(30 days)
The LIAISON® Rubella IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgM antibodies to rubella virus in human serum samples. It is intended for use as an aid in the diagnosis of a current or recent Rubella infection in individuals with signs and symptoms of Rubella, or suspected of having rubella virus infection, including women of child bearing age.
The LIAISON® Control Rubella IgM (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Rubella IgM assay.
The performance characteristics of LIAISON® Rubella IgM controls have not been established for any other assays or instrument platforms.
The LIAISON® Rubella IgM assay is an in vitro diagnostic device consisting of reagents provided in individual compartments within a plastic container called the Reagent Integral. The assay configuration for the LIAISON® Rubella IgM assay allows for the performance of 100 tests.
Reagent Integral Composition:
- a. Magnetic particles mouse monoclonal antibody IgG to human IgM
- b. Calibrator 1 human serum or defibrinated plasma containing low level of Rubella IqM
- c. Calibrator 2 human serum or defibrinated plasma containing high level of Rubella laM
- d. Antigen Inactivated rubella viral particles (HPV 77 strain)
- c. Specimen diluent buffer with BSA added
- d. Conjugate -- mouse monoclonal antibodies to rubella virus conjuqated to an isoluminol derivative
The LIAISON® Control Rubella IgM is an in vitro diagnostic device consisting of 2 levels of controls to monitor the performance of the LIAISON® Rubella IgM assay
Controls (2 vials of each level):
Negative control - human serum or defibrinated plasma non-reactive for Rubella IgM Positive control - human serum or defibrinated plasma reactive for Rubella IgM
Acceptance Criteria and Device Performance Study for LIAISON® Rubella IgM
This document describes the acceptance criteria and the study conducted to demonstrate the performance of the LIAISON® Rubella IgM assay.
1. Table of Acceptance Criteria and Reported Device Performance
The provided document details various analytical performance characteristics. While explicit "acceptance criteria" for all metrics (e.g., precision %CV thresholds) are not stated in a dedicated table, the studies were conducted to demonstrate acceptable performance for the intended use. The LIAISON® Rubella IgM performance is compared against these implicit standards and the FDA-cleared predicate device.
| Performance Characteristic | Acceptance Criteria (Implicit/Reference) | Reported Device Performance (LIAISON® Rubella IgM) |
|---|---|---|
| Precision (Total %CV) | Expected to be low for reliable results | Negative Control*: 12.3% |
| Positive Control: 12.8% | ||
| Rubella IgM-A*: 12.7% | ||
| Rubella IgM-B*: 15.9% | ||
| Rubella IgM-C: 14.8% | ||
| Rubella IgM-D: 14.1% | ||
| Rubella IgM-E: 13.4% | ||
| Rubella IgM-F: 13.0% | ||
| Rubella IgM-G: 11.9% | ||
| Cross-reactivity | No positive results from non-Rubella IgM | 0 positive, 0 equivocal out of 261 samples tested for various cross-reactants |
| High Dose Hook Effect | No misclassification due to high dose | No hook effect observed; samples with >400 AU/mL classified as above measuring range but not misclassified. |
| IgM Specificity | Loss of reactivity after DTT treatment | Absence of IgM anti-Rubella reactivity after DTT treatment for 10 positive samples. |
| Interference | % change in signal ≤ ±10% and no change in qualitative result at tested concentrations | No interference found for all 7 tested substances (Triglycerides, Hemoglobin, Bilirubin, Albumin, Cholesterol, Gamma-globulin, L-Ascorbic acid). |
| Propsective Study (Agreement with Predicate - Negative) | High agreement with predicate device for negative samples | 98.9% (433/438) with 95% CI: 97.3 - 99.5% |
| Propsective Study (Agreement with Predicate - Positive) | Acceptable agreement with predicate device for positive samples | 60.0% (6/10) with 95% CI: 30.8 - 83.3%^1 |
| Retrospective Study (Agreement with Predicate - Positive) | High agreement with predicate device from pre-selected positive samples | 98.9% (175/177) with 95% CI: 96.0 - 99.7% |
*Precision calculations for these samples were based on signal (RLU) as the dose was below the reading range.
