(179 days)
Not Found
Not Found
No
The device description and performance studies detail a standard ELISA assay, which relies on chemical reactions and photometric measurement, not AI/ML algorithms for analysis or interpretation. There is no mention of AI, ML, or related concepts in the document.
No.
This device is an in vitro diagnostic test designed to detect adenovirus antigen in fecal samples, aiding in the diagnosis of acute non-bacterial gastroenteritis. It does not provide any therapeutic effect or treatment.
Yes
The "Intended Use / Indications for Use" section explicitly states that the device is "an aid in the diagnosis of acute non-bacterial gastro-enteritis," and it is for "in vitro diagnostic use only."
No
The device is an Enzyme-Linked Immunosorbent Assay (ELISA) test system, which is a laboratory-based assay involving physical reagents, incubation steps, and photometric measurement, indicating it is a hardware-based in vitro diagnostic device, 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 test system is "for the qualitative determination of Adenovirus antigen in human fecal samples as an aid in the diagnosis of acute non-bacterial gastro-enteritis." This clearly indicates that the device is intended to be used in vitro (outside the body) to examine a human specimen (fecal sample) to provide information for diagnostic purposes.
- "For in vitro diagnostic use only": The final sentence of the "Intended Use / Indications for Use" section explicitly states "For in vitro diagnostic use only." This is a definitive statement that the device is intended for IVD purposes.
- Device Description: The description details a laboratory test procedure (ELISA) performed on a human specimen (diluted fecal sample) to detect a specific analyte (Adenovirus antigen). This aligns with the nature of an in vitro diagnostic test.
N/A
Intended Use / Indications for Use
The Adenovirus Antigen Detection ELISA Test System is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of Adenovirus antigen in human fecal samples as an aid in the diagnosis of acute non-bacterial gastro-enteritis. Performance for this assay has not been established on children over the age of five and immunocompromised patients. The antibody utilized in this assay is a group specific antigen and cannot differentiate between types of adenovirus. Performance of this assay has not been established for specimens other than human feces. For in vitro diagnostic use only.
Product codes (comma separated list FDA assigned to the subject device)
GOD
Device Description
The Adenovirus Antigen Detection ELISA test is an enzyme linked immunosorbent assay to detect adenovirus antigen in fecal samples. Purified monoclonal antibody specific to adenovirus is attached to a solid phase microtiter well. Diluted fecal sample is added to each well. If the adenovirus antigen is present, it will bind to the monoclonal antibody in the well. After incubation the wells are washed to remove unbound antigen. An enzyme labeled anti-adenovirus polyclonal antibody is added to each well. If antigen is present the conjugate antibody will bind to the antigen attached to the antibody on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
human fecal samples
Indicated Patient Age Range
Performance for this assay has not been established on children over the age of five and immunocompromised patients.
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)
- Relative sensitivity and specificity.
Study 1: One hundred and twenty retrospective frozen fecal specimens sent to a University Virus Reference Laboratory in Ireland for routine testing were tested with the Trinity Adenovirus Antigen detection ELISA and by cell culture isolation. 90% of the specimens were from adults. The samples were approximately 50% solid, and 50% liquid.
Key results: Sensitivity = 75/75 = 100.0% (95% Confidence Interval = 96.0-100.0%*), Specificity = 41/43 = 95.4% (95% Confidence Interval = 88.9-100.0%), Agreement = 116/118 = 98.3% (95% confidence Interval = 95.9-100.0%). The 95% confidence intervals were calculated using the regular method. * The 95% confidence interval was calculated assuming one false negative. Note: The positive cultures were identified by cytopathic effect (CPE) and confirmed by electron microscopy (EM) using a standard negative staining technique, which is considered presumptive for adenovirus types 40 and 41 when using fecal samples.
Study 2: Four hundred eighty one sera were tested on the Adenovirus Antigen Detection ELISA and an alternate commercially available adenovirus EIA at a large public health lab in the UK. 57% of the samples were from patients less than 5 years old and 43 % were from patients greater than five years old. All were retrospective frozen fecal specimens with half being solid and half liquid. After retesting discrepants, the remaining descrepants were tested by EM.
