REMEL's Xpect™ Giardia/Cryptosporidium kit is an in vitro qualitative immunoassay for the detection of Giardia and Cryptosporidium antigens in preserved and unpreserved fecal specimens. This test is intended as an aid in the laboratory diagnosis of suspected Giardia and Cryptosporidium infections.

Device Description

The Xpect™ Giardia/Cryptosporidium Lateral Flow Assay is a chromatographic immunoassay that detects the presence of Giardia and Cryptosporidium antigens. The test utilizes sample wicking to capture Giardia and Cryptosporidium antigens on discrete test lines containing antigen-specific antibodies for each organism. A specimen is added to a dilution tube containing a buffered solution. A conjugate containing colored micro-particles linked to monoclonal antibodies specific for Giardia and Cryptosporidium is added. The mixture is dispensed into the sample well of the device and wicks across a membrane containing capture antibody stripes. The Giardia/Cryptosporidium immune complexes if present react with anti-Giardia antibody and/or anti-Cryptosporidium antibody at the test line. Conjugates not bound at the test lines are later captured at the control line containing anti-mouse antibody. A blue line will appear at the Giardia test position if Giardia antigen is present and a pink line will appear at the Cryptosporidium test position if Cryptosporidium antigen is present. A line in the Control position indicates that the test is working properly.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Remel Xpect™ Giardia/Cryptosporidium Lateral Flow Assay, based on the provided text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance (Giardia)	Reported Device Performance (Cryptosporidium)
Intended Use	Aid in laboratory diagnosis of suspected Giardia infections	Aid in laboratory diagnosis of suspected Cryptosporidium infections
Sensitivity (vs. Microscopy)	95.8% (95% CI: 89.8-98.4%)	96.4% (95% CI: 91.2-98.6%)
Specificity (vs. Microscopy)	98.5% (95% CI: 97.0-99.3%)	98.5% (95% CI: 96.9-99.3%)
Agreement (vs. Microscopy)	95.2% (139/146)	95.2% (139/146)
Cross-reactivity	No cross-reactivity observed with tested organisms	No cross-reactivity observed with tested organisms
Interfering Substances	No interference except for Imodium® A-D at 20% (v/v) interfering with low levels of Cryptosporidium antigen	No interference except for Imodium® A-D at 20% (v/v) interfering with low levels of Cryptosporidium antigen
Reproducibility	100% of 630 samples produced expected result	100% of 630 samples produced expected result

Study Information

2. Sample size used for the test set and the data provenance:

Giardia Test Set Sample Size:
- Sensitivity/Specificity vs. Microscopy: 577 total specimens (96 positive, 481 negative by microscopy).
- Percent Agreement vs. Microscopy: 146 specimens (21 positive, 125 negative by microscopy).
Cryptosporidium Test Set Sample Size:
- Sensitivity/Specificity vs. Microscopy: 577 total specimens (112 positive, 465 negative by microscopy).
- Percent Agreement vs. Microscopy: 146 specimens (30 positive, 116 negative by microscopy).
Data Provenance: The studies were conducted at "six geographically diverse laboratories" for the primary sensitivity/specificity comparison and in a side-by-side comparison with a predicate device. The text does not specify the country of origin but implies a multi-site clinical evaluation. The studies appear to be retrospective as they involve analyzing collected fecal specimens.

3. 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 microscopy. The document does not specify the number of experts or their qualifications (e.g., years of experience for the microscopists).

4. Adjudication method for the test set:

The document does not specify an adjudication method for disagreements in establishing the ground truth via microscopy. It is simply stated that performance was "compared to microscopy on a single specimen."

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:

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not done. This device is a lateral flow immunoassay not an AI-assisted diagnostic.

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

Yes, this device is a standalone test. The Xpect™ Giardia/Cryptosporidium Lateral Flow Assay is a qualitative immunoassay designed to provide a direct result (presence or absence of colored lines) without human interpretation beyond reading the lines.

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

The ground truth used was microscopy for the detection of Giardia and Cryptosporidium.

8. The sample size for the training set:

The document does not explicitly mention a training set sample size. As a lateral flow immunoassay, the device itself is not "trained" in the same way an AI algorithm would be. The development and optimization of such assays involve laboratory work and validation, but not a distinct "training set" in the context of machine learning. The studies described are performance evaluations.

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

As noted above, there is no explicit "training set" for an AI algorithm. The development of the immunoassay would have involved internal validation and optimization to ensure the antibodies and detection system worked as intended. The ground truth for such development would likely rely on known positive and negative control samples, potentially confirmed by gold standard methods like microscopy or PCR, to select optimal reagents and assay conditions. However, the provided text does not detail these developmental activities or their ground truth establishment.

