The IVD Research, Inc. Giardia Fecal Antigen Detection Lateral Flow Kit is a qualitative immunoassay for the detection of Giardia antigens in preserved and unpreserved human fecal specimens. This test is indicated as an aid in the clinical laboratory diagnosis of suspected Giardia infections. For in vitro diagnostic use.

Device Description

The IVD Research, Inc. Giardia Fecal Antigen Detection Lateral Flow Kit is an immunochromatographic assay for the detection of Giardia lamblia antigen in human fecal samples. The test uses sample wicking to capture Giardia antigen on a discrete test line containing antibodies specific for Giardia antigen. A specimen is added to a dilution tube and mixed with a buffer solution. The mixture is dispensed into the sample well of the device which resolubilizes the Giardia specific mouse monoclonal antibody that has been conjugated to colored microparticles. This solution wicks along a membrane containing capture antibodies bound to the membrane at the Test and Control lines. The Giardia immune complex, if present, reacts with antibody at the Test line. Unbound conjugate not captured at the test line is captured at the Control line containing anti-mouse antibody. If Giardia antigens are present in the fecal sample, two pink-to-purple bands (one at the Sample line and one at the Control line) will appear in the test window. If no Giardia antigen is present, or if the level of antigen is below the detection limit of the assay, only one pink-to-purple band at the Control line will appear in the test window. For the test to be valid, a pink-to-purple band must always appear at the Control line position of the device test window regardless of whether the sample is positive or negative. This Control line indicates that the test is working properly.

AI/ML Overview

Acceptance Criteria and Study for IVD Research, Inc. Giardia Fecal Antigen Detection Lateral Flow Kit

This response will detail the acceptance criteria and the study performance for the Giardia Fecal Antigen Detection Lateral Flow Kit, as extracted from the provided 510(k) Pre-market Notification.

1. Table of Acceptance Criteria and Reported Device Performance

The provided document does not explicitly state pre-defined acceptance criteria in terms of numerical thresholds for sensitivity and specificity. Instead, the "acceptance" is implied through a comparison to a predicate device and a reference method, aiming for "substantial equivalence" and acceptable clinical performance.

Performance Metric	Acceptance Criteria (Implied)	Reported Device Performance
Sensitivity	Substantially equivalent to predicate device and reference method	97.2% (106/109) [95% CI = 92.2% to 99.4%]
Specificity	Substantially equivalent to predicate device and reference method	96% (97/101) [95% CI = 90.2% to 98.9%]
Reproducibility	100% agreement with expected results	100% (54/54 positive, 36/36 negative)
Analytical Sensitivity (LOD)	A detectable limit suitable for clinical diagnosis	20 ng/ml
Analytical Specificity/Cross-reactivity	No cross-reactivity with common related organisms/substances	No cross-reactivity observed with tested organisms/substances. No interference with blood, mucin, Imodium®.
Percent Positive Agreement (vs. Predicate)	High agreement with predicate device (Xpect™ Giardia Lateral Flow Assay)	98% (48/49)
Percent Negative Agreement (vs. Predicate)	High agreement with predicate device (Xpect™ Giardia Lateral Flow Assay)	100% (61/61)

2. Sample Size Used for the Test Set and Data Provenance

Clinical Performance Study:
- Sample Size: A total of 210 human fecal specimens were used.
- Data Provenance: Retrospective. The samples were "well-characterized, archived samples" collected in 10% formalin or SAF. They were submitted to an independent laboratory for testing. The country of origin is not specified but is implicitly the US given the FDA submission.
Unpreserved Fecal Specimens Study:
- Sample Size: 42 unpreserved fecal samples (15 positive, 27 negative)
- Data Provenance: Retrospective. These samples were from IVD Research's frozen sample bank, stored at -15℃ or lower. The country of origin is implicitly the US.
Reproducibility Study:
- Sample Size: A masked panel of ten samples (number of positive/negative not specified, but 6 positive and 4 negative in the summary table). These were tested repeatedly.
- Data Provenance: Not explicitly stated, but performed at three sites (one internal, two external), suggesting a multi-center study, likely within the US.
Predicate Device Comparison Study:
- Sample Size: Total of 110 samples (49 positive by predicate, 61 negative by predicate).
- Data Provenance: Not explicitly stated, but implies existing samples were used for comparison.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications

Clinical Performance Study (Reference Method: Microscopy or Direct Immunofluorescence Assay): The document does not specify the number of experts or their qualifications for establishing the ground truth using microscopy or direct immunofluorescence assay. It states that the specimens were "submitted to an independent laboratory for testing," implying expertise within that laboratory. For the 4 false positives, these were "re-tested using a direct immunofluorescence assay and shown to be positive," suggesting a re-evaluation by an expert or a highly sensitive method.
Unpreserved Fecal Specimens Study (Reference Method: Giardia lamblia Antigen Detection Microwell ELISA): The ground truth was established by another IVD Research, Inc. product, the Giardia lamblia Antigen Detection Microwell ELISA. No human experts are explicitly mentioned for this ground truth establishment, as it is an automated assay.

