K083188 · Phadia US, Inc. · LJM · Mar 13, 2009 · Immunology
Device Facts
Record ID
K083188
Device Name
VARELISA RECOMBI ANA SCREEN, MODEL 12 596
Applicant
Phadia US, Inc.
Product Code
LJM · Immunology
Decision Date
Mar 13, 2009
Decision
SESE
Submission Type
Traditional
Regulation
21 CFR 866.5100
Device Class
Class 2
Attributes
Real-World Evidence
Real-World Evidence
Submission
Device
Sponsor
RWD Sources
RWE Use Summary
Key Tags
K083188 · Mar 13, 2009
VARELISA RECOMBI ANA SCREEN, MODEL 12 596
Phadia US, Inc.
Clinically defined patient sera; Samples from apparently healthy subjects (normal population)
The sponsor used retrospective clinical samples (clinically defined disease controls and healthy subjects) to demonstrate laboratory equivalence between the new device and the predicate device.
Clinically defined sera; Healthy subjects; Laboratory equivalence
Clinical Evidence
Study Design
Population
Comparator
Key Endpoints
Comparison study; Retrospective analysis of clinical samples
The Varelisa ReCombi ANA Screen ElA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma (citrate/EDTA) to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/ dermatomyositis. The Varelisa ReCombi ANA Screen detects antibodies against dsDNA, UIRNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa,60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 in a single microwell.
Device Story
Varelisa ReCombi ANA Screen is an indirect noncompetitive ELISA for qualitative detection of 8 antinuclear antibodies in human serum or plasma. Microplate wells are coated with human recombinant nuclear antigens, synthetic peptides, and dsDNA. Patient sample antibodies bind to antigens; enzyme-labeled conjugate binds to antigen-antibody complex. Substrate addition produces color proportional to antibody concentration. Used in clinical laboratories; operated by trained technicians. Output is optical density (OD) measured at 450 nm and 620 nm via microplate reader. Results aid physicians in diagnosing systemic rheumatic diseases. Benefits include streamlined screening for multiple autoantibodies in a single microwell.
Clinical Evidence
Bench testing only. Method comparison study (n=253) against predicate showed 99.0% positive percent agreement and 96.7% negative percent agreement. Analytical specificity verified using CDC and AMLI reference panels. Precision evaluated across 5 runs with high negative, equivocal, and high positive samples; intra-assay variance 2.2-5.0% CV, inter-assay variance 3.9-6.6%. Endogenous interference testing (bilirubin, chyle, hemoglobin, rheumatoid factor) showed no adverse effects. Heparin plasma identified as interfering matrix.
Technological Characteristics
Indirect noncompetitive EIA. Microplate wells coated with nuclear antigens (dsDNA, U1RNP, Sm, SS-A/Ro, SS-B/La, Scl-70, CENP-B, Jo-1). Detection via horseradish peroxidase-conjugated anti-human IgG and TMB substrate. Requires microplate reader (450 nm). Storage 2-8°C. Synthetic human Sm peptide used as antigen.
Indications for Use
Indicated for qualitative determination of 8 antinuclear antibodies (dsDNA, U1RNP, Sm, SS-A/Ro, SS-B/La, Scl-70, CENP-B, Jo-1) in human serum or plasma to aid diagnosis of systemic rheumatic diseases (SLE, scleroderma, MCTD, Sjögren's syndrome, polymyositis/dermatomyositis).
Regulatory Classification
Identification
An antinuclear antibody immunological test system is a device that consists of the reagents used to measure by immunochemical techniques the autoimmune antibodies in serum, other body fluids, and tissues that react with cellular nuclear constituents (molecules present in the nucleus of a cell, such as ribonucleic acid, deoxyribonucleic acid, or nuclear proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues).
Predicate Devices
Varelisa ReCombi ANA Screen (k050625)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
k083188
B. Purpose for Submission:
Device modification [Replacement of SmD full-length peptide antigen with a 16 amino acid peptide fragment of the human SmD protein (k050625)]
C. Measurand:
dsDNA, U1RNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 antibodies
D. Type of Test:
Qualitative Enzyme Immunoassay (EIA)
E. Applicant:
Phadia US, Inc.
F. Proprietary and Established Names:
Varelisa® ReCombi ANA Screen
G. Regulatory Information:
1. Regulation section:
21 CFR§ 866.5100, Antinuclear Antibody Immunological Test System
2. Classification:
Class II
3. Product code:
LJM, Antinuclear antibody (enzyme-labeled), Antigen and Controls
4. Panel:
Immunology (82)
H. Intended Use:
1. Intended use(s):
See below.
2. Indication(s) for use:
The Varelisa ReCombi ANA Screen EIA kit is designed for the qualitative determination of eight antinuclear antibodies in human serum or plasma to aid in the diagnosis of systemic rheumatic diseases such as SLE (systemic lupus erythematosus), scleroderma (progressive systemic sclerosis), MCTD (mixed connective tissue disease), SS (Sjögren's syndrome) and polymyositis/dermatomyositis. The Varelisa ReCombi ANA Screen detects antibodies against dsDNA, U1RNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 in a single microwell.
