(98 days)
The Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay is intended for use with the Nichols Advantage® Specialty System for the qualitative determination of anti-H. pylori IgG in human serum to aid in the diagnosis of infection by H. pylori.
The Nichols Advantage® Helicobacter pylori IgG Antibodies Assay is a two-site chemiluminescence assay for use with the Nichols Advantage® Specialty System. Nichols Institute Diagnostics utilizes chemiluminescence acridinium esters as the label in its specialty chemiluminescence system. Acridinium esters emit light upon treatment with hydrogen peroxide and an alkaline solution. The Trigger 1 solution contains hydrogen peroxide in diluted acid and Trigger 2 solution contains diluted sodium hydroxide. The system automatically injects Trigger solutions 1 and 2 into the wells of the cuvette which oxidize the acridinium ester. The oxidized product is in an excited state. The subsequent return to ground state results in the emission of light, which is quantified in two seconds and is expressed in relative light units (RLU) by the integrated system luminometer. The Nichols Advantage® Anti-H. pylori IgG Assay is a two-site chemiluminescence immunoassay for the measurement of anti-H. pylori IgG in human serum. It utilizes an acridinium-ester-labeled mouse monoclonal anti-human IgG antibody and a biotinylated H. pylori antigen cocktail. The sample containing anti-H. pylori IgG antibodies is incubated with the biotinylated antigen cocktail and magnetic particles for 10 minutes at 37°C. Free, unbound biotinylated antigens and anti-H. pylori IgG antibodies are separated from the complex bound to the magnetic particles by aspiration of the reaction mixture and subsequent washing. Thereafter, acridinium-labeled anti-human IgG antibodies are added to the reaction mixture and a second 10 minute incubation follows creating the sandwich complex. Free, unbound acridinium-labeled anti-human IgG antibodies are separated from the complex bound to the magnetic particles by aspiration of the reaction mixture and subsequent washing. The wells containing the washed magnetic particles are transported into the system luminometer, which automatically injects Trigger 1 and Trigger 2, initiating the chemiluminescence reaction. The light is quantitated by the luminometer and expressed as RLU. The amount of bound-labeled antibody is directly proportional to the titer of anti-H. pylori IgG antibodies in the sample. The Nichols Advantage Specialty System automatically handles sample dilution as well as sample and reagent additions, the temperature-controlled incubation, separation/washing step, and measurement of the light output. It calculates test results for controls and patient samples from the stored calibration curve, and generates a printed report, which includes patient information.
Here's an analysis of the provided text, extracting the requested information about acceptance criteria and the supporting study:
Acceptance Criteria and Device Performance for Nichols Advantage® H. pylori IgG Antibodies Immunoassay
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" with numerical thresholds for performance metrics. Instead, it presents performance characteristics and compares them to the predicate device, implying that the Nichols Advantage® assay's performance is considered acceptable if its characteristics are comparable or superior and meet the intended use.
Based on the "Performance Characteristics" section, here are the reported performance details:
| Feature | Acceptance Criteria (Implied) | Reported Device Performance (Nichols Advantage® Chemiluminescence Anti- H. pylori IgG) |
|---|---|---|
| Intra-Assay | N/A (Compared to predicate) | Mean (titer): 34, SSD: 2.9, %CV: 8.5 Mean (titer): 241, SSD: 11.3, %CV: 4.7 Mean (titer): 1471, SSD: 133.9, %CV: 9.1 |
| Inter-Assay | N/A (Compared to predicate) | Mean (titer): 26, SSD: 6.0, %CV: 23 Mean (titer): 238, SSD: 38.1, %CV: 16 Mean (titer): 2225, SSD: 333.8, %CV: 15 |
| Recovery | N/A (Compared to predicate) | 92% - 118% |
| Parallelism | N/A (Compared to predicate) | 89% - 117% |
| High Dose Hook Effect | N/A (Compared to predicate) | Less Than 1:20,000 titer |
| Method Comparison | N/A (Concordance to predicate) | |
| Range of Results | N/A (For method comparison) | 1:13 to 1:5526 |
| Concordance | N/A (Compared to predicate) | 79.4% |
| Percent Agreement Positive | N/A (Compared to predicate) | 91.1% (95% CI: 87% to 95%) |
| Percent Agreement Negative | N/A (Compared to predicate) | 75.3% (95% CI: 70% to 81%) |
2. Sample Size Used for the Test Set and Data Provenance
The document does not explicitly state the sample size used for the "Method Comparison" test set, nor does it specify the country of origin of the data or whether the study was retrospective or prospective. It only presents the "Range of Results" for the method comparison as "1:13 to 1:5526" for the Nichols Advantage® assay and "1:97 to 1:9504" for the predicate device.
3. Number of Experts Used to Establish Ground Truth for the Test Set and Qualifications
The document does not describe the use of experts to establish ground truth for the method comparison. The comparison is between the Nichols Advantage® assay and a predicate device (Orion Diagnostica Pyloriset® EIA-G Immunoassay), suggesting the predicate device's results served as a reference.
