(181 days)
Not Found
No
The summary describes a molecular diagnostic test utilizing PCR and lateral flow technologies. There is no mention of AI, ML, or image processing, and the device description focuses on the biochemical and hardware components.
No.
This device is an in vitro diagnostic test intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections by detecting bacterial nucleic acid. It does not directly treat or prevent a disease.
Yes
The "Intended Use / Indications for Use" section explicitly states that the test is "intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections." This clearly indicates its purpose as a diagnostic device.
No
The device description explicitly states the system consists of a "small reusable Dock" and a "single-use disposable test cassette," indicating it includes hardware components beyond just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use/Indications for Use: The document explicitly states "The Accula™ Strep A Test performed on the Accula Dock is a molecular in vitro diagnostic test..." and describes its use for detecting bacterial nucleic acid from throat swabs to aid in the diagnosis of Group A Streptococcus infections. This clearly aligns with the definition of an in vitro diagnostic device, which is used to examine specimens from the human body to provide information for diagnosis, treatment, or prevention of disease.
- Device Description: The description details a system that analyzes a biological sample (throat swabs) using laboratory techniques (PCR, lateral flow) to detect a specific target (Strep A bacterial nucleic acid). This is characteristic of an IVD.
- Anatomical Site: The test is performed on "throat swabs," which are specimens collected from the human body.
- Intended User/Care Setting: The intended users are in "Clinical lab and CLIA-waived sites," which are typical settings for performing diagnostic tests.
- Performance Studies: The document includes detailed performance studies (clinical study, reproducibility, limit of detection, analytical reactivity, analytical specificity, interfering substances, CLIA waiver studies) with metrics like sensitivity, specificity, PPA, and NPA. These types of studies and metrics are standard for demonstrating the performance of an IVD.
- Predicate Device(s): The mention of a "Predicate Device(s)" with a K number (K141338, Roche cobas® Liat™ Strep A Test) is a strong indicator that this device is being submitted for regulatory review as an IVD, as predicate devices are used for comparison in the regulatory process for new IVDs.
All of these factors collectively confirm that the Accula™ Strep A Test is an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The Accula™ Strep A Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection of Streptococcus pyogenes (Group A B-hemolytic Streptococcus, Strep A) bacterial nucleic acid. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections from throat swabs of patients with signs and symptoms of pharyngitis.
All negative test results should be confirmed by bacterial culture because negative results do not preclude infection with Group A Streptococcus and should not be used as the sole basis for treatment.
Product codes (comma separated list FDA assigned to the subject device)
PGX
Device Description
The Accula™ Strep A Test is a semi-automated, colorimetric polymerase chain reaction (PCR) nucleic acid amplification test to qualitatively detect Streptococcus pyogenes (Group A Bhemolytic Streptococcus, Strep A) bacterial nucleic acid from unprocessed throat swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, a novel Mesa Biotech PCR nucleic acid amplification technology named OscAR™, and hybridization-based visual detection into a completely self-contained and automated system. The Accula Strep A system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
The Accula Strep A Test Kit contains all the materials needed to run a test, except for the Accula Dock, which is provided separately. The Accula Strep A Test Kit contains the following components:
- Sterile Swabs for throat swab collection (25)
- Accula Strep A Buffer (25)
- Accula Transfer Pipettes (25)
- Accula Strep A Test Cassettes (25)
- Strep A Positive Control Swab (1)
- Negative Control Swab (1)
- Instructions for Use
- Quick Reference Guide
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
throat swabs
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Clinical lab and CLIA-waived sites
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
Prospective Clinical Study:
A multi-site prospective study was conducted from May 2019 to January 2020 in the U.S. at nine (9) investigational Point of Care sites. Patients presenting with symptoms of pharyngitis were enrolled. Two throat swabs were collected from each subject: one using a Copan FLOOTM swab for Accula testing and a second using a Copan eSwab™ Liquid Amies Collection System for reference testing. The Accula swab was tested on the Accula Strep A Test after elution in 2.5 mL of Accula Strep A Buffer. The eSwab was transported to a central laboratory for testing by Blood Agar Culture and an FDA-cleared molecular test. Discrepant results between the Accula Strep A Test and Blood Agar Culture, or between Accula and the molecular comparator test, were resolved with a second FDA-cleared molecular test.
A total of 669 subjects were enrolled. For the Accula v. culture comparison, 15 samples were unevaluable due to transport/storage issues, inclusion/exclusion criteria non-compliance, protocol deviations, and invalid Accula results, leaving 654 evaluable samples. For the Accula v. molecular comparator analysis, 21 samples were unevaluable for similar reasons, leaving 648 evaluable samples.
Reproducibility/Near-Cutoff Study:
Performed at three CLIA waived sites that participated in the clinical study. The test panel consisted of three contrived throat swab samples: Low Positive (1x LoD), Moderate Positive (2x LoD), and Negative. Each positive sample was prepared by spiking Streptococcus pyogenes strain BAA-946 into clinical matrix. Negative sample contained no Strep A. Samples were blinded and coded and provided randomly to operators. Testing was performed in triplicate by two operators per site on five non-consecutive days over two weeks, concurrently with the clinical study.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Prospective Clinical Study:
- Sample size: 654 evaluable samples for Accula vs. Culture comparison; 648 evaluable samples for Accula vs. Molecular Comparator.
