(351 days)
The Helicobacter pylori (H. pylori) ELISA IgG test kit is intended for the qualitative detection of IgG antibodies to H. pylori in human serum in the adult population. This test is intended to aid in the diagnosis of H. pylori in patients suspected of having H. pylori infection, and in patients with gastrointestinal symptoms, and is to be used in conjunction with clinical findings.
The assay requires a total of 90 minutes incubation time. The test uses purified antigen coated on microtiter wells. Serum is added to each well and incubated for 30 minutes at 37°C. If H. pylori IgG antibodies are present they will bind to the antigen in the well. Unbound serum is removed by washing the wells three times. An HRP-conjugated anti-human IgG is then added to each well and incubated for 30 minutes at 37℃. If H. pylori antibody is present, it will bind to the antibody attached to the antigen on the wells are again washed three times to remove any unbound coniugate. A TMB substrate is added to each well and incubated for 30 minutes at 37°C. If enzyme is present, it will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a Stop Solution and the color intensity is measured spectrophotometrically.
Here's an analysis of the provided text regarding the Gold Standard Diagnostics Helicobacter pylori ELISA IgG Test Kit, focusing on the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The provided document does not explicitly state pre-defined acceptance criteria values for the clinical performance metrics (Positive Agreement, Negative Agreement, Overall Agreement). Instead, it compares the device's performance to a legally marketed predicate device (Micro Detect, Inc. Pylori Detect IgG kit) and argues for substantial equivalence based on the observed agreement percentages.
However, based on the context of 510(k) submissions, the implicit "acceptance criteria" are that the device's performance should be comparable to or not worse than the predicate device, demonstrating substantial equivalence. The reported device performance is as follows:
| Performance Metric | Acceptance Criteria (Implied: Comparable to Predicate Device) | Reported Device Performance | Comments |
|---|---|---|---|
| % Positive Agreement | Comparable to Predicate Device (Micro Detect IgG ELISA) | 92.7% (with 95% CI: 88.5% to 95.5%) | This indicates a high level of agreement between the new device and the predicate device for positive H. pylori cases. The 95% CI suggests reasonable precision for this estimate. |
| % Negative Agreement | Comparable to Predicate Device (Micro Detect IgG ELISA) | 94.7% (with 95% CI: 92.0% to 96.5%) | This indicates a high level of agreement between the new device and the predicate device for negative H. pylori cases. The 95% CI suggests reasonable precision for this estimate. |
| % Equivocal Agreement | Comparable to Predicate Device (Micro Detect IgG ELISA) | 20% (with 95% CI: 5.7% to 51.0%) | This agreement is significantly lower than positive and negative agreement. However, equivocal results often require further testing or clinical correlation, so a lower agreement for this category might be acceptable given the overall high positive and negative agreements. The wide CI suggests uncertainty in this estimate due to the small number of equivocal cases. |
| Overall Agreement | Comparable to Predicate Device (Micro Detect IgG ELISA) | 92.8% | This metric provides an overall measure of concordance between the two devices. |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size: 625 samples.
- Data Provenance: The samples were "routinely tested for H." at multiple sites. The document implies these were human serum samples collected as part of routine clinical practice. There is no specific mention of the country of origin, but given the submitter and review body (US FDA), it's highly probable the data is from the US. The study appears to be retrospective, as it used "samples being routinely tested."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The concept of "experts establishing ground truth" as it applies to image-based diagnostics with radiologists is not directly applicable here. For this type of serological assay (ELISA for H. pylori IgG antibodies), the "ground truth" for the comparative study was established by a legally marketed predicate device (Micro Detect, Inc. Pylori Detect IgG assay, K973508).
For discrepant samples, a "third assay, the DiaMedix H. pylori IgG assay (which is also commercially available)" was used for further testing. These commercially available assays themselves have their own validated performance characteristics, so they serve as the reference standard in this context rather than individual human experts adjudicating cases.
4. Adjudication Method for the Test Set
The adjudication method for the clinical comparison was a "third assay" (DiaMedix H. pylori IgG assay) for discrepant results between the new device and the predicate device.
- For the 11 samples where the Gold Standard Diagnostics device was negative and the Micro Detect Inc. device was positive, the third assay called: 9 positive, 2 negative.
