Biocode Gastrointestinal Pathogen Panel (GPP)

K190585 · Applied BioCode, Inc. · PCH · Jun 5, 2019 · Microbiology

Device Facts

• Record ID: K190585
• Device Name: Biocode Gastrointestinal Pathogen Panel (GPP)
• Applicant: Applied BioCode, Inc.
• Product Code: PCH · Microbiology
• Decision Date: Jun 5, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3990
• Device Class: Class 2

Indications for Use

The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with the BioCode MDx 3000 Instrument. The BioCode GPP is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites extracted directly from unpreserved stool samples or stool preserved in Cary-Blair transport medium obtained from individuals with signs and/or symptoms 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) 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. 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 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. 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.

Device Story

Multiplexed nucleic acid-based in vitro diagnostic test; uses BioCode MDx 3000 instrument. Inputs: unpreserved stool or stool in Cary-Blair medium. Process: nucleic acid extraction (Roche MagNA Pure 96 or easyMAG); PCR amplification; target capture; signal generation; optical detection via barcoded magnetic beads (BMB). Output: qualitative identification of 17 gastrointestinal pathogens. Used in clinical laboratories; operated by trained personnel. Results provided within 4 hours; used alongside clinical/epidemiological data to aid diagnosis. Benefits: rapid, simultaneous detection of multiple pathogens; aids clinical decision-making for gastrointestinal illness.

Clinical Evidence

Clinical study evaluated 466 archived specimens (275 frozen unpreserved, 191 inoculated Cary-Blair) and 53 fresh samples. Performance compared to historical reference results from K180041. PPA and NPA were calculated for 17 targets. Results showed high agreement across targets; some variability noted for specific organisms (e.g., Adenovirus 40/41, ETEC) consistent with low prevalence or sample type. Bench testing included LoD confirmation, reproducibility, and carry-over studies.

Technological Characteristics

Multiplex RT-PCR; probe hybridization to biotinylated PCR products; fluorescence detection; barcoded magnetic beads (BMB). Extraction: Roche MagNA Pure 96 or easyMAG. Instrument: BioCode MDx 3000. Connectivity: Standalone system. Software: Automated analysis of optical signals from barcoded beads.

Indications for Use

Indicated for individuals with signs/symptoms of gastrointestinal infection. Used as an aid in diagnosis of gastrointestinal illness. Not for monitoring/guiding C. difficile treatment.

Regulatory Classification

Identification

A gastrointestinal microorganism multiplex nucleic acid-based assay is a qualitative in 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.

Special Controls

*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).

Predicate Devices

• BioCode Gastrointestinal Pathogen Panel (GPP) (K180041)

Submission Summary (Full Text)

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# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

A. 510(k) Number:
K190585

B. Purpose for Submission:
To obtain a substantial equivalence determination for the BioCode Gastrointestinal Pathogen Panel (GPP) for the detection of microbial nucleic acids extracted from human stool specimens for use on the Applied BioCode MDx 3000 instrument, using an alternate sample extraction system, the Roche Diagnostics MagNA Pure 96.

C. Measurands:
Target nucleic acid sequences of the following gastrointestinal microorganisms: Campylobacter (C. jejuni/C. coli), Clostridium difficile (C. difficile) toxin A/B (Fresh samples only), 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 O157 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 and Rotavirus A

D. Type of Test:
Qualitative nucleic acid multiplex test

E. Applicant:
Applied BioCode, Inc.

F. Proprietary and Established Names:
BioCode Gastrointestinal Pathogen Panel (GPP)

G. Regulatory Information:
1. Regulation section:
21 CFR 866.3990. Gastrointestinal microorganisms multiplex nucleic acid-based assay

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2. Classification:

Class II (Special Controls)

3. Product code:

PCH, OOI

4. Panel:

Microbiology (83)

H. Indication(s) for Use:

1. Indications for Use(s):

The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with the BioCode MDx 3000 Instrument. The BioCode GPP is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites extracted directly from unpreserved stool samples or stool preserved in Cary-Blair transport medium obtained from individuals with signs and/or symptoms 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)
- 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 O157 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 specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical,

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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 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. 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 Adenovirus 40/41, Campylobacter, E. coli O157, Shigella/EIEC, Yersinia enterocolitica, and Giardia lamblia were established additionally with retrospective clinical specimens. Performance characteristics for Entamoeba histolytica, Giardia lamblia, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and V. cholerae) were established primarily using contrived clinical specimens.

2. Special conditions for use statement(s):

For in vitro diagnostic use only

For prescription use only.

3. Special instrument requirements:

For use with the BioCode MDx 3000 instrument.

I. Device Description:

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. 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.

J. Substantial Equivalence Information:

1. Predicate device name(s):

BioCode Gastrointestinal Pathogen Panel (GPP)

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2. Predicate 510(k) number(s):

K180041

3. Comparison with predicate:

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| Similarities | | |
| --- | --- | --- |
| Item | New Device: Applied BioCode Gastrointestinal Pathogen Panel (GPP)
K190585 | Predicate: Applied BioCode Gastrointestinal Pathogen Panel (GPP)
K180041 |
| Indications for Use | The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative multiplexed nucleic acid-based in vitro diagnostic test intended for use with the BioCode MDx 3000 Instrument. The BioCode GPP is capable of the simultaneous detection and identification of nucleic acids from multiple bacteria, viruses, and parasites extracted directly from unpreserved stool samples or stool preserved in Cary-Blair transport medium obtained from individuals with signs and/or symptoms 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)
• 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 O157 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 | The BioCode Gastrointestinal Pathogen Panel (GPP) is a qualitative, gastrointestinal microorganism multiplexed nucleic acid-based assay capable of detecting of nucleic acids from the following organisms in unpreserved stool and Cary-Blair media:
• Adenovirus 40/41
• Campylobacter (C. jejuni, C. coli)
• Clostridium difficile (C. difficile) toxin A/B (from fresh specimens only)
• Cryptosporidium (C. parvum, C. hominis)
• Entamoeba histolytica
• Escherichia coli (E. coli) O157
• Enterotoxigenic E. coli (ETEC) LT/ST
• Enteroaggregative E. coli (EAEC)
• Giardia lamblia (also known as G. intestinalis and G. duodenalis)
• Norovirus GI/GII
• Rotavirus A
• Salmonella spp.
• Shiga-like Toxin producing E. coli (STEC) stx1/stx2
• Shigella (S. boydii, S. sonnei, S. flexneri, S. dysenteriae)/EIEC
• Vibrio spp. (V. cholerae, V. parahaemolyticus, V. vulnificus), specific identification of V. parahaemolyticus
• Yersinia enterocolitica

