The Solana™ GAS Assay is a rapid in vitro diagnostic test for the qualitative detection of Group A B-hemolytic Streptococus (Streptococcus pyogenes) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The Solana™ GAS Assay is intended for use only with the Solana™ instrument.

Device Description

The Solana™ GAS Assay amplifies and detects GAS DNA present in throat swab specimens obtained from symptomatic patients.

The assay consists of two major steps: 1) specimen preparation, and 2) amplification and detection of target sequence specific to GAS using isothermal Helicase-Dependent Amplification (HDA) in the presence of target-specific fluorescence probe.

The target and PRC probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target and PRC probes carry a ribonucleic acid. Upon annealing to GAS or PRC amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. Solana measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana instrument will then report the test results to the user on its display screen, and it can print out the results via a printer.

AI/ML Overview

The Solana™ GAS Assay is a rapid in vitro diagnostic test for the qualitative detection of Group A β-hemolytic Streptococcus (Streptococcus pyogenes) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The assay is intended for use only with the Solana™ instrument.

1. Table of Acceptance Criteria and Reported Device Performance

Performance Metric	Acceptance Criteria (Implicit for predicate device)**	Reported Device Performance (Solana™ GAS Assay)
Clinical Sensitivity	96.5% (95% CI: 91.3% - 98.6%)*	98.2% (95% CI: 95.5% - 99.3%)
Clinical Specificity	98.0% (95% CI: 97.0% - 98.6%)*	97.2% (95% CI: 95.9% - 98.1%)
Analytical Sensitivity (LoD)	Not explicitly stated but expected to be comparable to predicate for substantial equivalence	6.81 x 10⁴ CFU/mL

*The predicate device's performance (Lyra™ Direct Strep Assay) in the "Comparison with predicate" section is used as a proxy for implicit acceptance criteria, as the submission aims to demonstrate substantial equivalence. Explicit acceptance criteria beyond this are not detailed in the provided text for the Solana™ GAS Assay's clinical performance.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 1082 fresh throat swab specimens.
Data Provenance: Prospective study conducted from December 2014 to February 2015 at four distinct geographical sites across the United States.

3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications of Those Experts

The document does not explicitly state the number of experts or their specific qualifications (e.g., radiologists with 10 years of experience). However, the ground truth was established by "conventional streak-stab culture technique onto a trypticase soy agar plate containing 5% horse red blood cells" and "typed as Lancefield group A by latex agglutination." This implies standard microbiology laboratory procedures and interpretation, which would typically be performed by trained clinical microbiologists or laboratory technologists.

4. Adjudication Method for the Test Set

The document describes discordant specimens. Of the 24 specimens that were Solana™ GAS Assay positive but Composite Culture negative, 16 were tested with an additional FDA-cleared molecular device, and 8 were negative. Of the 4 specimens that were Solana™ GAS Assay negative but Composite Culture positive, 3 were tested with an additional FDA-cleared molecular device. This indicates a form of secondary testing or adjudication for discordant results, though a formal 2+1 or 3+1 method is not explicitly named.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs. Without AI Assistance

No, an MRMC comparative effectiveness study involving human readers and AI assistance was not done. This device is an in-vitro diagnostic test for qualitative detection of nucleic acids, not an imaging or diagnostic aid for human readers.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Yes, the clinical performance study evaluated the Solana™ GAS Assay as a standalone device. The "Solana instrument measures and interprets the fluorescent signal, using on-board method-specific algorithms" and "report the test results to the user on its display screen."

7. The Type of Ground Truth Used

The ground truth used was composite bacterial culture. A specimen was considered positive if either the swab or the transport media was positive for β-hemolytic Streptococcus and typed as Lancefield group A by latex agglutination.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" for the clinical performance evaluation. The clinical sensitivity and specificity were established using a prospective clinical study where 1082 fresh throat swab specimens were collected and tested. This dataset largely serves as the evaluation or test set. For analytical performance, various specified quantities of bacterial strains were used.

9. How the Ground Truth for the Training Set Was Established

Given that a specific "training set" for clinical performance with a separate ground truth establishment method is not described, the approaches described for the test set (composite bacterial culture as detailed in point 7) would apply if any training data were used from clinical samples. For analytical studies, ground truth was established by using quantified (CFU/mL) cultures of known bacterial strains.

