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510(k) Data Aggregation
(260 days)
QUANTA Flash® Scl-70 is a chemiluminescent immunoassay for the semi-quantitative determination of IgG anti-Scl-70 autoantibodies in human serum. The presence of anti-Scl-70 autoantibodies, in conjunction with clinical findings and other laboratory tests, aids in the diagnosis of systemic sclerosis.
QUANTA Flash® Scl-70 Calibrators are intended for use with the QUANTA Flash® Scl-70 chemiluminescent immunoassay for the determination of IgG anti-Scl-70 autoantibodies in human serum. Each calibrator establishes a point of reference for the working curve that is used to calculate unit values.
QUANTA Flash® Scl-70 Controls are intended for use with the OUANTA Flash® Scl-70 chemiluminescent immunoassay for quality control in the determination of IgG anti-Scl-70 autoantibodies in human serum.
The QUANTA Flash Scl-70 assay is designed to run on the BIO-FLASH® instrument. This platform is a fully automated closed system with continuous load and random access capabilities that automatically processes the samples, runs the assay and reports the results. It includes liquid handling hardware, luminometer and computer with software-user interface. The QUANTA Flash Scl-70 assay utilizes a reagent cartridge format, which is compatible with the BIO-FLASH instrument.
Recombinant Scl-70 is coated onto paramagnetic beads. The bead suspension is lyophilized and stored in the bead tube. Prior to use in the BIO-FLASH system, the sealed reagent tubes are pierced with the reagent cartridge lid and the beads are rehydrated and resuspended using resuspension buffer by pipetting up and down with a transfer pipette. The reagent cartridge is then loaded onto the BIO-FLASH instrument. Samples are also loaded onto the instrument in sample racks. A patient serum sample is prediluted 1:23.5 by the BIO-FLASH with system rinse in a disposable plastic cuvette. Small amounts of the diluted patient serum, the beads, and assay buffer are all combined into a second cuvette, and mixed. This cuvette is then incubated at 37°C. The beads are magnetized and washed several times. Isoluminol conjugated anti-human IgG antibodies are then added to the cuvette, and again incubated at 37°C. The beads are magnetized and washed repeatedly. The isoluminol conjugate is oxidized when Trigger 1 (Fe(III) coproporphyrin in sodium hydroxide solution) and Trigger 2 (urea-hydrogen peroxide in sodium chloride solution) are added to the cuvette, and the flash of light produced from this reaction is measured as Relative Light Units (RLU) by the BIO-FLASH optical system. The RLU are proportional to the amount of isoluminol conjugate that is bound to the human IgG, which is in turn proportional to the amount of anti-Scl-70 antibodies bound to the corresponding Scl-70 on the beads.
For quantitation, the QUANTA Flash Scl-70 assay utilizes a predefined lot specific Master Curve that is uploaded onto the instrument through the reagent cartridge barcode. Every new lot number of reagent cartridge must be calibrated before first use, with the QUANTA Flash Scl-70 Calibrators. Based on the results obtained with the two Calibrators included in the Calibrator Set (sold separately), an instrument specific Working Curve is created, which is used to calculate chemiluminescent units (CU)mL from the instrument signal (RLU) obtained for each sample.
