(354 days)
The LIAISON® Rubella IgG uses chemiluminescencc immunoussay (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.
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).
The provided document describes the DiaSorin LIAISON® Rubella IgG Assay, a chemiluminescence immunoassay (CLIA) for the qualitative determination of IgG antibodies to rubella virus in human serum, intended as an aid in determining immune status, including in pregnant women.
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are not explicitly stated in numerical thresholds within the provided text. Instead, the document presents comparative study results against a "commercially available rubella chemiluminescence test kit" and consensus testing with three FDA-cleared ELISA devices for equivocal samples, as well as an evaluation using a CDC performance panel. The reported device performance is as follows:
| Performance Metric | Acceptance Criteria (Implied/Expected) | Reported Device Performance (Routine Samples) | Reported Device Performance (Pregnant Women) |
|---|---|---|---|
| Positive Agreement (LIAISON® vs. Comparator/Consensus) | High agreement with established methods | 97.2% (1984/2042) | 95.8% (416/434) |
| Negative Agreement (LIAISON® vs. Comparator/Consensus) | High agreement with established methods | 92.3% (108/117) | 64.3% (9/14)c* |
| Negative Agreement (Pre-selected Negative Subjects) | High agreement for known negative samples | 100% (85/85) | 100% (99/99) |
| CDC Performance Panel (82 positive sera) | Correctly identify positive status | 80 positive tests (97.6%) | N/A |
| CDC Performance Panel (18 negative sera) | Correctly identify negative status | 18 negative tests (100%) | N/A |
| Cross-Reactivity | No positive/equivocal results with interfering substances | 0/59 to 0/1 (depending on organism/condition) | N/A |
| Interfering Substances | No significant change in qualitative results | No significant change observed | N/A |
| Hook Effect | No specimen misclassification at high concentrations | No hook effect observed | N/A |
| Precision (Overall %CV) | Acceptable variability | Ranges from 5.9% to 15.7% (Single-site) and 5.70% to 15.62% (Multi-site) | N/A |
*c: Number of samples too low to reliably calculate % negative agreement for this group.
2. Sample Size Used for the Test Set and Data Provenance
- Comparative Study (Non-selected subjects):
- Total: 2806 prospectively collected frozen specimens.
- Routine Rubella IgG Testing: 2159 samples.
- Pregnant Women: 449 samples.
- Data Provenance: Prospectively collected specimens from U.S. subjects. The "routine rubella IgG testing" and "pregnant women" samples were part of this overall set. Samples were divided randomly, and testing sites were blinded to populations and comparator results.
- Comparative Study (Pre-selected Negative Subjects):
- Total: 198 pre-selected negative subjects.
- Routine Rubella IgG Testing: 98 subjects.
- Pregnant Women: 100 subjects.
- Data Provenance: Prospectively collected from U.S. subjects. These were pre-selected based on initial negative results from predicate device testing.
- CDC Performance Panel: 100 specimens (50 pairs of sera, 18 negative, 82 positive).
- Data Provenance: Obtained from the CDC (Centers for Disease Control and Prevention), a masked, characterized serum panel.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number or specific qualifications (e.g., "radiologist with 10 years of experience") of experts used to establish the ground truth.
For the comparative study, the ground truth was established by:
- "a commercially available rubella chemiluminescence test kit" (predicate device).
- For equivocal samples from the predicate device, a consensus of 2 out of 3 results from three FDA-cleared ELISA devices was used.
- For the pre-selected negative subjects, the initial predicate device testing (rubella antibody testing performed by the laboratories) was used to define samples as negative. For the 100 pregnant women, no equivocal results were found in the initial predicate test, so no consensus was needed for this cohort.
For the CDC Performance Panel, the samples were a "masked, characterized serum panel" with known status (titered by HI), implying the ground truth was established by the CDC through their characterization methods.
4. Adjudication Method for the Test Set
- For equivocal samples from the predicate device: A "2 out of 3 rule using 3 additional FDA cleared assays" was applied. If a sample had concordant results by at least two of the three methods, the consensus defined the result. If discordant or concordant equivocal, the sample remained classified as equivocal.
- For the pre-selected negative subjects: The initial predicate test results were used as the basis for definition (no explicit "adjudication" beyond that initial classification is mentioned in the context of validating the LIAISON device).
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This device is an in-vitro diagnostic assay that provides an objective measurement (Index value) and qualitative result (Positive, Negative, Equivocal) rather than relying on human interpretation of images or other subjective data. Therefore, the concept of "human readers improve with AI vs. without AI assistance" does not apply.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
Yes, the studies presented are standalone performance evaluations of the DiaSorin LIAISON® Rubella IgG Assay. The output is a numerical Index and a qualitative classification (Positive, Equivocal, Negative) generated by the automated LIAISON Analyzer based on the chemiluminescence immunoassay technology. There is no human-in-the-loop interpretation that impacts the device's direct output.