Summary

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K031834

Remel Inc. Lenexa, KS 66215

510(k) Notification Xpect™ Giardia/Cryptosporidium Lateral Flow Assay

NOV 1 0 2003

510(k) Summary

The 510(k) summary is being submitted in accordance with the requirements of SMDA 1990 and 21 CFR §807.92.

Submitter's Identification:

Submitter's Name and Address:

Remel Inc. 12076 Santa Fe Drive Lenexa, KS 66215 (913) 895-4185

Richard L. Tyson, Ph.D. Contact: 1) Director Product Development and Support Ramsey Operations (763) 712-2347 rtyson@remel.com

1. Earleen C. Parks Regulatory Affairs Manager Lenexa, KS (913) 895-4185 eparks@remel.com

Date Summary Prepared: November 6, 2003

Device Trade Name:

Xpect™ Giardia/Cryptosporidium Lateral Flow Assay

Predicate Device:

Becton Dickinson ColorPAC™ Giardia/Cryptosporidium Rapid Assay, (k)983399.

Classification Name:

Entamoeba histolytica serological reagents. Cryptosporidium SPP 866.3220 Code: MHJ Giardia SPP 866.3220 Code: MHI

Intended Use:

Page 1 of 5 Section 4

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Device Description:

Comparison with Predicate Device:

The following information supports the Statement of Equivalence between the Becton Dickinson ColorPAC™ Giardia/Cryptosporidium Rapid Assay and the Xpect™ Giardia/Cryptosporidium Lateral Flow Assay. The differences in technology do not raise additional concerns regarding safety and effectiveness. Safety and effectiveness are demonstrated to be substantially equivalent.

ProductFeature	Becton Dickinson ColorPAC™Giardia/Cryptosporidium Rapid Assay	Xpect™ Giardia/Cryptosporidium LateralFlow Assay
IntendedUse	Detection of Giardia and Cryptosporidiumantigens in aqueous extracts of fecalspecimens	Detection of Giardia and Cryptosporidiumspecific antigens in fecal specimens
Technology	Qualitative immunochromatographic assay	Qualitative immunochromatographic assay
CaptureAntibodiesorMolecules:Device	Mouse anti-Cryptosporidium, goat anti-mouse IgG, Avidin derivative	Rabbit anti-Giardia, rabbit anti-Cryptosporidium, goat anti-mouse IgG
Antibodies:Conjugate	Rabbit anti-Giardia, monoclonal anti-Giardiaand Cryptosporidium	Monoclonal anti-Giardia andCryptosporidium
Material:Membrane	Nitrocellulose	Mylar-backed nitrocellulose
Material:Conjugate	Colloidal dye labeled monoclonal antibodiesto Giardia and Cryptosporidium	Anti-Giardia, anti-mouse, and anti-Cryptosporidium colored polystyreneparticles diluted in buffer
SpecimenType	Human stool preserved in 10% formalin,SAF, MIF or Cary Blair	Human stool preserved in 10% formalin,SAF or Cary Blair
Samplevolume	50μl	100μl

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Specimen Stability:

. Fresh, untreated stool specimens should be stored at 2-8°C and tested within 48 hours of collection. If fresh specimens cannot be tested within 48 hours. they should be frozen at -20°C or below in a non-defrosting freezer and tested within 2 months of collection. Avoid multiple freeze-thaw cycles.
Stool specimens treated with 10% formalin or SAF fixatives may be ● refrigerated at 2-8°C or stored at room temperature (20-25°C) and should be tested within 2 months of collection.
Stool specimens collected in modified Cary Blair Transport Medium with indicator (or equivalent) should be refrigerated and tested within 1 week of collection or frozen (as above) and tested within 2 months of collection. Avoid multiple freeze-thaw cycles.
. Stool specimens that have been concentrated or treated with PVA fixatives are not suitable for use with this test.

Sensitivity and Specificity Compared to Microscopy:

The performance of the Xpect™ Giardia/Cryptosporidium was evaluated at six geographically diverse laboratories. The overall sensitivity and specificity of the test was compared to microscopy on a single specimen. Performance relative to patients' clinical status has not been established. The overall sensitivity and specificity for Giardia and Cryptosporidium is listed below.

