(127 days)
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test is an enzyme immunoassay for the qualitative detection of Giardia cyst and Cryptosporidium oocyst antigen in human fecal specimens. It is indicated for use as an aid in the diagnosis of patients with diarrhea suspected of Giardia and/or Cryptosporidium gastrointestinal infections.
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test uses monoclonal and polyclonal antibodies to cell-surface antigens of Giardia and an oocyst antigen of Cryptosporidium. The Microassay Plate in the kit contains immobilized monoclonal antibodies against the antigens and the Conjugate consists of polyclonal antibodies against the antigens. In the assay, an aliquot of a diluted fecal specimen is transferred to a microassay well. The immobilized monoclonal antibodies bind the Giardia and Cryptosporidium antigens if the antigens are present. Upon addition, Conjugate then binds to the antigen/antibody complex. Any unbound materials are removed during the washing steps. Following the addition of substrate, a color is detected due to the enzyme-antibody-antigen complexes that formed in the presence of Giardia or Cryptosporidium antigens and Conjugate.
Here's a summary of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state pre-defined acceptance criteria in terms of clinical performance thresholds. Instead, it presents the device's performance in comparison to predicate devices (ELISA) and microscopy. The implication is that the performance must be demonstrably comparable or superior to these established methods.
Here's the reported device performance:
| Performance Metric | Target/Comparison | Reported Device Performance (GIARDIA/CRYPTOSPORIDIUM CHEK™) |
|---|---|---|
| Comparison to Commercial ELISA | Agreement with ProSpecT® Giardia/Cryptosporidium Microplate Assay | |
| Positive Agreement | - | 98.6% (95% CI: 96.2% - 99.6%) |
| Negative Agreement | - | 98.7% (95% CI: 96.4% - 99.6%) |
| Overall Agreement | - | 98.6% (95% CI: 98.4% - 98.8%) |
| Comparison to Microscopy (IFA-confirmed) | Performance against Microscopic Analysis | |
| Sensitivity | - | 97.6% (95% CI: 92.6% - 99.4%) |
| Specificity | - | 100% (95% CI: 95.1% - 100%) |
| Predictive Positive Value | - | 100% (95% CI: 96.2% - 100%) |
| Predictive Negative Value | - | 96.9% (95% CI: 90.5% - 99.2%) |
| Correlation | - | 98.6% (95% CI: 98.2% - 98.9%) |
| Reproducibility | Consistent results across labs and trials | 100% correlation across 3 sites and 3 trials |
| Analytical Sensitivity | Detection limit for Giardia cysts and Cryptosporidium oocysts | 375 Giardia cysts/mL, 6250 Cryptosporidium oocysts/mL |
| Analytical Specificity | No cross-reactivity with common intestinal pathogens | No cross-reactivity observed |
| Interfering Substances | No effect on assay performance at tested concentrations | No effect on positive or negative results |
2. Sample Size Used for the Test Set and Data Provenance
- Sample Size (Clinical Evaluation compared to ELISA): n = 590 fecal specimens.
- Sample Size (Clinical Evaluation compared to Microscopy): n = 217 fecal specimens.
- Data Provenance: The samples were collected from "three clinical study sites" (Table 1) and specifically "Site 1" for the microscopy comparison (Table 2). The country of origin is not explicitly stated, but the submission is to the U.S. FDA, suggesting the studies were likely conducted in the U.S. The data appears to be prospective clinical evaluation data, as it describes "clinical evaluations" and samples "used in the clinical evaluation of the test."
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
The document does not specify the number of experts or their qualifications for establishing the ground truth.
- For the comparison to the commercially available ELISA (ProSpecT® Giardia/Cryptosporidium Microplate Assay), the ELISA itself served as a reference.
- For the comparison to microscopy, the ground truth was established by "IFA-confirmed microscopy results." The individuals performing or confirming these IFA microscopy results are not described.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method. The comparisons are made directly against the results of the reference methods (commercial ELISA or IFA-confirmed microscopy).
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
This device is an enzyme immunoassay (ELISA), not an AI-powered image analysis or diagnostic tool that involves human readers interpreting results with or without AI assistance. Therefore, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study of human readers with AI assistance is not applicable and was not performed.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) was done
Yes, the studies presented are for the device (GIARDIA/CRYPTOSPORIDIUM CHEK™) in a standalone capacity. The device itself performs the qualitative detection of antigens. The performance metrics (sensitivity, specificity, agreement) are for the assay's ability to detect the target antigens directly, without explicit human-in-the-loop interpretation that would significantly alter its performance.