3. Special conditions for use statement(s):
The device is for prescription use only.
4. Special instrument requirements:
Microplate reader capable of measuring OD at 450 nm.
I. Device Description:
The assay contains the following: microplate strips coated with nuclear antigens: dsDNA, U1RNP (RNP70, A, C), Sm, SS-A/Ro (52 kDa, 60 kDa), SS-B/La, Scl-70,
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CENP-B and Jo-1, calibrator, negative control, wash buffer concentrate, sample diluent, horseradish peroxidase conjugated anti-human IgG, 3,3',5,5 tetramethylbenzidine (TMB) substrate, and $\mathrm{H}_2\mathrm{SO}4$ stop solution.
# J. Substantial Equivalence Information:
1. Predicate device name(s):
Varelisa ReCombi ANA Screen
2. Predicate K number(s):
k050625
3. Comparison with predicate:
The new assay is similar to the predicate assay as follows: same indications for use, specimen type, assay principle, conjugate, and reagents. The new assay differs from the predicate assay by replacing the previous Sm antigen with a synthetic human Sm peptide and the elimination of a pre-washing step.
# K. Standard/Guidance Document Referenced (if applicable):
CLSI H18-A3: Procedures for the Handling and Processing of Blood Specimens; Approved Guideline—Third Edition
# L. Test Principle:
The Varelisa ReCombi ANA Screen is an indirect noncompetitive enzyme immunoassay for the qualitative determination of dsDNA, U1RNP (RNP 70, A, C), Sm[D], SS-A/Ro (52 kDa, 60 kDa), SS-B/La, Scl-70, CENP-B and Jo-1 antibodies in serum and plasma. If antibodies specific for the nuclear antigens are present in a patient sample they bind to these nuclear antigens coated to the assay wells. In the second step an enzyme labeled secondary antibody (conjugate) binds to the antigen-antibody complex. The enzyme labeled antigen-antibody complex converts the substrate to form a colored solution. The results are read spectrophotometrically and are interpreted as positive, equivocal, or negative by comparison to a cut-off calibrator.
# M. Performance Characteristics (if/when applicable):
# 1. Analytical performance:
# a. Precision/Reproducibility:
Three samples (high negative, equivocal and high positive) per parameter were analyzed in 5 runs, with 8 replicates per run. Each sample contained all eight antigens. The runs were carried out by one operator within one day.
| Sample | | Run 1 | Run 2 | Run 3 | Run 4 | Run 5 | Mean Ratio | Variance | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | | | | | intra | inter |
| High Negative | Mean(Ratio) | 0.9 | 0.9 | 0.8 | 0.9 | 0.8 | 0.9 | 3.2 | 4.4 |
| | CV% | 3.5 | 1.2 | 2.1 | 2.3 | 5.3 | | | |
| Equivocal | Mean(Ratio) | 1.2 | 1.0 | 1.0 | 1.0 | 1.0 | 1.0 | 3.5 | 6.6 |
| | CV% | 5.0 | 2.1 | 2.7 | 3.2 | 3.2 | | | |
| High positive | Mean(Ratio) | 3.4 | 3.1 | 3.1 | 3.2 | 3.2 | 3.2 | 2.2 | 3.9 |
| | CV% | 1.5 | 1.5 | 1.6 | 3.3 | 2.5 | | | |
# b. Linearity/assay reportable range:
Not applicable.
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c. Traceability, Stability, Expected values (controls, calibrators, or methods): The consistency of calibration material is ensured by a testing procedure comparing the new calibrators to corresponding master calibration material demonstrating that the internal target values are met. No international standards have been established for these analytes. The performance of the bulk production of positive and negative control sera is adjusted until the release criteria are met. Values have to be found in accordance to an established acceptance range.
Based on accelerated stability testing, unopened kits were projected to be stable for 12 months when stored at 2 – 8°C. Sample stability claims are based on the recommendations in CLSI H18-A3.
d. Detection limit: This study was intended to verify the previously established detection limit (k050625). Sample diluent was measured 90 times per run on two different lots. Analytical sensitivity (detection limit) was calculated as the mean of the optical densities (OD) of the sample diluent plus three times the standard deviations (SD) then converted to a ratio. The analytical sensitivity for the assay was 0.1.
e. Analytical specificity: Ten CDC ANA human reference sera from the Centers for Disease Control and Prevention and 10 sera of the AMLI Consensus Reference Panel 2002, were diluted and tested twice by two different operators on two different lots of the new device and one lot of the predicate device. Both the new assay and the predicate assay gave a positive result (> 1.4 mean ratio) for CDC 1, 2, 3, 4, 5, 7, 8, 9, and 10 which all contain antigens recognized by the Recombi ANA Screen. All other samples in the CDC panel were negative (CDC 6, 11, and 12). Both the new assay and the predicate assay gave a positive result for AMLI panel members AMLI 2, 3, 4, 5, 6, 7, 8, and 9 which contain target antigens recognized by the test. AMLI 1 and 10 were negative as expected.
