(86 days)
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No
The description details a standard enzyme immunoassay and an automated microplate system that performs routine laboratory functions. There is no mention of AI or ML in the device description, intended use, or performance studies.
No.
This device is an in vitro diagnostic (IVD) test used for the qualitative detection of IgM antibodies to hepatitis A virus in human serum or plasma. It is used for diagnosis, not treatment, of disease.
Yes
The device is intended for the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human serum or plasma. It is explicitly indicated for testing specimens from individuals with signs and symptoms consistent with acute hepatitis, and its results "may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A." These are all functions of a diagnostic device.
No
The device is an in vitro diagnostic (IVD) kit that includes reagents and is intended for manual use or with an automated microplate system. While it utilizes software for the automated system, the core device is a physical assay kit, not software only.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states that the MONOLISA™ Anti-HAV IgM EIA is an "in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma". This clearly indicates that the device is used to examine specimens taken from the human body to provide information for diagnostic purposes.
- Device Description: The description details a laboratory test procedure involving patient specimens (serum or plasma) and reagents to detect a specific analyte (IgM antibodies to HAV). This is characteristic of an in vitro diagnostic device.
- Performance Studies: The document describes performance studies (correlation/method comparison, precision, reproducibility) conducted on human samples, which are standard for evaluating the performance of IVD devices.
- Predicate Device: The mention of a "Predicate Device(s)" with a K number (K063319) and the name "MONOLISA™ Anti-HAV IgM EIA using the manual method" strongly suggests that this device is being submitted for regulatory clearance as an IVD, comparing it to a previously cleared IVD.
All of these elements align with the definition and characteristics of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results, in conjunction with other serological or clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A. The MONOLISA™ Anti-HAV IgM EIA is intended for manual use and with the Evolis™ Automated Microplate System in the detection of IgM antibodies to hepatitis A virus.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, and cord blood or neonatal specimens.
Warning: This assay is not intended for screening blood or solid or soft tissue donors.
Product codes (comma separated list FDA assigned to the subject device)
LOL, JJE
Device Description
The MONOLISA™ Anti-HAV IgM EIA is an enzyme immunoassay (IgM antibody capture format) for the detection of IgM antibodies to hepatitis A virus. In the assay procedure, patient specimens, a calibrator, and controls are incubated with antibodies coated on the microwells. If IgM antibodies to HAV are present in a specimen or control, they bind to the antibody. Excess sample is removed by a wash step. The HAV Viral Antigen and the Conjugate (containing horseradish peroxidase - labeled mouse monoclonal antibody to HAV) are successively added to the microwells and allowed to incubate. The presence of anti-HAV IgM in the sample enables the HAV Viral Antigen and the Conjugate to bind to the solid phase. Excess Conjugate and HAV Viral Antigen are removed by a wash step, and a TMB Chromogen /Substrate solution is added to the microwells and allowed to incubate. If a sample contains anti-HAV IgM, the bound enzyme (HRP) causes the colorless tetramethylbenzidine (TMB) in the Chromogen solution to change to blue. The blue color turns yellow after the addition of a Stopping Solution. If a sample does not contain anti-HAV IgM, the Chromogen/Substrate solution in the well remains colorless during the substrate incubation, and after the Stopping Solution. The color intensity is measured spectrophotometrically. Absorbance value readings for patient specimens are compared to the cutoff value.
The performance of the MONOLISA™ Anti-HAV IgM EIA was evaluated in conjunction with the EVOLIS™ Automated Microplate System. The EVOLIS™ Automated Microplate System is a fully automated microplate analyzer that performs all functions necessary for the complete processing of microplate assays. Functions include: barcode scanning, sample pre-dilutions, sample and reagent dispensing, plate incubations, plate wash cycles, photometric measurement of completed assay plates and results evaluation. The analyzer instrument is controlled via the EVOLIS™ software, a Windows® 2000 application running on a separate dedicated PC. An operator loads the appropriate microplates, assay reagents, and patient and control samples, then selects assay parameters, loads sample information, initiates instrument processing, and generates result reports.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Adult and pediatric
Intended User / Care Setting
Laboratory diagnosis, not intended for screening blood or solid or soft tissue donors.