^1 The lower positive agreement in the prospective study is likely due to the small number of positive samples in that cohort (only 10 identified as positive by the comparator assay). The retrospective study (designed for positive samples) shows much higher positive agreement.
2. Sample Size Used for the Test Set and Data Provenance
- Precision/Reproducibility Study Test Set: A coded panel was tested. The specific number of individual samples in the panel is not explicitly stated, but it was tested with two replicates per run, in two runs per day for 20 operating days across three sites.
- Data Provenance: The study was conducted at two external laboratories and DiaSorin Inc. The origin of the samples in the coded panel is not specified (e.g., country of origin). The study design (testing over 20 days) implies a prospective collection for the study itself, although the source of the panel samples could be retrospective.
- Cross-reactivity Study Test Set: 261 individual samples, each sero-positive for a specific cross-reactant and sero-negative for Rubella IgM by a commercially available Rubella IgM assay.
- Data Provenance: Not specified (retrospective or prospective, country of origin).
- High Dose Hook Effect Study Test Set: 3 samples with Rubella IgM levels > 400 AU/mL.
- Data Provenance: Not specified.
- IgM Specificity Study Test Set: 10 samples containing Rubella IgM antibodies covering the assay range.
- Data Provenance: Not specified.
- Interference Study Test Set: Two matched sample pools near the clinical decision point were tested neat and spiked with each interferent. The specific number of individual samples contributing to the pools or number of independent tests is not detailed beyond the two pools.
- Data Provenance: Not specified.
- Comparative Testing (Clinical Studies) Test Set:
- Prospective study: 448 samples from individuals sent to the laboratory for Rubella IgM testing.
- Retrospective study: 178 samples from individuals who had a positive Rubella IgM result (pre-selected population).
- Data Provenance: The clinical studies were conducted in the United States, as indicated by the mention of "validated in the United States during clinical studies" and the context of FDA submission. Both prospective and retrospective data were used.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications
- For the clinical comparative studies (prospective and retrospective): The ground truth was established by an "FDA-cleared predicate device" (ADVIA Centaur Rubella IgM Assay, K010668). No human experts were explicitly mentioned as establishing the ground truth for the test set samples in these comparative studies. The predicate device's results were considered the reference.
- For setting the assay cut-off: Ground truth was established based on consensus between "several comparison methods" and "available clinical and serological data". This implies the involvement of experts who interpreted these data, but the number and qualifications of these experts are not specified in the document. The European studies for cutoff establishment mention "subjects never infected by rubella virus, subjects affected by autoimmune diseases, patients affected by various infectious diseases with similar symptomology, subjects with past rubella infector or vaccine recipients, patients affected by acute rubella infection and subjects with long-lasting rubella virus IgM," which would require expert clinical and serological diagnosis to categorize.
4. Adjudication Method for the Test Set
- For the clinical comparative studies, the LIAISON® Rubella IgM assay results were compared directly against the results of the predicate device. There is no mention of an independent adjudication method (like 2+1, 3+1, etc.) for discrepancies between the new device and the predicate. The predicate device's classification was used as the reference.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
- No, an MRMC comparative effectiveness study was not done. The studies described are focused on comparing the performance of the new device (assay) against a predicate device, and analytical characteristics, not on the improvement of human readers with AI assistance.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
- Yes, this is a standalone device performance study. The LIAISON® Rubella IgM assay is an in vitro diagnostic device (a lab test system) that provides a qualitative result (Positive, Equivocal, Negative). The studies assess the analytical and clinical performance of this assay itself, generating results without human interpretive input into the device's determination. Human laboratory personnel would operate the instrument and interpret the final quantitative result based on the defined cut-offs to a qualitative diagnosis, but the core performance evaluation is of the assay's output.
