The Trinity Biotech Captia™ H. pylori IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to Helicobacter pylori, as an aid in the diagnosis of H. pylori infection in adult patients with clinical signs and symptoms of gastrointestinal disease, and is not intended for use in asymptomatic patients.

Device Description

The H. pylori IgG ELISA kit is an Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to antigen. The Trinity Pylori IgG ELISA assay may be used as an aid in the diagnosis of Helicobacter pylori infection in persons with gastrointestinal symptoms. For In Vitro Diagnostic Use Only.

The H. pylori IgG ELISA test is an enzyme linked immunosorbent assay to detect IgG antibodies to Helicobacter pylori. Purified Helicobacter pylori antigen is attached to a solid phase microtiter well. Diluted test sera is added to each well. If the antibodies are present that recognize the antigen, they will bind to the antigen in the well. After incubation, the wells are washed to remove unbound antibody. An enzyme labeled anti-human IgG is added to each well. If antibody is present it will bind to the antibody attached to the antigen on the well. After incubation, the wells are washed to remove unbound conjugate. A substrate solution is added to each well. If enzyme is present, the substrate will undergo a color change. After an incubation period, the reaction is stopped and the color intensity is measured photometrically, producing an indirect measurement of specific antibody in the patient specimen.

AI/ML Overview

The provided document is a 510(k) premarket notification for the Trinity Biotech H. pylori IgG ELISA test kit. It describes the device, its predicate device, and performance characteristics, but does not explicitly state formal acceptance criteria. However, we can infer the performance targets based on the comparison to the predicate device and the presented results.

Here is an analysis based on the provided information:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria (Inferred)	Reported Device Performance (Trinity Biotech H. pylori IgG ELISA)
Sensitivity relative to biopsy: Comparable to predicate (98.5%)	96.4% (95% CI: 94.1% - 98.8%)
Specificity relative to biopsy: Comparable to predicate (98.1%)	96.1% (95% CI: 92.3% - 99.9%)
Agreement relative to biopsy: Comparable to predicate (98.4%)	96.4% (95% CI: 94.4% - 98.3%)
% Agreement positive relative to predicate: High agreement expected	99.2% (95% CI: 98.1% - 100%)
% Agreement negative relative to predicate: High agreement expected	97.0% (95% CI: 93.6% - 100%)
Overall % Agreement relative to predicate: High agreement expected	98.6% (95% CI: 97.3% - 99.8%)
Precision (Coefficient of Variation - CV): Low variability expected across intra- and inter-assays, generally below a certain threshold.	Ranges from 4.75% to 67.0% (intra-assay) and 6.06% to 38.8% (inter-assay)
Cross-Reactivity: No significant cross-reactivity with closely related organisms (C. jejuni, C. fetus, Borrelia burgdorferi).	No rise in antibody for C. jejuni paired sera, negative responses for C. fetus and Borrelia burgdorferi.

Note on Inferred Acceptance Criteria: The document primarily demonstrates substantial equivalence to "biopsy" (culture or stain) and to a predicate device (Pylori Stat). Therefore, the "acceptance criteria" are implicitly met if the performance characteristics are deemed substantially equivalent to these established methods. The exact numerical thresholds for acceptance are not explicitly listed, but the device's performance falling within the confidence intervals and showing high agreement suggests it met the unstated bar for equivalence.

Study Details

Sample size used for the test set and the data provenance:
- Pylori Stat (Predicate Device) Evaluation: 386 serum samples.
  - Data Provenance: From five geographically different areas.
  - Retrospective/Prospective: Not explicitly stated, but samples were "having biopsy with stain or culture results," suggesting a retrospective collection of samples with known outcomes.
- Trinity Biotech H. pylori IgG ELISA Evaluation: 371 serum samples.
  - Data Provenance: From five geographically different areas.
  - Retrospective/Prospective: Not explicitly stated, but samples were "having biopsy with stain or culture results," suggesting a retrospective collection of samples with known outcomes.
- Precision Test: Six different serum samples, each tested ten times over three days (total of 180 individual tests for CV calculation).
- Cross-Reactivity Test: Paired sera from 5 C. jejuni infections, 4 single sera from C. fetus infections, and 10 sera positive for Borrelia burgdorferi.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The ground truth for the test set was established by "biopsy with stain or culture results for H. pylori."
- The document does not specify the number of experts, their qualifications (e.g., pathologist, microbiologist), or the process involved in interpreting these biopsy/culture results.
Adjudication method for the test set:
- The document explicitly states that "Equivocals were not included in the above calculations" for sensitivity, specificity, and agreement calculations. This implies that any samples yielding "equivocal" results from the ELISA tests were excluded from the primary performance metrics. There is no mention of an adjudication process to re-classify these equivocal results or conflicting ground truth interpretations.
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:
- No, an MRMC comparative effectiveness study was not done. This report describes the performance of an in vitro diagnostic (IVD) ELISA kit, which is a laboratory test, not an AI-assisted diagnostic tool for human readers. Therefore, there is no "human readers improve with AI vs without AI assistance" component.
If a standalone (i.e. algorithm only without human-in-the loop performance) was done:
- Yes, a standalone performance study was done. The entire evaluation of the Trinity Biotech H. pylori IgG ELISA against biopsy and against the predicate device is a standalone performance assessment of the diagnostic kit itself, without human interpretation influencing the test result once the serum is processed by the ELISA method. The "interpretation" of the ELISA results (positive, negative, equivocal) is inherent to the kit's design and predetermined cut-offs.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The primary ground truth used was pathology in the form of "biopsy with stain or culture results for H. pylori."
- For cross-reactivity, ground truth for C. jejuni and C. fetus was established by "culture" (fecal culture on Campylobacter-specific media for C. jejuni, blood culture for C. fetus). For Borrelia burgdorferi, it was "positive for antibodies by ELISA and Western Blot."
The sample size for the training set:
- The document does not mention a training set in the context of an algorithm or machine learning model. This is an ELISA kit, which is a biochemical assay with established protocols and reagents. Its "training" is more akin to assay development and optimization, rather than a data-driven machine learning training phase. The described studies are performance validation studies.
How the ground truth for the training set was established:
- As there is no explicit training set in the context of an algorithm, this question is not applicable. The development and optimization of such a kit would rely on known positive and negative samples, but these are part of the assay development, not a "training set" with ground truth in the current sense of diagnostic AI.

