(290 days)
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.
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. 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.
Here's a breakdown of the acceptance criteria and study information for the Sofia 2 Lyme FIA device, based on the provided text:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" in a single table, but rather presents performance data that would be used to demonstrate these criteria. Based on the "Substantial Equivalence Information" and "Performance Data" sections, the implied acceptance criteria are comparable performance to the predicate devices (Vidas Lyme IgM and Vidas Lyme IgG) in terms of precision, reproducibility, analytical specificity, clinical sensitivity, and method comparison (PPA and NPA).
Since specific numerical acceptance thresholds are not provided, the table below summarizes the reported performance values that are implicitly demonstrating compliance with "good" or "comparable" performance.
| Performance Metric | Acceptance Criteria (Implied: Comparable to Predicate) | Reported Device Performance (Sofia 2 Lyme FIA) |
|---|---|---|
| Precision | Negatives: 0% positivity | IgM Negative: 0% |
| (Within Run & Between Oper.) | High Negative (C5): 0% positivity | IgM High Negative (C5): 0% |
| Low Positive (C95): 100% positivity | IgM Low Positive (C95): 100% | |
| Moderate Positive (2-3X): 100% positivity | IgM Mod. Positive (2-3X): 100% | |
| IgG Negative: 0% | ||
| IgG High Negative (C5): 0% | ||
| IgG Low Positive (C95): 100% (Run 1), 95.8% (Run 2) – Table inconsistent: Row 3, IgG Positive, Run 2: 46/48; Table 2, IgG Low Positive: 48/48 & 48/48 | ||
| IgG Mod. Positive (2-3X): 100% | ||
| Reproducibility | Overall Agreement > 90% (based on reported CIs) | IgM Overall Agreement: |
| (Inter-Laboratory) | C0: 100% (95.1-100%) | |
| C5: 100% (95.1-100%) | ||
| C95: 96.7% (90.3-99.3%) | ||
| 2-3X LOD: 97.8% (91.8-99.9%) | ||
| IgG Overall Agreement: | ||
| C0: 100% (95.1-100%) | ||
| C5: 100% (95.1-100%) | ||
| C95: 94.4% (87.3-97.9%) | ||
| 2-3X LOD: 100% (95.1-100%) | ||
| Analytical Specificity | High percentage (e.g., >80-90%) | IgM Endemic: 86.0% |
| IgM Non-Endemic: 93.0% | ||
| IgM Total: 89.5% | ||
| IgG Endemic: 95.0% | ||
| IgG Non-Endemic: 98.0% | ||
| IgG Total: 96.5% | ||
| Clinical Sensitivity (IgM) | Comparable to predicate (e.g., within ~10% points) | Overall Sofia IgM Sens: 64.2% (54.2-73.1%) |
| Predicate IgM Sens: 58.9% (48.9-68.3%) | ||
| Clinical Sensitivity (IgG) | Comparable to predicate (e.g., within ~10% points) | Overall Sofia IgG Sens: 80.0% (70.8-86.9%) |
| Predicate IgG Sens: 49.5% (39.6-59.4%) | ||
| Method Comparison (IgM) | PPA and NPA comparable to predicate | 1st Tier PPA = 82.4% (73.2-89.0%) |
| (1st Tier) | 1st Tier NPA = 79.8% (74.2-84.5%) | |
| Method Comparison (IgG) | PPA and NPA comparable to predicate | 1st Tier PPA = 88.9% (77.5-95.2%) |
| (1st Tier) | 1st Tier NPA = 85.9% (81.2-89.6%) |
Notes on Inconsistencies: There is a minor inconsistency in the "Precision – Within Run" table for IgG Low Positive (C95) results. The "Run 2" column shows 46/48 (95.8%), while the "Total (n=96)" shows 100%. This might be a typo in the table, or the "Total" is derived differently.
2. Sample Size and Data Provenance
-
Precision and Reproducibility:
- Sample Size: Contrived samples. For precision, 96 tests per sample level (48 in Run 1, 48 in Run 2). For reproducibility, 30 tests per sample level per site (total 90 tests per sample level across 3 sites).
