(210 days)
BD MAX™ Enteric Bacterial Panel
The BD MAX™ Enteric Bacterial Panel performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct qualitative detection and differentiation of enteric bacterial pathogens. The BD MAX™ Enterial Panel detects nucleic acids from:
- · Salmonella spp.
- · Campylobacter spp. (jejuni and coli)
- · Shigella spp. / Enteroinvasive E. coli (EIEC)
· Shiga toxin 1 (stxl ) / Shiga toxin 2 (stx2) genes (found in Shiga toxin-producing E. coli [STEC]) as well as Shigella dysenteriae, which can possess a Shiga toxin gene (stx) that is identical to the stx1 gene of STEC.
Testing is performed on unpreserved soft to diartheal stool specimens or Cary-Blair preserved stool specimens from symptomatic patients with suspected acute gastroenteritis or colitis. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of SpaO, a Campylobacter specific tuf gene sequence, ipaH and strilstr2. The test utilizes fluorogenic sequence-specific hybridization of the amplified DNA.
This test is intended for use, in conjunction with clinical presentation, laboratory findings, and epidemiological information, as an aid in the differential diagnosis of Salmonella, Shigella/EIEC, Campylobacter and Shiga toxinproducing E. coli (STEC) infections. Results of this test should not be used as the sole basis for diagnosis, treatment, or other patient management decisions. Positive results do not rule out co-infection with other organisms that are not detected by this test and may not be the sole or definitive cause of patient illness. Negative results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or noninfectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.
BD MAX™ Extended Enteric Bacterial Panel
The BD MAX™ Extended Enteric Bacterial Panel performed on the BD MAX™ System, is an automated in vitro diagnostic test for the direct qualitative detection and differentiation of enteric bacterial pathogens. It is used in conjunction with the BD MAX™ Enteric Bacterial Panel as an optional Master Mix. The BD MAX™ Extended Enteric Bacterial Panel detects nucleic acids from:
- Plesiomonas shigelloides
- · Vibrio (V. vulnificus, V. parahaemolyticus, and V. cholerae)
- · Enterotoxigenic Escherichia coli (ETEC) heat-labile enterotoxin (LT)/ heat-stable enterotoxin (ST) genes
- Yersinia enterocolitica
Testing is performed on unpreserved soft to diar preserved stool specimens from symptomatic patients with suspected acute gastroenteritis or colitis. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of relevant gene target DNA. The test utilizes fluorogenic genespecific hybridization probes for the detection of the amplified DNA.
This test is intended for use, in conjunction with clinical presentation, laboratory findings, and epidemiological information, as an aid in the differential diagnosis of Plesiomonas shigelloides, Vibrio (V. vulnificus, V. parahaemolyticus, and V. cholerae) Enterotoxigenic Escherichia coli (ETEC) LT/ST and Yersinia enterocolitica infections. Results of this test should not be used as the sole basis for diagnosis, treatment, or other patient decisions. Positive results do not rule out co-infection with other organisms that are not detected by this test and may not be the sole or definitive cause of patient illness. Negative results in the setting of clinical illness compatible with gastroenteritis may be due to infection by pathogens that are not detected by this test or non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.
The BD MAX™ Enteric Bacterial Panel and BD MAX™ Extended Enteric Bacterial Panel assays along with the BD MAX System are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, and extraction reagents. The instrument automates sample preparation including target lysis. DNA extraction and concentration, reagent rehydration, target nucleic acid amplification and detection using real-time PCR. The assay includes a Sample Processing Control (SPC) that is present in the Extraction Tube. The SPC monitors DNA extraction steps, thermal cycling steps, reagent integrity and the presence of inhibitory substances. The BD MAX™ System software automatically interprets test results. For the BD MAXTM Enteric Bacterial Panel and BD MAX™ Extended Enteric Bacterial Panel, a test result may be called as POS, NEG or UNR (Unresolved) based on the amplification status of the targets and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.
