(354 days)
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No
The summary describes a standard chemiluminescence immunoassay (CLIA) for detecting rubella antibodies. There is no mention of AI, ML, or any related technologies in the device description, performance studies, or key metrics. The analysis is based on standard laboratory techniques and statistical measures of agreement.
No
This device is an in vitro diagnostic (IVD) test intended to aid in the determination of immune status to rubella. It analyzes a sample for the presence of antibodies but does not directly treat or prevent a disease.
Yes
Explanation: The device is described as aiding in the "qualitative determination of IgG antibodies to rubella virus in human serum specimens" and "intended for use as an aid in the determination of immune status to rubella". These functions directly support diagnosing a person's immune status regarding rubella.
No
The device is a laboratory assay that uses chemiluminescence technology on a specific analyzer (LIAISON Analyzer) to detect antibodies in human serum. This involves physical reagents and a hardware analyzer, not just software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative determination of IgG antibodies to rubella virus in human serum specimens." This involves testing biological samples (human serum) outside of the body to gain information about a person's health status (immune status to rubella).
- Device Description: The description details a "chemiluminescence immunoassay (CLIA)" method performed on a "LIAISON® Analyzer." This is a laboratory-based test using reagents and equipment to analyze a biological sample.
- Performance Studies: The document describes various performance studies conducted on human serum specimens to evaluate the assay's accuracy and reliability in detecting rubella IgG antibodies. This is a standard requirement for IVD devices.
The definition of an In Vitro Diagnostic (IVD) is a medical device that is used to perform tests on samples such as blood, urine, or tissues to detect diseases or other conditions. This device clearly fits that definition.
N/A
Intended Use / Indications for Use
The LIAISON® Rubella IgG uses chemiluminescence immunoassay (CLIA) technology on the LIAISON Analyzer for the qualitative determination of IgG antibodies to rubella virus in human serum specimens. It is intended for use as an aid in the determination of immune status to rubella in individuals including pregnant women.
The performance of this device has not been established for cord blood, neonatal samples, or for any matrices other than human serum. Likewise, performance has not been established for population(s) of immunocompromised or immunosuppressed individuals.
The LIAISON® Rubella IgG Tri-Control kit is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Rubella IgG assay.
Product codes (comma separated list FDA assigned to the subject device)
LFX, JJX
Device Description
The method for qualitative determination of specific IgG to Rubella virus is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Analyzer. The principal components of the test are magnetic particles (solid phase) coated with Rubella antigen and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, Rubella virus antibodies present in the calibrators, specimens or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with Rubella virus IgG already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal, and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU).
Mentions image processing
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Mentions AI, DNN, or ML
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Input Imaging Modality
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Anatomical Site
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Indicated Patient Age Range
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Intended User / Care Setting
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Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
A total of 2806 prospectively collected frozen specimens were tested in the comparative study. Of these, 2608 were from non-selected subjects: 2159 subjects sent to the laboratory for routine rubella IgG testing and 449 pregnant women. Samples were divided randomly and the testing sites were blinded to samples' populations and comparator results prior to LIAISON® testing. Given the lack of statistical power to properly assess the pregnant women negative agreement an unbiased analysis of pre-selected samples was performed. Of the 2806 specimens, 198 negative pre-selected subjects were tested: 98 subjects sent to the laboratory for routine Rubella IgG testing and 100 pregnant women tested for Rubella antibodies as part of their routine pre-natal care. The rubella antibody testing performed by the laboratories was used to define the samples as negative. All of these specimens were tested for the presence of Rubella IgG antibodies using the LIAISON® Rubella IgG assay and a commercially available rubella chemiluminescence test kit. Three FDA cleared devices were chosen as the additional methods to test the predicate device equivocal samples. The classification of samples equivocal by the predicate device was reassigned based on the consensus of the combined 2 out of 3 results from the three ELISA results, i.e. a sample with concordant result by at least two of the three methods was defined following the consensus. If the results by the three methods were either discordant among themselves or concordant equivocal, the sample was classified as equivocal.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
COMPATATIVE STUDY
- Description: A total of 2806 prospectively collected frozen specimens were tested. 2608 were from non-selected subjects (2159 samples from routine testing and 449 pregnant women samples). 198 were pre-selected negative subjects (98 from routine testing and 100 pregnant women samples). Specimens were tested using the LIAISON® Rubella IgG assay and a commercially available rubella chemiluminescence test kit. Equivocal results from the predicate device were reclassified based on a 2 out of 3 consensus rule using three additional FDA cleared ELISA assays.
