Search Results

The Sofia 2 SARS Antigen+ FlA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 instrument for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic) when testing is started within 6 days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when either: tested at least twice over three days with at least 48 hours between tests; or when tested once, and negative by the Sofia 2 SARS Antigen+ FIA and followed up with a molecular test.

The test does not differentiate between SARS-CoV and SARS-CoV-2.

A neqative test result is presumptive, and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay.

Positive results do not rule out co-infection with bacteria or other viruses and should not be used as the sole basis for treatment or other patient management decisions.

Performanc characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS CoV 2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variant are emerging, performance characteristics may vary.

This test is intended for prescription use only and can be used in Point-of-Care settings.

Sofia 2 SARS Antigen+ FIA Control Swab Set:

The Sofia 2 SARS Antigen+FIA Control Swabs are intended to be used as quality control samples with the Sofia 2 SARS Antigen+ FIA and are representative of positive and negative test samples. These Controls may be used to demonstrate that the reagents and assay procedure perform properly.

The Sofia 2 SARS Antigen+FIA is based upon a lateral flow technology that employs immunofluorescence technology in a sandwich design that is used with Sofia 2 to detect nucleocapsid protein from the SARS-CoV-2 virus in human anterior nasal swab specimens.

The patient sample is placed in the Reagent Tube, during which time the virus particles in the sample are disrupted, exposing internal viral nucleoproteins. After disruption, the sample is dispensed into the Test Cassette sample well. The Test Strip is composed of the following biochemical components dried and immobilized onto the nitrocellulose membrane: 1) sample pad that receives the specimen: 2) a label pad that contains detection fluorescent micro-particles, coated with monoclonal antibodies that are specific for SARS-CoV-2 nucleocapsid antigen; 3) embedded monoclonal antibodies specific for SARS-CoV-2 nucleocapsid antigen to capture the antigen-microparticle complex at the tocation. The sample pad facilitates migration of the sample fluid across the nitrocellulose strip into the absorbent pad (See Figure 4-1 in attachment). The test strip also contains a desiccant that does not participate in the assay but serves as a stabilizing agent during storage.

Sample is applied to in the sample well and migrates through a test strip, then passes through the test and control lines. If SARS-CoV-2 viral antigen is present, they will be bound by the fluorescent microparticles io the label pad reqion, forming an antigen-microparticle complex.

The test line is coated with monoclonal antibodies that are specific to SARS-CoV-2 nucleocapsid antigen and is intended to capture the antigen-microparticle complex. If SARS-CoV-2 viral antigen is not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia 2.

The Sofia 2 SARS Antigen+ FIA employs antibody tagged microparticles dyed with a fluorescent compound, to be detected and read by the Sofia 2 reader instrument. The Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and report the result as either positive, negative, or invalid.

Additionally, the Sofia 2 Antigen+ FIA utilizes a reference line for the Sofia 2 reader (to locate the test line and negative control line) and a procedural control (to assess for sample presence and adequate sample flow). No colored lines will be visible in the test window of the fluorescent assay cassette, thereby preventing visual interpretation of the test results. The operator must use the Sofia 2 analyzer to obtain a test result.

The Sofia 2 SARS Antigen+ FIA Control Swabs are intended to be used as quality control samples representative of positive and neqative test samples, to demonstrate that the reagents are that the assay procedure is correctly perform.

This document is a 510(k) Premarket Notification from the FDA regarding the Sofia 2 SARS Antigen+ FIA. It primarily details the device's indications for use, its description, and a comparison to a legally marketed predicate device.

Here's an analysis of the provided information to address your request:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in terms of performance metrics (e.g., sensitivity, specificity thresholds) for the currently reviewed device (K233688). This submission (K233688) is for a modification to the labeling of an already cleared device (DEN220039). The core performance characteristics were established during the clearance of the predicate device (DEN220039).

The "510(k) Summary" section explicitly states under "Non-Clinical and/or Clinical Tests Summary & Conclusions": "Not applicable." This indicates that no new performance studies were conducted or provided with this specific submission because the design, material, chemical composition, and principle of operation are unchanged from the predicate device. The changes are limited to a minor revision of the intended use statement on labeling.

