(465 days)
The DiaSorin LIAISON® EBNA IgG kit uses chemiluminescence immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative detection of specific IgG antibodies to EBV nuclear antigen synthetic peptide (EBNA) in human serum. When performed in conjunction with other EBV marker tests, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM). LIAISON® Control EBNA IgG kit is used in conjunction with LIAISON® EBNA IgG immunoassay for quality control of assay runs.
The LIAISON® EBV IgM assay uses chemiluminescent immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative determination of IgM antibodies to Epstein-Barr virus (EBV) viral capsid antigen (VCA) p-18 synthetic peptide in human serum. When performed in conjunction with other EBV markers, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM). LIAISON® Control EBV IgM kit is used in conjunction with LIAISON® EBV IgM immunoassay for quality control of assay runs.
The DiaSorin LIAISON® VCA IgG kit uses chemiluminescence immunoassay (CLIA) technology on the LIAISON® Analyzer for the qualitative detection of specific IqG antibodies to EBV viral capsid antigen (VCA) p-18 synthetic peptide in human serum. When performed in conjunction with other EBV marker tests, this assay can be used as an aid in the clinical laboratory diagnosis of Epstein-Barr viral Syndrome in patients with signs and symptoms of EBV infection such as infectious mononucleosis (IM). LIAISON® Control VCA IgG kit is used in conjunction with LIAISON® VCA IgG immunoassay for quality control of assay runs.
The method for qualitative determination of specific IgG to EBNA 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 EBNA-1 synthetic peptide and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, EBNA antibodies present in the calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with EBNA 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) and is indicative of the presence of EBNA IgG in calibrators, samples or controls.
The method for qualitative determination of specific IgM to Epstein-Barr viral capsid antigens (VCA) is an indirect chemiluminescence immunoassay (CLIA). All assay steps (with the exception of magnetic particle resuspension) and incubations are performed by the LIAISON® Chemiluminescence Analyzer. The principal components of the test are magnetic particles (solid phase) coated with p18 synthetic peptide and a conjugate of mouse monoclonal antibody to human IgM linked to an isoluminol derivative (isoluminolantibody conjugate). In the first step, samples and controls are diluted with Buffer A, which contains goat IgG to human IgG as an absorbent reagent to curb interference from human IgG specific to VCA or from rheumatoid factor. During the first incubation, VCA IgM antibodies present in the calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with VCA IgM 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 hy a photomultiplier as relative light units (RLU) and is indicative of the presence of VCA IgM in calibrators, samples or controls.
The method for qualititative determination of specific IgG to EBV viral capsid antigen (VCA) 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 EBV VCA p-18 synthetic peptide and a conjugate of mouse monoclonal antibody to human IgG linked to an isoluminol derivative (isoluminol-antibody conjugate). During the first incubation, VCA IgG antibodies present in calibrators, samples or controls bind to the solid phase. During the second incubation, the antibody conjugate reacts with VCA IgG antibodies that are already bound to the solid phase. After each incubation, unbound material is removed Subsequently, the starter reagents are added and a flash with a wash cycle. 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 the presence of EBV VCA IgG antibodies present in calibrators, samples or controls.
Here's an analysis of the acceptance criteria and study details for the DiaSorin LIAISON® EBNA IgG, LIAISON® EBV IgM, and LIAISON® VCA IgG assays, based on the provided text.
DiaSorin LIAISON® EBNA IgG Assay
This device is an immunoassay for the qualitative detection of IgG antibodies to EBV Nuclear Antigen (EBNA). It is intended to aid in the clinical diagnosis of Epstein-Barr viral Syndrome when used with other EBV marker tests.
1. Acceptance Criteria and Reported Device Performance
The provided text does not explicitly state pre-defined acceptance criteria for the DiaSorin LIAISON® EBNA IgG assay. However, performance is evaluated by "Percent Agreement" with a predicate device (DiaSorin ETI-EBNA-G Kit) and with serological classifications based on multiple reference assays. The conclusion states that the device showed "equivalent performance to the corresponding FDA-cleared assay" and "demonstrated agreement with the comparison method higher then 95% among prospectively collected samples and 94% among selected retrospective samples."