7. The Type of Ground Truth Used
- Predicate Device/Reference Methods and Clinical Data Consensus.
- For the comparative clinical studies, the FDA-cleared predicate device (ADVIA Centaur Rubella IgM Assay) served as the primary ground truth for comparison.
- For establishing the assay cut-off, the ground truth was derived from "consensus between several comparison methods as well as the available clinical and serological data." This falls under a form of expert consensus and reference method agreement based on clinical and laboratory findings.
- For analytical studies (e.g., cross-reactivity, IgM specificity), the ground truth was based on known characteristics of the samples (e.g., known sero-positivity for a cross-reactant, known Rubella IgM presence/absence, DTT treatment effect).
8. The Sample Size for the Training Set
- Not explicitly specified for a distinct "training set" in the context of machine learning. As an immunoassay, the device's "training" involves the development and calibration of reagents and the establishment of cut-offs.
- The assay cut-off was established based on studies including "1662 subjects from different populations" (subjects never infected by rubella virus, subjects affected by autoimmune diseases, patients affected by various infectious diseases with similar symptomology, subjects with past rubella infector or vaccine recipients, patients affected by acute rubella infection and subjects with long-lasting rubella virus IgM) in European studies. This large cohort of 1662 subjects would serve as the primary dataset used to "train" or optimize the assay's interpretive criteria (i.e., the cut-off values).
9. How the Ground Truth for the Training Set Was Established
- The ground truth for the 1662 subjects used to establish the cut-off was determined by:
- "several comparison methods" (implying other established serological tests for Rubella IgM), and
- "available clinical and serological data" (suggesting a comprehensive evaluation of patient history, symptoms, and other laboratory findings).
- The "consensus between the methods as well as the available clinical and serological data" was applied to define the expected results for these subjects. This indicates a robust method involving multiple lines of evidence and expert review.
{0}------------------------------------------------
510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION EXECUTIVE SUMMARY
| A. 510(k) Number: | K122397 SEP 6 2012 |
|---|---|
| B. Purpose for Submission: | New Device |
| C. Measurand: | IgM Antibody to Rubella Virus |
| D. Type of Test: | Qualitative, Chemiluminescence Immunoassay (CLIA) |
| E. Applicant: | DiaSorin Inc. |
| F. Proprietary and Established Names: | LIAISON® Rubella IgMLIAISON® Control Rubella IgM |
| G. Regulatory Information: | |
| 1. Regulation section: | 21 CFR §866.3510 Rubella Virus Serological Reagents21 CFR §862.1660 Quality control material |
| 2. Classification: | Class II |
| 3. Product code: | LFX (Enzyme Linked Immunoabsorbent Assay, Rubella)JJX (Quality control material, assayed and unassayed) |
-
- Panel: 83 Microbiology
H. Intended Use:
1. Intended use(s):
The LIAISON® Rubella IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgM antibodies to rubella virus in human serum samples. It is intended for use as an aid in the diagnosis of a current or recent Rubella infection in individuals with signs and symptoms of Rubella, or suspected of having rubella virus infection, including women of child bearing age.
The LIAISON® Control Rubella IgM (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Rubella IgM assay.
The performance characteristics of LIAISON® Rubella IgM controls have not been established for any other assays or instrument platforms.
- Indication(s) for use:
Same as Intended Use.
3. Special conditions for use statement(s):
For prescription use only
4. Special instrument requirements:
LIAISON® Analyzer family of instruments is required to perform the testing.
1
{1}------------------------------------------------
I. Device Description:
The LIAISON® Rubella IgM assay is an in vitro diagnostic device consisting of reagents provided in individual compartments within a plastic container called the Reagent Integral. The assay configuration for the LIAISON® Rubella IgM assay allows for the performance of 100 tests.
