LogoFDA 510(k) Search
K Number
K140111
Device Name
BD MAX(TM) ENTERIC BACTERIAL PANEL;BD MAX(TM) INSTRUMENT
Manufacturer
Becton, Dickinson and Company
Date Cleared
2014-05-06

(111 days)

Product Code
PCIOOIPCH
Regulation Number
866.3990
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP Authorized
Intended Use
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.
Device Description
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.
More Information

K123274

Not Found

No
The description details a real-time PCR system with automated sample processing and software interpretation based on amplification status and controls. There is no mention of AI or ML algorithms being used for data analysis or interpretation.

No
The device is an in vitro diagnostic test designed to detect and differentiate enteric bacterial pathogens, aiding in diagnosis. It does not provide treatment or directly interact with the patient for therapeutic purposes.

Yes
The document explicitly states under "Intended Use / Indications for Use" that the BD MAX™ Enteric Bacterial Panel is an "automated in vitro diagnostic test".

No

The device description explicitly states that the system is comprised of an instrument with associated hardware and accessories, disposable microfluidic cartridges, master mixes, unitized reagent strips, extraction reagents, and sample buffer tubes, in addition to the software. This indicates it is a hardware and software system, not software-only.

Yes, this device is an IVD (In Vitro Diagnostic).

The document explicitly states in the "Intended Use / Indications for Use" section: "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."

This statement, along with the description of the test being performed on patient specimens (stool) to aid in the diagnosis of infections, clearly identifies it as an in vitro diagnostic device.

N/A

Intended Use / Indications for Use

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 unpreserved 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.

Product codes

PCI, PCH, OOI

Device Description

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.

A stool specimen is collected and transported to the laboratory in a dry, clean container (for unpreserved specimens) or in Cary-Blair transport media. The specimen is vortexed for 15 seconds and then a 10 µL loop is used to inoculate a BD MAX™ Enteric Bacterial Panel Sample Buffer Tube. The Sample Buffer Tube is closed with a septum cap and vortexed. A worklist is created and the Sample Buffer Tube, the BD MAX™ Enteric Bacterial Panel unitized reagent strip (URS) and the BD MAX™ PCR Cartridge are loaded onto the BD MAX ™ System.

Following enzymatic cell lysis, the released nucleic acids are captured on magnetic beads. The beads, with the bound nucleic acids, are washed using Wash Buffer and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized using Neutralization Buffer and transferred to a Master Mix to rehydrate PCR reagents, After reconstitution, the BD MAX™ System dispenses a fixed volume of PCR-ready solution containing extracted nucleic acids into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to contain the amplification mixture, thus preventing evaporation and contamination.

The amplified DNA targets are detected using hydrolysis (TagMan®) probes, labeled at one end with a fluorescent reporter dye (fluorophore) and at the other end with a quencher moiety. Probes labeled with different fluorophores are used to detect amplicons for enteric bacterial targets (Campylobacter specific tuf gene sequence variants, the SpaO gene for specific detection of Salmonella spp., the ipaH gene for specific detection of Shigella spp. / Enteroinvasive E. coli (EIEC), the stx1 & stx2 genes associated with production of Shiga toxins in STEC and S. dysenteriae) and the SPC in five different optical channels of the BD MAX System. When the probes are in their native state, the fluorescence of the fluorophore is quenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the optical channels used for the BD MAX™ Enteric Bacterial Panel is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System measures these signals at the end of each amplification cycle, and interprets the data to provide a result.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Stool specimens

Indicated Patient Age Range

Not Found (Patients are symptomatic, and age ranges ( 1x10^8 CFU/mL in the SBT was spiked along with 10 uL of unpreserved stool.

Clinical Performance Studies:

  • Multi-center study involving eight (8) geographically diverse clinical centers for specimen collection and BD MAX™ testing.
  • An internal site was also involved to perform BD MAX™ testing on specimens supplied by other collection centers.
  • Collection centers were selected based on high similarity in culture and identification methods. Centers with different methodologies sent specimens to a central laboratory for reference method testing.
  • Prospective (fresh) specimens: Collected on an "all-comers" basis between June and September, 2013. Total enrolled: 3457 (2112 Cary-Blair preserved, 1345 unpreserved).
  • Retrospective (frozen) specimens: Collected from sites between March 2012 and August 2013, and from June to September 2007 and October to December 2011 from one site. Stored frozen (-20 °C or lower) and did not undergo freeze-thaw cycles. Thawed at time of testing. Total enrolled: 785 (464 Cary-Blair preserved, 321 unpreserved).
  • Reference Method: For prospective specimens, not explicitly detailed beyond "reference method" in table. For retrospective specimens, historical culture results were confirmed using an alternate PCR and bi-directional amplicon sequencing as part of the composite reference method.
  • Annotation protocol: Historical culture results for retrospective specimens were confirmed using an alternate PCR and bi-directional amplicon sequencing to confirm target DNA presence. Performance calculations excluded 104 retrospective specimens where historical results were not confirmed by alternate PCR and bi-directional sequencing. Species identification was obtained from culture/identification (reference method) or sequencing (for retrospective confirmation and discrepant prospective specimens).

