(21 days)
The Copalis® Multiplex EBV Antibody Assay uses Coupled Particle Light Scattering technology in a microparticle agglutination-based assay for the qualitative or semiquantitative detection of antibodies to EBV VCA (total antibodies), EBNA (IgG), and EA (IgG and IgM) antigens. The assay is designed for human serum using the Copalis® I Immunoassay System. The presence of VCA, EBNA and EA antibodies is used as an aid in the diagnosis of EBV associated mononucleosis when used in conjunction with other EBV serologies in pediatric, adult, transplant donor and transplant recipient populations. The disease state distinction is made based on the antibody pattern of reactivity. When evaluating properly paired sera, the results of these assays are used to demonstrate seroconversion or significant change in antibody titer as evidence of recent infection. Both specimens should be tested simultaneously.
Coupled Particle Light Scattering (Copalis®) technology provides a rapid method for the measurement of antibodies to specific pathogens. The Copalis® Multiplex EBV Antibody Assay is a microparticle agglutination test using the Copalis® light scattering technology. Polystyrene microparticles of 3 sizes are coated with VCA synthetic peptide, EBNA recombinant antigen or EA recombinant antigen and are contained within a special covered reaction well in the test cup. The dried reagent is reconstituted with a reaction buffer on the instrument at the start of the assay. Patient sample is added to the reaction mixture and incubated for 10 minutes. The presence of antibodies specific to EBV antigens in the patient sample results in agglutination of the monomer microparticles to form aggregates. The reaction mixture is passed through a flow cell and the instrument uses light scattering technology to measure the monomer concentration. The decrease in the monomer population resulting from agglutination is related to the amount of antibody in the sample. The residual monomer concentration in each reaction mixture is compared to a cutoff value to determine sample reactivity and nonreactivity.
The provided document does not explicitly state acceptance criteria in the typical format of pre-defined thresholds that the device must meet. Instead, the study aims to demonstrate substantial equivalence to existing predicate devices (Gull Laboratories EBV IgG IFA, Gull Laboratories EBV-NA IFA, Gull Laboratories EBV-EA IFA) by comparing the Copalis® Multiplex EBV Antibody Assay's performance to expected marker patterns and agreement with IFA results.
Here's an interpretation of the "acceptance criteria" based on the presented data, which appear to be the results obtained to support the claim of substantial equivalence, and the study details:
1. Table of Acceptance Criteria and Reported Device Performance
Since no explicit quantitative acceptance criteria are given, the "acceptance criteria" are inferred from the goal of demonstrating comparable performance to IFA and expected serological patterns. The reported device performance is taken directly from the provided tables. The values in the "Acceptance Criteria" column reflect the general ranges or levels that would likely be considered acceptable for demonstrating substantial equivalence based on the comparison to IFA and expected patterns.
| Test Parameter / Population | Antigen Detected | Inferred Acceptance Criteria (Based on demonstrating comparability with IFA and expected patterns) | Reported Device Performance (Copalis® Multiplex EBV Antibody Assay) |
|---|---|---|---|
| Primary Disease State - Adult | VCA | Relative Sensitivity: High (e.g., >90%) | 100.0% (94.1 - 100%) |
| EBNA | Relative Specificity: High (e.g., >90%) | 94.9% (85.8 - 98.9%) | |
| EA vs Heterophile/IFA | Relative Sensitivity: High (e.g., >90%) | 94.9% (85.8 - 98.9%) | |
| Primary Disease State - Pediatric | VCA | Relative Sensitivity: High (e.g., >90%) | 100.0% (73.5 - 100.0%) |
| EBNA | Relative Specificity: Good (e.g., >50-70%) | 50.0% (21.1 - 78.9%) | |
| EA vs Heterophile/IFA | Relative Sensitivity: High (e.g., >90%) | 100.0% (73.5 - 100.0%) | |
| Reactivated Disease State | VCA | Relative Sensitivity: High (e.g., >90%) | 100.0% (91.8 - 100%) |
| EBNA | Relative Sensitivity: High (e.g., >85%) | 89.7% (75.8 - 97.1%) | |
| EA | Relative Sensitivity: High (e.g., >90%) | 100.0% (91.0 - 100%) | |
| EBV Screening Population - Adult | VCA | Relative Sensitivity: Good (e.g., >90%) | 96.8% (83.3 - 99.9%) |
| Relative Specificity: Good (e.g., >70%) | 100.0% (15.8 - 100.0%) | ||