7. The Type of Ground Truth Used
- Comparative Studies:
- Comparator Assay / Predicate Device: A commercially available rubella chemiluminescence test kit.
- Consensus Testing: For equivocal samples, results from "three FDA cleared devices" (ELISA assays) using a 2 out of 3 rule.
- Pre-selected Negatives: Initial negative classification by existing laboratory rubella IgG testing.
- CDC Performance Panel: Characterized serum panel with known rubella IgG status, likely established through a combination of serological methods, including HI (Hemagglutination Inhibition).
8. The Sample Size for the Training Set
The document does not explicitly describe a separate "training set" in the context of machine learning or AI development. Since this is an immunoassay, the device's "training" would typically involve optimization and calibration during development using internal panels, but these are not explicitly detailed as a distinct "training set" in a manner typical for AI algorithms in this regulatory submission. All the sample sizes mentioned (2806 for comparative, 100 for CDC) are used for performance evaluation/testing.
9. How the Ground Truth for the Training Set Was Established
As no explicit "training set" in the AI sense is provided, the method for establishing its ground truth is not applicable or detailed in this document. The assay's parameters would have been established and optimized during its development using various internal reference materials and panels, but these are not outlined as a formal "training set" with established ground truth in the context of this 510(k) summary.
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i073390
| 5.0 | 510(k) SUMMARY | NOV 21 2008 | |
|---|---|---|---|
| SUBMITTED BY: | Mari MeyerSenior Manager, Regulatory AffairsDiaSorin Inc.1951 Northwestern AvenueP.O. Box 285Stillwater, MN 55082-0285Phone (651) 439-9710Fax (651) 351-5669E-mail: mari.meyer@diasorin.com | ||
| NAME OF DEVICE:Trade Name: | DiaSorin LIAISON® Rubella IgG AssayDiaSorin 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 IgGassay, 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,
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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) | |||||
| < 20 | 285 | 24 | 1 | 260 | 91.2% |
| 20 - 39 | 1427 | 101 | 13 | 1313 | 92.0% |
| 40 - 59 | 381 | 28 | 2 | 353 | 92.6% |
| >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) | ||||||||
| <20 | 66 | 2 | 1 | 63 | 95.4% | |||
| 20 – 29 | 259 | 8 | 2 | 249 | 96.1% | |||
| 30 - 39 | 117 | 3 | 0 | 114 | 97.4% | |||
| >40 | 6 | 0 | 0 | 6 | 100% | |||
| Unknown | 1 | 0 | 0 | 1 | 100% |
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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.
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Prospective Non-selected Subjects
| LIAISON®RubellaIgG Results | Routine SamplesConsensus Result | Pregnant Women SamplesConsensus 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 SamplesConsensus 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.
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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.
| SampleID# | N | mean(Index) | withinrunsd | withinrun%CV | betweenrunsd | betweenrun%CV | overallsd | overall%CV |
|---|---|---|---|---|---|---|---|---|
| Neg Ctl | 80 | <<0.1 | NA | NA | NA | NA | NA | NA |
| Low Pos Ctl | 80 | 1.63 | 0.08 | 5.12 | 0.14 | 8.40 | 0.16 | 9.6 |
| Hi Pos Ctl | 80 | 14 | 1.75 | 13.1 | 1.34 | 9.66 | 2.17 | 15.7 |
| R01 | 80 | 0.68 | 0.03 | 4.06 | 0.04 | 5.23 | 0.04 | 6.3 |
| R02 | 80 | 0.61 | 0.02 | 3.32 | 0.03 | 5.07 | 0.04 | 5.9 |
| R03 | 80 | 0.90 | 0.03 | 3.64 | 0.04 | 4.74 | 0.05 | 5.9 |
| R04 | 80 | 1.07 | 0.04 | 4.19 | 0.05 | 4.99 | 0.07 | 6.5 |
| R05 | 80 | 0.88 | 0.03 | 3.42 | 0.04 | 5.09 | 0.05 | 6.0 |
| R06 | 80 | 1.16 | 0.05 | 4.52 | 0.10 | 8.38 | 0.11 | 9.4 |
| R07 | 80 | 2.4 | 0.11 | 4.85 | 0.21 | 9.13 | 0.23 | 9.9 |
| R08 | 80 | 2.5 | 0.17 | 7.05 | 0.24 | 9.64 | 0.29 | 11.5 |
| R09 | 80 | 3.1 | 0.19 | 6.20 | 0.27 | 8.68 | 0.32 | 10.3 |
| R10 | 80 | 3.2 | 0.21 | 6.52 | 0.30 | 9.45 | 0.36 | 10.9 |
| R11 | 80 | 15 | 1.37 | 9.26 | 1.69 | 11.3 | 2.14 | 13.9 |
| R12 | 80 | 24 | 2.21 | 10.2 | 2.99 | 12.8 | 3.65 | 15.3 |
An assay reproducibility study was conducted at two external U.S. laboratories and at DiaSorin, according to CLSI document EP15-A2. The study included 3 different kit lots and the same coded panel as described in the twenty day study. The same coded panel was tested at all three sites, in four replicates per run for five runs. The results are summarized in the following table.