- Data Provenance: Not explicitly stated, but "Contrived samples were prepared" suggests laboratory-generated, possibly in the US (Quidel site).
-
Matrix Equivalency:
- Sample Size: 321 patients
- Data Provenance: "A field study was conducted." Location not specified, but likely within the US.
-
CDC Reference Panel:
- Sample Size: IgM: 190 Negative Controls, 60 Early Lyme EM Positive, 30 Late Lyme. IgG: 190 Negative Controls, 60 Early Lyme EM Positive, 30 Late Lyme.
- Data Provenance: CDC Reference Panel (implies US government source).
-
Specificity Study:
- Sample Size: 200 samples (100 endemic, 100 non-endemic).
- Data Provenance: Samples "obtained from asymptomatic (healthy, normal) populations in both endemic and non-endemic regions." Regions are not specified.
-
Sensitivity Study:
- Sample Size: 95 "well-characterized clinically or culture confirmed Lyme disease samples."
- Data Provenance: Not explicitly stated, but described as "well-characterized clinically or culture confirmed Lyme disease samples."
-
Method Comparison (Clinical Study):
- Sample Size: Total 326 samples for IgM (62 Positive, 29 Equivocal, 233 Negative by Predicate). Total 324 samples for IgG (54 Positive, 270 Negative by Predicate).
- Data Provenance: "prospectively collected specimens from subjects suspected of having Lyme disease." Country of origin not specified, but typically US for FDA 510(k) submissions unless stated otherwise.
3. Number of Experts and Qualifications for Ground Truth
- The document does not specify the number of experts used or their qualifications for establishing ground truth for the test set samples in any of the clinical or specificity/sensitivity studies.
- For the CDC Reference Panel, the panel itself implies expert consensus or well-established diagnostic criteria as its ground truth, but the individual experts involved are not mentioned.
- For the Sensitivity Study, "well-characterized clinically or culture confirmed Lyme disease samples" implies diagnosis by medical professionals following established guidelines, but specific expert details are absent.
4. Adjudication Method for the Test Set
- The document does not explicitly mention any adjudication method (e.g., 2+1, 3+1) for resolving discrepancies in the test set's ground truth determination. Ground truth is inferred primarily from clinical diagnosis, culture confirmation, or established reference panels/predicate assays.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
- No, a MRMC comparative effectiveness study was not explicitly described. The studies focus on the analytical and clinical performance of the device itself, and its comparison to predicate devices, rather than a study evaluating improvement in human reader performance with or without AI assistance. The device is an automated immunofluorescence assay (FIA), not an AI-assisted diagnostic imaging or interpretation tool.
6. Standalone Performance
- Yes, standalone performance was done. The entire "Performance Data" section (sections a-j) describes the performance of the Sofia 2 Lyme FIA algorithm/device in a standalone capacity, without human interpretation of the results to establish the initial diagnosis. The device's output (positive/negative) is directly compared to various ground truth standards.
7. Type of Ground Truth Used
The types of ground truth used vary by study:
- Precision/Reproducibility: Contrived samples (known concentrations/status).
- Matrix Equivalency: Clinical diagnosis based on patient outcome or other diagnostic procedures (implied by comparing finger-stick whole blood to serum/plasma, which are standard clinical samples).
- CDC Reference Panel: "Clinical Status" (established by CDC, likely involving clinical diagnosis and confirmed lab results) and "Western Blot" (a gold standard serological confirmation for Lyme disease).
- Specificity Study: Asymptomatic/healthy status from endemic and non-endemic populations.
- Sensitivity Study: "Well-characterized clinically or culture confirmed Lyme disease samples."
- Method Comparison: Predicate assays (Vidas Lyme IgM and IgG) as a benchmark, and second-tier Western Blot for confirmation of first-tier positive or equivocal results.
8. Sample Size for the Training Set
- The document does not explicitly state the sample size used for a "training set." This device is an immunoassay, not a machine learning or AI model in the typical sense that requires a training set of images or data for algorithm development. The "Assay Cutoff" study mentions establishing cutoffs, which is an optimization process, but not a "training set" in the context of deep learning.
