(7 days)
None
Not Found
No
The device description details a standard enzyme immunoassay (EIA) process with photometric reading. There is no mention of AI, ML, or any computational analysis beyond basic signal intensity measurement.
No.
The device is an in vitro diagnostic test for detecting norovirus in human feces, which aids in investigating the cause of acute gastroenteritis outbreaks; it does not treat or prevent disease.
Yes
The device is described as a "qualitative enzyme immunoassay (EIA) intended for the detection of selected genogroup I (...) and genogroup II (...) norovirus strains in human feces as an aid in investigating the cause of acute gastroenteritis outbreaks." This directly indicates its use in identifying a disease-causing agent, which is a diagnostic purpose. The performance metrics listed (sensitivity, specificity, positive agreement, negative agreement) are also typical for diagnostic tests.
No
The device description clearly outlines a solid phase sandwich-type EIA which involves physical components like microwell strips, antibodies, and chemical reactions. This is a laboratory-based assay, not a software-only device.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it is "intended for the detection of selected genogroup I and genogroup II norovirus strains in human feces as an aid in investigating the cause of acute gastroenteritis outbreaks." This clearly indicates it is used to examine specimens derived from the human body (feces) to provide information for diagnostic purposes (aiding in investigating the cause of outbreaks).
- Device Description: The description details a "solid phase sandwich-type EIA for the detection of genogroups GI and GII noroviruses in stool samples." This describes a laboratory test performed on a biological sample.
- Anatomical Site: The anatomical site is "human feces," which is a human specimen.
- Performance Studies: The document describes a "Clinical Study" comparing the device to a "composite reference standard" (RT-PCR and Electron Microscopy) using "samples collected from patients with diarrhea and vomiting." This is typical of studies conducted to evaluate the performance of an IVD.
- Key Metrics: The document provides "Key Metrics" such as "Positive agreement (Sensitivity)" and "Negative agreement (Specificity)," which are standard performance indicators for diagnostic tests.
All these elements align with the definition of an In Vitro Diagnostic device, which is a medical device intended for use in vitro for the examination of specimens derived from the human body solely or principally for the purpose of providing information concerning a physiological or pathological state, or concerning a congenital abnormality, or to determine the compatibility of a transplant, or to monitor therapeutic measures.
N/A
Intended Use / Indications for Use
The RIDASCREEN® Norovirus 3td Generation test is a qualitative enzyme immunoassay (EIA) intended for the detection of selected genogroup I (GI.1, GL.2, GI.3, GI.4, GL.7) and genogroup II (GII.1, GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.8, GII.10, GII.12, GII.13, GII.14, GII.17) norovirus strains in human feces as an aid in investigating the cause of acute gastroenteritis outbreaks. The likelihood of detecting a norovirus outbreak by use of the RIDASCREEN® Norovirus 3td Generation test improves as the number of patients tested during an outbreak increases, as well as when quality of the specimens increases. Preliminary identification of norovirus as the cause of an acute gastroenteritis outbreak by RIDASCREEN® Norovirus 3td Generation testing should be confirmed by reference methods as appropriate, particularly if only a limited number of positive samples are associated with a suspected outbreak. Additional testing of negative samples by other methods should be performed if norovirus is strongly suspected as the cause of an acute gastroenteritis outbreak.
Indication(s) for use: Identical to intended use
Product codes (comma separated list FDA assigned to the subject device)
OUC
Device Description
RIDASCREEN® Norovirus 3rd Generation test is a solid phase sandwich-type EIA for the detection of genogroups GI and GII noroviruses in stool samples. Microwell strips are coated with a mixture of GI and GII norovirus specific monoclonal antibodies. An aliquot of fecal suspension is added to the microwell together with biotinylated monoclonal norovirus antibodies. After washing, streptavidin peroxidase conjugate is added. Norovirus antigens that are present in the stool sample are captured in a sandwich complex of the immobilized antibodies, the norovirus antigens and the monoclonal antibodies conjugated with the biotin-streptavidin-peroxidase complex. Unbound streptavidin peroxidase conjugate is removed by washing and a chromogenic colorless substrate solution (hydrogen peroxide/TMB) is added. The substrate is hydrolyzed by any bound peroxidase, changing the chromogen to a blue color. Stopping the reaction with acid converts the blue to a yellow color indicating the presence of norovirus antigens.