Key results: Sensitivity = 141/160 = 88.13% (95% Confidence Interval = 83.01 - 93.24%), Specificity = 296/307 = 96.42% (95% Confidence Interval = 94.30 - 98.54%), Agreement = 437/467 = 93.58% (95% confidence Interval = 91.31 - 95.85%). The 95% confidence intervals were calculated using the normal method. After retesting discordant samples on the Wampole Adenovirus Antigen Detection ELISA, 15 samples remained discordant and were tested by Electron Microscopy (EM). Eight of the 15 discordants were false negatives and two were false positives versus EM. 'relative' refers to the comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.
-
Limit of Detection. Plaque assays were carried out in HEK-293 cells on fecal clinical samples containing Adenovirus 40 and Adenovirus 41.
Key results: The number of PFU/mL was established for each specificity with was found to be 125 PFU for Adenovirus 40 and 39 PFU for Adenovirus 41.
Limits of Detection: Adenovirus 40: 2 x 10^4 PFU/mL; Adenovirus 41: 2.5 x 10^3 PFU/mL. -
Precision. Six samples containing Type 2 adenovirus from cell culture and the positive and negative controls were each run in triplicate on three consecutive days at three different sites. A total of 216 determinations were made at the three sites.
Key results: In all 216 determinations there was not a case a positive result for a negative sample or a negative result for a positive sample. X = Mean O.D., SD = standard deviation, CV = coefficient of variation = SD/X x 100. The methods in NCCLS EP5 were utilized for precision parameters. -
Cross-Reactivity. Common intestinal pathogens and other organisms occasionally found in feces were tested. Specimens from the bacteria panel contained 3 x 10 particles per mL. The Chlamydia trachomatis L2 strain contained 1 x 10^6 inclusion forming units per mL. With the exception of Norwalk virus and Hepatitis A virus, all the viruses included in the panel were cell culture isolates which were passaged at least once. The titers of the viruses were unknown. The Norwalk virus was obtained from a vomitus sample shown to be positive by immune electron microscopy. The Hepatitis A sample was obtained from a hepatitis A specific immunoglobulin assay kit. The organisms were spiked with Type 2 adenovirus from cell culture harvests (titer unknown).
Key results: Tables of Optical Density (OD) values for various bacteria and viruses, both alone and when spiked with adenovirus, are provided, indicating low OD for organisms alone and higher OD when adenovirus is present, suggesting low cross-reactivity.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Sensitivity = 100.0% (95% Confidence Interval = 96.0-100.0%*)
Specificity = 95.4% (95% Confidence Interval = 88.9-100.0%)
Agreement = 98.3% (95% confidence Interval = 95.9-100.0%)
Sensitivity = 88.13% (95% Confidence Interval = 83.01 - 93.24%)
Specificity = 96.42% (95% Confidence Interval = 94.30 - 98.54%)
Agreement = 93.58% (95% confidence Interval = 91.31 - 95.85%)
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.
The Adenovirus Antigen Detection ELISA test is substantially equivalent to cell culture of adenovirus from fecal samples.
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
§ 866.3020 Adenovirus serological reagents.
(a)
Identification. Adenovirus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to adenovirus in serum. Additionally, some of these reagents consist of adenovirus antisera conjugated with a fluorescent dye and are used to identify adenoviruses directly from clinical specimens. The identification aids in the diagnosis of disease caused by adenoviruses and provides epidemiological information on these diseases. Adenovirus infections may cause pharyngitis (inflammation of the throat), acute respiratory diseases, and certain external diseases of the eye (e.g., conjunctivitis).(b)
Classification. Class I (general 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.
0
510(k) Summary Adenovirus Antigen Detection ELISA Test Kit
KA72406
DEC 2 4 1997
I. Trinity Biotech plc. Three Rocks Road Sandyford Industrial Estate Dublin 18, Ireland Contact person: Sinead Flynn Telephone: 011-353-1-295-5111 Date of preparation: June 23, 1997
II. Description of Device
The Adenovirus Antigen Detection ELISA Test System is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of Adenovirus antigen in human fecal samples as an aid in the diagnosis of acute non-bacterial gastro-enteritis. Performance for this assay has not been established on children over the age of five and immunocompromised patients. The antibody utilized in this assay is a group specific antigen and cannot differentiate between types of adenovirus. Performance of this assay has not been established for specimens other than human feces. For in vitro diagnostic use only.