Giardia		Microscopy
		+	-
XpectTM	+	92	7
	-	4	474
	Total	96	481

Sensitivity: 95.8% (92/96); 95% CI = 89.8-98.4% Specificity: 98.5% (474/481); 95% CI = 97.0-99.3%

Cryptosporidium		Microscopy
		+	-
XpectTM	+	108	7
	-	4	458
	Total	112	465

Sensitivity: 96.4% (108/112); 95% CI = 91.2-98.6% Specificity: 98.5% (458/465); 95% CI = 96.9-99.3%

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Percent Agreement: Xpect™ & Predicate Device vs. Microscopy:

The Xpect™ Giardia/Cryptosporidium and a commercially available lateral flow test (the "Predicate Device") were compared side-by-side to microscopy. The Percent Agreement of each assay versus microscopy was as follows:

		Microscopy
Giardia		+	-
XpectTM	+	19	5
	-	2	120	Agreement95.2% (139/146)
	Total	21	125
Predicate	+	19	7
	-	2	118	Agreement93.8% (137/146)
	Total	21	125

		Microscopy
Cryptosporidium		+	-
XpectTM	+	28	5
	-	2	111	Agreement
	Total	30	116	95.2% (139/146)
Predicate	+	29	21
	-	1	95	Agreement
	Total	30	116	84.9% (124/146)

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Cross-reactivity:

No cross-reactivity was observed using samples containing the following organisms: Ascaris lumbricoides, Blastocystis hominis, Campylobacter coli, Campylobacter jejuni, Candida albicans, Chilomastix mesnili, Cyclospora cayetanensis, Dientamoeba fragilis, Endolimax nana, Entamoeba coli, Entamoeba hartmanni, Entamoeba histolytica, Enterobius vermicularis, Escherichia coli, hookworm, Hymenolepis nana, Iodamoeba bütschlii, Isospora sp., Microsporidia, Rotavirus, Salmonella choleraesuis subsp. choleraesuis serotype Typhimurium, Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Strongyloides stercoralis, Taenia sp., and Trichura. There was no crossreactivity of Giardia lamblia in the Cryptosporidium test area or of Cryptosporidium parvum in the Giardia test area. Cross-reactivity to Astrovirus and Caliciviruses has not been established.

Interfering Substances:

Prior to testing, positive and negative samples were spiked (20% v/v) with blood, mucin, fecal fat or the following over-the-counter anti-diarrheal products: Pepto-Bismol®, Imodium® A-D, and Kaopectate® (active ingredients: bismuth subsalicylate, loperamide HCl, and attapugite respectively). Testing indicated that none of these substances interfered with the expected result except for Imodium® A-D. Imodium® A-D at 20% (v/v) in stool interfered with the detection of low levels of Cryptosporidium antigen.

Reproducibility:

Reproducibility testing was conducted at seven sites, including one in-house site, on three separate days with ten blinded samples of varying activity. 100% of the 630 samples tested for Giardia and 630 samples tested for Cryptosporidium produced the expected result.

Conclusion:

Overall, the results from the clinical and POL investigation demonstrate that the Xpect™ Giardia/Cryptosporidium Lateral Flow Assay is substantially equivalent to microscopic examination and the Becton Dickinson ColorPAC™ Giardia/Cryptosporidium Rapid Assay when used in accordance with the proposed labeling.

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Image /page/5/Picture/1 description: The image shows the logo for the Department of Health & Human Services (CA). The logo consists of a stylized depiction of a bird in flight, composed of three curved lines that suggest feathers or wings. The bird is oriented towards the upper right. Encircling the bird is the text "DEPARTMENT OF HEALTH & HUMAN SERVICES (CA)" in a circular arrangement.

Public Health Service

Food and Drug Administration 2098 Gaither Road Rockville MD 20850

NOV 1 0 2003

Remel Inc. c/o Earleen C. Parks Regulatory Affairs Manager 12076 Santa Fe Drive Lenexa, KS 66215

Re: K031834

Trade/Device Name: Xpect™ Giardia/Cryptosporidium Lateral Flow Assay Regulation Number: 21 CFR 866.3220 Regulation Name: Entamoeba Histolytica Serological Reagents Regulatory Class: Class II Product Code: MHI, MHJ Dated: October 1, 2003 Received: October 3, 2003

Dear Ms. Parks:

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. Iisting 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). 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/cdrh/dsma/dsmamain.html.

Sincerely vours.

Steven Butman

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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INDICATIONS FOR USE

510(k) Number (if known):

Xpect™ Giardia/Cryptosporidium Device Name:

Indications For Use: REMEL's Xpect™ Giardia/Cryptosporidium kit is an in vitro qualitative immunoassay for the detection of Giardia and Cryptosporidium antigens in preserved and unpreserved fecal specimens. This test is intended as an aid in the laboratory diagnosis of suspected Giardia and Cryptosporidium infections.

(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)	✓
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Over-The-Counter Use
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Division Sign-Off
	Say
	4/10/03

Office of In Vitro Diagnostic Device
Evaluation and Safety

510(k)	K031834
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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.