- Key Results (Accula Strep A Test compared to Blood Agar Culture):
- Sensitivity: 96.2% (126/131) (95% CI: 91.4%-98.4%)
- Specificity: 97.5% (510/523) (95% CI: 95.8%-98.5%)
- Accuracy: 97.2% (636/654) (95% CI: 95.7%-98.3%)
- NPV: 99% (510/515) (95% CI: 97.7%-99.6%)
- NPV (at 30% Prevalence): 98.3%
- Discrepant Evaluation: Strep A was detected in 7/13 False Positives specimens using the discrepant evaluation molecular method. Strep A was not detected in 2/5 False Negative specimens using the discrepant evaluation molecular method.
- Key Results (Accula Strep A Test compared to FDA-cleared molecular method):
- PPA (Positive Percent Agreement): 93.8% (137/146) (95% CI: 88.7%-96.7%)
- NPA (Negative Percent Agreement): 99.8% (501/502) (95% CI: 98.9%-100%)
- Discrepant Evaluation: Strep A was detected in 0/1 False Positives specimens using the discrepant evaluation molecular method. Strep A was not detected in 5/9 False Negative specimens using the discrepant evaluation molecular method.
Reproducibility/Near-Cutoff Study:
- Study type: Reproducibility study performed at three CLIA waived sites.
- Sample size: Not explicitly stated as a single number, but results are based on triplicate swab preparations by two operators per site, on five non-consecutive days, for each of three sample types (Low Positive, Moderate Positive, Negative).
- Key Results: No significant differences were observed within run, between runs, between operators or between sites.
- Agreement for Low Positive sample: 98.9% (89/90) (95% CI: 94.0%-99.8%)
- Agreement for Moderate Positive sample: 97.8% (87/89) (95% CI: 92.2%-99.4%)
- Agreement for Negative sample: 97.8% (88/90) (95% CI: 92.3%-99.4%)
Limit of Detection (LoD) Study:
- Study type: Analytical study to determine the lowest detectable concentration.
- Key Results:
- BAA-946: 75 CFU/mL
- ATCC 19615: 10 CFU/mL
Analytical Reactivity (Inclusivity) Study:
- Study type: Analytical study to verify inclusivity of additional Strep A strains.
- Key Results: All four tested Strep A strains were detected at 1.5x LoD and 3.0x LoD concentrations, with one strain (ATCC 21548) showing 66.67% detection at 1.5x LoD and 100% at 3.0x LoD.
Analytical Specificity (Cross-Reactivity) Study:
- Study type: Analytical study to evaluate cross-reactivity with other organisms.
- Key Results: All 47 tested organisms gave negative results when tested in the absence of 3x LoD Strep A. None of the 47 organisms interfered with the detection of Strep A when tested in the presence of 3x LoD Strep A.
Interfering Substances Study:
- Study type: Analytical study to assess the effect of potentially interfering substances.
- Key Results: Most tested substances showed 100% agreement with expected results for both Strep A positive and negative samples at specified concentrations. Some substances (Human Blood, Tums, Whole Milk, Orange Juice) showed inhibition at higher concentrations but no inhibition at lower, optimized concentrations.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
- Sensitivity: 96.2% (126/131) (95% CI: 91.4%-98.4%)
- Specificity: 97.5% (510/523) (95% CI: 95.8%-98.5%)
- Accuracy: 97.2% (636/654) (95% CI: 95.7%-98.3%)
- NPV: 99% (510/515) (95% CI: 97.7%-99.6%)
- NPV (at 30% Prevalence): 98.3%
- PPA (Positive Percent Agreement): 93.8% (137/146) (95% CI: 88.7%-96.7%) (compared to molecular comparator)
- NPA (Negative Percent Agreement): 99.8% (501/502) (95% CI: 98.9%-100%) (compared to molecular comparator)
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
K141338, Roche cobas® Liat™ Strep A Test
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 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.
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.
November 9, 2020
Mesa Biotech, Inc. Barbara Stevens Regulatory Consultant 6190 Cornerstone Court, Suite 220 San Diego, California 92121
Re: K201269
Trade/Device Name: Accula Strep A Test Regulation Number: 21 CFR 866.2680 Regulation Name: Streptococcus Spp. Nucleic Acid-Based Assay Regulatory Class: Class II Product Code: PGX Dated: May 11, 2020 Received: May 12, 2020
Dear Barbara Stevens:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. 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 Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR
1
- for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
Ribhi Shawar, Ph.D. (ABMM) Chief. General Bacteriology and Antimicrobial Susceptibility Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Section 5. 510(k) Summary of Safety and Effectiveness
This 510(k) summary of safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
The assigned 510(k) number is: _K201269
Sponsor/Applicant Name and Address 1. Mesa Biotech, Inc. Company Name: Address: 6190 Cornerstone Court, Suite 220 San Diego, CA 92121 Telephone: 858-800-4929 Contact Person: Barbara Stevens Regulatory Consultant Date Summary Prepared: 05/11/2020 Device Name and Classification 2. Trade Name: Accula™ Strep A Test Classification of Device: 21 CFR 866.2680, Streptococcus spp. Nucleic-acid based assay PGX Product Code
Predicate Device 3.
K141338, Roche cobas® Liat™ Strep A Test
Device Description 4.