The BioCode Gastrointestinal Pathogen Panel (GPP) is indicated as an aid in the diagnosis of specific agents of gastrointestinal illness and results are meant to be used in conjunction with other clinical, laboratory, and epidemiological data.

Positive results do not rule out co-infection with organisms not included in the |

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| Similarities | | |
| --- | --- | --- |
| | • Norovirus GI/GII
• Rotavirus A
The BioCode GPP is indicated as an aid in the diagnosis of specific agents 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 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. 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 Adenovirus 40/41, Campylobacter, E. coli O157, Shigella/EIEC, Yersinia enterocolitica, and Giardia lamblia were established additionally with retrospective clinical specimens. Performance characteristics for Entamoeba histolytica, Giardia lamblia, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and V. cholerae) were established primarily using contrived clinical specimens. | BioCode Gastrointestinal Pathogen Panel (GPP). The agent detected may not be the 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. 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 Campylobacter spp., E. coli O157, Shigella/EIEC, Yersinia enterocolitica, and Adenovirus 40/41 were established primarily with retrospective clinical specimens.

Performance characteristics for Entamoeba histolytica, and Vibrio spp. (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens. |
| Sample Type | Same | Unpreserved stool and stool in Cary- |

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| Similarities | | |
| --- | --- | --- |
| | | Blair medium |
| Control | Same | Externally sourced |
| Instrument | Same | BioCode MDx 3000 |
| Assay Methodology | Same | Multiplex PCR and probe hybridization followed by fluorescence detection and decoding of barcoded magnetic beads (BMB) that are coupled to biotinylated products with streptavidin conjugate |
| Test Interpretation | Same | Automated test interpretation and report generation. |
| Calibrators | Same | Internal Calibration |
| Differences | | |
| --- | --- | --- |
| Item | New Device: Applied BioCode Gastrointestinal Pathogen Panel (GPP) K190585 | Applied BioCode Gastrointestinal Pathogen Panel (GPP) K180041 |
| Sample Extraction | Roche MagNA Pure 96 | bioMérieux NucliSENSE easyMAG |
| Time to Result | Approximately 4 hours | Approximately 5 hours |

K. Standard/Guidance Document Referenced (if applicable):

Not applicable.

L. Test Principle:

The BioCode Gastrointestinal Pathogen Panel (GPP) is an automated system that integrates PCR amplification, target capture, signal generation and optical detection for multiple gastrointestinal pathogens from a single stool specimen. Stool specimens are processed, and nucleic acids are extracted with the bioMérieux NucliSENSE easyMAG or Roche MagNA Pure 96 automated systems. Once the PCR plate is set up and sealed, all other operations are automated.

M. Performance Characteristics:

1. Analytical performance:

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# a. Reproducibility:

A study was performed to assess the Reproducibility of the BioCode GPP using samples extracted with the MagNA Pure 96. This study was designed to assess intra-assay (within run), inter-assay (run-to-run), day-to-day and instrument-to-instrument (operator-to-operator) reproducibility. One lot of reagents was assayed at Applied BioCode on 3 instruments by 3 operators, 2 runs per day per operator for 5 days (total of 30 runs). The reproducibility panel consisted of 7 contrived samples (sample 7 is a negative control) extracted in triplicate and each assayed in singlet. The samples consisted of combinations of 12 representative targets at $1.5\mathrm{x}$ LoD (Low) and $3\mathrm{x}$ LoD (Medium). Results from the study are shown in Table 1 below.

Table 1: Reproducibility of BioCode GPP with MagNA Pure 96 Extractions- Qualitative results.

| Organism Tested | Target Probe | Concentration Tested | Expected Results | % Agreement with Expected Result | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Instrument 1 Operator 1 | Instrument 2 Operator 2 | Instrument 3 Operator 3 | All Instruments/Operators |
| Campylobacter jejuni spp. jejuni ATCC 33292 | Campy | Medium Positive 3xLoD 1.05 x 103CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 5.25 x 102CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Clostridium difficile (toxinotype III; Nap1) Zeptometrix 0801619cf | tcdB | Medium Positive 3xLoD 1.25 x 103CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 6.23 x 102CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Enteroaggregative E. coli O92:H33 (EAEC) STEC TW04440 | EAEC | Medium Positive 3xLoD 2.10 x 103CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 1.05 x 103CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Enterotoxigenic E. coli O78:H11 H10407 (ETEC) ATCC 35401 | ST-1a | Medium Positive 3xLoD 8.40 x 102CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 4.20 x 102CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not | 150/150 | 150/150 | 150/150 | 450/450 |