4. Adjudication Method for the Test Set

The document does not explicitly describe an adjudication method for reconciling discrepancies for the primary clinical performance test set. For the "false positive" samples identified with the Giardia LF test (4 cases), they were "re-tested using a direct immunofluorescence assay and shown to be positive," which implies a secondary, definitive reference method was used to adjudicate these discrepancies and re-classify them as true positives. For the comparison with the predicate device, the agreement was calculated directly, without mention of an adjudication process for discordant results.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No MRMC comparative effectiveness study was mentioned. The device is a Lateral Flow Kit, which generally involves visual interpretation by a single user, not an AI or human reader improvement scenario.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

This information is not applicable. The device is a Lateral Flow Kit, which is a diagnostic assay that provides a visual result (bands) requiring human interpretation, not an algorithm running independently.

7. Type of Ground Truth Used for Clinical Performance

Clinical Performance Study: The ground truth was established by "Microscopy or Direct Immunofluorescence Assay." This represents an expert-determined or highly sensitive laboratory reference method, likely considered the gold standard for clinical diagnosis of Giardia at the time.
Unpreserved Fecal Specimens Study: The ground truth was established by a Giardia lamblia Antigen Detection Microwell ELISA (IVD Research, Inc.). This is a laboratory assay serving as the reference.

8. Sample Size for the Training Set

The document does not provide information about a "training set" in the context of an algorithm or machine learning model. The studies described are performance evaluations of the completed device. For IVD diagnostic kits, development typically involves internal analytical studies and optimization, rather than a distinct "training set" as understood in AI/ML.

9. How the Ground Truth for the Training Set Was Established

As there is no explicit mention of a "training set" or a machine learning algorithm, this question is not applicable to the provided information.

Summary

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IVD Research, Inc. Premarket Notification 510(k) - Giardia Fecal Antigen Detection Lateral Flow Kit

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Korioby

JAN 1 4 2009

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Section 5

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510(k) Summary

Section 5 Page 1 of 6

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IVD Research, Inc. Premarket Notification 510(k) - Giardia Fecal Antigen Detection Lateral Flow Kit

510(k) Summary

This 510(k) summary is submitted in accordance with 21 CFR §807.92.

Owner:	IVD Research, Inc.5909 Sea Lion Place, Suite DCarlsbad, CA 92010 USATelephone: 760-929-7744; Fax 760-431-7759Contact: Dave Lambillotte, President
Prepared:	April 12, 2008
Trade name:	IVD Research, Inc. Giardia Fecal Antigen DetectionLateral Flow Kit
Common name:	Giardia Fecal Antigen Detection Lateral Flow Kit
Classification name:	Entamoeba histolytica serological reagents(21 CFR §866.3220; Product Code: MHI)
Predicate device:	Xpect™ Giardia Lateral Flow Assay, K031942

Device description:

The IVD Research, Inc. Giardia Fecal Antigen Detection Lateral Flow Kit is an immunochromatographic assay for the detection of Giardia lamblia antigen in human fecal samples. The test uses sample wicking to capture Giardia antigen on a discrete test line containing antibodies specific for Giardia antigen. A specimen is added to a dilution tube and mixed with a buffer solution. The mixture is dispensed into the sample well of the device which resolubilizes the Giardia specific mouse monoclonal antibody that has been conjugated to colored microparticles. This solution wicks along a membrane containing capture antibodies bound to the membrane at the Test and Control lines. The Giardia immune complex, if present, reacts with antibody at the Test line. Unbound conjugate not captured at the test line is captured at the Control line containing anti-mouse antibody. If Giardia antigens are present in the fecal sample, two pink-topurple bands (one at the Sample line and one at the Control line) will appear in the test window. If no Giardia antigen is present, or if the level of antigen is below the detection limit of the assay, only one pink-to-purple band at the Control line will appear in the test window. For the test to be valid, a pink-to-purple band must always appear at the Control line position of the device test window regardless of whether the sample is positive or negative. This Control line indicates that the test is working properly.

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Intended use:

Comparison with the predicate device:

The technological characteristics of the IVD Research Inc. Giardia Fecal Antigen Detection Lateral Flow Kit are compared with the Xpect™ Giardia Lateral Flow Assay (K031942) in the table below. This comparison demonstrates the substantial equivalence of this device to the predicate device. The devices are similar in intended use, assay technology and materials used to construct the test strip, and both devices use the same Giardia specific monoclonal antibodies for the conjugate. Both devices have similar clinical performance. Differences between the two devices in the sample size and materials used in the membrane are minimal.