Reagent Integral Composition:
- a. Magnetic particles mouse monoclonal antibody IgG to human IgM
- b. Calibrator 1 human serum or defibrinated plasma containing low level of Rubella IqM
- c. Calibrator 2 human serum or defibrinated plasma containing high level of Rubella laM
- d. Antigen Inactivated rubella viral particles (HPV 77 strain)
- c. Specimen diluent buffer with BSA added
- d. Conjugate -- mouse monoclonal antibodies to rubella virus conjuqated to an isoluminol derivative
The LIAISON® Control Rubella IgM is an in vitro diagnostic device consisting of 2 levels of controls to monitor the performance of the LIAISON® Rubella IgM assay
Controls (2 vials of each level):
Negative control - human serum or defibrinated plasma non-reactive for Rubella IgM Positive control - human serum or defibrinated plasma reactive for Rubella IgM
J. Substantial Equivalence Information:
-
- Predicate device name(s): ADVIA Centaur Rubella IgM Assay
-
- Predicate 510k number(s): K010668
-
- Comparison with predicate:
| Table 1: Table of Similarities | ||
|---|---|---|
| Characteristic | New DeviceLIAISON® Rubella IgM Assay | Predicate DeviceADVIA Centaur Rubella IgM(K010668) |
| Intended Use | The LIAISON® Rubella IgM assay useschemiluminescent immunoassay (CLIA)technology on the LIAISON® Analyzer for thequalitative determination of IgM antibodies torubella virus in human serum samples. It isintended for use as an aid in the diagnosis ofa current or recent Rubella infection inindividuals with signs and symptoms ofRubella, or suspected of having rubellainfection, including women of child bearingage. | The ADVIA Centaur Rubella IgMassay is an IgM antibody capturemicroparticle directchemiluminometric in vitro diagnosticassay for the qualitative detection ofIgM antibodies to the rubella virus inserum or plasma (EDTA, heparin) asan aid in the presumptive diagnosis ofcurrent or recent infection withrubella. |
| Assay Type | Chemiluminescent Immunoassay | Chemiluminometric immunoassay |
| Measured Analyte | IgM antibodies to rubella virus | IgM antibodies to rubella virus |
{2}------------------------------------------------
| Table 2 : Table of Differences | |||
|---|---|---|---|
| Characteristic | New DeviceLIAISON® Rubella IgM Assay | Predicate DeviceADVIA Centaur Rubella IgM(K010668) | |
| Sample Matrix | Serum | Serum and plasma (EDTA, heparin) |
K. Standard/Guidance Document Referenced (if applicable):
CLSI: EP05-A2 Evaluation of Precision Performance of Quantitative Measurement Methods; Approved Guideline Second Edition 2004
CLSI: EP15-A2: User Verification of Performance for Precision and Trueness; Approved Guideline, 2006
CLSI: EP07-A2: Interference Testing in Clinical Chemistry; Approved Guideline -Second Edition 2005
L. Test Principle:
Chemiluminescence Immunoassay (CLIA) - Immunoassay technology based on the emission of light as a result of a chemical reaction.
In the 1st incubation the IgM antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, rubella virus antigen reacts with IgM directed against rubella virus that is already bound to the solid phase. During the third incubation, the antibody conjuqate reacts with the immune complex formed during the second incubation, thus revealing that the immunological reaction has taken place. After the first and third incubations, 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) and is indicative of rubella virus IgM concentration present in calibrators, samples or controls.
M. Performance Characteristics (if/when applicable):
- Analytical performance:
a. Precision/Reproducibility:
A twenty-day reproducibility/precision study was conducted at two external laboratories and DiaSorin Inc. The CLSI document EP5-A2 was consulted in the preparation of the testing protocol.
A coded panel was tested at all three sites, using two replicates per run in two runs per day for 20 operating days. The 20 day combined results for all 3 sites are summarized as mean AU/mL value, standard deviation, and coefficient of variation (%CV) for within run and Total across lots and across sites.
The AU/mL values for the Negative control, and 2 of the Negative precision panels gave results less than the low end of the assay range of 10 AU/mL, therefore, the RLUs were used to perform the statistical calculations for these three sample types.