7. The Type of Ground Truth Used (expert consensus, pathology, outcomes data, etc.)
The ground truth for the clinical evaluations was established by:
- Predicate Device Performance: Comparison to a "commercially available ELISA" (ProSpecT® Giardia/Cryptosporidium Microplate Assay) which itself is an established diagnostic method.
- IFA-Confirmed Microscopy: This is a laboratory diagnostic method where trained personnel visualize parasites in samples, and the "IFA-confirmed" implies an additional, highly specific immunological staining technique to confirm the identity of Giardia cysts and Cryptosporidium oocysts. This can be considered a form of expert-driven laboratory confirmation.
8. The Sample Size for the Training Set
This document describes a diagnostic test kit (ELISA), not a machine learning or AI algorithm. Therefore, the concept of a "training set" in the context of AI development is not applicable. The device's components (antibodies, reagents) are developed and optimized through laboratory research, but not via training on a data set in the same manner as an AI model.
9. How the Ground Truth for the Training Set Was Established
As noted above, the concept of a "training set" is not applicable for this type of device. The ground truth for the analytical studies (sensitivity, specificity, cross-reactivity) was established using known positive and negative controls, spiked samples with quantified antigen levels, and samples positive for other specific pathogens.
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7. 510(k) SUMMARY
NOV 1 7 2005
| Contact Information | David M. LyerlyVice-President, Research & DevelopmentTECHLAB®, Inc.2001 Kraft DriveCorporate Research CenterBlacksburg, VA 24060-6364Phone: 540-953-1664FAX: 540-953-1665Email: dlyerly@techlab.com | |
|---|---|---|
| Date Prepared | July 12, 2005 | |
| Product and Trade Name | GIARDIA/CRYPTOSPORIDIUM CHEKTM | |
| Classification | Giardia spp.21 CFR 866.3220 | Product Code: MHI |
| Cryptosporidium spp.21 CFR 866.3220 | Product Code: MHJ | |
| Predicate Devices | ProSpecT® Giardia/Cryptosporidium Microplate AssayRemel (Lenexa, KS - formerly Alexon Biomedical, Inc.)K955157MerifluorTM Cryptosporidium / Giardia KitMeridian Diagnostics (Cincinnati, Ohio) |
Intended Use
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test is an enzyme immunoassay for the qualitative detection of Giardia cyst and Cryptosporidium oocyst antigen in buman fer al specimens. It is indicated for use as an aid in the diagnosis of patients with diaman tour .
Clearly and and and Giardia and/or Cryptosporidium gastrointestinal infections.
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Device Description
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test uses monoclonal and polyclonal antibodies to cell-surface antigens of Giardia and an oocyst antigen of Cryptosporidium. The Microassay Plate in the kit contains immobilized monoclonal antibodies against the antigens and the Conjugate consists of polyclonal antibodies against the antigens. In the assay, an aliquot of a diluted fecal specimen is transferred to a microassay well. The immobilized monoclonal antibodies bind the Giardia and Cryptosporidium antigens if the antigens are present. Upon addition, Conjugate then binds to the antigen/antibody complex. Any unbound materials are removed during the washing steps. Following the addition of substrate, a color is detected due to the enzyme-antibody-antigen complexes that formed in the presence of Giardia or Cryptosporidium antigens and Conjugate.
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| Kit Name | 510(k)Numbers | Intended Use | Format | Materials | TargetPopulation |
|---|---|---|---|---|---|
| GIARDIA/CRYPTOSPORIDIUMCHEKTM | Subject tothis 510(k) | Detection ofGiardia cyst andCryptosporidiumoocyst antigen infecal specimens | ELISA | Highly specificantibodies againstGiardia andCryptosporidium | Persons suspectedof having GiardiaOTCryptosporidiuminfection |
| Microscopy | N/A | Direct detection ofGiardia cysts andCryptosporidiumoocysts in fecalspecimens | Microscopy | Various Stains | Persons suspectedof having GiardiaorCryptosporidiuminfection |
| ProSpecT® Giardia/CryptosporidiumMicroplate Assay | K955157 | Detection ofGiardia cyst andCryptosporidiumoocyst antigen infecal specimens | ELISA | Highly specificantibodies againstGiardia andCryptosporidium | Persons suspectedof having GiardiaorCryptosporidiuminfection |
| Merifluor™Cryptosporidium/Giardia Kit | K912408 | Direct detection ofGiardia cysts andCryptosporidiumoocysts in fecalspecimens | DFA -Immuno-fluorescence | Highly specificantibodies againstGiardia andCryptosporidium | Persons suspectedof having GiardiaOrCryptosporidiuminfection |
7.1 Comparative Information of Equivalent Devices
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7.2 Summary of Performance Data
Summary of Clinical Evaluations 7.2.1
Tables 1 and 2 display the comparison of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test to a commercially available ELISA and to microscopy. Results are compiled from the three clinical study sites and include all samples used in the clinical evaluation of the test.