| EBNA | Relative Sensitivity: Good (e.g., >90%) | 92.0% (74.0 - 99.0%) | |
| Relative Specificity: Good (e.g., >70%) | 75.0% (19.4 - 99.4%) | ||
| EA | Relative Sensitivity: Moderate (e.g., >70%) | 83.3% (58.6 - 96.4%) | |
| Relative Specificity: Moderate (e.g., >70%) | 77.8% (40.0 - 97.2%) | ||
| Seronegative Population - Adult | VCA | Relative Specificity: Moderate (e.g., >60%) | 62.5% (24.5 - 91.5%) |
| EBNA | Relative Specificity: High (e.g., >90%) | 100.0% (63.1 - 100.0%) | |
| EA | Relative Specificity: High (e.g., >90%) | 100% (59.0 - 100.0%) | |
| Reproducibility (VCA, EBNA, EA) | Control Samples | Total %CV: Low (e.g., <25%) | Neg Control: 3.9% (VCA), 2.8% (EBNA), 5.4% (EA); Low Pos Control: 12.3% (VCA), 7.3% (EBNA), 8.7% (EA); High Pos Control: 21.8% (VCA), 14.5% (EBNA), 19.5% (EA) |
| RP Samples | Within Run %CV: Low (e.g., <10%); Total %CV: Low (e.g., <25%) | Generally <10% for Within Run %CV, and <25% for Total %CV across all RPs and antigens. |
2. Sample Size Used for the Test Set and Data Provenance
- Total Sample Size: 423 samples (50 fresh (12%) and 373 frozen (88%))
- Disease State Sample Sizes:
- Primary Disease State - Adult: 61 samples (for VCA, EBNA, Heterophile/IFA comparison, but EA had 59 samples for some comparisons)
- Primary Disease State - Pediatric: 12 samples
- Reactivated Disease State: 43 samples (for VCA, EBNA, EA comparison, with slight variations for specific antigen comparisons)
- EBV Screening Population - Adult: 29 samples
- EBV Screening Population - Pediatric: 13 samples
- Seronegative Population - Adult: 8 samples (for VCA, EBNA, EA comparison, with slight variations per antigen)
- Seronegative Population - Pediatric: 34-42 samples (depending on antigen)
- Apparently Healthy Population: 98-102 samples (depending on antigen)
- Transplant Recipients: 48 samples
- Transplant Donors: 50-53 samples (depending on antigen)
- Data Provenance: The samples were collected from patients representing the eastern, midwestern, and western United States. The study was conducted at "two clinical laboratories and at DiaSorin," indicating a multi-site clinical study. The samples were retrospective (frozen) and prospective (fresh).
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
The document does not explicitly state the "number of experts" or their specific "qualifications" (e.g., "radiologist with 10 years of experience") used to establish the ground truth.
However, the ground truth was established by:
- "expected patterns of serological testing results for the 4 EBV markers (EBV VCA IgG and IgM, EBNA, and EA), and for primary infection, heterophile test."
- This implies a reliance on established diagnostic algorithms and interpretation of results from multiple serological tests, including IFA and heterophile tests. This process would typically involve clinical laboratory professionals or infectious disease specialists, but their number and specific qualifications are not detailed.
4. Adjudication Method for the Test Set
The document does not describe a formal "adjudication method" in the sense of a panel reviewing conflicting results from multiple readers. Instead, the ground truth was "based on comparison to expected patterns of serological testing results" and "IFA results for VCA IgM, VCA IgG and EBNA" and heterophile test results. Discrepancies (e.g., "Equivocal results by Copalis or IFA or non-specific staining by IFA") were "not included in the calculations." This indicates a methodical approach to classifying samples based on a pre-defined diagnostic algorithm using a combination of established tests, rather than an adjudication among human readers.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. The study compares the performance of the Copalis® device to predicate devices (IFA) and established serological patterns, not to human readers with or without AI assistance.
6. If a Standalone Study (Algorithm Only Without Human-in-the-Loop Performance) Was Done
Yes, this was a standalone study. The Copalis® Multiplex EBV Antibody Assay is an automated immunoassay system. The reported performance metrics (sensitivity, specificity, agreement) directly reflect the algorithm's performance in detecting antibodies based on its light scattering technology, without human intervention in the result generation or interpretation process for the purpose of the device's output. The comparison to IFA serves as validation against a recognized lab test, not as a human-in-the-loop comparison.
