ADVIA Centaur CMV IgG and ADVIA Centaur CMV IgG Quality Control
Device Facts
| Record ID | K181213 |
|---|---|
| Device Name | ADVIA Centaur CMV IgG and ADVIA Centaur CMV IgG Quality Control |
| Applicant | Siemens Healthcare Diagnostics, Inc. |
| Product Code | LFZ · Microbiology |
| Decision Date | Jul 30, 2018 |
| Decision | SESE |
| Submission Type | Traditional |
| Regulation | 21 CFR 866.3175 |
| Device Class | Class 2 |
| Attributes | Real-World Evidence, Pediatric |
Real-World Evidence
| Submission | Device | Sponsor | RWD Sources | RWE Use Summary | Key Tags |
|---|---|---|---|---|---|
| K181213 · Jul 30, 2018 | ADVIA Centaur CMV IgG and ADVIA Centaur CMV IgG Quality Control | Siemens Healthcare Diagnostics, Inc. | Retrospective remnant clinical samples; Prospective routine clinical specimens | Retrospective and prospective clinical samples were used to establish method comparison, clinical sensitivity, and expected values for the ADVIA Centaur CMV IgG assay. | Retrospective remnant samples; Routine clinical specimens; Method comparison |
Clinical Evidence
| Study Design | Population | Comparator | Key Endpoints |
|---|---|---|---|
| Retrospective HIV-Positive Patient Subgroup; Retrospective analysis of remnant clinical samples | 143 HIV-positive patients; Sample Size: 143; Number of Sites: 1 | Comparator CMV IgG assay | Percent agreement |
Indications for Use
The ADVIA Centaur® CMV IgG (CMV IgG) assay is for in vitro diagnostic use in the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma (dipotassium EDTA, lithium heparin) using the ADVIA Centaur XP system. The assay is used to determine CMV IgG serological status and as an aid in the diagnosis of CMV infection in individuals for whom a CMV IgG test was ordered, including pregnant women. The ADVIA Centaur CMV IgG assay is not intended for blood and tissue donor screening. The ADVIA Centaur® CMV IgG Quality Control material is for in vitro diagnostic use for monitoring the performance of the ADVIA Centaur CMV IgG (CMV IgG) assay on ADVIA Centaur systems.
Device Story
Fully automated, 2-step sandwich immunoassay using indirect chemiluminometric technology on ADVIA Centaur XP system. Input: human serum or plasma samples. Process: sample diluted; incubated with biotinylated CMV viral lysate antigens on streptavidin-coated magnetic particles; CMV-specific antibodies captured; washed; Lite reagent (acridinium-ester-labeled anti-human IgG mouse monoclonal antibody) added; complex washed; chemiluminescent reaction initiated by acid/base reagents. Output: relative light units (RLUs) proportional to bound anti-CMV IgG; results reported as reactive or nonreactive based on Index value (<1.00 nonreactive, ≥1.00 reactive). Used in clinical laboratories by trained personnel. Benefits: aids in diagnosis of CMV infection and determination of serological status.
Clinical Evidence
Clinical performance evaluated via method comparison study with 1,842 samples (1,699 prospective, 143 retrospective) across diverse populations (general, pregnant, pediatric, HIV-positive, transplant patients). Compared to a predicate CMV IgG assay, overall positive agreement was 99.6% (1037/1041) and negative agreement was 96.8% (637/658). CDC panel of 80 characterized samples showed 100% agreement. Precision/reproducibility studies (CLSI EP05-A3) showed within-lab CVs 3.0-3.9% and reproducibility CVs 4.6-7.0%. Interference and cross-reactivity testing showed no significant impact on clinical interpretation.
Technological Characteristics
Fully automated 2-step sandwich immunoassay; indirect chemiluminometric technology. Uses biotinylated CMV viral lysate antigens on streptavidin-coated magnetic particles. Detection reagent: acridinium-ester-labeled anti-human IgG mouse monoclonal antibody. Sample volume: 20 μL. Platform: ADVIA Centaur XP system. Qualitative output based on 1.0 Index cutoff. No specific material standards (e.g., ASTM) cited.