9. How the Ground Truth for the Training Set was Established
- Given that a specific "training set" for an AI/ML model is not described, the method for establishing its ground truth is not applicable/not provided. The "Assay Cutoff" study involved testing "matched finger-stick whole blood, serum and plasma samples with the aim of setting the whole blood assay cutoff so that the clinical performance... is statistically similar to the FDA cleared Sofia Lyme FIA serum and plasma assay." This suggests that the ground truth for establishing cutoffs was based on a combination of clinical performance (likely against a known diagnosis or reference method) and comparison to an already cleared device.
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ട്. 510(K) SUMMARY
5.1. Submitter
Quidel Corporation 12544 High Bluff Drive, Suite 200 San Diego, California 92130 Telephone: 858-552-7910 Fax: 858-646-8045
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 andMicrobiology 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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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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Substantial Equivalence Information: 5.10.
-
- 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 withSofia | Biomerieux Vidas LymeIgM | Biomerieux Vidas LymeIgG |
| Intended Use | Sofia 2 Lyme FIA:The Sofia 2 Lyme FIAemploysimmunofluorescence forthe rapid differentialdetection of human IgMand IgG antibodies toBorrelia burgdorferifrom finger-stick wholeblood specimens frompatients suspected of B.burgdorferi infection ofat least 2 weeks'duration. The Sofia 2Lyme FIA is intendedfor use as an aid indiagnosis of Lymedisease. A negativeresult does not precludeinfection with B.burgdorferi. Positiveresults must beconfirmed by testingwith a correspondingsecond-tier B.burgdorferi Westernblot assay. Test resultsare to be used inconjunction withinformation obtainedfrom the patient'sclinical evaluation andother diagnosticprocedures. The assay isto be performed on theSofia 2 instrument.Professional guidelinesshould be consultedregarding testing and | The VIDAS Lyme IgMassay is an automatedqualitative enzymeimmunoassay intended foruse on the instruments of theVIDAS family in thepresumptive detection ofhuman IgM antibodies toBorrelia burdorferi inhuman serum or plasma. Itshould be used to testpatients with a historyand/or symptoms ofinfection with B.burgdorferi. All VIDASLyme IgG positivespecimens should be furthertested with a Western BlotIgG assay to obtainsupportive evidence ofinfection with B.burgdorferi. | The VIDAS Lyme IgGassay is an automatedqualitative enzymeimmunoassay intended foruse on the instruments of theVIDAS family in thepresumptive detection ofhuman IgG antibodies toBorrelia burdorferi inhuman serum or plasma. Itshould be used to testpatients with a historyand/or symptoms ofinfection with B.burgdorferi. All VIDASLyme IgG positivespecimens should be furthertested with a Western BlotIgG assay to obtainsupportive evidence ofinfection with B.burgdorferi. |
| Item | Proposed Device | Predicate IgM Device | Predicate IgG Device |
| Features | Sofia 2 Lyme FIA withSofia | Biomerieux Vidas LymeIgM | Biomerieux Vidas LymeIgG |
| Features | treatment for Lymedisease when acute B.burgdorferi infection issuspected.Sofia Lyme Control Set:The Sofia Lyme ControlSet is intended for use asassayed quality controlmaterials to verify theperformance of the SofiaLyme FIA and Sofia 2Lyme FIA test system. | ||
| Instrument | Sofia 2 | VIDAS and miniVIDAS | VIDAS and miniVIDAS |
| Analyte | Human IgM and IgGantibodies against B.burgdorferi proteins | Human IgM antibodiesagainst B. burgdorferiproteins | Human IgG antibodiesagainst B. burgdorferiproteins |
| AutomatedAnalysis | Yes | Yes | Yes |
| Read Results | Read results on instrumentscreen or print withoptional printer | Result report is printed | Result report is printed |