Here's a summary of the acceptance criteria and study findings based on the provided text, structured as requested:
1. Table of Acceptance Criteria and Reported Device Performance
| Performance Characteristic | Acceptance Criteria | Reported Device Performance |
|---|---|---|
| Precision | Total %CV values within 10%. | All total %CV values for 13 samples across various concentrations were within 10%. (Range: 3.4% - 5.9%) |
| Reproducibility (Between sites) | All %CV values within 15%. | All %CV values for 8 samples across three sites were within 15%. (Range: 1.3% - 8.3%) |
| Reproducibility (Between lots) | All %CV values within 10%. | All %CV values for 8 samples across three different lots were within 10%. (Range: 1.5% - 9.6%) |
| Limit of Quantitation (LoQ) | Total error (TE) < 25% (accuracy goal). | LoQ is 1.2 CU, meeting the accuracy goal. |
| Limit of Detection (LoD) | Proportions of false positives (alpha) < 5% and false negatives (beta) < 5%. | LoD is 0.2 CU, determined with alpha and beta less than 5%. |
| Limit of Blank (LoB) | Not explicitly stated as a separate criterion, but derived from method. | LoB is 0.1 CU. |
| Analytical Measuring Range (AMR) | Defined by LoQ and highest Master Curve Standard. | 1.2 CU - 786.3 CU. |
| Auto-rerun function | % recovery values for auto-rerun results compared to manual dilution within ± 20%. | % recovery values for auto-rerun were 104%, 101%, and 91% (average 102%), all within ± 20%. |
| Linearity | 80%-120% recovery, 0.9-1.1 slope, and ≥0.95 R² for linear regression analysis. | Percent recovery for all data points ranged from 80.2% to 118.4%. Slopes for individual samples ranged from 0.96 to 1.03 (all within 0.9-1.1). R² values for all samples were 0.99 or 1.00 (all ≥0.95). Combined results: Slope 1.01, R² 0.99. |
| Interference | 85% - 115% recovery for unit values. | No interference detected. Recoveries for Bilirubin (88-101%), Hemoglobin (93-105%), Triglycerides (89-97%), Cholesterol (93-106%), Human IgG (90-109% or < 4 CU), RF IgM (97-111%), Prednisone (100.0-109.7%), and Naproxen (97.7-109.7%) were all within the 85-115% range. |
| Sample Stability | 90-110% average recovery compared to control (Day Zero, 2-8°C). | All samples fulfilled acceptance criteria at each time point (up to 21 days at 2-8°C, up to 48 hours at room temperature, up to 3 freeze/thaw cycles). |
| Reagent Stability (Accelerated) | Microparticles: 95% CI of regression line between 85-115% at 2 weeks, no individual data point outside 75-125% recovery at 2 weeks. Controls & Calibrators: Lower 95% CI of regression line between 90-110% at 2 weeks, no individual data point outside 80-120% recovery at 2 weeks. | All components tested fulfilled the acceptance criteria, leading to a one-year expiration dating assignment. |
| Reagent Stability (Real-time) | Controls: Results within established acceptable ranges. Calibrators: % recovery of average of triplicates between 85-115%, %CV of triplicates < 10%. Reagent Cartridge: %CV of replicates < 15%, % recovery of each sample between 80-120%. | All results were within the acceptance limits for controls, calibrators, and reagent cartridges up to 6 months. |
| In-use Stability (Calibrators) | 5 successful calibrations in 8.5 hours, Calibrator average RLU recovery 90-110% compared to first use. | 5 successful calibrations performed over 8.5 hours. Calibrator RLU values remained within 90-110% range. Patient samples ran within expected range. Supports claim of up to 4 calibrations over 8 hours. |
| In-use Stability (Controls) | Replicates run within established range, linear regression line of %recovery vs. runs between 85-115% at run 15. | Low and High Controls ran within their acceptable range for all runs. Linear regression line of %recovery for both controls was within 85-115% at run 15. Supports claim of up to 15 uses. |
| In-use Stability (Reagent Cartridge) | Stability claim precedes 95% CI of regression line reaching 85% or 115% recovery OR 2 data points or ≥2% of recovery data is ≤ 75% or ≥ 125% recovery. | In-use (onboard) stability of 60 days was set. (Implies criteria were met up to that point). |
| Clinical Sensitivity (SSc) | Not explicitly stated as a numerical acceptance criterion, but validation sought to demonstrate performance. | 42.3% (95% CI: 33.9% - 51.1%) |
| Clinical Specificity (Controls) | Not explicitly stated as a numerical acceptance criterion, but validation sought to demonstrate performance. | 98.7% (95% CI: 96.9% - 99.4%) |
| Overall Agreement with Predicate | Not explicitly stated as a numerical acceptance criterion (e.g., >X%). However, the comparison aimed to show substantial equivalence. | Total Agreement: 97.6% (95% CI: 95.9% – 98.6%) for all 539 samples. Agreement within AMR (193 samples): Negative Agreement = 93.3% (95% CI: 88.1% – 96.3%), Positive Agreement = 95.5% (95% CI: 84.9% – 98.7%), Total Agreement = 93.8% (95% CI: 89.4% – 96.4%). |
2. Sample Size Used for the Test Set and Data Provenance
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Clinical Performance (Validation Set):
- Sample Size: 498 samples.