Indications for Use
Indicated for qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma. Used to determine CMV IgG serological status and aid in diagnosis of CMV infection in patients, including pregnant women. Not for blood or tissue donor screening.
Regulatory Classification
Identification
Cytomegalovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to cytomegalovirus in serum. The identification aids in the diagnosis of diseases caused by cytomegaloviruses (principally cytomegalic inclusion disease) and provides epidemiological information on these diseases. Cytomegalic inclusion disease is a generalized infection of infants and is caused by intrauterine or early postnatal infection with the virus. The disease may cause severe congenital abnormalities, such as microcephaly (abnormal smallness of the head), motor disability, and mental retardation. Cytomegalovirus infection has also been associated with acquired hemolytic anemia, acute and chronic hepatitis, and an infectious mononucleosis-like syndrome.
Predicate Devices
- bioMerieux VIDAS CMV IgG (CMVG) Assay (k920661)
Submission Summary (Full Text)
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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION
DECISION SUMMARY
A. 510(k) Number: K181213
B. Purpose for Submission: To obtain a substantial equivalence determination and FDA clearance for a new device.
C. Measurand: Anti-CMV IgG antibodies
D. Type of Test: Enzyme Immunoassay
E. Applicant: Siemens Healthcare Diagnostics, Inc.
F. Proprietary and Established Names: ADVIA Centaur CMV IgG
ADVIA Centaur CMV IgG Quality Control
G. Regulatory Information:
1. Regulation section:
21 CFR §866.3175; Cytomegalovirus serological reagents
2. Classification:
Class II
3. Product code:
LFZ
4. Panel:
Microbiology (83)
H. Intended Use:
1. Intended use(s):
ADVIA Centaur CMV IgG
The ADVIA Centaur CMV IgG (CMV IgG) assay is for in vitro diagnostic use in the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma (dipotassium EDTA, lithium heparin) using the ADVIA Centaur XP system. This assay is used to determine CMV IgG serological status and as an aid in the diagnosis of CMV infection in individuals for whom a CMV IgG test was ordered, including pregnant women.
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The ADVIA Centaur CMV IgG assay is not intended for blood and tissue donor screening.
ADVIA Centaur CMV IgG Quality Control
The ADVIA Centaur CMV IgG (CMV IgG) Quality Control material is for in vitro diagnostic use for monitoring the performance of the ADVIA Centaur CMV IgG (CMV IgG) assay on ADVIA Centaur systems.
2. Indication(s) for use: Same as Intended Use
3. Special conditions for use statement(s): N/A
4. Special instrument requirements: ADVIA Centaur XP system
I. Device Description: The ADVIA Centaur CMV IgG Assay is a fully automated, 2-step sandwich immunoassay using indirect chemiluminometric technology. The patient specimen is diluted with ADVIA Centaur CMV IgG Diluent and incubated with the Solid Phase reagent. The Solid Phase reagent contains a heterogeneous mixture of biotinylated CMV viral lysate antigens, preformed to streptavidin-coated magnetic particles. The antigen coated particles subsequently capture CMV specific antibodies in the specimen. The antibody-antigen complex is washed and detection reagent is added. The detection reagent consists of an acridinium-ester (AE)-labeled anti-human IgG mouse monoclonal antibody. The entire complex is washed and the signal is generated in the presence of Lite Reagent bound to the Solid Phase via the CMV IgG-CMV antigen complex. The system reports results according to the selected option, as described in the system operating Instructions.
