(83 days)
Not Found
No
The device description details a lateral flow immunochromatographic assay that relies on visual interpretation of lines. There is no mention of any computational analysis, image processing, or algorithms that would suggest the use of AI/ML.
No
The device is an in vitro diagnostic (IVD) device used for the qualitative detection of H. pylori antigen in human stool samples to aid in diagnosis, not to treat or cure a disease.
Yes
The device qualitatively detects H. pylori antigen in human stool specimens, and the text explicitly states that test results "are intended to aid in the initial diagnosis and treatment of H. pylori infection." It also refers to the device as an "in vitro diagnostic device."
No
The device is a lateral flow immunochromatographic assay, which is a physical test kit containing antibodies, reagents, and a test strip. It is an in vitro diagnostic device that relies on a chemical reaction and visual interpretation of lines on a physical strip, not software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use explicitly states it's for the "qualitative detection of H. pylori antigen in unpreserved human stool specimens" and that the "Test results are intended to aid in the initial diagnosis and treatment of H. pylori infection." This clearly indicates it's used to test a sample taken from the human body to provide information for diagnosis.
- Device Description: The description refers to it as an "in vitro diagnostic device" and states it's used for "qualitative detection of H. pylori antigen in human stool samples."
- Sample Type: It uses "human stool specimens," which are biological samples taken from the body.
- Purpose: The purpose is to detect a specific analyte (H. pylori antigen) in the sample to aid in the diagnosis of a medical condition (H. pylori infection).
All of these points align with the definition of an In Vitro Diagnostic device.
N/A
Intended Use / Indications for Use
Vstrip® H.pylori Antigen Rapid Test is a single use immunochromatographic assay for the qualitative detection of H. pylori antigen in unpreserved human stool specimens. Test results are intended to aid in the initial diagnosis and treatment of H. pylori infection. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.
Product codes (comma separated list FDA assigned to the subject device)
LYR
Device Description
The Vstrip® H.pylori Antigen Rapid Test (Vstrip®) is a Helicobacter pylori (H. pylori) antigen rapid test. It is a lateral flow immunochromatographic assay which employs antibody-coated latex beads to detect H. pylori antigens in stool specimens from patients suspected of H. pylori infection. This test is an in vitro diagnostic device to be used for the qualitative detection of H. pylori antigen in human stool samples, and test results are intended to aid in the diagnosis and treatment of H. pylori infection. This test utilizes a pair of H. pylori-specific monoclonal antibodies that are capable of detecting H.pylori antigens in human stool. The assay kit includes a foil pouch containing test cassette which houses a strip incorporated with a pair of H. pylori-specific monoclonal antibodies, sample preparation tubes that contain sample diluent buffer for dilution of stool sampler tool attached to the underside of the tube cap and a dispenser tool attached to the top of the tube, positive control reagent containing inactivated H.pylori, and the package insert and instructions. Each diagnostic strip is enclosed in a plastic frame with a window to display the results. To perform the test, a diluted stool sample which is first prepared by a sample preparation tube is added to the Test Cassette. If the sample contains H.pylori antigen, a pink-red test to the letter T) along with a blue control line (next to the letter C) will be visible in the rectangle "Result Window", as depicted in Figure 1. A blue control line is a line to show that adequate flow of the sample has occurred and active components have been employed during a test run. The presence of the blue line at the control position on the device confirms that the device is working properly. If H. pylori antigen is absent or below the level of detection, no pink-red line will appear in the rectangle "Result Window" of the cassette next to the letter T, but a distinct blue line shows next to the letter C, as depicted in Figure 1. For invalid result, no visible blue line in the rectangle "Result Window" of the cassette next to the letter C, with or without a visually detectable pink-red line, as depicted in Figure 1. It may occur with the deteriorated materials, but an excess of stool sample and incorrect procedure is mostly the main reason for control line failure. When an invalid result appears, review the test procedure and re- test same specimen. If the test fails again, repeat the test with different specimens. If the problem persists, the use of concerned test kit lot should be discontinued.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Stool specimens
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Prescription Use (Part 21 CFR 801 Subpart D)
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)
Comparison Study:
A multi-center study including sites from USA and Taiwan was conducted to evaluate the performance of the study test device (Vstrip® H.pylori Antigen Rapid Test) for detecting H. pylori stool antigen (HpSA) in human stool from patients suspected of H. pylori infection. Test results were compared to results from an FDA cleared H. pylori stool antigen ELISA that was previously evaluated relative to the endoscopy biopsy composite reference method (i.e., culture, histology, and RUT) for initial H. pylori diagnosis with a demonstrated sensitivity and specificity greater than or equal to 95% and a lower bound of the two-sided 95% confidence interval (CI) greater than 89%.