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

Precision Study:

  • Study Type: Within-laboratory precision.
  • Sample Size: 72 replicates per target and concentration level (e.g., 72 TN, 72 HN, 72 LP, 72 MP).
  • Key Results:
    • Moderate Positives (MP): Overall correct percentage approximately 100% (95% CI).
    • Low Positives (LP): Overall correct percentage approximately 95% (95% CI).
    • True Negatives (TN): Overall correct percentage approximately 100% (95% CI).
    • High Negatives (HN): Overall correct percentage between 20 and 80%.
    • Specific percentages: Shiga toxins (TN 100%, HN 27.78%, LP 98.61%, MP 100%), Campylobacter (TN 100%, HN 54.17%, LP 100%, MP 98.61%), Shigella (TN 100%, HN 30.56%, LP 98.61%, MP 98.61%), Salmonella (TN 100%, HN 25%, LP 100%, MP 100%).

Reproducibility Study (Site-to-Site):

  • Study Type: Multi-site reproducibility.
  • Sample Size: 90 replicates per target and concentration level across all sites.
  • Key Results:
    • Overall Site-to-Site Reproducibility percent agreement:
      • TN category: 100% for all targets.
      • HN category: 41.1% to 77.8%.
      • LP category: 96.7% to 100%.
      • MP category: 98.9% to 100%.
    • Qualitative reproducibility for Campylobacter: TN 100%, HN 77.8%, LP 100%, MP 100%.
    • Qualitative reproducibility for Salmonella: TN 100%, HN 44.4%, LP 96.7%, MP 98.9%.
    • Qualitative reproducibility for Shigella: TN 100%, HN 41.1%, LP 97.8%, MP 100%.
    • Qualitative reproducibility for Shiga toxins: TN 100%, HN 50.0%, LP 100%, MP 98.9%.
    • Quantitative reproducibility assessed via Ct.Score mean and variance components.

Lot-to-Lot Reproducibility Study:

  • Study Type: Lot-to-lot reproducibility.
  • Sample Size: 90 replicates per target and concentration level for each lot.
  • Key Results:
    • Overall Lot-to-Lot reproducibility percent agreement:
      • TN category: 100% for all targets.
      • HN category: 13.33% to 62.22%.
      • LP category: 95.56% to 100%.
      • MP category: 97.78% to 100%.
    • Specific percentages: STEC (TN 100%, HN 30%, LP 98.89%, MP 100%), Campy (TN 100%, HN 62.22%, LP 100%, MP 97.78%), Shig (TN 100%, HN 16.67%, LP 95.56%, MP 98.89%), Sal (TN 100%, HN 13.33%, LP 98.89%, MP 100%).

Analytical Sensitivity (Limit of Detection - LoD):

  • Study Type: Analytical sensitivity determination.
  • Sample Size: Not specified for each organism, but presented as positive results out of total tests with 95% CI.
  • Key Results: LoD in CFU/mL in stool for unpreserved/Cary-Blair preserved samples:
    • Salmonella typhimurium: 44,400 / 28,950
    • Shigella sonnei: 12,600 / 18,600
    • Campylobacter coli: 14,250 / 8,250
    • E. coli stx1/stx2: 136,500 / 97,950
    • Salmonella enteriditis: 93,000 / 75,300
    • Shigella flexneri: 56,100 / 34,350
    • Campylobacter jejuni: 6,300 / 1,500
    • E. coli stx2: 108,300 / 89,850
    • E. coli stx1: 38,202 / 33,495

Analytical Inclusivity:

  • Study Type: Inclusivity validation.
  • Sample Size: 121 enteric target organism strains, serovars, or subspecies.
  • Key Results: The assay correctly identified 120 of the 121 strains tested at the LoD. One strain of Shigella sonnei (ENF 15987) demonstrated 79.17% positivity at a concentration of 56.1 CFU/mL, but 100% positivity at 405 CFU/mL.

Analytical Specificity:

  • Study Type: Specificity testing.
  • Sample Size: 9 Campylobacter strains, 6 E. coli strains, 99 other bacterial strains, 15 viruses, 3 ova/parasites, 16 Enteric organisms.
  • Key Results:
    • 9/9 Campylobacter strains (undetectable tuf gene) produced negative results.
    • 6/6 E. coli strains (non-STEC) produced negative results.
    • 98/99 other bacterial strains produced negative results. (S. boydii (ATCC 12028) produced 1 replicate out of 3 as positive for stx, with subsequent testing showing 8 out of 20 replicates positive).
    • 15/15 viruses produced negative results.
    • 3/3 ova and parasites produced negative results.
    • 16/16 Enteric organisms representing each target (Campylobacter, E.coli, Salmonella, Shigella) produced positive results for their respective target and negative for others, except for an S. boydii strain briefly mentioned again as positive for stx.

