(111 days)
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 Enteric Bacterial Panel detects nucleic acids from:
- Salmonella spp. .
- Campylobacter spp. (jejuni and coli) .
- Shigella spp. / Enteroinvasive E. coli (EIEC) .
- Shiga toxin 1 (stx1) / 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 unoreserved soft to diarrheal stool specimens or Cary-Blair preserved stool specimens from symptomatic patients with suspected acute gastroenteritis, enteritis 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 stx1/stx2. The test utilizes fluorogenic sequence-specific hybridization probes for 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 Salmonella, Shigella/EIEC, Campylobacter and Shiga toxin-producing 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 non-infectious causes such as ulcerative colitis, irritable bowel syndrome, or Crohn's disease.
The BD MAX™ System and the BD MAX™ Enteric Bacterial Panel are comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges. master mixes, unitized reagent strips, extraction reagents, and sample buffer tubes. The instrument automates sample preparation including target lysis, DNA extraction and concentration, reagent rehydration, and 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 result may be called as POS. NEG or UNR for each of the assay's targets, based on the amplification status of the target and of the Sample Processing Control. IND (Indeterminate) or INC (Incomplete) results are due to BD MAX™ System failure.
Here's a breakdown of the acceptance criteria and study details for the BD MAX™ Enteric Bacterial Panel, based on the provided document:
Acceptance Criteria and Device Performance
The document describes various analytical and clinical performance studies, each with inherent acceptance criteria demonstrated by the reported results. The explicit acceptance criteria are outlined in the "Precision" section for analytical performance. For clinical performance, the acceptance is implied by the achieved PPA (Positive Percent Agreement) and NPA (Negative Percent Agreement) values with corresponding confidence intervals.
Table of Acceptance Criteria and Reported Device Performance
| Study Type | Target | Acceptance Criteria | Reported Device Performance (Summary) |
|---|---|---|---|
| Analytical Performance | |||
| Precision (Within-laboratory) | MP | Overall correct percentage of approximately 100% with 95% CI | Shiga toxins: 100.00% (72/72) |
| Campylobacter: 98.61% (71/72) | |||
| Shigella: 98.61% (71/72) | |||
| Salmonella: 100.00% (72/72) | |||
| LP | Overall correct percentage of approximately 95% with 95% CI | Shiga toxins: 98.61% (71/72) | |
| Campylobacter: 100.00% (72/72) | |||
| Shigella: 98.61% (71/72) | |||
| Salmonella: 100.00% (72/72) | |||
| TN | Overall correct percentage of approximately 100% with 95% CI | Shiga toxins: 100.00% (72/72) | |
| Campylobacter: 100.00% (72/72) | |||
| Shigella: 100.00% (72/72) | |||
| Salmonella: 100.00% (72/72) | |||
| HN | Overall correct percentage between 20% and 80% | Shiga toxins: 27.78% (20/72) | |
| Campylobacter: 54.17% (39/72) | |||
| Shigella: 30.56% (22/72) | |||
| Salmonella: 25.00% (18/72) | |||
| Reproducibility (Site-to-Site) | TN | 100% agreement (implied by categories) | All Targets: 100.0% |
| HN | Agreement range 41.1% to 77.8% (implied by categories) | Campylobacter: 77.8% | |
| Salmonella: 44.4% | |||
| Shigella: 41.1% | |||
| Shiga toxins: 50.0% | |||
| LP | Agreement range 96.7% to 100% (implied by categories) | Campylobacter: 100.0% | |
| Salmonella: 96.7% | |||
| Shigella: 97.8% | |||
| Shiga toxins: 100.0% | |||
| MP | Agreement range 98.9% to 100% (implied by categories) | Campylobacter: 100.0% | |
| Salmonella: 98.9% | |||
| Shigella: 100.0% | |||
| Shiga toxins: 98.9% | |||
| Reproducibility (Lot-to-Lot) | TN | 100% agreement (implied by categories) | All Targets: 100.00% |
| HN | Agreement range 13.33% to 62.22% (implied by categories) | STEC: 30.00% | |
| Campy: 62.22% | |||
| Shig: 16.67% | |||
| Sal: 13.33% | |||
| LP | Agreement range 95.56% to 100% (implied by categories) | STEC: 98.89% | |
| Campy: 100.00% | |||
| Shig: 95.56% | |||
| Sal: 98.89% | |||