| Read ResultTime | Potential for early read inWalk-Away Mode. Sofia2 will image cassette at 3,5, 8, 10, and 15 minutesuntil both IgM and IgGpositive results arereceived. | 27 minutes | 27 minutes |
| SpecimenTypes | Finger-stick whole blood | Serum and plasma | Serum and plasma |
| Qualitative | Yes | Yes | Yes |
| Test Principle | ImmunofluorescenceDevice | Immunofluorescence Device | Immunofluorescence Device |
| Format | Lateral-flow Bi-directionalTest Cassette | Enzyme-linked fluorescentassay (ELFA) | Enzyme-linked fluorescentassay (ELFA) |
| AntibodiesUsed | Monoclonal anti-humanIgG and polyclonal anti-human IgM | Anti-human IgM antibodies | Anti-human IgG antibodies |
| Item | Proposed Device | Predicate IgM Device | Predicate IgG Device |
| Features | Sofia 2 Lyme FIA withSofia | Biomerieux Vidas LymeIgM | Biomerieux Vidas LymeIgG |
| Antigens Used | Recombinant Proteins andsynthetic peptides of B.burgdorferi | Recombinant proteins of B.burgdorferi | Recombinant proteins of B.burgdorferi |
| DetectionMethod | Polystyrene microparticlesdyed with Europiumchelate | Alkaline phosphatase/4-MUP | Alkaline phosphatase/4-MUP |
| Storage | Room Temperature (15-30°C) | 2-8°C | 2-8°C |
| RunningBufferSolution | One pre-filled vialcontaining PBS | Sample diluent and washbuffer | Sample diluent and washbuffer |
| QualityControlFeatures | Built-in features include:• Built-in proceduralcontrol zone scannedby the analyzer todetermine whetheradequate flowoccurred on the IgGside of the assay.• Built-in referencecontrol line scannedby the analyzer todetermine whetheradequate flowoccurred on the IgMside of the assay.• Analyzer preventsused or expiredcartridge from beingread by the reader• Cassette must beproperly inserted | • One positive and onenegative control areincluded and must betested after opening anew kit to monitorreagent failure. | • One positive and onenegative control areincluded and must betested after opening anew kit to monitorreagent failure. |
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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 IgGSample | IgM Positive | IgM % Positivity | IgG Positive | IgG %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% |
| HighNegative (C5) | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| Low Positive(C95) | 48/48 | 48/48 | 100% | 48/48 | 46/48 | 100% |
| ModeratePositive (2-3X) | 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 IgGSample | IgM Positive | IgM %PositivityTotal (n=96) | IgG Positive | IgG %PositivityTotal(n=96) | ||
|---|---|---|---|---|---|---|
| Operator 1 | Operator 2 | Operator 1 | Operator 2 | |||
| Negative | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| HighNegative(C5) | 0/48 | 0/48 | 0% | 0/48 | 0/48 | 0% |
| Low Positive(C95) | 48/48 | 48/48 | 100% | 48/48 | 48/48 | 100% |
| ModeratePositive (2-3X) | 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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| Site | IgMNegative(C₀) | IgM HighNegative(C₅) | IgM LowPositive(C₉₅) | IgMModeratePositive(2-3XLOD) | IgGNegative(C₀) | IgG HighNegative(C₅) | IgG LowPositive(C₉₅) | IgGModeratePositive(2-3XLOD) |
|---|---|---|---|---|---|---|---|---|
| 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 |
| % OverallAgreement(95% CI) | 100%(95.1-100%) | 100%(95.1-100%) | 96.7%(90.3-99.3%) | 97.8%(91.8-99.9%) | 100%(95.1-100%) | 100%(95.1-100%) | 94.4%(87.3-97.9%) | 100%(95.1-100%) |
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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| 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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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-stickWhole Blood | Serum | Plasma | Finger-stickWhole Blood | Serum | Plasma | |
| Positive | 136 | 135 | 133 | 105 | 96 | 98 | |
| Negative | 185 | 186 | 188 | 216 | 225 | 223 | |
| %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.