Test results are read photometrically; intensity significantly above background levels is indicative of the presence of Norovirus antigen in the specimen or control. The RIDASCREEN® Norovirus 3rd Generation test does not identify specific norovirus strains.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
human feces
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Analytical performance:
- Precision/Reproducibility: Inter-assay, Intra-assay, and Inter-lot reproducibility were assessed using fecal samples.
- Inter-assay reproducibility: 6 fecal samples run in triplicates on 10 consecutive days by three different operators using 3 separate test kits. Results showed varying CVs across samples and kits (e.g., Sample 1, Kit 1 CV 11.66%; Sample 6, Kit 3 CV 20.86%).
- Intra-assay reproducibility: 40 replicates of six fecal samples run within one assay. CVs were generally lower than inter-assay (e.g., Sample 1, Kit 1 CV 2.54%; Sample 6, Kit 3 CV 5.11%).
- Detection limit: Determined using conventional RT-PCR, bi-directional sequencing, and electron microscopy (EM) for GI.1 and GII.4 isolates. The ELISA detected positive results at higher concentrations (1x10^0, 1x10^1, 1x10^2 dilutions) compared to RT-PCR which detected lower concentrations (1x10^3, 1x10^4, 1x10^5, 1x10^6 dilutions).
- Stability: Assessed for 3 lots over 12 months using positive and negative controls and 4 norovirus samples. Decrement in OD values for positive samples at 12 months was
§ 866.3395 Norovirus serological reagents.
(a)
Identification. Norovirus serological reagents are devices that consist of antigens and antisera used in serological tests to detect the presence of norovirus antigens in fecal samples. These devices aid in the diagnosis of norovirus infection in the setting of an individual patient with symptoms of acute gastroenteritis when the individual patient is epidemiologically linked to other patients with symptoms of acute gastroenteritis and/or aid in the identification of norovirus as the etiology of an outbreak of acute gastroenteritis in the setting of epidemiologically linked patients with symptoms of acute gastroenteritis.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9. The special control is FDA's guidance document entitled “Class II Special Controls Guidance Document: Norovirus Serological Reagents.” See § 866.1(e) for the availability of this guidance document.
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510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY
A. 510(k) Number:
B. Purpose for Submission:
Substantial equivalence determination for a new device
C. Measurand:
Norovirus, genogroup 1 and genogroup 2.
D. Type of Test:
Qualitative enzyme immunoassay
E. Applicant:
R-Biopharm AG An der neuen Bergstraße 17 64297 Darmstadt Germany
F. Proprietary and Established Names:
RIDASCREEN® Norovirus 3rd Generation EIA
G. Regulatory Information:
-
- Regulation section: 21 CFR 866.3395
-
- Classification: Class: II (de novo)
-
- Product code: OUC (Norovirus serological reagent)
-
- Panel: 83- Microbiology
H. Intended Use:
-
- Intended use(s):
The RIDASCREEN® Norovirus 3td Generation test is a qualitative enzyme immunoassay (EIA) intended for the detection of selected genogroup I (GI.1, GL.2, GI.3, GI.4, GL.7) and genogroup II (GII.1, GII.2, GII.3, GII.4, GII.5, GII.6, GII.7, GII.8, GII.10, GII.12, GII.13, GII.14, GII.17) norovirus strains in human feces as an aid in investigating the cause of acute gastroenteritis outbreaks. The likelihood of detecting a norovirus outbreak by use of the RIDASCREEN®
- Intended use(s):
1
Norovirus 3td Generation test improves as the number of patients tested during an outbreak increases, as well as when quality of the specimens increases. Preliminary identification of norovirus as the cause of an acute gastroenteritis outbreak by RIDASCREEN® Norovirus 3td Generation testing should be confirmed by reference methods as appropriate, particularly if only a limited number of positive samples are associated with a suspected outbreak. Additional testing of negative samples by other methods should be performed if norovirus is strongly suspected as the cause of an acute gastroenteritis outbreak.
-
- Indication(s) for use:
Identical to intended use
- Indication(s) for use:
-
- Special conditions for use statement(s): For prescription use
.
.
.
