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The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplexed in vitro diagnostic test intended for use with the BioCode MDx 3000 Instrument. The BioCode GPP is capable of the simultaneous detection of nucleic acids from multiple bacteria, viruses, and parasites extracted directly from unpreserved in Cary-Blair transport medium obtained from individuals with simptoms of gastrointestinal infection. The following bacteria, parasites, and viruses are identified using the BioCode Gastrointestinal Pathogen Panel:

• . Campylobacter (C. jejuni/C. coli)
• Clostridium difficile (C. difficile) toxin A/B (Fresh samples only)
• l Salmonella spp
• Vibrio (V. parahaemolyticus/V. vulnificus/ V. cholerae), including specific identification of Vibrio parahaemolyticus .
• . Yersinia enterocolitica
• . Enteroaggregative Escherichia coli (EAEC)
• Enterotoxigenic Escherichia coli (ETEC) lt/st
• E. coli 0157 serogroup
• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2
• Shigella/ Enteroinvasive Escherichia coli (EIEC)
• Cryptosporidium spp (C. parvum/C. hominis)
• Entamoeba histolytica
• Giardia lamblia (also known as G. intestinalis and G. duodenalis)
• . Adenovirus F 40/41
• Norovirus GI/GII ■
• . Rotavirus A

The BioCode GPP is indicated as an aid in the diagnosis of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data. For In Vitro Diagnostic Use Only. For Prescription Use Only.

Positive results do not rule out co-infection with organisms not included in the BioCode GPP. The agent detected may not be the definite cause of the disease. Negative results in the setting of clinical illness compatible with gastroenteriis 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. Concomitant culture is necessary for organism recovery and further typing of bacterial agents. This device is not intended to monitor or guide treatment for C. difficile infection.

Due to the small number of positive specimens collected for certain organisms during the prospective clinical study, performance characteristics for Adenovinus 40/41, Campylobacter, E. coli 0157, Shigella(EIEC, Yersinia enterocolitica, and Giardia lamblia were established additionally with retrospective clinical specimens. Performance characteristica, Giardia lamblia, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. cholerae) were established primarily using contrived clinical specimens.

The BioCode® Gastrointestinal Pathogen Panel (GPP) is a multiplexed nucleic acid-based test designed to be used with the BioCode MDx-3000 system. The BioCode MDx-3000 is an automated system that integrates PCR amplification, target capture, signal generation and optical detection for multiple gastrointestinal pathogens from a single stool specimen, either unpreserved or in Cary Blair. Stool specimens are processed, and nucleic acids extracted with easyMAG, MagNA Pure 96, KingFisher Flex and KingFisher Apex Dx. Once the PCR plate is set up and sealed, all other operations are automated on MDx-3000. The BioCode MDx-3000 Gastrointestinal Infection Panel simultaneously tests for 17 pathogens (see table below) from unpreserved stool specimens or stool collected in Cary-Blair transport medium. Results from the BioCode Gastrointestinal Pathogen Panel (GPP) test are available within less than 4 hours.

The provided text describes the BioCode Gastrointestinal Pathogen Panel (GPP), a diagnostic test for gastrointestinal pathogens, and a study to demonstrate its substantial equivalence to a predicate device.

Here's an analysis of the acceptance criteria and study data:

1. Acceptance Criteria and Reported Device Performance

The acceptance criteria for each pathogen are implied by the reported Positive Percent Agreement (PPA) and Negative Percent Agreement (NPA) compared to the easyMAG extraction method (used with the predicate device) for each extraction system (KingFisher Flex and KingFisher Apex Dx). While explicit pre-defined acceptance criteria values are not stated, the tables present the achieved performance with 95% Confidence Intervals. Generally, a high PPA and NPA (typically >90-95%) with narrow confidence intervals are expected for substantial equivalence for diagnostic tests.

Here's a summary of the reported performance for the BioCode GPP using KingFisher Flex and KingFisher Apex Dx, focusing on the "All Archived" data as it covers a larger sample size for each target. Targets with PPA < 90% are highlighted as indicated in the document; however, the document notes that these are "Positive agreement <90%" for Archived samples only, and specifically points out individual false positives/negatives that were retested and often resolved. Targets for which "N/A" is reported for PPA/NPA indicate no positive/negative archived samples were available for comparison, and thus performance was primarily established with contrived samples (as indicated in the 'Indications for Use' section).

Table of Device Performance (Archived Samples - All Combined)

Note:

• Asterisks (**) in the table indicate that the specific performance measure (PPA) was below 90% for archived samples. The document explicitly notes for Vibrio spp. (not parahaemolyticus) that 1 out of 2 positive concordance was observed for both KingFisher Flex and KingFisher Apex Dx, resulting in 50% PPA.
• Retesting of discordant samples often showed resolution in favor of the predicate or new device, but the summary tables reflect the initial comparison. The footnotes (a-q) provide detailed explanations for discordant cases, including instances where samples were invalid or initial false results were later identified as true negatives/positives upon retesting.