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| Organism Tested | Target Probe | Concentration Tested | Expected Results | % Agreement with Expected Result | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Instrument 1 Operator 1 | Instrument 2 Operator 2 | Instrument 3 Operator 3 | All Instruments/Operators |
| | | | Detected | (100%) | (100%) | (100%) | (100%) |
| Salmonella enterica ssp. enterica ATCC 14028 | Salm | Medium Positive 3xLoD 3.30 x 10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 1.65 x 10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Shiga-like toxin producing E. coli (STEC) ATCC BAA-2217 | stx2 | Medium Positive 3xLoD 3.75 x 10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 1.88 x10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Shigella sonnei ATCC 29930 | Shig | Medium Positive 3xLoD 6.60 x 10^{2} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 3.30 x 10^{2} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Vibrio parahaemolyticus ATCC 17802 | V. para | Medium Positive 3xLoD 1.95 x10^{1} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 9.75x10^{0} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Yersinia enterocolitica ATCC 23715 | Y.ent | Medium Positive 3xLoD 2.25 x10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive 1.5xLoD 1.13 x10^{3} CFU/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Cryptosporidium Parvum waterborne P102 | Crypto | Medium Positive 3xLoD 9.30 x 10^{3} oocysts/mL | Detected | 30/30 (100%) | 30/30 (100%) | 29/30 (97%) | 89/90 (99%) |
| | | Low Positive | Detected | 30/30 | 30/30 | 29/30 | 89/90 |

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| Organism Tested | Target Probe | Concentration Tested | Expected Results | % Agreement with Expected Result | | | |
| --- | --- | --- | --- | --- | --- | --- | --- |
| | | | | Instrument 1 Operator 1 | Instrument 2 Operator 2 | Instrument 3 Operator 3 | All Instruments/Operators |
| | | 1.5xLoD
4.65 x 10^{3} oocysts/mL | | (100%) | (100%) | (97%) | (99%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Giardia intestinalis
(aka G. lamblia)
waterborne P101 | G.lam | Medium Positive
3xLoD
2.70 x 10^{3} cysts/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive
1.5xLoD
1.35 x 10^{3} cysts/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |
| Rotavirus
ATCC VR-2018 | Rota | Medium Positive
3xLoD
3.75 x 10^{3} TCID_{50}/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | Low Positive
1.5xLoD
1.88 x 10^{2} TCID_{50}/mL | Detected | 30/30 (100%) | 30/30 (100%) | 30/30 (100%) | 90/90 (100%) |
| | | None | Not Detected | 150/150 (100%) | 150/150 (100%) | 150/150 (100%) | 450/450 (100%) |

b. Fresh vs. Frozen Study:

Please refer to previously FDA-cleared 510(k) Premarket Notifications, k180041 for Fresh vs. Frozen performance. No additional testing was conducted.

c. Specimen Stability:

Please refer to previously FDA-cleared 510(k) Premarket Notifications, k180041 for Specimen Stability performance. No additional testing was conducted.

d. Limit of detection:

A study was performed to assess the performance of the BioCode GPP on the BioCode MDx 3000 at the Limit of Detection (LoD) for both unpreserved Stool and Cary-Blair specimens. In this study the GI Panel was tested with quantified bacteria, virus or parasite stocks (except norovirus which used clinical samples). For initial screening, four replicates of each concentration (near LoD for the predicate) in negative stool and Cary-Blair were extracted on the easyMAG and MagNA Pure 96 Systems and tested in singlet with the BioCode GPP on the BioCode MDx 3000 system. The LoD was confirmed by extracting 20 replicates of

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each sample type/extraction method and testing each in singlet for a total of 20 replicates at or near presumptive LoD. LoD for each stock was defined as the lowest concentration with $\geq 95\%$ detection of 20 replicates (19 out of 20). Results are shown in the Tables below.

Table 2: Limit of Detection Summary of Unpreserved Stool Extracted with the easyMAG and MagNA Pure 96 and Assayed with BioCode GPP.

| Strain | Source | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Unpreserved Stool LoD | Detection | Unpreserved Stool LoD | Detection |
| Campylobacter coli | ATCC 33559 | 2.81 x 10^1 CFU/mL | 19/20 | 2.81 x 10^1 CFU/mL | 20/20 |
| Campylobacter jejuni spp. jejuni | ATCC 33292 | 3.50 x 10^2 CFU/mL | 19/20 | 3.50 x 10^2 CFU/mL | 19/20 |
| Clostridium difficile (toxinotype 0) | ATCC 9689 | 9.50 x 10^1 CFU/mL | 20/20 | 9.50 x 10^1 CFU/mL | 20/20 |
| Clostridium difficile (toxinotype III; Nap1) | Zeptometrix 0801619cf | 4.15 x 10^2 CFU/mL | 20/20 | 4.15 x 10^2 CFU/mL | 20/20 |
| Enteroaggregative E. coli O92:H33 (EAEC) | STEC TW04440 | 7.00 x 10^2 CFU/mL | 20/20 | 7.00 x 10^2 CFU/mL | 20/20 |
| Enteroinvasive E. coli O29:NM (EIEC) | ATCC 43892 | 3.60 x 10^2 CFU/mL | 20/20 | 1.80 x 10^2 CFU/mL | 20/20 |
| Enterotoxigenic E. coli O78:H11 H10407 (ETEC) | ATCC 35401 | 2.80 x 10^2 CFU/mL | 20/20 | 2.80 x 10^2 CFU/mL | 20/20 |
| Salmonella bongori | SGSC 4900 | 1.40 x 10^3 CFU/mL | 20/20 | 1.40 x 10^3 CFU/mL | 20/20 |
| Salmonella enterica ssp. enterica | ATCC 14028 | 1.10 x 10^3 CFU/mL | 20/20 | 1.10 x 10^3 CFU/mL | 20/20 |
| Shiga-like toxin producing E. coli (STEC) | ATCC BAA-2217 | 1.25 x 10^3 CFU/mL | 20/20 | 1.25 x 10^3 CFU/mL | 20/20 |
| E. coli O157 | ATCC 700376 | 1.65 x 10^3 CFU/mL | 20/20 | 1.65 x 10^3 CFU/mL | 20/20 |
| Shigella sonnei | ATCC 29930 | 2.20 x 10^2 CFU/mL | 20/20 | 2.20 x 10^2 CFU/mL | 20/20 |
| Vibrio cholerae | ATCC 25870 | 2.45 x 10^2 CFU/mL | 20/20 | 2.45 x 10^2 CFU/mL | 20/20 |
| Vibrio parahaemolyticus | ATCC 17802 | 6.50 x 10^0 CFU/mL | 20/20 | 6.50 x 10^0 CFU/mL | 20/20 |
| Yersinia enterocolitica | ATCC 23715 | 7.50 x 10^2 CFU/mL | 20/20 | 7.50 x 10^2 CFU/mL | 20/20 |
| Cryptosporidium parvum | waterborne P102C | 3.10 x 10^3 oocysts/mL | 20/20 | 3.10 x 10^3 oocysts/mL | 20/20 |