This document describes the performance evaluation of the BD MAX™ Enteric Bacterial Panel and BD MAX™ Extended Enteric Bacterial Panel when used with the BD FecalSwab™ Collection, Transport and Preservation System. The primary goal of the studies was to demonstrate substantial equivalence to the existing Cary-Blair Para-Pak® specimen collection method.
Here's a breakdown of the requested information:
1. Table of Acceptance Criteria and Reported Device Performance
The acceptance criteria varied across the different studies. For the user variability study, specific percentage targets were set. For the clinical evaluation, the performance was presented as Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to the Cary-Blair method.
User Variability Study Acceptance Criteria and Performance:
| Target | Panel Member | Acceptance Criteria | Assay Results | Result |
|---|---|---|---|---|
| Campylobacter jejuni and ETEC | Moderate-Positive | 100% POS | 100% POS | Pass |
| Campylobacter jejuni and ETEC | Low-Positive | ≥ 95% POS | 100% POS | Pass |
| Negative samples | Negative | 100% NEG | 100% NEG | Pass |
Clinical Evaluation Performance (FecalSwab™ vs. Cary-Blair):
| Pathogen | Specimen Origin | Positive Percent Agreement (PPA) | Negative Percent Agreement (NPA) |
|---|---|---|---|
| Campylobacter spp. | Prospective | 100.0% | 99.8% |
| Retrospective | 100.0% | 97.1% | |
| Salmonella spp. | Prospective | 100.0% | 100.0% |
| Retrospective | 93.3% | 95.9% | |
| Shigella spp. | Prospective | 100.0% | 100.0% |
| Retrospective | 98.1% | 99.6% | |
| stx1/stx2 (STX) | Prospective | 100.0% | 99.5% |
| Retrospective | 92.9% | 100.0% | |
| stx1/stx2 (STX) | Contrived | 100.0% | 100.0% |
| Plesiomonas shigelloides | Prospective | 100.0% | 99.0% |
| Retrospective | 33.3% * | 100.0% | |
| Plesiomonas shigelloides | Contrived | 100.0% | 100.0% |
| Vibrio spp. | Prospective | Not Available | 99.7% |
| Retrospective | 100.0% | 100.0% | |
| Vibrio spp. | Contrived | 98.1% | 100.0% |
| ETEC | Prospective | 100.0% | 100.0% |
| Retrospective | 100.0% | 99.6% | |
| ETEC | Contrived | 100.0% | 100.0% |
| Yersinia enterocolitica | Prospective | Not Available | 100.0% |
| Retrospective | 100.0% | 99.0% | |
| Yersinia enterocolitica | Contrived | 98.1% | 100.0% |
*Note on Plesiomonas shigelloides retrospective PPA: The low PPA (33.3%) is due to a very small sample size of positive specimens (3 total, with only 1 detected by FecalSwab). The contrived specimen data shows 100% PPA for this pathogen.
2. Sample Size for the Test Set and Data Provenance
-
Limiting Dilution LoD Study:
- Test Set Sample Size: For each organism and each collection type (FecalSwab and Para-Pak®), 24 replicates were tested per concentration level. For Plesiomonas shigelloides, Y. enterocolitica, V. parahaemolyticus, and E. coli ETEC, one non-reportable sample in the Para-Pak® group for Conc 1 resulted in 23 replicates.
- Data Provenance: Not explicitly stated, but likely laboratory-prepared samples.
-
User Variability Study:
- Test Set Sample Size: 12 negative samples (6 users x 2 samples), 36 low-positive samples (6 users x 2 samples x 3 panel members), and 12 moderate-positive samples (6 users x 2 samples x 1 panel member).
- Data Provenance: Laboratory-prepared FecalSwab specimens.
-
Clinical Evaluation:
- Test Set Sample Size: 618 prospective specimens and 295 retrospective specimens were initially enrolled (Total 913). After exclusions, the final data analysis included 897 compliant subjects.