- Sample Size: 2806
- Results:
- Prospective Non-selected Subjects (Routine Samples):
- Positive Agreement: 97.2% (1984/2042) with 95% CI 96.5 - 97.7%
- Negative Agreement: 92.3% (108/117) with 95% CI 87.0 - 95.9%
- Prospective Non-selected Subjects (Pregnant Women Samples):
- Positive Agreement: 95.8% (416/434) with 95% CI 93.9 - 97.3%
- Negative Agreement: 64.3% (9/14) with 95% CI 39.1 - 84.7%
- Pre-selected Negative Subjects (Routine Samples):
- Positive Agreement: 69% (9/13) with 95% CI 42.8 - 88.7%
- Negative Agreement: 100% (85/85) with 95% CI 89.6 - 98.0%
- Pre-selected Negative Subjects (Pregnant Women Samples):
- Positive Agreement: N/A
- Negative Agreement: 100% (99/99) with 95% CI 97.0 - 100.0%
- Prospective Non-selected Subjects (Routine Samples):
CDC Performance Panel Results
- Description: A serum panel of 100 specimens from the CDC (Centers for Disease Control and Prevention), consisting of 50 pairs of sera titered by HI (18 negative specimens, 82 positive specimens). The panel was tested on the LIAISON® Rubella IgG assay.
- Sample Size: 100 specimens
- Results:
- 80 positive tests out of 82 positive sera.
- 2 negative tests out of 82 positive sera.
- 18 negative tests out of 18 negative sera.
Precision Study
- Description: Established at DiaSorin according to CLSI document, EP5-A2. A coded panel of 12 frozen repository samples was prepared and tested in the LIAISON® Rubella IgG assay. Panel members represented negative, low to mid positive, and moderate to high positive analyte levels. Tested in four replicates per run for twenty runs.
- Sample Size: 80 replicates per sample ID (12 samples)
- Key Metrics: Within-run SD, within-run %CV, between-run SD, between-run %CV, overall SD, overall %CV for various index values.
- Low Pos Ctl: mean 1.63, overall %CV 9.6
- Hi Pos Ctl: mean 14, overall %CV 15.7
Assay Reproducibility Study
- Description: Conducted at two external U.S. laboratories and at DiaSorin, according to CLSI document EP15-A2. Included 3 different kit lots and the same coded panel as the precision study. The panel was tested at all three sites, in four replicates per run for five runs.
- Sample Size: 60 replicates per sample ID (12 samples)
- Key Metrics: Within-run SD, within-run %CV, between-run SD, between-run %CV, between-site SD, between-site CV, overall SD, overall %CV for various index values.
- Low Pos Ctl: mean 1.50, overall %CV 8.78
- Hi Pos Ctl: mean 12.6, overall %CV 13.09
Traceability Study
- Description: Compared to the international preparation RUBI-1-94 - NIBSC (WHO 1st International Standard for anti-Rubella Immunoglobulin, Human - 1997) using serial dilutions.
- Results: The cut-off (=1 Index) corresponds to 32400 RLUs, which is 9.42 IU/mL.
- Linear regression between WHO doses (IU/mL) vs Index:
- Lot 1: R square 0.9987, Intercept 0.1081, Slope 0.1086, Result at WHO cut off 0.98 Index
- Lot 2: R square 0.9982, Intercept 0.1542, Slope 0.0962, Result at WHO cut off 0.81 Index
Cross-reactivity
- Description: Evaluated potential interference from other organisms (VZV, Measles, Mumps, HAV, HBV, HDV, HIV, CMV, HSV, EBV, Toxoplasma gondii, Parvovirus, Treponema pallidum) and conditions (hypergammaglobulin, antinuclear autoantibodies, Rheumatoid Factor). Samples were pre-screened as negative for Rubella IgG and confirmed for potential cross-reactants using FDA-cleared assays.
- Results: No positive result was found for the specimens when tested by LIAISON® Rubella IgG.