The Adenovirus Antigen Detection ELISA test is an enzyme linked immunosorbent assay to detect adenovirus antigen in fecal samples. Purified monoclonal antibody specific to adenovirus is attached to a solid phase microtiter well. Diluted fecal sample is added to each well. If the adenovirus antigen is present, it will bind to the monoclonal antibody in the well. After incubation the wells are washed to remove unbound antigen. An enzyme labeled anti-adenovirus polyclonal antibody is added to each well. If antigen is present the conjugate antibody will bind to the antigen attached to the antibody on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
III. Predicate Device
The Adenovirus Antigen Detection ELISA test is substantially equivalent to cell culture of adenovirus from fecal samples. Equivalence is demonstrated by the following comparative results:
1
Performance Characteristics
- Relative sensitivity and specificity. One hundred and twenty retrospective frozen fecal specimens sent to a University Virus Reference Laboratory in Ireland for routine testing were tested with the Trinity Adenovirus Antigen detection ELISA and by cell culture isolation. 90% of the specimens were from adults. The samples were approximately 50% solid, and 50% liquid. The data in Table 1 illustrates good sensitivity and specificity of the Adenovirus Antigen Detection ELISA relative to cell culture isolation.
Table 1 Adenovirus Antigen Detection ELISA Sensitivity & Specificity Relative to Cell Culture Study 1
Wampole Adenovirus Antigen Detection ELISA
| + | E | - | Total | |
|---|---|---|---|---|
| Cell | ||||
| Culture | 75 | 2 | 0 | 77 |
| - | 2 | 0 | 41 | 43 |
| Total | 77 | 2 | 41 | 120 |
Equivocals are not included in the following calculations:
| Sensitivity = 75/75 = 100.0% | 95% Confidence Interval = 96.0-100.0%* |
|---|---|
| Specificity = 41/43 = 95.4% | 95% Confidence Interval = 88.9-100.0% |
| Agreement = 116/118 = 98.3% | 95% confidence Interval = 95.9-100.0% |
The 95% confidence intervals were calculated using the regular method. * The 95% confidence interval was calculated assuming one false negative.
Note: The positive cultures were identified by cytopathic effect (CPE) and confirmed by electron microscopy (EM) using a standard negative staining technique, which is considered presumptive for adenovirus types 40 and 41 when using fecal samples.
2
Four hundred eighty one sera were tested on the Adenovirus Antigen Detection ELISA and an alternate commercially available adenovirus EIA at a large public health lab in the UK. 57% of the samples were from patients less than 5 years old and 43 % were from patients greater than five years old. All were retrospective frozen fecal specimens with half being solid and half liquid. After retesting discrepants, the remaining descrepants were tested by EM. The data in Table 2 illustrates good sensitivity and specificity of the Adenovirus Antigen Detection ELISA relative to an alternate commercially available EIA.
Table 2 Adenovirus Antigen Detection ELISA Sensitivity & Specificity Relative to an Alternate adenovirus EIA Study 2
Wampole Adenovirus Antigen Detection ELISA
| + | E | - | Total | ||
|---|---|---|---|---|---|
| Alternate | |||||
| ELISA | + | 141 | 8 | 19 | 168 |
| - | 11 | 6 | 296 | 313 | |
| Total | 152 | 14 | 315 | 481 |
Equivocals are not included in the following calculations:
| Sensitivity = 141/160 = 88.13% | 95% Confidence Interval = 83.01 - 93.24% |
|---|---|
| Specificity = 296/307 = 96.42% | 95% Confidence Interval = 94.30 - 98.54% |
| Agreement = 437/467 = 93.58% | 95% confidence Interval = 91.31 - 95.85% |
The 95% confidence intervals were calculated using the normal method.
After retesting discordant samples on the Wampole Adenovirus Antigen Detection ELISA, 15 samples remained discordant and were tested by Electron Microscopy (EM). Eight of the 15 discordants were false negatives and two were false positives versus EM.
