Sofia 2 Lyme FIA, Sofia Lyme Control Set

K173496 · Quidel Corporation · LSR · Aug 30, 2018 · Microbiology

Device Facts

• Record ID: K173496
• Device Name: Sofia 2 Lyme FIA, Sofia Lyme Control Set
• Applicant: Quidel Corporation
• Product Code: LSR · Microbiology
• Decision Date: Aug 30, 2018
• Decision: SESE
• Submission Type: Dual Track
• Regulation: 21 CFR 866.3830
• Device Class: Class 2

Intended Use

The Sofia 2 Lyme FIA employs immunofluorescence for the rapid differential detection of human IgM and IgG antibodies to Borrelia burgdorferi from finger-stick whole blood specimens from patients suspected of B. burgdorferi infection of at least 2 weeks' duration. The Sofia 2 Lyme FIA is intended for use as an aid in diagnosis of Lyme disease. A negative result does not preclude infection with B. burgdorferi. Positive results must be confirmed by testing with a corresponding second-tier B. burgdorferi Western blot assay. Test results are to be used in conjunction with information obtained from the patient's clinical evaluation and other diagnostic procedures. The assay is to be performed on the Sofia 2 instrument. Professional guidelines should be consulted regarding testing and treatment for Lyme disease when acute B. burgdorferi infection is suspected. The Sofia Lyme Control Set is intended for use as assayed quality control materials to verify the performance of the Sofia Lyme FIA and Sofia 2 Lyme FIA test system.

Device Story

Sofia 2 Lyme FIA is an immunofluorescence-based lateral flow assay for qualitative detection of IgM and IgG antibodies to Borrelia burgdorferi. Input: finger-stick whole blood collected via capillary tube (whole blood separator). Process: blood flows through sample pad coated with rabbit anti-human RBC antibodies; diluted sample added to test cassette; cassette inserted into Sofia 2 instrument. Instrument performs automated analysis of test strip at 3, 5, 8, 10, and 15 minutes. Output: qualitative IgM and IgG results displayed on instrument screen or printed. Used in clinical settings by healthcare professionals. Benefits: rapid differential detection, early read times via 'Walk Away' mode, and automated interpretation to aid Lyme disease diagnosis.

Clinical Evidence

Clinical performance evaluated via prospective study of 321 subjects and CDC reference panel. Sensitivity for IgM (all categories) was 64.2% (95% CI: 54.2-73.1%) and for IgG was 80.0% (95% CI: 70.8-86.9%). Specificity study (n=200) showed 89.5% for IgM and 96.5% for IgG. Matrix equivalency confirmed finger-stick whole blood is equivalent to serum/plasma. Comparison to predicate showed comparable PPA/NPA. No interference or cross-reactivity observed with tested substances or disease states.

Technological Characteristics

Immunofluorescence-based lateral flow assay. Uses recombinant proteins and synthetic peptides of B. burgdorferi. Detection via polystyrene microparticles dyed with Europium chelate. Analyte: human IgM and IgG antibodies. Platform: Sofia 2 instrument (automated reader). Connectivity: screen/printer output. Storage: room temperature (15-30°C).

Indications for Use

Indicated for patients suspected of Borrelia burgdorferi infection of at least 2 weeks' duration. Used as an aid in the diagnosis of Lyme disease. Positive results require confirmation via second-tier Western blot assay.

Regulatory Classification

Identification

Treponema pallidum treponemal test reagents are devices that consist of the antigens, antisera and all control reagents (standardized reagents with which test results are compared) which are derived from treponemal sources and that are used in the fluorescent treponemal antibody absorption test (FTA-ABS), the Treponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies to Treponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genus Treponema and provides epidemiological information on syphilis.

Predicate Devices

• Vidas Lyme IgM (K122979)
• Vidas Lyme IgG (K122986)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image features the logo for QuidelOrtho Corporation. The logo consists of a square shape with rounded corners, filled with a gradient of colors resembling a rainbow. The bottom right corner of the square is a darker shade of blue. Below the square is the word "QUIDEL" in a modern, sans-serif font.