- Data Provenance:
- Country of Origin: Not explicitly stated, but collected from "eight (8) geographically diverse clinical centers" which typically implies within the United States for FDA submissions.
- Retrospective/Prospective: Both. 618 prospective specimens and 295 retrospective specimens.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
For these in vitro diagnostic assays, the "ground truth" for the clinical evaluation is based on the results from the predicate device (Cary-Blair Para-Pak® preserved stool samples tested with the BD MAX™ Enteric Bacterial Panel and BD MAX™ Extended Enteric Bacterial Panel). No human "experts" like radiologists are mentioned for establishing ground truth in this context; instead, it relies on an established laboratory method.
4. Adjudication Method for the Test Set
The document does not describe an adjudication method in the sense of expert review for discrepancies between the FecalSwab and Cary-Blair results. The comparison is a direct statistical agreement between the two methods (FecalSwab vs. Cary-Blair). For contrived specimens, the ground truth was "expected results," implying a predefined status based on specimen preparation.
5. If a Multi Reader Multi Case (MRMC) Comparative Effectiveness Study was done
No, an MRMC comparative effectiveness study was not done. This device is an in vitro diagnostic (IVD) test, not an AI imaging or diagnostic algorithm that humans would interpret in a multi-reader, multi-case setting. The evaluation focuses on the analytical and clinical performance of the assay itself.
6. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, the device (BD MAX™ System with the assay panels) operates in a standalone manner. The test is "automated" and produces qualitative results (POS, NEG, UNR) directly. No human interpretation of the assay results is detailed as part of the core performance, other than the system software interpreting the results.
7. The Type of Ground Truth Used
- Limiting Dilution LoD Study: The ground truth was based on the known concentration of serially diluted organisms spiked into negative stool.
- User Variability Study: The ground truth was based on the known status (negative, low-positive, moderate-positive) of laboratory-prepared panel members.
- Clinical Evaluation: The ground truth for comparing the FecalSwab™ system was the results obtained from the predicate device method (Cary-Blair Para-Pak® preserved stool samples tested with the BD MAX™ Enteric Bacterial Panel and BD MAX™ Extended Enteric Bacterial Panel). For the additional contrived specimens, the ground truth was the "expected results" (known positive or negative status of the prepared specimens).
8. The Sample Size for the Training Set
The provided text describes performance evaluation studies for substantial equivalence, focusing on validating the FecalSwab collection method. It does not mention a "training set" in the context of machine learning or AI development. The BD MAX™ assays are PCR-based in vitro diagnostic tests, which typically do not involve machine learning training sets in the same way an AI algorithm might. Their "training" or development would involve optimizing primers, probes, and reaction conditions through laboratory experiments.
9. How the Ground Truth for the Training Set Was Established
As no "training set" in the AI sense is explicitly mentioned or relevant for this type of IVD device, this question is not applicable. The development of the assay's ability to detect specific nucleic acids relies on molecular biology principles and analytical validation, not statistical training on labeled data in the way an AI model is trained.
§ 866.3990 Gastrointestinal microorganism multiplex nucleic acid-based assay.
(a)
Identification. A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitativein vitro diagnostic device intended to simultaneously detect and identify multiple gastrointestinal microbial nucleic acids extracted from human stool specimens. The device detects specific nucleic acid sequences for organism identification as well as for determining the presence of toxin genes. The detection and identification of a specific gastrointestinal microbial nucleic acid from individuals exhibiting signs and symptoms of gastrointestinal infection aids in the diagnosis of gastrointestinal infection when used in conjunction with clinical evaluation and other laboratory findings. A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.(b)
Classification. Class II (special controls). The special controls are set forth in FDA's guideline document entitled: “Class II Special Controls Guideline: Gastrointestinal Microorganism Multiplex Nucleic Acid-Based Assays for Detection and Identification of Microorganisms and Toxin Genes from Human Stool Specimens.” For availability of the guideline document, see § 866.1(e).