Description of the training set, sample size, data source, and annotation protocol
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Description of the test set, sample size, data source, and annotation protocol
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Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Correlation/method comparison:
- Study 1: 691 retrospective samples were tested on the MONOLISA™ Anti-HAV IgM assay using four (4) EVOLIS™ instruments at three sites and compared to manual method.
- Study 2: 313 samples were tested with the MONOLISA™ Anti-HAV IgM EIA on a combination plate format on EVOLIS™ and compared to manual method (reference method, individual plate format).
Precision Study (Within-Laboratory):
- A 21-member panel (3 serum samples with 6 corresponding plasma samples at 3 different levels) was tested. Two replicates of the 24-member panel were assayed twice a day for 20 days.
- The data was analyzed following CLSI guidance EP5-A2. Mean ratio, SD, and %CV were calculated.
Reproducibility Study:
- A 6-member panel (diluted plasma, negative and different levels of positive) was tested in triplicate, once a day for 5 days at 3 separate clinical trial sites. Each panel was coded to blind the operator.
- Data from all sites combined to obtain SD and %CV for within run, between day, between site, and total variance, analyzed according to CLSI guidance EP15-A2.
Pipettor and washer carry-over:
- Studies verified that disposable tip pipettes and the washer on the EVOLIS™ do not carry residuals.
Pipetting accuracy:
- Dye studies were performed using 2 different volumes for samples and controls, demonstrating pipetting accuracy with a CV of ≤7.7%.
Key Results:
- Correlation/method comparison:
- Study 1 (EVOLIS™ vs. Manual): Positive percent agreement: 100% (94/94), 95% CI: 96.1 - 100%. Negative percent agreement: 99.7% (595/597), 95% CI: 98.8 - 99.9%. Overall percent agreement: 99.7% (689/691), 95% CI: 98.9 - 99.9%.
- Study 2 (EVOLIS™ Combination Plate vs. Manual): Positive percent agreement: 100% (49/49), 95% CI: 92.7 – 100%. Negative percent agreement: 99.2% (262/264), 95% CI: 97.3 - 99.8%. Overall percent agreement: 99.4% (311/313), 95% CI: 97.7 - 99.8%.
- Precision and Reproducibility studies showed acceptable variability for the assay performance.
- The MONOLISA™ Anti-HAV IgM EIA tested with the EVOLIS™ Automated Microplate System demonstrated equivalent performance to the MONOLISA™ Anti-HAV IgM EIA tested with the manual assay method.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive percent agreement, Negative percent agreement, Overall percent agreement, Standard Deviation (SD), percent coefficient of variation (%CV).
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
§ 866.3310 Hepatitis A virus (HAV) serological assays.
(a)
Identification. HAV serological assays are devices that consist of antigens and antisera for the detection of hepatitis A virus-specific IgM, IgG, or total antibodies (IgM and IgG), in human serum or plasma. These devices are used for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis to determine if an individual has been previously infected with HAV, or as an aid to identify HAV-susceptible individuals. The detection of these antibodies aids in the clinical laboratory diagnosis of an acute or past infection by HAV in conjunction with other clinical laboratory findings. These devices are not intended for screening blood or solid or soft tissue donors.(b)
Classification. Class II (special controls). The special control is “Guidance for Industry and FDA Staff: Class II Special Controls Guidance Document: Hepatitis A Virus Serological Assays.” See § 866.1(e) for the availability of this guidance document.
0
510(k) Summary
OCT 29 2009
| 1. Company: | Bio-Rad Laboratories
6565 185th Avenue NE
Redmond, WA 98052
Phone: 425 881-8300
Fax: 425 498-1651 |
|------------------------|---------------------------------------------------------------------------------------------------------------|
| Contact: | Linda Staswick |
| Date Summary Prepared: | October 22, 2009 |
2. Device Name:
| Device Trade Name: | MONOLISA™ Anti-HAV IgM EIA | EVOLIS™ Automated Microplate
System |
|----------------------|-----------------------------------------------------------------|-------------------------------------------------------------|
| Common Name: | IgM Antibody to Hepatitis A Virus Automated Laboratory Analyzer | |
| Classification Name: | Hepatitis A Virus (HAV)
serological assays | Discrete photometric chemistry
analyzer for clinical use |
| Product Code: | LOL | JJE |
| Regulation Number: | 21 CFR 866.3310 | 21 CFR 862.2160 |
| Regulatory Class: | Class II | Class I |
| Panel: | Microbiology | Chemistry |
3. Substantial Equivalence:
The MONOLISA™ Anti-HAV IgM EIA used with the EVOLIS™ Automated Microplate System is substantially equivalent to the MONOLISA™ Anti-HAV IgM EIA using the manual method (KO63319)
Description of the Device: 4.