### ട്. 510(K) SUMMARY

#### 5.1. Submitter

Quidel Corporation 12544 High Bluff Drive, Suite 200 San Diego, California 92130 Telephone: [phone] Fax: [phone]

#### Submission Contact 5.2.

Jennifer S. Rial

#### 5.3. Date Prepared

November 10, 2017

#### 5.4. Proprietary and Established Names

Sofia 2 Lyme FIA Sofia Lyme Control Set

#### 5.5. Common Name

Lyme IgG and Lyme IgM test and assayed external controls

### 5.6. Regulatory Information

| Product Code | Classification | Regulatory Section | Panel |
|--------------|----------------|--------------------|----------------------------------------|
| LSR | II | 21 CFR 866.3830 | Immunology and<br>Microbiology Devices |

#### 5.7. Predicate Device

Vidas Lyme IgG and Vidas Lyme IgM

### 5.8. Device Description

The Sofia 2 Lyme FIA is an immunofluorescence-based, lateral flow assay for detection of IgM and/or IgG antibodies to Borrelia burgdorferi in patient specimens. Reagents for the assay are ready-to-use and provided in the kit.

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Image /page/1/Picture/0 description: The image features the logo of Quidel. The logo consists of a square shape divided into two sections. The larger section is a gradient of colors, transitioning from yellow to green to blue to red. The smaller section is a solid dark blue. Below the square is the word "QUIDEL" in a modern, sans-serif font, with a small trademark symbol next to the "L".

The assay uses a bidirectional test strip format to detect both IgM and IgG antibodies to B. burgdorferi. One side of the test strip detects IgM antibodies to B. burgdorferi and the other side of the test strip detects IgG antibodies to B. burgdorferi.

To perform the test, the patient finger-stick whole blood specimen is obtained with the provided Capillary Tube (a.k.a. whole blood separator device). The Capillary Tube stands or is held vertically to allow the blood to drain. This device separates the red blood cells from the whole blood specimen using a gravimetric flow through a sample pad coated with rabbit anti-human red blood cell (RBC) antibodies. The user dispenses all of the Reagent Solution into the Reagent Tube and inserts the Capillary Tube into the Reagent Tube and shakes the tube vigorously. Two drops of diluted sample are dispensed into the round sample well located near the center of the Test Cassette.

The Test Cassette is loaded into Sofia 2 in either the READ NOW Mode or WALK AWAY Mode. In READ NOW Mode, the user allows the cassette to develop on the countertop for 15 minutes. In WALK AWAY Mode, the user immediately after adding the specimen to the cassette, the cassette is inserted into Sofia 2. Sofia 2 will analyze the test strip at 3, 5, 8, 10, and 15 minutes until both IgM and IgG positive results are received. This feature allows for earlier read times.

Each Sofia 2 Lyme FIA kit will contain one Positive and one Negative Control—each provided in separate dropper bottles. The external controls will be provided separately as well in a Sofia Lyme Control Set. The Positive and Negative QC controls are formulated with patient Lyme IgM and IgG positive serum that are diluted into 1X PBS and 0.3% Microcide is added to the solution as an antimicrobial. The External Controls will be tested by adding 2 drops to the test cassette.

### 5.9. Intended Use

Intended Use Statements for Sofia 2 Lyme FIA and Sofia Lyme Control Set:

## Sofia 2 Lyme FIA:

The Sofia 2 Lyme FIA employs immunofluorescence for the rapid differential detection of human IgM and IgG antibodies to Borrelia burgdorferi from finger-stick whole blood specimens from patients suspected of B. burgdorferi infection of at least 2 weeks' duration. The Sofia 2 Lyme FIA is intended for use as an aid in diagnosis of Lyme disease. A negative result does not preclude infection with B. burgdorferi. Positive results must be confirmed by testing with a corresponding second-tier B. burgdorferi Western blot assay. Test results are to be used in conjunction with information obtained from the patient's clinical evaluation and other diagnostic procedures. The assay is to be performed on the Sofia 2 instrument. Professional guidelines should be consulted regarding testing and treatment for Lyme disease when acute B. burgdorferi infection is suspected.

## Sofia Lyme Control Set:

The Sofia Lyme Control Set is intended for use as assayed quality control materials to verify the performance of the Sofia Lyme FIA and Sofia 2 Lyme FIA test system.

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Image /page/2/Picture/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square with rounded corners, filled with a gradient of colors from yellow to red to blue. Below the square is the word "QUIDEL" in a simple, sans-serif font. The logo is clean and modern, with the colorful square representing the company's diverse range of products and services.

