | 0.1% (w/v)/μL2  |
|  Barium sulfate | 0.1 mg/mL  |
|  Benzalkonium Chloride Towelettes | 0.002% (v/v)  |
|  Body Powder | 0.1% (w/v)/μL2  |
|  Cortizone 10 (Hydrocortisone) | 0.1% (w/w)/μL2  |
|  Desitin (Zinc Oxide) | 0.1% (w/w)/μL2  |
|  Ethanol | 0.2% (v/v)  |
|  Fecal Fat - Palmitic acid | 0.026 mg/mL  |
|  Fecal Fat - Stearic Acid | 0.52 mg/mL  |
|  Fecal Sugar - Dextrose | 0.02 mg/mL  |
|  Fleet Mineral Oil Enema | 0.2% (v/v)  |
|  Gynol II Vaginal Contraceptive (Nonoxynol-9) | 0.1% (w/w)/μL2  |
|  Hemoglobin | 0.064 mg/mL  |
|  Hemorrhoidal Cream | 0.1% (w/v)/μL2  |
|  Human Serum Albumin | 0.2 mg/mL  |
|  Imodium AD (Loperamide) | 0.02 mg/mL  |
|  KY Jelly | 0.1% (w/v)/μL2  |
|  Meconium | 0.1% (w/v)/μL2  |
|  Miconazole Nitrate Salt | 0.04% (w/v)  |
|  Mucin | 0.06 mg/mL  |
|  Mylanta (Al(OH)3, Mg(OH)3) | 0.002 mg/mL  |
|  Nystatin | 200 U/mL  |
|  Pepto Bismol (Bismuth subsalicylate) | 0.017 mg/mL  |
|  Petroleum Jelly | 0.1% (w/v)/μL2  |
|  Preparation H (Phenylephrine) | 0.04% (w/v)  |
|  Prilosec (Esomeprazole magnesium hydrate) | 0.01 mg/mL  |
|  Stool | 0.1% (w/v)/μL2  |
|  Tagamet (Cimetidine) | 0.01 mg/mL  |
|  Triclosan | 0.002% (w/v)  |
|  Tucks Personal Cleaning Pads (Witch-hazel) | 2% (v/v)  |
|  Tums (Calcium carbonate) | 0.01 mg/mL  |
|  Urine | 2% (v/v)  |
|  Whole Blood | 2% (v/v)  |

1 Concentration in the cultured vaginal/rectal swab Lim broth matrix
2  $0.1\%$  of the quantity adsorbed on the collection swab/  $\mu \mathrm{L}$  of matrix

# Microbial Interference

The potential for interference with the Solana GBS Assay by organisms and viruses that may be present in vaginal/rectal swab specimens was evaluated using the same list of species that were evaluated for potential cross-reactivity (Section M(1)(e); Table 5). Testing was performed by mixing each potentially interfering organism or virus with S. agalactiae strain ATCC 12403 at a concentration of  $2\mathrm{X}$  LoD in Process Buffer containing Lim broth-enriched vaginal/rectal swab matrix. For bacteria and yeasts, the final concentrations were  $10^{6}$  CFU/mL, while viruses were tested at  $10^{5}$  TCID $_{50}$ /mL (except as noted in Table 5). No false negative or Invalid results were obtained with any of the organisms or viruses tested. These results are acceptable.

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2. Comparison studies:

a. Method comparison with predicate device:

Not applicable.

b. Matrix comparison:

The LoD of the Solana GBS Assay was initially established using samples prepared with matrix derived from Lim broth vaginal/rectal swab cultures. The claimed LoD was subsequently confirmed by testing samples prepared in matrix derived from Carrot broth vaginal/rectal swab cultures. Refer to Section M(1)(d). Additional studies also demonstrated that equivalent Solana GBS Assay results are obtained with Lim and Carrot broth cultures that are incubated for 18 or 24 hours.

3. Clinical studies:

a. Clinical Sensitivity:

The performance of the Solana GBS Assay was evaluated in a prospective Clinical Study that was performed at four (4) sites in the U.S. Vaginal/rectal swab specimens were obtained from a total of 753 pregnant women at between 35 and 37 weeks of gestation. The age of the subjects ranged from 15 to 44 years old. The specimens were inoculated into either Lim broth (403) or Carrot broth (350) and incubated for between 18 and 24 hours at 35°C after which the cultures were tested using the Solana GBS Assay and the results were compared to those obtained from subculture of the broth to blood agar, followed by Gram staining of suspected colonies of S. agalactiae, catalase testing (S. agalactiae is catalase negative) and latex agglutination using GBS-specific reagents. The results of the study are summarized in Table 7. One specimen produced repeated Invalid results with the Solana assay and was excluded from the analysis of performance.