Summary

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Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

July 1st, 2015

QUIDEL CORPORATION RONALD H. LOLLAR SENIOR DIRECTOR, CLINICAL AND REGULATORY AFFAIRS 2005 EAST STATE STREET, SUITE 100 ATHENS, OH 45701

Re: K150868

Trade/Device Name: Solana™ Gas Assay, Solana™ Instrument Regulation Number: 21 CFR 866.2680 Regulation Name: Streptococcus spp. nucleic acid-based assay Regulatory Class: II Product Code: PGX Dated: March 31, 2015 Received: April 1, 2015

Dear Mr. Lollar:

This letter corrects our substantially equivalent letter of June 23, 2015.

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. Iisting of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of

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medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Sally A. Hojvat -S

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

Enclosure

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Indications for Use

510(k) Number (if known) K150868

Device Name Solana™ GAS Assay, Solana™ Instrument

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
X Prescription Use (Part 21 CFR 801 Subpart D)	Over-The-Counter Use (21 CFR 801 Subpart C)

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Applicant:

Quidel Corporation 12544 High Bluff Drive, Suite 200 San Diego, California 92130 Telephone: 858-552-7910 Fax: 858-646-8045

Contact Information:

Ronald H. Lollar, Senior Director Clinical and Regulatory Affairs 2005 East State Street, Suite 100 Athens, Ohio 45701 740-589-3300 – Corporate number 740-589-3373 – Desk phone 858-552-6451—Fax Ron.Lollar@quidel.com

Date of preparation of 510(k) summary:

March 31, 2015

A. 510(k) Number:

K150868

B. Purpose for Submission:

To obtain substantial equivalence for the Solana™ GAS Assay when performed on the Solana™ instrument

C. Measurand:

DNase B (sdaB) sequence of Streptococcus pyogenes (Group A Streptococcus)

D. Type of Test:

Helicase-dependent amplification (HDA)

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E. Applicant:

Quidel Corporation

F. Proprietary and Established Names:

Solana™ GAS Assay Solana™ instrument

G. Regulatory Information:

Product Code	Classification	Regulation Section	Panel
PGX – Groups A, C and G Beta-HemolyticStreptococcusNucleic AcidAmplification	Class II (Non-exempt)	21 CFR 866.2680 – Streptococcus spp. Nucleic Acid-Based Assay	Microbiology (83)

H. Intended Use:

1. Intended Use(s):
  The Solana™ GAS Assay is a rapid in vitro diagnostic test for the qualitative detection of Group A β-hemolytic Streptococcus (Streptococcus pyogenes) nucleic acids isolated from throat swab specimens obtained from patients with signs and symptoms of pharyngitis, such as sore throat. The Solana™ GAS Assay is intended for use only with the Solana™ instrument.
1. Indication(s) for Use:
  Same as intended Use
1. Special conditions for use statement(s):
- For in vitro diagnostic use only
- . For prescription use only

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4. Special instrument requirements:

Solana™ instrument

l. Device Description:

The Solana™ GAS Assay amplifies and detects GAS DNA present in throat swab specimens obtained from symptomatic patients.

Materials Provided:

48 Tests per Kit

Component	Quantity	Storage
Dilution Buffer	48 tubes/kit 0. 5 mL	2° to 8°C
Lysis Buffer	48 tubes/kit 0. 5 mL	2° to 8°C
Reaction Tubes	48 tubes/kit	2° to 8°C

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Materials required but not provided:

. External controls for Group A Streptococcus (e.g. Quidel Molecular A + G Streptococci Control Set #M111, 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 ●
Solana Instrument
Thermometer