The MONQLISA™ Anti-HAV IgM EIA is an enzyme immunoassay (IgM antibody capture format) for the detection of IgM antibodies to hepatitis A virus. In the assay procedure, patient specimens, a calibrator, and controls are incubated with antibodies coated on the microwells. If IgM antibodies to HAV are present in a specimen or control, they bind to the antibody. Excess sample is removed by a wash step. The HAV Viral Antigen and the Conjugate (containing horseradish peroxidase - labeled mouse monoclonal antibody to HAV) are successively added to the microwells and allowed to incubate. The presence of anti-HAV IgM in the sample enables the HAV Viral Antigen and the Conjugate to bind to the solid phase. Excess Conjugate and HAV Viral Antigen are removed by a wash step, and a TMB Chromogen /Substrate solution is added to the microwells and allowed to incubate. If a sample contains anti-HAV IgM, the bound enzyme (HRP) causes the colorless tetramethylbenzidine (TMB) in the Chromogen solution to change to blue. The blue color turns vellow after the addition of a Stopping Solution. . If a sample does not contain anti-HAV IgM, the Chromogen/Substrate solution in the well remains colorless during the substrate incubation, and after the Stopping Solution. The color intensity is measured spectrophotometrically. Absorbance value readings for patient specimens are compared to the cutoff value.
The performance of the MONOLISA™ Anti-HAV IgM EIA was evaluated in conjunction with the EVOLIS™ Automated Microplate System. The EVOLIS™ Automated Microplate System is a fully automated microplate analyzer that performs all functions necessary for the complete processing of microplate assays. Functions include: barcode scanning, sample
1
pre-dilutions, sample and reagent dispensing, plate incubations, plate wash cycles, photometric measurement of completed assay plates and results evaluation. The analyzer instrument is controlled via the EVOLIS™ software, a Windows® 2000 application running on a separate dedicated PC. An operator loads the appropriate microplates, assay reagents, and patient and control samples, then selects assay parameters, loads sample information, initiates instrument processing, and generates result reports.
5. Intended Use:
The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results, in conjunction with other serological or clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A. The MONOLISA™ Anti-HAV IqM EIA is intended for manual use and with the Evolis™ Automated Microplate System in the detection of IgM antibodies to hepatitis A virus.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, and cord blood or neonatal specimens.
Warning: This assay is not intended for screening blood or solid or soft tissue donors.
6. Technological Characteristics
The following tables summarize similarities and differences between the MONOLISA™ Anti-HAV IqM EIA tested manually and the MONOLISA™ Anti-HAV IqM EIA tested with the EVOLIS™ Automated Microplate System.