Potentially Interfering Substances
- Description: Evaluated according to CLSI Document EP7. A panel of 12 samples (rubella Index 0.61 - 19.4) was tested with two levels each of hemoglobin (500 and 1000 mg/dL), bilirubin (10 and 20 mg/dL) and triglycerides (500 and 3000 mg/dL).
- Results: None of the interferents at the levels tested produced a significant change in the qualitative results of the assay.
Hook effect
- Description: Two specimens with high levels of anti-rubella IgG were tested neat and after serial dilution. Each point was tested in triplicate using one kit lot.
- Results: No hook effect was found. The specimens resulted in estimated index values above the measuring range as expected, indicating no specimen misclassification.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Comparative Study - % Agreement:
- Prospective Non-selected Subjects (Routine Samples):
- Positive Agreement: 97.2%
- Negative Agreement: 92.3%
- Prospective Non-selected Subjects (Pregnant Women Samples):
- Positive Agreement: 95.8%
- Negative Agreement: 64.3%
- Pre-selected Negative Subjects (Routine Samples):
- Positive Agreement: 69%
- Negative Agreement: 100%
- Pre-selected Negative Subjects (Pregnant Women Samples):
- Positive Agreement: N/A
- Negative Agreement: 100%
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Bayer Diagnostics, ADVIA Centaur Rubella IgG assay, K003412
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
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Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
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§ 866.3510 Rubella virus serological reagents.
(a)
Identification. Rubella virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to rubella virus in serum. The identification aids in the diagnosis of rubella (German measles) or confirmation of a person's immune status from past infections or immunizations and provides epidemiological information on German measles. Newborns infected in the uterus with rubella virus may be born with multiple congenital defects (rubella syndrome).(b)
Classification. Class II. The special controls for this device are:(1) National Committee for Clinical Laboratory Standards':
(i) 1/LA6 “Detection and Quantitation of Rubella IgG Antibody: Evaluation and Performance Criteria for Multiple Component Test Products, Speciment Handling, and Use of the Test Products in the Clinical Laboratory, October 1997,”
(ii) 1/LA18 “Specifications for Immunological Testing for Infectious Diseases, December 1994,”
(iii) D13 “Agglutination Characteristics, Methodology, Limitations, and Clinical Validation, October 1993,”
(iv) EP5 “Evaluation of Precision Performance of Clinical Chemistry Devices, February 1999,” and
(v) EP10 “Preliminary Evaluation of the Linearity of Quantitive Clinical Laboratory Methods, May 1998,”
(2) Centers for Disease Control's:
(i) Low Titer Rubella Standard,
(ii) Reference Panel of Well Characterized Rubella Sera, and
(3) World Health Organization's International Rubella Standard.
0
i073390
| 5.0 | 510(k) SUMMARY | NOV 21 2008 | |
|---|---|---|---|
| SUBMITTED BY: | Mari Meyer | ||
| Senior Manager, Regulatory Affairs | |||
| DiaSorin Inc. | |||
| 1951 Northwestern Avenue | |||
| P.O. Box 285 | |||
| Stillwater, MN 55082-0285 | |||
| Phone (651) 439-9710 | |||
| Fax (651) 351-5669 | |||
| E-mail: mari.meyer@diasorin.com | |||
| NAME OF DEVICE: | |||
| Trade Name: | DiaSorin LIAISON® Rubella IgG Assay | ||
| DiaSorin LIAISON® Rubella IgG Tri-Controls | |||
| Common Names/Descriptions: | Rubella IgG Test Reagents and Controls | ||
| Classification Names: | Rubella Virus Serological Reagent | ||
| Product Code: | LFX, JJX | ||
| PREDICATE DEVICE: | Bayer Diagnostics, ADVIA Centaur Rubella IgG | ||
| assay, K003412 |
DEVICE DESCRIPTION:
INTENDED USE: The LIAISON Rubella IgG uses chemiluminescence immunoassay (CLIA) technology on the LIAISON Analyzer for the qualitative determination of IgG antibodies to rubella virus in human serum specimens. It is intended for use as an aid in the determination of immune status to rubella in individuals including pregnant women.
The performance of this device has not been established for cord blood, neonatal samples, or for any matrices other than human serum. Likewise, performance has not been established for population(s) of immunocompromised or immunosuppressed individuals.
The LIAISON® Rubella IgG Tri-Control kit is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Rubella IgG assay.