J. Substantial Equivalence Information:

1. Predicate device name(s):
  Lyra™ Direct Strep
1. Predicate 510(k) number(s): K133883
1. Comparison with predicate:

Similarities
Item	Solana™ GAS Assay	Lyra™ Direct Strep Assay(K133883)
Intended Use	The Solana™ GAS Assay is arapid in vitro diagnostic testfor the qualitative detectionof Group A β-hemolyticStreptococcus( Streptococcus pyogenes )nucleic acids isolated fromthroat swab specimensobtained from patients withsigns and symptoms ofpharyngitis, such as sorethroat. The Solana™ GAS	The Lyra Direct StrepAssay is a Real-Time PCRin vitro diagnostic test forthe qualitative detectionand differentiation ofGroup A β-hemolyticStreptococcus( Streptococcus pyogenes )and pyogenic Group Cand G β-hemolytic
Similarities
Item	Solana™ GAS Assay	Lyra™ Direct Strep Assay(K133883)
	Assay is intended for useonly with the Solana™instrument.	Streptococcus nucleicacids isolated fromthroat swab specimensobtained from patientswith signs and symptomsof pharyngitis, such assore throat. The assaydoes not differentiatebetween pyogenicGroups C and G β-hemolytic Streptococcus .All negative test resultsshould be confirmed bybacterial culture,because negative resultsdo not preclude Group A,C or G Strep infectionand should not be usedas the sole basis fortreatment.The assay is intended foruse in hospital, reference,or state laboratorysettings. The device is notintended for point-of-careuse.
Similarities
Item	Solana™ GAS Assay	Lyra™ Direct Strep Assay(K133883)
Sample Types	Throat swab specimens	Same
Sample Heat Lysis	Manual	Same
Detection Technique	Automatically detectsfluorescence afterdissociation of fluorophorefrom quencher duringamplification	Same
Testing Time	45 minutes	60 - 70 minutes

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Differences
Item	Solana™ GAS Assay	Lyra™ Direct Strep Assay(K133883)
DNA AmplificationTechnology	Helicase-dependentamplification (HDA); self-contained	Real time polymerasechain reaction
Instrument	Solana™	ABI 7500 Fast DXThermocycler
Target Sequence Detected	78 base pair (bp) sequenceS. pyogenes genome,resident in the DNase B( sdaB ) gene	GAS* – 99bp product inthe putative competence( comX1.1 ) genePyo GCS/GGS* – 188bpproduct in the tagatose-6-phosphate kinase ( lacC )gene
Clinical Sensitivity	98.2% (95% CI: 95.5-99.3%)	GAS Sensitivity:96.5%[95% CI: 91.3% -

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Differences
Item	Solana™ GAS Assay	Lyra™ Direct Strep Assay (K133883)
		98.6%Pyo GCS/GGS Sensitivity:95.7%[95% CI: 88.1% - 98.5%]
Clinical Specificity	97.1% (95% CI: 95.7-98.0%)	GAS Specificity:98.0%[95% CI: 97.0% - 98.6%]Pyo GCS/GGS Specificity:98.3%[95% CI: 97.4% - 98.9%]

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

screen, and it can print out the results via a printer.

Not applicable

L. Test Principle:

Patient specimen on a throat swab is transferred to a Lysis Tube and subjected to heattreatment at 95°C for 5 minutes. The heat-treated sample is added to a Dilution Tube, and then transferred to a Reaction Tube. The Reaction Tube contains lyophilized HDA reagents, dNTPs, primers and probes. Once rehydrated with the diluted sample, the Reaction Tube is placed in Solana for amplification and detection of GAS-specific target sequence. In Solana, the target sequence is amplified by GAS specific primers and detected by a GAS specific fluorescence probe included in the Reaction Tube. A competitive process control (PRC) is included in the Lysis Tube to monitor sample processing, inhibitory substances in clinical samples, reagent failure or device failure. The PRC target is amplified by GAS specific primers and detected by a PRC specific fluorescence probe. The target and PRC probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target and PRC probes carry a ribonucleic acid. Upon annealing to GAS or PRC amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. Solana measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana instrument will then report the test results to the user on its display

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M. Performance Characteristics:

1. Analytical performance:

a. Precision/Reproducibility:

Reproducibility

In order to confirm the reproducibility of the Solana™ GAS Assay, a blinded and randomized study panel containing Streptococcus pyogenes negative and positive samples were tested at three test sites (one in-house laboratory and two clinical sites) with three (3) instruments. 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 Solana™ GAS Assay. A total of 540 specimens were tested (including controls). The Solana™ GAS Assay generated the following reproducible results in this study.

