(82 days)
This direct fluorescent antigen (DFA) detection kit is an in vitro diagnostic (IVD) immunoassay for the detection of Cryptosporidium oocysts and Giardia Cysts in human feces using fluorescent microscopic visualization. This IVD assay is intended to be used with stools preserved in 10% formalin, SAF or Medical Chemical Corporation's (MCC's) Universal fixative. Such samples may be concentrated or unconcentrated.
This IVD Research, Inc. Cryptosporidium/Giardia Direct Fluorescent Antigen Detection Kit (DFA Assay) is intended for use as an in vitro diagnostic (IVD) fluorescent immunoassay for the qualitative determination of Cryptosporidium oocysts and Giardia cysts in stool feces. This assay may be used with stool samples that are preserved in 10% formalin, SAF, or Medical Chemical Corporation's (MCC's) Universal Fixative.
This DFA Assay corresponds to FDA Classification Name: Entamoeba Histolytica Serological Reagent, a class II (non-exempt) Device, within the Microbiology Classification Panel, having FDA Reg. Citation Number: 21 CFR 866.3220, and FDA Product Codes: MHI and MHJ, and, as such, utilizes the principle of direct immunofluorescence microscopy. The conjugate contains a mixture of FITC-labeled monoclonal antibodies (derived from hybridized mouse B-cells) directed against Cryptosporidium oocysts and Giardia cysts, which, if present, are affixed to a treated slide (provided). The slide with sample material is then rinsed with wash solution to remove unbound conjugate and debris, and air-dried. The prepared slide is then examined using a fluorescent microscope, looking for an apple-green color and the characteristic morphology of the Cryptosporidium oocysts and the Giardia cysts.
The IVD Research, Inc.'s Cryptosporidium/Giardia Direct Fluorescent Antigen (DFA) Detection Kit is intended for use as an in vitro diagnostic (IVD) fluorescent immunoassay for the qualitative determination of Cryptosporidium oocysts and Giardia cysts in stool feces.
Here's an analysis of the provided information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria are implied by the desire to demonstrate substantial equivalence to the gold standard (O&P microscopy) and the predicate device, Meridian Diagnostic's Merifiuor™ Cryptosporidium/Giardia Direct Fluorescent Antigen Detection Kit, with "equivalent sensitivity and specificity." While explicit numerical acceptance criteria (e.g., "sensitivity must be >90%") are not stated, the study results consistently report 100% or near 100% sensitivity and specificity with narrow 95% Confidence Intervals.
| Outcome | Acceptance Criteria (Implied) | Reported Device Performance (Worst Case Across Studies) |
|---|---|---|
| Giardia Sensitivity | Equivalent to O&P microscopy and predicate device | 100% (95% CI: 79% to 100%) |
| Giardia Specificity | Equivalent to O&P microscopy and predicate device | 100% (95% CI: 90% to 100%) |
| Cryptosporidium Sensitivity | Equivalent to O&P microscopy and predicate device | 95% (95% CI: 74% to 100%) |
| Cryptosporidium Specificity | Equivalent to O&P microscopy and predicate device | 100% (95% CI: 92% to 100%) |
| Correlation with Predicate Device | 100% correlation with predicate device | 100% (Study #4) |
| Analytical Sensitivity | Not explicitly stated, but detection of low parasite counts is desirable. | Capable of detecting 1 oocyst or cyst per 10 ul of unconcentrated sample. |
| Cross-Reactivity | No cross-reactivity with common non-target organisms. | No cross-reactions with 21 specified organisms/cells. |
2. Sample Size Used for the Test Set and Data Provenance
- Study #1: 170 stools (145 human, 25 bovine). Unconcentrated.
- Study #2: 53 unconcentrated stools.
- Study #3: 74 formalin and SAF preserved stools.
- Study #4: 69 formalin and SAF preserved stools (used for predicate device comparison).
- Data Provenance: The document explicitly states, "Unless otherwise indicated, all fecal samples are derived from humans." The inclusion of 25 bovine stools in Study #1 indicates a mix of human and non-human samples in that specific study; other studies imply human origin. The data is retrospective, as it compares the new DFA assay against existing O&P microscopy results or a predicate device. The country of origin of the data is not specified.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The document does not explicitly state the number of experts or their qualifications. However, the ground truth for Studies #1, #2, and #3 was established using "O&P microscopy," which is a standard parasitological examination typically performed by trained medical technologists or clinical microbiologists with expertise in identifying parasites.
4. Adjudication Method for the Test Set
The document does not describe an explicit adjudication method (e.g., 2+1, 3+1). It implies that the O&P microscopy results (the "Micro +" and "Micro -" columns in the tables) were considered the definitive ground truth against which the DFA assay was compared. There is no mention of discrepancies being adjudicated.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size of Human Readers Improving with AI vs. Without AI Assistance
No, an MRMC comparative effectiveness study was not done. This device is a diagnostic kit (DFA assay) for microscopic visualization, not an AI-powered image analysis tool. Therefore, the concept of human readers improving with AI assistance does not apply here.
6. If a Standalone (Algorithm Only Without Human-in-The-Loop Performance) Was Done
Yes, the studies presented (Studies #1, #2, and #3) represent standalone performance of the IVD Research DFA Assay. The results of the DFA assay were directly compared to O&P microscopy (the ground truth) without human interpretation factors other than the inherent microscopic examination of the DFA slides. Effectively, the "algorithm" here is the DFA assay methodology itself, and its performance is evaluated directly.
7. The Type of Ground Truth Used
The primary ground truth used for Studies #1, #2, and #3 was expert consensus via O&P microscopy (Ova and Parasite microscopy). This is considered the "gold standard for parasitology" as stated in the document. For Study #4, the ground truth was the results obtained from the predicate device.
8. The Sample Size for the Training Set
The document does not explicitly describe a "training set" in the context of machine learning or algorithm development. This is a traditional IVD kit validation, not an AI/ML device. The studies described are performance validation studies for the finished product. Therefore, there is no specified training set size for an algorithm.
9. How the Ground Truth for the Training Set Was Established
Since there is no explicit training set in the context of an AI/ML algorithm, this question is not applicable. The device relies on chemical reactions and fluorescent microscopy, not machine learning.
§ 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.