{3}------------------------------------------------
| Mean | Within-Run | Total(Across lots and Sites) | ||||
|---|---|---|---|---|---|---|
| Sample ID | AU/mL | SD | %CV | SD | %CV | |
| Negative Control* | <10* | 50.1* | 3.6%* | 170.9* | 12.3%* | |
| Positive Control | 72.5 | 3.0 | 4.2% | 9.3 | 12.8% | |
| Rubella IgM-A* | <10* | 52.8* | 3.7%* | 183.3* | 12.7%* | |
| Rubella IgM-B* | <10* | 115.2* | 3.4%* | 533.4* | 15.9%* | |
| Rubella IgM-C | 19.3 | 0.9 | 4.9% | 2.9 | 14.8% | |
| Rubella IgM-D | 23.3 | 1.0 | 4.4% | 3.3 | 14.1% | |
| Rubella IgM-E | 33.7 | 1.6 | 4.7% | 4.5 | 13.4% | |
| Rubella IgM-F | 115 | 4.8 | 4.1% | 14.9 | 13.0% | |
| Rubella IgM-G | 251 | 9.2 | 3.7% | 29.7 | 11.9% |
Combined sites 20 day precision results
- Dose was below the reading range of the assay. Precision calculations are based on signal (RLU) for the 3 samples.
b. Linearity/assay reportable range:
Not applicable
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:
There is no international standard available for measuring anti-Rubella IgM in serum, therefore, calibrators are traceable to an in-house reference preparation. Positive human serum/defibrinated plasma is serially diluted with negative serum/defibrinated plasma and tested in several assays and assigned Arbitrary Units (AU/mL) values spanning the range of the assay. Aliquots are stored frozen and used during the manufacturing of the kit calibrators.
Stability:
Reagent Integral
Open use stability at 2-8°C was performed on one Reagent Integral Lot. At specified intervals, the stored opened kit was evaluated in parallel with a freshly opened kit. All testing was acceptable to 9 weeks. An open use stability of 8 weeks at 2-8°C is claimed.
Open use stability on board the LIAISON® Analyzer was performed on one Reagent Intearal Lot. At specified intervals, the opened kit was evaluated in parallel with a freshly opened kit. All testing was acceptable to 9 weeks. An open use stability of 8 weeks on board the LIAISON® Analyzer is claimed.
Controls
Open Use stability at 2-8°C was performed on 3 different lots of LIAISON® Control Rubella IgM. At specified intervals, the stored opened controls were evaluated in parallel with a freshly opened vial of each control. All testing was acceptable to 9 weeks. Open use stability at 2-8°C of 8 weeks is claimed.
Expected Values:
Calibrator 1 is manufactured to have a concentration between 20-35 AU/mL. Calibrator 2 is manufactured to have a concentration between 70-250 AU/mL.
4
{4}------------------------------------------------
The Negative Control is manufactured to have a target range 0-12 AU/mL. The Positive Control is manufactured to have a target range 40-110 AU/mL. .
d. Detection limit:
Not applicable
e. Analytical specificity:
Cross-reactivity
The cross-reactivity study for the LIAISON® Rubella IgM assay was designed to evaluate potential interference from the presence of potentially cross-reactive antibodies or substances and other viruses that may cause symptoms similar to or that may mimic Rubella infection. Only samples that were sero-positive for the cross reactant and seronegative for Rubella IgM by a commercially available Rubella IgM assay were used to test for potentially cross-reactive organisms.