Category	SITE						Overall Percent Positive	95% Confidence Interval
	Site #1		Site #2		Site #3
	Detected:#positive /# tested	% Positive	Detected:#positive /# tested	% Positive	Detected:#positive /# tested	% Positive
GAS High Negative	24/30	80%	20/30	67%	14/30	47%	58/90	64%	54-74%
GAS Low Positive	30/30	100%	30/30	100%	30/30	100%	90/90	100%	96%-100%
GAS Moderate Positive	30/30	100%	30/30	100%	30/30	100%	90/90	100%	96%-100%
GAS Negative	0/30	0%	0/30	0%	0/30	0%	0/90	0%	0%-4%
GAS Positive Control	30/30	100%	30/30	100%	30/30	100%	90/90	100%	96%-100%
GAS Negative Control	0/30	0%	0/30	0%	0/30	0%	0/90	0%	0%-4%

The results suggest that there are no significant differences between different users using different instruments at different sites on different days.

b. Linearity/assay reportable range:
Not applicable - This assay is qualitative.
c. Traceability, Stability, Expected values (controls, calibrators, or methods):

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Traceability:

Not applicable. This assay is qualitative.

Specimen Stability:

A study was performed to determine the stability of samples collected in a number of routinely used swab systems: nylon flocked swabs in amies media, Rayon swab in amies media, polyester swab in amies media, Rayon swab in stuart media, polyester swab in stuart media, and Rayon in amies gel.

A freshly grown stock of GAS bacteria of known titer was used to spike the swabs listed above. The spiked samples were stored at 25°C ± 2°C for 2 days and then at 2 to 8°C for up to 8 more days prior to being tested in the Solana™ GAS Assay. A separate study was performed where the spiked samples were stored at ≤-15℃ or <-70°C for a minimum of 32 days before testing.

Based on this study, specimens collected using various collection/transport systems listed above can be stored at 25°C ± 2°C for 2 days and then at 2 to 8°C for up to 8 more days before testing or at ≤-15°C or ≤-70°C for up to 32 days before testing.

Controls:

Controls (Quidel Molecular A + G Streptococci Control Set #M111, which contains positive and negative controls, serves as an external processing and extraction control) were run on the Solana™ GAS Assay each day of testing. These controls are described as follows:

a. The process control is used to monitor sample processing, to detect HDA inhibitory specimens and to confirm the integrity of assay reagents and cassette detection. The process control is included in the Lysis Buffer tube.
b. The external positive control may be treated as a patient specimen. The control should be sampled and tested as if it were a swab specimen and processed as described in the Assay Procedure. The external positive control is intended to monitor substantial reagent and cassette failure.

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Quidel Corporation

c. The external neqative control may be treated as a patient specimen. The control should be sampled and tested as if it were a swab specimen and processed as described in the Assay Procedure. The external negative control is used to detect reagent or environmental contamination (or carry-over) by GAS DNA or amplicon.
d. Detection limit:

The analytical sensitivity (limit of detection or LoD) of the Solana™ GAS Assay was determined using quantified (CFU/mL) cultures of two Streptococcus pyoqenes strains by serial dilution. The LoD is defined as the lowest concentration at which 95% of all replicates tested positive.

The GAS bacterial strains were freshly grown. The cell density of these bacterial suspensions was estimated using the OD600 reading. After a cell suspension with OD600 of 0.1 (0.5 McFarland units) were established, the bacteria were serially diluted in to densities ranging from 3x to 0.3x LoD levels based on preliminary studies.

Each test dilution was run as 20 replicates in the Solana™ assay and plated on 20 TSA + 5% blood plates. The study was performed in 5 experiments of 14 assays per strain. For each experiment, 4 replicates of each of the three bacterial dilutions were performed, along with a positive and a negative run control. All five experiments of the LoD study for each strain were completed within 8 hours. The stocks of cells were stored on ice or at 4 °C when not in use.

The highest dilution where at least 19 of 20 replicates show detection of GAS (95% positivity) was assigned the Limit of Detection of the strain. The CFU/mL was calculated based on the average bacterial plate count of the dilution.

The LoD for the 2 Streptococcus pyogenes strains tested were 2.44 x10ª CFU/mL (ATCC #19615) and 6.81 x10 CFU/mL (ATCC #12344). Based on this data the reported LoD for the Solana™ GAS Assay is 6.81 x104 CFU/mL.

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e. Analytical specificity:

Cross Reactivity:

An in silico BLAST analysis of primers used in the Solana™ GAS Assay against sixtyone (61) potential interfering organisms (see below) did not show evidence of crossreactivity.