4. Adjudication Method for the Test Set
No adjudication method is described, as the comparison is primarily assay-to-assay.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC study was conducted or mentioned in the document. This is an in vitro diagnostic device, and MRMC studies are typically for imaging or interpretation tasks where human readers are involved.
6. Standalone Performance (Algorithm Only without Human-in-the-Loop Performance)
The device itself is an automated immunoassay system. The performance characteristics described for the Nichols Advantage® system are inherently standalone (algorithm/device only) without human-in-the-loop performance influencing the assay's raw output. The system automatically handles processes and calculates results.
7. Type of Ground Truth Used
The ground truth for the method comparison study appears to be the results obtained from the predicate device, the Orion Diagnostica Pyloriset® EIA-G Immunoassay. The document states a "Method Comparison" was performed, and then provides "Concordance," "Percent Agreement Positive," and "Percent Agreement Negative" between the new device and the predicate. This implies the predicate's results were used as a reference for comparison.
8. Sample Size for the Training Set
The document describes an immunoassay, not a machine learning algorithm that typically has a "training set." Therefore, a "training set" in the context of data used to train an algorithm is not applicable here. The assay relies on established chemical and immunological principles, with performance validated through analytical and clinical studies.
9. How the Ground Truth for the Training Set Was Established
As noted above, a "training set" for an algorithm is not applicable for this type of device. The assay's analytical performance (intra-assay, inter-assay, recovery, parallelism) would have been established using characterized samples with known concentrations/titer ranges, but this is part of analytical validation, not algorithm training.
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K022356
2.5 2002
Nichols Institute Diagnostics Nichols Advantage® H. pvlori IgG Antibodies 510(k) Notification
11.0 510(k) SUMMARY
This summary of 510(k) safety and effectiveness is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR 807.92.
510(k) Number: not known
1. Name of Submitter, Contact Person and Date Summary Prepared:
Nichols Institute Diagnostics 1311 Calle Batido San Clemente, CA 92673 Phone: 949-240-5260 Fax: 949-940-7313
Contact Person: James A. Rybski, Ph.D. Date Prepared: July 16, 2002
2. Device Name:
| Trade/Proprietary Name: | Nichols Advantage® Chemiluminescence Helicobacterpylori IgG Antibodies Immunoassay |
|---|---|
| Common/Usual Name: | Anti-H. pylori IgG Assay |
| Classification Name: | Campylobacter pylori Serological Reagents |
3. Predicate Device:
We claim substantial equivalence to the Orion Diagnostica Pyloriset® EIA-G Immunoassay (K971537, Cleared June 27, 1997).
4. Device Description:
The Nichols Advantage® Helicobacter pylori IgG Antibodies Assay is a two-site chemiluminescence assay for use with the Nichols Advantage® Specialty System.
Chemiluminescence
Nichols Institute Diagnostics utilizes chemiluminescence acridinium esters as the label in its specialty chemiluminescence system. Acridinium esters emit light upon treatment with hydrogen peroxide and an alkaline solution. The Trigger 1 solution contains hydrogen peroxide in diluted acid and Trigger 2 solution contains diluted sodium hydroxide. The system automatically injects Trigger solutions 1 and 2 into the
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wells of the cuvette which oxidize the acridinium ester. The oxidized product is in an excited state. The subsequent return to ground state results in the emission of light, which is quantified in two seconds and is expressed in relative light units (RLU) by the integrated system luminometer.
Immunometric Assay
The Nichols Advantage® Anti-H. pylori IgG Assay is a two-site chemiluminescence immunoassay for the measurement of anti-H. pylori IgG in human serum. It utilizes an acridinium-ester-labeled mouse monoclonal anti-human IgG antibody and a biotinylated H. pylori antigen cocktail. The sample containing anti-H. pylori IgG antibodies is incubated with the biotinylated antigen cocktail and magnetic particles for 10 minutes at 37°C. Free, unbound biotinylated antigens and anti-H. pylori IgG antibodies are separated from the complex bound to the magnetic particles by aspiration of the reaction mixture and subsequent washing. Thereafter, acridinium-labeled anti-human IgG antibodies are added to the reaction mixture and a second 10 minute incubation follows creating the sandwich complex. Free, unbound acridinium-labeled anti-human IgG antibodies are separated from the complex bound to the magnetic particles by aspiration of the reaction mixture and subsequent washing. The wells containing the washed magnetic particles are transported into the system luminometer, which automatically injects Trigger 1 and Trigger 2, initiating the chemiluminescence reaction. The light is quantitated by the luminometer and expressed as RLU. The amount of bound-labeled antibody is directly proportional to the titer of anti-H. pylori IgG antibodies in the sample.
Automation
The Nichols Advantage Specialty System automatically handles sample dilution as well as sample and reagent additions, the temperature-controlled incubation, separation/washing step, and measurement of the light output. It calculates test results for controls and patient samples from the stored calibration curve, and generates a printed report, which includes patient information.