Operating Principle
The Accula™ Strep A Test is a semi-automated, colorimetric polymerase chain reaction (PCR) nucleic acid amplification test to qualitatively detect Streptococcus pyogenes (Group A Bhemolytic Streptococcus, Strep A) bacterial nucleic acid from unprocessed throat swabs that have not undergone prior nucleic acid extraction. The system integrates nucleic acid extraction, a novel Mesa Biotech PCR nucleic acid amplification technology named OscAR™, and hybridization-based visual detection into a completely self-contained and automated system. The Accula Strep A system consists of a small reusable Dock to drive the automated testing process, and a single-use disposable test cassette that contains all the enzymes and reagents.
Strep A Kit Contents
The Accula Strep A Test Kit contains all the materials needed to run a test, except for the Accula Dock, which is provided separately. The Accula Strep A Test Kit contains the following components.
3
- Sterile Swabs for throat swab collection (25) ●
- Accula Strep A Buffer (25) ●
- Accula Transfer Pipettes (25)
- Accula Strep A Test Cassettes (25)
- Strep A Positive Control Swab (1)
- Negative Control Swab (1)
- Instructions for Use
- Quick Reference Guide
Indications for Use ട്.
The Accula Strep A Test performed on the Accula Dock is a molecular in vitro diagnostic test utilizing polymerase chain reaction (PCR) and lateral flow technologies for the qualitative, visual detection of Streptococcus pyogenes (Group A B-hemolytic Streptococcus, Strep A) bacterial nucleic acid. It is intended to aid in the rapid diagnosis of Group A Streptococcus bacterial infections from throat swabs of patients with signs and symptoms of pharyngitis.
All negative test results should be confirmed by bacterial culture because negative results do not preclude infection with Group A Streptococcus and should not be used as the sole basis for treatment.
Comparison to Predicate Device 6.
The following table provides a comparison of the characteristics of the Accula Strep A Test to the predicate device, the Roche cobas® Liat™ Strep A Test.
| Item | 510(k) Device:
Mesa Biotech
Accula Strep A Test | Predicate Device:
Roche cobas® Liat™ Strep A
Test (K141338) |
|-------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | The Accula Strep A Test
performed on the Accula
Dock is a molecular in vitro diagnostic test
utilizing polymerase
chain reaction (PCR)
and lateral flow
technologies for the
qualitative, visual
detection of
Streptococcus pyogenes
(Group A β-hemolytic
Streptococcus , Strep A)
bacterial nucleic acid. It
is intended to aid in the
rapid diagnosis of Group
A Streptococcus | The cobas® Strep A nucleic
acid test for use on the cobas
Liat System (cobas Strep A) is
a qualitative in vitro diagnostic
test for the detection of
Streptococcus pyogenes
(Group A β-hemolytic
Streptococcus , Strep A) in
throat swab specimens from
patients with signs and
symptoms of pharyngitis.
The cobas Strep A assay
utilizes nucleic acid
purification and polymerase
chain reaction (PCR) |
| | bacterial infections from
throat swabs of patients
with signs and
symptoms of
pharyngitis.
All negative test results should
be confirmed by bacterial
culture because negative
results do not preclude
infection with Group A
Streptococcus and should not
be used as the sole basis for
treatment. | technology to detect
Streptococcus pyogenes by
targeting a segment of the
Streptococcus pyogenes
genome. |
| Product Code | PGX | PGX |
| Analyte | Group A Streptococcus ( S. pyogenes ) | Group A Streptococcus ( S. pyogenes ) |
| Strep A Target | Conserved region of Group A
Streptococcus genome | Conserved region of Group A
Streptococcus genome |
| Sample Type | Throat swab | Throat swab |
| Assay Results | Qualitative | Qualitative |
| Intended Users and
Use Locations | Clinical lab and CLIA-waived
sites | Clinical lab and CLIA-waived
sites |
| Bacterial Lysis/DNA
Extraction | Detergent and heat | Chaotrope and enzymatic
digestion |
| Nucleic Acid
Purification | No | Solid phase magnetic affinity
capture |
| Reagent Format | Unitized, ready for use | Unitized, ready for use |
| Internal Control | Yes | Yes |
| Positive and
Negative Control
Swabs | Yes | Yes |
| Assay Technology | PCR amplification and visual
identification of amplification
products by hybridization to a
test strip. | PCR nucleic acid amplification
and detection of specific
amplification products using
molecular TaqMan |
| | | fluorescent probes. |
| Detection | Uses dyed microparticle
conjugates to specifically
detect and identify
amplification reaction
products.
Visual interpretation of the
presence or the absence of
colored lines on a test strip. | Uses fluorescently-labeled
Taqman probe to specifically
identify amplified cDNA
products.
Optical detection of
fluorescence |
| Instrument | Amplification controlled by
the Accula Dock.