Assuming the predicate device's performance benchmarks implicitly serve as acceptance criteria, here's a table based on the reported agreement:
Table of Acceptance Criteria (Implied) and Reported Device Performance for LIAISON® EBNA IgG
| Performance Metric | Implied Acceptance Criteria (based on predicate equivalence and stated conclusion) | Reported Device Performance (Prospective Samples) | Reported Device Performance (Retrospective Samples) |
|---|---|---|---|
| Agreement with Predicate Device: | |||
| Positive Percent Agreement | > 95% | 95.9% (632/659) | |
| (95% CI: 94.1 - 97.3%) | 100.0% (61/61) | ||
| (95% CI: 94.1 - 100.0%) | |||
| Negative Percent Agreement | Not explicitly stated/Implied high | 92.7% (152/164) | |
| (95% CI: 87.6 - 96.2%) | N.C.* (7/9) | ||
| *N.C. - Not Calculated - inadequate sample number | |||
| Overall Percent Agreement | > 95% | 95.3% (784/823) | |
| (95% CI: 93.6 - 96.6%) | 94.3% (66/70) | ||
| (95% CI: 86.0 - 98.4%) | |||
| Agreement with Serological Classification: | |||
| Overall Percent Agreement | > 95% | 95.2% (780/819) | |
| (95% CI: 93.6 - 96.6%) | 94.3% (66/70) | ||
| (95% CI: 86.0 - 98.4%) | |||
| Acute Infection Agreement | Implied high | 100.0% (29/29) | |
| (95% CI: 90.2 - 100.0%) | 55.6% (5/9) | ||
| (95% CI: 21.2 - 86.3%) | |||
| Past Infection Agreement | Implied high | 98.1% (562/573) | |
| (95% CI: 96.6 - 99.0%) | N/A (0/0) | ||
| EBV Seronegative Agreement | Implied high | 100.0% (62/62) | |
| (95% CI: 95.3 - 100.0%) | N/A (0/0) | ||
| Indeterminate Agreement | Implied acceptable | 81.9% (127/155) | |
| (95% CI: 75.0 - 87.7%) | 100.0% (61/61) | ||
| (95% CI: 95.2 - 100.0%) |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Prospective Samples:
- Comparison to Predicate: 823 samples
- Comparison to Serological Classification: 819 samples (4 samples omitted due to insufficient volume)
- Retrospective Samples:
- Comparison to Predicate: 70 samples (VCA IgM-positive)
- Comparison to Serological Classification: 70 samples
- Prospective Samples:
- Data Provenance: The clinical trials were conducted at "two external US laboratories and at DiaSorin." The samples were described as "repository and prospective samples." This indicates a mix of retrospective (repository) and prospective data, all from the USA.
3. Number of Experts and Qualifications for Ground Truth
The text does not mention the use of experts to establish ground truth. The ground truth for comparative clinical trials was based on:
* Predicate device: DiaSorin ETI-EBNA-G Kit.
* Serological classification: A panel of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA).
4. Adjudication Method
No explicit adjudication method (e.g., 2+1, 3+1) is described for resolving discrepancies or establishing ground truth. Agreement was determined by direct comparison to the predicate device and serological classification.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No MRMC study was performed or described. This is an in-vitro diagnostic device, not an imaging AI device that involves human readers.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The performance data presented (e.g., percent agreement) reflects the algorithm-only performance of the DiaSorin LIAISON® EBNA IgG assay against the predicate and against serological classifications.
7. Type of Ground Truth Used
The ground truth used was:
- Comparison to a predicate device: DiaSorin ETI-EBNA-G Kit (an existing FDA-cleared immunoassay).
- Serological classification: Established by the results of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA). This acts as a composite "truth" for different EBV infection stages.
8. Sample Size for Training Set
No information is provided about a separate training set. Immunoassays typically do not have "training sets" in the same way machine learning algorithms do. The development and validation process relies on reagents, calibration, and analytical performance studies rather than data-driven model training.
9. How Ground Truth for Training Set Was Established
Not applicable, as there is no described training set for this type of device.
DiaSorin LIAISON® EBV IgM Assay
This device is an immunoassay for the qualitative detection of IgM antibodies to EBV Viral Capsid Antigen (VCA) p-18 synthetic peptide. It is intended to aid in the clinical diagnosis of Epstein-Barr viral Syndrome when used with other EBV marker tests.