A total of 333 fresh fecal specimens from the intended use population (150 fresh fecal samples collected in the USA and 183 fresh fecal samples collected in Taiwan) along with test device and comparator kits were provided by the Sponsor to the selected study laboratories. Trained laboratory operators were recruited for this study and were blinded to the samples designations.
Positive, negative and overall percent agreement were determined between Vstrip® H.pylori Antigen Rapid Test and the comparator ELISA in detecting the H. pylori antigen in human stool. No invalid results were observed for the investigational test or the comparator ELISA.
Key results: The Vstrip H.pylori Antigen Rapid Test demonstrated a positive percent of 96.67% [58/60; 95% CI 88.64% - 99.08%] and a negative percent agreement of 98.17% [268/273; 95% CI 95.79% -99.22%] with the comparator ELISA. The study acceptance criteria were met.
Reproducibility Study:
A study was conducted to evaluate the reproducibility of Vstrip® H.pylori Antigen Rapid Test results in detecting H.pylori antigen in human stool, as performed by different operators in multiple laboratories.
Five (5) panels of 12 frozen fecal samples each with random distributions of medium positive (4xLOD), low positive (1-2xLOD, near C95 concentration), high negative (near C5 concentration) and negative samples) were analyzed using the Vstrip® H.pylori Antigen Rapid Test by each operator at each site over five (5) days (one (1) panel per day per operator).
Key results: Across all sites and operators, agreement with the expected result was 97.8% (88/90) for the moderate positive panel member, 97.8% (88/90) for the low positive panel member, 98.9% (89/90) for the high negative panel member, and 100% (90/90) for the true negative panel member. The reproducibility study analyses demonstrated that results of the Vstrip® H.pylori Antigen Rapid Test are reproducible by different operators in multiple locations.
Analytical Sensitivity:
A study was done to establish the limit of detection (LOD) for the Vstrip® H.pylori Antigen Rapid test. The LOD testing was conducted in a stool matrix background comprised from three negative stool samples spiked with serial dilutions of two strains of cultured H. pylori (ATCC 43504 and ATCC 51653). Each dilution was tested with the Vstrip® H.pylori Antigen Rapid test 10 times each by four operators (a total of 40 replicates). The LOD value for Vstrip® H.pylori Antigen Rapid Test was defined as the concentration producing a positive result at least 95% of the time.
Key results: The LOD value for Vstrip® H.pylori Antigen Rapid Test based on 95% positive results was 8.5X10 CFU/mL for H.pylori strain ATCC 43504 and 1.9 X10 CFU/mL for H.pvlori strain ATCC 51653.
Inclusivity:
Key results: An additional three H. pylori strains produced a positive result at least 95% of the time with the Vstrip H.pylori Antigen Rapid Test when tested at the following concentrations: ATCC700392 (3.8 x 10 CFU/mL), ATCC 51110 (1.9 x 105 CFU/mL), and BCRC 17132 (3.8 x 106 CFU/mL).
Analytical Specificity:
A study was done to determine analytical specificity (cross reactivity) of the Vstrip® H.pylori Antigen Rapid Test with panels of viruses and bacteria. The test was performed on positive and negative samples containing high levels of non-target microorganisms (bacteria spiked at ≥1x10' CFU/mL, viruses spiked at ≥1x10 TCID50/mL). Testing included thirty seven (37) bacteria and seven (7) virus types. Various strains of viruses and bacteria panels were diluted and tested with the Vstrip® H.pylori Antigen Rapid Test to detect any potential cross-reactivity. Results were recorded at 10 minutes interval. Each condition was run in triplicate.
Key results: None of the microorganisms tested produced false positive or false negative results.