Arcanobacterium sp.	Human adenovirus F	Lactobacillus sp.1
Bacillus sp.	Human adenovirus G	Legionella pneumophila
Bacteroides sp.2	Human coronavirus 229E	Measles virus
Bordetella sp.	Human coronavirus HKU1	Human Metapneumovirus
Branhamella sp.	Human coronavirus NL63	Moraxella sp.
Burkholderia sp.	Human enterovirus A	Mumps virus
Campylobacter sp.3	Human enterovirus B	Mycoplasma pneumoniae
Candida sp.	Human enterovirus C	Neisseria sp.
Corynebacterium sp.	Human enterovirus D	Peptostreptococcus sp.
Cytomegalovirus	Human herpesvirus 1	Proteus sp.
Enterobacterio phage MS2	Human herpesvirus 2	Pseudomonas sp.
Enterococcus sp.	Human herpesvirus 4	Respiratory syncytial virus Type B
Escherichia coli	Human parainfluenza virus 1	Saccharomyces cerevisiae
Fusobacterium sp.	Human parainfluenza virus 2	Serratia sp.
Haemophilus sp.	Human parainfluenza virus 3	Staphylococcus sp.
Human adenovirus A	Human parainfluenza virus4a and 4b	Treponema sp.
Human adenovirus B	Influenza virus A	Veillonella sp.
Human adenovirus C	Influenza virus B	Yersinia sp.
Human adenovirus D	Influenza virus C	Prevotella oralis4
Human adenovirus E	Klebsiella sp.	Parvimonas micra5
Veillonella parvula

¹ Includes L. acidophilus

2 Includes B. ovatus

3 Includes C. rectus

4 In NCBI, Bacteroides oralis is Prevotella oralis.

5 In NCBI, Peptostreptococcus micros is Parvimonas micra.

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A study was performed to evaluate the performance of the Solana™ GAS Assay in the presence of forty-six (46) other microorganisms commonly found in throat specimens. Each potentially interfering microorganism was tested in the presence of 2 x LoD Group A Streptococcus (2 strains) in the presence of clinically relevant levels of viruses (10 pfu/ml) and bacteria (10 cfu/mL) or higher. All strain combinations were spiked on to swabs. The strains included in the cross-reactivity study are shown in the table below.

Acinetobacter Iwoffii	Staphylococcus epidermidis MRSE
Arcanobacterium haemolyticum	Stenotrophomonas maltophilia
Bacillus cereus	Streptococcus agalactiae
Bordetella pertussis	Streptococcus anginosus
Burkholderia cepacia	Streptococcus bovis
Corynebacterium diphtheria	Streptococcus canis
Enterococcus faecalis	Streptococcus dysgalactiae subsp equisimilis
Escherichia coli	Streptococcus gordonii (Virdans type)
Fusobacterium necrophorum	Streptococcus intermedius
Haemophilus influenza type A	Streptococcus mitis
Klebsiella pneumonia	Streptococcus mutans
Lactobacillus acidophilus	Streptococcus oralis
Lactococcus lactis	Streptococcus pneumoniae
Legionella jordanis	Streptococcus salivarius
Legionella micdadei	Streptococcus sanguinis
Legionella pneumophila	Streptococcus suis
Moraxella cartarrhalis	Candida albicans
Neisseria gonorrhoeae	Adenovirus Type 1
Neisseria subflava	Adenovirus Type 11 (Slobitski)
Peptostreptococcus micros (aka Parvimonasmicra)	Influenza A
Pseudomonas aeruginosa	Influenza B
Serratia marcescens	Parainfluenza Type 4B (VR-1377)
Staphylococcus aureus MRSA	Rhinovirus Type 15 (1734)

None of the organisms or viruses tested above cross-reacts with the performance of the Solana™ GAS Assay.

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Interference:

A study was conducted using two strains of Streptococcus pyogenes (ATCC 19615 and 12344) tested near LoD to evaluate the Solana™ GAS Assay for potential interference using a panel consisting of twenty-eight (28) common biological and chemical substances found in throat samples. Substances were introduced into the assay dilution tubes at concentrations which were medically relevant. Each of the strains was tested for each substance. None of the substances tested were found to interfere with the Solana™ GAS Assay.