Interfering Substances:

  • Study Type: Evaluation of interference.
  • Sample Size: 19 substances.
  • Key Results: Vagisil, Nystatin cream, and spermicidal lubricant demonstrated potential interference at certain concentrations. No reportable interference with other tested substances.

Carryover / Cross-Contamination:

  • Study Type: Contamination potential evaluation.
  • Sample Size: 167 valid results.
  • Key Results: 166 valid negative results. 4 false positive results from 1 sample tube. Overall contamination rate: 0.6%.

Mixed Infection/Competitive Interference:

  • Study Type: Evaluation of detection in mixed infections.
  • Sample Size: Not explicitly stated but inferred from the description of 4 low target organisms combined with 3 high target organisms.
  • Key Results: All four low target organisms were successfully detected when combined with their respective simulated high target concentration mixed infection preparations.

Clinical Performance Studies:

  • Study Type: Clinical Accuracy (Prospective and Retrospective).

  • Sample Size:

    • Prospective: 3457 enrolled (3038-3069 for analysis depending on target; 2502 for Shigatoxins).
    • Retrospective: 785 enrolled (507 for Campylobacter, 543 for Shigella, 618 for Salmonella, 156 for Shigatoxins in analysis, 104 excluded due to unconfirmed historical results).

  • Key Results (Overall Performance by Specimen Type and Target):

    • Campylobacter spp.:
      • Cary-Blair Prospective: PPA 96.2% (95% CI: 81.1%, 99.3%), NPA 98.7% (95% CI: 98.1%, 99.1%).
      • Cary-Blair Retrospective: PPA 97% (95% CI: 89.6%, 99.2%), NPA 100% (95% CI: 97.5%, 100%).
      • Unpreserved Prospective: PPA 100% (95% CI: 85.1%, 100%), NPA 97.5% (95% CI: 96.4%, 98.2%).
      • Unpreserved Retrospective: PPA 97% (95% CI: 89.8%, 99.2%), NPA 99.1% (95% CI: 96.8%, 99.8%).
    • Salmonella spp.:
      • Cary-Blair Prospective: PPA 85% (95% CI: 64%, 94.8%), NPA 99.1% (95% CI: 98.5%, 99.4%).
      • Cary-Blair Retrospective: PPA 99.1% (95% CI: 94.8%, 99.8%), NPA 100% (95% CI: 98.2%, 100%).
      • Unpreserved Prospective: PPA 91.7% (95% CI: 74.2%, 97.7%), NPA 98.9% (95% CI: 98.2%, 99.4%).
      • Unpreserved Retrospective: PPA 100% (95% CI: 94.1%, 100%), NPA 99.6% (95% CI: 97.7%, 99.9%).
    • Shigella spp. / EIEC:
      • Cary-Blair Prospective: PPA 100% (95% CI: 83.2%, 100%), NPA 99.7% (95% CI: 99.4%, 99.9%).
      • Cary-Blair Retrospective: PPA 98% (95% CI: 89.7%, 99.7%), NPA 100% (95% CI: 98%, 100%).
      • Unpreserved Prospective: PPA 100% (95% CI: 85.1%, 100%), NPA 99.4% (95% CI: 98.8%, 99.7%).
      • Unpreserved Retrospective: PPA 100% (95% CI: 91.4%, 100%), NPA 100% (95% CI: 98.6%, 100%).
    • Shiga toxins (stx1/stx2):
      • Cary-Blair Prospective: PPA 75% (95% CI: 40.9%, 92.9%), NPA 99.3% (95% CI: 98.8%, 99.6%).
      • Cary-Blair Retrospective: PPA 100% (95% CI: 91.4%, 100%), NPA 100% (95% CI: 95.4%, 100%).
      • Unpreserved Prospective: PPA 100% (95% CI: 34.2%, 100%), NPA 99% (95% CI: 98%, 99.5%).
      • Unpreserved Retrospective: PPA 100% (95% CI: 86.7%, 100%), NPA 100% (95% CI: 74.1%, 100%).

  • Unresolved Rates:

    • Initial Unresolved Rates: Cary-Blair Prospective 4.0%, Cary-Blair Retrospective 2.2%, Unpreserved Prospective 7.8%, Unpreserved Retrospective 4.1%.
    • Unresolved Rates After Repeat: Cary-Blair Prospective 0.1%, Cary-Blair Retrospective 0.2%, Unpreserved Prospective 1.0%, Unpreserved Retrospective 0.6%.

  • Indeterminate Rates:

    • Initial Indeterminate Rates: Cary-Blair Prospective 1.7%, Cary-Blair Retrospective 1.5%, Unpreserved Prospective 1.6%, Unpreserved Retrospective 1.9%.
    • Final Indeterminate Rates After Repeat: Cary-Blair Prospective 0.0%, Cary-Blair Retrospective 0.0%, Unpreserved Prospective 0.2%, Unpreserved Retrospective 0.0%.