2
| Table 1: Similarities between devices | ||
|---|---|---|
| Parameter | MONOLISA™ Anti-HAV IgM EIA tested with the EVOLIS™ Automated Microplate System | MONOLISA™ Anti-HAV IgM EIA tested manually |
| Intended Use/Indications for Use | The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). | The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). |
| Assay procedure | Per the instructions in the package insert | Per the instructions in the package insert |
| Plate incubation | $60 \pm 5$ minutes at 37°C + 2°C | $60 \pm 5$ minutes at 37°C + 2°C |
| Plate washing | Wash with ≥ 370 µL of Working Wash Solution per well, and 30 - 60 second soak between each wash cycle for a total of 5 cycles. | Wash with ≥ 370 µL of Working Wash Solution per well, and 30 - 60 second soak between each wash cycle for a total of 5 cycles. |
| Result interpretation | Result interpretations, based on sample O.D.s, are determined according to package insert criteria. | Result interpretations, based on sample O.D.s, are determined according to package insert criteria. |
| Photometric measurement of completed assay plates | Read absorbance using 450 nm filter with 620 nm as the reference | Read absorbance using 450 nm filter with 615 to 630 nm as the reference |
Table 1· Similarities between devices
| Table 2: Differences between devices | ||
|---|---|---|
| Parameter | MONOLISA™ Anti-HAV IgM EIA | |
| tested with the EVOLIS™ | ||
| Automated Microplate System | MONOLISA™ Anti-HAV IgM EIA | |
| tested manually | ||
| Sample and reagent | ||
| dispensing | Samples and reagents are dispensed | |
| by the automated system | Samples and reagents are dispensed | |
| manually | ||
| Barcode reading | Sample and reagent ID are verified | |
| automatically | NA or can be performed manually | |
| with barcode wand | ||
| Plate incubation | Plates are automatically moved to | |
| the incubation chamber | Plates are moved manually to the | |
| incubation chamber | ||
| Plate wash cycles | Plates are automatically washed | Plates are moved manually to an |
| automated plate washer | ||
| Data management | Archives and retrieves data and | |
| sample information | NA | |
| Spectrophotometric | ||
| verification of sample and | ||
| reagent pipeting | Performed automatically | Optional verification visually or with |
| microplate reader |
7. Performance Characteristics:
The performance of the MONOLISA™ Anti-HAV IgM EIA with the EVOLIS™ Automated Micropiate System was compared to the MONOLISA™ Anti-HAV IgM EIA tested manually, which wad previously received marketing clearance from the Agency. Substantial equivalence of the MONOLISA™ Anti-HAV IgM EIA, using manual equipment, was determined May 3, 2007 (K063319).
3
Correlation/method comparison
Studies have been performed with the MONOLISA™ Anti-HAV IgM EIA on the EVOLIS™ Automated System and compared to the results of testing the same kits and samples with the manual method. In this study 691 retrospective samples were tested on the MONOLISA™ Anti-HAV IgM assay using four (4) EVOLIS™ instruments at three sites. The same samples were tested manually (reference method) on the MONOLISA™ Anti-HAV IdM assay. The positive, neqative and overall percent along with the 95% confidence interval are presented below. In determining the percent agreement on borderline results, specimens that were borderline with the reference assay and negative with EVOLIS™ were considered as false negative for the EVOLIS ™.
| EVOLIS™ Anti-HAV IgM Results | ||||
|---|---|---|---|---|
| Manual Anti-HAV IgM Results | Reactive | Borderline | Nonreactive | Total |
| Reactive | 94 | 0 | 0 | 94 |
| Borderline | 1 | 0 | 0 | 1 |
| Nonreactive | 1 | 0 | 595 | 596 |
| Total | 96 | 0 | 595 | 691 |
| Table 2: MONOLISA™ Anti-HAV IgM EIA on EVOLIS™ vs. Manual Results | ||
|---|---|---|
The positive percent agreement with the reference method, manual testing, is 100% (94/94) with a 95% confidence interval of 96.1 - 100%. The negative percent agreement with the reference method is 99.7% (595/597) with a 95% confidence interval of 98.8 - 99.9%. The overall percent agreement is 99.7% (689/691) with a 95% confidence interval of 98.9 - 99.9%
The EVOLIS™ was also evaluated by performing a combination of 2 assays on the same plate. In this study 313 samples were tested with the MONOLISA™ Anti-HAV IgM EIA on a combination plate format on EVOLIS™ (two separate MONOLISA™ hepatitis assays run in a single microplate frame). Results were compared to the same samples tested manually (the reference method, individual plate format) on the MONOLISA™ Anti-HAV IgM assay. In determining the percent agreement on borderline results, specimens that were borderline with the reference assay (manual individual plate) and negative with EVOLIS™ (combination plate) were considered as false negative for the EVOLIS™ (combination plate).
