(214 days)
The Diagnostic Hybrids, Inc. D3 Ultra DFA (direct fluorescent antibody) RESPIRATORY VIRUS SCREENING & ID KIT is intended for the qualitative detection and identification of the Influenza A, Influenza B, Respiratory Syncytial Virus (RSV), Adenovirus, Parainfluenza 1, Parainfluenza 2 and Parainfluenza 3 virus in respiratory specimens, by either direct detection or cell culture method, by immunofluorescence using fluoresceinated monoclonal antibodies (MAbs). It is recommended that specimens found to be negative after examination of the direct specimen result be confirmed by cell culture. Negative results do not preclude respiratory virus infection and should not be used as the sole basis for diagnosis, treatment or other management decisions.
The Diagnostic Hybrids, Inc. D3 Ultra DFA RESPIRATORY VIRUS SCREENING & ID KIT includes a DFA Screening Reagent that contains a blend of murine monoclonal antibodies (MAbs) directed against seven respiratory viruses (Influenza A. Influenza B. Respiratory Syncytial Virus, Adenovirus, Parainfluenza 1, Parainfluenza 2, and Parainfluenza 3) plus seven separate DFA Reagents, each consisting of MAb blends directed against a single respiratory virus. The kit can be used for direct specimen or cell culture screening and final virus identification.
Here's a breakdown of the acceptance criteria and study information for the Diagnostic Hybrids, Inc. D3 Ultra DFA Respiratory Virus Screening & ID Kit, based on the provided 510(k) summary:
Acceptance Criteria and Device Performance (Comparison of Subject Device vs. Predicate Device)
The study's acceptance criteria are implicitly defined by the demonstration of substantial equivalence to the predicate device. The performance is reported in terms of Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) with 95% Confidence Intervals (CI).
| Test Type & Specimen Status | Agreement Type | Predicate Result (Count) | Subject Result (Count) | Reported Performance (PPA/NPA) | 95% Confidence Interval |
|---|---|---|---|---|---|
| Direct Specimen Testing - Fresh Prospectively Collected Specimens (n=326) | |||||
| Screen + | PPA | 90 | 94 | 95.5% | 89.0-98.2% |
| Negative | NPA | 236 | 232 | 98.3% | 95.7-99.3% |
| Adenovirus | PPA | 18 | 18 | 100.0% | 82.4-100% |
| Adenovirus | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100.0% | 95.2-100% |
| Influenza A | PPA | 32 | 32 | 100.0% | 89.3-100% |
| Influenza A | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100.0% | 94.2-100% |
| Influenza B | PPA | 18 | 19 | 100.0% | 82.4-100% |
| Influenza B | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 98.7% | 92.9-99.8% |
| Parainfluenza 1 | PPA | 2 | 2 | 100.0% | 34.2-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100.0% | 96.0-100% |
| Parainfluenza 2 | PPA | 0 | 0 | --- (n=0) | --- |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100.0% | 96.1-100% |
| Parainfluenza 3 | PPA | 2 | 5 | 100.0% | 34.2-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 96.7% | 90.8-98.9% |
| RSV | PPA | 18 | 18 | 100.0% | 82.4-100% |
| RSV | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100.0% | 95.2-100% |
| Direct Specimen Testing - Frozen Prospectively Collected Specimens (n=474) | |||||
| Screen + | PPA | 168 | 168 | 100% | 97.8-100% |
| Negative | NPA | 306 | 306 | 100% | 98.8-100% |
| Adenovirus | PPA | 8 | 8 | 100% | 63.1-100% |
| Adenovirus | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.7-100% |
| Influenza A | PPA | 85 | 85 | 100% | 95.7-100% |
| Influenza A | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 95.6-100% |
| Influenza B | PPA | 19 | 19 | 100% | 82.3-100% |
| Influenza B | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.6-100% |
| Parainfluenza 1 | PPA | 3 | 3 | 100% | 38.3-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.8-100% |
| Parainfluenza 2 | PPA | 3 | 3 | 100% | 38.3-100% |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.8-100% |