- For the 13 samples where the Gold Standard Diagnostics device was positive and the Micro Detect Inc. device was negative, the third assay called: 1 borderline, 2 negative, 10 positive.
This acts as a tie-breaker or further confirmatory test for discordant results, though the final calculation of agreement percentages is primarily based on the direct comparison between the new device and the predicate.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, an MRMC comparative effectiveness study was not done. This type of study typically involves multiple human readers interpreting cases with and without AI assistance, which is not relevant for a laboratory-based serological assay like the one described.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) Was Done
Yes, a standalone performance evaluation was done for the Gold Standard Diagnostics H. pylori ELISA IgG Test Kit. The clinical comparison study directly measures the performance of the device itself (the "algorithm only") against a predicate device. The results (Positive Agreement, Negative Agreement, Overall Agreement) represent the direct output of the assay for each sample.
7. The Type of Ground Truth Used
The primary "ground truth" or reference standard for the clinical comparison was the predicate device (Micro Detect, Inc. Pylori Detect IgG ELISA). For discrepant samples, a secondary commercially available assay (DiaMedix H. pylori IgG assay) was used for further analysis. This is a common approach for establishing substantial equivalence for in vitro diagnostic devices when a definitive "gold standard" (like pathology for cancer) is not directly applicable or available for all samples.
8. The Sample Size for the Training Set
The document does not mention a training set or its sample size. This is expected because the device is an ELISA kit, which is a laboratory assay with fixed chemical and biological reagents and protocols, not a machine learning algorithm that requires a training set for model development. The performance characteristics are inherent to the assay's design and are evaluated through analytical and clinical validation studies.
9. How the Ground Truth for the Training Set Was Established
As no training set is mentioned or applicable for this type of device, this point is not relevant.
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MAR - 2 2012
510(k) Summary of Safety and Effectiveness
This 510(k) summary of safety and effectiveness information is being submitted in accordance with the requirement of SMDA 1990 and 21 CFR 807.92.
| 1) Submitter's Name: | Gold Standard Diagnostics |
|---|---|
| Address: | 2851 Spafford St. Davis, CA. 95618 |
| Phone Number: | 530-759-8000 |
| Contact Person: | Napoleon Monce |
| Date: | September 20, 2011 |
-
- Product and Trade Name: Helicobacter pylori IgG ELISA
Common Name or Classification Name: Campylobacter pylori
- Product and Trade Name: Helicobacter pylori IgG ELISA
Product Code: LYR
3) Legally marketed device to which the submitter claims equivalence:
Micro Detect, Inc. Pylori Detect IgG ELISA for the qualitative detection of IgG antibodies against H. pylori in human serum. The test is intended as an aid in the diagnosis of infection by H. pylori in patients with gastrointestinal symptoms. K973508.
4) Description of the device:
The assay requires a total of 90 minutes incubation time. The test uses purified antigen coated on microtiter wells. Serum is added to each well and incubated for 30 minutes at 37°C. If H. pylori IgG antibodies are present they will bind to the antigen in the well. Unbound serum is removed by washing the wells three times. An HRP-conjugated anti-human IgG is then added to each well and incubated for 30 minutes at 37℃. If H. pylori antibody is present, it will bind to the antibody attached to the antigen on the wells are again washed three times to remove any unbound coniugate. A TMB substrate is added to each well and incubated for 30 minutes at 37°C. If enzyme is present, it will react with the substrate to generate a colored product. After the incubation period, the reaction is stopped with a Stop Solution and the color intensity is measured spectrophotometrically.
Intended use of the device: 5)
The Helicobacter pylori (H. pylori) ELISA IgG test kit is intended for the qualitative detection of IgG antibodies to H. pylori in human serum in the adult population. This test is intended to aid in the diagnosis of H. pylori in patients suspected of having H. pylori infection, and in patients with gastrointestinal symptoms, and is to be used in conjunction with clinical findings.