1. Acceptance Criteria and Reported Device Performance
Similar to the EBNA IgG assay, the provided text does not explicitly state pre-defined acceptance criteria. Performance is evaluated by "Percent Agreement" with a predicate device (DiaSorin ETI-EBV-M reverse ELISA Kit) and with serological classifications. The conclusion states the device "demonstrated agreement with the comparison method higher than 89% among prospectively collected samples and 95% agreement among retrospective selected samples."
Table of Acceptance Criteria (Implied) and Reported Device Performance for LIAISON® EBV IgM
| Performance Metric | Implied Acceptance Criteria (based on predicate equivalence and stated conclusion) | Reported Device Performance (Prospective Samples) | Reported Device Performance (Retrospective Samples) |
|---|---|---|---|
| Agreement with Predicate Device: | |||
| Positive Percent Agreement | Implied acceptable (>50% as reported performance is 54.2%) | 54.2% (58/107) | |
| (95% CI: 44.3 - 63.9%) | 95.7% (67/70) | ||
| (95% CI: 88.0 - 99.1%) | |||
| Negative Percent Agreement | Implied high (>90% as reported performance is 94.7%) | 94.7% (674/712) | |
| (95% CI: 92.8 - 96.2%) | N.C.* (0/0) | ||
| *N.C. - Not Calculated - inadequate sample number | |||
| Overall Percent Agreement | > 89% for prospective, > 95% for retrospective | 89.4% (732/819) | |
| (95% CI: 87.1 - 91.4%) | 95.7% (67/70) | ||
| (95% CI: 88.0 - 99.1%) | |||
| Agreement with Serological Classification: | |||
| Overall Percent Agreement | > 89% for prospective, > 95% for retrospective | 89.4% (732/819) | |
| (95% CI: 87.1 - 91.4%) | 95.7% (67/70) | ||
| (95% CI: 88.0 - 99.1%) | |||
| Acute Infection Agreement | Implied high | 100.0% (29/29) | |
| (95% CI: 90.2 - 100.0%) | 77.8% (7/9) | ||
| (95% CI: 40.0 - 97.2%) | |||
| Past Infection Agreement | Implied high | 95.3% (546/573) | |
| (95% CI: 93.2 - 96.9%) | N/A (0/0) | ||
| EBV Seronegative Agreement | Implied high | 93.5% (58/62) | |
| (95% CI: 84.3 - 98.2%) | N/A (0/0) | ||
| Indeterminate Agreement | Implied acceptable | 63.9% (99/155) | |
| (95% CI: 55.8 - 71.4%) | 98.4% (60/61) | ||
| (95% CI: 91.2 - 100.0%) |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Prospective Samples: 819 samples (for both predicate and serological classification comparison).
- Retrospective Samples: 70 samples (VCA IgM-positive) (for both predicate and serological classification comparison).
- Data Provenance: The clinical trials were conducted at "two external US laboratories and at DiaSorin." The samples were described as "repository and prospective samples." This indicates a mix of retrospective (repository) and prospective data, all from the USA.
3. Number of Experts and Qualifications for Ground Truth
Not mentioned. Ground truth derived from a predicate device and a panel of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA).
4. Adjudication Method
No explicit adjudication method described. Agreement was determined by direct comparison to the predicate device and serological classification.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No MRMC study was performed or described. This is an in-vitro diagnostic device.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The performance data presented reflects the algorithm-only performance of the DiaSorin LIAISON® EBV IgM assay against the predicate and against serological classifications.
7. Type of Ground Truth Used
The ground truth used was:
- Comparison to a predicate device: DiaSorin ETI-EBV-M reverse ELISA Kit (an existing FDA-cleared immunoassay).
- Serological classification: Established by the results of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA).
8. Sample Size for Training Set
No information is provided about a separate training set.
9. How Ground Truth for Training Set Was Established
Not applicable.
DiaSorin LIAISON® VCA IgG Assay
This device is an immunoassay for the qualitative detection of IgG antibodies to EBV Viral Capsid Antigen (VCA) p-18 synthetic peptide. It is intended to aid in the clinical diagnosis of Epstein-Barr viral Syndrome when used with other EBV marker tests.
1. Acceptance Criteria and Reported Device Performance
The text presents performance in "Percent Agreement" with a predicate device (DiaSorin ETI-VCA-G Kit) and with serological classifications. The conclusion states the device "demonstrated agreement with the comparison method higher then 96% among prospectively collected samples and 100% agreement among retrospective selected samples."