| Parainfluenza 3 | PPA | 9 | 9 | 100% | 70.1-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.6-100% |
| RSV | PPA | 51 | 51 | 100% | 93.0-100% |
| RSV | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 96.7-100% |
| Cell Culture Testing - Frozen Prospectively Collected Specimens (n=490) | |||||
| Screen + | PPA | 181 | 181 | 100% | 98.0-100% |
| Negative | NPA | 309 | 309 | 100% | 98.5-100% |
| Adenovirus | PPA | 13 | 13 | 100% | 73.4-100% |
| Adenovirus | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.3-100% |
| Influenza A | PPA | 93 | 93 | 100% | 95.2-100% |
| Influenza A | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 95.0-100% |
| Influenza B | PPA | 23 | 23 | 100% | 83.1-100% |
| Influenza B | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.1-100% |
| Parainfluenza 1 | PPA | 6 | 6 | 100% | 55.7-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.4-100% |
| Parainfluenza 2 | PPA | 4 | 4 | 100% | 45.4-100% |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 97.4-100% |
| Parainfluenza 3 | PPA | 9 | 9 | 100% | 65.5-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 96.6-100% |
| RSV | PPA | 49 | 49 | 100% | 91.3-100% |
| RSV | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 96.6-100% |
| Study 3a-DS – Archival Parainfluenza Specimens (n=26) | |||||
| Screen + | PPA | 17 | 18 | 100% | 78.4-100% |
| Negative | NPA | 9 | 8 | 88.9% | 54.3->99.9% |
| Parainfluenza 1 | PPA | 1 | 1 | 100% | 16.8-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 78.4-100% |
| Parainfluenza 2 | PPA | 5 | 5 | 100% | 51.1-100% |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 73.4-100% |
| Parainfluenza 3 | PPA | 11 | 12 | 100% | 70.0-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 85.7% | 46.7-99.5% |
| Study 3a-CC - Archival Parainfluenza Specimens (n=29) | |||||
| Screen + | PPA | 21 | 21 | 100% | 81.8-100% |
| Negative | NPA | 8 | 8 | 100% | 62.8-100% |
| Parainfluenza 1 | PPA | 3 | 3 | 100% | 38.3-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 79.3-100% |
| Parainfluenza 2 | PPA | 5 | 5 | 100% | 51.1-100% |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 77.3-100% |
| Parainfluenza 3 | PPA | 13 | 13 | 100% | 73.4-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 62.8-100% |
| Study 3b-CC - Archival Clinical Isolates (n=81) | |||||
| Screen + | PPA | 81 | 81 | 100% | 94.6-100% |
| Negative | NPA | 0 | 0 | 100% (n=0) | 97.3-100% |
| Adenovirus | PPA | 11 | 11 | 100% | 70.0-100% |
| Adenovirus | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 93.8-100% |
| Influenza A | PPA | 18 | 18 | 100% | 79.3-100% |
| Influenza A | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 93.1-100% |
| Influenza B | PPA | 17 | 17 | 100% | 78.4-100% |
| Influenza B | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 93.2-100% |
| Parainfluenza 1 | PPA | 4 | 4 | 100% | 45.4-100% |
| Parainfluenza 1 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 94.3-100% |
| Parainfluenza 2 | PPA | 1 | 1 | 100% | 16.8-100% |
| Parainfluenza 2 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 94.5-100% |
| Parainfluenza 3 | PPA | 26 | 26 | 100% | 84.8-100% |
| Parainfluenza 3 | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 92.2-100% |
| RSV | PPA | 5 | 5 | 100% | 51.1-100% |
| RSV | NPA | (not directly given but inferred from overall negative) | (not directly given but inferred from overall negative) | 100% | 94.2-100% |
1. Sample sizes used for the test set and the data provenance:
- Comparison Studies (Primary Clinical Evaluation):
- Total specimens: 849 original specimens.
- Direct Specimen (DS) Testing:
- Fresh prospectively collected: 326 specimens.
- Frozen prospectively collected: 474 specimens.
- Cell Culture (CC) Method Testing: 520 specimens (subset of the 849). Of these, 490 were frozen prospectively collected.