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6) Comparison with the predicate device:
The Gold Standard Diagnostics H. pylori ELISA IgG Test Kit was compared to a commercially marketed kit by Micro Detect, Inc. the Pylori Detect IgG (K973508) catalog number HpKi-G. Both kits have the same intended use and use the same methodology. Below are tables comparing the reagents provided, the procedures, and their performances.
| Table 1: Reagent Comparison | ||
|---|---|---|
| Gold Standard Diagnostics H. pyloriELISA IgG Test Kit | Micro Detect Inc. Pylori Detect IgG |
|---|---|
| Antigen coated Microtiter Plate - 96 wells | Antigen coated Microtiter Plate - 96 wells |
| Wash Solution - 20x | Diluent/Wash Concentrate - 25x |
| Diluent - Ready to Use | Diluent/Wash Concentrate - 25x |
| IgG Conjugate - Anti Human HRP | IgG Conjugate - Anti Human Peroxidase |
| Substrate - Tetramethylbenzidine (TMB) | Substrate - Tetramethylbenzidine (TMB) |
| Stop Solution - Acid mixture | Stop Solution - Sulfuric Acid |
| H. pylori IgG Positive Control | H. pylori IgG Positive Control |
| H. pylori IgG Cutoff Control | H. pylori IgG Calibrator |
| H. pylori IgG Negative Control | H. pylori IgG Negative Control |
Table 2: Procedure Comparison
| Gold Standard Diagnostics H. pyloriELISA IgG Test Kit | Micro Detect Inc. Pylori Detect IgG |
|---|---|
| Dilute Samples 1:101 in Diluent | · Dilute Samples 1:101 in reconstitutedDiluent/Wash |
| Add 100ul of Samples and Controls | Add 100ul of Samples and Controls |
| Incubate for 30 minutes at 37°C | Incubate for 20 minutes at RoomTemperature |
| Wash four times with reconstituted Wash | Wash three times with reconstituted Wash |
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| Solution | Solution |
|---|---|
| Add 100ul of Conjugate | Add 100ul of Conjugate |
| Incubate for 30 minutes at 37°C | Incubate for 20 minutes at RoomTemperature |
| Wash four times with reconstituted WashSolution | Wash three times with reconstituted WashSolution |
| Add 100ul of Substrate | Add 100ul of Substrate |
| Incubate for 30 minutes at 37°C | Incubate for 15 minutes at RoomTemperature |
| Add 50ul of Stop Solution | Add 100ul of Stop Solution |
| Read with Spectrophotometer at 450nm | Read with Spectrophotometer at 450nm |
Nonclinical tests: 6(b1)
The intra and inter assay precision was calculated by running six patient sera (four positives and two negatives) at three different sites. The results are summarized in the table below:
| Sample 1 | Sample 2 | Sample 3 | Sample 4 | Sample 5 | Sample 6 | ||
|---|---|---|---|---|---|---|---|
| Site 1 | Ave: | 0.884 | 1.022 | 0.965 | 1.302 | 0.185 | 0.168 |
| SD: | 0.063 | 0.043 | 0.050 | 0.006 | 0.011 | 0.016 | |
| Intra-Assay | CV: | 7.2% | 4.3% | 5.2% | 0.4% | 6.0% | 9.5% |
| Site 2 | Ave: | 0.935 | 0.958 | 0.817 | 1.329 | 0.147 | 0.153 |
| SD: | 0.028 | 0.034 | 0.042 | 0.015 | 0.005 | 0.007 | |
| Intra-Assay | CV: | 3.0% | 3.6% | 5.1% | 1.1% | 3.4% | 4.3% |
| Site 3 | Ave: | 1.013 | 1.093 | 0.933 | 1.476 | 0.181 | 0.177 |
| SD: | 0.016 | 0.103 | 0.068 | 0.106 | 0.013 | 0.011 | |
| Intra-Assay | CV: | 4.5% | 9.4% | 7.3% | 7.2% | 7.0% | 6.4% |
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| Ave: | 0.974 | 1.057 | 0.925 | 1.414 | 0.177 | 0.172 | |
|---|---|---|---|---|---|---|---|
| Inter-Assay | SD: | 0.070 | 0.098 | 0.078 | 0.114 | 0.018 | 0.014 |
| CV: | 7.2% | 9.3% | 8.4% | 8.0% | 10.1% | 8.4% |