### J. Substantial Equivalence Information:
1. Predicate device name(s): bioMerieux VIDAS CMV IgG (CMVG) Assay
2. Predicate 510(k) number(s): k920661
3. Comparison with predicate:
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| Similarities | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Intended Use | The ADVIA Centaur CMV IgG (CMV IgG) assay is for *in vitro* diagnostic use in the qualitative detection of IgG antibodies to cytomegalovirus (CMV) in human pediatric and adult serum and plasma (dipotassium EDTA, lithium heparin) using the ADVIA Centaur XP system. This assay is used to determine CMV IgG serological status and as an aid in the diagnosis of CMV infection in individuals for whom a CMV IgG test was ordered, including pregnant women. The ADVIA Centaur CMV IgG assay is not intended for blood and tissue donor screening. The assay is not intended for use in neonatal screening or for use at point-of-care facilities. | The VIDAS CMV IgG (CMVG) Assay is intended for use on the instruments of the VIDAS family (Vitek ImmunoDiagnostic Assay System) as a semi-quantitative automated enzyme-linked fluorescent immunoassay (ELFA). It is intended for use in determination of CMV immunological experience from a single serum sample, or as an aid in the diagnosis of current CMV infection through evaluation of paired sera for a significant increase in CMV-specific IgG. It is not intended for use in testing (screening) blood or plasma donors. |
| Assay Protocol | sandwich immunoassay | sandwich immunoassay |
| Controls | Negative and Positive | Negative and Positive |
| Calibrator fill volume | Liquid, 2 mL | Liquid, 2 mL |
| Differences | | |
| --- | --- | --- |
| Item | Device | Predicate |
| Instrument | ADVIA Centaur | VIDAS/mini-VIDAS |
| Measurement | Qualitative | Semi-Quantitative |
| Technology | Chemiluminescence | enzyme-linked fluorescent immunoassay |
| Sample type | Serum, Plasma | Serum |
| Cut-Offs | < 1.0 (Index) - nonreactive ≥ 1.0 (Index) - reactive | < 4 AU/mL - negative ≥4 to < 6 AU/mL - equivocal ≥ 6 AU/mL - positive |
| Sample Volume | 20 μL | 100 μL |
| Calibrators matrix | Human plasma | Human serum |
| Calibrator fill volume | Liquid, 2 mL | Liquid, 2 mL |
# K. Standard/Guidance Document Referenced (if applicable):
N/A
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### L. Test Principle:
Indirect chemiluminometric technology
### M. Performance Characteristics (if/when applicable):
#### 1. Analytical performance:
a. Precision/Reproducibility:
Precision: Precision was evaluated according to CLSI document EP05-A3. Repeatability and Within-Lab imprecision were evaluated by testing 5 serum-based samples (serum sample pools), and 2 plasma-based samples (negative and positive controls). The samples were assayed in duplicate over 20 days, 2 runs per day, for a total of 40 runs and 80 replicates. The results are shown below.
Table 1: Precision Study
| Sample Type | N | Mean | Repeatability | | Between-Run | | Between-Day | | Within-Lab | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | % CV | SD | % CV | SD | % CV | SD | % CV |
| Control 1 (negative) | 80 | 0.08 | 0.00 | \( NA^a \) | 0.00 | 0.0 | 0.00 | 0.0 | 0.01 | NA |
| Control 2 (positive) | 80 | 4.54 | 0.09 | 2.0 | 0.12 | 2.6 | 0.09 | 2.0 | 0.18 | 3.9 |
| Serum Pool 1 | 80 | 0.07 | 0.00 | NA | 0.00 | 0.6 | 0.00 | NA | 0.01 | NA |
| Serum Pool 2 | 80 | 0.90 | 0.02 | 2.1 | 0.01 | 1.3 | 0.02 | 2.3 | 0.03 | 3.4 |
| Serum Pool 3 | 80 | 1.36 | 0.03 | 2.5 | 0.02 | 1.1 | 0.02 | 2.1 | 0.05 | 3.5 |
| Serum Pool 4 | 80 | 2.70 | 0.06 | 2.2 | 0.07 | 2.5 | 0.07 | 1.7 | 0.10 | 3.7 |
| Serum Pool 5 | 80 | 9.68 | 0.20 | 2.1 | 0.12 | 1.3 | 0.12 | 1.8 | 0.29 | 3.0 |
\( ^{a} \) NA = not applicable.