| MP | Agreement range 97.78% to 100% (implied by categories) | STEC: 100.00% | |
| Campy: 97.78% | |||
| Shig: 98.89% | |||
| Sal: 100.00% | |||
| Clinical Performance | |||
| Clinical Accuracy (PPA, NPA) | Varies | High PPA and NPA with tight 95% CIs (implied by successful comparison to reference method) | Campylobacter: PPA (96.2%-100%), NPA (97.5%-100%) |
| Salmonella: PPA (85%-100%), NPA (98.9%-100%) | |||
| Shigella/EIEC: PPA (98%-100%), NPA (99.4%-100%) | |||
| Shiga toxins: PPA (75%-100%), NPA (99%-100%) | |||
| (Specific ranges depend on specimen type and origin, detailed in the tables 19-22 of the document) | |||
| Unresolved Rates (Initial) | All | Low unresolved rates (implied by successful operation and repeat testing) | Cary-Blair Preserved: Prospective 4.0%, Retrospective 2.2% |
| Unpreserved: Prospective 7.8%, Retrospective 4.1% | |||
| Unresolved Rates (After Repeat) | All | Very low unresolved rates after repeat (implied by successful operation and repeat testing) | Cary-Blair Preserved: Prospective 0.1%, Retrospective 0.2% |
| Unpreserved: Prospective 1.0%, Retrospective 0.6% | |||
| Indeterminate Rates (Initial) | All | Low indeterminate rates (implied by successful operation and repeat testing) | Cary-Blair Preserved: Prospective 1.7%, Retrospective 1.5% |
| Unpreserved: Prospective 1.6%, Retrospective 1.9% | |||
| Indeterminate Rates (After Repeat) | All | Very low indeterminate rates after repeat (implied by successful operation and repeat testing) | Cary-Blair Preserved: Prospective 0.0%, Retrospective 0.0% |
| Unpreserved: Prospective 0.2%, Retrospective 0.0% | |||
| Incomplete Rates (Initial) | All | Low incomplete rates (implied by successful operation) | Cary-Blair Preserved: Prospective 1.3%, Retrospective 1.3% |
| Unpreserved: Prospective 2.0%, Retrospective 0.0% | |||
| Incomplete Rates (After Repeat) | All | Very low incomplete rates after repeat (implied by successful operation) | Cary-Blair Preserved: Prospective 0.0%, Retrospective 0.0% |
| Unpreserved: Prospective 0.0%, Retrospective 0.0% |
Study Details
The provided document describes both Analytical Performance and Clinical Performance studies.
Analytical Performance Studies
These studies evaluate the device's technical capabilities in detecting the target pathogens.
- Sample Size Used for the Test Set and Data Provenance:
- Precision:
- Within-laboratory: For each of 4 different target types (Shiga toxins, Campylobacter, Shigella, Salmonella), 4 sample categories (TN, HN, LP, MP) were tested in triplicate over 12 days, with 2 runs per day. This results in 72 replicates per category per target.
- Site-to-Site Reproducibility: 3 clinical sites were provided with 10 panels, each with 12 tubes. Each site performed the study over 5 distinct days, with 2 panels tested per day by 2 technologists. This results in 90 replicates per category per target across all sites (though specific numbers vary slightly when looking at site-by-site data for positive/negative agreement).
- Lot-to-Lot Reproducibility: Data from 5 days of an accuracy and precision study, using 12 panel members per lot, with two users for each of two lots, was used. This equates to 90 replicates per category per target across the lots.
- Data Provenance: Not explicitly stated as real-world patient data. These appear to be spiked samples (engineered to be near LoD, etc.) into negative stool matrix. The origin of the negative stool matrix is stated as "from patients".
- Precision:
- Number of Experts and Qualifications for Ground Truth: Not applicable for analytical studies, as ground truth is established by spiked concentrations of known organisms.
- Adjudication Method: Not applicable for analytical studies.
- Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study: Not applicable. These are analytical studies of the device's performance, not comparative effectiveness of human readers with/without AI assistance.
- Standalone Performance: Yes, these studies evaluate the standalone performance of the BD MAX™ Enteric Bacterial Panel system.
- Type of Ground Truth Used: For precision and reproducibility, known concentrations of target strains were used (e.g., "5 CFU/mL" for HN, "≥1 and
§ 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).