| | EVOLIS™ Anti-HAV IgM Results
Individual Plate | | | |
|--------------------------------------------------|--------------------------------------------------|------------|-------------|-------|
| Manual Anti-HAV IgM Results
Combination Plate | Reactive | Borderline | Nonreactive | Total |
| Reactive | 49 | 0 | 0 | 49 |
| Borderline | 1 | 0 | 0 | 1 |
| Nonreactive | 0 | 1 | 262 | 263 |
| Total | 50 | 1 | 262 | 313 |
Table 3: MONOLISA™ Anti-HAV IgM ElA on EVOLIS™ Combination Plate Testing vs. Manual Results
The positive percent agreement with the reference method, manual testing, is 100% (49/49) with a 95% confidence interval of 92.7 – 100%. The negative percent agreement with the reference method is 99.2% (262/264) with a 95% confidence interval of 97.3 - 99.8%. The overall percent agreement is 99.4% (311/313) with a 95% confidence interval of 97.7 - 99.8%
4
Precision Study (Within-Laboratory)
A 21-member panel was tested: three (3) serum samples with six (6) corresponding plasma samples (EDTA K2, EDTA K3, Sodium Citrate, Sodium Heparin, Lithium Heparin, ACD) at three (3) different levels [1 low positive near the cutoff (Panel Set 1), 1 negative near the cutoff (Panel Set 2) and 1 negative (Panel Set 3)]. Two replicates each of the twenty-four (24) member panel were assayed twice a day for 20 days. The data were analyzed following the CLSI guidance EP5-A2, Evaluation of Precision Performance of Quantitative Measurement Methods. The mean ratio, the Standard Deviation (SD) and percent coefficient of variation (%CV) were calculated for each panel member.
The data summary is shown in the following tables, which summarize testing with the EVOLIS™ Automated System:
| N | Mean | Within run¹ | Between Run ² | Between Day ³ | Total ⁴ | |||||
|---|---|---|---|---|---|---|---|---|---|---|
| Panel Member | S/CO | SD | CV (%) | SD | CV (%) | SD | CV (%) | SD | CV (%) | |
| Positive Control | 80 | 1.97 | 0.035 | 1.8 | 0.091 | 4.6 | 0.163 | 8.3 | 0.190 | 9.7 |
| High Negative | 80 | 0.10 | 0.006 | 6.1 | 0.015 | 14.9 | 0.015 | 14.7 | 0.022 | 21.8 |
| Cutoff Control | 80 | 3.78 | 0.146 | 3.9 | 0.132 | 3.5 | 0.166 | 4.4 | 0.258 | 6.8 |
| Serum (1) | 80 | 1.55 | 0.036 | 2.3 | 0.076 | 4.9 | 0.138 | 8.9 | 0.161 | 10.4 |
| EDTA K2 (1) | 80 | 1.44 | 0.020 | 1.4 | 0.075 | 5.2 | 0.131 | 9.1 | 0.152 | 10.6 |
| EDTA K3 (1) | 80 | 1.49 | 0.030 | 2.0 | 0.083 | 5.6 | 0.126 | 8.5 | 0.154 | 10.3 |
| Sodium Citrate (1) | 80 | 1.48 | 0.033 | 2.2 | 0.086 | 5.8 | 0.140 | 9.5 | 0.168 | 11.3 |
| Sodium Heparin (1) | 80 | 1.41 | 0.024 | 1.7 | 0.080 | 5.7 | 0.132 | 9.4 | 0.156 | 11.1 |
| Lithium Heparin (1) | 80 | 1.39 | 0.026 | 1.9 | 0.077 | 5.5 | 0.120 | 8.7 | 0.145 | 10.5 |
| ACD (1) | 80 | 1.64 | 0.021 | 1.3 | 0.107 | 6.6 | 0.144 | 8.8 | 0.181 | 11.0 |
| Serum (2) | 80 | 0.62 | 0.016 | 2.7 | 0.031 | 5.0 | 0.059 | 9.5 | 0.068 | 11.1 |
| EDTA K2 (2) | 80 | 0.69 | 0.016 | 2.3 | 0.034 | 5.0 | 0.077 | 11.3 | 0.086 | 12.5 |
| EDTA K3 (2) | 80 | 0.69 | 0.014 | 2.0 | 0.046 | 6.6 | 0.073 | 10.5 | 0.087 | 12.5 |
| Sodium Citrate (2) | 80 | 0.74 | 0.014 | 1.9 | 0.044 | 5.9 | 0.075 | 10.1 | 0.088 | 11.9 |
| Sodium Heparin (2) | 80 | 0.66 | 0.011 | 1.6 | 0.041 | 6.2 | 0.061 | 9.2 | 0.074 | 11.2 |
| Lithium Heparin (2) | 80 | 0.66 | 0.020 | 3.0 | 0.040 | 6.1 | 0.058 | 8.9 | 0.073 | 11.1 |