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| Strain | Source | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Unpreserved Stool LoD | Detection | Unpreserved Stool LoD | Detection |
| Entamoeba histolytica HB-301:NIH | BEI NR-178 | 1.55 x 10-1cysts/mL | 20/20 | 1.55 x10-1cysts/mL | 20/20 |
| Giardia intestinalis (aka G. lamblia) | waterborne P101 | 9.00 x 102cysts/mL | 20/20 | 9.00 x102cysts/mL | 20/20 |
| Adenovirus 40 (dugan) | Zeptometrix 0810084 | 2.00 x 10-1TCID50/mL | 20/20 | 1.00 x10-1TCID50/mL | 20/20 |
| Adenovirus 41 (TAK) | Zeptometrix 0810085 | 9.4 x 10-2TCID50/mL | 20/20 | 4.70 x10-2TCID50/mL | 20/20 |
| Rotavirus A | ATCC VR-2018 | 2.5 x 103TCID50/mL | 20/20 | 1.25 x103TCID50/mL | 20/20 |

Table 3: Limit of Detection Summary of Cary-Blair Stool Extracted with the easyMAG and MagNA Pure 96 and Assayed with BioCode GPP.

| Strain | Source | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Cary-Blair Stool LoD | Detection | Cary-Blair Stool LoD | Detection |
| Campylobacter coli | ATCC 33559 | 5.61 x 101CFU/mL | 20/20 | 2.81 x 101CFU/mL | 20/20 |
| Campylobacter jejuni spp. jejuni | ATCC 33292 | 3.50 x102CFU/mL | 20/20 | 7.00 x102CFU/mL | 20/20 |
| Clostridium difficile(toxinotype 0) | ATCC 9689 | 9.50 x 101CFU/mL | 20/20 | 9.50 x 101CFU/mL | 20/20 |
| Clostridium difficile(toxinotype III;Nap1) | Zeptometrix 0801619cf | 4.15 x102CFU/mL | 20/20 | 4.15 x102CFU/mL | 20/20 |
| EnteroaggregativeE. coli O92:H33(EAEC) | STEC TW04440 | 7.00 x102CFU/mL | 20/20 | 7.00 x102CFU/mL | 20/20 |
| Enteroinvasive E.coliO29:NM (EIEC) | ATCC 43892 | 3.60 x102CFU/mL | 20/20 | 1.80 x102CFU/mL | 20/20 |
| Enterotoxigenic E.coliO78:H11 H10407(ETEC) | ATCC 35401 | 2.80 x102CFU/mL | 20/20 | 2.80 x102CFU/mL | 19/20 |
| Salmonella bongori | SGSC 4900 | 1.40 x103CFU/mL | 19/20 | 1.40 x103CFU/mL | 20/20 |
| Salmonella enterica ssp. enterica | ATCC 14028 | 1.10 x103CFU/mL | 20/20 | 1.10 x103CFU/mL | 20/20 |

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| Strain | Source | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Cary-Blair Stool LoD | Detection | Cary-Blair Stool LoD | Detection |
| Shiga-like toxin producing E. coli (STEC) | ATCC BAA-2217 | 1.25 x103CFU/mL | 20/20 | 1.25 x103CFU/mL | 20/20 |
| E. coli O157 | ATCC 700376 | 3.30 x103CFU/mL | 20/20 | 1.65 x103CFU/mL | 20/20 |
| Shigella sonnei | ATCC 29930 | 2.20 x102CFU/mL | 20/20 | 2.20 x102CFU/mL | 20/20 |
| Vibrio cholerae | ATCC 25870 | 2.45 x102CFU/mL | 20/20 | 2.45 x102CFU/mL | 20/20 |
| Vibrio parahaemolyticus | ATCC 17802 | 6.50 x100CFU/mL | 20/20 | 6.50 x100CFU/mL | 20/20 |
| Yersinia enterocolitica | ATCC 23715 | 7.50 x102CFU/mL | 20/20 | 7.50 x102CFU/mL | 20/20 |
| Cryptosporidium parvum | waterborne P102C | 3.10 x103oocysts/mL | 20/20 | 3.10 x103oocysts/mL | 20/20 |
| Entamoeba histolytica HB-301:NIH | BEI NR-178 | 1.55 x10-1cysts/mL | 20/20 | 1.55 x10-1cysts/mL | 20/20 |
| Giardia intestinalis (aka G. lamblia) | waterborne P101 | 9.00 x102cysts/mL | 20/20 | 9.00 x102cysts/mL | 20/20 |
| Adenovirus 40 (dugan) | Zeptometri x 0810084 | 2.00 x10-1TCID50/mL | 20/20 | 1.00 x10-1TCID50/mL | 20/20 |
| Adenovirus 41 (TAK) | Zeptometri x 0810085 | 4.70 x10-2TCID50/mL | 20/20 | 4.70 x10-2TCID50/mL | 20/20 |
| Rotavirus A | ATCC VR-2018 | 1.25 x103TCID50/mL | 20/20 | 1.25 x103TCID50/mL | 20/20 |