No detection by the
instrument. | Amplification and detection
performed on the Liat
instrument. |
4
5
7. Performance Summary
Expected Values
A total of 654 specimens were tested in a prospective clinical study conducted at nine U.S sites from May 2019 to January 2020. The overall prevalence of S. pyogenes as determined by bacterial culture was 20.0% (131/654), and as determined by the Accula Strep A Test, the overall positivity rate was 21.3% (139/654). The positivity rate by age range of the subjects is shown below.
| Strep A Positivity Rate by Accula Strep A Test | |||
|---|---|---|---|
| Age Group | Number of Swab | ||
| Specimens | Number of Strep A | ||
| Positives | Strep A Positivity Rate | ||
| ≤ 5 Years | 112 | 34 | $34/112 = 30.36%$ |
| 6 to 21 Years | 292 | 70 | $70/292 = 23.97%$ |
| 22 to 59 Years | 224 | 34 | $34/224 = 15.18%$ |
| ≥ 60 Years | 26 | 1 | $1/26 = 3.85%$ |
| Total | 654 | 139 | $139/654 = 21.25%$ |
Prospective Clinical Study:
Clinical performance characteristics of the Accula Strep A Test were evaluated in a multi-site prospective study from May 2019 to January 2020 in the U.S. A total of nine (9) investigational Point of Care sites participated in the study. To be enrolled in the study, patients had to be presenting at the participating study centers with symptoms of pharyngitis. Two throat swabs were collected from each subject using standard collection methods, a Copan FLOOTM swab for the Accula testing and a second swab using the Copan eSwab™ Liquid Amies Collection System
6
for the reference testing. One throat swab was tested, following elution in 2.5 mL of Accula Strep A Buffer, on the Accula Strep A Test, according to product instructions. The other throat swab was collected with the eSwab system in accordance with the instructions from the reference laboratory and the test manufacturer and transported to the central laboratory for testing by Blood Agar Culture and an FDA-cleared molecular test. All specimens generating discrepant results between the Accula Strep A Test and Blood Agar Culture, or between Accula and the molecular comparator test, were tested with a second FDA-cleared molecular test.
A total of 669 subjects were enrolled in this study. Of those, 15 samples were unevaluable for the Accula v. culture comparison due to sample transport and storage issues, failure to comply with inclusion/exclusion criteria, protocol deviations, and invalid results with the Accula test. A total of 654 samples were considered evaluable for this analysis. The performance of the Accula Strep A Test compared to Blood Agar Culture is shown in the table below. Results of the discrepant evaluations against both molecular methods are shown in the footnotes.
| Mesa Biotech Accula™ | Blood Agar Culture | ||
|---|---|---|---|
| Strep A Test | Positive | Negative | Total |
| Positive | 126 | 13a | 139 |
| Negative | 5b | 510 | 515 |
| Total | 131 | 523 | 654 |
| Sensitivity: | 96.2% (126/131) (95% CI:91.4%-98.4%) | ||
| Specificity: | 97.5% (510/523) (95% CI:95.8%-98.5%) | ||
| Accuracy: | 97.2% (636/654) (95% CI:95.7%-98.3%) | ||
| NPV: | 99% (510/515) (95% CI:97.7%-99.6%) | ||
| NPV (at 30% Prevalence): | 98.3% |
Accula Strep A Test Performance against Reference Culture
ªStrep A was detected in 7/13 False Positives specimens using the discrepant evaluation molecular method
*Strep A was not detected in 2/5 False Negative specimens using the discrepant evaluation molecular method
In addition, the Accula Strep A Test results were compared with an FDA-clear molecular comparative method. For this analysis, 21 of the samples from the 669 enrolled subjects were unevaluable due to sample transport and storage issues, failure to comply with inclusion/exclusion criteria, protocol deviations, invalid results with the molecular comparator method, and invalid results with the Accula test. A total of 648 samples were considered evaluable for this analysis. The performance of the Accula Strep A Test compared to the FDAcleared molecular method are shown in the table below. Results of the discrepant evaluation against the discrepant analysis molecular method are shown in the footnotes.
Accula™ Strep A Test Strep A Performance Against the Molecular Comparator
| Mesa Biotech Accula™
| Strep A Test | Molecular Comparator | ||
|---|---|---|---|
| Positive | Negative | Total | |
| Positive | 137 | 1a | 138 |
| Negative | 9b | 501 | 510 |
| Total | 146 | 502 | 648 |
7
| PPA (Positive Percent | |
|---|---|
| Agreement): | 93.8% (137/146) (95% CI:88.7%-96.7%) |
| NPA (Negative | |
| Percent Agreement): | 99.8% (501/502) (95% CI:98.9%-100%) |
a Strep A was detected in 0/1 False Positives specimens using the discrepant evaluation molecular method
b Strep A was not detected in 5/9 False Negative specimens using the discrepant evaluation molecular method
Reproducibility/Near-Cutoff Study
The Reproducibility study was performed to demonstrate the reproducibility of the Accula Strep A Test with contrived throat swabs, including samples at analyte concentrations near the assay cutoff, at three CLIA waived sites that also participated in the clinical study. The objective of the study was to demonstrate reproducibility of the assay in the hands of multiple users at multiple sites over multiple non-consecutive days.
The test panel consisted of three samples at varying Strep A concentrations, two of which are at or near the assay cutoff. Each positive sample was prepared by spiking the Streptococcus pyogenes strain BAA-946 into clinical matrix. The targeted concentration for the Low Positive Sample was 1x LoD and for the Moderate Positive Sample was 2x LoD. The Negative Sample contained no Strep A.
Samples were blinded and coded and were provided to testing operators in a random fashion. Testing was performed with triplicate swab preparations, by two operators per site, on five nonconsecutive days over a period of two weeks, concurrently with the clinical study.