| ACD (2) | 80 | 0.78 | 0.012 | 1.5 | 0.052 | 6.7 | 0.072 | 9.2 | 0.090 | 11.5 |
| Serum (3) | 80 | 0.10 | 0.004 | 3.6 | 0.010 | 9.7 | 0.010 | 10.1 | 0.015 | 14.5 |
| EDTA K2 (3) | 80 | 0.11 | 0.005 | 4.7 | 0.011 | 10.3 | 0.009 | 8.2 | 0.015 | 14.0 |
| EDTA K3 (3) | 80 | 0.10 | 0.004 | 4.2 | 0.010 | 9.5 | 0.011 | 10.6 | 0.015 | 14.8 |
| Sodium Citrate (3) | 80 | 0.10 | 0.003 | 2.9 | 0.009 | 9.2 | 0.010 | 9.8 | 0.014 | 13.8 |
| Sodium Heparin (3) | 80 | 0.10 | 0.004 | 3.8 | 0.009 | 8.7 | 0.010 | 9.9 | 0.014 | 13.7 |
| Lithium Heparin (3) | 80 | 0.10 | 0.015 | 4.5 | 0.010 | 9.5 | 0.010 | 9.2 | 0.014 | 14.0 |
| ACD (3) | 78 | 0.10 | 0.005 | 4.3 | 0.010 | 10.0 | 0.009 | 8.7 | 0.015 | 13.9 |
Table 4: MONOLISA™ Anti-HAV IgM EIA Precision Results by Panel Member Signal to Cutoff (S/CO)
Within Run: variability of the assay performance from replicate to replicate
Between Run: variability of the assay performance from run to run
3 Between Day: variability of the assay performance from day to day
4 Total: total variability of the assay performance includes within run, between run and between day.
5
Reproducibility Study
A 6-member panel consisting of diluted plasma specimens (negative and different levels of positive) was tested in triplicate, once a day for 5 days with the MONOLISA™ Anti-HAV IgM EIA at 3 separate clinical trial sites. Each panel was coded with a different number on each day tested in order to blind the operator to the expected value of the sample. One (1) lot was used at each of 3 sites.
The data from all sites were combined to obtain standard deviation (SD) and percent coefficient of variation (CV) for within run, between day, between site and total variance. The data were analyzed according to the principles described in the Clinical Laboratory Standards Institute guidance EP15-A2, User Protocol for Evaluation of Qualitative Test Performance. The summaries are shown in the following tables:
| Test
Site | ID # | Panel Member | N | Mean
(S/CO) | Within Run1 | | Between Day2 | | Total3 | |
|--------------|------|-------------------|----|----------------|-------------|------|--------------|------|--------|------|
| | | | | | SD | %CV | SD | %CV | SD | %CV |
| Site #1 | P1 | Negative | 30 | 0.16 | 0.033 | 20.5 | 0.014 | 9.0 | 0.036 | 22.4 |
| | P2 | High Negative | 30 | 0.74 | 0.023 | 3.0 | 0.024 | 3.2 | 0.033 | 4.4 |
| | P3 | Low Positive | 30 | 1.21 | 0.036 | 3.0 | 0.034 | 2.8 | 0.050 | 4.1 |
| | P4 | Low Positive | 30 | 1.21 | 0.051 | 4.2 | 0.031 | 2.5 | 0.059 | 4.9 |
| | P5 | Positive | 30 | 3.13 | 0.082 | 2.6 | 0.117 | 3.7 | 0.143 | 4.6 |
| | P6 | Positive | 29 | 3.68 | 0.110 | 3.0 | 0.136 | 3.7 | 0.175 | 4.8 |
| | P7 | Positive Control | 30 | 1.95 | 0.079 | 4.1 | 0.093 | 4.8 | 0.122 | 6.3 |
| | P8 | Negative Control | 30 | 0.11 | 0.008 | 6.9 | 0.011 | 10.4 | 0.014 | 12.5 |
| | P9 | Cutoff Calibrator | 30 | 3.28 | 0.139 | 4.2 | 0.159 | 4.9 | 0.211 | 6.4 |
| Site #2 | P1 | Negative | 30 | 0.17 | 0.013 | 7.7 | 0.008 | 5.0 | 0.016 | 9.2 |
| | P2 | High Negative | 30 | 0.72 | 0.019 | 2.7 | 0.010 | 1.4 | 0.022 | 3.0 |
| | P3 | Low Positive | 30 | 1.18 | 0.029 | 2.5 | 0.004 | 0.4 | 0.029 | 2.5 |
| | P4 | Low Positive | 30 | 1.17 | 0.036 | 3.1 | 0.022 | 1.8 | 0.042 | 3.6 |