For Norovirus GI and GII targets, positive clinical specimens were used, and serial dilutions (initial 10- fold dilution series followed by finer dilutions) were performed. Four replicates of each dilution in negative unpreserved stool and Cary-Blair stool were extracted with the easyMAG and MagNA Pure 96 Systems and tested with the BioCode GPP on the BioCode MDx 3000 system. The LoD was confirmed by extracting 20 replicates of each sample type with each extraction method and testing at or near presumptive LoD. For unpreserved stool, LoD with the easyMAG extraction was 2-fold and 8.3-fold lower than the MagNA Pure 96 extraction for Norovirus GI and Norovirus GII, respectively. For Cary-Blair stool, LoD with the easyMAG extraction was less than 2-fold lower than the MagNA Pure 96 extraction for both Norovirus GI and GII. Results are shown in the tables below.

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Table 4: Norovirus - Limit of Detection Summary of Unpreserved Stool Extracted with the easyMAG and MagNA Pure 96 and Assayed with BioCode GPP.

| Target | Source | Target Probe | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Unpreserved Stool Dilution | Detection | Unpreserved Stool Dilution | Detection |
| Norovirus GI | Clinical Sample ID#60 | NoVG1 | 1:10,000 | 20/20 | 1:5,000 | 19/20 |
| Norovirus GII | Clinical Sample ID#54 | NoVG2 | 1:250,000 | 20/20 | 1:30,000 | 20/20 |

Table 5: Norovirus - Limit of Detection Summary of Cary-Blair Stool Extracted with the easyMAG and MagNA Pure 96 and Assayed with BioCode GPP.

| Target | Source | Target Probe | EasyMAG | | MagNA Pure 96 | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | Unpreserved Stool Dilution | Detection | Unpreserved Stool Dilution | Detection |
| Norovirus GI | Clinical Sample ID#60 | NoVG1 | 1:50,000 | 20/20 | 1:80,000 | 19/20 |
| Norovirus GII | Clinical Sample ID#54 | NoVG2 | 1:100,000 | 20/20 | 1:80,000 | 20/20 |

e. Analytical Reactivity:

Please refer to previously FDA-cleared 510(k) Premarket Notifications, K180041 for Analytical Reactivity performance. No additional testing was conducted.

f. Analytical Specificity:

Please refer to previously FDA-cleared 510(k) Premarket Notifications, K180041 for Analytical Specificity performance. No additional testing was conducted.

g. Interference:

Please refer to previously FDA-cleared 510(k) Premarket Notifications, K180041 for Potentially Interfering Substances study information and results. No additional testing was conducted.

h. Carry-Over/Cross-Contamination study:

A study was performed to demonstrate the absence of carryover or cross-contamination of the MagNA Pure 96. High-positive samples (Shigella sonnei, ATCC 29930 at $5.42 \times 10^{6}$ CFU/mL) were tested alternating with no-template control samples in a "checkerboard" pattern. Samples were extracted an alternating pattern of high and low concentration then and assayed individually. The study consisted of

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five complete MagNA Pure 96 well runs and assayed on two BioCode MDx 3000 instruments. No evidence of carry-over contamination was observed.

## 2. Comparison studies:

a. Method comparison with predicate device:

Not applicable

b. Matrix Comparison :

Not applicable

## 3. Clinical studies:

A clinical investigational study was performed in which a total of 466 leftover, de-identified archived specimens (275 frozen unpreserved and 191 inoculated Cary-Blair) that were previously characterized as positive from the BioCode Gastrointestinal Pathogen Panel (K180041) clinical study were collected. Fifty-three (53) freshly collected leftover samples were used for C. difficile testing. In addition, a total of 120 samples were contrived and tested to determine the performance characteristics for Entamoeba histolytica, Yersinia enterocolitica and Vibrio (V. parahaemolyticus, V. vulnificus, and V. cholerae). Specimens were extracted using the MagNA Pure 96 and the easyMAG and tested with the BioCode Gastrointestinal Pathogen Panel (GPP) on the MDx 3000 system.

Table 6: Demographic Data for Archived Specimens (Frozen Unpreserved and Inoculated Cary-Blair

| Archived Samples | |
| --- | --- |
| Total Specimen Count | 466 |
| Gender | |
| Male | 248/466 (53.22%) |
| Female | 211/466 (45.28%) |
| Unknown | 7/466 (1.50%) |
| Age Category | |
| ≤ 5 yrs | 85/466 (18.24%) |
| 6-21 yrs | 91/466 (19.53%) |
| 22-59 yrs | 194/466 (41.63%) |
| 60+yrs | 89/466 (19.10%) |
| Unknown | 7/466 (1.50%) |

Table 7: Demographic Data for Fresh Specimens (Unpreserved)

| Fresh Samples | |
| --- | --- |
| Total Specimen Count | 53 |
| Gender | |

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Table 8: Summary of Clinical Investigational Study Results (Archived Specimens)