Interfering Substances:
A study was conducted to determine if various over-the-counter medications or endogenous substances could interfere with the assay results. Fifteen potentially interfering substances were spiked in both positive and negative samples tested in triplicate with the Vstrip® H.pylori Antigen Rapid Test.
Key results: None of substances with the indicated concentrations interfered with the performance of Vstrip® H.pylori Antigen Rapid Test.
Sample Stability:
Studies were conducted to examine the stability of stool samples when stored refrigerated at 2-8° C or frozen at -20° C.
Key results: The study results supported the recommendations that stool samples can be stored up to seven days refrigerated at 2-8° C, up to 20 days frozen at -20° C, and that samples can undergo up to three freeze/thaw cycles.
Dose-Hook Effect Study:
A dose hook effect (prozone) study was carried out to examine whether high concentrations of H. pylori antigen negatively affects the performance of the Vstrip®. The hook effect or the prozone effect is a type of interference which produces false negatives or inaccurately low results in the presence of high analyte concentrations. Five H pylori strains were tested in triplicate at 10° 10′ CFU/mL (10 - 100X LoD) concentration range with the Vstrip® H.pylori Antigen Rapid Test.
Key results: No dose hook effect was observed at the tested concentrations.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Positive percent agreement: 96.67% [58/60; 95% CI 88.64% - 99.08%]
Negative percent agreement: 98.17% [268/273; 95% CI 95.79% -99.22%]
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.
ImmunoCard STAT!® HpSA® [K032222]
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
§ 866.3110
Campylobacter fetus serological reagents.(a)
Identification. Campylobacter fetus serological reagents are devices that consist of antisera conjugated with a fluorescent dye used to identifyCampylobacter fetus from clinical specimens or cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by this bacterium and provides epidemiological information on these diseases.Campylobacter fetus is a frequent cause of abortion in sheep and cattle and is sometimes responsible for endocarditis (inflammation of certain membranes of the heart) and enteritis (inflammation of the intestines) in humans.(b)
Classification. Class I (general controls).
0
Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo in blue. Underneath the FDA logo is the word "ADMINISTRATION".
March 14, 2019
Panion & BF Biotech Inc. % Kazem Kazempour CEO & President Amarex Clinical Research, LLC 20201 Century Blvd. Fourth Floor Germantown, Maryland 20874
Re: K183573
Trade/Device Name: Vstrip H. pylori Antigen Rapid Test Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: Class I Product Code: LYR Dated: December 19, 2018 Received: December 21, 2018
Dear Kazem Kazempour:
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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. 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 CFR Part 807); labeling (21 CFR Part
1
801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Steven R. Gitterman -S for
Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known)
Device Name
Vstrip® H.pylori Antigen Rapid Test
Indications for Use (Describe)
Vstrip® H.pylori Antigen Rapid Test is a single use immunochromatographic assay for the qualitative detection of H. pylori antigen in unpreserved human stool specimens. Test results are intended to aid in the initial diagnosis and treatment of H. pylori infection. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.
| Type of Use (Select one or both, as applicable) | |
|---|---|
| X Prescription Use (Part 21 CFR 801 Subpart D) | |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
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3
Table of Contents
| 1. | Date of Preparation: March 13, 2019 | 2 |
|---|---|---|
| 2. | Owner Information | 2 |
| 3. | Device | 2 |
| 4. | Device Description | 2 |
| 5. | Principle of the Test and Assay Procedures | 3 |
| 6. | Rationale of Antibody Selection and Information of Selective H pylori Strains | 4 |
| 7. | Intended Use | 4 |
| 8. | Indications of Use | 4 |
| 9. | Comparison of Vstrip® H.pylori Antigen Rapid Test with the Predicate Device | 4 |
| 10. | Performance Data | 6 |
| 11. | Conclusions | 7 |
4
510(K) SUMMARY
Date of Preparation: March 13, 2019 1.