  • Incomplete Rates:

    • Initial Incomplete Rates: Cary-Blair Prospective 1.3%, Cary-Blair Retrospective 1.3%, Unpreserved Prospective 2.0%, Unpreserved Retrospective 0.0%.
    • Final Incomplete Rates After Repeat: Cary-Blair Prospective 0.0%, Cary-Blair Retrospective 0.0%, Unpreserved Prospective 0.0%, Unpreserved Retrospective 0.0%.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Sensitivity is referred to as PPA (Positive Percent Agreement), and Specificity is referred to as NPA (Negative Percent Agreement).

For Campylobacter spp.:

  • Cary-Blair Pros.: PPA 96.2% (CI: 81.1%, 99.3%), NPA 98.7% (CI: 98.1%, 99.1%)
  • Cary-Blair Retros.: PPA 97% (CI: 89.6%, 99.2%), NPA 100% (CI: 97.5%, 100%)
  • Unpreserved Pros.: PPA 100% (CI: 85.1%, 100%), NPA 97.5% (CI: 96.4%, 98.2%)
  • Unpreserved Retros.: PPA 97% (CI: 89.8%, 99.2%), NPA 99.1% (CI: 96.8%, 99.8%)

For Salmonella spp.:

  • Cary-Blair Pros.: PPA 85% (CI: 64%, 94.8%), NPA 99.1% (CI: 98.5%, 99.4%)
  • Cary-Blair Retros.: PPA 99.1% (CI: 94.8%, 99.8%), NPA 100% (CI: 98.2%, 100%)
  • Unpreserved Pros.: PPA 91.7% (CI: 74.2%, 97.7%), NPA 98.9% (CI: 98.2%, 99.4%)
  • Unpreserved Retros.: PPA 100% (CI: 94.1%, 100%), NPA 99.6% (CI: 97.7%, 99.9%)

For Shigella spp. / EIEC:

  • Cary-Blair Pros.: PPA 100% (CI: 83.2%, 100%), NPA 99.7% (CI: 99.4%, 99.9%)
  • Cary-Blair Retros.: PPA 98% (CI: 89.7%, 99.7%), NPA 100% (CI: 98%, 100%)
  • Unpreserved Pros.: PPA 100% (CI: 85.1%, 100%), NPA 99.4% (CI: 98.8%, 99.7%)
  • Unpreserved Retros.: PPA 100% (CI: 91.4%, 100%), NPA 100% (CI: 98.6%, 100%)

For Shiga toxins (stx1/stx2):

  • Cary-Blair Pros.: PPA 75% (CI: 40.9%, 92.9%), NPA 99.3% (CI: 98.8%, 99.6%)
  • Cary-Blair Retros.: PPA 100% (CI: 91.4%, 100%), NPA 100% (CI: 95.4%, 100%)
  • Unpreserved Pros.: PPA 100% (CI: 34.2%, 100%), NPA 99% (CI: 98%, 99.5%)
  • Unpreserved Retros.: PPA 100% (CI: 86.7%, 100%), NPA 100% (CI: 74.1%, 100%)

Predicate Device(s):

Gen-Probe Prodesse, Inc. ProGastro SSCS Assay, K123274

Reference Device(s):

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

§ 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).

0

K140111

BD MAX™ Enteric Bacterial Panel

CONFIDENTIAL AND PROPRIETARY

510(k) Summary

MAY 0 6 2014

May 5, 2014

BD MAX™ Enteric Bacterial Panel

Regulatory Affairs Project Manager

Becton, Dickinson and Company Submitted by: 7 Loveton Circle Sparks, MD 21152 Phone: 410-316-4905 Fax: 410-316-4499

Contact:

Device:

510(k) Number: K140111

Trade Name: BD MAX™ Enteric Bacterial Panel

Common Name: Gastrointestinal pathogen panel multiplex nucleic acidbased assay system

Paul Swift, RAC

Classification: Class II

Regulation Number: 866.3990

Product Code: PCI, PCH, OOI

Microbiology (83) Panel:

Predicate Device: Gen-Probe Prodesse, Inc. ProGastro SSCS Assay

Predicate 510(k) Numbers: K123274

Intended Use

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.

BD Diagnostic Systems Becton, Dickinson and Company

1

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.

Special Conditions for Use Statement:

Special Instrument Requirements:

BD MAX™ System

For prescription use

Device Description

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.

Test Principle

The BD MAX™ Enteric Bacterial Panel performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct, qualitative detection of enteric bacterial pathogens responsible for gastreoenteritis due to Salmonella spp., Campylobacter spp. (jejuni and coli), Shigella spp. / Enteroinvasive E. coli (EIEC), and 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. The BD MAX Enteric Bacterial Panel detects target DNA from unpreserved soft to diarrheal stool specimens or Cary-Blair preserved stool specimens from symptomatic patients with suspected acute gastroenteritis, enteritis or colitis.