Results are reported as percent: observed result/expected result x 100. No significant differences were observed within run, between runs, between operators or between sites. Agreement by site is summarized in the table below.
| Site | |||||||
|---|---|---|---|---|---|---|---|
| 1 | 2 | 3 | Overall | ||||
| Sample | |||||||
| Type | Percent | ||||||
| Agreement | Count | Percent | |||||
| Agreement | Count | Percent | |||||
| Agreement | Count | Percent | |||||
| Agreement | |||||||
| (95% CI) | |||||||
| Low | |||||||
| Positive | 96.7% | 29/30 | 100.0% | 30/30 | 100.0% | 30/30 | 98.9% (89/90) |
| (94.0%-99.8%) | |||||||
| Moderate | |||||||
| Positive | 96.7% | 29/30 | 100.0% | 30/30 | 96.6% | 28/29 | 97.8% (87/89) |
| (92.2%-99.4%) | |||||||
| Negative | 100.0% | 30/30 | 100.0% | 30/30 | 93.3% | 28/30 | 97.8% (88/90) |
| (92.3%-99.4%) |
Site to Site Reproducibility: Percent Agreement and Total Counts (Observed/Expected)
Limit of Detection
8
Two Strep A strains were tested at multiple analyte levels until the LoD was determined (the level at which at least 19/20 results are positive). Bacteria were serially diluted into a pooled negative clinical matrix and spiked onto a swab for each replicate to create the contrived test samples. Confirmatory testing was performed in replicates of twenty (20) on multiple days. The results are summarized in the table below.
| Strep A Strain | LoD Level1 |
|---|---|
| BAA-946 | 75 CFU/mL |
| ATCC 19615 | 10 CFU/mL |
Accula Strep A Limit of Detection
1 Final concentration of organisms after 10 uL of bacterial dilution is spiked onto swab and eluted in 2.5 mL Strep A Buffer (assuming 100% recovery of bacteria).
Analytical Reactivity
Inclusivity verification was evaluated for the Accula Strep A Test at Mesa Biotech. The panel consisted of four (4) additional Strep A strains that were not included in the LoD study. Each strain was tested in triplicate at concentrations of approximately 1.5x LoD and 3.0x LoD. Test results are summarized in the table below. All strains were detected at the levels tested.
Inclusivity Results by Strain
| Strep A Strain | 1.5X LoD
Concentration | Percent Detection
(# Positive/3) | 3.0X LoD
Concentration | Percent Detection
(# Positive/3) |
|----------------|---------------------------|-------------------------------------|---------------------------|-------------------------------------|
| ATCC 10403 | 112.5 CFU/mL | 100% (3/3) | 225 CFU/mL | 100% (3/3) |
| ATCC 21548 | 112.5 CFU/mL | 66.67% (2/3) | 225 CFU/mL | 100% (3/3) |
| ATCC 700294 | 112.5 CFU/mL | 100% (3/3) | 225 CFU/mL | 100% (3/3) |
| ATCC 700497 | 112.5 CFU/mL | 100% (3/3) | 225 CFU/mL | 100% (3/3) |
The Analytical Specificity (Cross-Reactivity)
Cross-reactivity was evaluated by testing 47 potentially cross-reacting organisms with the Accula Strep A Test. Each organism was diluted in a clinical matrix, both in the absence and in the presence of 3x LoD Strep A, and tested in triplicate. The organisms, concentrations, and test results are shown in the tables below. All 47 organisms gave negative results when tested in the absence of 3x LoD Strep A. None of the 47 organisms interfered with the detection of Strep A when tested in the presence of 3x LoD Strep A.
Testing of Potential Cross-Reactive Organisms in the Absence of Strep A
| Organism
Key # | Organism Name | Test Level | Test Results (# of
Strep A Pos /3) |
|-------------------|--------------------------------------------------|--------------------|---------------------------------------|
| 1 | Adenovirus Type 1 | 1.00E+06 TCID50/mL | 0/3 |
| 2 | Arcanobacterium
haemolyticum | 2.00E+07 CFU/ml | 0/3 |