Please be advised that 'relative' refers to the comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.
3
- Limit of Detection. Plaque assays were carried out in HEK-293 cells on fecal clinical samples of 2. Limit of Detection. Plaque assays were carrict our in rial played online milliliter
containing Adenovirus 40 and Adenovirus 41. The number of plaqued and assaved on the containing Adenovirus 40 and Adenovitus +1. The names. Wy diluted and assayed on the (PFU/mL) was established for each specificit with was found to be 125 PFU for Adenovirus 40 and 39 PFU for Adenovirus 41.
| Limits of Detection: Enteric Adenoviruses | |||||
|---|---|---|---|---|---|
| Adenovirus 40: 2 X $10^4$ PFU/mL | Adenovirus 41: 2.5 X $10^3$ PFU/mL | ||||
| Dilution | OD | PFU/100ul | Dilution | OD | PFU/100ul |
| Neat | 0.521 | 2 X $10^3$ | Neat | 0.259 | 2.5 X $10^2$ |
| 1/8 | 0.385 | 0.25 X $10^3$ | 1/8 | 0.161 | 0.312 X $10^2$ |
| 1/16 | 0.201* | 0.125 X $10^3$ | 1/16 | 0.271 | 0.156 X $10^2$ |
| 1/32 | 0.165 | 0.062 X $10^3$ | 1/32 | 0.201 | 0.078 X $10^2$ |
| 1/64 | 0.063 | 0.031 X $10^3$ | 1/64 | 0.183* | 0.039 X $10^2$ |
| 1/128 | 0.061 | 0.015 X $10^3$ | 1/128 | 0.126 | 0.019 X $10^2$ |
| 1/256 | 0.053 | 0.007 X $10^3$ | 1/256 | 0.092 | 0.009 X $10^2$ |
| 1/512 | 0.121 | 0.003 X $10^3$ | 1/512 | 0.063 | 0.004 X $10^2$ |
| 1/1024 | 0.041 | 0.001 X $10^3$ | 1/1024 | 0.065 | 0.002 X $10^2$ |
| 1/2048 | - | 1/2048 | 0.052 | 0.001 X $10^2$ |
*Limit of Detection
4
- Precision. Six samples containing Type 2 adenovirus from cell culture and the positive and negative controls were each run in triplicate on three consecutive days at three different sites. The results are shown below in Table 3.
Table 3
| Adenovirus Antigen Detection ELISA Inter Assay Precision Between Sites | ||||
|---|---|---|---|---|
| Inter-Assay (n=27) | ||||
| # | X | SD | CV | n |
| 1. | 1.558 | 0.091 | 5.87% | 27 |
| 2. | 1.275 | 0.051 | 4.01% | 27 |
| 3. | 0.501 | 0.018 | 3.65% | 27 |
| 4. | 0.435 | 0.016 | 3.78% | 27 |
| 5. | 0.295 | 0.012 | 4.12% | 27 |
| 6. | 0.054 | 0.005 | 9.22% | 27 |
| PC | 1.211 | 0.051 | 4.23% | 27 |
| NC | 0.050 | 0.003 | 6.11% | 27 |
A total of 216 determinations were made at the three sites. In all 216 determinations there was not a case a positive result for a negative sample or a negative result for a positive sample.
X = Mean O.D. SD = standard deviation CV = coefficient of variation = SD/X x 100
The methods in NCCLS EP5 were utilized for precision parameters.
12
5
4. Cross-Reactivity.
The following common intestinal pathogens and other organisms occasionally found in feces were The tonewing common antigen detection kit. Specimens from the bacteria panel contained 3 X 10 particles per mL. The Chlamydia trachomatis L2 strain contained 1 X 106 inclusion forming units per ml. With the exception of Norwalk virus and Hepatitis A virus, all the viruses included in the panel were cell culture isolates which were passaged at least once. The titers of the viruses were unknown. The Norwalk virus was obtained from a vomitus sample shown to be positive by immune electron microscopy. The Hepatitis A sample was obtained from a hepatitis A specific immunoglobulin assay kit. The organisms were spiked with Type 2 adenovirus from cell culture harvests (titer unknown).