7. The Type of Ground Truth Used
The ground truth used was a composite reference standard based on:
- Expert Consensus/Established Serological Patterns: "Expected patterns of serological testing results for the 4 EBV markers" and for primary infection, heterophile test.
- Reference Laboratory Testing (Predicate Devices): Specifically, IFA results for VCA IgM, VCA IgG, EBNA, and EA, as well as heterophile test results. The inclusion/exclusion criteria for different disease states were defined by these reference test results.
8. The Sample Size for the Training Set
The document does not describe a separate "training set" for the Copalis® device in the context of a machine learning algorithm. The device is an immunoassay, the "training" would refer to its development and calibration, which is not detailed here. The clinical samples discussed are the "test set" used for performance evaluation.
9. How the Ground Truth for the Training Set Was Established
As there is no explicitly mentioned "training set" for a machine learning algorithm, this question is not directly applicable. For the immunoassay's development and calibration, general laboratory practices for standard curves, controls, and characterization would have been used, but specific details on how ground truth was established for that phase are not provided in this regulatory submission.
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JUN 4 . . .
May 25, 1999
510(k) SUMMARY
SUBMITTED BY:
Judith J. Smith DiaSorin, Inc. 9175 Guilford Rd. Suite 100 Columbia, MD 21046
NAME OF DEVICES: Trade Name:
Copalis® Multiplex EBV Antibody Assay
Common Names/Descriptions:
Immunoassay for the Detection of Total Antibodies to Epstein Barr Virus
Classification Names:
EBV Serology Test
Gull Laboratories EBV IgG IFA Gull Laboratories EBV-NA IFA Gull Laboratories EBV-EA IFA
DEVICE DESCRIPTION:
PREDICATE DEVICES:
INTENDED USE: The Copalis® Multiplex EBV Antibody Assay uses Coupled Particle Light Scattering technology in a microparticle agglutination-based assay for the qualitative or semiquantitative detection of antibodies to EBV VCA (total antibodies), EBNA (IgG), and EA (IgG and IgM) antigens. The assay is designed for human serum using the Copalis® I Immunoassay System. The presence of VCA, EBNA and EA antibodies is used as an aid in the diagnosis of EBV associated mononucleosis when used in conjunction with other EBV serologies in pediatric, adult, transplant donor and transplant recipient populations. The disease state distinction is made based on the antibody pattern of reactivity. When evaluating properly paired sera, the results of these assays are used to demonstrate seroconversion or significant change in antibody titer as evidence of recent infection. Both specimens should be tested simultaneously.
KIT DESCRIPTION: Coupled Particle Light Scattering (Copalis®) technology provides a rapid method for the measurement of antibodies to specific pathogens. The Copalis® Multiplex EBV Antibody Assay is a microparticle agglutination test using the Copalis® light scattering technology. Polystyrene microparticles of 3 sizes are coated with VCA synthetic peptide, EBNA recombinant antigen or EA recombinant antigen and are contained within a special covered reaction well in the test cup. The dried reagent is reconstituted with a reaction buffer on the instrument at the start of the assay. Patient sample is added to the reaction mixture and incubated for 10 minutes. The presence of antibodies specific to EBV antigens in the patient sample results in agglutination of the monomer microparticles to form aggregates. The reaction mixture is passed through a flow cell and the instrument uses light scattering technology to measure the monomer concentration. The decrease in the monomer population resulting from agglutination is related to the amount of antibody in the sample. The residual monomer concentration in each reaction mixture is compared to a cutoff value to determine sample reactivity and nonreactivity.
B-1
{1}------------------------------------------------
PERFORMANCE DATA:
Clinical Correlation: Fifty fresh (12%) and 373 frozen (88%) samples were analyzed at two clinical laboratories and at DiaSorin. Patients from the disease states defined below and representing the eastern, midwestern and western United States were tested. The screening population is a group of samples from patients suspected of disease. The samples were chosen for each disease state population based upon comparison to expected patterns of serological testing results for the 4 EBV markers (EBV VCA IgG and IgM, EBNA, and EA), and for primary infection, heterophile test . For primary infection, the first level of inclusion/exclusion was based on IFA results for VCA IgM, VCA IgG and EBNA. Samples with positive results for the VCA antigen and negative results for the EBNA were included and further examined. The next level of inclusion/exclusion criteria was based upon the heterophile results. A positive result is expected for this test in acute EBV infection. Samples with positive VCA IgG, and heterophile test and negative EBNA result were included in the primary infection population. If a negative result was obtained on the heterophile test, the results of the EA IFA test were examined. A positive EA IFA resulted in inclusion of the sample. A negative EA IFA result resulted in exclusion of the sample. A summary of the expected marker patterns for the EBV markers is summarized below.