Reproducibility: Reproducibility was evaluated according to CLSI document EP05-A3. A reproducibility study was conducted at 3 external sites using two reagent lots. The protocol was run over 5 days, 2 runs per day. There were 3 replicates per run for the serum pools and 6 replicates per run for the negative and positive control materials. Reproducibility data was pooled across 3 sites. Data are presented for 1 representative reagent lot.
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Table 2: Reproducibility Study
| Sample Type | N | Mean | Repeatability | | Between-Run | | Between-Day | | Between-Site | | Reproducibility | |
| --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- | --- |
| | | | SD | % CV | SD | % CV | SD | % CV | SD | % CV | SD | % CV |
| Control 1 (negative) | 180 | 0.10 | 0.01 | \( NA^a \) | 0.00 | NA | 0.00 | NA | 0.02 | NA | 0.02 | NA |
| Control 2 (positive) | 180 | 4.55 | 0.12 | 2.7 | 0.07 | 1.5 | 0.02 | 0.3 | 0.15 | 3.4 | 0.21 | 4.6 |
| Serum Pool 1 | 90 | 0.10 | 0.01 | NA | 0.00 | NA | 0.00 | NA | 0.01 | NA | 0.01 | NA |
| Serum Pool 2 | \( 89^b \) | 0.80 | 0.01 | 1.8 | 0.02 | 1.9 | 0.01 | 1.1 | 0.05 | 6.1 | 0.05 | 6.7 |
| Serum Pool 3 | 90 | 1.23 | 0.02 | 1.9 | 0.02 | 2.0 | 0.00 | 0.0 | 0.07 | 5.4 | 0.07 | 6.0 |
| Serum Pool 4 | 90 | 2.98 | 0.06 | 1.9 | 0.06 | 1.9 | 0.05 | 1.7 | 0.13 | 4.2 | 0.16 | 5.3 |
| Serum Pool 5 | 90 | 25.25 | 0.45 | 1.8 | 0.40 | 1.6 | 0.26 | 1.0 | 1.64 | 6.5 | 1.77 | 7.0 |
\( ^{a} \) NA = not applicable.
\( ^{b} \) One run had 2 replicates instead of 3.
b. Linearity/assay reportable range:
N/A
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
N/A
d. Detection limit:
N/A
e. Analytical specificity:
Cross-Reactivity: The ADVIA Centaur CMV IgG assay was evaluated for potential cross-reactivity in specimens with other viral and microbial antibodies and disease states. The CMV IgG status of each sample was compared using the comparator assay and the true nature of the reactive samples shown below is not determined.
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Table 3: Cross-Reactivity Study
| Clinical Category | Number Tested | ADVIA Centaur CMV IgG Reactive | Comparator CMV IgG Reactive |
| --- | --- | --- | --- |
| Chlamydia IgG | 11 | 4 | 4 |
| CMV IgM | 10 | 6 | 6 |
| Epstein-Barr virus (EBV) IgG | 13 | 0 | 0 |
| Epstein-Barr virus (EBV) IgM | 10 | 4 | 4 |
| Graves' disease | 3* | 0 | 0 |
| Hepatitis A infection (HAV) IgG | 10 | 3 | 3 |
| Hepatitis B Core (HBc) IgG | 10 | 3 | 4 |
| Hepatitis C infection (HCV) IgG | 10 | 1 | 1 |
| Herpes simplex virus 1 (HSV1) | 13 | 3 | 3 |
| Herpes simplex virus 2 (HSV2) | 12 | 0 | 0 |
| Human anti-mouse antibody (HAMA) | 14 | 7 | 6 |
| Human chorionic gonadotropin (hCG) | 11 | 0 | 0 |
| Human herpes virus (HHV6) IgG | 11 | 0 | 0 |
| Human immunodeficiency virus (HIV) Antibodies | 16 | 9 | 9 |
| Influenza Antibodies | 11 | 7 | 7 |
| Measles IgG | 11 | 0 | 0 |
| Multiparity | 20 | 18 | 18 |
| Multiple myeloma | 23 | 11 | 11 |
| Parvovirus B19 IgG | 11 | 3 | 3 |
| Rheumatoid factor (RF) | 10 | 1 | 1 |
| Rubella IgG | 13 | 0 | 0 |
| Sjogren's Syndrome | 4* | 0 | 0 |
| Systemic lupus erythematosus (SLE)* | 3* | 0 | 0 |
| Syphilis IgG | 11 | 4 | 4 |
| Toxoplasma IgG | 10 | 4 | 4 |
| Varicella zoster virus (VZV) IgG | 16 | 0 | 0 |
| Total | 297 | 88 | 88 |
* Results may not be conclusive due to low number of samples tested.