| Target | Specimen Type | (n) | Positive Agreement | | Negative Agreement | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | PPA (%) | 95% CI | NPA (%) | 95% CI |
| Campylobacter spp.a | Inoculated Cary-Blair | 190 | 22/23 (95.65) | 79.0 – 99.2 | 164/167 (98.20) | 94.9 – 99.4 |
| | Unpreserved (Frozen) | 274 | 27/27 (100) | 87.5 - 100 | 244/247 (98.80) | 96.5 – 99.6 |
| | All Archived | 464 | 49/50 (98.0) | 89.5 – 99.6 | 408/414 (98.60) | 96.9 – 99.3 |
| Clostridium difficileb | Inoculated Cary-Blair | 190 | 10/11 (90.91) | 62.3 – 98.4 | 178/179 (99.44) | 96.9 – 99.9 |
| | Unpreserved (Frozen) | 274 | 21/22 (95.45) | 78.2 – 99.2 | 250/252 (99.20) | 97.2 – 99.8 |
| | All Archived | 464 | 31/33 (93.94) | 80.4 – 98.3 | 428/431 (99.30) | 98.0 – 99.8 |
| E. coli O157 | Inoculated Cary-Blair | 190 | 3/3 (100) | 43.9 - 100 | 187/187 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 14/14 (100) | 78.5 - 100 | 260/260 (100) | 98.5 - 100 |
| | All Archived | 464 | 17/17 (100) | 81.6 - 100 | 447/447 (100) | 99.1 - 100 |
| Enteroaggregative E. coli (EAEC)c | Inoculated Cary-Blair | 190 | 15/17 (88.24) | 65.7 – 96.7 | 171/173 (98.8) | 95.9 – 99.7 |
| | Unpreserved (Frozen) | 274 | 29/29 (100) | 88.3 - 100 | 244/245 (99.59) | 97.7 – 99.9 |
| | All Archived | 464 | 44/46 (95.65) | 85.5 – 98.8 | 415/418 (99.30) | 97.9 -99.8 |
| Enterotoxigenic E. coli (ETEC)d | Inoculated Cary-Blair | 190 | 3/5 (60.00) | 23.1 – 88.2 | 185/185 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 13/13 (100) | 77.2 - 100 | 261/261 (100) | 98.5 - 100 |

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| Target | Specimen Type | (n) | Positive Agreement | | Negative Agreement | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | PPA (%) | 95% CI | NPA (%) | 95% CI |
| Shiga toxin-producing *E. coli* (STEC)^{e} | All Archived | 464 | 16/18 (88.89) | 67.2 – 96.9 | 446/446 (100) | 99.1 - 100 |
| | Inoculated Cary-Blair | 190 | 12/13 (92.31) | 66.7 – 98.6 | 177/177 (100) | 97.9 - 100 |
| | Unpreserved (Frozen) | 274 | 29/30 (96.67) | 83.3 – 99.4 | 243/244 (99.60) | 97.7 – 99.9 |
| | All Archived | 464 | 41/43 (95.35) | 84.5 – 98.7 | 420/421 (99.80) | 98.7 - 100 |
| Salmonella spp.^{f} | Inoculated Cary-Blair | 190 | 17/17 (100) | 81.6 - 100 | 169/173 (97.70) | 94.2 – 99.1 |
| | Unpreserved (Fresh) | 274 | 25/27 (92.59) | 76.6 – 97.9 | 246/247 (99.60) | 97.7 – 99.9 |
| | All Archived | 464 | 42/44 (95.45) | 84.9 – 98.7 | 415/420 (98.80) | 97.2 – 99.5 |
| Shigella/ EIEC^{g} | Inoculated Cary-Blair | 190 | 9/9 (100) | 70.1 - 100 | 181/181 (100) | 97.9 - 100 |
| | Unpreserved (Frozen) | 274 | 20/22 (90.91) | 72.2 – 97.5 | 252/252 (100) | 98.5 - 100 |
| | All Archived | 464 | 29/31 (93.55) | 79.3 – 98.2 | 433/433 (100) | 99.1 - 100 |
| Vibrio parahaemolyticus^{h} | Inoculated Cary-Blair | 190 | 1/1 (100) | 20.7 - 100 | 189/189 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 1/1 (100) | 20.7 - 100 | 272/273 (99.6) | 98.0 – 99.9 |
| | All Archived | 464 | 2/2 (100) | 34.2 – 100 | 461/462 (99.8) | 99.8 - 100 |
| Vibrio spp. (not parahaemolyticus)^{i} | Inoculated Cary-Blair | 190 | N/A | N/A | 190/190 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 0/1 (0%) | N/A | 273/273 (100) | 98.6 – 100 |
| | All Archived | 464 | 0/1 (0%) | N/A | 463/463 (100) | 99.2 - 100 |
| Yersinia enterocolitica^{j} | Inoculated Cary-Blair | 190 | 3/3 (100) | 43.9 - 100 | 187/187 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 3/3 (100) | 43.9 - 100 | 269/271 (99.26) | 97.3 – 99.8 |
| | All Archived | 464 | 6/6 (100) | 61.0 – 100 | 456/458 (99.6) | 98.4- 99.9 |
| Cryptosporidium spp.^{k} | Inoculated Cary-Blair | 190 | 11/12 (91.67) | 64.6 – 98.5 | 178/178 (100) | 97.9 - 100 |
| | Unpreserved (Frozen) | 274 | 22/24 (91.67) | 74.2 – 97.7 | 248/250 (99.20) | 97.1 – 99.8 |
| | All Archived | 464 | 33/36 (91.67) | 78.2 – 97.1 | 426/428 (99.5) | 98.3 – 99.9 |