Table 1 displays the comparison of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test to a commercially available ELISA and to microscopy from all three test sites. The results show that, compared to a commercially available ELISA, the GIARDIA/CRYPTOSPORIDIUM CHEK™ test exhibited 98.6% agreement for positive specimens, 98.7% agreement for negative specimens, and 98.6% agreement overall.
Table 2 displays the comparison of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test to IFA-confirmed microscopy results from Site 1. The results show that, compared to microscopic analysis, the GIARDIA/CRYPTOSPORIDIUM CHEK™ test exhibited 97.6% sensitivity, 100% specificity, and 98.6% correlation.
| TABLE 1: SUMMARY OF ALL STUDIESGIARDIA/CRYPTOSPORIDIUM CHEK™Comparison to a commercially available ELISA(n = 590) | ProSpecT® Giardia/CryptosporidiumMicroplate Assay | |||
|---|---|---|---|---|
| Positive | Negative | Total | ||
| GIARDIA/CRYPTOSPORIDIUM CHEK™ | Positive | 283 | 4 | 287 |
| TECHLAB®, Inc. | Negative | 4 | 299 | 303 |
| Total | 287 | 303 | 590 |
| GIARDIA/CRYPTOSPORIDIUM CHEK™vs. ProSpecT® Giardia/CryptosporidiumMicroplate Assay | PercentAgreement | 95%Confidence Interval |
|---|---|---|
| Percent Agreement - Positive Specimens | 98.6% | 96.2% - 99.6% |
| Percent Agreement - Negative Specimens | 98.7% | 96.4% - 99.6% |
| Percent Agreement - Overall | 98.6% | 98.4% - 98.8% |
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| TABLE 2: SUMMARY OF ALL STUDIESGIARDIA/CRYPTOSPORIDIUM CHEK™Comparison to Microscopy | Microscopy | |||
|---|---|---|---|---|
| (n = 217) | Positive | Negative | Total | |
| GIARDIA/CRYPTOSPORIDIUM CHEK™ | Positive | 121 | 0 | 121 |
| Negative | ಗೆ | ਹੈ ਤੇ | 96 | |
| Total | 124 | ਹੈਤੇ | 217 |
| GIARDIA/CRYPTOSPORIDIUM CHEKTMvs. Microscopy | Result | 95%Confidence Interval |
|---|---|---|
| Sensitivity | 97.6% | 92.6% - 99.4% |
| Specificity | 100% | 95.1% - 100% |
| Predictive Positive Value | 100% | 96.2% - 100% |
| Predictive Negative Value | 96.9% | 90.5% - 99.2% |
| Correlation | 98.6% | 98.2% - 98.9% |
7.2.2 Reproducibility
Multi-site proficiency testing was conducted to establish the ability of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test to provide reproducible results in laboratory settings. A fecal panel was assembled and tested at TECHLAB®, Inc. Identical aliquots of the panel were tested at TECHLAB®, Inc. and two independent laboratories using the GIARDIA/CRYPTOSPORIDIUM CHEK™ test. The fecal panel consisted of 24 samples: eight Giardia-positive samples, eight Cryptosporidium-positive samples, and eight samples negative for both parasites. Samples were selected that provided a range of absorbance values over the working range of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test (OD450 reading 0.0 - 4.0), including positive samples close to the positive/negative cut-off absorbance (OD450 0.150). Each sample was tested during three independent trials over a three-day period. Proficiency testing demonstrated 100% correlation for all samples from all three testing sites.
7.2.3 Sensitivity
Sensitivity to each antigen preparation was evaluated in 6 separate trials, using three different lots of the GIARDIA/CRYPTOSPORIDIUM CHEK™ test. The GIARDIA/CRYPTOSPORIDIUM CHEK™ test was consistently positive at 375 Giardia cysts/mL, 0.8 ng recombinant cyst wall protein/mL, and 6250 Cryptosporidium oocysts/mL.