2. Owner Information
This Premarket Notification is submitted by:
Panion & BF Biotech Inc. 1F, No.308-8, Sec. 1 Datong Rd., Xizhi Dist. New Taipei City 22146, Taiwan
Contact Information:
Kazem Kazempour, CEO Amarex Clinical Research, LLC 20201 Century Blvd, Fourth Floor Germantown, MD 20874 Phone: 240-688-0800 Fax: 301-528-2300 Email: kazemk@amarexcro.com
3. Device
| Name of Device: | Vstrip® H. pylori Antigen Rapid Test |
|---|---|
| Common Name: | Helicobacter pylori antigen assay |
| Classification Name: | Campylobacter fetus serological reagents (21 CFR 866.3110) |
| Regulatory Class: | Class I |
| Product Code: | LYR |
| Predicate Device: | ImmunoCard STAT!® HpSA® [K032222] |
Device Description 4.
The Vstrip® H.pylori Antigen Rapid Test (Vstrip®) is a Helicobacter pylori (H. pylori) antigen rapid test. It is a lateral flow immunochromatographic assay which employs antibody-coated latex beads to detect H. pylori antigens in stool specimens from patients suspected of H. pylori infection. This test is an in vitro diagnostic device to be used for the qualitative detection of H. pylori antigen in human
5
stool samples, and test results are intended to aid in the diagnosis and treatment of H. pylori infection. This test utilizes a pair of H. pylori-specific monoclonal antibodies that are capable of detecting H.pylori antigens in human stool. The assay kit includes a foil pouch containing test cassette which houses a strip incorporated with a pair of H. pylori-specific monoclonal antibodies, sample preparation tubes that contain sample diluent buffer for dilution of stool sampler tool attached to the underside of the tube cap and a dispenser tool attached to the top of the tube, positive control reagent containing inactivated H.pylori, and the package insert and instructions. Each diagnostic strip is enclosed in a plastic frame with a window to display the results. To perform the test, a diluted stool sample which is first prepared by a sample preparation tube is added to the Test Cassette. If the sample contains H.pylori antigen, a pink-red test to the letter T) along with a blue control line (next to the letter C) will be visible in the rectangle "Result Window", as depicted in Figure 1. A blue control line is a line to show that adequate flow of the sample has occurred and active components have been employed during a test run. The presence of the blue line at the control position on the device confirms that the device is working properly. If H. pylori antigen is absent or below the level of detection, no pink-red line will appear in the rectangle "Result Window" of the cassette next to the letter T, but a distinct blue line shows next to the letter C, as depicted in Figure 1. For invalid result, no visible blue line in the rectangle "Result Window" of the cassette next to the letter C, with or without a visually detectable pink-red line, as depicted in Figure 1. It may occur with the deteriorated materials, but an excess of stool sample and incorrect procedure is mostly the main reason for control line failure. When an invalid result appears, review the test procedure and re- test same specimen. If the test fails again, repeat the test with different specimens. If the problem persists, the use of concerned test kit lot should be discontinued.
Figure 1: Schematic Diagram of Device with all possible outcomes
Image /page/5/Figure/4 description: The image shows four different H. pylori Ag tests. The first test is positive, as indicated by the presence of two lines, one at the control (C) and one at the test (T) position. The second test is negative, as indicated by the presence of only one line at the control (C) position. The third and fourth tests are invalid, as indicated by the presence of only one line at the test (T) position or no lines at all.
Principle of the Test and Assay Procedures 5.
Vstrip® H.pylori Antigen Rapid immunochromatographic assay that utilizes a pair of
6
H. pylori-specific monoclonal antibodies to detect the presence of fecal H. pylori antigens indicated by a pink-red color line.
To perform the test, a diluted stool sample which is first prepared by a sample preparation tube is added to the Test Cassette and read the result at 10 minutes. All stool specimens and assay procedures must be handled at room temperature and on a flat surface.
Rationale of Antibody Selection and Information of Selective H. pylori Strains 6.
In literature, the flagella part of H.pylori has been studied extensively and demonstrated the key role of their colonization in bacteria, inflammation, and immune evasion. Filament, a copolymer of the flagellin subunits, is an important subunit of H.pylori flagella and plays an important role in motility. As motility is essential for H. pylori colonization in the human gastric mucosa, anti- H.pylori monoclonal antibody (Ab) against flagellin was utilized to develop Vstrip® H.pylori Antigen Rapid Test.