### Substantial Equivalence Information: 5.10.

- 1. Predicate Device Name: Vidas Lyme IgM and Vidas Lyme IgG
## 2. Predicate 510(k) Numbers: K122979 and K122986 Comparison with Predicate

| Item | Proposed Device | Predicate IgM Device | Predicate IgG Device |
|--------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Features | Sofia 2 Lyme FIA with<br>Sofia | Biomerieux Vidas Lyme<br>IgM | Biomerieux Vidas Lyme<br>IgG |
| Intended Use | Sofia 2 Lyme FIA:<br>The Sofia 2 Lyme FIA<br>employs<br>immunofluorescence for<br>the rapid differential<br>detection of human IgM<br>and IgG antibodies to<br>Borrelia burgdorferi<br>from finger-stick whole<br>blood specimens from<br>patients suspected of B.<br>burgdorferi infection of<br>at least 2 weeks'<br>duration. The Sofia 2<br>Lyme FIA is intended<br>for use as an aid in<br>diagnosis of Lyme<br>disease. A negative<br>result does not preclude<br>infection with B.<br>burgdorferi. Positive<br>results must be<br>confirmed by testing<br>with a corresponding<br>second-tier B.<br>burgdorferi Western<br>blot assay. Test results<br>are to be used in<br>conjunction with<br>information obtained<br>from the patient's<br>clinical evaluation and<br>other diagnostic<br>procedures. The assay is<br>to be performed on the<br>Sofia 2 instrument.<br>Professional guidelines<br>should be consulted<br>regarding testing and | The VIDAS Lyme IgM<br>assay is an automated<br>qualitative enzyme<br>immunoassay intended for<br>use on the instruments of the<br>VIDAS family in the<br>presumptive detection of<br>human IgM antibodies to<br>Borrelia burdorferi in<br>human serum or plasma. It<br>should be used to test<br>patients with a history<br>and/or symptoms of<br>infection with B.<br>burgdorferi. All VIDAS<br>Lyme IgG positive<br>specimens should be further<br>tested with a Western Blot<br>IgG assay to obtain<br>supportive evidence of<br>infection with B.<br>burgdorferi. | The VIDAS Lyme IgG<br>assay is an automated<br>qualitative enzyme<br>immunoassay intended for<br>use on the instruments of the<br>VIDAS family in the<br>presumptive detection of<br>human IgG antibodies to<br>Borrelia burdorferi in<br>human serum or plasma. It<br>should be used to test<br>patients with a history<br>and/or symptoms of<br>infection with B.<br>burgdorferi. All VIDAS<br>Lyme IgG positive<br>specimens should be further<br>tested with a Western Blot<br>IgG assay to obtain<br>supportive evidence of<br>infection with B.<br>burgdorferi. |
| Item | Proposed Device | Predicate IgM Device | Predicate IgG Device |
| Features | Sofia 2 Lyme FIA with<br>Sofia | Biomerieux Vidas Lyme<br>IgM | Biomerieux Vidas Lyme<br>IgG |
| Features | treatment for Lyme<br>disease when acute B.<br>burgdorferi infection is<br>suspected.<br><br>Sofia Lyme Control Set:<br>The Sofia Lyme Control<br>Set is intended for use as<br>assayed quality control<br>materials to verify the<br>performance of the Sofia<br>Lyme FIA and Sofia 2<br>Lyme FIA test system. | | |
| Instrument | Sofia 2 | VIDAS and miniVIDAS | VIDAS and miniVIDAS |
| Analyte | Human IgM and IgG<br>antibodies against B.<br>burgdorferi proteins | Human IgM antibodies<br>against B. burgdorferi<br>proteins | Human IgG antibodies<br>against B. burgdorferi<br>proteins |
| Automated<br>Analysis | Yes | Yes | Yes |
| Read Results | Read results on instrument<br>screen or print with<br>optional printer | Result report is printed | Result report is printed |
| Read Result<br>Time | Potential for early read in<br>Walk-Away Mode. Sofia<br>2 will image cassette at 3,<br>5, 8, 10, and 15 minutes<br>until both IgM and IgG<br>positive results are<br>received. | 27 minutes | 27 minutes |
| Specimen<br>Types | Finger-stick whole blood | Serum and plasma | Serum and plasma |
| Qualitative | Yes | Yes | Yes |
| Test Principle | Immunofluorescence<br>Device | Immunofluorescence Device | Immunofluorescence Device |
| Format | Lateral-flow Bi-directional<br>Test Cassette | Enzyme-linked fluorescent<br>assay (ELFA) | Enzyme-linked fluorescent<br>assay (ELFA) |
| Antibodies<br>Used | Monoclonal anti-human<br>IgG and polyclonal anti-<br>human IgM | Anti-human IgM antibodies | Anti-human IgG antibodies |
| Item | Proposed Device | Predicate IgM Device | Predicate IgG Device |
| Features | Sofia 2 Lyme FIA with<br>Sofia | Biomerieux Vidas Lyme<br>IgM | Biomerieux Vidas Lyme<br>IgG |
| Antigens Used | Recombinant Proteins and<br>synthetic peptides of B.<br>burgdorferi | Recombinant proteins of B.<br>burgdorferi | Recombinant proteins of B.<br>burgdorferi |
| Detection<br>Method | Polystyrene microparticles<br>dyed with Europium<br>chelate | Alkaline phosphatase/4-<br>MUP | Alkaline phosphatase/4-<br>MUP |
| Storage | Room Temperature (15-<br>30°C) | 2-8°C | 2-8°C |
| Running<br>Buffer<br>Solution | One pre-filled vial<br>containing PBS | Sample diluent and wash<br>buffer | Sample diluent and wash<br>buffer |
| Quality<br>Control<br>Features | Built-in features include:<br>• Built-in procedural<br>control zone scanned<br>by the analyzer to<br>determine whether<br>adequate flow<br>occurred on the IgG<br>side of the assay.<br>• Built-in reference<br>control line scanned<br>by the analyzer to<br>determine whether<br>adequate flow<br>occurred on the IgM<br>side of the assay.<br>• Analyzer prevents<br>used or expired<br>cartridge from being<br>read by the reader<br>• Cassette must be<br>properly inserted | • One positive and one<br>negative control are<br>included and must be<br>tested after opening a<br>new kit to monitor<br>reagent failure. | • One positive and one<br>negative control are<br>included and must be<br>tested after opening a<br>new kit to monitor<br>reagent failure. |