Therefore, performance data to directly prove acceptance criteria for this specific submission is not provided in this document. The document refers to the established performance characteristics from the predicate device, stating: "Performanc characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS CoV 2 Omicron was the predominant SARS-CoV-2 variant in circulation."

If we were to infer the implied acceptance criteria from the predicate device's clearance, it would be that the device performs "as safe, as effective, and performs as well as the predicate device." However, no specific numerical performance metrics are listed in this document.

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

As stated above, no new performance studies were conducted for this specific submission (K233688). The document explicitly states "Not applicable" for clinical tests. Therefore, there is no sample size for an additional test set, nor new data provenance provided here. Performance characteristics were established during the 2021-2022 SARS-CoV-2 pandemic for the predicate device.

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

Since no new studies were conducted, this information is not provided in the document.

4. Adjudication Method for the Test Set

Since no new studies were conducted, this information is not provided in the document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and Effect Size

No MRMC study is mentioned or implied for this submission. The device is an in vitro diagnostic (IVD) rapid antigen test read by an instrument (Sofia 2 analyzer), not typically involving multiple human readers for interpretation in the same way an imaging AI would. The Sofia 2 analyzer automatically scans, collects, analyzes fluorescence data, and reports results as positive, negative, or invalid, preventing visual interpretation.

6. If a Standalone (Algorithm Only Without Human-in-the-Loop Performance) Was Done

Yes, this device inherently operates in a "standalone" fashion as an algorithm-only device in terms of result interpretation. The Sofia 2 analyzer processes the test strip by detecting and reading fluorescent microparticles, analyzing the fluorescence data, and automatically reporting the result without human interpretation of the signal on the test strip. The human interaction is limited to collecting the sample, performing the assay steps, and reading the final result from the instrument.

7. The Type of Ground Truth Used

The document indicates the test is intended as an aid in diagnosis, and negative test results are presumptive and "recommended these results be confirmed by a molecular SARS-CoV-2 assay." This strongly implies that the ground truth for establishing the device's performance characteristics (for the predicate device) would have been molecular SARS-CoV-2 assays (e.g., RT-PCR), which are considered the gold standard for SARS-CoV-2 detection.

8. The Sample Size for the Training Set

No information about a training set or its sample size is provided in this document, as no new performance studies were conducted for this submission. The initial development and training (if applicable, for the Sofia 2 analyzer's signal processing algorithm) would have occurred prior to the predicate device's clearance.

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

Since no information on a training set is provided, the method for establishing its ground truth is also not mentioned. It is likely that for the predicate device, if machine learning was involved in interpreting the fluorescent signal, the training data's ground truth would have been established against molecular SARS-CoV-2 assays, similar to the test set ground truth.

Ask a specific question about this device

The Sofia 2 SARS Antigen+ FIA is a lateral flow immunofluorescent sandwich assay that is used with the Sofia 2 instrument for the rapid, qualitative detection of SARS-CoV-2 nucleocapsid protein antigens directly in anterior nasal swab specimens from individuals with signs and symptoms of upper respiratory infection (i.e., symptomatic) when testing is started within 6 days of symptom onset. The test is intended for use as an aid in the diagnosis of SARS-CoV-2 infections (COVID-19) in symptomatic individuals when tested at least twice over three days with at least 48 hours between tests.

The test does not differentiate between SARS-CoV and SARS-CoV-2.

A negative test result is presumptive, and it is recommended these results be confirmed by a molecular SARS-CoV-2 assay. Negative results do not preclude SARS-CoV-2 infections and should not be used as the sole basis for treatment or other patient management decisions.

Positive results do not rule out co-infection with other respiratory pathogens.

Performance characteristics for SARS-CoV-2 were established during the 2021-2022 SARS-CoV-2 pandemic when SARS-CoV-2 Omicron was the predominant SARS-CoV-2 variant in circulation. When other SARS-CoV-2 virus variant are emerging, performance characteristics mav vary.

This test is intended for prescription use only and can be used in Point-of-Care settings.

The Sofia 2 SARS Antigen+FIA is based upon a lateral flow technology that employs immunofluorescence technology in a sandwich design that is used with Sofia 2 to detect nucleocapsid protein from the SARS-CoV-2 virus in human anterior nasal swab specimens.