| | P5 | Positive | 30 | 3.06 | 0.070 | 2.3 | 0.052 | 1.7 | 0.087 | 2.9 |
| | P6 | Positive | 30 | 3.65 | 0.093 | 2.5 | 0.071 | 1.9 | 0.116 | 3.2 |
| | P7 | Positive Control | 30 | 1.91 | 0.073 | 3.8 | 0.023 | 1.2 | 0.076 | 4.0 |
| | P8 | Negative Control | 30 | 0.12 | 0.009 | 7.4 | 0.009 | 7.7 | 0.013 | 10.7 |
| | P9 | Cutoff Calibrator | 30 | 3.54 | 0.245 | 6.9 | 0.118 | 3.3 | 0.272 | 7.7 |
| Site #3 | P1 | Negative | 30 | 0.16 | 0.015 | 9.0 | 0.021 | 13.0 | 0.025 | 15.8 |
| | P2 | High Negative | 29 | 0.69 | 0.029 | 4.2 | 0.040 | 5.7 | 0.049 | 7.1 |
| | P3 | Low Positive | 30 | 1.14 | 0.051 | 4.4 | 0.047 | 4.2 | 0.069 | 6.1 |
| | P4 | Low Positive | 30 | 1.14 | 0.048 | 4.2 | 0.050 | 4.4 | 0.069 | 6.1 |
| | P5 | Positive | 29 | 2.94 | 0.082 | 2.8 | 0.111 | 3.8 | 0.138 | 4.7 |
| | P6 | Positive | 29 | 3.57 | 0.269 | 7.6 | 0.208 | 5.8 | 0.340 | 9.5 |
| | P7 | Positive Control | 30 | 1.84 | 0.078 | 4.2 | 0.075 | 4.1 | 0.108 | 5.9 |
| | P8 | Negative Control | 28 | 0.11 | 0.015 | 14.1 | 0.021 | 19.4 | 0.026 | 23.9 |
| | P9 | Cutoff Calibrator | 28 | 3.56 | 0.278 | 7.8 | 0.343 | 9.6 | 0.441 | 12.4 |
| Table 5: MONOLISA ™ Anti-HAV IgM EIA Reproducibility Results by Panel Member Signal to Cutoff (S/CO) | |||||
|---|---|---|---|---|---|
| -- | -- | ------------------------------------------------------------------------------------------------------ | -- | -- | -- |
1 Within Run: variability of the assay performance from replicate to replicate
2 Between Day: variability of the assay performance from day to day
3 Total: total variability of the assay performance includes within run and between day
6
| Panel Member | N | Mean
S/CO | Within Run1 | | | Between Day2 | | Between Site3 | | Total4 | |
|--------------|----|--------------|-------------|------|--|--------------|------|---------------|-----|--------|------|
| | | | SD | %CV | | SD | %CV | SD | %CV | SD | %CV |
| P1 | 90 | 0.16 | 0.022 | 13.5 | | 0.014 | 8.9 | 0.0005 | 0.0 | 0.026 | 16.1 |
| P2 | 89 | 0.72 | 0.024 | 3.3 | | 0.027 | 3.8 | 0.021 | 2.9 | 0.042 | 5.8 |
| P3 | 90 | 1.18 | 0.040 | 3.4 | | 0.034 | 2.9 | 0.031 | 2.6 | 0.061 | 5.2 |
| P4 | 90 | 1.17 | 0.045 | 3.9 | | 0.036 | 3.1 | 0.032 | 2.8 | 0.066 | 5.7 |
| P5 | 89 | 3.05 | 0.078 | 2.6 | | 0.098 | 3.2 | 0.084 | 2.8 | 0.151 | 5.0 |
| P6 | 88 | 3.63 | 0.176 | 4.8 | | 0.144 | 4.0 | 0.0005 | 0.0 | 0.227 | 6.3 |
| P7 | 90 | 1.90 | 0.077 | 4.0 | | 0.070 | 3.7 | 0.044 | 2.3 | 0.113 | 5.9 |
| P8 | 88 | 0.11 | 0.011 | 9.7 | | 0.015 | 13.0 | 0.0005 | 0.0 | 0.018 | 16.2 |
| P9 | 88 | 3.46 | 0.227 | 6.6 | | 0.229 | 6.6 | 0.106 | 3.1 | 0.339 | 9.8 |
Table 6: MONOLISA™ Anti-HAV IgM EIA Reproducibility Summary by Panel Member Signal to Cutoff (S/CO)
1 Within Run: variability of the assay performance from replicate to replicate
2 Between Day: variability of the assay performance from day to day
3 Between Site: variability of the assay performance from site to site
4 Total: total variability of the assay performance includes within run and between site
5 Negative variances were rounded to zero, per statistical convention
Pipettor and washer carry-over
The pipette carryover study verified that the disposable tip pipettes on the EVOLIS™ do not carry residuals from one sample or well to another. In a washer carryover study, it was verified that the washer on the EVOLIS™ does not carry residuals from one well to another during the washing steps.