- Special conditions for use statement(s): For prescription use
-
- Special instrument requirements: None
I. Device Description:
RIDASCREEN® Norovirus 3rd Generation test is a solid phase sandwich-type EIA for the detection of genogroups GI and GII noroviruses in stool samples. Microwell strips are coated with a mixture of GI and GII norovirus specific monoclonal antibodies. An aliquot of fecal suspension is added to the microwell together with biotinylated monoclonal norovirus antibodies. After washing, streptavidin peroxidase conjugate is added. Norovirus antigens that are present in the stool sample are captured in a sandwich complex of the immobilized antibodies, the norovirus antigens and the monoclonal antibodies conjugated with the biotin-streptavidin-peroxidase complex. Unbound streptavidin peroxidase conjugate is removed by washing and a chromogenic colorless substrate solution (hydrogen peroxide/TMB) is added. The substrate is hydrolyzed by any bound peroxidase, changing the chromogen to a blue color. Stopping the reaction with acid converts the blue to a yellow color indicating the presence of norovirus antigens.
Test results are read photometrically; intensity significantly above background levels is indicative of the presence of Norovirus antigen in the specimen or control. The RIDASCREEN® Norovirus 3rd Generation test does not identify specific norovirus strains.
J. Substantial Equivalence Information:
-
- Predicate device name(s): None
-
- Predicate 510(k) numbers: None
-
- Comparison with predicate: Not applicable
2
K. Standard/Guidance Document Referenced (if applicable):
A special control guidance document will be promulgated.
L. Test Principle:
Enzyme immunoassay
M. Performance Characteristics:
1. Analytical performance:
- a. Precision/Reproducibility:
- i. Inter-assay reproducibility:
Inter-assay precision was studied with 6 fecal samples run in triplicates on 10 consecutive days by three different operators using 3 separate test kits.
| | | Sample 1
High
Positive | Sample 2
Medium
Positive | Sample 3
Medium
Positive | Sample 4
Low
Positive | Sample 5
Low
Positive | Sample 6
Negative |
|------------------------------------|----|------------------------------|--------------------------------|--------------------------------|-----------------------------|-----------------------------|----------------------|
| Min/max
Standard
[OD
450] | | 1.303/2.420 | 0.811/1.506 | 0.568/1.088 | 0.499/0.927 | 0.392/0.728 | 0.000/0.200 |
| Kit 1 | | 1.533 | 1.108 | 0.882 | 0.616 | 0.460 | 0.085 |
| | SD | 0.179 | 0.084 | 0.142 | 0.062 | 0.058 | 0.024 |
| | CV | 11.66% | 7.55% | 16.09% | 10.11% | 12.54% | 28.02% |
| Kit 2 | | 1.690 | 1.181 | 0.920 | 0.705 | 0.506 | 0.092 |
| | SD | 0.124 | 0.070 | 0.088 | 0.119 | 0.051 | 0.019 |
| | CV | 7.33% | 5.89% | 9.53% | 16.93% | 10.04% | 20.45% |
| Kit 3 | | 1.716 | 1.213 | 0.924 | 0.666 | 0.492 | 0.084 |
| | SD | 0.181 | 0.113 | 0.158 | 0.080 | 0.077 | 0.018 |
| | CV | 10.53% | 9.28% | 17.10% | 12.08% | 15.66% | 20.86% |
Inter-assay Reproducibility (Results reported are for Total Precision)
ii. Intra-assay reproducibility:
Intra-assay precision was determined by measuring 40 replicates of six fecal samples within one assay run. The accepted OD levels of the samples are listed below. Positive and negative controls were measured in triplicates each run, and three independent kit lots were tested. Mean values, standard deviations and coefficients of variance (CV) are summarized below.