The patient sample is placed in the Reagent Tube, during which time the virus particles in the sample are disrupted, exposing internal viral nucleoproteins. After disruption, the sample is dispensed into the Test Cassette sample well. The Test strip is composed of the following biochemical components dried and immobilized onto the nitrocellulose membrane: 1) sample pad that receives the specimen; 2) a label pad that contains detection fluorescent micro-particles, coated with monoclonal antibodies that are specific for SARS-CoV-2 nucleocapsid antigen: 3) embedded monoclonal antibodies specific for SARS-CoV-2 nucleocapsid antigen to capture the antigen-microparticle complex at the test line location. The sample pad facilitates migration of the sample fluid across the nitrocellulose strip into the absorbent pad. The test strip also contains a desiccant that does not participate in the assay but serves as a stabilizing agent during storage.

Sample is applied to in the sample well and migrates through a test strip, then passes through the test and control lines. If SARS-CoV-2 viral antigen is present, they will be bound by the fluorescent microparticles in the label pad region, forming an antigen-microparticle complex. The test line is coated with monoclonal antibodies that are specific to SARS-CoV-2 nucleocapsid antigen and is intended to capture the antigen-microparticle complex. If SARS-CoV-2 viral antigen is not present, the fluorescent microparticles will not be trapped by the capture antibodies nor detected by Sofia 2.

The Sofia 2 SARS Antigen+FIA employs antibody-tagged microparticles dyed with a fluorescent compound, to be detected and read by the Sofia 2 reader instrument. The Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and then calculate and report the result as either positive, negative, or invalid.

Additionally, the Sofia 2 Antigen+ FIA utilizes a reference line for the Sofia 2 reader (to locate the test line and negative control line) and a procedural control (to assess for sample presence and adequate sample flow). No colored lines will be visible in the test window of the fluorescent assay cassette, thereby preventing visual interpretation of the test results. The operator must use the Sofia 2 analyzer to obtain a test result.

The Sofia SARS Antigen FIA Control Swabs are intended to be used as quality control samples representative of positive and negative test samples, to demonstrate that the reagents are functional and that the assay procedure is correctly perform.

Acceptance Criteria and Device Performance for Sofia 2 SARS Antigen+ FIA

The Sofia 2 SARS Antigen+ FIA is a qualitative lateral flow immunoassay designed for rapid detection of SARS-CoV-2 nucleocapsid protein antigens in anterior nasal swab specimens. The following details outline the acceptance criteria and the studies conducted to prove the device meets these criteria.