Bacteria Panel
| Bacteria Panel | ||
|---|---|---|
| Organism alone | Organism and Adenovirus | |
| Haemophilus influenza | 0.025 | 0.605 |
| Actinobacter spp. | 0.022 | 0.595 |
| Bacillus spp. | 0.017 | 0.554 |
| Shigella sunnei | 0.021 | 0.489 |
| Neisseria meningitiidis | 0.032 | 0.582 |
| Pseudomonas aeruginosa | 0.043 | 0.519 |
| Candida albicans | 0.022 | 0.441 |
| Campylobacter spp. | 0.029 | 0.489 |
| Clostridium welchii | 0.041 | 0.475 |
| Escherichia coli | 0.023 | 0.534 |
| Aeromonas spp. | 0.022 | 0.548 |
| Salmonella spp. | 0.037 | 0.526 |
| Gardinella spp. | 0.031 | 0.628 |
| Klebsiella pneumoniae | 0.026 | 0.497 |
| Staphylococcus aureus (Cowan) | 0.028 | 0.483 |
| Streptococcus pneumoniae | 0.035 | 0.440 |
| Streptococcus group G | 0.029 | 0.486 |
| Streptococcus group F | 0.034 | 0.573 |
| Streptococcus group A | 0.035 | 0.495 |
| Chlamydia trachomatis L2 strain | 0.026 | 0.562 |
6
:
:
Viral Panel
| Varicella Zoster virus | 0.022 | 0.655 |
|---|---|---|
| Herpes Simplex type 1 | 0.026 | 0.770 |
| Herpes Simplex type 2 | 0.027 | 0.653 |
| Cytomegalovirus | 0.018 | 0.762 |
| Epstein-Barr virus | 0.038 | 0.837 |
| Rhinovirus | 0.021 | 0.827 |
| Poliovirus 1 | 0.022 | 0.655 |
| Poliovirus 2 | 0.025 | 0.689 |
| Poliovirus 3 | 0.035 | 0.741 |
| Coxsackievirus B5 | 0.032 | 0.602 |
| Coxsackievirus B4 | 0.028 | 0.676 |
| Echovirus 7 | 0.042 | 0.592 |
| Echovirus 20 | 0.035 | 0.681 |
| RS virus | 0.023 | 0.786 |
| Parainfluenza virus 1 | 0.029 | 0.666 |
| Parainfluenza virus 2 | 0.023 | 0.833 |
| Parainfluenza virus 3 | 0.032 | 0.846 |
| Influenza A virus | 0.026 | 0.553 |
| Influenza B virus | 0.022 | 0.694 |
| Hepatitis A virus | 0.033 | 0.764 |
| Rotavirus | 0.022 | 0.712 |
| Norwalk virus | 0.031 | 0.654 |
7
Image /page/7/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 2 2 1997
William L. Boteler, Jr. President Immuno Probe, Inc. 1306F Bailes Lane Frederick, Maryland 21701
Re: K972406
Trade Name: Adenovirus Antigen Detection ELISA Test System Regulatory Class: I Product Code: GOD Dated: October 3, 1997 Received: October 6, 1997
Dear Mr. Boteler:
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 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.
8
Page 2
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 Autman
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
9
510(k) Summary Adenovirus Antigen Detection ELISA Test Kit
KA72406
DEC 2 4 1997
I. Trinity Biotech plc. Three Rocks Road Sandyford Industrial Estate Dublin 18, Ireland Contact person: Sinead Flynn Telephone: 011-353-1-295-5111 Date of preparation: June 23, 1997
II. Description of Device
The Adenovirus Antigen Detection ELISA Test System is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of Adenovirus antigen in human fecal samples as an aid in the diagnosis of acute non-bacterial gastro-enteritis. Performance for this assay has not been established on children over the age of five and immunocompromised patients. The antibody utilized in this assay is a group specific antigen and cannot differentiate between types of adenovirus. Performance of this assay has not been established for specimens other than human feces. For in vitro diagnostic use only.