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DiaSorin LIAISON® Rubella Premarket Notification
| sampleID# | N | meanIndex | withinrunSD | withinrun%CV | betweenrunSD | betweenrun%CV | betweensiteSD | betweensiteCV | overallsd | overall%CV |
|---|---|---|---|---|---|---|---|---|---|---|
| Neg Ctl | 60 | <<0.1 | NA | NA | NA | NA | NA | NA | NA | NA |
| Low Pos Ctl | 60 | 1.50 | 0.06 | 4.02 | 0.12 | 4.23 | 0.12 | 8.37 | 0.13 | 8.78 |
| Hi Pos Ctl | 60 | 12.6 | 1.0 | 8.17 | 1.30 | 6.04 | 1.28 | 17.0 | 1.64 | 13.09 |
| R01 | 60 | 0.67 | 0.02 | 3.56 | 0.03 | 4.27 | 0.02 | 16.8 | 0.04 | 5.70 |
| R02 | 60 | 0.59 | 0.02 | 3.02 | 0.04 | 4.90 | 0.02 | 12.6 | 0.04 | 6.90 |
| R03 | 60 | 0.90 | 0.02 | 2.51 | 0.06 | 6.12 | 0.02 | 4.21 | 0.06 | 6.73 |
| R04 | 60 | 1.06 | 0.04 | 4.15 | 0.09 | 6.37 | 0.05 | 1.12 | 0.10 | 9.07 |
| R05 | 60 | 0.88 | 0.03 | 3.21 | 0.06 | 6.50 | 0.02 | 6.47 | 0.07 | 7.53 |
| R06 | 60 | 1.12 | 0.03 | 2.77 | 0.09 | 6.44 | 0.06 | 6.83 | 0.10 | 8.59 |
| R07 | 60 | 2.3 | 0.1 | 3.36 | 0.22 | 4.14 | 0.20 | 10.3 | 0.22 | 9.54 |
| R08 | 60 | 2.4 | 0.1 | 4.03 | 0.26 | 7.52 | 0.17 | 8.02 | 0.27 | 11.07 |
| R09 | 60 | 3.1 | 0.1 | 4.77 | 0.26 | 7.68 | 0.15 | 9.56 | 2.90 | 9.46 |
| R10 | 60 | 3.2 | 0.2 | 5.87 | 0.28 | 7.82 | 0.10 | 8.05 | 0.33 | 10.45 |
| R11 | 60 | 14.3 | 1.0 | 7.05 | 2.03 | 11.32 | 1.19 | 18.6 | 2.2 | 15.62 |
| R12 | 60 | 21.7 | 1.4 | 6.56 | 2.24 | 6.79 | 1.95 | 18.8 | 2.66 | 12.25 |
Traceability as Compared to the international preparation RUBI-1-94 - NIBSC (WHO 1st International Standard for anti-Rubella Immunoglobulin, Human - 1997): The concordance of the assay with the WHO International Standard was evaluated using serial dilutions of the standard preparation. The dilutions were tested with two lots of in the LIAISON® Rubella IgG. The cut-off (=1 Index) calculated by interpolation on Index doses corresponds to 32400 RLUs. This RLU value calculated by interpolation on the WHO curve is 9.42 IU/mL.
