The Helicobacter pyloxi IgG ELISA test is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of human IgG class antibodies to Helicobacter pylori in serum and in EDTA or heparin-treated plasma. The test is intended to aid in the diagnosis of Helicobacter pylori infection in adult patients with clinical symptoms of gastritis. FOR INVITRO DIAGNOSTIC USE.

Device Description

The Helicobacter pylori IgG ELISA is an immunoassay to detect IgG antibodies to Helicobacter pylori. The assay requires a total of 90-minutes incubation. The test uses partially purified Helicobacter pylori bacterial antigen adsorbed to a solid phase microassay well. Prediluted test serum or plasma is added to each well and incubated for 30 minutes at 37℃. If Helicobacter pylori-specific IgG antibodies are present, they will bind to the antigen in the well. After the incubation, the wells are washed three times to remove any unbound serum or plasma. An HRP-conjugated monoclonal anti-human IgG is added to each well, and the test is incubated for 30 minutes at 37℃. If Helicobacter pylori antibody is present, it will bind to the antibody attached to the antigen on the well. The wells are washed again to remove any unbound conjugate. A TMB-substrate is added to each well and incubated for 30 minutes at room temperature (20-25°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. The Helicobacter pylori IgG ELISA is highly sensitive for the detection of IgG antibodies to Helicobacter pvlori in serum or plasma samples.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Biohit Helicobacter pylori IgG ELISA, based on the provided 510(k) summary:

Acceptance Criteria and Device Performance

The provided document does not explicitly state pre-defined acceptance criteria in terms of target percentages for sensitivity, specificity, or agreement. Instead, it reports the device's performance when compared to two different reference methods: histology (considered the "gold standard") and a legally marketed predicate ELISA. The conclusion for substantial equivalence is based on these reported performance metrics aligning with clinical expectations for such a device.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance (vs. Histology)	Reported Device Performance (vs. Predicate ELISA)
Sensitivity	Clinically acceptable	80.9%	88.6%
Specificity	Clinically acceptable	75.8%	100%
Predictive Positive Value (PPV)	Clinically acceptable	64.6%	100%
Predictive Negative Value (PNV)	Clinically acceptable	87.9%	96.2%
Agreement	Clinically acceptable	77.6%	97.0%

Study Details

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

The document does not explicitly state the sample size of the test set or the provenance of the data (country of origin, retrospective/prospective). It simply refers to "clinical evaluations" and comparison studies.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

The document does not specify the number of experts or their qualifications for establishing the ground truth. It states that "Culture of the organism and/or histologic staining from a biopsy sample obtained at endoscopy is considered by the FDA to be the current 'Gold Standard' for detection of Helicobacter pylori". This implies a reliance on standard laboratory procedures and interpretation.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

The document does not describe any specific adjudication method for the test set. The ground truth was established by "Gold Standard" methods (histology) and comparison to a commercial ELISA.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

A multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is an immunoassay (ELISA) for detecting antibodies, not an imaging or diagnostic algorithm requiring human interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

The entire study reported describes the standalone performance of the Biohit Helicobacter pylori IgG ELISA kit. This device is an in vitro diagnostic test, meaning its output is a direct result from the assay and does not involve a human-in-the-loop interpretation for its primary function.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

The primary ground truth used was histology of biopsy samples, which is considered the "Gold Standard" by the FDA for the detection of Helicobacter pylori. Bacterial culture of biopsy samples is also mentioned as a "Gold Standard" method. The study also uses a legally marketed commercial enzyme immunoassay (IMMULITE® Helicobacter pylori IgG) as a comparative reference.

8. The sample size for the training set

The document does not provide information about a separate training set or its sample size. This is typical for a diagnostic kit submission, where development and internal validation (which might involve a "training" phase) are distinct from the clinical performance study reported for regulatory submission.

9. How the ground truth for the training set was established

Since a training set is not explicitly mentioned or detailed, the method for establishing its ground truth is not provided. The ground truth methods for the performance evaluation set are as described in point 7.

Summary

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DEC 1 3 2004

510(k) Summary

Please note that this 510(k) Summary follows the guidelines set forth in Title 21 (Food and Drugs), Chapter I (Food and Drug Administration Department of Health and Human Services), Subchapter H (Medical Devices), Part 807 (Establishment Registration and device Listing for Manufacturers and Initial Importers of Devices), Subpart E (Premarket Notification Procedures, Sec. 807.92 (Content and format of a 510(k) Summary).