Pipetting accuracy
Dye studies were performed to determine pipetting accuracy for samples and reagents. These studies were conducted using 2 different volumes for samples and controls, and demonstrated pipetting accuracy with a CV of ≤7.7% across the microwell plate.
8. Conclusion
The MONOLISA™ Anti-HAV IgM EIA tested with the EVOLIS™ Automated Microplate System demonstrated equivalent performance to the MONOLISA™ Anti-HAV IgM EIA tested with the manual assay method, which had previously received FDA 510(k) clearance.
7
Image /page/7/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized eagle with three lines representing its wings and body. The eagle is facing to the right. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular fashion around the eagle.
DEPARTMENT OF HEALTH & HUMAN SERVICES
Public Health Service
Food and Drug Administration 10903 New Hampshire Avenue Building 66 Silver Spring, MD 20993
Bio-Rad Laboratories Attn: Linda Staswick 6565 185" Ave. NE Redmond, WA 98052
CT 9 9 2009
Re: K092353
Trade/Device Name: MONOLISA™ Anti-HAV IgM ELA with the EVOLIS™ Automated Microplate System Regulation Number: 21 CFR 866.3310 Regulation Name: Hepatitis A virus (HAV) serological assays Regulatory Class: Class II Product Codes: LOL, JJE Dated: July 30, 2009 Received: August 4, 2009
Dear Ms. Staswick:
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 or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21
8
Page 2 - Linda Staswick
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 will allow you to begin marketing your device as described in your Section 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 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 yours.
foqatra
Sally Hojvat, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics Center for Devices and Radiological Health
Enclosure
9
Indications for Use
510(k) Number (if known): K092353
Device Name: MONOLISA™ Anti-HAV IgM EIA
Indication For Use:
The MONOLISA™ Anti-HAV IgM EIA is an in vitro enzyme immunoassay kit intended for use in the qualitative detection of IgM antibodies to hepatitis A virus (anti-HAV IgM) in human (adult and pediatric) serum or plasma (EDTA, Heparin, Citrate, ACD). This assay is indicated for testing specimens from individuals who have signs and symptoms consistent with acute hepatitis. Assay results, in conjunction with other serological or clinical information, may be used for the laboratory diagnosis of individuals with acute or recent hepatitis A. The MONOLISA™ Anti-HAV IgM EIA is intended for manual use and with the Evolis™ Automated Microplate System in the detection of IgM antibodies to hepatitis A virus.
Assay performance characteristics have not been established for immunocompromised or immunosuppressed patients, and cord blood or neonatal specimens.
Warning: This assay is not intended for screening blood or soft tissue donors.
Prescription Use X (21 CFR Part 801 Subpart D) Over the Counter Use (21 CFR Part 801 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OIVD)
And/Or
Uve Schuf
Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety
4092353 510(k)