Table of Acceptance Criteria (Implied) and Reported Device Performance for LIAISON® VCA IgG
| Performance Metric | Implied Acceptance Criteria (based on predicate equivalence and stated conclusion) | Reported Device Performance (Prospective Samples) | Reported Device Performance (Retrospective Samples) |
|---|---|---|---|
| Agreement with Predicate Device: | |||
| Positive Percent Agreement | > 96% | 96.2% (717/745) | |
| (95% CI: 94.6 - 97.5%) | 100.0% (70/70) | ||
| (95% CI: 94.1 - 100.0%) | |||
| Negative Percent Agreement | Implied acceptable (>90% as reported performance is 94.9%) | 94.9% (74/78) | |
| (95% CI: 87.4 - 98.6%) | N.C.* (0/0) | ||
| *N.C. - Not Calculated - Inadequate sample number | |||
| Overall Percent Agreement | > 96% for prospective, 100% for retrospective | 96.1% (791/823) | |
| (95% CI: 94.6 - 97.3%) | 100.0% (70/70) | ||
| (95% CI: 94.1 - 100.0%) | |||
| Agreement with Serological Classification: | |||
| Overall Percent Agreement | > 96% for prospective, 100% for retrospective | 96.1% (787/819) | |
| (95% CI: 94.5 - 97.3%) | 100.0% (70/70) | ||
| (95% CI: 95.8 - 100.0%) | |||
| Acute Infection Agreement | Implied acceptable | 82.8% (24/29) | |
| (95% CI: 64.2 - 94.2%) | 100.0% (9/9) | ||
| (95% CI: 71.7 - 100.0%) | |||
| Past Infection Agreement | Implied high | 98.3% (563/573) | |
| (95% CI: 96.8 - 99.2%) | N/A (0/0) | ||
| EBV Seronegative Agreement | Implied high | 98.4% (61/62) | |
| (95% CI: 91.3 - 100.0%) | N/A (0/0) | ||
| Indeterminate Agreement | Implied acceptable | 89.7% (139/155) | |
| (95% CI: 83.8 - 94.0%) | 100.0% (61/61) | ||
| (95% CI: 95.2 - 100.0%) |
2. Sample Size and Data Provenance
- Test Set Sample Size:
- Prospective Samples:
- Comparison to Predicate: 823 samples
- Comparison to Serological Classification: 819 samples (4 samples omitted due to insufficient volume)
- Retrospective Samples: 70 samples (VCA IgM-positive) (for both predicate and serological classification comparison).
- Prospective Samples:
- Data Provenance: The clinical trials were conducted at "two external US laboratories and at DiaSorin." The samples were described as "repository and prospective samples." This indicates a mix of retrospective (repository) and prospective data, all from the USA.
3. Number of Experts and Qualifications for Ground Truth
Not mentioned. Ground truth derived from a predicate device and a panel of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA).
4. Adjudication Method
No explicit adjudication method described. Agreement was determined by direct comparison to the predicate device and serological classification.
5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study
No MRMC study was performed or described. This is an in-vitro diagnostic device.
6. Standalone Performance Study
Yes, a standalone performance study was conducted. The performance data presented reflects the algorithm-only performance of the DiaSorin LIAISON® VCA IgG assay against the predicate and against serological classifications.
7. Type of Ground Truth Used
The ground truth used was:
- Comparison to a predicate device: DiaSorin ETI-VCA-G Kit (an existing FDA-cleared immunoassay).
- Serological classification: Established by the results of three reference assays (VCA IgG, EBNA-1 IgG, VCA IgM ELISA).
8. Sample Size for Training Set
No information is provided about a separate training set.
9. How Ground Truth for Training Set Was Established
Not applicable.
§ 866.3235 Epstein-Barr virus serological reagents.
(a)
Identification. Epstein-Barr virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to Epstein-Barr virus in serum. The identification aids in the diagnosis of Epstein-Barr virus infections and provides epidemiological information on diseases caused by these viruses. Epstein-Barr viruses are thought to cause infectious mononucleosis and have been associated with Burkitt's lymphoma (a tumor of the jaw in African children and young adults) and postnasal carcinoma (cancer).(b)
Classification. Class I (general controls).