(1)	Submitter's Name:	Biohit Plc.
	Address:	Laippatie 1, Fin-00880 Helsinki, Finland
	Phone Number:	800-922-0784
	Contact Person:	Robert P. Gearty, Director, U.S. Operations
	Date:	April 29, 2004

(2) Product and Trade Name

Helicobacter pylori IgG ELISA

Common Name or Classification Name

An ELISA kit for the qualitative detection of IgG class antibodies to Helicobacter pylori in human serum and EDTA or Heparin plasma. Product Code: LYR

Legally marketed device to which the submitter claims equivalence (3)

IMMULITE® Helicobacter pylori IgG, a two-step immunometric assay for the qualitative detection of IgG antibodies to Helicobacter pylori (Diagnostic Products Corporation (DPC - Los Angeles, CA) (K000463)

(4) Description of the device

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ELISA is highly sensitive for the detection of IgG antibodies to Helicobacter pvlori in serum or plasma samples.

Intended Use of the device (5)

The Helicobacter pylori IgG ELISA test is an enzyme-linked immunosorbent assay (ELISA) for the qualitative detection of human IgG class antibodies to Helicobacter pylori in serum and in EDTA or heparin-treated plasma. The test is intended to aid in the diagnosis of Helicobacter pylori infection in adult patients with clinical symptoms of gastritis. FOR IN VITRO DIAGNOSTIC USE.

(6a and 6b1) Summary of the technological characteristics of the device in comparison to those of the predicate device:

Commercial enzyme-linked immunosorbent assays (ELISAs) detecting anti-Helicobacter pylori serum IgG are available. These are the tests of choice due to ease of use, sensitivity, specificity and cost effectiveness. ELISAs also offer versatility with regard to the type of immunoglobulin detected (IgG vs IgA). Serum IgG assays are generally more sensitive and specific than serum IgA assays due to more consistent elevation of serum IgG levels (1). The IMMULITE® Helicobacter pylori IgG from Diagnostic Products Corporation was used as a predicate device in our evaluation of the Biohit device. A comparison of the predicate devices is presented in the following table:

Name	510(k)Numbers	Sample	Format	Materials	Advantages/Disadvantages
Helicobacterpylori IgGELISA	Subject tothis 510(k)	Serumand/orPlasma	ELISA	AntigenagainstHelicobacterpylori	Advantages - 90minute assay, easy touse, cost effective,batch method,sensitive and specificDisadvantages - maynot distinguish activefrom past infection
IMMULITE®Helicobacterpylori IgG	K000463	Serum	ChemiluminescentEIA	AntigenagainstHelicobacterpylori	Advantages - 65minute assayDisadvantages -requires aluminometer; maynot distinguish activefrom past infection

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(6b2) Safety and Effectiveness

Culture of the organism and/or histologic staining from a biopsy sample obtained at endoscopy is considered by the FDA to be the current "Gold Standard" for detection of Helicobacter pylori. Culture media for isolation of Helicobacter pylori from biopsy specimens and various histological stains are available from different sources. Biopsy/bacterial culture was used in clinical laboratories before 1976. Thus no 510(k) number is applicable.

Detecting the organism - Culture and/or Histological Staining from a gastric biopsy is considered by the FDA to be the "Gold Standard" for the detection of Helicobacter pylori. An invasive endoscopic procedure is required to obtain biopsy samples for the direct detection of Helicobacter pylori. Biopsy is expensive and subject to sampling errors. This invasive procedure also presents some risk to the patient. In comparison studies to the enzyme-linked immunosorbent (ELISA) assays from serum, there have been differences in results, due first of all to sampling errors. Additionally, if the H. pylori has been successfully eradicated from the stomach mucosa, the biopsy H. pylori result has been negative, but serological tests such as ELISA still exhibit the H. pylori antibodies titer positive for quite some time diminishing in 4-6 months into half of its original value.

Culture of a gastric biopsy sample requires the use of non-selective culture media supplemented with blood or serum and microaerophilic conditions. The culture isolates are then identified as Helicobacter pylori by morphology, cytochrome oxidase, catalase, and urease activities (1).