- Archived Parainfluenza Specimens (Study 3a-DS/CC):
- DS: 26 specimens
- CC: 29 specimens
- Archived Clinical Isolates (Study 3b-CC): 81 clinical isolates.
- Data Provenance:
- Main study (849 specimens): All but 30 were prospectively collected during the 2005-2006 season. These 30 were archived as Parainfluenza-positive.
- Archived Parainfluenza Specimens (Study 3a): Frozen original specimens previously determined to contain Parainfluenza (types 1, 2, or 3) during the 2006 "respiratory season," obtained from an additional laboratory.
- Archived Clinical Isolates (Study 3b): Banked clinical isolates known to contain respiratory viruses from the 2005/2006 respiratory season.
- Country of Origin: Not explicitly stated, but the submission is to the US FDA by "Diagnostic Hybrids, Inc. Athens, OHIO 45701", implying US-based studies.
2. Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document implies that the "Predicate device" results acted as the reference or ground truth for the comparison studies. Therefore, the "experts" are the lab personnel who interpreted the predicate device results.
- The number and specific qualifications of these experts are not explicitly stated in the provided text. The evaluation was conducted at three laboratory sites.
3. Adjudication method for the test set:
- The document does not describe a specific adjudication method (e.g., 2+1, 3+1). It states that the "Subject" results were compared to "Predicate Results." This implies the predicate results were taken as the standard. In the case of Study 3a (Archived Parainfluenza), it mentions that "Original results reported by the laboratory were unknown to the study investigator," suggesting an independent comparison to pre-existing results rather than a real-time adjudication process.
4. 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, this section is not applicable. The device is an in vitro diagnostic (IVD) test kit for direct detection or cell culture by immunofluorescence using monoclonal antibodies. It is not an AI-assisted diagnostic tool for human readers. Therefore, an MRMC study comparing human readers with and without AI assistance was not performed.
5. If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Yes, in a sense. The described performance is the "Subject device" (the test kit itself) compared against a "Predicate device" (another test kit). This represents the performance of the assay/reagent system in a laboratory setting, which is analogous to a "standalone" performance for such an IVD device, as it doesn't involve an AI algorithm or human interpretation outside of standard microscopy and reading of fluorescent signals.
6. The type of ground truth used:
- The primary ground truth used for the comparison studies was the results obtained from a legally marketed predicate device (Diagnostic Hybrids, Inc. DFA Respiratory Virus Screening & ID Kit, K022713).
- For the "Archived Parainfluenza Specimens" (Study 3a) and "Archived Clinical Isolates" (Study 3b), the ground truth was also based on previously determined results (implicitly from a predicate or similar method) for known positive specimens/isolates.
7. The sample size for the training set:
- For the comparative effectiveness studies (clinical evaluations), there is no explicit mention of a separate "training set" for the device itself in the context of an algorithm or machine learning. The studies described are validation studies comparing the performance of the new device to a predicate. The device is a reagent-based test kit, not an algorithm that requires a training set in the typical AI sense.
- However, during the development of the monoclonal antibodies (MAbs) and the kit, internal analytical studies would have been performed. The closest equivalent to "training" for such a device would be the extensive analytical testing described, such as detection limits and analytical specificity testing across various viral strains, host cell types, and bacterial cultures.
8. How the ground truth for the training set was established:
- As mentioned above, the concept of a "training set" in the context of an algorithm is not directly applicable here.
- For the analytical studies (detection limit, analytical specificity), the "ground truth" was established by:
- Known viral stocks: Inoculating cell culture plates with specific viruses at known concentrations (e.g., "50 viral particles," "1 viral particle per every 2 wells," "250 virus/mL").
- Known microorganisms and cell types: Testing against "64 virus strains (cultured and processed for staining)," "18 host culture cell types," and "18 bacterial cultures," where their identity was pre-established.
§ 866.3330 Influenza virus serological reagents.
(a)
Identification. Influenza virus serological reagents are devices that consist of antigens and antisera used in serological tests to identify antibodies to influenza in serum. The identification aids in the diagnosis of influenza (flu) and provides epidemiological information on influenza. Influenza is an acute respiratory tract disease, which is often epidemic.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 866.9.