KIT DESCRIPTION:
The method for qualitative determination of specific IgG to Rubella virus is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Analyzer. The principal components of the test are magnetic particles (solid phase) coated with Rubella antigen and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, Rubella virus antibodies present in the calibrators, specimens or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with Rubella virus IgG already bound to the solid phase. After each incubation, the unbound material is removed with a wash cycle. Subsequently, the starter reagents are added and a flash chemiluminescence reaction is thus induced. The light signal,
1
and hence the amount of isoluminol-antibody conjugate, is measured by a photomultiplier as relative light units (RLU)
PERFORMANCE DATA: EXPECTED VALUES
The LIAISON® Rubella IgG assay was tested with prospectively collected specimens from U.S. subjects routinely sent to the laboratory for rubella IgG testing (n=2159) and from pregnant women (n=449) to evaluate the assay's performance in these populations. Of the 2159 samples sent to the laboratory for routine rubella IgG testing, 91.7% were positive. Of the 449 pregnant women samples, 96.4% were positive. The distribution of results for IgG antibodies to rubella in these populations as determined by the LIAISON® Rubella IgG assay is summarized as follows.
Prospectively-collected Samples from Subjects sent to the Laboratory for Rubella IgG Testing:
| N | Negative | Equivocal | Positive | Prevalence | |
|---|---|---|---|---|---|
| Total | 2159 | 154 | 15 | 1990 | 91.7% |
| Gender | |||||
| Female | 1848 | 127 | 14 | 1707 | 92.4% |
| Male | 310 | 27 | 1 | 282 | 91.8% |
| Unknown | 1 | 0 | 0 | 1 | 100% |
| Age (years) | |||||
| 60 | 61 | 1 | 1 | 59 | 96.7% |
| Unknown | 5 | 0 | 0 | 5 | 100% |
Prospectively-collected Samples from Pregnant Women
| LIAISON® Rubella IgG | ||||||||
|---|---|---|---|---|---|---|---|---|
| N | Negative | Equivocal | Positive | Prevalence | ||||
| Total | 449 | 13 | 3 | 433 | 96.4% | |||
| Age (years) | ||||||||
| 40 | 6 | 0 | 0 | 6 | 100% | |||
| Unknown | 1 | 0 | 0 | 1 | 100% |
2
COMPARATIVE STUDY
A total of 2806 prospectively collected frozen specimens were tested in the study. Of these, 2608 were from non-selected subjects: 2159 subjects sent to the laboratory for routine rubella IgG testing and 449 pregnant women. Samples were divided randomly and the testing sites were blinded to samples' populations and comparator results prior to LIAISON® testing. Given the lack of statistical power to properly assess the pregnant women negative agreement an unbiased analysis of pre-selected samples was performed as shown below. Of the 2.806 specimens, 198 negative pre-selected subjects were tested: 98 subjects sent to the laboratory for routine Rubella IgG testing and 100 pregnant women tested for Rubella antibodies as part of their routine pre-natal care. The rubella antibody testing performed by the laboratories was used to define the samples as negative. No equivocal results were found in the initial predicate test of the 100 pregnant women, hence there was no need for consensus result to be performed on this cohort.
All of these specimens were tested for the presence of Rubella IgG antibodies using the LIAISON® Rubella IgG assay and a commercially available rubella chemiluminescence test kit. Three FDA cleared devices were chosen as the additional methods to test the predicate device equivocal samples. The classification of samples equivocal by the predicate device was reassigned based on the consensus of the combined 2 out of 3 results from the three ELISA results, i.e. a sample with concordant result by at least two of the three methods was defined following the consensus. If the results by the three methods were either discordant among themselves or concordant equivocal, the sample was classified as equivocal. The following tables compare the results obtained for the LIAISON® Rubella IgG assay and commercially available Rubella tests.
Specimens that were equivocal by both, the LIAISON® Rubella IgG assay and the consensus from the three ELISA tests were not included in the percent calculation. Positive or negative results from the LIAISON® Rubella IgG assay were considered as non-agreements in the calculation of percent positive agreement and percent negative agreement when the corresponding comparator method result was equivocal.
Compared number of samples positive on both assays to sum of all positive samples on the reference assay + samples equivocal on the comparator method and negative on the LIAISON® Rubella IgG.