Interferences: Interference by endogenous substances in the ADVIA Centaur CMV IgG assay was evaluated at four CMV IgG levels (low negative, high negative, low positive,
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and high positive). Interfering substances at the levels indicated were tested as described in CLSI Document EP07-A2. There was no change in clinical interpretation throughout the assay range at the levels indicated.
Table 4: Endogenous Interfering Substances Study
| Interferent | Concentration |
| --- | --- |
| Hemoglobin (hemolyzed) | 500 mg/dL |
| Conjugated bilirubin (Icteric) | 20 mg/dL |
| Unconjugated bilirubin (Icteric) | 20 mg/dL |
| Triglycerides (Lipemic) | 3000 mg/dL (Intralipids) |
| Total protein* | 9g/dL of protein |
| Immunoglobulins* | 3g/dL of immunoglobulin |
| Biotin | 4500 ng/mL of biotin |
| Cholesterol | 400 mg/dL of cholesterol |
* Total protein and immunoglobulins were tested using clinical samples with high serum protein and samples from multiple myeloma patients respectively.
#### f. Assay cut-off:
Cutoff Determination: A comparison study between the ADVIA Centaur CMV IgG assay and a comparator CMV IgG assay was performed to determine the placement of the cutoff value at a 1.00 Index by testing 389 remnant clinical samples. Of these, 196 samples were negative, 186 samples were positive, and the rest were equivocal by the comparator device. The cutoff value was set at \( \geq \) 95% positive agreement and \( \geq \) 95% negative agreement to the comparator device.
### 2. Comparison studies:
a. Method comparison with predicate device:
Method Comparison: Percent agreement was determined by comparing the performance of the ADVIA Centaur CMV IgG assay to a comparator CMV IgG assay. A total of 1842 samples that were sent for CMV IgG testing were analyzed, including:
• 1699 prospectively collected specimens
○ 684 subjects sent for CMV IgG testing
○ 348 pregnant subjects
○ 229 pediatric subjects (2–21 years old)
○ 44 HIV-positive subjects
○ 394 transplant-patient subjects
• 143 retrospective HIV-positive specimens
Prospective Study: A total of 1699 clinical routine specimens (from people aged 6 months – 91 years, both male and female) were obtained from 6 collection sites in the
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United States. The specimens were from subjects sent for CMV IgG testing, pediatric subjects (aged 2–21 years), pregnant women, HIV-positive subjects, and transplant patients. The following results were obtained:
Table 5: Prospective Study - Combined Population
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 1037 | 11 | 10 | 1058 |
| Nonreactive | 1 | 3 | 637 | 641 |
| Total | 1038 | 14 | 647 | 1699 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 99.6% (1037/1041) | | 99.0%–99.9% | |
| Negative agreement | 96.8% (637/658) | | 95.2%–98.0% | |
Note: Fourteen samples that tested equivocal on the comparator assay were further tested on two other CMV IgG assays. Of these 14 samples, 10 remained equivocal, and 3 agreed and 1 did not agree with the ADVIA Centaur CMV IgG assay when compared to the two out of three consensus result.
The results obtained with the different subgroup prospective populations are presented in the sections that follow.