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| Target | Specimen Type | (n) | Positive Agreement | | Negative Agreement | |
| --- | --- | --- | --- | --- | --- | --- |
| | | | PPA (%) | 95% CI | NPA (%) | 95% CI |
| Entamoeba histolytica | Inoculated Cary-Blair | 190 | N/A | N/A | 190/190 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | N/A | N/A | 274/274 (100) | 98.6 - 100 |
| | All Archived | 464 | N/A | N/A | 464/464 (100) | 99.2 - 100 |
| Giardia lamblia1 | Inoculated Cary-Blair | 190 | 3/3 (100) | 43.90 - 100 | 187/187 (100) | 98.0 - 100 |
| | Unpreserved (Frozen) | 274 | 14/14 (100) | 78.5 - 100 | 255/260 (98.1) | 95.6 - 99.2 |
| | All Archived | 464 | 17/17 (100) | 81.6 - 100 | 442/447 (98.9) | 97.4 - 99.5 |
| Adenovirus 40/41 m | Inoculated Cary-Blair | 190 | 7/10 (70.00) | 39.7 - 89.2 | 177/180 (98.32) | 95.2 - 99.4 |
| | Unpreserved (Frozen) | 274 | 11/14 (78.60) | 52.4 - 92.4 | 252/260 (96.90) | 94.0 - 98.4 |
| | All Archived | 464 | 18/24 (75.00) | 55.1 - 88.0 | 429/440 (97.5) | 95.6 - 98.6 |
| Norovirus (GI/GII)n | Inoculated Cary-Blair | 190 | 19/19 (100) | 83.2 - 100 | 168/171 (98.20) | 95.0 - 99.4 |
| | Unpreserved (Frozen) | 274 | 21/22 (95.45) | 78.2 - 99.2 | 248/252 (98.40) | 96.0 - 99.4 |
| | All Archived | 464 | 40/41 (97.6) | 87.4 - 96.6 | 416/423 (98.3) | 96.6 - 99.2 |
| Rotavirus A o | Inoculated Cary-Blair | 190 | 12/13 (92.31) | 66.7 - 98.6 | 176/177 (99.44) | 96.9 - 99.9 |
| | Unpreserved (Frozen) | 274 | 15/15 (100) | 79.6 - 100 | 255/259 (98.5) | 96.1 - 99.4 |
| | All Archived | 464 | 27/28 (96.43) | 82.3 - 99.4 | 431/436 (98.9) | 97.3 - 99.5 |

Performance of archived specimens were also compared to the historical comparator method result from the BioCode Gastrointestinal Pathogen Panel (K180041) clinical study. Results are shown in Table 9 below.

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Table 9: Performance Compared to Historical Reference results. (Stratified by sample type and extraction method). N=290 samples. 1 Invalid for EasyMAG (Cary-Blair sample); 3 Invalid for MP96 (1 Cary-Blair, 2 Unpreserved).

| Target | Specimen Type | EasyMAG | | MagNa Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Positive Agreement | Negative Agreement | Positive Agreement | Negative Agreement |
| | | PPA (%) | NPA (%) | PPA (%) | NPA (%) |
| Campylobacter spp. | Inoculated Cary-Blair | 3/3 (100%) | 135/140 (96%) | 3/3 (100%) | 134/140 (96%) |
| | Unpreserved | 1/1 (100%) | 139/145 (96%) | 1/1 (100%) | 135/143 (94%) |
| | All Archived | 4/4 (100%) | 274/285 (96%) | 4/4 (100%) | 269/283 (95%) |
| Clostridium difficile | Inoculated Cary-Blair | 9/12 (75%) | 131/131 (100%) | 9/12 (75%) | 131/131 (100%) |
| | Unpreserved | 12/13 (92%) | 131/133 (98%) | 12/13 (92%) | 127/131 (97%) |
| | All Archived | 21/25 (84%) | 262/264 (99%) | 21/25 (84%) | 258/262 (98%) |
| E. coli O157 | Inoculated Cary-Blair | 1/1 (100%) | 141/142 (99%) | 0/1 (N/A) | 141/142 (99%) |
| | Unpreserved | 0/0 (N/A) | 144/146 (99%) | 0/0 (N/A) | 142/144 (99%) |
| | All Archived | 1/1 (100%) | 285/288 (99%) | 0/1 (N/A) | 283/286 (99%) |
| Enteroaggregative E. coli (EAEC) | Inoculated Cary-Blair | 14/14 (100%) | 128/129 (99%) | 13/14 (93%) | 127/129 (98%) |
| | Unpreserved | 13/14 (93%) | 131/132 (99%) | 13/14 (93%) | 130/131 (99%) |
| | All Archived | 27/28 (96%) | 259/261 (99%) | 26/28 (93%) | 257/260 (99%) |
| Enterotoxigenic E. coli (ETEC) | Inoculated Cary-Blair | 3/6 (50%) | 137/137 (100%) | 3/6 (50%) | 137/137 (100%) |
| | Unpreserved | 6/7 (86%) | 139/139 (100%) | 6/7 (86%) | 138/138 (100%) |
| | All Archived | 9/13 (69%) | 276/276 (100%) | 9/13 (69%) | 275/275 (100%) |
| Shiga toxin-producing E. coli (STEC) | Inoculated Cary-Blair | 1/3 (33%) | 139/140 (99%) | 1/3 (33%) | 139/140 (99%) |
| | Unpreserved | 0/0 (N/A) | 144/146 (99%) | 0/0 (N/A) | 142/144 (99%) |
| | All Archived | 1/3 (33%) | 283/286 (99%) | 1/3 (33%) | 281/284 (99%) |