| Antibody | Seronegative | Primary | Reactivated | Past |
|---|---|---|---|---|
| IgM anti-VCA | - | + | - | - |
| IgG anti-VCA | - | + | + | + |
| Anti EBNA | - | - | + | -/+ |
| Anti-EA | - | + | + | + |
| Heterophile | - | + | N/A | N/A |
Summary of Expected Patterns for EBV Antigen Reactivity
The age of the primary disease population varied from 1 to 48 years of age (mean and median age: 22 years old). The age of the patients with reactivated disease varied from 3 to 68 (mean: 27, median 23). The age range of the seronegative group was 1 to 74 (mean: 14, median: 12). The components of the Copalis Multiplex EBV Antibody Assay were compared to expected marker patterns in the defined disease states and separated into adult and pediatric populations. The results of these studies are summarized below with the 95% confidence intervals (95% Cl). Equivocal results by Copalis or IFA or non-specific staining by IFA were not included in the calculations.
Primary Disease State Population - Adult
| Expected Pattern4Copalis®/IFA | +VCA | -EBNAa | +EA vs Heterophile/IFAb |
|---|---|---|---|
| Relative Sensitivity(95% CI) | 61/61 = 100.0%(94.1 - 100%) | N/A | 56/59 = 94.9%(85.8 - 98.9%) |
| Relative Specificity(95% CI) | N/A | 56/59 = 94.9%(85.8 - 98.9%) | N/A |
| Agreement with IFA | 61/61 = 100.0% | 56/59 = 94.9% | 56/59 = 94.9% |
| Prevalence Copalis® | 61/61 = 100.0% | 3/61 = 4.9% | 56/59 = 94.9% |
| Prevalence IFA | 61/61 = 100.0% | 0/59 = 0% | 13/54 = 24.1% |
| Prevalence Heterophile | N/A | N/A | 56/61 = 91.8% |
| Prevalence Htphl/IFA | N/A | N/A | 61/61 = 100% |
2 Copalis negative/IFA equivocal
02 Copalis equivocal/IFA positive
{2}------------------------------------------------
Primary Disease State Population - Pediatric
| Expected Pattern4 | + | - | + |
|---|---|---|---|
| Copalis®/IFA | VCA | EBNA | EA vs Heterophile/IFA |
| Relative Sensitivity(95% Cl) | 12/12 = 100%(73.5 - 100.0%) | N/A | 12/12 = 100.0%(73.5 - 100.0%) |
| Relative Specificity(95% Cl) | N/A | 6/12 = 50.0%(21.1 - 78.9%) | N/A |
| Agreement with IFA | 12/12 = 100.0% | 6/12 = 50.0% | 12/12 = 100.0% |
| Prevalence Copalis® | 12/12 = 100.0% | 6/12 = 50.0% | 12/12 = 100.0% |
| Prevalence IFA | 12/12 = 100.0% | 0/12 = 0% | 8/11c = 32.3% |
| Prevalence Heterophile | N/A | N/A | 8/12 = 66.6% |
| Prevalence Htphl/IFA | N/A | N/A | 12/12 = 100% |
61 Copalis + //FA equivocal
Reactivated Disease State Population
| Expected Pattern | + | + | + |
|---|---|---|---|
| Copalis®/IFA | VCA | EBNAd | EAe |
| Relative Sensitivity | 43/43 = 100.0% | 35/39 = 89.7% | 39/39 = 100.0% |
| (95% CI) | (91.8 - 100%) | (75.8 - 97.1%) | (91.0 - 100%) |
| Relative Specificity | N/A | N/A | N/A |
| Agreement | 43/43 = 100.0% | 35/39 = 89.7% | 39/39 = 100.0% |
| Prevalence Copalis® | 43/43 = 100.0% | 39/43 = 90.7% | 42/42 = 100% |
| Prevalence IFA | 43/43 = 100.0% | 39/39 = 100% | 40/40 = 100% |