| 3 | Bacillus cereus | 1.00E+06 CFU/ml | 0/3 |
| 4 | Bordetella pertussis | 2.00E+06 CFU/ml | 0/3 |
| 5 | Burkholderia cepacia | 2.00E+07 CFU/ml | 0/3 |
| Organism
Key # | Organism Name | Test Level | Test Results (# of
Strep A Pos /3) |
| 6 | Campylobacter rectus | 1.00E+06 CFU/ml | 0/3 |
| 7 | Candida albicans | 2.00E+06 CFU/ml | 0/3 |
| 8 | Corynebacterium diphtheriae | 5.00E+06 CFU/ml | 0/3 |
| 9 | Enterococcus faecalis | 2.00E+06 CFU/ml | 0/3 |
| 10 | Escherichia coli | 2.00E+07 CFU/ml | 0/3 |
| 11 | Fusobacterium necrophorum | 1.00E+06 CFU/ml | 0/3 |
| 12 | Haemophilus influenzae | 1.00E+06 CFU/ml | 0/3 |
| 13 | Human Influenza virus A**** | 1.00E+06 TCID50/mL | 0/3 |
| 14 | Human Influenza virus B | 1.00E+06 TCID50/mL | 0/3 |
| 15 | Human metapneumovirus | 1.00E+06 TCID50/mL | 0/3 |
| 16 | Klebsiella pneumoniae | 2.00E+07 CFU/ml | 0/3 |
| 17 | Lactobacillus acidophilus | 2.00E+06 CFU/ml | 0/3 |
| 18 | Lactococcus lactis | 2.00E+07 CFU/ml | 0/3 |
| 19 | Legionella longbeachae | 1.00E+07 CFU/ml | 0/3 |
| 20 | Moraxella catarrhalis | 1.00E+06 CFU/ml | 0/3 |
| 21 | Mycoplasma pneumoniae | 1.00E+06 CCU/ml | 0/3 |
| 22 | Neisseria gonorrhoeae | 3.00E+06 CFU/ml | 0/3 |
| 23 | Parainfluenza Type 3 | 1.00E+06 TCID50/mL | 0/3 |
| 24 | Parvimonas micra
(Peptostreptococcus micros) | 1.50E+06 CFU/ml | 0/3 |
| 25 | Prevotella oralis (Bacteroides
oralis) | 1.00E+06 CFU/ml | 0/3 |
| 26 | Pseudomonas aeruginosa | 1.00E+06 CFU/ml | 0/3 |
| 27 | Respiratory syncytial virus
Type B | 1.00E+06 TCID50/mL | 0/3 |
| 28 | Rhinovirus | 1.00E+06 TCID50/mL | 0/3 |
| 29 | Saccharomyces cerevisiae | 2.00E+06 CFU/ml | 0/3 |
| 30 | Staphylococcus epidermidis | 5.00E+07 CFU/ml | 0/3 |
| 31 | Stenotrophomonas
maltophilia | 5.00E+07 CFU/ml | 0/3 |
| 32 | Streptococcus agalactiae | 2.00E+06 CFU/ml | 0/3 |
| 33 | Streptococcus anginosus | 2.00E+06 CFU/ml | 0/3 |
| 34 | Streptococcus bovis | 5.00E+06 CFU/ml | 0/3 |
| 35 | Streptococcus canis | 2.00E+07 CFU/ml | 0/3 |
| 36 | Streptococcus constellatus
subsp. Pharyngis | 3.00E+06 CFU/ml | 0/3 |
| 37 | Streptococcus dysgalactiae
subsp. Equisimilis | 1.00E+06 CFU/ml | 0/3 |
| 38 | Streptococcus gallolyticus | 2.00E+06 CFU/ml | 0/3 |
| 39 | Streptococcus intermedius | 2.00E+06 CFU/ml | 0/3 |
| 40 | Streptococcus mitis | 2.00E+06 CFU/ml | 0/3 |
| Organism
Key # | Organism Name | Test Level | Test Results (# of
Strep A Pos /3) |
| 41 | Streptococcus mutans | 2.00E+07 CFU/ml | 0/3 |
| 42 | Streptococcus oralis | 2.00E+06 CFU/ml | 0/3 |
| 43 | Streptococcus pneumonia | 2.00E+06 CFU/ml | 0/3 |
| 44 | Streptococcus salivarius | 2.00E+06 CFU/ml | 0/3 |
| 45 | Streptococcus sanguinus | 2.00E+06 CFU/ml | 0/3 |
| 46 | Treponema denticola | 2.00E+06 CFU/ml | 0/3 |
| 47 | Veillonella parvula | 2.00E+07 CFU/ml | 0/3 |
9
10
Testing of Potential Cross-Reactive Organisms in the Presence of 3x LoD Strep A
| Organism Key # | Organism Name | Test Level | Test Results (# of
Strep A Pos /3) |
|----------------|-------------------------------------------------|--------------------|---------------------------------------|
| 1 | Adenovirus Type 1 | 1.00E+06 TCID50/mL | 3/3 |
| 2 | Arcanobacterium
haemolyticum | 2.00E+07 CFU/ml | 3/3 |
| 3 | Bacillus cereus | 1.00E+06 CFU/ml | 3/3 |
| 4 | Bordetella pertussis | 2.00E+06 CFU/ml | 3/3 |
| 5 | Burkholderia cepacia | 2.00E+07 CFU/ml | 3/3 |
| 6 | Campylobacter rectus | 1.00E+06 CFU/ml | 3/3 |
| 7 | Candida albicans | 2.00E+06 CFU/ml | 3/3 |
| 8 | Corynebacterium diphtheriae | 5.00E+06 CFU/ml | 3/3 |
| 9 | Enterococcus faecalis | 2.00E+06 CFU/ml | 3/3 |
| 10 | Escherichia coli 1 | 1.00E+07 CFU/ml | 3/3 |