| dilutions | Expected index | Actual index(mean) | Expected WHOdose (IU/mL) |
|---|---|---|---|
| 1:8 | 20.0 | 20.4 | 200 |
| 1:16 | 10.0 | 10.1 | 100 |
| 1:32 | 5.0 | 4.7 | 50 |
| 1:64 | 2.5 | 2.2 | 25 |
| 1:128 | 1.3 | 1.32 | 12.5 |
| 1:256 | 0.63 | 0.67 | 6.25 |
| 1:512 | 0.31 | 0.24 | 3.13 |
Linear regression between WHO doses (IU/mL) vs Index:
| Linear regression | Lot 1 | Lot 2 |
|---|---|---|
| R square | 0.9987 | 0.9982 |
| Intercept | 0.1081 | 0.1542 |
| Slope | 0.1086 | 0.0962 |
| Result at WHO cut off | 0.98 Index | 0.81 Index |
Cross-reactions: The cross-reactivity study for the LIAISON® Rubella IgG assay was designed to evaluate potential interference from other organisms that may cause symptoms similar to Rubella virus infection (VZV, Measles, Mumps), other organisms that may cause infectious disease (HAV, HBV, HDV, HIV, CMV, HSV, EBV, Toxoplasma gondii. Parvovirus, Treponema pallidum) and from other conditions that may result from atypical immune system activity (hypergammaglobulin, antinuclear autoantibodies, Rheumatoid Factor). Samples for these studies were pre-screened with another commercially available Rubella IgG assay. If found negative for Rubella IgG antibodies they were used to study potential cross-reactivity. The presence of IgG antibodies to the potential cross-reactants in the samples was confirmed using FDA-cleared assays.
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| Organism/condition | Number of ExpectedNegative Samples | LIAISON® Positive orequivocal Result |
|---|---|---|
| anti-HAV | 59 | 0/59 |
| CMV IgG | 58 | 0/58 |
| HBsAg | 3 | 0/3 |
| HSV ½ IgG | 67 | 0/67 |
| Toxoplasma IgG | 12 | 0/12 |
| VCA IgG | 70 | 0/70 |
| VZV IgG | 50 | 0/50 |
| Measles IgG | 3 | 0/3 |
| Mumps IgG | 2 | 0/2 |
| Anti-HCV | 3 | 0/3 |
| Anti-HIV 1/2 | 2 | 0/2 |
| Parvovirus IgG | 2 | 0/2 |
| y-globulin | 3 | 0/3 |
| ANA | 11 | 0/11 |
| RF | 1 | 0/1 |
| Treponema pallidum | 1 | 0/1 |
No positive result was found for the specimens when tested by LIAISON® Rubella IgG.
WARNING: Assay Interference due to circulating HAMA has not been evaluated. The user is responsible for establishing cross-reactivity performance with these antibodies.
Potentially Interfering Substances
The DiaSorin LIAISON® Rubella IgG assay was evaluated for interference according to CLSI Document EP7. A panel of 12 samples with rubella Index values ranging from 0.61 - 19.4 were tested with two levels each of hemoglobin (500 and 1000 mg/dL), billirubin (10 and 20 mg/dL) and triglycerides (500 and 3000 mg/dL). None of the interferents at the levels tested produced a significant change in the qualitative results of the assay.
Hook effect
No hook effect was found when two specimens with high level of anti-rubella IgG were tested. The specimens were tested neat and after serial dilution. Each point was tested in triplicate usina one kit lot.
The specimens resulted in the estimated index values above the measuring range as expected for specimens with high level of anti-rubella IgG, indicating no specimen misclassification.
CONCLUSION
The submitted material in this premarket notification is complete and supports a substantial equivalence decision. The labeling is sufficient and it satisfies the requirements of 21 CFR Part 809.10.
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DEPARTMENT OF HEALTH & HUMAN SERVICES
Image /page/7/Picture/1 description: The image shows the logo for the Department of Health & Human Services - USA. The logo is a stylized image of a person with their arms outstretched, and it is surrounded by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA". The logo is black and white, and it is simple in design.
Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-002
JAN 11 2013
DiaSorin, Inc. C/O Mari Meyer Senior Manager, Regulatory Affairs 1951 Northwestern Avenue Stillwater, MN 55082
Re: K073390 Trade/Device Name: LIAISON® Rubella IgG LIAISON® Rubella IgG Tri-Controls Regulation Number: 21 CFR 866.3510 Regulation Name: Rubella Virus Serological Reagents Regulatory Class: II Product Code: LFX, JJX Dated: November 10, 2008 Received: November 12, 2008
Dear Ms. Meyer:
This letter corrects our substantially equivalent letter of November 21, 2008.
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. 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.
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
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comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
If you desire specific advice for your device on our labeling regulation (21 CFR Parts 801 and 809), please contact the Office of In Vitro Diagnostics and Radiological Health at (301) 796-5450. 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Uwe Scherf for
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
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Indication for Use
510(k) Number (if known): K073390
Device Name:
LIAISON® Rubella IgG and LIAISON® Rubella IgG Tri-Controls.
Indication For Use:
The LIAISON® Rubella IgG uses chemiluminescencc immunoussay (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.
Prescription Use X (21 CFR Part 801 Subpart D)
And/Or
Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
Uhe Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K073310
Page 1 of 2
§ 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.