- Data Provenance: The text does not explicitly state the country of origin. It indicates the samples were a "separate set of samples, none of which were used in establishing the reference range." The patient groups include Systemic Sclerosis (SSc) and various control groups (Systemic Lupus Erythematosus, Rheumatoid Arthritis, Idiopathic Inflammatory Myopathy, Mixed Connective Tissue Disease, Celiac disease, Autoimmune thyroiditis, Sjögren's syndrome, Infectious disease, Crohn's disease, Osteoarthritis, COPD, Chronic Kidney Disease, Vasculitis, Raynaud's, Diabetes, Asthma, Skin Disease). The infectious disease samples specify Hepatitis C virus, Epstein-Barr virus, Toxoplasmosis, Cytomegalovirus, Mycoplasma infection, and Borrelia virus. The study is presented as evidence for the device's performance, suggesting prospective collection or a well-characterized retrospective cohort.
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Comparison with Predicate Device:
- Sample Size: 539 samples (the 498 samples from the Validation Set plus 41 additional contrived samples).
- Data Provenance: Same as the clinical performance validation set, with additional contrived samples (diluted Scl-70 positive serum with negative serum).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth for the clinical diagnosis of systemic sclerosis (SSc) or other conditions used in the clinical validation set. It simply refers to "Diagnosis" in the tables relating to sensitivity and specificity. Given this is an in vitro diagnostic device, the ground truth for clinical conditions would typically be established by clinical diagnosis by treating physicians, potentially corroborated by other clinical and laboratory findings.
4. Adjudication Method for the Test Set
The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for establishing the ground truth diagnoses in the test set.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No multi-reader multi-case (MRMC) comparative effectiveness study is mentioned. This device is an automated chemiluminescent immunoassay; therefore, human reader assistance and improvement with AI assistance are not applicable. The comparison is between the new automated device and a predicate ELISA (enzyme-linked immunosorbent assay), not human readers.
6. Standalone Performance Study
Yes, a standalone performance study was done. The entire document describes the standalone performance of the QUANTA Flash® Scl-70 assay system (algorithm/device only without human-in-the-loop performance, as it's an automated immunoassay) across various analytical and clinical characteristics. The clinical sensitivity and specificity are direct measures of this standalone performance.
7. Type of Ground Truth Used
- Clinical Performance (Sensitivity/Specificity): The ground truth was clinical diagnosis. For systemic sclerosis (SSc), this means patients diagnosed with SSc. For control groups, this refers to patients diagnosed with other autoimmune diseases or infectious diseases, or healthy individuals.
- Analytical Performance: Ground truth was established by controlled experimental conditions, such as known concentrations for precision, linearity, and interference studies, or controlled conditions for stability studies.
- Comparison with Predicate Device: The ground truth for this comparison was the result obtained from the legally marketed predicate device, QUANTA Lite® Scl-70 ELISA.
8. Sample Size for the Training Set
- Reference Range Establishment (for Cut-off): 254 subjects were used. The sample groups included individuals with Rheumatoid Arthritis, Systemic Lupus Erythematosus, Hashimoto's Thyroiditis, Hepatitis B Virus, Hepatitis C Virus, Inflammatory Bowel Disease, Drug Induced Lupus, Autoimmune atrophic gastritis, Biliary anastomatic stricture, and Healthy Individuals.
- Cut-off Adjustment: 19 systemic sclerosis samples that were positive on the predicate device were also used to aid in the final determination of the cutoff.
- The document does not explicitly describe a separate "training set" in the context of machine learning, as this is an immunoassay, but rather samples used for establishing the reference range/cut-off.
9. How the Ground Truth for the Training Set was Established
- Reference Range Establishment: The ground truth for the 254 subjects used to establish the reference range was based on their clinical diagnosis (e.g., Rheumatoid Arthritis, Systemic Lupus Erythematosus, or Healthy Individuals).
- Cut-off Adjustment: The additional 19 systemic sclerosis samples had a ground truth based on their positive results on the predicate device (QUANTA Lite® Scl-70 ELISA) and their clinical diagnosis of systemic sclerosis.
The cut-off was established in accordance with CLSI C28-A3c ("Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline - Third Edition") and adjusted based on the results from the SSc samples positive on the predicate device to optimize differentiation.
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