Reproducibility :
The reproducibility of the assay was done by testing three samples in triplicate (a high negative, low positive and a moderate positive) for five days, twice a day, at three sites with two technicians per site. The results are summarized in the table below:
| 5 Day Average: | Sample 1 | Sample 2 | Sample 3 | ||
|---|---|---|---|---|---|
| Site 1 | Tech 1 | OD: | 0.338 | 0.708 | 1.030 |
| SD: | 0.047 | 0.074 | 0.095 | ||
| CV: | 13.9% | 10.4% | 9.2% | ||
| Site 1 | Tech 2 | OD: | 0.354 | 0.692 | 1.055 |
| SD: | 0.043 | 0.060 | 0.107 | ||
| CV: | 12.2% | 8.7% | 10.1% | ||
| Site 2 | Tech 1 | OD: | 0.329 | 0.693 | 1.034 |
| SD: | 0.044 | 0.037 | 0.050 | ||
| CV: | 13.4% | 5.4% | 4.9% | ||
| Site 2 | Tech 2 | OD: | 0.360 | 0.693 | 1.022 |
| SD: | 0.052 | 0.032 | 0.049 | ||
| CV: | 14.4% | 4.7% | 4.8% | ||
| Site 3 | Tech 1 | OD: | 0.300 | 0.516 | 0.888 |
| SD: | 0.048 | 0.054 | 0.032 | ||
| CV: | 16.1% | 10.5% | 3.6% | ||
| Site 3 | Tech 2 | OD: | 0.374 | 0.642 | 0.928 |
| SD: | 0.041 | 0.094 | 0.128 | ||
| CV: | 11.0% | 14.6% | 13.7% |
Cross Reactivity:
An adsorption study was performed to evaluate any cross reactivity. Briefly, sera with different levels of antibodies to H. pylori were adsorbed with either H. pylori, Candida albicans, E. coli, Borrelia burgdorferi, Clostridium' spp., Campylobacter, Bacillus, Enterobacter, Pseudomonas, Haemophilus Influenza, and Proteus. The identity of the bacteria used were identified by the ATCC and confirmed with the MALDI-TOF method. The bacteria were evaluated at a concentration of 10' cfu/ml or higher.
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Sera with different levels of antibodies to H. pylori, were adsorbed with the recommended organisms. The adsorbed samples were compared to the untreated samples and the mean percent inhibition was calculated. The results are summarized in the following table:
| Organism | Concentration (cfu/ml) | Mean percentinhibition |
|---|---|---|
| Helicobacter pylori | 96% | |
| Candida albicans | 2.40x107 | 1.8% |
| Escherichia coli | 6.90x107 | 9.5% |
| Borrelia burgdorferi | 1.00x108 | 5.5% |
| Clostridium spp. | 1.20x107 | 6.0% |
| Campylobacter | 1.50x109 | 4.7% |
| Bacillus Cereus | 4.40x107 | 18.2% |
| Enterobacter | 1.80x108 | 2.1% |
| Pseudomonas | 1.45x108 | 5.1% |
| Haemophilus Influenza | 7.90x107 | 3.8% |
| Proteus | 1.40x108 | 4.6% |
The mean percent inhibition for H. pylori was 96%, and 1.8% to 9.5% with the other organisms. There seems to be a weak cross reactivity with Bacillus Cereus. Taking into account the normal test variation, the remaining cross reactivity with Bacillus Cereus may affect high negative samples close to the equivocal range. Overall no effects on the analytical specificity were seen on the Gold Standard Diagnostics H. pylori ELISA IgG assay.
Interfering Substance
The effect of potential interfering substances on samples using the Gold Standard Diagnostics H. pylori ELISA IgG assay was evaluated. High levels of hemoglobin, bilirubin, cholesterol and triglycerides in serum samples were tested at the assay cutoff (9-11 units) in triplicate. The recommended concentrations from the guideline "Interference Testing InClinical Chemistry" from the Clinical and Laboratory Standards Institute were used (see table below). The tested substances did not affect the performance of the Gold Standard Diagnostics H. pylori ELISA IgG assay.