Summary

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NOV 26 2003

K033067

Summary of Safety and Effectiveness Information H. pylori IgG ELISA Test Kit

I. Trinity Biotech 2823 Girts Road Jamestown, NY 14701 Contact person: Bonnie B. DeJoy Telephone: 716-483-3851 Date of preparation: Nov. 20, 2003

II. Description of Device

III. Predicate Device

The H. pylori IgG ELISA test is substantially equivalent to biopsy. Equivalence is demonstrated by the following comparative results:

Performance Characteristics

A. Evaluation of Pylori IgG ELISA Sensitivity and Specificity Relative to Biopsy

The Trinity Biotech H. pylori IgG ELISA is a modification of Pylori Stat. Pylori Stat was originally evaluated by masked testing 386 serum from five geographically different areas. having biopsy with stain or culture results for H. pylori. The serum were from patients with random gender and various ages with the following clinical diagnoses: gastric ulcer, duodenal ulcer, non-ulcer dyspepsia, esophagitis and normal. Table 1 illustrates the sensitivity and specificity of the Pylori Stat to biopsy.

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Table 1 Pylori Stat IgG ELISA Sensitivity and Specificity

		Pylori Stat
		+	eq	-	Total
biopsy*	+	261	12	4	277
	-	2	2	105	109
	Total	263	14	109	386
Sensitivity = 261/265 = 98.5%Specificity = 105/107 = 98.1%Agreement = 366/372 = 98.4%			95% Confidence interval = 97.0% - 100%95% Confidence interval = 95.5% - 100%95% Confidence interval = 97.1% - 99.7%

* Culture or stain

Equivocals were not included in the above calculations.

The 95% confidence intervals were calculated using the normal method.

The Trinity Biotech H. pylori IgG ELISA was evaluated by masked testing 371 serum from five geographically different areas, having biopsy with stain or culture results for H pvlori. The serum were from patients with random gender and various ages with the following clinical diagnoses: gastric ulcer, duodenal ulcer, non-ulcer dyspepsia, esophagitis and normal. Tables 2 and 3 illustrate the sensitivity and specificity of the Trinity Biotech H. pvlori IgG ELISA to biopsy and the % agreement positive and % agreement negative of the Trinity Biotech H. pylori IgG ELISA to Biowhittaker Pylori Stat.

Table 2 Trinity Biotech H. pylori IgG ELISA Sensitivity and Specificity

Trinity Biotech H. pylori IgG ELISA

	+	eq	-	Total
+	244	13	9	266
biopsy*	4	2	99	105
Total	248	15	108	371
Sensitivity = 244/253 = 96.4%95%Specificity = 99/103 = 96.1% 95%Agreement = 343/356 = 96.4%		Confidence Interval = 94.1% - 98.8%Confidence Interval = 92.3% - 99.9%95% Confidence Interval = 94.4% - 98.3%

Culture or stain

Equivocals were not included in the above calculations.

The 95% Confidence Intervals were calculated using the normal method.

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Evaluation of Pylori IgG ELISA % Agreement Positive and % Agreement Negative Relative to Biowhittaker Pylori Stat

Table3
------------

Trinity Biotech H. pylori IgG ELISA

		+	ed		Total
	+	246	8	2	256
	eq			6	12
BiowhittakerPylori Stat		ನ	ನ	97	103
	Total	250	16	102	371
01 1	:	A 1 C 10 10 00 /	Comment Comments of Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comments of Children Comment		10001

% Agreement positive = 246/248 = 99.2%	95% Confidence Interval = 98.1% - 100%
% Agreement negative = 97/100 = 97.0%	95% Confidence Interval = 93.6% - 100%
% Agreement = 343/348 = 98.6%	95% Confidence Interval = 97.3% - 99.8%

Equivocals were not included in the above calculations. The 95% Confidence Intervals were calculated using the normal method.