Item	IVD Research, Inc. Giardia FecalAntigen Detection Lateral Flow Kit(Device)	Xpect™ Giardia Lateral Flow Assay(K031942)(Predicate)
	Similarities
Intended Use	Detection of Giardia antigens infecal specimens.	Detection of Giardia antigens in fecalspecimens.
Technology	Qualitative immunochromatographicassay.	Qualitative immunochromatographicassay.
Capture antibodies ormolecules	Rabbit anti-Giardia and goat anti-mouse IgG.	Rabbit anti-Giardia and goat anti-mouse IgG.
Material: Membrane	Mylar-backed nitrocellulose.	Mylar-backed nitrocellulose.
	Differences
Antibodies: Conjugate	Monoclonal anti-Giardia.	Monoclonal anti-Giardia and normalmouse IgG.
Material: Conjugate	Colloidal gold labeled monoclonalantibody to Giardia.	Anti-Giardia and mouse IgG coloredpolystyrene particles diluted in buffer.
Specimen Type	Human stool preserved in 10%formalin or SAF.	Human stool preserved in 10%formalin, SAF or Cary Blair.
Sample Volume	50 uL	100 uL

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Reproducibility:

Reproducibility testing was performed at three sites (one internal; two external) using a masked panel of ten samples of varying reactivity tested over three days along with positive and negative contols. All samples tested for Giardia produced the expected result, as summarized in the table below.

	No. Positivesamples tested	No. Negativesamples tested	Total results		PercentReproducibilityObtained
Number of tests(sites x test occasions)			NumberExpected	NumberObtained
9	6		54	54	100
9		4	36	36	100

Analytical Sensitivity:

Analytical sensitivity was determined by diluting cultured Giardia lamblia (WB strain) in negative human stool and testing across an antigen concentration range of 2.5 ng/mL to 80 ng/mL. Test results determined the limit of detection for the device to be 20 ng/ml.

Analytical Specificity/cross-reactivity/interfering substances:

No cross-reactivity was observed using samples containing the following organisms: Entamoeba hartmanni, Endolimax nana, Entamoeba histolytica/dispar, Entamoeba coli, Blastocystis hominis, Dientamoeba fragilis, Chilomastix mesnili, Cyclospora cavetanensis. Strongyloides stercoralis, Cryptosporidium, Ascaris lumbricoides, Enterobius vermicularis. Diphyllobothrium species. Hymenolepis nana, Clonorchis sinensis. Enteromonas hominis, Trichuris trichiura, Iodamoeba buetschlii, Schistosoma mansoni, rotavirus, Taenia eggs, Fasciola eggs, Isospora belli, adenovirus, rotavirus and twenty-two (22) bacterial species (Salmonella typhimurium, Proteus vulgaris, E. coli 43887, Campylobacter coli, Salmonella enteritidis, Campylobacter fetus, Staphylococcus aureus. Pseudomonas aeruginosa, Klebsiella pneumoniae, Serratia liquefaciens, Enterobacter cloacae, Citrobacter braakii, Shigella flexneri, Shigella sonneii, Shigella dysenteria, E. hermanii, Campylobacter jejuni, Salmonella hadar, Salmonella infantis, Yersinia enterocolitica, Enterococcus fecalis, Helicobacter cinaedi). Additionally, six common microorganisms (Campylobacter coli, E. coli, Salmonella enteritidis, Shigella flexneri, Campylobacter jejuni, Yersinia enetrocolitica) spiked into preserved positive and negative fecal specimens did not affect the test result.

Human feces samples positive and negative for Giardia antigen were spiked with blood, mucin, or Imodium® prior to testing with the Giardia Fecal Antigen Detection Lateral Flow Kit. Testing indicated that none of these substances interfered with the test.

Specimen stability:

Assay performance in preserved specimen types claimed in the labeling was verified during assay development using specimens from an internal QC bank as follows: fifteen positive samples preserved in either 10% formalin or sodium acetate-acetic acid-formalin

Section 5 Page 4 of 6

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IVD Research, Inc. Premarket Notification 510(k) - Giardia Fecal Antigen Detection Lateral Flow Kit

(SAF) with a maximum age of 7 years; twenty-three 10% formalin/SAF negative samples (maximum age 18 months); three fresh-frozen, un-preserved samples (2 positive; 1 negative) approximately 10 years old which had undergone numerous freeze/thaw cycles; and eleven fresh negative samples that had undergone three freeze/thaw cycles. All samples gave the expected result when tested according to the assay procedure.

Unpreserved Fecal Specimens

Assay performance in unpreserved specimens was verified using a total of 42 unpreserved samples fecal samples that were positive for antigens of Giardia lamblia as determined by a non-lateral flow methodology (Giardia lamblia Antigen Detection Microwell ELISA, IVD Research, Inc.). Fifteen of these samples tested positive in the ELISA test and 27 tested negative in the ELISA. All 15 of the positive samples and 20 of the negative samples were part of IVD Research's frozen sample bank and are stored at -15℃ or lower.