1. Acceptance Criteria and Reported Device Performance

• Low Positive samples (1 x LoD) should demonstrate an expected positive agreement (e.g., >95%).
• Moderate Positive samples (3 x LoD) should demonstrate high expected positive agreement (e.g., >95%).
• Zero invalid test results throughout the study (or very low %). | - Negative samples: 99.4% expected negative agreement (159/160)
• High Negative samples (0.04 x LoD): 95.0% expected negative agreement (152/160)
• Low Positive samples (1 x LoD): 98.1% expected positive agreement (157/160)
• Moderate Positive samples (3 x LoD): 99.4% expected positive agreement (159/160)
• 0 invalid test results (out of 640 replicates) |
  | Reproducibility (Inter-site)| - High Negative samples (0.04 x LoD) should demonstrate reasonable negative agreement across sites and operators.
• Low Positive samples (1 x LoD) should demonstrate high positive agreement across sites and operators.
• Moderate Positive samples (3 x LoD) should demonstrate high positive agreement across sites and operators.
• Zero invalid test results throughout the study (or very low %). | - Negative samples: 100.0% expected negative agreement (120/120)
• High Negative samples (0.04 x LoD): 55.0% expected negative agreement (66/120) - Note: This is lower than typical ideal scenarios, but likely deemed acceptable given the nature of a "high negative" near the detection limit.
• Low Positive samples (1 x LoD): 99.2% expected positive agreement (119/120)
• Moderate Positive samples (3 x LoD): 99.2% expected positive agreement (119/120)
• 0 invalid test results (out of 480 samples) |
  | Analytical Specificity (Cross-reactivity & Interference) | - No cross-reactivity with a defined panel of common respiratory pathogens (bacteria, viruses, fungus) at specified concentrations.
• No interference from common endogenous and exogenous substances found in nasal specimens at specified concentrations.
• 100% negative agreement in the absence of SARS-CoV-2.
• 100% positive agreement in the presence of SARS-CoV-2. | - All 28 organisms/viruses tested showed 100.0% negative agreement (5/5 replicates) for cross-reactivity and 100.0% positive agreement (5/5 replicates) for interference.
• All 13 endogenous/exogenous substances tested showed 100.0% positive agreement (5/5 replicates) and 100.0% negative agreement (5/5 replicates). |
  | Limit of Detection (LoD) | - The device should consistently detect SARS-CoV-2 at a specific low concentration (LoD) with high positivity (e.g., 95% or 100%) in confirmatory studies.
• Negative clinical matrix should consistently result in negative readings. | - Confirmed LoD: 1.44 x 10^4 TCID50/mL.
• At confirmed LoD: 100% positivity (20/20 replicates) across both tested lots.
• NCM (Negative Clinical Matrix): 0% positivity (0/5 replicates). |
  | High-dose Hook Effect | - No false negative results should be observed at very high concentrations of SARS-CoV-2. | - All spiked samples from 10X LoD up to a maximum virus concentration (unspecified highest concentration) were 100% positive (5/5 replicates each). No hook effect observed. |
  | Inclusivity | - The device should detect various clinically relevant SARS-CoV-2 strains/variants (e.g., Delta, Omicron BA.1, BA.2) with high positivity. | - Heat-inactivated SARS-CoV-2 (isolate Italy-INMI1): 100.0% positivity (5/5 replicates) at 2.43E+05 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Delta B.1.617.2): 100.0% positivity (5/5 replicates) at 1.00E+04 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Omicron BA.1): 100.0% positivity (5/5 replicates) at 2.36E+04 TCID50/mL.
• Heat-inactivated SARS-CoV-2 (Omicron BA.2): 100.0% positivity (5/5 replicates) at 8.22E+03 TCID50/mL. |
  | Clinical Performance | - Demonstrate acceptable Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to a highly sensitive RT-PCR comparator, within defined confidence intervals. The specific thresholds would be pre-defined by regulatory guidelines (e.g., FDA's EUA templates or De Novo requirements for diagnostics). While not explicitly stated as a numerical criterion, the presented results suggest approval, implying the performance met the agency's expectations for a Class II device. | - PPA (Clinical Sensitivity): 89.0% (97/109; 95% CI: 81.7% - 93.6%)
• NPA (Clinical Specificity): 99.6% (470/472; 95% CI: 98.5% - 99.9%) |

2. Sample Size and Data Provenance

Test Set Sample Sizes:

• Precision/Repeatability: 640 replicates (160 replicates per analyte level/kit lot for 4 levels x 2 lots).
• Reproducibility: 480 replicates (120 replicates per analyte level x 4 levels).
• Analytical Specificity (Cross-reactivity & Interference):
  • Cross-reactivity: 5 replicates per organism/virus (28 tested) = 140 replicates for negative agreement. 5 replicates per organism/virus + 2xLoD SARS-CoV-2 (25 tested, some "Not Tested" for interference) = 125 positive replicates for interference.
  • Interfering Substances: 5 replicates per substance (13 tested) for both positive and negative agreement = 130 replicates.
• Limit of Detection (LoD):
  • Preliminary LoD: 5 replicates per dilution (6 dilutions) x 2 lots = 60 replicates.
  • Confirmatory LoD: 20 replicates at preliminary LoD concentration for each of 2 lots = 40 replicates.
• High-dose Hook Effect: 5 replicates per concentration (4 concentrations) = 20 replicates.
• Inclusivity: 5 replicates per strain/variant (4 tested) = 20 replicates.
• Clinical Study (Accuracy): 581 evaluable subjects.