® 1 Copalis equivocal/IFA positive; 3 Copalis positive/IFA equivocal 0 4 Copalis positive/IFA equivocal
EBV Screening Population - Adult
| Copalis®/IFA | VCA | EBNA | EAr |
|---|---|---|---|
| Relative Sensitivity | $26/27 = 96.8%$ | $23/25 = 92.0%$ | $15/18 = 83.3%$ |
| (95% CI) | (83.3 - 99.9%) | (74.0 - 99.0%) | (58.6 - 96.4%) |
| Relative Specificity | $2/2 = 100.0%$ | $3/4 = 75.0%$ | $7/9=77.8%$ |
| (95% CI) | (15.8 - 100.0%) | (19.4 - 99.4%) | (40.0 - 97.2%) |
| Agreement with IFA | $28/29 = 96.6%$ | $26/29 = 89.7$ | $22/27 = 81.5%$ |
| Prevalence Copalis® | $26/29 = 89.7%$ | $24/29 = 82.9%$ | $17/29 = 58.6%$ |
| Prevalence IFA | $27/29 = 93.1%$ | $25/29 = 86.2%$ | $18/29 = 62.1%$ |
1 Copalis equivocal/IFA positive; 1 Copalis equivocal/IFA negative
EBV Screening Population - Pediatric
| Copalis®/IFA | VCA | EBNA | EA |
|---|---|---|---|
| Relative Sensitivity | 5/6 = 83.3% | 6/6 = 100.0% | 4/6 = 66.7% |
| (95% CI) | (35.9 - 99.6%) | (54.1 - 100.0%) | (22.3 - 95.7%) |
| Relative Specificity | 6/7 = 85.7% | 7/7 = 100.0% | 6/7 = 85.7% |
| (95% CI) | (42.1 - 99.6%) | (59.0 - 100.0%) | (42.1 - 99.6%) |
| Agreement with IFA | 11/13 = 84.6% | 13/13 = 100.0% | 10/13 = 76.9% |
| Prevalence Copalis® | 6/13 = 46.2% | 6/13 = 46.2% | 5/13 = 38.5% |
| Prevalence IFA | 6/13 = 46.2% | 6/13 = 46.2% | 6/13 = 46.2% |
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Seronegative Population - Adult
| Expected Pattern | - | - | - |
|---|---|---|---|
| Copalis®/IFA | VCA | EBNA | EA9 |
| Relative Sensitivity(95% CI) | N/A | N/A | N/A |
| Relative Specificity(95% CI) | 5/8 = 62.5%(24.5 - 91.5%) | 8/8 = 100.0%(63.1 - 100.0%) | 7/7 = 100%(59.0 - 100.0%) |
| Agreement | 5/8 = 62.5% | 8/8 = 100.0% | 7/7 = 100.0% |
| Prevalence Copalis® | 3/8 = 37.5% | 0/8 = 0% | 0/7 = 0% |
| Prevalence IFA | 0/8 = 0% | 0/8 = 0% | 0/7 = 0% |
9 1 Copalis negative/IFA non-specific staining
Seronegative Population - Pediatric
| Expected Pattern | - | - | - |
|---|---|---|---|
| Copalis®/IFA | VCA" | EBNA | EA' |
| Relative Sensitivity(95% CI) | N/A | N/A | N/A |
| Relative Specificity(95% CI) | 29/34 = 85.3%(68.9 - 95.0%) | 40/42 = 95.2%(83.8 - 99.4%) | 34/39 = 87.2%(72.6 - 95.7%) |
| Agreement | 29/34 = 85.3% | 40/42 = 95.2% | 34/39 = 87.2% |
| Prevalence Copalis® | 5/36 = 13.9% | 2/42 = 4.8% | 5/39 = 12.8% |
| Prevalence IFA | 0/40 = 0% | 0/42 = 0% | 0/42 = 0% |
11 6 Copalis equivocal/IFA negative; 2 Copalis negative/IFA equivocal
¹ 3 Copalis equivocal/IFA negative
Apparently Healthy Population
| Copalis®/IFA | VCAj | EBNA | EAk |
|---|---|---|---|
| Relative Sensitivity | 94/98 = 95.9% | 95/102 = 93.1% | 26/65 = 40.0% |
| (95% CI) | (89.9 - 98.9%) | (86.4 - 97.2%) | (28.0 - 52.9%) |
| Relative Specificity | N/A | N/A | 25/31 = 80.6% |
| (95% CI) | (62.5 - 92.6%) | ||
| Agreement with IFA | 94/98 = 95.9% | 95/102 = 93.1% | 51/96 = 53.1% |
| Prevalence Copalis® | 94/98 = 95.9% | 95/102 = 93.1% | 33/98 = 33.7% |