Subjects Sent for CMV IgG Testing: A total of 684 other prospective serum samples sent for CMV IgG testing were analyzed. The following results were obtained:
Table 6: Subjects Sent for CMV IgG Testing
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 375 | 6 | 7 | 388 |
| Nonreactive | 1 | 1 | 294 | 296 |
| Total | 376 | 7 | 301 | 684 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 99.5% (375/377) | | 98.1%–99.9% | |
| Negative agreement | 95.8% (294/307) | | 92.9%–97.7% | |
Note: Seven samples that tested equivocal on the comparator assay were further tested on two other CMV IgG assays. Of these 7 samples, 5 remained equivocal and 2 agreed with the ADVIA Centaur CMV IgG assay when compared to the two out of three consensus result.
Pregnant Women Subgroup: Serum samples sent for CMV IgG testing from 348 pregnant women prospectively collected from 4 sites were tested. The following results were obtained:
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Table 7: Pregnant Women Subgroup
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 287 | 0 | 1 | 288 |
| Nonreactive | 0 | 0 | 60 | 60 |
| Total | 287 | 0 | 61 | 348 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 100.0% (287/287) | | 98.7%-100.0% | |
| Negative agreement | 98.4% (60/61) | | 91.2%-9.9% | |
Pediatric Subgroup: A total of 229 pediatric prospective serum samples were tested at 3 sites. Specimens were obtained from 4 sites, from males and from females who were not pregnant. The subjects' ages ranged from 2–21 years. The following results were obtained:
Table 8: Pediatric Subgroup
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 80 | 1 | 1 | 82 |
| Nonreactive | 0 | 1 | 146 | 147 |
| Total | 80 | 2 | 147 | 229 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 98.8% (80/81) | | 93.3%-99.9% | |
| Negative agreement | 98.6% (146/148) | | 95.2%-99.8% | |
Note: Two samples that tested equivocal on the comparator assay were further tested on 2 other CMV IgG assays and remained equivocal.
Human Immunodeficiency Virus (HIV) Patient Subgroup: Serum specimens sent for CMV IgG testing were prospectively collected at 5 sites, from 44 HIV-positive patients and were tested. The following results were obtained:
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Table 9: HIV-Positive Patient Subgroup
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 43 | 0 | 0 | 43 |
| Nonreactive | 0 | 0 | 1 | 1 |
| **Total** | **43** | **0** | **1** | **44** |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 100.0% (43/43) | | 91.8%–100.0% | |
| Negative agreement | 100.0% (1/1) | | 2.5%–100.0% | |
**Transplant Patient Subgroup:** Serum samples from 238 preoperative transplant patients from 3 sites were tested. The following results were obtained:
Table 10: Transplant Patient Subgroup - Preoperative
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 151 | 0 | 0 | 151 |
| Nonreactive | 0 | 0 | 87 | 87 |
| **Total** | **151** | **0** | **87** | **238** |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 100.0% (151/151) | | 97.6%–100.0% | |
| Negative agreement | 100.0% (87/87) | | 95.8%–100.0% | |
**Post Transplant:** Serum samples from 156 transplant patients were collected from 3 sites that perform kidney, pancreas, bone and marrow stem cell, liver, face and limb, heart, and lung transplants. After testing the following results were obtained:
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Table 11: Transplant Patient Subgroup - Postoperative
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 101 | 4 | 1 | 106 |
| Nonreactive | 0 | 1 | 49 | 50 |
| Total | 101 | 5 | 50 | 156 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 99.0% (101/102) | | 94.7%-99.9% | |
| Negative agreement | 90.7% (49/54) | | 79.7%-96.9% | |
Note: Five samples that tested equivocal by the comparator assay were further tested on two other CMV IgG assays. Of these 5 samples, 3 remained equivocal, and 1 agreed and 1 did not agree with the ADVIA Centaur CMV IgG assay when compared to the two out of three consensus result.