| 11 | Fusobacterium necrophorum | 1.00E+06 CFU/ml | 3/3 |
| 12 | Haemophilus influenzae | 1.00E+06 CFU/ml | 3/3 |
| 13 | Human Influenza virus A | 1.00E+06 TCID50/mL | 3/3 |
| 14 | Human Influenza virus B | 1.00E+06 TCID50/mL | 3/3 |
| 15 | Human metapneumovirus | 1.00E+06 TCID50/mL | 3/3 |
| 16 | Klebsiella pneumoniae | 2.00E+07 CFU/ml | 3/3 |
| 17 | Lactobacillus acidophilus | 2.00E+06 CFU/ml | 3/3 |
| 18 | Lactococcus lactis | 2.00E+07 CFU/ml | 3/3 |
| 19 | Legionella longbeachae | 1.00E+07 CFU/ml | 3/3 |
| 20 | Moraxella catarrhalis | 1.00E+06 CFU/ml | 3/3 |
| 21 | Mycoplasma pneumoniae | 1.00E+06 CCU/ml | 3/3 |
| 22 | Neisseria gonorrhoeae | 3.00E+06 CFU/ml | 3/3 |
| 23 | Parainfluenza Type 3 | 1.00E+06 TCID50/mL | 3/3 |
| 24 | Parvimonas micra
(Peptostreptococcus micros) | 1.50E+06 CFU/ml | 3/3 |
| | | | |
| 25 | Prevotella oralis (Bacteroides
oralis) | 1.00E+06 CFU/ml | 3/3 |
| | | | |
| 26 | Pseudomonas aeruginosa | 1.00E+06 CFU/ml | 3/3 |
11
| Organism
Key # | Organism Name | Test Level | Test Results (# of
Strep A Pos /3) |
|-------------------|--------------------------------------------------|--------------------|---------------------------------------|
| 27 | Respiratory syncytial virus
Type B | 1.00E+06 TCID50/mL | 3/3 |
| 28 | Rhinovirus 2 | 5.00E+05 TCID50/mL | 3/3 |
| 29 | Saccharomyces cerevisiae | 2.00E+06 CFU/ml | 3/3 |
| 30 | Staphylococcus epidermidis | 5.00E+07 CFU/ml | 3/3 |
| 31 | Stenotrophomonas
maltophilia | 5.00E+07 CFU/ml | 3/3 |
| 32 | Streptococcus agalactiae | 2.00E+06 CFU/ml | 3/3 |
| 33 | Streptococcus anginosus | 2.00E+06 CFU/ml | 3/3 |
| 34 | Streptococcus bovis | 5.00E+06 CFU/ml | 3/3 |
| 35 | Streptococcus canis | 2.00E+07 CFU/ml | 3/3 |
| 36 | Streptococcus constellatus
subsp. pharyngis | 3.00E+06 CFU/ml | 3/3 |
| 37 | Streptococcus dysgalactiae
subsp. equisimilis | 1.00E+06 CFU/ml | 3/3 |
| 38 | Streptococcus gallolyticus | 2.00E+06 CFU/ml | 3/3 |
| 39 | Streptococcus intermedius | 2.00E+06 CFU/ml | 3/3 |
| 40 | Streptococcus mitis | 2.00E+06 CFU/ml | 3/3 |
| 41 | Streptococcus mutans | 2.00E+07 CFU/ml | 3/3 |
| 42 | Streptococcus oralis | 2.00E+06 CFU/ml | 3/3 |
| 43 | Streptococcus pneumonia | 2.00E+06 CFU/ml | 3/3 |
| 44 | Streptococcus salivarius | 2.00E+06 CFU/ml | 3/3 |
| 45 | Streptococcus sanguinus | 2.00E+06 CFU/ml | 3/3 |
| 46 | Treponema denticola | 2.00E+06 CFU/ml | 3/3 |
| 47 | Veillonella parvula | 2.00E+07 CFU/ml | 3/3 |
1 Escherichia coli was originally tested at 2 x 107 CFU/mL and gave 2/3 positive results in the presence of Strep A. No cross-reactivity was observed at 1 x 107 CFU/mL.
2 Rhinovirus was tested at 1 x 106 TCID50/mL and gave the expected 3/3 in the presence of Strep A. However, the visually graded maximum line intensity of "3" was not observed. No interference with line intensity was observed at a concentration of 5 x 105 TCID50/mL.
Interfering Substances
To assess substances with the potential to interfere with the performance of the Accula Strep A Test, samples with and without Strep A were tested in replicates of three (3) with each interfering substance at "worst case" concentrations, in addition to a "no interferent" control sample. Positive Strep A contrived samples were prepared by spiking the Strep A strain BAA-946 into a clinical throat swab matrix. The Negative sample was the clinical throat swab matrix alone. Any potential interferents that showed inhibition in the Accula Strep A Test were diluted and re-tested at a lower concentration. The table below summarizes the interferents tested, the highest concentration that showed no inhibition, the samples tested and the test results.