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Image /page/3/Picture/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square with rounded corners, divided into four sections. The top and left sections are filled with a gradient of colors, including yellow, orange, red, and green. The bottom right section is filled with shades of blue and purple. Below the square is the word "QUIDEL" in a sans-serif font.

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Image /page/4/Picture/0 description: The image features the logo for Quidel. The logo consists of a square with rounded corners, filled with a gradient of colors resembling a mosaic. The colors transition from yellow and green in the upper-left corner to red in the upper-right, and blue in the lower-right. Below the square is the word "QUIDEL" in a simple, sans-serif font.

### 5.11. Performance Data

Studies were undertaken to document the performance characteristics of Sofia 2 Lyme FIA and the Sofia Lyme Control Set, as well as to compare the performance between Sofia 2 Lyme and the Vidas IgG and IgM tests. The studies included the following:

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## ANALYTICAL STUDIES

- Precision a.
The precision of the Sofia Lyme FIA with Sofia 2 was evaluated at one Quidel site utilizing 2 operators and 2 Sofia 2 instruments. Contrived samples were prepared at levels that ranged from negative to moderate positive for both IgM and IgG. Each sample was tested by 2 operators in duplicate with a total of 24 different runs (2 runs per day over a total of 12 days) for a total of 96 times over the course of the study.

| IgM or IgG<br>Sample | IgM Positive | | IgM % Positivity | | IgG Positive | IgG %<br>Positivity |
|---------------------------------|--------------|-------|------------------|-------|--------------|---------------------|
| | Run 1 | Run 2 | Total (n=96) | Run 1 | Run 2 | Total (n=96) |
| Negative | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| High<br>Negative (C5) | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| Low Positive<br>(C95) | 48/48 | 48/48 | 100% | 48/48 | 46/48 | 100% |
| Moderate<br>Positive (2-<br>3X) | 48/48 | 48/48 | 100% | 48/48 | 48/48 | 100% |

Sofia Lyme FIA with Sofia 2 Precision – Within Run

| | Sofia Lyme FIA with Sofia 2 Precision - Between Operator | |
|--|----------------------------------------------------------|--|
|--|----------------------------------------------------------|--|

| IgM or IgG<br>Sample | IgM Positive | | IgM %<br>Positivity<br>Total (n=96) | IgG Positive | | IgG %<br>Positivity<br>Total<br>(n=96) |
|---------------------------------|--------------|------------|-------------------------------------|--------------|------------|----------------------------------------|
| | Operator 1 | Operator 2 | | Operator 1 | Operator 2 | |
| Negative | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| High<br>Negative<br>(C5) | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| Low Positive<br>(C95) | 48/48 | 48/48 | 100% | 48/48 | 48/48 | 100% |
| Moderate<br>Positive (2-<br>3X) | 48/48 | 48/48 | 100% | 48/48 | 48/48 | 100% |

## b. Reproducibility

This study demonstrated intra- and inter-laboratory reproducibility with a panel of test samples at various concentrations of IgM and IgG antibodies to B. burgdorferi. The operators and laboratories obtained accurate results with the Sofia Lyme FIA on Sofia 2.