Compared number of samples negative on both assay to sum of all negative samples on the reference assay + samples equivocal on the comparator method and positive on the LIAISON® Rubella IgG.
3
Prospective Non-selected Subjects
| LIAISON®
Rubella
IgG Results | Routine Samples
Consensus Result | | | | Pregnant Women Samples
Consensus Result | | | |
|------------------------------------|-------------------------------------|-------|-----|-------|--------------------------------------------|-------|-----|-------|
| | Pos | Equiv | Neg | Total | Pos | Equiv | Neg | Total |
| Pos | 1985 | 2 | 3 | 1990 | 416 | 1 | 2 | 419 |
| Equiv | 11 | 0 | 4 | 15 | 4 | 1 | 2 | 7 |
| Neg | 40 | 6 | 108 | 154 | 13 | 1 | 9 | 23 |
| Total | 2036 | 8 | 115 | 2159 | 433 | 3 | 13 | 449 |
| % Agreement | 95% CIb | % Agreement | 95% CIb | |
|---|---|---|---|---|
| Positive | 97.2% (1984/2042) | 96.5 - 97.7% | 95.8% (416/434) | 93.9 - 97.3% |
| Negative | 92.3% (108/117) | 87.0 - 95.9% | 64.3% (9/14)c | 39.1 - 84.7% |
2 out of 3 rule using 3 additional FDA cleared assays performed on initial festing equivocals only Confidence Interval
- Confidence Interval
- Number of samples in
e Number of samples too low to reliably calculate % negalive agreement.
Pre-selected Negative Subjects
| LIAISON® Rubella | Routine Samples
Consensus Result* | | | | Pregnant Women Samples | | | |
|------------------|--------------------------------------|-------|-----|-------|------------------------|-------|-----|-------|
| IgG Results | Pos | Equiv | Neg | Total | Pos | Equiv | Neg | Total |
| Pos | 9 | 0 | 0 | 9 | 0 | 0 | 0 | 0 |
| Equiv | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Neg | 3 | 1 | 85 | 89 | 1 | 0 | 99 | 100 |
| Total | 12 | 1 | 85 | 98 | 1 | 0 | 99 | 100 |
| % Agreement | 95% CI | % Agreement | 95% CI | |
|---|---|---|---|---|
| Positive | 69% (9/13) | 42.8 - 88.7% | N/A | N/A |
| Negative | 100% (85/85) | 89.6 - 98.0% | 100% (99/99) | 97.0 - 100.0% |
4 2 out of 3 rule using 3 additional FDA cleared assays performed on initial testing equivocals only
CDC Performance Panel Results
The following information is from a serum panel obtained from the CDC (Centers for Disease Control and Prevention) and tested on the LIAISON® Rubella IgG assay. The results are presented as a means to convey further information on the performance of this assay with a masked, characterized serum panel. This does not imply an endorsement of the assay by the CDC.
The sera panel consists of 100 specimens, 50 pairs of sera titered by HI. There are 9 negative sera resulting in 18 negative specimens and 41 positive sera resulting in 82 positive specimens. The obtained data were submitted to the CDC for data analysis. As communicated by the CDC, the LIAISON® Rubella IgG assay resulted in 80 positive tests and 2 negative tests on the 82 positive sera, and 18 negative tests on the 18 negative sera.
4
CDC Biological Standard Results
The low titer (21.0 IU/mL) anti-rubella human reference serum CDC biological standard was tested neat and diluted 1:2 as described in the CLSI document I/LA6-A. The mean result of the neat standard was 3.3 Index. The mean result of the two fold diluted standard was 1.68 Index.
Precision
Assay precision performance was established at DiaSorin following protocol outlined in CLSI document, EP5-A2. A coded panel comprised of 12 frozen repository samples was prepared by DiaSorin and tested in the LIAISON® Rubella IgG assay. The panel contained samples prepared to represent negative levels, low to mid positive analyte levels and moderate to high positive levels. All panel members were divided into aliquots and stored frozen prior to testing. The coded panel was tested in four replicates per run for twenty runs. The results are summarized in the following table.
| Sample
ID# | N | mean
(Index) | within
run
sd | within
run
%CV | between
run
sd | between
run
%CV | overall
sd | overall
%CV |
|---------------|----|-----------------|---------------------|----------------------|----------------------|-----------------------|---------------|----------------|
| Neg Ctl | 80 |