Endogenous interferences: The following interfering substances (up to the listed concentration) did not adversely affect the test results (i.e. change the outcome): Bilirubin C (21.6 mg/dL), Bilirubin F (19.1 mg/dL), Chyle (1590 FTU), Hemoglobin (494 mg/dL), and Rheumatoid Factor (550 IU/mL).
f. Assay cut-off: The equivocal range and cut-off of the assay were determined in k05625. The sponsor presented a study of 460 healthy Caucasian blood donors evenly distributed by age and sex that confirmed the established cut-offs.
2. Comparison studies:
a. Method comparison with predicate device: The performance of the new device was compared to the performance of the old device using 253 samples from patients with known clinical background (50 infectious disease, 50 non-connective tissue disease (CTD), 103 CTD, and
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50 Rheumatoid Arthritis) and 92 blood donor samples. Equivocal results were regarded as negative:
| | Predicate ReCombi ANA Screen | | | |
| --- | --- | --- | --- | --- |
| | | Positive | Negative | Total |
| New ReCombi ANA Screen | Positive | 102 | 5 | 107 |
| | Negative | 1 | 145 | 146 |
| | Total | 103 | 150 | 253 |
Positive Percent Agreement: 99.0% (102/103) 95% CI: 94.7 – 100%
Negative Percent Agreement: 96.7% (145/150) 95% CI: 92.4 – 98.9%
Total Percent Agreement: 97.6% (247/253) 95% CI: 94.9 – 99.1%
b. Matrix comparison:
26 negative samples from healthy donors and 13 samples spiked with different amounts of sera from ANA+ donors each available as serum, citrate plasma, EDTA plasma, and heparin plasma were run in duplicate. Performance was acceptable in citrate plasma and EDTA plasma however heparin plasma samples interfered with correct test results. The labeling contains a warning not to use heparin plasma.
3. Clinical studies:
a. Clinical Sensitivity:
Not applicable.
b. Clinical specificity:
Not applicable.
c. Other clinical supportive data (when a. and b. are not applicable):
Not applicable.
4. Clinical cut-off:
See Assay Cut-off above.
5. Expected values/Reference range:
See Assay Cut-off above.
N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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Scroll right in the results table. The intended use is extracted for you — no need to open the PDF. The device story gives a high-level snapshot of what the device does and how it's used. The AI Performance sub-table shows each output name, acceptance criteria, observed values, and development/test dataset descriptions — the same format Innolitics uses for regulatory strategy outputs, and the fastest high-level fingerprint of an AI device. It is AI-generated but has been very reliable in practice.
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Scroll right in the search results table. The intended use column is extracted for you; no need to dig into the 510(k) summary PDF.
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Output name, acceptance criteria, observed values, development dataset description, and test dataset description. It's the same format we use for regulatory strategy output and Fast 510(k) input, and the fastest high-level fingerprint of an AI device. AI-generated but reliable in practice.
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Fuzzy results trail off in relevance as you scroll. Use three signals to decide how far down to go: the fuzzy badge explanations, the intended use column, and whether your target output (e.g., Cobb angle) still appears in the AI Performance sub-table. Once it stops appearing, you're past the relevant zone. A top hit with a low score (~0.4) and a stretched explanation is a hint the closest predicates are far away — the project may be headed for De Novo. Note the fuzzy search is a pattern match: it doesn't handle negation ("not") well, and hardware devices can appear — filter by SaMD/AI ML to cut them.
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Open the Predicates tab for a family-tree view of predicate relationships. Click a node to trace its parents and children; selections from search carry over pre-selected. Commonly predicated devices are worth reading — a lot of people predicated them for a reason. The visual lineage is also handy on client calls, e.g. to show how a predicate family evolved and justify why your predicate still holds.
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The Embeddings tab plots every matching document in a 2-D "galaxy map" where semantically similar devices cluster together. Hover or click clusters to explore, and let AI label the clusters for you. Embeddings beat product codes for grouping: two devices can carry different product codes (LLZ vs. QIH) yet do the same thing — the embedding captures the meaning of the intended use and device story. This is also exactly how retrieval-augmented generation (RAG) works under the hood, and it makes a great visual on client calls.
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Head to the search page and work through a few of these AI/ML fuzzy searches to build intuition: perivascular fat on CT · aortic valve calcification opportunistic screening on noncontrast CT · breast cancer prediction on digital pathology slides · autism detection · gestational age prediction · a hearing aid that can also detect a pulse · foundation model based analysis of ECG · large language models · penetration test. Watch how the relevance scores, intended use, and AI Performance tables tell you when results stop being meaningful.