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Image /page/6/Picture/0 description: The image shows the Quidel logo. The logo features a square shape with a gradient of colors, including red, orange, yellow, green, blue, and purple. The word "QUIDEL" is written in a sans-serif font below the square.

| Site | IgM<br>Negative<br>(C₀) | IgM High<br>Negative<br>(C₅) | IgM Low<br>Positive<br>(C₉₅) | IgM<br>Moderate<br>Positive<br>(2-3X<br>LOD) | IgG<br>Negative<br>(C₀) | IgG High<br>Negative<br>(C₅) | IgG Low<br>Positive<br>(C₉₅) | IgG<br>Moderate<br>Positive<br>(2-3X<br>LOD) |
|------------------------------------|-------------------------|------------------------------|------------------------------|----------------------------------------------|-------------------------|------------------------------|------------------------------|----------------------------------------------|
| 1 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 |
| 2 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 | 30/30 |
| 3 | 30/30 | 30/30 | 27/30 | 28/30 | 30/30 | 30/30 | 25/30 | 30/30 |
| Total | 90/90 | 90/90 | 87/90 | 88/90 | 90/90 | 90/90 | 85/90 | 90/90 |
| % Overall<br>Agreement<br>(95% CI) | 100%<br>(95.1-<br>100%) | 100%<br>(95.1-<br>100%) | 96.7%<br>(90.3-<br>99.3%) | 97.8%<br>(91.8-<br>99.9%) | 100%<br>(95.1-<br>100%) | 100%<br>(95.1-<br>100%) | 94.4%<br>(87.3-<br>97.9%) | 100%<br>(95.1-<br>100%) |

### Sofia Lyme FIA with Sofia 2 Reproducibility Study Inter-Laboratory Agreement

#### Assay Cutoff C.

An Assay Cutoff Study was performed to determine and confirm the two separate assay cutoff limits for the Sofia 2 Lyme FIA. One cutoff limit was established for Lyme IgG and one cutoff limit was established for Lyme IgM. The general procedure was to test matched finger-stick whole blood, serum and plasma samples with the aim of setting the whole blood assay cutoff so that the clinical performance, percent positive agreement (PPA) and the percent negative agreement (NPA), of the whole blood assay is statistically similar to the FDA cleared Sofia Lyme FIA serum and plasma assay. After the cutoffs were established, the values were validated as part of the clinical trial as well as other analytical studies

## d. Interference Substances

A study was performed to assess potential interfering substances with the Sofia Lyme FIA with Sofia. There was no interference or cross-reactivity results when tested with the Sofia Lyme FIA.

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Image /page/7/Picture/0 description: The image features the logo for Quidel. The logo consists of a square shape with a smaller square cut out of the lower right corner. The larger square is filled with a mosaic of colors, including red, orange, yellow, green, blue, and purple. Below the square is the word "QUIDEL" in a simple, sans-serif font.

| ia Lyme FIA with Sofia Interfering Substances | | | | |
|-----------------------------------------------|-----------------------|--|--|--|
| Interfering Substance | Concentrations Tested | | | |
| Bilirubin | 15 mg/dL | | | |
| Hemoglobin | 20 g/dL | | | |
| Lipids | 750 mg/dL | | | |
| Albumin | 5.0 g/dL | | | |
| Acetylsalicylic Acid | 3.62 mmol/L | | | |
| Amoxicillin | 206 umol/L | | | |
| Azithromycin | 15.3 umol/L | | | |
| Ceftriaxone | 1460 umol/L | | | |
| Cefuroxime Axetil | 1416 umol/L | | | |
| Doxycycline Hyclate | 67.5 umol/L | | | |
| Erythromycin | 81.6 umol/L | | | |
| Ibuprofen | 2425 umol/L | | | |
| Minocycline | 10.33 umol/L | | | |
| Penicillin G | 33.67 umol/L | | | |
| Penicillin Phenoxymethyl | 14.27 umol/L | | | |
| Prednisolone | 8.31 umol/L | | | |
| Tetracyclines | 34 umol/L | | | |