| Number of | LIAISON® Rubella IgM | ||||
|---|---|---|---|---|---|
| Cross-reactive organism | samplestested | ReferenceIgM Result | POS | EQV | NEG |
| IgG anti-VCA | 10 | Negative | 0 | 0 | 10 |
| IgM anti-EBV | 10 | Negative | 0 | 0 | 10 |
| IgM anti-CMV | 10 | Negative | 0 | 0 | 10 |
| IgG anti-VZV | 10 | Negative | 0 | 0 | 10 |
| IgM anti-VZV | 10 | Negative | 0 | 0 | 10 |
| Anti-Treponema Pallidum | 10 | Negative | 0 | 0 | 10 |
| IgG anti-Toxoplasma gondii | 10 | Negative | 0 | 0 | 10 |
| IgM anti-Toxoplasma gondii | 10 | Negative | 0 | 0 | 10 |
| Anti-HAV / IgM anti-HAV | 10 | Negative | 0 | 0 | 10 |
| Anti-HBs | 10 | Negative | 0 | 0 | 10 |
| IgM anti-Measles | 10 | Negative | 0 | 0 | 10 |
| IgM anti-Parvovirus B19 | 10 | Negative | 0 | 0 | 10 |
| IgM anti-HSV 1/2 | 10 | Negative | 0 | 0 | 10 |
| IgG anti-HSV 1 | 11 | Negative | 0 | 0 | 11 |
| IgG anti-HSV 2 | 4 | Negative | 0 | 0 | 4 |
| HHV6 | 10 | Negative | 0 | 0 | 10 |
| ANA IgG | 10 | Negative | 0 | 0 | 10 |
| Chlamydia IgG | 10 | Negative | 0 | 0 | 10 |
| Chlamydia IgM | 10 | Negative | 0 | 0 | 10 |
| anti-HIV | 10 | Negative | 0 | 0 | 10 |
| hCG | 10 | Negative | 0 | 0 | 10 |
| Influenza A | 7 | Negative | 0 | 0 | 7 |
| Influenza B | 6 | Negative | 0 | 0 | 6 |
| Parainfluenza I | 8 | Negative | 0 | 0 | 8 |
| Parainfluenza II | 2 | Negative | 0 | 0 | 2 |
| Parainfluenza III | 6 | Negative | 0 | 0 | 6 |
| anti-HCV | 10 | Negative | 0 | 0 | 10 |
| Rheumatoid Factor | 10 | Negative | 0 | 0 | 10 |
| HAMA | 10 | Negative | 0 | 0 | 10 |
| Multiple Myeloma | 10 | Negative | 0 | 0 | 10 |
| Total | 261 | 0 | 0 | 261 |
{5}------------------------------------------------
High Dose Hook Effect
Analysis of high-dose hook effect was evaluated by testing three samples with rubella IqM levels out-of-range > 400 AU/mL. The samples resulted in calculated concentration values above the measuring range. There was no sample misclassification indicating no hook effect was observed.
IgM Specificity
Ten samples containing Rubella IgM antibodies covering the assay range from value around cut-off level to clearly positive samples were treated with 10 mM dithiotreitol (DTT) to denature the IgM. These DTT treated samples were then tested in singlicate in parallel with the non-treated samples showed absence of IdM anti-Rubella reactivity after treatment with DTT. These data demonstrate the specificity of the LIAISON® Rubella IgM assay for IgM immunoglobulins.
| Sample ID | LIAISON® Rubella IgM assay Results (AU/mL) | |
|---|---|---|
| Before DTT treatment | After DTT treatment | |
| Sample-1 | 18.0 | <10.0 |
| Sample-2 | 17.1 | <10.0 |
| Sample-3 | 22.0 | <10.0 |
| Sample-4 | 34.7 | <10.0 |
| Sample-5 | 227 | <10.0 |
| Sample-6 | 109 | <10.0 |
| Sample-7 | 145 | <10.0 |
| Sample-8 | 86.4 | <10.0 |
| Sample-9 | 116 | <10.0 |
| Sample-10 | 148 | <10.0 |
Interference
Testing was performed to determine whether the presence of endogenous or exogenous substances may interfere with assay results. Two matched sample pools containing antibodies to Rubella IgM near the clinical decision point were tested neat and spiked with the respective interferent. The acceptance criteria were defined as the % change in signal must not be more than +10% and no change in the qualitative result.