The results summarized below demonstrate that the IVD Research Giardia Fecal Antigen Detection Lateral Flow Kit produces acceptable test results when samples are unpreserved.

	ELISA +	ELISA -
LF +	15	0
LF -	0	27

Sensitivity: 100% 95% CI = 78.2% to 100% Specificity: 100% 95% CI = 87.2% to 100%

Specimen collection/preparation/stability:

Fresh, unpreserved stool samples should be stored at 2℃ - 8℃ and tested within 24 hours of collection. Samples that cannot be tested within this time should be frozen at -15°C to -25°C until use.

Stool specimens preserved in 10% formalin or SAF may be kept at room temperature (15℃ - 25℃) and tested within 18 months of collection.

Do not freeze preserved specimens.

Do not concentrate stool specimens. The assay will not give accurate results on a concentrated sample.

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Clinical performance:

The performance of the Giardia Fecal Antigen Detection Lateral Flow Kit was determined in retrospective studies using well-characterized, archived samples. Performance relative to patients' clinical status has not been established.

1. Sensitivity and Specificity Compared to Microscopy or Direct Immunofluorescence Assay

Clinical performance was evaluated using a total of 210 human fecal specimens collected in 10% formalin or SAF and submitted to an independent laboratory for testing with the Giardia Fecal Antigen Detection Lateral Flow Kit. The following results were obtained.

	Ref +	Ref -
LF +	106	4
LF -	3	97

Sensitivity: 97.2% (106/109) 95% CI = 92,2% to 99.4% Specificity: 96% (97/101) 95% CI = 90.2% to 98.9%

Four "negative" specimens gave a false positive result when tested with the Giardia LF test. These samples were re-tested using a direct immunofluorescence assay and shown to be positive.

2. Percent Agreement vs. Predicate Device

The Percent Agreement of the IVD Research, Inc. Giardia Fecal Antigen Detection Lateral Flow Kit versus the predicate device was as follows:

	Remel Xpect®	Remel Xpect®
LF +	48	0
LF -	1	61

98% (48/49) Positive Agreement Negative Agreement 100% (61/61)

The results of the bench and clinical performance testing demonstrate that the IVD Research Inc., Giardia Fecal Antigen Detection Lateral Flow Kit is substantially equivalent in performance to the predicate device and to microscopic examination for the detection of Giardia in human fecal specimens.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/6/Picture/1 description: The image shows the seal of the U.S. Department of Health and Human Services. The seal features a stylized eagle with three legs, representing the department's mission to protect the health of all Americans and provide essential human services. The seal is surrounded by the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" in a circular arrangement. The image is in black and white.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

IVD Research, Inc. c/o Mr. Michael Wienholt Regulatory Consulting, LLC 5470 E. Edwin Road Tucson. AZ 85739

JAN 1 4 2009

Re: K081064

Trade/Device Name: Giardia Fecal Antigen Detection Lateral Flow Kit Regulation Number: 21 CFR 866.3220 Regulation Name: Entamoeba histolytica serological reagents. Regulatory Class: Class II Product Code: MHI Dated: December 30, 2008 Received: December 31, 2008

Dear Mr. Wienholt:

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 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 (240)276-0484. 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/industry/support/index.html

Sincerely yours,

Sale, a Form

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 Statement

510(k) Number (if known): K081064

Giardia Fecal Antigen Detection Lateral Flow Kit Device Name:

Indications for Use:

Prescription Use V (21 CFR Part 801 Subpart D) And/Or

Over the Counter Use (21 CFR Part 801 Subpart C)

(PLEASE DO NOT WRITE BELOW THIS LINE; CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of In Vitro Diagnostic Device Evaluation and Safety (OVD)

Andrew Stone

Division Sign-Off Office of In Vitro Diagnostic Device Evaluation and Safety

510(k) K081064

Regulation Number and Section

§ 866.3220

Entamoeba histolytica serological reagents.(a)
Identification. Entamoeba histolytica serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies toEntamoeba histolytica in serum. Additionally, some of these reagents consist of antisera conjugated with a fluorescent dye (immunofluorescent reagents) used to identifyEntamoeba histolytica directly from clinical specimens. The identification aids in the diagnosis of amebiasis caused by the microscopic protozoan parasiteEntamoeba histolytica and provides epidemiological information on diseases caused by this parasite. The parasite may invade the skin, liver, intestines, lungs, and diaphragm, causing disease conditions such as indolent ulcers, an amebic hepatitis, amebic dysentery, and pulmonary lesions.(b)
Classification. Class II (special controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.