The Adenovirus Antigen Detection ELISA test is an enzyme linked immunosorbent assay to detect adenovirus antigen in fecal samples. Purified monoclonal antibody specific to adenovirus is attached to a solid phase microtiter well. Diluted fecal sample is added to each well. If the adenovirus antigen is present, it will bind to the monoclonal antibody in the well. After incubation the wells are washed to remove unbound antigen. An enzyme labeled anti-adenovirus polyclonal antibody is added to each well. If antigen is present the conjugate antibody will bind to the antigen attached to the antibody on the well. After incubation the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present the substrate will undergo a color change. After an incubation period the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.
III. Predicate Device
The Adenovirus Antigen Detection ELISA test is substantially equivalent to cell culture of adenovirus from fecal samples. Equivalence is demonstrated by the following comparative results:
10
Performance Characteristics
- Relative sensitivity and specificity. One hundred and twenty retrospective frozen fecal specimens sent to a University Virus Reference Laboratory in Ireland for routine testing were tested with the Trinity Adenovirus Antigen detection ELISA and by cell culture isolation. 90% of the specimens were from adults. The samples were approximately 50% solid, and 50% liquid. The data in Table 1 illustrates good sensitivity and specificity of the Adenovirus Antigen Detection ELISA relative to cell culture isolation.
Table 1 Adenovirus Antigen Detection ELISA Sensitivity & Specificity Relative to Cell Culture Study 1
Wampole Adenovirus Antigen Detection ELISA
| + | E | - | Total | |
|---|---|---|---|---|
| Cell | ||||
| Culture | 75 | 2 | 0 | 77 |
| - | 2 | 0 | 41 | 43 |
| Total | 77 | 2 | 41 | 120 |
Equivocals are not included in the following calculations:
| Sensitivity = 75/75 = 100.0% | 95% Confidence Interval = 96.0-100.0%* |
|---|---|
| Specificity = 41/43 = 95.4% | 95% Confidence Interval = 88.9-100.0% |
| Agreement = 116/118 = 98.3% | 95% confidence Interval = 95.9-100.0% |
The 95% confidence intervals were calculated using the regular method. * The 95% confidence interval was calculated assuming one false negative.
Note: The positive cultures were identified by cytopathic effect (CPE) and confirmed by electron microscopy (EM) using a standard negative staining technique, which is considered presumptive for adenovirus types 40 and 41 when using fecal samples.
11
Four hundred eighty one sera were tested on the Adenovirus Antigen Detection ELISA and an alternate commercially available adenovirus EIA at a large public health lab in the UK. 57% of the samples were from patients less than 5 years old and 43 % were from patients greater than five years old. All were retrospective frozen fecal specimens with half being solid and half liquid. After retesting discrepants, the remaining descrepants were tested by EM. The data in Table 2 illustrates good sensitivity and specificity of the Adenovirus Antigen Detection ELISA relative to an alternate commercially available EIA.
Table 2 Adenovirus Antigen Detection ELISA Sensitivity & Specificity Relative to an Alternate adenovirus EIA Study 2
Wampole Adenovirus Antigen Detection ELISA
| + | E | - | Total | ||
|---|---|---|---|---|---|
| Alternate | |||||
| ELISA | + | 141 | 8 | 19 | 168 |
| - | 11 | 6 | 296 | 313 | |
| Total | 152 | 14 | 315 | 481 |
Equivocals are not included in the following calculations:
| Sensitivity = 141/160 = 88.13% | 95% Confidence Interval = 83.01 - 93.24% |
|---|---|
| Specificity = 296/307 = 96.42% | 95% Confidence Interval = 94.30 - 98.54% |
| Agreement = 437/467 = 93.58% | 95% confidence Interval = 91.31 - 95.85% |
The 95% confidence intervals were calculated using the normal method.
After retesting discordant samples on the Wampole Adenovirus Antigen Detection ELISA, 15 samples remained discordant and were tested by Electron Microscopy (EM). Eight of the 15 discordants were false negatives and two were false positives versus EM.
Please be advised that 'relative' refers to the comparison of this assay's results to that of a similar assay. There was not an attempt to correlate the assay's results with disease presence or absence. No judgment can be made on the comparison assay's accuracy to predict disease.