| ClinicalStatus | Sofia Lyme IgM | Western Blot Lyme IgM | |||||
|---|---|---|---|---|---|---|---|
| n | Pos | Neg | % Agreementwith clinical Status | Pos | Neg | % Agreementwith clinical Status | |
| NegativeControls | 190 | 33 | 157 | 82.6% | 0 | 190 | 100.0% |
| EarlyLyme EMPositive | 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
| ClinicalStatus | n | Sofia Lyme IgG | Western Blot Lyme IgG | ||||
|---|---|---|---|---|---|---|---|
| Pos | Neg | % Agreement withclinical Status | Pos | Neg | % Agreement withclinical Status | ||
| NegativeControls | 190 | 25 | 165 | 86.8% | 0 | 190 | 100.0% |
| Early LymeEM 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 | SofiaIgM | Predicate IgM* | Sofia IgG | PredicateIgG | |
|---|---|---|---|---|---|
| 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,with EM | 64 | 39 | 25 | 60.9% | 48.7-72.0% | 28 | 8 | 28 | 56.3% | 44.1-67.7% |
| Acute, 1-2 months,with EM | 4 | 3 | 1 | 75.0% | 28.9-96.6% | 2 | 0 | 2 | 50.0% | 15.0-85.0% |
| Convalescent, 3-12months, with EM | 15 | 11 | 4 | 73.3% | 47.6-89.5% | 6 | 2 | 7 | 53.3% | 30.1-75.2% |
| Late Lyme (>1 yr),Neuro or Arthritic | 12 | 8 | 4 | 66.7% | 38.8-86.5% | 7 | 3 | 2 | 83.3% | 54.0-96.5% |
| All Categories | 95 | 61 | 34 | 64.2% | 54.2-73.1% | 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,with EM | 64 | 50 | 14 | 78.1% | 66.5-86.6% | 28 | 36 | 43.8% | 32.3-55.9% | |
| Acute, 1-2 months,with EM | 4 | 4 | 0 | 100% | 54.3-100.0% | 3 | 1 | 75.0% | 28.9-96.6% | |
| Convalescent, 3-12months, with EM | 15 | 10 | 5 | 66.7% | 41.5-85.0% | 6 | 9 | 40.0% | 19.8-64.3% | |
| Late Lyme (>1 yr),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 | |||
| Sofia2 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(95% CI) | |||
|---|---|---|---|---|---|---|
| Predicate IgM | 91 | 51 | 40 | 82.4%(73.2-89.0%) | 75/91 | |
| Sofia 2 IgM | 122 | 52 | 70 | 2nd Tier PPA(95% CI) | 94.1%(83.5-98.6%) | 48/51 |
| Predicate +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 | ||
| Sofia2IgG | 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 - | |
|---|---|---|---|
| PredicateIgG | 54 | 23 | 31 |
| Sofia 2IgG | 86 | 23 | 63 |
| Predicate+ Sofia 2IgG | 48 | 22 | 26 |
| 1st Tier PPA(95% CI) | 88.9%(77.5-95.2%) | 48/54 |
|---|---|---|
| 2nd Tier PPA(95% CI) | 95.7%(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
510(k) Number (if known)
Device Name
Indications for Use (Describe)
| Type of Use ( Select one or both, as applicable ) |
|---|
| ---------------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
| Over-The-Counter Use (21 CFR 801 Subpart C)
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Image /page/13/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: a symbol on the left and the text "FDA U.S. FOOD & DRUG ADMINISTRATION" on the right. The symbol on the left is a stylized image of a human figure. The text on the right is in blue and white, with "FDA" in a larger font size than the rest of the text.
August 30, 2018
Quidel Corporation Jennifer Rial Director, Regulatory Affairs 12544 High Bluff Drive, Suite 200 San Diego, California 92130
Re: K173496
Trade/Device Name: Sofia 2 Lyme FIA Sofia Lyme Control Set Regulation Number: 21 CFR 866.3830 Regulation Name: Treponema pallidum treponemal test reagents Regulatory Class: Class II Product Code: LSR, QCH Dated: November 10, 2017 Received: November 13, 2017
Dear Jennifer Rial:
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
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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 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.
For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). 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 (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely.
for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
§ 866.3830
Treponema pallidum treponemal test reagents.(a)
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), theTreponema pallidum immobilization test (T.P.I.), and other treponemal tests used to identify antibodies toTreponema pallidum directly from infecting treponemal organisms in serum. The identification aids in the diagnosis of syphilis caused by bacteria belonging to the genusTreponema and provides epidemiological information on syphilis.(b)
Classification. Class II (performance standards).