| Prevalence IFA | 102/102 = 100% | 102/102 = 100% | 69/100 = 69% |
4 Copalis equivocal/IFA positive
- 4 Copalis equivocal/IFA positive/IFA equivocal; 1 Copalis negative/IFA equivocal
Transplant Recipients
| Copalis®/IFA | VCA | EBNAl | EAm |
|---|---|---|---|
| Relative Sensitivity | 48/48 = 100% | 35/40 = 87.5% | 44/44 = 100% |
| (95% CI) | (92.6 – 100%) | (73.2 - 95.8%) | (92.0 - 100%) |
| Relative Specificity | N/A | 3/3 = 100.0% | N/A |
| (95% CI) | (29.2 – 100%) | ||
| Agreement with IFA | 48/48 = 100.0% | 38/43 = 88.4% | 45/44 = 100% |
| Prevalence Copalis® | 48/48 = 100% | 40/48 = 83.3% | 47/48 = 97.9% |
| Prevalence IFA | 48/48 = 100% | 40/48 = 83.3% | 45/48 = 93.8 |
5 Copalis positive/IFA equivocal
™ 1 Copalis equivocal/IFA positive; 3 Copalis positive/IFA nss
{4}------------------------------------------------
Transplant Donors
| Copalis®/IFA | VCAn | EBNA | EAo |
|---|---|---|---|
| Relative Sensitivity(95% CI) | 50/50 = 100.0%(92.9 - 100%) | 50/53 = 94.3%(84.3 - 98.8%) | 20/43 = 46.5%(31.2 - 62.3%) |
| Relative Specificity(95% CI) | N/A | N/A | 4/4 = 100.0%(39.8 - 100.0%) |
| Agreement with IFA | 50/50 = 100.0% | 50/50 = 94.3% | 24/47 = 51.1% |
| Prevalence Copalis® | 50/53 = 94.3% | 50/50 = 94.3% | 21/53 = 39.6% |
| Prevalence IFA | 53/53 = 100.0% | 53/53 = 100.0% | 47/51 = 92.9% |
3 Copalis positive/IFA equivocal
º 4 Copalis equivocal/IFA positive; 1 Copalis positive/ IFA nss; 1 Copalis negative/IFA nss
When viewed as a panel of results, the Copalis® Multiplex EBV Antibody Assay gives equivalent performance to IFA. Prevalence by Copalis® Multiplex EBV Antibody Assay components in the defined disease states more closely matches expected prevalences than IFA. This is especially noticeable with EA IFA which shows poor correlation to disease state or heterophile result. The EA IFA prevalence in the primary infection population was lower than expected and in the apparently healthy population was higher than expected. The same pattern was seen in the recipient/donor population study. The poor agreement between the EA component of the Copalis® assay and EA IFA is also due to the EA IFA results that do not correlate to clinical state. Copalis® Multiplex EBV EA component detects EA(D) whereas EA IFA detects both EA(D) and EA(R). This could account for the large number of apparently false positive EA IFA results since EA(D) is present only in primary infection and EA(R) is present long after recovery. Regarding EBNA comparison, it has been reported that recombinant EBNA assays are more sensitive to EBNA IgG than IFA.
Reproducibility: Reproducibility studies were performed at the 3 sites using one lot of tests. Assay reproducibility was determined by testing 6 samples that spanned the range of the assay components CTRs. Samples were tested in duplicate once a day for 5 days. The results are summarized below.