7. Intended Use
Vstrip® H.pylori Antigen Rapid Test is a single use immunochromatographic assay for the qualitative detection of H. pylori antigen in unpreserved human stool specimens. Test results are intended to aid in the initial diagnosis and treatment of H. pylori infection. Test results should be taken into consideration by the physician in conjunction with the patient history and symptoms.
Indications of Use 8.
Same as Intended Use
Comparison of Vstrip® H.pylori Antigen Rapid Test with the Predicate Device 9.
The comparison of assay methods between Vstrip® H. pylori Antigen Rapid Test and ImmunoCard STAT! " HpSA" is shown in Table 1. Panion & BF Biotech Inc. (PBF) believes that Vstrip® H.pylori Antigen Rapid Test employs the same technological characteristics for the same intended use as the predicate.
7
| Characteristic | Device: Vstrip® H. pylori Antigen
Rapid Test | Predicate: ImmunoCard STAT!® HpSA®
K032222 |
|---------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended
Use/Indication for
Use | Vstrip® H.pylori Antigen Rapid Test is a
single use immunochromatographic
assay for the qualitative detection of H.
pylori antigen in unpreserved human
stool specimens. Test results are
intended to aid in the initial diagnosis
and treatment of H. pylori infection. Test
results should be taken into consideration
by the physician in conjunction with the
patient history and symptoms. | The ImmunoCard STAT! HpSA is a rapid in
vitro qualitative procedure for the detection of H
pylori antigens in human stool. The stool antigen
detection is intended to aid in the diagnosis of H.
pylori infection and to demonstrate loss of
H.pylori stool antigen following treatment.
Conventional medical practice recommends that
testing by any method to confirm loss of antigen
be done at least four weeks following completion
of therapy. |
| Product Code | LYR | Same |
| Test Type | Qualitative | Same |
| Specimen Required | Formed stool, semi-solid stool, | Same |
| Technology | Lateral flow chromatography | Same |
| Capture Antibody | Monoclonal anti-H. pylori | Same |
| Conjugate | Red-latex conjugated anti-H. pylori | Same |
| Assay Steps | Dilute specimen in provided sample diluents Add diluted specimen to test port Incubate for room temperature for 10 minutes Read results visually | Dilute specimen in provided sample diluents Add diluted specimen to test port Incubate for room temperature for 5 minutes Read results visually |
| End point | Visual color bands | Same |
| Interpretation of
test results | NEGATIVE = Only Blue band at control
line close to letter "C".
POSITIVE = Blue line at control line
plus Pink-red band at the test line close
to letter "T". | Same |
| Differences | | |
| Level of skill
required | Laboratory setting | Untrained Users |
| Kit Storage
temperature | 15-30 °C | 2-8 °C |
| Time to read | 10 min | 5 min |
Table 1: Comparison with Predicate
8
10. Performance Data
Comparison Study
A multi-center study including sites from USA and Taiwan was conducted to evaluate the performance of the study test device (Vstrip® H.pylori Antigen Rapid Test) for detecting H. pylori stool antigen (HpSA) in human stool from patients suspected of H. pylori infection. Test results were compared to results from an FDA cleared H. pylori stool antigen ELISA that was previously evaluated relative to the endoscopy biopsy composite reference method (i.e., culture, histology, and RUT) for initial H. pylori diagnosis with a demonstrated sensitivity and specificity greater than or equal to 95% and a lower bound of the two-sided 95% confidence interval (CI) greater than 89%.
A total of 333 fresh fecal specimens from the intended use population (150 fresh fecal samples collected in the USA and 183 fresh fecal samples collected in Taiwan) along with test device and comparator kits were provided by the Sponsor to the selected study laboratories. Trained laboratory operators were recruited for this study and were blinded to the samples designations.
Positive, negative and overall percent agreement were determined between Vstrip® H.pylori Antigen Rapid Test and the comparator ELISA in detecting the H. pylori antigen in human stool. No invalid results were observed for the investigational test or the comparator ELISA. The Vstrip H.pylori Antigen Rapid Test demonstrated a positive percent of 96.67% [58/60; 95% CI 88.64% - 99.08%] and a negative percent agreement of 98.17% [268/273; 95% CI 95.79% -99.22%] with the comparator ELISA. The study acceptance criteria were met.