Effect of Potentially Interfering Substances on Accula Strep A Test Performance
12
| Potential Interferent | Active Ingredient | Final
Concentration | Target | % Agreement
with Expected
Results |
|----------------------------------------------|------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------|---------------|-----------------------------------------|
| Blood (Human) 1 | NA | 50% (v/v)
12.5% (v/v) | Strep A
IC | 100% (3/3) |
| Chloroseptic Max | Phenol 1.5%,
Glycerin 33% | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Cold&Flu Relief Cough
Syrup | Acetaminophen
21.7 mg/mL,
Dextromethorphan
0.67 mg/mL,
Guaifenesin 13.3
mg/mL,
Phenylephrine 0.33
mg/mL | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Listerine Cool Mint
Antiseptic Mouth Wash | Eucalyptol 0.092%,
Menthol 0.042%,
Methyl Salicylate
0.060%, Thymol
0.064% | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Cepacol (throat lozenge) | Benzocaine,
Menthol | 0.3% Benzocaine
(w/v), 0.046%
Menthol (w/v) | Strep A
IC | 100% (3/3) |
| Sucrets | Dyclonine
Hydrochloride,
Menthol | 0.06%
Dyclonine
Hydrochloride
(w/v), 0.12%
Menthol (w/v) | Strep A
IC | 100% (3/3) |
| Crest Pro Health
Fluoride Toothpaste | Stannous Fluoride
0.454% (0.14%
W/V Fluoride Ion) | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Halls Triple Soothing
Cough Drops* | Eucalyptus Oil | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Advil Liqui-Gels | Ibuprofen | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Miralax | Polyethylene
Glycol | 30.4% (w/v) | Strep A
IC | 100% (3/3) |
| Tums Extra Strength 2 | Calcium Carbonate | 20 mg/mL
30 mg/mL | Strep A
IC | 100% (3/3) |
| Food Dye | N/A | 100% (v/v) | Strep A
IC | 100% (3/3) |
| Whole Milk (Dairy) 3 | N/A | 12.50% (v/v)
50.00% (v/v) | Strep A
IC | 100% (3/3) |
| Orange Juice 4 | N/A | 50% (v/v)
100% (v/v) | Strep A
IC | 100% (3/3) |
| Penicillin G | Penicillin G
Sodium Salt | 100 mg/mL | Strep A
IC | 100% (3/3) |
| Potential Interferent | Active Ingredient | Final
Concentration | Target | % Agreement
with Expected
Results |
| Cephalexin | Cephalexin | 25 mg/mL | Strep A | 100% (3/3) |
| Cephalexin | Cephalexin | 25 mg/mL | IC | 100% (3/3) |
| Mucin, Type II (from
porcine stomach) | Purified mucin
protein | 50 mg/mL | Strep A | 100% (3/3) |
| Mucin, Type II (from
porcine stomach) | Purified mucin
protein | 100 mg/mL | IC | 100% (3/3) |
| Tobramycin
(antibacterial) | Tobramycin | 75 mg/mL | Strep A | 100% (3/3) |
| Tobramycin
(antibacterial) | Tobramycin | 75 mg/mL | IC | 100% (3/3) |
| Amoxicillin | Amoxicillin | 100 mg/mL | Strep A | 100% (3/3) |
| Amoxicillin | Amoxicillin | 100 mg/mL | IC | 100% (3/3) |
| No interferent | N/A | N/A | Strep A | 100% (3/3) |
| No interferent | N/A | N/A | IC | 100% (3/3) |
13
IC: Internal Control, for negative samples
*Eucalyptus oil, an active ingredient in Halls cough drops, was used in place of Halls Triple Soothing
Cough Drops.
- 1 Human blood showed inhibition at 100% concentration for Strep A detection in the positive sample, but no inhibition at 50% concentration. Human blood showed inhibition at 100%. 50% and 25% concentrations for IC detection in the negative sample, but no inhibition at 12.5% concentration.
- 2 Tums was initially tested with a solution of 1.5 g/mL (1 Tum dissolved into 2.5 mL of Strep A Buffer). This inhibited all reactions. The Strep A Positive sample was inhibited when tested with an additional 8x and 32x dilution. No inhibition was observed at a concentration of 20 mg/mL for the Strep A Positive sample. The Negative Strep A sample showed inhibition when tested with an additional 8x dilution. No inhibition was observed at a concentration of 30 mg/mL for the Strep A Negative sample.
- 3 Milk showed inhibition at 100%, 50% and 25% concentrations for Strep A detection in the positive sample, but no inhibition at 12.5% concentration. Milk showed inhibition at the 100% concentration for IC detection in the negative sample, but no inhibition at 50% concentration.
- 4 Orange juice showed inhibition at 100% concentration for detection of Strep A in the positive sample, but no inhibition at 50%.
CLIA Waiver Studies
Comparison with a Reference Method:
The performance of the Accula Strep A Test was evaluated at nine Point of Care sites by nonlaboratory personnel in a prospective clinical study from May 2019 to January 2020 in the U.S. Throat swabs were collected from patients with symptoms of pharyngitis and were tested with the Accula Strep A Test, the Blood Agar Culture reference method, and an FDA-cleared molecular comparator method. All specimens generating discrepant results were evaluated using a second molecular comparative method.
14
The comparison with culture showed a sensitivity of 96.2% (95% confidence interval: 91.4%-98.4%) and a specificity of 97.5% (95% CI: 95.8%-98.5%). The comparison with the molecular comparator method showed Positive Percent Agreement of 93.8% (95% CI: 88.7%-96.7%) and Negative Percent Agreement of 99.8% (95% CI: 98.9%-100%). The study demonstrates that non-laboratory personnel in an intended use environment can obtain results with the Accula Strep A test equivalent to results for the comparator methods.
Test Performance near the Assay Cutoff
Three CLIA-waived sites that participated in the prospective clinical study also participated in the Reproducibility Study. Two non-laboratory operators per site tested contrived throat swab samples at and above the assay cutoff, in addition to a negative sample, on five non-consecutive days. Results showed good agreement of observed test results with expected results. For the Low Positive sample (1x LoD), agreement was 98.9% (95% CI: 94.0%-99.8%). For the Moderate Positive sample (2x LoD), agreement was 97.8% (95% CI: 92.2%-99.4%). For the Negative sample, agreement was 97.8% (95% CI: 92.3%-99.4%).
The study demonstrates that non-laboratory personnel in CLIA waived settings can achieve accurate results when testing samples at or near the assay cutoff.
8. Conclusion
The information presented in this Premarket Notification demonstrates that the performance of the Accula Strep A Test is substantially equivalent in intended use, technological characteristics, and performance to the predicate device, thereby supporting 510(k) clearance.