Substance Name	TestConcentration	Interference?(Y/N)
Children's DimetappDM Cold & CoughElixir	25% v/v	No
Chloraseptic Max:Sore Throat Relief	10% v/v	No
BreathSavers 3 HourMint-Spearmint	10% w/v	No
Cepacol Sore Throat:Cherry Flavor	5% w/v	No
Robitussin Cough &Cold-CF Max	10% v/v	No
Ricola MountainHerb ThroatDrops-Sugar Free	15% w/v	No
Human Saliva	10% v/v	No
Robitussin NighttimeCold, & Flu	10% v/v	No
Crest Pro-HealthNight Mint	25% v/v	No
CVS Tussin CF	15% v/v	No
Chloraseptic ThroatCherry lozenge	10% w/v	No
Halls CherryMentholyptus	15% w/v	No
Tic Tac Freshmints	10% w/v	No
Zicam® Oral Mist	0.625% v/v	No

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Substance Name	TestConcentration	Interference?(Y/N)
SucretsComplete-VaporCherry	5% w/v	No
Acetaminophen	19.5 mg/mL	No
Aspirin	12.3 mg/mL	No
Ibuprofen	15.6 mg/mL	No
Benadryl	2.7 mg/mL	No
Crest® CompleteToothpaste	5% w/v	No
Contac® Cold + FluCaplets Night	10% w/v	No
Children's Wal-TapElixir Cold & Allergy(Dimetap Children'sCold and Allergy)	25% v/v	No
Children's Wal-TapDM Elixir Cold &Cough	25% v/v	No
Robitussin NighttimeCough, Cold, & Flu(peak cold)	10% v/v	No
Halls Mentholyptus(not cherry flavor)	15% w/v	No
Listerine Cool MintAntiseptic	15% v/v	No
Whole Blood	5% v/v	No
Mucin (BovineSubmaxillary Gland,type I-S)	5.0 mg/mL	No

Analytical Reactivity (Inclusivity):

The reactivity of the Solana™ GAS Assay was evaluated against an additional seven (7) strains of Streptococcus pyogenes (GAS) at concentrations near the limit of detection (LoD) of the assay.

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Each strain was tested as three replicates in the Solana™ GAS Assay. The study was performed in multiple experiments. For each experiment, three replicates of up to three strains were performed, along with a positive and a negative run control. All seven strains were detected by the Solana™ GAS Assay.

Bacterial Strain	ConcentrationCFU/mL	Strain Detected(Yes/No)
ATCC 12384	$6.81 x10^4$	Yes
NCIMB 13285	$6.81 x10^4$	Yes
CCUG 33061	$6.81 x10^4$	Yes
CCUG 33409	$6.81 x10^4$	Yes
CCUG 39158	$6.81 x10^4$	Yes
ATCC 49399	$6.81 x10^4$	Yes
CCUG 53553	$6.81 x10^4$	Yes

f. Assay cut-off:
Not applicable.

2. Comparison studies:

a. Method comparison with predicate device:
Not applicable
b. Matrix comparison:
A comparison study was conducted between negative clinical matrix and the contrived negative matrices used in the analytical studies in order to validate their use. The matrix comparison study results are shown in the table below.

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		Contrived NegativeMatrix		Pooled Negative ClinicalMatrix
		Detected	% Pos	Detected	% Pos
StreptococcuspyogenesATCC 19615	1 x LoD	20/20	100%	20/20	100%

These studies demonstrate that the contrived negative matrices do not alter the performance of the device in the context of these analytical studies.

3. Clinical studies:

a. Clinical Sensitivity:

Performance characteristics of the Solana GAS Assay were established during a prospective study conducted December 2014 to February 2015. One thousand eighty-two (1082) fresh throat swab specimens from female and male patients were collected at four distinct geographical sites across the United States. A single specimen was collected per patient. Samples were collected on Polyester, Nylon or Rayon Swab with liquid Amies or Polyester Swab or Rayon with liquid Stuart's. The swabs were inoculated by conventional streak-stab culture technique onto a trypticase soy agar plate containing 5% horse red blood cells. Testing with the Solana device was performed at the four external laboratories using the same swab that was plated for the culture. All residual specimen transport media from the samples was shipped daily (with cold packs) to a central location. The transport media was cultured using the same testing protocol as that employed by the clinical sites.

One thousand eighty-two (1082) fresh throat specimens were cultured for Group A β-hemolytic Streptococcus and tested with the Solana GAS Assay. The specimens were cultured at the testing sites and the transport media was cultured at a central location. The specimen was considered positive if either the swab or the transport media was positive for ß-hemolytic Streptococcus (Composite Culture) and typed as Lancefield group A by latex agglutination. The table below details the overall performance using composite culture results as a reference.