A stool specimen is collected and transported to the laboratory in a dry, clean conta for unpreserved specimens) or in Cary-Blair transport media. The specimen is vortexed BD Diagnostic Systems Becton, Dickinson and Company

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2

for 15 seconds and then a 10 µL loop is used to inoculate a BD MAX™ Enteric Bacterial Panel Sample Buffer Tube. The Sample Buffer Tube is closed with a septum cap and vortexed. A worklist is created and the Sample Buffer Tube, the BD MAX™ Enteric Bacterial Panel unitized reagent strip (URS) and the BD MAX™ PCR Cartridge are loaded onto the BD MAX ™ System.

Following enzymatic cell lysis, the released nucleic acids are captured on magnetic beads. The beads, with the bound nucleic acids, are washed using Wash Buffer and the nucleic acids are eluted by heat in Elution Buffer. Eluted DNA is neutralized using Neutralization Buffer and transferred to a Master Mix to rehydrate PCR reagents, After reconstitution, the BD MAX™ System dispenses a fixed volume of PCR-ready solution containing extracted nucleic acids into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system prior to initiating PCR to contain the amplification mixture, thus preventing evaporation and contamination.

The amplified DNA targets are detected using hydrolysis (TagMan®) probes, labeled at one end with a fluorescent reporter dye (fluorophore) and at the other end with a quencher moiety. Probes labeled with different fluorophores are used to detect amplicons for enteric bacterial targets (Campylobacter specific tuf gene sequence variants, the SpaO gene for specific detection of Salmonella spp., the ipaH gene for specific detection of Shigella spp. / Enteroinvasive E. coli (EIEC), the stx1 & stx2 genes associated with production of Shiga toxins in STEC and S. dysenteriae) and the SPC in five different optical channels of the BD MAX System. When the probes are in their native state, the fluorescence of the fluorophore is guenched due to its proximity to the quencher. However, in the presence of target DNA, the probes hybridize to their complementary sequences and are hydrolyzed by the 5-3' exonuclease activity of the DNA polymerase as it synthesizes the nascent strand along the DNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The amount of fluorescence detected in the optical channels used for the BD MAX™ Enteric Bacterial Panel is directly proportional to the quantity of the corresponding probe that is hydrolyzed. The BD MAX™ System measures these signals at the end of each amplification cvcle, and interprets the data to provide a result.

Substantial Equivalence

Table 1 shows the similarities and differences between the BD MAX™ Enteric Bacterial Panel and the predicate device.

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| ITEM | BD MAX™ Enteric Bacterial Panel | Hologic® Prodesse®
ProGastro™ SSCS (K123274) |
|-------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Intended Use | 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 unpreserved 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 | The Prodesse® ProGastro SSCS
Assay is a multiplex real time PCR
in vitro diagnostic test for the
qualitative detection and
differentiation of Salmonella,
Shigella , and Campylobacter (C.
jejuni and C. coli only,
undifferentiated) nucleic acids and
Shiga Toxin 1 ( stx1 ) and Shiga
Toxin 2 ( stx2 ) genes. Shiga toxin
producing E. coli (STEC) typically
harbor one or both genes that
encode for Shiga Toxins 1 and 2.
Nucleic acids are isolated and
purified from preserved stool
specimens obtained from
symptomatic patients exhibiting
signs and symptoms of
gastroenteritis. This test is
intended for use, in conjunction
with clinical presentation and
epidemiological risk factors, as an
aid in the differential diagnosis of
Salmonella, Shigella,
Campylobacter
jejuni/Campylobacter coli , and
STEC infections in humans.

The 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
ProGastro SSCS Assay results in
the setting of clinical illness
compatible with gastroenteritis may
be due to infection by pathogens |
| ITEM | BD MAX™ Enteric Bacterial Panel | Hologic® Prodesse®
ProGastro™ SSCS (K123274) |
| | 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. | that are not detected by this test or
non-infectious causes such as
ulcerative colitis, irritable bowel
syndrome, or Crohn's disease. |
| Specimen type | Unpreserved and Cary-Blair preserved
stool. | Stool in Cary-Blair preserved or
Para-Pak® C&S transport medium. |
| Assay Format | Amplification: PCR
Detection: fluorogenic target-specific
hybridization. | Same |
| Mode of
Detection for
Campylobacter | Presence of tuf gene specific for
Campylobacter. | Presence of glyA gene specific for
Campylobacter jejuni and cadF
gene specific for C. coli . |
| Mode of
Detection for
Salmonella | Presence of SpaO gene specific for
Salmonella. | Presence of orgC gene specific for
Salmonella. |
| Mode of
Detection for
Shigella | Presence of ipaH gene specific for
Shigella/EIEC. | Presence of ipaH gene specific for
Shigella. |
| Mode of
Detection for
Shiga toxins | Presence of stx1 and stx2 genes specific to
Shiga toxin-producing organisms. | Presence of stx1 and stx2 genes
specific to Shiga toxin-producing
organisms. |
| Interpretation of
Test Results | Automated (BD MAX™ System diagnostic
software) | Automated (Cepheid SmartCycler® II) |
| Analysis
Platform | BD MAX ™ System | Cepheid SmartCycler® II |
| PCR Sample
Preparation | Automated by the BD MAX™ System | bioMérieux NucliSENS®
easyMAG® |
| Detection
Probes | TaqMan® Probe | TaqMan® Probe |
| Assay Controls | Sample Processing Control (SPC) | Internal Control |