Histological Staining of a biopsy sample may be performed using a variety of stains that demonstrate the presence of Helicobacter pylori in histological specimens. These stains include, but are not limited to, Geimsa, Warthin-Starry silver stain, Acridine orange stain and hematoxylin-and-eosin stain (1).

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BacterialCulture ofbiopsy sample	Used before1976,510(k) notapplicable.	Gastricbiopsysample	Biopsy andculture	Non-selectivemediasupplementedwith serum orblood	Advantages - directdetection of theorganismDisadvantages -Invasive and biopsysampling is expensiveand places patients atsome risk, subject tosampling errors.
HistologicalStaining ofbiopsy sample	Used before1976,510(k) notapplicable.	Gastricbiopsysample	Biopsy andstain	Various stains	Advantages - directdetection of theorganism.Disadvantages -Invasive and biopsysampling is expensiveand places patients atsome risk, subject tosampling errors.

The Helicobacter pvlori IgG ELISA test was compared to clinical diagnosis by The Helicobacter pylori IgG ELISA test was also compared to a bionsv. commercially available enzyme immunoassay for Helicobacter pylori IgG. The results of our clinical evaluations show that the Helicobacter pylori IgG ELISA test exhibited a 77.6% agreement with biopsy and a 97.0% agreement with the commercial test. These results demonstrate that the test is useful for the detection of Helicobacter pylori IgG antibody in human serum and plasma samples.

(6b3) Conclusions demonstrating that the Biohit Helicobacter pylori IgG ELISA is as safe, as effective, and performs as well as or better than the legally marketed devices identified in (3):

The purpose of this study was to evaluate the Helicobacter pylori IgG ELISA developed by Biohit, Plc. Our evaluation demonstrates the following:

. The Helicobacter pylori IgG ELISA exhibits a sensitivity and specificity of 80.9% and 75.8%, respectively, when compared with histology, which is considered the "gold standard". The test demonstrates predictive positive and negative values of 64.6% and 87.9%, respectively, with an agreement of 77.6% when compared with histology. When compared with another commercial ELISA for H. pylori IgG, the test exhibited a sensitivity and specificity of 88.6% and 100%, respectively. The predictive positive and negative values were 100% and 96.2%, respectively, with an agreement of 97.0%.

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The Helicobacter pylori IgG ELISA is specific for Helicobacter pylori. The test . does not react with antigens from intestinal bacteria or with serum components including hemoglobin, bilirubin, and lipid.
The Helicobacter pylori IgG ELISA can be performed in 90 minutes, providing . the clinical laboratory with rapid and reliable results.
. The Helicobacter pylori IgG ELISA is an ELISA that can be used for batch processing large numbers of serum samples.

In summary, the Helicobacter pylori IgG ELISA represents a new ELISA test that detects Helicobacter pylori IgG in serum and plasma specimens. The test can be used an in vitro diagnostic aid for persons suspected of having H. pylori infections.

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Image /page/5/Picture/1 description: The image shows the seal of the Department of Health & Human Services USA. The seal features a stylized eagle with three stripes extending from its head, representing health, human services, and the USA. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" is arranged around the eagle in a circular fashion.

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

DEC 1 3 2004

Mr. Robert P. Gearty Managing Director Biohit Inc. 3535 Route 66, Bldg #4 P.O. Box 308 Neptune, NJ 07754-0308

K041238 Re:

Trade/Device Name: Helicobacter pylori IgG ELISA Test Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter Fetus Serological Reagents Regulatory Class: Class I Product Code: LYR Dated: November 23, 2004 Received: November 26, 2004

Dear Mr. Gearty:

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 for assumer in 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 Title 21, Code of Federal Regulations (CFR), Parts 800 to 895. 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); and good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820).

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Page 2

This letter will allow you to begin marketing your device as described in your Section 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 information about the application of labeling requirements to your device, or questions on the promotion and advertising of your device, please contact the Office of In Vitro Diagnostic Device Evaluation and Safety at (301) 594-3084. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). 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) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html.

Sincerely yours,

Salgado

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): K041238.

Device Name: Helicobacter Pylori IgG ELISA test kit.

Indications For Use:

Prescription Use (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)

Ludhi.boi.

Division Sign-Off

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Office of In Vitro Diagnostic Device Office of in and Safety

510(k) K041238

Regulation Number and Section

§ 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).