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| Substance | Concentration | H. pyloriconcentrationn | Mean PercentInhibition |
|---|---|---|---|
| Hemoglobin | 2 g/L | 9-11 units | 3% |
| Bilirubin | 342 μmol/L | 9-11 units | 11% |
| Cholesterol | 13 mmol/L | 9-11 units | 1% |
| Triglyceride | 37 mmol/L | 9-11 units | -19% |
Leukocytes, intestinal secretions or mucus, fat, and medications used to relieve diarrhea or other gastric symptoms were not tested, therefore, it is not known if these substances will interfere with the assay as they were not evaluated.
6(b2): Clinical Comparison:
The performance of the Gold Standard Diagnostics H. pylori ELISA 1gG assay was determined by conducting a correlation study using 625 samples being routinely tested for H. The samples were tested on both the Gold Standard Diagnostics H. pylori ELISA IgG assay and a commercially available ELISA assay (Micro Detect Inc. K973508) as the predicate device. The results are summarized in the following table:
| Micro Detect IgG ELISA | ||||
|---|---|---|---|---|
| Positive | Equivocal | Negative | ||
| Gold Standard | Positive | 203 | 3 | 13 |
| Diagnostics IgG | Equivocal | 5 | 2 | 8 |
| ELISA | Negative | 11 | 5 | 375 |
| Total | 219 | 10 | 396 |
The discrepant samples were further tested on a third assay, the DiaMedix H. pylori IgG assay (which is also commercially available). Of the 11 Gold Standard Diagnostics negative samples, Micro Detect Inc. positive samples, the third assay called nine samples positive and two samples negative. Of the 13 Gold Standard Diagnostics positive samples, Micro Detect Inc. negative samples, the third assay called one sample borderline, two negative, and ten samples positive. The comparison data produced the following:
- % Positive Agreement = 92.7% (203/219) with 95% CI: 88.5% to 95.5%;
- % Negative Agreement = 94.7% (375/396) with 95% CI: 92.0% to 96.5%
- % Equivocal Agreement = 20% (2/10) with 95% CI: 5.7% to 51.0%
Overall Agreement = 92.8% (580/625)
6(b3) Conclusion:
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From the data and comparison above, it is our contention that the Gold Standard Diagnostic H. pylori IgG ELISA test is substantially equivalent to the commercially marketed Micro Detect, Inc. Pylori Detect IgG kit. . . . . . . . .
:
:
. . . . .
:
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DEPARTMENT OF HEALTH & HUMAN SERVICES
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 text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is a stylized symbol of three human profiles facing to the right, with flowing lines representing hair or movement.
10903 New Hampshire Avenue Silver Spring, MD 20993
Gold Standard Diagnostics c/o Napoleon Monce Director, Product Development 2851 Spafford Street Davis, California 95618
MAR - 2 2012
Re: K110745
Trade Name: Helicobacter pylori ELISA IgG Test Kit Regulation Number: 21 CFR §866.3110 Regulation Name: Campylocbacter fetus serological reagents. Regulatory Class: Class I Product Code: LYR Dated: February 21, 2012 Received: February 23, 2012
Dear Mr. Monce:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration.
If your device is classified (see above) into class II (Special Controls), it may be subject to such additional controls. Existing major regulations affecting your device can be found in 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 Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050. This letter will allow you to begin marketing your device as described in your Section
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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 809), please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 796-5450. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to
http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.
You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/cdrh/industry/support/index.html.
Sincerely yours,
Sayatgan
Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known): K110745
Device Name: Gold Standard Diagnostics Helicobacter pylori ELISA IgG Test Kit
Indications For Use:
The Helicobacter pylori (H. pylori) ELISA lgG test kit is intended for the qualitative detection of IgG antibodies to H. pylori in human serum in the adult population. This test is intended to aid in the diagnosis of H. pylori in patients suspected of having H. pylori infection, and in patients with gastrointestinal symptoms, and is to be used in conjunction with clinical findings.
Prescription Use X (Part 21 CFR 801 Subpart D)
AND/OR
Over-The-Counter Use (21 CFR 807 Subpart C)
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of In Vitro Diagnostic Devices (OIVD)
Freddie W. Poole
Division Sign-Off
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K110745
1.1
§ 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).