5. Intended Use:
The Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay is intended for use with the Nichols Advantage® Specialty System for the qualitative determination of anti-H. pylori IgG antibodies in human serum to aid in the diagnosis of infection by H. pylori.
6. Comparison to predicate device:
The Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay is substantially equivalent to other products in commercial distribution
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for similar use. Most notably, it is substantially equivalent to the Orion Diagnostica Pyloriset® EIA-G Immunoassay.
The following tables compare the Nichols Advantage Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay with the predicate device, Orion Diagnostica's Pyloriset EIA-G Immunoassay.
Similarities:
- Intended Use: For the qualitative determination of anti-H. pylori IgG antibodies in . human serum.
- Both assays use an H. pylori antigen cocktail to bind human anti-H. pylori . antibodies.
- Both assays use human serum for the test sample. .
- Both assays rely upon a sandwich formation by antibodies specific to human IgG . to detect anti-H. pylori IgG antibodies.
- The sensitivity of both assays is sufficient to measure anti-H. pylori IgG antibody . levels found in Helicobacter pylori-infected patients.
| Nichols Advantage®Helicobacter pylori IgGAntibodies Assay | Orion DiagnosticaPyloriset® EIA-GImmunoassay | |
|---|---|---|
| Feature | ||
| Sample Size | Five (5) microliters | 0.5 microliters**100 microliters of a 1:201dilution of the sample |
| Calibration | Two point calibration every twoweeks (maximum) of storedworking calibration curve; orwhen controls out of range. | Four point standard curve runwith each assay. |
| Solid Phase | Streptavidin-coated magneticparticles. Streptavidin-biotinseparation technology. | Helicobacter pylori antigencocktail adsorbed to microtiterplate wells. Antibodysandwich-formation separationtechnology. |
| Incubation | Two Incubations:Total of 20 minutes at 37°C | Three Incubations:Total of 2 hr 30 min at roomtemperature (20-25°C) |
| Sensitivity | Less than or equal to 1:10 titer | Not described in the DirectionalInsert |
Differences:
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Performance Characteristics:
| FEATURE | Nichols Advantage®ChemiluminescenceAnti- H. pylori IgG | Orion DiagnosticaPyloriset® EIA-G Immunoassay | ||
|---|---|---|---|---|
| Mean(titer) | SSD | %CV | ||
| Intra-Assay | 34 | 2.9 | 8.5 | None given |
| 241 | 11.3 | 4.7 | ||
| 1471 | 133.9 | 9.1 | ||
| Inter-Assay | 26 | 6.0 | 23 | None given |
| 238 | 38.1 | 16 | ||
| 2225 | 333.8 | 15 | ||
| Recovery | 92% - 118% | None given | ||
| Parallelism | 89% - 117% | None given | ||
| High Dose Hook Effect | Less Than 1:20,000 titer | None given | ||
| Method Comparison | ||||
| Range of Results | 1:13 to 1:5526 | 1:97 to 1:9504 | ||
| Concordance: | 79.4% | |||
| Percent Agreement Positive: | 91.1% (95%CI: 87% to 95%) | |||
| Percent AgreementNegative: | 75.3% (95%CI: 70% to 81%) |
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Image /page/4/Picture/0 description: The image shows the text "DEPARTMENT OF HEALTH & HUMAN SERVICES". The text is in all caps and is written in a serif font. The text is centered on the image and is the only element present.
Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a stylized caduceus symbol, which features three abstract human figures. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged in a circular pattern around the symbol.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
OCT 2 5 2002
James A. Rybski, Ph.D. Manager, R&D Scientific and Clinical Affairs Nichols Institute Diagnostics 1311 Calle Batido San Clemente, California 92673
Re: K022356
Trade/Device Name: Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Assay Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter Fetus Serological Reagents Regulatory Class: Class I Product Code: LYR Dated: September 30, 2002 Received: October 18, 2002
Dear Dr. Rybski:
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 either class II (Special Controls) or class III (PMA), 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 mav 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 801); 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,
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Page 2 -
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" (21CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrb/dsma/dsmamain.html".
Sincerely yours,
Steven Butman
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
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Nichols Institute Diagnostics Nichols Advantage™ H. pylori IgG Antibodies 510(k) Notification
INDICATIONS FOR USE STATEMENT 4.0
INDICATIONS FOR USE STATEMENT
510(k) Number (if known): _ KO323562
Device Name: Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay
Indications For Use: The Nichols Advantage® Chemiluminescence Helicobacter pylori IgG Antibodies Immunoassay is intended for use with the Nichols Advantage® Specialty System for the qualitative determination of anti-H. pylori IgG in human serum to aid in the diagnosis of infection by H. pylori.
Freddie M. Poole
(Division Sign-Off) Division of Clinical 510(k) Number -
OR
(PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)
Concurrence of CDRH, Office of Device Evaluation (ODE)
Prescription Use (Per 21 CFR 801.109)
Over-The-Counter Use (Optional Format 1-2-96)
§ 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).