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| | | Sample 1
High
Positive | Sample 2
Medium
Positive | Sample 3
Medium
Positive | Sample 4
Low
Positive | Sample 5
Low
Positive | Sample 6
Negative |
|------------------------------------|----|------------------------------|--------------------------------|--------------------------------|-----------------------------|-----------------------------|----------------------|
| Min/max
Standard
[OD
450] | | 1.172/
2.176 | 1.001/
1.859 | 0.737/
1.369 | 0.484/
0.900 | 0.284/
0.527 | 0.000/
0.200 |
| Kit 1 | | 1.653 | 1.205 | 1.014 | 0.563 | 0.309 | 0.051 |
| | SD | 0.042 | 0.114 | 0.034 | 0.021 | 0.016 | 0.002 |
| | CV | 2.54% | 9.48% | 3.39% | 3.80% | 5.16% | 4.35% |
| Kit 2 | | 1.643 | 1.198 | 1.012 | 0.561 | 0.308 | 0.051 |
| | SD | 0.041 | 0.114 | 0.035 | 0.021 | 0.016 | 0.002 |
| | CV | 2.50% | 9.50% | 3.42% | 3.72% | 5.14% | 4.41% |
| Kit 3 | | 1.481 | 0.953 | 1.006 | 0.559 | 0.307 | 0.051 |
| | SD | 0.101 | 0.066 | 0.035 | 0.021 | 0.016 | 0.003 |
| | CV | 6.81% | 6.92% | 3.43% | 3.78% | 5.19% | 5.11% |
Intra-assay Reproducibility (Results Reported are for Total Precision)
iii. Inter-lot reproducibility:
Inter-lot reproducibility was determined with three kits, each tested in triplicate over 10 days. As part of the inter-assay reproducibility study reported above. The following results are from the same data analyzed across kits:
Inter-lot Reproducibility (Results reported are for Total Precision)
| | Sample
1
High
Positive | Sample 2
Medium
Positive | Sample
3
Medium
Positive | Sample
4
Low
Positive | Sample
5
Low
Positive | Sample
6
Negative |
|-------------------------------------------|---------------------------------|--------------------------------|-----------------------------------|--------------------------------|--------------------------------|-------------------------|
| No. Days | 10 | 10 | 10 | 10 | 10 | 10 |
| No. Results | 90 | 90 | 90 | 90 | 90 | 90 |
| No. Kit
Lots | 3 | 3 | 3 | 3 | 3 | 3 |
| Total precision:
Mean value
[OD450] | 1.646 | 1.167 | 0.909 | 0.662 | 0.486 | 0.087 |
| SD | 0.185 | 0.103 | 0.133 | 0.098 | 0.065 | 0.020 |
| CV | 11.23% | 8.82% | 14.60% | 14.84% | 13.33% | 23.26% |
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-
b. Linearity/assay reportable range:
Not applicable -
c. Traceability, Stability, Expected values (controls, calibrators, or methods):
The sponsor conducted LoD validation of their Region B and region D conventional PCR assays using Norovirus positive samples of known viral concentrations. Serial dilution testing of G1.3b. G1.7, GII.3, and GII.4 containing stool samples using the sponsor's conventional Region B and Region D PCR assays estimated assay sensitivity at between 1 - 100 copies/ul for all strains, or approximately 250 - 3.500 mean copies/gm of stool. Additional strain reactivity studies examining Genogroup I: GI.2, GI.3b, GI.4, G1.6, G1.8, and Genogroup II: GII.1-4, GII.6, GII.7, GII.12, GII.14, GII.16, GII.17 samples found similar sensitivity using the Region D and region B assays, with the exception of GII.16 and GII.17, where sensitivity was approximately 1 - 2 logs less. Region B and region D conventional PCR sensitivities were similar (i.e., within 1 - 2 logs) for each strain tested with the exceptions of GII.14 and GII.17 which differed between the two assays by three logs: in both cases Region B conventional PCR was more sensitive than Region D testing. The sensitivity from combined use of the Region B and Region D assays was deemed acceptable for use as a reference standard for the clinical studies. -
d. Detection limit:
The limit of detection was determined by conventional RT-PCR followed by bi-directional sequencing for norovirus regions B and Region D, and for electron microscopy. One GI.1 and one GII.4 isolate were studied. Results were reported as follows:
| Genotype | Dilution | RIDASCREEN®
Norovirus 3rd
Generation ELISA | Conventional
RT-PCR | Real-time
RT-PCR | EM |
|----------|----------|--------------------------------------------------|------------------------|-------------------------|----------------------|
| | | Result | Result | Genomic
copies per g | Particles per
g** |
| | 1x100 * | positive | positive | 1.10E+08 | 2.9E+08 |
| | 1x101 | positive | positive | 5.78E+07 | 3.5E+07 |
| | 1x102 | positive | positive | 5.45E+06 | 2.4E+07 |
| GI.1 | 1x103 | negative | positive | 6.70E+05 | negative |
| | 1x104 | negative | positive | 1.24E+05 | n/a |
| | 1x105 | negative | positive | negative | n/a |
| | 1x106 | negative | positive | negative | n/a |
| GII.4 | 1x100 * | positive | positive | 1.91E+09 | 4.7E+08 |
| | 1x101 | positive | positive | 7.35E+08 | 5.9E+07 |
Limit of Detection
5
| $1x10^2$ | positive | positive | 2.89E+07 | 1.6E+07 |
|---|---|---|---|---|
| $1x10^3$ | negative | positive | 6.65E+05 | negative |
| $1x10^4$ | negative | positive | negative | n/a |
| $1x10^5$ | negative | positive | negative | n/a |
| $1x10^6$ | negative | negative | negative | n/a |
1x10º equals 20% dilution
** Genomic copies per gram and number of viral particles in the native fecal samples were calculated back from each positive dilution and the mean values are presented here
- Stability: e.