Data Provenance:

• Country of Origin: Not explicitly stated for analytical studies, but given the FDA review, it is implicitly expected to be a regulated environment. For the clinical study, it was a multi-center study in a "CLIA-waived" setting, which refers to US clinical laboratories.
• Retrospective or Prospective:
  • Analytical Performance Studies (Precision, Reproducibility, Analytical Specificity, LoD, Hook Effect, Inclusivity): These are typically prospective, lab-controlled experiments with contrived samples designed specifically for the study.
  • Clinical Studies: "multi-center, prospective study conducted from August 2021 to November 2022."

3. Number of Experts and Qualifications for Ground Truth

• Analytical Studies: For analytical studies (Precision, Reproducibility, LoD, Cross-reactivity, Interference, Hook Effect, Inclusivity), the ground truth is established by the known concentrations of spiked analytes (e.g., heat-inactivated SARS-CoV-2, other microbes, interfering substances). This does not involve human experts establishing ground truth beyond standard laboratory technician expertise in preparing and measuring these concentrations.
• Clinical Study: The ground truth for the clinical study was established by an "highly sensitive Emergency Use Authorization (EUA) authorized RT-PCR comparator assay." This is a laboratory-based molecular test, often considered the gold standard for SARS-CoV-2 detection, and does not involve human experts in the conventional sense of image adjudication or clinical consensus. The RT-PCR results themselves serve as the ground truth.

4. Adjudication Method for the Test Set

• Analytical Studies: Not applicable. Ground truth is determined by precise laboratory methods and known concentrations.
• Clinical Study: Not applicable. The comparator RT-PCR assay is a definitive laboratory test; there is no mention of a human-based adjudication process for the RT-PCR results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

• No, a MRMC comparative effectiveness study was not done.
• This device is an automated, instrument-read diagnostic assay (Sofia 2 SARS Antigen+ FIA). The results are generated by the instrument (Sofia 2 Analyzer) based on fluorescent signals and programmed algorithms, not by human interpretation of images or signals. Therefore, a human-in-the-loop study to assess how human readers improve with AI assistance is not relevant to this type of device. The study evaluates the standalone performance of the device compared to a reference method (RT-PCR).

6. Standalone Performance (Algorithm Only without Human-in-the-Loop)

• Yes, the performance data presented for the Sofia 2 SARS Antigen+ FIA are standalone performance, i.e., algorithm only without human-in-the-loop performance.
• The "Sofia 2 analyzers automatically scan/image the test strip, collect and analyze the fluorescence data, and then calculate and report the result as either positive, negative, or invalid." The operator only uses the analyzer to obtain the result; they do not visually interpret the test or make diagnostic decisions based on human observation of the test strip.

7. Type of Ground Truth Used

• Analytical Studies: The ground truth was based on known concentrations of heat-inactivated SARS-CoV-2 or other microorganisms/substances in controlled laboratory settings. This is a form of "spiked sample" ground truth.
• Clinical Study: The ground truth was established using an "highly sensitive Emergency Use Authorization (EUA) authorized RT-PCR comparator assay." This is a laboratory-based molecular diagnostic method, considered the gold standard for detecting SARS-CoV-2 RNA.

8. Sample Size for the Training Set

• No information is provided about a specific "training set" related to an AI/algorithm development in the context of machine learning. The algorithms referenced ("method-specific algorithms," "software specific cutoff," "specific algorithms") for the Sofia 2 analyzer relate to processing fluorescent signals and determining thresholds for positive/negative results, which are typically derived from extensive analytical characterization and optimization using laboratory-controlled samples, rather than a distinct "training set" in the machine learning sense often seen with image-based AI. The document implies these algorithms are developed and refined through the analytical performance studies (such as LoD, linearity, etc.) using various known concentrations.

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

• As mentioned above, a traditional "training set" as understood in a machine learning context is not explicitly described. The "ground truth" for establishing the device's operational algorithms and cut-offs would have been determined through laboratory experiments with precisely known concentrations of analytes. This process involves:
  • Identifying the Limit of Detection (LoD).
  • Evaluating signal response across a range of concentrations.
  • Using reference lots and known values during development to establish parameters for calculations and cut-offs.
  • "Final cut-off values were further validated as part of the analytical and clinical studies." This suggests an iterative process of development, testing, and validation against a known ground truth (spiked samples for analytical studies, RT-PCR for clinical).

Ask a specific question about this device