14

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Table 7. Performance of the Solana GBS Assay with enriched vaginal/rectal swab cultures in comparison to conventional microbiological isolation and identification of S. agalactiae

|  Lim Broth | Reference Method  |   |   |   |
| --- | --- | --- | --- | --- |
|   |   |  Positive | Negative | Total  |
|  Solana GBS Assay | Positive | 88 | 131 | 101  |
|   |  Negative | 0 | 301 | 301  |
|   |  Total | 88 | 314 | 402  |
|  Sensitivity |   | 88/88 = 100% (95% CI: 95.8-100%)  |   |   |
|  Specificity |   | 301/314 = 95.9% (95% CI: 93.0-97.6%)  |   |   |
|  Positive Predictive Value |   | 88/101 = 87.1% (95% CI: 79.2-92.3%)  |   |   |
|  Negative Predictive Value |   | 301/301 = 100% (95% CI: 98.7-100%)  |   |   |
|  Carrot Broth | Reference Method  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  Solana GBS Assay | Positive | 97 | 102 | 107  |
|   |  Negative | 0 | 243 | 243  |
|   |  Total | 97 | 253 | 350  |
|  Sensitivity |   | 97/97 = 100% (95% CI: 96.2-100%)  |   |   |
|  Specificity |   | 243/253 = 96.0% (95% CI: 92.9-97.8%)  |   |   |
|  Positive Predictive Value |   | 97/107 = 90.7% (95% CI: 83.6-94.8%)  |   |   |
|  Negative Predictive Value |   | 243/243 = 100% (95% CI: 98.4-100%)  |   |   |
|  Lim & Carrot Broth Combined | Reference Method  |   |   |   |
|   |   |  Positive | Negative | Total  |
|  Solana GBS Assay | Positive | 185 | 233 | 208  |
|   |  Negative | 0 | 544 | 545  |
|   |  Total | 185 | 567 | 752  |
|  Sensitivity |   | 185/185 = 100% (95% CI: 98.0-100%)  |   |   |
|  Specificity |   | 544/567 = 95.9% (95% CI: 94.0-97.3%)  |   |   |
|  Positive Predictive Value |   | 185/208 = 88.9% (95% CI: 84.0-92.5%)  |   |   |
|  Negative Predictive Value |   | 301/301 = 100% (95% CI: 99.3-100%)  |   |   |

1 12/13 (92.3%) cultures were positive by another FDA-cleared test method
2 7/10 (70.0%) cultures were positive by another FDA-cleared test method
3 19/23 (82.6%) cultures were positive by another FDA-cleared test method

The sensitivity and specificity of the Solana GBS Assay for the detection of S. agalactiae in Lim broth cultures compared to standard microbiological isolation and identification were  $100\%$  (95% Confidence Interval: 95.8-100%) and  $95.9\%$  (95% CI: 93.1-97.6%), respectively. Whereas with Carrot broth, the sensitivity and specificity

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were 100% (95% CI: 96.2-100%) and 96.0% (95% CI: 92.9-97.8%), respectively. Overall, for both types of broth culture combined, the sensitivity and specificity were 100% (95% CI: 98.0-100%) and 95.9% (95% CI: 94.0-97.3%).

The performance of the Solana GBS Assay with each type of broth culture medium, stratified by clinical site is shown in Table 8. The point estimate for sensitivity relative to conventional culture was 100% at each site, irrespective of the type of enrichment broth, while the specificity of the Solana GBS Assay ranged from 93.4 to 100% with Lim broth, and 94.7 to 97.1% with Carrot broth.