#### Sofia L .............................................................................................................................................................................. Class

### Cross Reactivity e.

The cross-reactivity of the Sofia Lyme FIA with Sofia was evaluated with 17 disease state sample types that have the potential to interfere.

| Disease State Diagnosis | # of Samples | IgM Positive Results | IgG Positive Results |
|------------------------------|--------------|----------------------|----------------------|
| Anti-Nuclear Antibodies | 10 | 4/10 | 1/10 |
| Babesiosis | 12 | 3/12 | 4/12 |
| Chronic Fatigue Syndrome | 12 | 2/12 | 2/12 |
| Cytomegalovirus | 11 | 2/11 | 1/11 |
| Epstein Barr Virus | 10 | 4/10 | 0/10 |
| Fibromyalgia | 10 | 1/10 | 0/10 |
| H. pylori | 10 | 4/10 | 0/10 |
| HIV | 11 | 2/11 | 0/11 |
| Influenza | 11 | 0/11 | 0/11 |
| Leptospirosis | 6 | 1/6 | 2/6 |
| Lupus | 20 | 8/20 | 4/20 |
| Multiple Sclerosis | 10 | 1/10 | 1/10 |
| Parvovirus B19 | 15 | 4/15 | 1/15 |
| Rheumatoid Factor | 10 | 0/10 | 0/10 |
| Rickettsia | 3 | 0/3 | 0/3 |
| Rocky Mountain Spotted Fever | 10 | 0/10 | 0/10 |
| Syphilis | 28 | 8/28 | 4/28 |

Sofia Lyme FIA with Sofia Cross-Reactivity

Note: The results obtained with Leptospirosis (6) and Rickettsia (3) samples may not be conclusive due to low number of samples tested. See also the Limitations section.

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Image /page/8/Picture/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square shape with rounded corners, filled with a gradient of colors ranging from green to red. A smaller, blue square is positioned in the lower right corner of the larger square. Below the square is the word "QUIDEL" in a sans-serif font.

## CLINICAL STUDIES

### f. Matrix Equivalency

The finger-stick whole blood matrix on the Sofia 2 Lyme FIA was demonstrated to be equivalent to the serum/plasma matrix on the Sofia Lyme FIA. A field study was conducted using matched finger-stick whole blood, serum and plasma.

| | | IgM | | | IgG | | |
|-----------------|--|-----------------------------|-------|--------|-----------------------------|-------|--------|
| n=321 | | Finger-stick<br>Whole Blood | Serum | Plasma | Finger-stick<br>Whole Blood | Serum | Plasma |
| Positive | | 136 | 135 | 133 | 105 | 96 | 98 |
| Negative | | 185 | 186 | 188 | 216 | 225 | 223 |
| %<br>Positivity | | 42.4% | 42.1% | 41.4% | 32.7% | 29.9% | 30.5% |

Matrix Equivalency

### CDC Reference Panel g.

When testing the CDC reference panel, the overall agreement for Clinical Status of IgG and IgM samples between Sofia Lyme FIA and Clinical Status and Western Blot was good.

| Clinical<br>Status | | Sofia Lyme IgM | | | Western Blot Lyme IgM | | |
|------------------------------|-----|----------------|-----|-------------------------------------|-----------------------|-----|-------------------------------------|
| | n | Pos | Neg | % Agreement<br>with clinical Status | Pos | Neg | % Agreement<br>with clinical Status |
| Negative<br>Controls | 190 | 33 | 157 | 82.6% | 0 | 190 | 100.0% |
| Early<br>Lyme EM<br>Positive | 60 | 49 | 11 | 81.7% | 31 | 29 | 51.7% |
| Late Lyme | 30 | 22 | 8 | 73.3% | 17 | 13 | 56.7% |