Stability was assessed by kit for 3 lots against a panel including positive and negative controls, and 4 samples with different norovirus OD readings. Analyte stability was tested after sample freeze/thawing, in suspension ('ready to use'), and transport (shipping of samples internationally). Overall, decrement in OD values for positive samples at 12 months was 10% above the cut-off and negative if > 10% below the cut-off. Values between these two limits are considered equivocal and the test repeated.
The following are the results for 100 negative stool isolates tested by the sponsor, sorted in ascending order: 98/100 were below 1 Of the two equivocal sample was Clinical Diagnostic Truth (+) and the other (-).
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ii. Sensitivity for specific Norovirus strains (strain reactivity)
As noted earlier, the RIDASCREEN® Norovirus 3rd Generation assay shows differential sensitivity across norovirus genotypes. The sponsor reports that 167 'PCR positive' specimens were analyzed for genogroup/subtype with the following results:
| Genogroup I | Genogroup II | ||||
|---|---|---|---|---|---|
| Subtype | No. of PCR positive samples | No. of samples detected by ELISA | Subtype | No. of PCR positive samples | No. of samples detected by ELISA |
| 2 | 2 | 1 | 1 | 1 | 1 |
| 3 | 10 | 2 | 3 | 3 | 3 |
| 3b | 2 | 0 | 4 | 123 | 96 |
| 4 | 8 | 6 | 7 | 1 | 1 |
| 5 | 1 | 0 | Unable to type | 5 | 4 |
| Unable to type | 11 | 0 |
Clinical Genotypes Detected
The performance was better in the archived, higher inoculum wellcharacterized specimens described earlier relative to clinical specimens; several strains were not detected in the archived panel, e.g., GI.1, GI7, GI.8, and GII.9, and limited detection of others, e.g., only 1/5 GII.6 samples were ELISA positive. However, strains other than GII.4 and GI.3 were relatively uncommon in the clinical study, and literature supports GII.4 as the predominant strain in the US. Performance in the clinical study generally parallels that seen for archived specimens.
- Other clinical supportive data (when a. and b. are not applicable): C.
Not applicable.
4. Clinical cut-off:
Not applicable.
5. Expected values/Reference range:
Noroviruses are a frequent cause of gastroenteritis outbreaks in semi-closed settings that involve children and/or adults such as day-care centers, nurseries. hospitals, nursing homes, prisons, and cruise ships, or other settings that may facilitate person-person spread. Noroviruses account for ~50% of all acute gastroenteritis outbreaks worldwide, although the proportion of outbreaks expected to be positive and the rate of positive test results within an outbreak depend on a number of factors, including (among others), the prevalence of
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norovirus within the population, the specific genotype(s) circulating, how rapidly specimens are taken, and the setting of the outbreak.
The expected value for RIDASCREEN® Norovirus 3rd Generation should be negative, although approximately 1/3 of infected patients may be asymptomatic. The design of the clinical study did not permit definitive analysis of the effects of age or gender on test performance, but exploratory analysis suggested that performance was similar across all age ranges and for both genders.
N. Proposed Labeling:
The labeling is sufficient and satisfies the requirements of 21 CFR Part 809.10.
O. Conclusion:
The petition for Evaluation of Automatic Class III Designation for this device is accepted. The device is classified as Class II under regulation 21 CFR 866.3395 with special controls. The special control guidance document "Class II Special Controls Guidance Document: Immunoassay or Antigen Detection-based In Vitro Diagnostic Devices for Norovirus Detection" will be available shortly.