12
- Limit of Detection. Plaque assays were carried out in HEK-293 cells on fecal clinical samples of 2. Limit of Detection. Plaque assays were carrict our in rial played online milliliter
containing Adenovirus 40 and Adenovirus 41. The number of plaqued and assaved on the containing Adenovirus 40 and Adenovitus +1. The names. Wy diluted and assayed on the (PFU/mL) was established for each specificit with was found to be 125 PFU for Adenovirus 40 and 39 PFU for Adenovirus 41.
| Limits of Detection: Enteric Adenoviruses | |||||
|---|---|---|---|---|---|
| Adenovirus 40: 2 X $10^4$ PFU/mL | Adenovirus 41: 2.5 X $10^3$ PFU/mL | ||||
| Dilution | OD | PFU/100ul | Dilution | OD | PFU/100ul |
| Neat | 0.521 | 2 X $10^3$ | Neat | 0.259 | 2.5 X $10^2$ |
| 1/8 | 0.385 | 0.25 X $10^3$ | 1/8 | 0.161 | 0.312 X $10^2$ |
| 1/16 | 0.201* | 0.125 X $10^3$ | 1/16 | 0.271 | 0.156 X $10^2$ |
| 1/32 | 0.165 | 0.062 X $10^3$ | 1/32 | 0.201 | 0.078 X $10^2$ |
| 1/64 | 0.063 | 0.031 X $10^3$ | 1/64 | 0.183* | 0.039 X $10^2$ |
| 1/128 | 0.061 | 0.015 X $10^3$ | 1/128 | 0.126 | 0.019 X $10^2$ |
| 1/256 | 0.053 | 0.007 X $10^3$ | 1/256 | 0.092 | 0.009 X $10^2$ |
| 1/512 | 0.121 | 0.003 X $10^3$ | 1/512 | 0.063 | 0.004 X $10^2$ |
| 1/1024 | 0.041 | 0.001 X $10^3$ | 1/1024 | 0.065 | 0.002 X $10^2$ |
| 1/2048 | - | 1/2048 | 0.052 | 0.001 X $10^2$ |
*Limit of Detection
13
- Precision. Six samples containing Type 2 adenovirus from cell culture and the positive and negative controls were each run in triplicate on three consecutive days at three different sites. The results are shown below in Table 3.
Table 3
| Adenovirus Antigen Detection ELISA Inter Assay Precision Between Sites | ||||
|---|---|---|---|---|
| Inter-Assay (n=27) | ||||
| # | X | SD | CV | n |
| 1. | 1.558 | 0.091 | 5.87% | 27 |
| 2. | 1.275 | 0.051 | 4.01% | 27 |
| 3. | 0.501 | 0.018 | 3.65% | 27 |
| 4. | 0.435 | 0.016 | 3.78% | 27 |
| 5. | 0.295 | 0.012 | 4.12% | 27 |
| 6. | 0.054 | 0.005 | 9.22% | 27 |
| PC | 1.211 | 0.051 | 4.23% | 27 |
| NC | 0.050 | 0.003 | 6.11% | 27 |
A total of 216 determinations were made at the three sites. In all 216 determinations there was not a case a positive result for a negative sample or a negative result for a positive sample.
X = Mean O.D. SD = standard deviation CV = coefficient of variation = SD/X x 100
The methods in NCCLS EP5 were utilized for precision parameters.
12
14
4. Cross-Reactivity.
The following common intestinal pathogens and other organisms occasionally found in feces were The tonewing common antigen detection kit. Specimens from the bacteria panel contained 3 X 10 particles per mL. The Chlamydia trachomatis L2 strain contained 1 X 106 inclusion forming units per ml. With the exception of Norwalk virus and Hepatitis A virus, all the viruses included in the panel were cell culture isolates which were passaged at least once. The titers of the viruses were unknown. The Norwalk virus was obtained from a vomitus sample shown to be positive by immune electron microscopy. The Hepatitis A sample was obtained from a hepatitis A specific immunoglobulin assay kit. The organisms were spiked with Type 2 adenovirus from cell culture harvests (titer unknown).