Reproducibility Study
A study was conducted to evaluate the reproducibility of Vstrip® H.pylori Antigen Rapid Test results in detecting H.pylori antigen in human stool, as performed by different operators in multiple laboratories.
Five (5) panels of 12 frozen fecal samples each with random distributions of medium positive (4xLOD), low positive (1-2xLOD, near C95 concentration), high negative (near C5 concentration) and negative samples) were analyzed using the Vstrip® H.pylori Antigen Rapid Test by each operator at each site over five (5) days (one (1) panel per day per operator).
Across all sites and operators, agreement with the expected result was 97.8% (88/90) for the moderate positive panel member, 97.8% (88/90) for the low positive panel member, 98.9% (89/90) for the high negative panel member, and 100% (90/90) for the true negative panel member. The reproducibility study analyses demonstrated that results of the Vstrip® H.pylori Antigen Rapid Test are reproducible by different operators in multiple locations.
Analytical Sensitivity
A study was done to establish the limit of detection (LOD) for the Vstrip® H.pylori Antigen Rapid test. The LOD testing was conducted in a stool matrix background comprised from three negative stool samples spiked with serial dilutions of two strains of cultured H. pylori (ATCC 43504 and ATCC 51653). Each dilution was tested with the Vstrip® H.pylori Antigen Rapid test 10 times each by four operators (a total of 40 replicates). The LOD value for Vstrip® H.pylori Antigen Rapid Test was defined as the concentration producing a positive result at least 95% of the time. The LOD value for Vstrip® H.pylori Antigen Rapid Test based on 95% positive results was 8.5X10 CFU/mL
9
for H.pylori strain ATCC 43504 and 1.9 X10 CFU/mL for H.pvlori strain ATCC 51653.
Inclusivity
An additional three H. pylori strains produced a positive result at least 95% of the time with the Vstrip H.pylori Antigen Rapid Test when tested at the following concentrations: ATCC700392 (3.8 x 10 CFU/mL), ATCC 51110 (1.9 x 105 CFU/mL), and BCRC 17132 (3.8 x 106 CFU/mL).
Analytical Specificity
A study was done to determine analytical specificity (cross reactivity) of the Vstrip® H.pylori Antigen Rapid Test with panels of viruses and bacteria. The test was performed on positive and negative samples containing high levels of non-target microorganisms (bacteria spiked at ≥1x10' CFU/mL, viruses spiked at ≥1x10 TCID50/mL). Testing included thirty seven (37) bacteria and seven (7) virus types. Various strains of viruses and bacteria panels were diluted and tested with the Vstrip® H.pylori Antigen Rapid Test to detect any potential cross-reactivity. Results were recorded at 10 minutes interval. Each condition was run in triplicate. None of the microorganisms tested produced false positive or false negative results.
Interfering Substances
A study was conducted to determine if various over-the-counter medications or endogenous substances could interfere with the assay results. Fifteen potentially interfering substances were spiked in both positive and negative samples tested in triplicate with the Vstrip® H.pylori Antigen Rapid Test. None of substances with the indicated concentrations interfered with the performance of Vstrip® H.pylori Antigen Rapid Test.
Sample Stability
Studies were conducted to examine the stability of stool samples when stored refrigerated at 2-8° C or frozen at -20° C. The study results supported the recommendations that stool samples can be stored up to seven days refrigerated at 2-8° C, up to 20 days frozen at -20° C, and that samples can undergo up to three freeze/thaw cycles.
Dose-Hook Effect Study
A dose hook effect (prozone) study was carried out to examine whether high concentrations of H. pylori antigen negatively affects the performance of the Vstrip®. The hook effect or the prozone effect is a type of interference which produces false negatives or inaccurately low results in the presence of high analyte concentrations. Five H pylori strains were tested in triplicate at 10° 10′ CFU/mL (10 - 100X LoD) concentration range with the Vstrip® H.pylori Antigen Rapid Test. No dose hook effect was observed at the tested concentrations.
11. Conclusions
The conclusions drawn from the nonclinical and clinical studies demonstrate that the Vstrip® H.pylori Antigen Rapid Test is safe and effective and substantially equivalent to the predicate device in performance.