Table 8. Performance of the Solana GBS Assay stratified by clinical site and culture medium

|  Culture Medium | Site Number | Culture Positive (%) | Solana GBS (%; 95% Score Confidence Interval)  |   |
| --- | --- | --- | --- | --- |
|   |   |   |  Sensitivity | Specificity  |
|  Lim Broth | 1 | 33/147
(22.4) | 33/33
(100; 89.6-100) | 114/114
(100; 96.7-100)  |
|   |  3^{1} | 42/181
(23.2) | 42/42
(100; 91.6-100) | 130/139
(93.5; 88.2-96.6)  |
|   |  4 | 13/74
(17.6) | 13/13
(100; 77.2-100) | 57/61
(93.4; 84.3-97.4)  |
|   |  Overall | 88/402
(21.9) | 88/88
(100; 95.8-100) | 301/314
(95.9; 93.0-97.6)  |
|  Carrot Broth | 2 | 44/183
(24.0) | 44/44
(100; 92.0-100) | 135/139
(97.1; 92.8-98.9)  |
|   |  3^{1} | 53/167
(31.7) | 53/53
(100; 93.2-100) | 108/114
(94.7; 90.0-97.6)  |
|   |  Overall | 97/350
(27.7) | 97/97
(100; 96.2-100) | 243/253
(96.0; 92.9-97.8)  |
|  Total |   | 185/752
(24.6) | 185/185
(100; 98.0-100) | 544/567
(95.9; 94.0-97.3)  |

* At Site 3, testing with the Solana GBS Assay was performed sequentially using Lim and Carrot broth enrichment media; the first 181 contiguous specimens were inoculated into Lim broth and the next 167 were cultured in Carrot broth

The overall performance of the Solana GBS Assay in comparison to conventional microbiological identification of S. agalactiae in Lim and Carrot broth enrichment cultures of vaginal/rectal swabs is acceptable.

b. Clinical specificity:

Refer to Section M(3)(a), above.

c. Other clinical supportive data (when a. and b. are not applicable):

Not applicable.

4. Clinical cut-off:

Not applicable.

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# 5. Expected values/Reference range:

The performance of the Solana GBS Assay was evaluated in a prospective Clinical Study of pregnant women conducted at four sites in the U.S. (Section M(3)(a)). Overall, the prevalence of GBS colonization as determined by the Solana GBS Assay was  $27.7\%$  (208/752) whereas by conventional culture it was  $24.6\%$  (185/752). In Table 9, the prevalence as determined by the Solana assay is shown stratified by clinical site and the type of broth culture used.

Table 9. Observed prevalence of GBS colonization in pregnant women as determined by the Solana GBS Assay, stratified by clinical site and culture medium

|  Culture Medium | Site | Number | Solana Positive | % Prevalence  |
| --- | --- | --- | --- | --- |
|  Lim Broth | 1 | 147 | 33 | 22.4  |
|   |  3 | 181 | 51 | 28.2  |
|   |  4 | 74 | 17 | 23.0  |
|   |  Overall | 402 | 101 | 25.1  |
|  Carrot Broth | 2 | 183 | 48 | 26.2  |
|   |  3 | 167 | 59 | 35.3  |
|   |  Overall | 350 | 107 | 30.6  |
|  Combined | Overall | 752 | 208 | 27.7  |

At Site 3, testing with the Solana GBS Assay was performed sequentially using Lim and Carrot broth enrichment media; the first 181 contiguous specimens were inoculated into Lim broth and the next 167 were cultured in Carrot broth

# N. Instrument Name:

Solana Instrument

# O. System Descriptions:

# 1. Modes of Operation:

Does the applicant's device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes X or No

Does the applicant's device transmit data to a computer, webserver, or mobile device using wireless transmission?

Yes or No X

# 2. Software:

FDA has reviewed applicant's Hazard Analysis and software development processes for

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this line of product types:

Yes ☐ X ☐ or No ☐

3. Specimen Identification:

Specimens are identified by scanning a barcode or by manual entry.

4. Specimen Sampling and Handling:

Swab specimens are cultured in Lim or Carrot broth for 18-24 hours after which 50μL the medium is transferred to a tube containing Process Buffer which is then heated at 95±2°C for 5 min to lyse the target organisms. A 50μL aliquot of the lysate is then used to rehydrate Reaction Tubes that contain lyophilized reagents for amplification and detection of the target sequence (and Process Control). Refer to Sections I and L for additional details.

5. Calibration:

The end user is not required to calibrate the instrument. Automated calibration happens by comparing between the measured magnitude of the optical signal of and an integrated calibration standard and the expected magnitude of the optical signal.

6. Quality Control:

Refer to Section M(1)(a) and Section M(1)(c) for information on the internal and external controls associated with the Solana GBS Assay and their performance.

P. Other Supportive Instrument Performance Characteristics Data Not Covered In The "Performance Characteristics" Section above:

Not applicable.

Q. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable.

R. Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/NJR/K173250](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/NJR/K173250)

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