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| Target | Specimen Type | EasyMAG | | MagNa Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Positive Agreement | Negative Agreement | Positive Agreement | Negative Agreement |
| | | PPA (%) | NPA (%) | PPA (%) | NPA (%) |
| Salmonella spp. | Inoculated Cary-Blair | 8/10 (80%) | 129/133 (97%) | 9/10 (90%) | 126/133 (95%) |
| | Unpreserved | 10/10 (100%) | 132/136 (97%) | 10/10 (100%) | 131/134 (98%) |
| | All Archived | 18/20 (90%) | 261/269 (97%) | 19/20 (95%) | 257/267 (96%) |
| Shigella/ EIEC | Inoculated Cary-Blair | 3/3 (100%) | 134/140 (96%) | 3/3 (100%) | 134/140 (96%) |
| | Unpreserved | 2/2 (100%) | 136/144 (94%) | 2/2 (100%) | 135/142 (95%) |
| | All Archived | 5/5 (100%) | 270/284 (95%) | 5/5 (100%) | 269/282 (95%) |
| Vibrio parahaemolyticus | Inoculated Cary-Blair | 0/0 (N/A) | 142/143 (99%) | 0/0 (N/A) | 142/143 (99%) |
| | Unpreserved | 0/0 (N/A) | 145/146 (99%) | 0/0 (N/A) | 143/144 (99%) |
| | All Archived | 0/0 (N/A) | 287/289 (99%) | 0/0 (N/A) | 285/287 (99%) |
| Vibrio spp. (not parahaemolyticus) | Inoculated Cary-Blair | 0/0 (N/A) | 143/143 (100%) | 0/0 (N/A) | 143/143 (100%) |
| | Unpreserved | 0/0 (N/A) | 146/146 (100%) | 0/0 (N/A) | 144/144 (100%) |
| | All Archived | 0/0 (N/A) | 289/289 (100%) | 0/0 (N/A) | 287/287 (100%) |
| Yersinia enterocolitica | Inoculated Cary-Blair | 0/0 (N/A) | 141/143 (99%) | 0/0 (N/A) | 141/143 (99%) |
| | Unpreserved | 0/0 (N/A) | 146/146 (100%) | 0/0 (N/A) | 144/144 (100%) |
| | All Archived | 0/0 (N/A) | 287/289 (99%) | 0/0 (N/A) | 285/287 (99%) |
| Cryptosporidium spp. | Inoculated Cary-Blair | 3/4 (75%) | 139/139 (100%) | 2/4 (50%) | 139/139 (100%) |
| | Unpreserved | 3/4 (75%) | 142/142 (100%) | 3/4 (75%) | 140/140 (100%) |
| | All Archived | 6/8 (75%) | 281/281 (100%) | 5/8 (63%) | 279/279 (100%) |
| Entamoeba histolytica | Inoculated Cary-Blair | 0/0 (N/A) | 143/143 (100%) | 0/0 (N/A) | 143/143 (100%) |
| | Unpreserved | 0/0 (N/A) | 146/146 (100%) | 0/0 (N/A) | 144/144 (100%) |
| | All Archived | 0/0 (N/A) | 289/289 (100%) | 0/0 (N/A) | 287/287 (100%) |

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| Target | Specimen Type | EasyMAG | | MagNa Pure 96 | |
| --- | --- | --- | --- | --- | --- |
| | | Positive Agreement | Negative Agreement | Positive Agreement | Negative Agreement |
| | | PPA (%) | NPA (%) | PPA (%) | NPA (%) |
| Giardia lamblia | Inoculated Cary-Blair | 1/1 (100%) | 141/142 (99%) | 1/1 (100%) | 141/142 (99%) |
| | Unpreserved | 1/1 (100%) | 142/145 (98%) | 1/1 (100%) | 140/143 (98%) |
| | All Archived | 2/2 (100%) | 283/287 (99%) | 2/2 (100%) | 281/285 (99%) |
| Adenovirus 40/41 | Inoculated Cary-Blair | ½ (50%) | 142/142 (100%) | 1/2 (50%) | 138/141 (98%) |
| | Unpreserved | 5/6 (83%) | 137/140 (98%) | 5/6 (83%) | 134/138 (97%) |
| | All Archived | 6/8 (75%) | 279/282 (99%) | 6/8 (75%) | 272/279 (97%) |
| Norovirus (GI/GII) | Inoculated Cary-Blair | 19/19 (100%) | 124/124 (100%) | 19/19 (100%) | 122/124 (98%) |
| | Unpreserved | 19/19 (100%) | 125/127 (98%) | 19/19 (100%) | 124/125 (99%) |
| | All Archived | 38/38 (100%) | 249/251 (99%) | 38/38 (100%) | 246/249 (99%) |
| Rotavirus A | Inoculated Cary-Blair | 11/11 (100%) | 130/132 (98%) | 11/11 (100%) | 132/133 (99%) |
| | Unpreserved | 9/9 (100%) | 135/137 (99%) | 9/9 (100%) | 130/135 (96%) |
| | All Archived | 20/20 (100%) | 264/269 (99%) | 20/20 (100%) | 262/268 (98%) |

# N. Instrument Name:

BioCode MDx 3000 instrument

# O. System Descriptions:

# 1. Modes of Operation:

Does the applicant's device contain the ability to transmit data to a computer, webserver, or mobile device?

Yes

Does the applicant's device transmit data to a computer, webserver, or mobile device using wireless transmission?

No

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2. Software:

FDA has reviewed applicant’s Hazard Analysis and software development processes for this line of product types:

Yes

3. Specimen Identification:

Specimen identity is provided by barcode magnetic beads.

4. Specimen Sampling and Handling:

After extraction with the easyMAG or MagNA Pure 96 system and loading samples into a 96well formatted plate, the BioCode MDx 3000 processes all RT-PCR steps automatically.

5. Calibration:

Optical calibration of the MDx 3000 is performed twice a year by Applied BioCode. No calibration kit is available.

6. Quality Control:

Each laboratory should establish its own Quality Control ranges and frequency of QC testing based on applicable local laws, regulations and good laboratory practices. The BioCode Gastrointestinal Pathogen Panel (GPP) uses an internal control (bacteriophage MS2) which is added to each sample during pre-treatment. The internal control monitors the efficiency of the extraction, reverse transcription, amplification and detection stages of the assay. Positive results may be reported in the absence of RNA IC detection. The BioCode Gastrointestinal Pathogen Panel (GPP) software will suppress negative results for any wells with invalid RNA IC results.

P. Other Supportive Instrument Performance Characteristics Data Not Covered in the "Performance Characteristics" Section above:

Not applicable.

Q. Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

R. Conclusion:

The submitted information in this premarket notification is sufficient to support a substantial equivalence decision for the BioCode Gastrointestinal Pathogen Panel (GPP).

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