2. Sample Size and Data Provenance

• Test Set (Clinical Method Comparison Study):
  • Archived Samples: 468 remnant, de-identified samples (254 frozen unpreserved stool and 214 inoculated Cary-Blair stool). These samples were prospectively collected for the clinical study that resulted in the predicate device (K180041 BioCode® GPP FDA clearance). The country of origin is not explicitly stated, but clinical studies for FDA clearance typically involve multi-center studies within the US or compliant international sites. "Mayo-GI" and "TRI" sample names suggest US clinical sites.
  • Fresh Samples (for C. difficile testing): 54 freshly collected leftover samples (unpreserved).
  • Contrived Samples: 120 samples (15 at 3x LoD and 15 at 6xLoD for each of three targets: Entamoeba histolytica, Yersinia enterocolitica, and Vibrio spp.).

3. Number of Experts to Establish Ground Truth for Test Set and Qualifications

The ground truth for the clinical method comparison study was established by comparing the results of the new device (BioCode GPP with KingFisher Flex and KingFisher Apex Dx extraction) against the results obtained with the easyMAG extraction, which was used with the predicate device (BioCode GPP K190585). The predicate device itself would have undergone its own clinical validation against a pre-established ground truth. Therefore, the "ground truth" for this specific study is the performance of the BioCode GPP with easyMAG extraction.

The document does not explicitly state the number or qualifications of experts used for establishing the initial ground truth of the predicate device, or for adjudicating discordant results in this study. However, the retesting notes for discordant samples mention "consensus results" were not used in the agreement calculation, implying that the retesting was performed to understand the discrepancy rather than to establish a new ground truth.

4. Adjudication Method for the Test Set

The adjudication method is described in the footnotes for Tables 11 and 16. For discordant results between the easyMAG (reference) and the KingFisher Flex/Apex Dx (new device), samples were retested twice with both original extraction methods. The outcome of these retests served to clarify the discrepancy, though the initial raw comparison was used to calculate the agreement, with retest findings noted in the footnotes. For example, a "false negative" for the new device might become a "true negative" upon retesting if the reference system also failed to detect it consistently. However, "consensus results of the discordant samples were not used in the calculation of the agreements" in the main tables but rather for detailed understanding.

5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study

No Multi-Reader Multi-Case (MRMC) comparative effectiveness study was done. This study focuses on a laboratory diagnostic device, not an imaging device requiring human reader interpretation. Therefore, the concept of "human readers improve with AI vs without AI assistance" is not applicable here.

6. Standalone Performance Study

Yes, a standalone performance study was done for the device in the context of the new extraction platforms. The "Nonclinical testing summary" details a Reproducibility Study and a Limit of Detection (LoD) study. These studies evaluate the algorithm's (BioCode GPP assay's) consistency and sensitivity when integrated with the new KingFisher Flex and KingFisher Apex Dx extraction systems, independent of direct human interpretative input beyond standard lab procedures.

• Reproducibility Study: Assessed intra-assay, inter-assay, day-to-day, and instrument-to-instrument (operator-to-operator) reproducibility using quantitative controls diluted in stool.
• Limit of Detection (LoD) Study: Determined the lowest concentration at which ≥95% detection was achieved in 20 replicates for each target, for both unpreserved and Cary-Blair stool, using the new extraction methods.

7. Type of Ground Truth Used

For the clinical method comparison study (test set), the ground truth was the result generated by the predicate device's established extraction method (easyMAG). This is a comparative effectiveness study where the predicate device's performance established the "truth" for evaluating the new device's substantial equivalence.

For the LoD and reproducibility studies, the ground truth was based on quantified stocks of bacteria, viruses, or parasites (except for Norovirus GI/GII which used positive clinical specimens with serial dilutions) introduced into negative stool matrices.

8. Sample Size for the Training Set

The document does not explicitly describe a "training set" for the BioCode GPP itself, as it's a multiplex nucleic acid-based test rather than a machine learning or AI algorithm in the common sense requiring explicit training data. The assay's design (probes, primers, etc.) would have been developed and optimized against a range of target and non-target organisms.
The 468 remnant clinical samples used in the method comparison study were prospectively collected for the predicate device's clinical study (K180041 BioCode® GPP FDA clearance), suggesting they were part of the validation for the predicate, not a training set for the current device's underlying assay design.

9. How the Ground Truth for the Training Set Was Established

As noted above, an explicit "training set" with ground truth in the AI/ML context isn't specified for this type of diagnostic assay. The development of such an assay involves extensive analytical validation to establish specificity, sensitivity, and inclusivity using characterized microbial strains, clinical isolates, and negative controls. The ground truth for these developmental studies would be based on molecular characterization (e.g., sequencing), culture, or other reference methods for the target organisms. The performance of the predicate device (K190585) would have been established through a clinical study where its results were compared against clinical diagnosis, culture, or other validated reference methods.

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