B. Precision

The precision of the Trinity Biotech H. pylori IgG ELISA was determined by testing six different sera ten times each on three days. The mean coefficients of variation from the intra- and inter- assays are presented in Table 6.

Table 4
Trinity Biotech H. pylori IgG ELISA Precision

Assay 1 (n=10)			Assay 2 (n=10)			Assay 3 (n=10)			Inter-Assay (n=30)
X	SD	CV	X	SD	CV	X	SD	CV	X	SD	CV
3.13	0.209	6.68%	3.05	0.145	4.75%	3.13	0.210	6.71%	3.10	0.188	6.06%
2.08	0.151	7.26%	2.15	0.156	7.26%	2.01	0.127	6.32%	2.08	0.151	7.26%
2.31	0.258	11.2%	2.29	0.115	5.02%	2.24	0.173	7.72%	2.28	0.187	8.20%
1.17	0.184	15.7%	1.47	0.148	10.1%	1.30	0.179	13.8%	1.31	0.207	15.8%
0.06	0.018	30.0%	0.12	0.014	11.7%	0.11	0.056	50.9%	0.08	0.031	38.8%
0.10	0.016	16.0%	0.14	0.020	14.3%	0.10	0.067	67.0%	0.12	0.023	19.2%

C. Cross Reactivity

The Trinity Biotech H. pylori IgG ELISA ISR values were determined for paired sera from C. jejuni infections and single sera from C. fetus infections. The data in Table 7 shows no rise in antibody for C. jejuni paired sera, and negative responses for C. fetus infections indicating a lack of cross reactivity to these closely related organisms. Serum pairs 1, 2 and 3 demonstrate antibody to H. pylori. However, the pairs do not show a rise in antibody as would be expected in acute C. jejuni infection. Therefore, the response is considered to be specific for H. pylori with no cross reaction with C. jejuni. Sera positive

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for Borrelia burgdorferi by ELISA and Western Blot were negative indicating a lack of cross-reactivity.

Serum #	Diagnosis*	H. pylori IgG ISR
Acute 1	C. jejuni Diarrhea	2.30
Convalescent 1		2.41
Acute 2	C. jejuni Diarrhea	2.11
Convalescent 2		2.23
Acute 3	C. jejuni Diarrhea	1.23
Convalescent 3		1.20
Acute 4	C. jejuni Diarrhea	0.40
Convalescent 4		0.57
Acute 5	C. jejuni Diarrhea	0.88
Convalescent 5		0.89
6.	C. fetus Endocarditis	0.59
7.	C. fetus Endocarditis	0.63
8.	C. fetus Endocarditis	0.72
9.	C. fetus Bacteremia	0.38

Table 5 Trinity Biotech H. nylori IgG ELISA Results with

*All cases diagnosed by culture; C. jejuni infection by fecal culture on Camplylobacterspecific media, C. fetus infection by blood culture.

10.	Borrelia burgdorferi	0.44
11.	Borrelia burgdorferi	0.20
12.	Borrelia burgdorferi	0.22
13.	Borrelia burgdorferi	0.89
14.	Borrelia burgdorferi	0.11
15.	Borrelia burgdorferi	0.20
16.	Borrelia burgdorferi	0.16
17.	Borrelia burgdorferi	0.59
18.	Borrelia burgdorferi	0.09
19.	Borrelia burgdorferi	0.13

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All Borrelia burgdorferi sera were positive for antibodies by ELISA and Western Blot.
Their clinical histories were suggestive of Lyme Disease.

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Image /page/5/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 a staff with a serpent entwined around it, and three 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

NOV 26 2003

Ms. Bonnie B. DeJoy Director, Quality Systems Trinity Biotech USA P.O. Box 1059 Jamestown, NY 14702-1059

K033067 Trade/Device Name: Captia H. Pylori IgG ELISA Regulation Number: 21 CFR 866.3110 Regulation Name: Campylobacter fetus serological reagents Regulatory Class: Class I Product Code: LYR Dated: September 17, 2003 Received: September 29, 2003

Dear Ms. DeJoy:

Re:

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 vour 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,

Steven Sutman

Steven I. Gutman, M.D., M.B.A. Director Office of In Vitro Diagnostic Device Evaluation and Safety Center for Devices and Radiological Health

Enclosure

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Page 1 of 1

510(k) Number: K033067

Device Name: Trinity Biotech Captia™ H. pylori IgG ELISA

The Trinity Biotech Captia™ H. pylori IgG ELISA kit is an Indications For Use: Enzyme-Linked Immunosorbent Assay (ELISA) for the qualitative determination of IgG antibodies in human serum to Helicobacter pylori, as an aid in the diagnosis of H. pylori infection in adult patients with clinical signs and symptoms of gastrointestinal disease, and is not intended for use in asymptomatic patients.

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 XFR 801.109)

Over-The-Counter Use
(Optional Format 1-2-96)

Division Sign-Off
for FMP

Office of In Vitro Diagnostic Device
Evaluation and Safety

510(k) Ro33067

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).