| Sample | MeanCI | Within Run%CV | Total%CV |
|---|---|---|---|
| Neg Control | 0.78 | -- | 3.9% |
| Low Pos Control | 2.17 | -- | 12.3% |
| High Pos Control | 11.23 | -- | 21.8% |
| RP 1 | 0.81 | 1.9% | 6.4% |
| RP 2 | 0.81 | 2.0% | 6.1% |
| RP 3 | 13.78 | 7.3% | 15.5% |
| RP 4 | 34.89 | 18.5% | 18.7% |
| RP 5 | 5.39 | 8.6% | 12.5% |
| RP 6 | 1.05 | 2.8% | 7.3% |
| RP 7 | 1.35 | 7.6% | 13.3% |
Reproducibility Results, Combined Sites ~ VCA
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Reproducibility Results, Combined – EBNA
| Sample | Mean | Within Run%CV | Total |
|---|---|---|---|
| CI | %CV | ||
| Neg Control | 0.82 | -- | 2.8% |
| Low Pos Control | 1.80 | -- | 7.3% |
| High Pos Control | 8.95 | -- | 14.5% |
| RP 1 | 0.84 | 3.1% | 4.9% |
| RP 2 | 0.85 | 2.6% | 4.2% |
| RP 3 | 0.92 | 2.6% | 6.9% |
| RP 4 | 31.36 | 13.9% | 13.0% |
| RP 5 | 2.10 | 8.2% | 10.2% |
| RP 6 | 60.20 | 13.8% | 18.0% |
| RP 7 | 2.65 | 9.7% | 12.8% |
Reproducibility Results, Combined --EA
. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
| ults, Combined -EA | |||
|---|---|---|---|
| Sample | MeanCI | Within Run%CV | Total%CV |
| Neg Control | 0.84 | -- | 5.4% |
| Low Pos Control | 1.83 | -- | 8.7% |
| High Pos Control | 7.37 | -- | 19.5% |
| RP 1 | 0.86 | 1.9% | 6.1% |
| RP 2 | 0.87 | 0.8% | 5.9% |
| RP 3 | 16.68 | 9.1% | 23.4% |
| RP 4 | 2.18 | 8.6% | 22.3% |
| RP 5 | 5.50 | 9.0% | 16.3% |
| RP 6 | 0.99 | 4.0% | 12.4% |
| RP 7 | 0.96 | 4.7% | 10.4% |
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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which is a staff with a serpent entwined around it. The caduceus is positioned to the right of the text "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA", which is arranged in a circular fashion around the symbol. The logo is black and white.
Public Health Service
Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850
4 1999 JUN
DiaSorin, Inc. c/o Carole Stamp TUV Product Service. Inc. 1775 Old Highway 8 NW New Brighton, MN 55112
Re: K991660
Trade Name: Copalis® Multiplex EBV Antibody Assay Regulatory Class: I Product Code: LSE Dated: May 27, 1999 Received: May 28, 1999
Dear Ms. Stamp:
We have reviewed your Section 510(k) notification of intent to market the device referenced above and we 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). 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 (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the Current Good Manufacturing Practice requirements, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic QS inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.
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Under the Clinical Laboratory Improvement Amendments of 1988 (CLIA-88), this device may require a CLIA complexity categorization. To determine if it does, you should contact the Centers for Disease Control and Prevention (CDC) at (770)488-7655.
This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate 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 Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4588. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll free number (800) 638-2041 or at (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html"
Sincerely yours,
Steven Sutman
Steven I. Gutman, M.D., M.B.A. Director Division of Clinical Laboratory Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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INDICATIONS FOR USE
510(k) Number (if known): not known
Copalis® Multiplex EBV Antibody Assay Device Name: Indications For Use: The Copalis® Multiplex EBV Antibody Assay uses Coupled Particle Light Scattering technology in a micropaticle agglutination-based assay for the qualitative or semiquantitative detection of antibodies to EBV VCA (total antibodies), EBNA (IgG), and EA (IgG and IgM) antigens. The assay is designed for human serum using the Copalis® I Immunoassay System. The presence of VCA, EBNA and EA antibodies is used as an aid in the diagnosis of EBV associated mononucleosis when used in conjunction with other EBV serologies in pediatric, adult, transplant donor and transplant recipient populations. The disease state distinction is made based on the antibody pattern of reactivity. When evaluating properly paired sera, the results of these assays are used to demonstrate seroconversion or significant change in antibody titer as evidence of recent infection. Both specimens should be tested simultaneously.
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Concurrence of CDRH, Office of Device Evaluation (ODE)
Woody Dubois
n of Clinical Laboratory Dev 510(k) Number
Prescription Use X
(Per 21 CFR 801.109)
OR
Over-The-Counter Use
(Optional Format 1-2-96)
§ 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).