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Performance Results of Solana GAS Assay for Group A β-hemolytic Streptococcus
Overall Performance (All Sites)
Solana GAS Assay	Composite Culture Positive	Negative	Total
Positive	220	24*	244
Negative	4**	833	837
Total	224	857	1081
95% CI
Sensitivity	220/224	98.2%	95.5% to 99.3%
Specificity	833/857	97.2%	95.9% to 98.1%
* Of the twenty-four (24) discordant specimens, sixteen (16) of these specimens werepositive for GAS when tested with an additional FDA-cleared molecular device, eight (8)were negative.** Of the four (4) discordant specimen, three (3) were negative when tested with anadditional FDA-cleared molecular device.
Site 1 Performance
Solana® GAS Assay	Composite Culture Positive	Negative	Total
Positive	60	5	65
Negative	1	333	334
Total	61	338	399
95% CI
Sensitivity	60/61	98.4%	91.3% to 99.7%
Specificity	333/338	98.5%	96.6 % to 99.4%
Site 2 Performance
Solana® GAS Assay	Composite Culture Positive	Negative	Total
Positive	69	9	78
Negative	1	134	135
Total	70	143	213
95% CI
Sensitivity	69/70	98.6%	92.3% to 99.7%
Specificity	134/143	93.7%	88.5 % to 96.7%
Site 3 Performance
Solana® GAS Assay	Composite Culture Positive	Negative	Total
Positive	29	6	35
Negative	0	186	186
Total	29	192	221
95% CI
Sensitivity	29/29	100%	88.3% to 100%
Specificity	186/192	96.9%	93.4 % to 98.6%

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b. Clinical specificity:
See Section 3a.
ﻥ Other clinical supportive data (when a. and b. are not applicable):
Not applicable

4. Clinical cut-off:

Not applicable

5. Expected values:

The overall prevalence of Group A ß-hemolytic Streptococcus in patients tested during this study was 20.7% (224/1081) based on composite bacterial culture and 22.6% (244/1081) based on the Solana™ GAS Assay. All clinical specimens collected during this study were collected between December 2014 and February 2015.

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

Instrument: Solana™ Instrument

O. System Descriptions:

1. Modes of Operation:

The Solana instrument heats each reaction tube to 64°C. If present, the target sequence is amplified by GAS specific primers and detected by a GAS specific fluorescence probe included in the Reaction Tube. The target probes are labeled with a quencher on one end and a fluorophore on the other end. In addition, the target probes carry a ribonucleic acid. Upon annealing to GAS amplicons, the fluorescence probes are cleaved by RNaseH2 and the fluorescence signal increases due to physical separation of fluorophore from quencher. The Solana instrument measures and interprets the fluorescent signal, using on-board method-specific algorithms. Solana instrument will then report the test results to the user on its display screen, and it can print out the results via a printer.

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2. Software:

FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes __________________________________________________________________________________________________________________________________________________________________________ No ___________________________________________________________________________________________________________________________________________________________________________

P. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10, 21 CFR 801.109, and the special controls.

Regulation Number and Section

§ 866.2680

Streptococcus spp. nucleic acid-based assay.(a)
Identification. AStreptococcus spp. nucleic acid-based assay is a qualitative in vitro diagnostic device intended to simultaneously detect and identify variousStreptococcus spp. nucleic acids extracted directly from clinical specimens. The device detects specific nucleic acid sequences for organism identification. 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 II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation, including the device components, ancillary reagents required but not provided, and a detailed explanation of the methodology including primer/probe sequence, design, and rationale for sequence selection.
(2) Premarket notification submissions must include detailed documentation from the following analytical and clinical performance studies: Analytical sensitivity (Limit of Detection), reactivity, inclusivity, precision, reproducibility, interference, cross reactivity, carry-over, and cross contamination.
(3) Premarket notification submissions must include detailed documentation from a clinical study. The study, performed on a study population consistent with the intended use population, must compare the device performance to results obtained from well-accepted reference methods.
(4) Premarket notification submissions must include detailed documentation for device software, including, but not limited to, software applications and hardware-based devices that incorporate software.
(5) Premarket notification submissions must include database implementation methodology, construction parameters, and quality assurance protocols, as appropriate.
(6) The device labeling must include limitations regarding the need for culture confirmation of negative specimens, as appropriate.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling.
(8) Premarket notification submissions must include details on an end user device training program that will be offered while marketing the device, as appropriate.