Sofia Lyme FIA with Sofia tested with CDC Panel – IgM Results

### Sofia Lyme FIA with Sofia tested with CDC Panel – IgG Results

| Clinical<br>Status | n | Sofia Lyme IgG | | | Western Blot Lyme IgG | | |
|---------------------------|-----|----------------|-----|-------------------------------------|-----------------------|-----|-------------------------------------|
| | | Pos | Neg | % Agreement with<br>clinical Status | Pos | Neg | % Agreement with<br>clinical Status |
| Negative<br>Controls | 190 | 25 | 165 | 86.8% | 0 | 190 | 100.0% |
| Early Lyme<br>EM Positive | 60 | 49 | 11 | 81.7% | 19 | 41 | 31.7% |
| Late Lyme | 30 | 30 | 0 | 100% | 26 | 4 | 86.7% |

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Image /page/9/Picture/0 description: The image shows the logo for QuidelOrtho Corporation. The logo features a square shape with a smaller square cut out of the bottom right corner. The larger square is filled with a gradient of colors, ranging from red and orange to yellow, green, blue, and purple. The company name, "QUIDEL," is written in a simple, sans-serif font below the square.

## h. Specificity Study

This study evaluated the analytical specificity of the Sofia Lyme FIA on Sofia 2 using samples obtained from asymptomatic (healthy, normal) populations in both endemic and non-endemic regions. The overall specificity of the Sofia Lyme FIA was very good.

| | n | Sofia<br>IgM | Predicate IgM* | Sofia IgG | Predicate<br>IgG |
|-------------|-----|--------------|----------------|-----------|------------------|
| Endemic | 100 | 86.0% | 80.0% | 95.0% | 98.0% |
| Non-Endemic | 100 | 93.0% | 93.0% | 98.0% | 99.0% |
| Total | 200 | 89.5% | 86.5% | 96.5% | 98.5% |

### Sofia Lyme FIA with Sofia 2 and Predicate Analytical Specificity

*Equivocal results were considered Positive.

### i. Sensitivity Study

This study evaluated the clinical sensitivity of the Sofia Lyme FIA device using wellcharacterized clinically or culture confirmed Lyme disease samples. The clinical sensitivity was compared to a 510(k) cleared test and the performance was comparable.

## Lyme IgM Results for Sofia Lyme FIA with Sofia Compared to Predicate Assay

| Category | n | Pos | Neg | Sofia IgM | | Predicate IgM | | | | |
|------------------------------------------|----|-----|-----|-----------|----------------|---------------|-------|-----|-------|------------|
| | | | | Sens | 95% CI | Pos | Equiv | Neg | Sens¹ | 95% CI |
| Acute, < 1 month,<br>with EM | 64 | 39 | 25 | 60.9% | 48.7-<br>72.0% | 28 | 8 | 28 | 56.3% | 44.1-67.7% |
| Acute, 1-2 months,<br>with EM | 4 | 3 | 1 | 75.0% | 28.9-<br>96.6% | 2 | 0 | 2 | 50.0% | 15.0-85.0% |
| Convalescent, 3-12<br>months, with EM | 15 | 11 | 4 | 73.3% | 47.6-<br>89.5% | 6 | 2 | 7 | 53.3% | 30.1-75.2% |
| Late Lyme (>1 yr),<br>Neuro or Arthritic | 12 | 8 | 4 | 66.7% | 38.8-<br>86.5% | 7 | 3 | 2 | 83.3% | 54.0-96.5% |
| All Categories | 95 | 61 | 34 | 64.2% | 54.2-<br>73.1% | 43 | 13 | 39 | 58.9% | 48.9-68.3% |

1 Of the 13 samples that were "equivocal" by the predicate, 12 of 13 were negative by FDA approved western blot.

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Image /page/10/Picture/0 description: The image shows the logo for Quidel. The logo consists of a square with rounded corners, filled with a gradient of colors from red to blue. A smaller square is located in the lower right corner of the larger square, filled with a blue and purple gradient. Below the square is the word "QUIDEL" in a sans-serif font.

| Lyme IgG Results for Sofia Lyme FIA with Sofia Compared to Predicate Assay | | | | | | | | | | |
|----------------------------------------------------------------------------|-----------|-----|-----|-------|-------------|---------------|-----|-------|------------|--|
| | Sofia IgG | | | | | Predicate IgG | | | | |
| Category | n | Pos | Neg | Sens | 95%CI | Pos | Neg | Sens | 95%CI | |
| Acute, < 1 month,<br>with EM | 64 | 50 | 14 | 78.1% | 66.5-86.6% | 28 | 36 | 43.8% | 32.3-55.9% | |
| Acute, 1-2 months,<br>with EM | 4 | 4 | 0 | 100% | 54.3-100.0% | 3 | 1 | 75.0% | 28.9-96.6% | |
| Convalescent, 3-12<br>months, with EM | 15 | 10 | 5 | 66.7% | 41.5-85.0% | 6 | 9 | 40.0% | 19.8-64.3% | |
| Late Lyme (>1 yr),<br>Neuro or Arthritic | 12 | 12 | 0 | 100% | 78.4-100.0% | 10 | 2 | 83.3% | 54.0-96.5% | |
| All Categories | 95 | 76 | 19 | 80.0% | 70.8-86.9% | 47 | 48 | 49.5% | 39.6-59.4% | |