### Retrospective Study
HIV-Positive Patient Subgroup: A total of 143 retrospective remnant samples from the HIV-positive patient subgroup collected at 1 site were tested. The following results were obtained:
Table 12: Retrospective HIV-Positive Patient Subgroup
| ADVIA Centaur CMV IgG Assay | Comparator CMV IgG Assay | | | |
| --- | --- | --- | --- | --- |
| | Positive | Equivocal | Negative | Total |
| Reactive | 135 | 0 | 0 | 135 |
| Nonreactive | 0 | 0 | 8 | 8 |
| Total | 135 | 0 | 8 | 143 |
| ADVIA Centaur CMV IgG Assay | Agreement (%) | | 95% Confidence Interval | |
| Positive agreement | 100.0% (135/135) | | 97.3%-100.0% | |
| Negative agreement | 100.0% (8/8) | | 63.1%-100.0% | |
#### b. Matrix comparison:
Specimen Collection Tube Comparison: The ADVIA Centaur CMV IgG assay was evaluated using different specimen matrices. ADVIA Centaur CMV IgG results that ranged from 0.74–28.55 Index were analyzed using orthogonal regression. The following results were obtained:
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Table 13: Matrix Comparison
| Serum (x) vs. | N | Mean (Index) | Slope | Intercept (Index) | Correlation Coefficient (r) |
| --- | --- | --- | --- | --- | --- |
| Dipotassium EDTA plasma (y) | 38 | 10.76 | 1.01 | -0.08 | 0.99 |
| Lithium heparin plasma (y) | 38 | 10.76 | 1.01 | -0.07 | 0.96 |
#### 3. Clinical studies:
##### a. Clinical Sensitivity:
Centers for Disease Control (CDC) Panel: A panel of 80 previously characterized serum samples was obtained from the CDC and evaluated with the ADVIA Centaur CMV IgG assay to determine the performance of the assay. There was 100% agreement with the serological status provided by the CDC.
Table 14: CDC Panel Testing
| ADVIA Centaur CMV IgG Assay | Expected CDC Panel Results | | |
| --- | --- | --- | --- |
| | Positive | Negative | Total |
| Reactive | 39 | 0 | 39 |
| Nonreactive | 0 | 41 | 41 |
| Total | 39 | 41 | 80 |
Note: The results are presented as a means to convey further information on the performance of this assay with a characterized serum panel from the CDC. This does not imply an endorsement of the assay by the CDC.
b. Clinical specificity: N/A
c. Other clinical supportive data (when a. and b. are not applicable): N/A
#### 4. Clinical cut-off: N/A
#### 5. Expected values/Reference range:
CMV is a universally dispersed pathogen with approximately 40%–100% of the world's population having CMV antibody present in blood. Age, socioeconomic status, and geographic location have all been suggested to play a role in the overall incidence of CMV IgG. A population of 1842 male and female subjects (1827 subjects from the US), were tested in the clinical studies described above using the ADVIA Centaur CMV IgG assay. The values obtained and the demographic information are shown in the table below.
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Table 15: Expected Values
| Population | N | Reactive | Nonreactive |
| --- | --- | --- | --- |
| Subjects sent for CMV IgG testing (6 months–85 years) (45.9% male and 54.1% female) | 684 | 388 (56.7%) | 296 (43.3%) |
| Pregnant women (20–45 years) | 348 | 288 (82.8%) | 60 (17.2%) |
| HIV-positive patients (prospective: 25–73 years) (68.2% male and 31.8% female) | 44 | 43 (97.7%) | 1 (2.3%) |
| HIV-positive patients (retrospective: 18–70 years) (69.9% male and 30.1% female) | 143 | 135 (94.4%) | 8 (5.6%) |
| Transplant patients (20–45 years) (60.4% male and 39.6% female) | 394 | 257 (65.2%) | 137 (34.8%) |
| Pediatric subjects (2–<12 years) (53.6% male and 46.3% female) | 69 | 25 (36.2%) | 44 (63.7%) |
| Pediatric subjects (12-21 years) (35.0% male and 65.0% female) | 160 | 57 (35.6%) | 103 (64.4%) |
| **Total** | **1842** | **1193 (64.8%)** | **649 (35.2%)** |
As with all *in vitro* diagnostic assays, each laboratory should determine its own reference range(s) for the diagnostic evaluation of patient results.
#### N. Proposed Labeling:
The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809, as applicable
#### O. Conclusion:
The submitted information in this premarket notification is complete and supports a substantial equivalence decision.
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