No interference was found at the concentration for each substance listed below in the LIAISON® Rubella IgM assay. The testing was based on CLSI-EP07-A2.
| Substance | Tested Concentration |
|---|---|
| Triglycerides | 3000 mg/dL |
| Hemoglobin | 1000 mg/dL |
| Unconjugated bilirubin | 20 mg/dL |
| Conjugated bilirubin | 30 mg/dL |
| Albumin | 6 g/dL |
| Cholesterol | 510 mg/dL |
| Gamma-globulin | 6000 mg/dL |
| L-Ascorbic acid | 3 mg/dL |
{6}------------------------------------------------
f. Assay cut-off:
The cutoff for the LIAISON® Rubella IgM assay was set at an Arbitrary Unit value of 25 AU/mL based on European studies by testing 1662 subjects from different populations (subjects never infected by rubella virus, subjects affected by autoimmune diseases, patients affected by various infectious diseases with similar symptomology, subjects with past rubella infector or vaccine recipients, patients affected by acute rubella infection and subjects with long-lasting rubella virus IgM). The specimens were tested by several comparison methods and the consensus between the methods as well as the available clinical and serological data were applied to define the expected results.
The assay cut-off was validated in the United States during clinical studies by testing a prospective population of 448 samples from individuals sent to the laboratory for Rubella lgM testing, and a retrospective population of 178 samples from individuals who had a positive Rubella IgM result. Based on the comparison studies this cutoff is appropriate for the LIAISON® Rubella IgM.
In the LIAISON® Rubella IgM assay, a sample is defined as positive if the Arbitrary Unit value is greater than or equal to 25 AU/mL, and defined as negative if the Arbitrary Unit value is less than 20 AU/mL. Samples with results greater than or equal to 20 AU/mL and less than 25 AU/mL are classified as equivocal.
- Comparison studies:
a. Method comparison with predicate device:
Not applicable
b. Matrix comparison:
Not applicable
- Clinical studies:
a. Clinical Sensitivity:
Not applicable
b. Clinical specificity:
Not applicable
c. Other clinical supportive data (when a. and b. are not applicable):
Comparative testing
Prospective and Retrospective studies were performed to compare the performance of the LIAISON® Rubeila IgM assay to an FDA-cleared predicate device.
The prospective study consisted of 448 samples from individuals who were sent to the laboratory for Rubella IgM testing.
The retrospective study consisted of 178 samples selected from individuals who had a positive Rubella IgM result.
{7}------------------------------------------------
Prospective study
The prospective population consisting of 448 individuals were 89.7% Female (n=402) ranging in age from <1 to 67 years, and 9.2% Male (n=41) ranging in age from <1 to 59 years. There were 5 samples from patients where the gender was unknown (1.1%).
The agreement with 95% Confidence intervals for the prospective population is shown in the table below.
| LIAISON®Rubella IgM | Comparator Assay | Total | ||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Positive | 6 | 0 | 2 | 8 |
| Equivocal | 0 | 0 | 3 | 3 |
| Negative | 3 | 1 | 433 | 437 |
| Total | 9 | 1 | 438 | 448 |
| Percent Agreement | Exact 95% Confidence Interval | ||
|---|---|---|---|
| Negative | 433/438 | 98.9% | 97.3 - 99.5% |
| Positive | 6/10 | 60.0% | 30.8 - 83.3% |
Retrospective study
The retrospective population consisted of 178 samples from individuals who had a positive Centaur Rubella IgM result. There were 37.1% Females (n=66) and 23% Males (n=41) ranging in age from 2 to 59. For 39.9% (n=71) of the samples, gender and age were unknown.