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7.2.4 Specificity
Crossreactivity
An independent diagnostics laboratory evaluated the GIARDIA/CRYPTOSPORIDIUM CHEK™ test using fecal specimens found to be positive for a variety of intestinal pathogens. No cross reactivity was observed with fecal specimens that contained any of the pathogens listed below. The number of specimens tested with each organism is shown in parentheses.
| Ascaris lumbricoides eggs (26) | Entamoeba coli (17) |
|---|---|
| Blastocystis hominis (31) | Entamoeba hartmanni (4) |
| Chilomastix mesnili (2) | Enterobius vermicularis eggs (6) |
| Cyclospora cayetanensis (1) | Hymenolepis nana eggs (4) |
| Dientamoeba fragilis (10) | Iodamoeba bütschlii (4) |
| Diphyllobothrium latum eggs (1) | Strongyloides stercoralis larvae (2) |
| Endolimax nana (36) | Taenia spp. eggs (2) |
| Entamoeba histolytica/dispar (9) | Trichuris trichiura eggs (20) |
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test was evaluated for crossreactivity with the bacterial and viral strains listed below. None of the strains were shown to crossreact with the GIARDIA/CRYPTOSPORIDIUM CHEK™ test.
| Escherichia coli | Escherichia coli ETEC (enterotoxic) |
|---|---|
| Escherichia coli 0157H7 | Escherichia coli EPEC (enteropathogenic) |
| Yersinia enterocolitica | Escherichia coli EIEC (enteroinvasive) |
| Aeromonas hydrophila | Salmonella typhimurium |
| Shigella dysenteriae | Shigella flexneri |
| Salmonella typhimurium | Campylobacter coli |
| Campylobacter fetus | Clostridium difficile |
| Vibrio parahaemolyticus | Staphylococcus aureus (Cowan's) |
| Staphylococcus aureus | Staphylococcus epidermidis |
| Klebsiella pneumoniae | Enterococcus faecalis |
| Clostridium bifermentans | Bacteroides fragilis |
| Bacillus subtilis | Bacillus cereus |
| Adenovirus type 1 | Adenovirus type 2 |
| Adenovirus type 3 | Adenovirus type 5 |
| Adenovirus type 40 | Adenovirus type 41 |
| Human coronavirus | Coxsackievirus B2 |
| Coxsackievirus B3 | Coxsackievirus B4 |
| Coxsackievirus B5 | Echovirus 9 |
| Echovirus 11 | Echovirus 18 |
| Echovirus 22 | Echovirus 33 |
| Enterovirus type 68 | Enterovirus type 69 |
| Enterovirus type 70 | Enterovirus type 71 |
Interfering Substances
The following substances had no effect on positive or negative test results analyzed at the concentrations indicated: mucin (3.5% w/v), human blood (40% w/v), Imodium® (5% w/v), Kaopectate® (5 mg/mL), Pepto-Bismol® (5% w/v), fecal fat (stearic acid - 40% w/v), Metronidazole (0.25% w/v), Vancomycin (0.25% w/v).
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Image /page/6/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle with three stylized lines representing its wings.
Food and Drug Administration 2098 Gaither Road Rockville MD 20850
NOV 1 7 2005
David M. Lverly, Ph.D. Vice President of Research and Development TECHLAB®, Inc. 2001 Kraft Drive Blacksburg, VA 24060-6358
K051929 Trade/Device Name: GIARDIA/CRYTOSPORIDIUM CHECK™ Regulation Number: 21 CFR 866.3220 Regulation Name: Entamoeba Histolytica Serological Reagents Regulatory Class: Class II Product Code: MHJ Dated: October 20, 2005 Received: October 25, 2005
Dear Dr. Lyerly:
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 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 Hom
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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2. INDICATIONS FOR USE
510(k) Number (if known): K 051929
GIARDIA/CRYPTOSPORIDIUM CHEK™ Device Name:
Indications For Use:
The GIARDIA/CRYPTOSPORIDIUM CHEK™ test is an enzyme immunoassay for the qualitative detection of Giardia cyst and Cryptosporidium oocyst antigen in human fecal specimens. It is indicated for use as an aid in the diagnosis of patients with diarrhea suspected of Giardia and/or Cryptosporidium gastrointestinal infections.
FOR IN VITRO DIAGNOSTIC USE.
Prescription Use v (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)
Luddi L. Poole
sion Sign-Off
Page 1 of 1
Office of In Vitro Diagnostic Device Evaluation and Safety
510(k) K051929
11
§ 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.