### Lyme IgG Results for Sofia Lyme FIA with Sofia Compared to Predicate Assay

### j. Method Comparison

This study demonstrated that Sofia 2 Lyme FIA with Sofia 2 has comparable performance to the Vidas Lyme IgG and Vidas Lyme IgM tests when testing prospectively collected specimens from subjects suspected of having Lyme disease.

### Lyme IgM Results for Sofia 2 Lyme FIA with Sofia 2 Compared to Predicate Assay IgM Method Comparison: 1st Tier PPA and NPA Analysis

| | | | Predicate Lyme IgM | | | | |
|----------------|----------|----|--------------------|-----------|----------------------|-------------|--------|
| | | | Positive | Equivocal | Negative | % Agreement | 95% CI |
| Sofia<br>2 IgM | Positive | 57 | 18 | 47 | PPA = 82.4% (75/91) | 73.2%-89.0% | |
| | Negative | 5 | 11 | 186 | NPA =79.8% (186/233) | 74.2%-84.5% | |
| Total | | 62 | 29 | 233 | | | |

### IgM Second Tier Testing IgM Method Comparison: 2st Tier PPA Analysis

| | Tier 1 + or ± | IgM WB + | IgM WB - | 1st Tier PPA<br>(95% CI) | | |
|--------------------------|---------------|----------|----------|--------------------------|-----------------------|-------|
| Predicate IgM | 91 | 51 | 40 | 82.4%<br>(73.2-89.0%) | 75/91 | |
| Sofia 2 IgM | 122 | 52 | 70 | 2nd Tier PPA<br>(95% CI) | 94.1%<br>(83.5-98.6%) | 48/51 |
| Predicate +<br>Sofia IgM | 75 | 48 | 27 | | | |

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Image /page/11/Picture/0 description: The image features the logo of Quidel. The logo consists of a square shape with rounded corners, divided into two sections. The upper section is a gradient of colors, transitioning from yellow to red to blue, creating a rainbow effect. The lower section is a solid blue color. Below the square is the word "QUIDEL" in a simple, sans-serif font.

### Lyme IgG Results for Sofia 2 Lyme FIA with Sofia 2 Compared to Predicate Assay IgG Method Comparison: 1st Tier PPA and NPA Analysis

| | | Predicate Lyme IgG | | | |
|-------------------|----------|--------------------|----------|-----------------------|-------------|
| | | Positive | Negative | % Agreement | 95% CI |
| Sofia<br>2<br>IgG | Positive | 48 | 38 | PPA = 88.9% (48/54) | 77.5%-95.2% |
| | Negative | 6 | 232 | NPA = 85.9% (232/270) | 81.2%-89.6% |
| Total | | 54 | 270 | | |

### IgG Second Tier Testing IgG Method Comparison: 2st Tier PPA Analysis

| | Tier 1 + | IgG WB + | IgG WB - |
|-------------------------------|----------|----------|----------|
| Predicate<br>IgG | 54 | 23 | 31 |
| Sofia 2<br>IgG | 86 | 23 | 63 |
| Predicate<br>+ Sofia 2<br>IgG | 48 | 22 | 26 |

| 1st Tier PPA<br>(95% CI) | 88.9%<br>(77.5-95.2%) | 48/54 |
|--------------------------|-----------------------|-------|
| 2nd Tier PPA<br>(95% CI) | 95.7%<br>(77.3->99.9) | 22/23 |

### 5.12. Conclusion

These studies demonstrated the substantial equivalence of the Sofia 2 Lyme FIA to the Vidas Lyme IgG and Vidas Lyme IgM tests. Such studies are a critical element in establishing the fundamental safety and effectiveness of the product and its appropriateness for commercial distribution.

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# Indications for Use

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Device Name

Indications for Use (Describe)

| Type of Use ( <i>Select…