Table 1: Substantial Equivalence1 Information

1 The term "substantial equivalence" as used in this 510(k) notification is limited to the definition of substantial equivalence as found in the Federal Food, Drug and Cosmetic Act, as amended and as applied under 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification. A determination of substantial equivalency under this not intended to have any bearing whatsoever on the resolution of patent infringement suits or any other patent matters. No statements related to, or in support of substantial equivalence herein shall be construed as an admission against interest under the US Patent Laws or their application by the courts.

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Analytical Performance

Precision

Within-laboratory precision was evaluated for the BD MAX™ Enteric Bacterial Panel at one (1) site. The Precision panel consisted of 4 sample categories near the LoD. Each specimen contained negative stool matrix. Target strains were tested as follows:

  • For moderate positives (MP): overall correct percentage of approximately 100% with . 95% Cl
  • For low positives (LP): overall correct percentage of approximately 95% with 95% C1 .
  • For true neqatives (TN): overall correct percentage of approximately 100% with 95% . Cl
  • For high neqatives (HN): overall correct percentage between 20 and 80% .

Testing was performed in triplicate, over 12 days, with 2 runs per day, by 2 different technologists. Precision study results are summarized below in Table 2.

TargetLevelCorrectTotal% Correct
TN'7272100.00%
Shiga toxinsHN,207227.78%
Гр717298.61%
MP7272100.00%
1:N7272100.00%
CampylobacterHN397254.17%
lP7272100.00%
5
ﺔ ﺍﻟﺘﻲ ﺗﻌﻠﻴﻘﺎﺕ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪﺓ ﺍﻟﻤﺘﺤﺪMP717298.61%
TN7272100.00%
ShigellaHN227230.56%
LP7 17298.61%
MP7 17298.61%
TN7272100.00%
SalmonellaHN187225.00% ·
P7272100.00%
MP7272100.00%

Table 2: Within-laboratory Precision Testing

For the True Negative (TN) and High Negative (HN) categories, the expected assay result was deemed to be negative. Therefore, percent agreement was calculated for negative results.

Reproducibility

For the Site-to-Site reproducibility study, three (3) clinical sites were provided with a fotal of ten (10) panels, each consisting of 12 tubes. The panels used were the same as described under the Precision heading, above. Each site was asked to perform the study on five (5) distinct days (consecutive or not), wherein each day, two (2) panels were tested, one (1) for each of two (2) technologists.

The overall Site-to-Site Reproducibility percent agreement was 100% for the TN category for all targets, and ranged from 41.1% to 77.8%, 96.7% to 100% and 98.9% to 100% for the HN, LP and MP categories, respectively (Table 3). The qualitative and

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.

quantitative reproducibility across sites and by target is presented below in Tables 4 through 10. Ct.Score is an internal criterion used to determine final assay results and was selected as an additional means of assay reproducibility. Overall mean Ct.Score values with variance components (SD and %CV) are shown in Tables 4, 6, 8 and 10.

| Category | Campylobacter
( coli and jejuni )
[n], (95% CI) | Salmonella spp.
[n], (95% CI) | Shigella spp.
[n], (95% CI) | Shiga toxins
( stx1 and stx2 )
[n], (95% CI) |
|----------|----------------------------------------------------------------------------|-----------------------------------------|---------------------------------------|-------------------------------------------------------------------------|
| TN* | 100.0%, [90/90],
(95.9%, 100.0%) | 100.0%, [90/90], (95.9%,
100.0%) | 100.0%, [90/90], (95.9%,
100.0%) | 100.0%, [90/90], (95.9%,
100.0%) |
| HN* | 77.8%, [70/90],
(68.2%, 85.1%) | 44.4%, [40/90], (34.6%,
54.7%) | 41.1%, [37/90], (31.5%,
51.4%) | 50.0%, [45/90], (39.9%,
60.1%) |
| LP | 100.0%, [90/90],
(95.9%, 100.0%) | 96.7%, [87/90], (90.7%,
98.9%) | 97.8%, [88/90], (92.3%,
99.4%) | 100.0%, [90/90], (95.9%,
100.0%) |
| MP | 100.0%, [90/90],
(95.9%, 100.0%) | 98.9%, [89/90], (94.0%,
99.8%) | 100.0%, [90/90], (95.9%,
100.0%) | 98.9%, [89/90], (94.0%,
99.8%) |

Table 3: Site-to-Site Reproducibility Study Results using one lot of the BD MAX Enteric Bacterial Panel

  • For the True Negative (TN) and High Negative (HN) categories, the expected assay result was deemed to be negative. Therefore, percent was calculated for negative results
CategoryConcentrationSITETotal
235
CorrectIncorrectCorrectIncorrectCorrectIncorrectCorrectIncorrect
N%N%N%N%
TNBlank30100.00030100.00030100.00090100.000
HN5 CFU/mL2273.3826.72480.0620.02480.0620.07077.82022.2
LP≥1 and 1x10 CFU/mL in the SBT was spiked into the SBT along with 10 uL of unpreserved stool and tested to simulate mixed infections. All four low target orqanisms were successfully detected by the BD MAX Enteric Bacterial Panel when combined with their respective simulated high target concentration mixed infection preparations.