The agreement with 95% Confidence intervals for the pre-selected population is shown in the table below.
| LIAISON®Rubella IgM | Comparator Assay | Total | ||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Positive | 175 | 1 | 0 | 176 |
| Equivocal | 1 | 0 | 0 | 1 |
| Negative | 1 | 0 | 0 | 1 |
| Total | 177 | 1 | 0 | 178 |
| Percent Agreement | Exact 95% Confidence Interval | |
|---|---|---|
| Positive | 175/17798.9% | 96.0 - 99.7% |
8
{8}------------------------------------------------
4. Clinical cut-off:
Not applicable
5. Expected values:
The observed prevalence/ expected values using the LIAISON® Rubella IgM assay was calculated with the 448 samples from patients sent to the lab for Rubella IgM testing. The samples were from 41 males (9.2%) and 402 females (89.7%). There were 5 samples from patients where the gender was unknown (1.1%). Ages ranged from < 1 year to 67 years. There were 11 samples where age was unknown.
The prevalence may vary depending upon geographical location, age, gender, type of test employed, specimen collection and handling procedures as well as clinical history of the patient.
The observed prevalence of LIAISON® Rubella IgM is 1.8%. The results are stratified by age and gender in the following table. Three (3) equivocal results were not used in the prevalence calculation.
| Gender | LIAISON® Rubella IgMresults | % | ||||||
|---|---|---|---|---|---|---|---|---|
| Total | Age | Male | Female | Unknown | Pos | Eqv | Neg | Prevalence |
| 17 | <1 | 9 | 6 | 2 | 1 | 0 | 16 | 5.9% |
| 8 | 1-10 | 4 | 3 | 1 | 0 | 0 | 8 | 0.0% |
| 33 | 11-20 | 6 | 27 | 0 | 1 | 0 | 32 | 3.0% |
| 218 | 21-30 | 11 | 206 | 1 | 6 | 2 | 210 | 2.8% |
| 137 | 31-40 | 7 | 130 | 0 | 0 | 1 | 136 | 0 |
| 14 | 41-50 | 2 | 12 | 0 | 0 | 0 | 14 | 0 |
| 8 | 51-60 | 2 | 6 | 0 | 0 | 0 | 8 | 0 |
| 2 | 61-70 | 0 | 2 | 0 | 0 | 0 | 2 | 0 |
| 11 | Unknown | 0 | 10 | 1 | 0 | 0 | 11 | 0 |
{9}------------------------------------------------
Image /page/9/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" arranged around the perimeter. Inside the circle is a stylized emblem featuring a symbol that resembles an abstract human form or a caduceus, with flowing lines suggesting movement or energy.
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993
6 2012 SEP
DiaSorin, Inc. C/O Carol DePouw 1951 Northwestern Avenue Stillwater, MN 55082
Re: K122397
Trade/Device Name: LIAISON® Rubella IgM, LIAISON® Control Rubella IgM Regulation Number: 21 CFR 866.3510 Regulation Name: Rubella Virus Serological Reagents Regulatory Class: Class II Product Code: LFX, JJX Dated: August 6, 2012 Received: August 7, 2012
Dear Ms. DePouw:
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 class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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 that 1 27 deral statutes and regulations administered by other Federal agencies. You must or uny I with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820). This letter requirences as be form arketing your device as described in your Section 510(k) premarket
{10}------------------------------------------------
Page 2 – Ms Carol DePouw
notification. The FDA finding of substantial equivalence of your device to a legally marketed nredicate device results in a classification for your device and thus, permits your device to proceed to the market.
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 Diagnostic Device Evaluation and Safety 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 vours.
Salgado
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
{11}------------------------------------------------
510(k) Number:
Device Name:
Indication For Use:
LIAISON® Rubella IgM and LIAISON® Control Rubella laM
The LIAISON® Rubella IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgM antibodies to rubella virus in human serum samples. It is intended for use as an aid in the diagnosis of a current or recent Rubella infection in individuals with signs and symptoms of Rubella, or suspected of having rubella virus infection, including women of child bearing age.
The LIAISON® Control Rubella IgM (negative and positive) is intended for use as assayed quality control samples to monitor the performance of the LIAISON® Rubella IgM assay. The performance characteristics of LIAISON® Rubella IgM controls have not been established for any other assays or instrument platforms.
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 (OVD)
Jayath
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
K122 397 510(k)_
§ 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.