Bacteria Panel
| Bacteria Panel | ||
|---|---|---|
| Organism alone | Organism and Adenovirus | |
| Haemophilus influenza | 0.025 | 0.605 |
| Actinobacter spp. | 0.022 | 0.595 |
| Bacillus spp. | 0.017 | 0.554 |
| Shigella sunnei | 0.021 | 0.489 |
| Neisseria meningitiidis | 0.032 | 0.582 |
| Pseudomonas aeruginosa | 0.043 | 0.519 |
| Candida albicans | 0.022 | 0.441 |
| Campylobacter spp. | 0.029 | 0.489 |
| Clostridium welchii | 0.041 | 0.475 |
| Escherichia coli | 0.023 | 0.534 |
| Aeromonas spp. | 0.022 | 0.548 |
| Salmonella spp. | 0.037 | 0.526 |
| Gardinella spp. | 0.031 | 0.628 |
| Klebsiella pneumoniae | 0.026 | 0.497 |
| Staphylococcus aureus (Cowan) | 0.028 | 0.483 |
| Streptococcus pneumoniae | 0.035 | 0.440 |
| Streptococcus group G | 0.029 | 0.486 |
| Streptococcus group F | 0.034 | 0.573 |
| Streptococcus group A | 0.035 | 0.495 |
| Chlamydia trachomatis L2 strain | 0.026 | 0.562 |
15
:
:
Viral Panel
| Varicella Zoster virus | 0.022 | 0.655 |
|---|---|---|
| Herpes Simplex type 1 | 0.026 | 0.770 |
| Herpes Simplex type 2 | 0.027 | 0.653 |
| Cytomegalovirus | 0.018 | 0.762 |
| Epstein-Barr virus | 0.038 | 0.837 |
| Rhinovirus | 0.021 | 0.827 |
| Poliovirus 1 | 0.022 | 0.655 |
| Poliovirus 2 | 0.025 | 0.689 |
| Poliovirus 3 | 0.035 | 0.741 |
| Coxsackievirus B5 | 0.032 | 0.602 |
| Coxsackievirus B4 | 0.028 | 0.676 |
| Echovirus 7 | 0.042 | 0.592 |
| Echovirus 20 | 0.035 | 0.681 |
| RS virus | 0.023 | 0.786 |
| Parainfluenza virus 1 | 0.029 | 0.666 |
| Parainfluenza virus 2 | 0.023 | 0.833 |
| Parainfluenza virus 3 | 0.032 | 0.846 |
| Influenza A virus | 0.026 | 0.553 |
| Influenza B virus | 0.022 | 0.694 |
| Hepatitis A virus | 0.033 | 0.764 |
| Rotavirus | 0.022 | 0.712 |
| Norwalk virus | 0.031 | 0.654 |
16
Image /page/16/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" arranged around the perimeter. Inside the circle is a stylized image of an eagle with its wings spread, symbolizing the department's mission to protect the health of all Americans.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
DEC 2 2 1997
William L. Boteler, Jr. President Immuno Probe, Inc. 1306F Bailes Lane Frederick, Maryland 21701
Re: K972406
Trade Name: Adenovirus Antigen Detection ELISA Test System Regulatory Class: I Product Code: GOD Dated: October 3, 1997 Received: October 6, 1997
Dear Mr. Boteler:
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 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.
17
Page 2
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 Autman
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
18
Page 1 of 1
510(k) Number: K972406
Device Name: Adenovirus Antigen Detection ELISA
Indications For Use: The Adenovirus Antigen Detection ELISA Test System is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of Adenovirus antigen in human fecal samples as an aid in the diagnosis of acute nonbacterial gastro-enteritis. Performance for this assay has not been established on children over the age of five and immunocompromised patients. The antibody utilized in this assay is a group specific antigen and cannot differentiate between types of adenovirus. Performance of this assay has not been established for specimens other than human feces.
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Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
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OR
Over-The Counter Use (Optional Format 1-2-96)
Sally 1. Selipuk
An J. Teccehied
(Division Sign-Off) Division of Clinical Laboratory Devices
510(k) Number _