Clinical Performance Studies

The Clinical Accuracy study was designed to assess the performance of the BD MAX™ Enteric Bacterial Panel for the identification of Campylobacter (ieiuni & coli), Salmonella spp. Shigella spp. and EIEC as well as shiga toxin-producing organisms , from unpreserved or Cary-Blair preserved soft to diarrheal stool specimens. This multicenter study evaluated results obtained with the BD MAX Enteric Bacterial Panel compared to those obtained with the reference method. Clinical centers were employed to collect and test patient specimens; whereas collection centers were employed to collect and test patient specimens using the reference method, with BD MAX™ Enteric Bacterial Panel testing being performed by a testing center.

The study involved a total of eight (8) geographically diverse clinical centers where specimens were collected as part of routine patient care, enrolled into the trial, and tested on the BD MAX™ Enteric Bacterial Panel. Only excess, de-identified palient specimens were used. Additionally, an internal site was involved as a clinical center to perform BD MAX™ testing on specimens supplied by other collection centers.

Clinical centers were selected for the clinical study based on a number of criteria, such as investigator and site personnel availability, number of specimens of interest tested for each target, prevalence, and familiarity with PCR methodology. The clinical centers were also selected according to the specimen types that they routinely collect. Collection centers were selected for their high level of similarity with clinical centers in the culture and identification methods used for the study targets. Clinical centers utilizing methodologies that did not have a high degree of similarity sent specimens to a central laboratory for reference method testing. Prospective (fresh) specimens collected at the collection centers consisted of a mix of Cary-Blair preserved and unpreserved specimens, and were not pre-selected but rather collected on an "all-comers" basis between June and September, 2013. Accordingly, the specimens were enrolled as prospective specimens.

Retrospective (frozen) specimens were collected from sites between March 2012 and August 2013. Further, one site enrolled unpreserved specimens collected and archived from June to September 2007 and from October to December 2011. Inclusion and exclusion criteria were identical to those as for prospective specimens. Retrospective specimens were stored frozen (-20 °C or lower) after collection and did not undergo

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freeze-thaw cycles. Specimens were thawed at the time of testing with the BD MAX™ Enteric Bacterial Panel.

For retrospective specimens, the historical culture results were recorded at the collection site and the specimens were not re-cultured. The historical culture results were confirmed using an alternate PCR and bi-directional amplicon sequencing as part of the composite reference method in order to confirm the presence of target DNA.

A total of 3457 prospective specimens (2112 Cary-Blair preserved and 1345 unpreserved) and 785 retrospective specimens (464 Cary-Blair preserved and 321 unpreserved) were enrolled. Table 16 below presents the number of prospective compliant specimens for which a reportable (positive or negative) result was obtained by the reference method and for which a reportable result was obtained by the BD MAX EBP (i.e., the total compliant dataset used for PPA and NPA calculations), by target and specimen type. A total of 104 retrospective specimens were not included in the performance calculations below as the historical results were not confirmed by an alternate PCR and bi-directional sequencing.

CampylobacterShigellaSalmonellaShigatoxins
Positive
Cary-Blair2619208
Unpreserved2222242
Sub-Total48414410
Negative
Cary-Blair1774180918081781
Unpreserved121612191215711
Sub-Total2990302830232492
Grand Total3038306930672502

Table 16: Summary of Prospective Enrollment, by Target and Specimen Type

Table 17 describes the number of compliant specimens enrolled by patient age and specimen type. A total of 104 retrospective specimens were not included in the performance calculations below as the historical results were not confirmed by an alternate PCR and bi-directional sequencing. Tables 19 through 22 describe the performance characteristics of the BD MAX™ Enteric Bacterial Panel that were observed during the clinical trial.

