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The EntericBio" Dx assay, performed on ABI 7500 Fast Dx real-time instrument, is an in vitro multiplexed nucleic acid test for the direct, simultaneous, qualitative detection and identification of multiple enteric pathogens in Cary-Blair preserved stool specimens from individuals with signs and symptoms of infectious colitis or gastroenteritis. The test is based on detection of nucleic acids from:

• . Salmonella enterica spp.
• Shigella spp./ Enteroinvasive E. coli (EIEC)
• Campylobacter spp. (jejuni, coli and lari)
• STEC (Shiga-like toxin-producing E. coli), stx1/stx2 genes
• Vibrio spp. (cholerae and parahaemolyticus)
• . Giardia lamblia (also known as G. intestinalis and G. duodenalis)
• Entamoeba histolytica

Testing is performed on Cary-Blair preserved diarrheal specimens from symptomatic patients with suspected acute gastroenteritis, enteritis or colitis of bacterial or parasitic origin. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of Salmonella-specific, Campylobacter-specific, Shigella/ EIEC-specific ipaH, stx1/stx2, Vibrio-specific, Entamoeba-specific and Giardia-specific gene sequences. The test utilizes fluorogenic sequence-specific 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 diagnosis of Salmonella, Shigella / EIEC, Shigalike toxin-producing E. coli, Campylobacter spp., Entamoeba histolytica and Giardia spp. infections in humans.

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 EntericBio" Dx assay 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 EntericBio® Dx Assay provides PCR reagents to be used in conjunction with an automated pipetting system and the ABI 7500 Fast Dx instrument using standard filters. Results are interpreted using the EntericBio FastFinder plugin. The system provides automated, real-time amplification, detection and analysis and a user constructed template suitable for the EntericBio® Dx Assay.

The assay is composed of Stool Preparation Solution (SPS) tubes, PCR reagent strips containing lyophilized reagents, Resuspension Buffer (Negative Kit Control), Positive Kit Control containing DNA from all target analytes (with appropriate reconstitution buffer), and associated accessories,instruments and software for detection of bacterial and parasitic causes of gastroenteritis in humans.

The EntericBio" Dx assay detects target DNA from diarrheal Cary-Blair stool specimens from symptomatic individuals with suspected gastroenteritis or infectious colitis.

The assay works directly from a Cary-Blair preserved stool sample and does not require commercial nucleic acid extraction /purification. The PCR master mix with all the reagents required to perform each test is lyophilized into individual reaction wells on a strip. Each reaction well contains an Internal Amplification Control (IAC) to monitor for PCR inhibition.

Here's a breakdown of the acceptance criteria and the study proving the device's performance, based on the provided FDA 510(k) summary for the Serosep, Ltd. EntericBio® Dx Assay:

Acceptance Criteria and Reported Device Performance

The acceptance criteria are implicitly defined by the performance targets outlined for the analytical and clinical studies. Due to the nature of this 510(k) summary, specific numerical acceptance thresholds for clinical performance (e.g., minimum sensitivity/specificity) are not explicitly stated, but rather the observed performance metrics are presented. The reproducibility study explicitly states acceptance criteria.

Table of Acceptance Criteria and Reported Device Performance

Study Details:

1. Sample Sizes Used for the Test Set and Data Provenance:

   • Reproducibility Study (Test Set): Contrived stool samples spiked with various combinations of Vibrio parahaemolyticus, Shigella sonnei, and Giardia lamblia. Each analyte evaluated at True Negative, Low Positive (1.5x LoD), and Moderate Positive (3x LoD).
     • Sample Size: For accuracy, 30 samples per concentration per site (90 total per concentration per analyte across 3 sites). For negative, 60 samples per site (180 total across 3 sites).
     • Data Provenance: In-house (simulating multi-site) from Serosep. Retrospective.
   • LoD Study (Test Set): Contrived samples with target analytes spiked into negative stool matrix.
     • Sample Size: 20 replicates for each sample type/concentration.
     • Data Provenance: In-house, retrospective.
   • Analytical Reactivity/Exclusivity/Interference/Competitive Inhibition/Carry-Over (Test Sets): Contrived samples spiked into negative stool matrix or genomic DNA/RNA.
     • Sample Size: Generally 3 replicates for analytical reactivity/exclusivity/interference/carry-over. Competitive inhibition tested in triplicate.
     • Data Provenance: In-house, retrospective.
   • Clinical Performance Study (Test Set):
     • Fresh Clinical Samples (Prospective): 1491 prospective, 32 select. Total 1523 enrolled, 1472 evaluable.
       • Data Provenance: Multi-site clinical study, including two (2) US clinical sites and one (1) non-US clinical site. Prospective collection from symptomatic patients.
     • Frozen Clinical Samples (Archived): 212 enrolled, 209 evaluable.
       • Data Provenance: Archived samples from unknown collection sites, selected based on previous positive testing. Retrospective.
     • Contrived Samples (Simulated): 310 evaluable samples.
       • Data Provenance: Prepared using residual fresh specimens that tested negative. Retrospective, in-house.

2. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:

   • For the EntericBio® Dx Assay, the ground truth for the clinical study was established by comparator methods, not directly by human experts classifying images/data. The summary does not specify the number or qualifications of experts involved in running or interpreting the results of the FDA-cleared comparator assays, or for establishing the initial diagnosis for the archived samples. In diagnostics studies like this, the "ground truth" is typically another diagnostic method (often a laboratory reference method or a composite of multiple methods), which itself is run by trained laboratory personnel.

3. Adjudication Method for the Test Set:

   • For STEC and Campylobacter in fresh specimens, a composite comparator method was used: a specimen was positive if 2 out of 3 comparator assays were positive, and negative if 2 out of 3 were negative.
   • For all other target analytes and archived specimens, the comparator method consisted of one FDA-cleared assay.
   • This implies an adjudication method for the composite comparator (2/3 rule) but not for single comparator methods. There is no mention of human expert adjudication post-test to resolve discrepancies.

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, an MRMC comparative effectiveness study was not done. This device is a molecular diagnostic assay (PCR-based), not an AI-assisted diagnostic imaging device that involves human "readers" interpreting images. Therefore, the concept of human readers improving with AI assistance is not applicable here.

5. If a Standalone (i.e. algorithm only without human-in-the-loop performance) was done:

   • The EntericBio® Dx Assay is a standalone diagnostic test in the sense that its performance is evaluated directly against comparator methods. It does not inherently involve a "human-in-the-loop" decision-making process in the same way an AI-CAD (Computer-Aided Detection) system for radiology would. The device provides a result (positive/negative) based on its PCR analysis, and clinical interpretation occurs downstream by lab personnel and clinicians. The clinical performance tables (e.g., Table 12a-g) represent this standalone performance of the assay.

6. The type of ground truth used (expert consensus, pathology, outcomes data, etc.):

   • The ground truth for the clinical performance study was established by comparator methods, specifically:
     • For STEC and Campylobacter (fresh specimens): A composite comparator method of three FDA-cleared assays (2/3 rule).
     • For other targets (fresh) and all archived specimens: One FDA-cleared assay.
     • For contrived samples: The known spike concentration/strain was the ground truth.

7. The Sample Size for the Training Set:

   • This document is a 510(k) summary for an in vitro diagnostic (IVD) assay based on PCR, not a machine learning/AI model. Therefore, the concept of a "training set" for an algorithm is not directly applicable in the same way it would be for AI/ML device development. The device's design and optimization (analogous to "training") would have occurred during its development phase, using proprietary methods, and is not explicitly detailed as a distinct 'training set' of clinical samples in this regulatory submission.

8. How the Ground Truth for the Training Set was Established:

   • As explained above, this product is not an AI/ML algorithm requiring a "training set" in the conventional sense. The "ground truth" for the analytical studies (e.g., LoD, exclusivity) was based on precisely prepared samples with known concentrations and identities of microorganisms. For the development and validation of the molecular targets (primers/probes), ground truth would have been established through extensive molecular biology techniques, including sequencing and controlled lab cultures. These methods are inherent to the development of robust PCR assays.

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