Table 17: Compliant clinical trial enrollment summary by age group and specimen type

| Age Group | Cary-Blair
Preserved | Unpreserved | Combined |
|-----------|-------------------------|-------------|----------|
| jejuni | 95.8% (23/24) | (79.8%, 99.3%) |
| | Retrospective
(Frozen) | Untyped | 100.0% (2/2) | (34.2%, 100.0%) |
| | Retrospective
(Frozen) | coli | 100.0% (2/2) | (34.2%, 100.0%) |
| | Prospective
(Fresh) | jejuni | 96.9% (62/64) | (89.3%, 99.1%) |
| Unpreserved | Prospective
(Fresh) | jejuni | 100.0% (19/19) | (83.2%, 100.0%) |
| | Retrospective
(Frozen) | jejuni or coli | 100.0% (1/1) | (20.7%, 100.0%) |
| | Retrospective
(Frozen) | Untyped | 100.0% (2/2) | (34.2%, 100.0%) |
| | Prospective
(Fresh) | coli | 100.0% (5/5) | (56.6%, 100.0%) |
| | Prospective
(Fresh) | jejuni | 96.8% (60/62) | (89.0%, 99.1%) |

Table 23: Campylobacter performance per species observed during the clinical trial

1 Of these specimens, one (1) prospective specimen was also tested using a validated PCR assay followed by bi-directional sequencing and gave a negative result.

ShigellaPPA
Specimen
TypeSpecimen OriginSpeciesEstimate95% CI
Cary-Blair
PreservedProspective
(Fresh)flexneri100.0% (1/1)(20.7%, 100.0%)
Prospective
(Fresh)sonnei100.0% (18/18)(82.4%, 100.0%)
Retrospective
(Frozen)sonnei98.0% (50/51)(89.7%, 99.7%)
UnpreservedProspective
(Fresh)flexneri100.0% (2/2)(34.2%, 100.0%)
Prospective
(Fresh)sonnei100.0% (20/20)(83.9%, 100.0%)
Retrospective
(Frozen)flexneri100.0% (1/1)(20.7%, 100.0%)
Retrospective
(Frozen)sonnei100.0% (40/40)(91.2%, 100.0%)

Table 24: Shigella performance per species type observed during the clinical trial

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Shiga toxinsPPA
Specimen
TypeSpecimen OriginToxin TypeEstimate95% CI
Cary-Blair
PreservedProspective
(Fresh)stx1100.0% (4/4)(51.0%, 100.0%)
Prospective
(Fresh)stx2100.0% (1/1)(20.7%, 100.0%)
Prospective
(Fresh)stx1 and stx2¹33.3% (1/3)(6.1%, 79.2%)
Cary-Blair
PreservedRetrospective
(Frozen)stx1100.0% (28/28)(87.9%, 100.0%)
Retrospective
(Frozen)stx2100.0% (6/6)(61.0%, 100.0%)
Retrospective
(Frozen)stx1 and stx2100.0% (7/7)(64.6%, 100.0%)
UnpreservedProspective
(Fresh)stx1100.0% (1/1)(20.7%, 100.0%)
Prospective
(Fresh)stx1 and stx2100.0% (1/1)(20.7%, 100.0%)
UnpreservedRetrospective
(Frozen)stx1100.0% (5/5)(56.6%, 100.0%)
Retrospective
(Frozen)stx2100.0% (6/6)(61.0%, 100.0%)
Retrospective
(Frozen)stx1 and stx2100.0% (14/14)(78.5%, 100.0%)

Table 25: Shiga toxins performance per toxin type observed during the clinical trial

1 Two (2) prospective specimens were also tested using a validated PCR assay followed by bi-directional sequencing and gave a negative result.

Table 26 below shows the co-infections detected by the BD MAX Enteric Bacterial Panel during the prospective segment of the clinical trial. Note that there were no co-infections detected by the reference method during the prospective segment of the clinical trial.

Table 26: Co-infections observed during the BD MAX Enteric Bacterial Panel prospective clinical trial

| Distinct Co-infection Combinations
Detected by BD MAX Enteric Bacterial
Assay | | Number of
Discrepant Co-
Infections | Discrepant Analyte(s)1 |
|-------------------------------------------------------------------------------------|---------------|-------------------------------------------|------------------------------------|
| Analyte 1 | Analyte 2 | | |
| Shigella | stx | 1 | stx2 |
| stx | Campylobacter | 1 | stx3 |
| stx | Salmonella | 2 | stx (2) and Salmonella (1)4 |
| Campylobacter | Salmonella | 2 | Campylobacter (2), Salmonella (1)5 |

A discrepant co-infection or discrepant analyte was defined as one that was detected by the BD MAX assay but not detected by the reference method.

2 One (1) discrepant six was investigated using an alternate method; bi-directional sequence analysis identified the analyte in 0/1 cases.

3 One (1) discrepant stx was investigated using an alternate method; bi-directional sequence analysis identified the analyte in 1/1 cases.

4 Two (2) discrepant stx were investigated using an alternate method; bi-directional sequence analysis identified the analyte in 0/2 cases. One (1) discrepant Salmonella was investigated using an allernate method; bi-directional sequence analysis identified the analyte in 1/1 cases.

Two (2) discrepant Campylobacter were investigated using an allernate method; bi-directional sequence analysis identified the analyte in 0/2 cases. One (1) discrepant Salmonella was investigated using an alternate method; bi-directional sequence analysis identified the analyte in 0/1 cases.

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Of the 3183 prospective specimens initially evaluated with the BD MAX™ Enteric Bacterial Panel, 4.0% of the Carv-Blair preserved and 7.8% of the unpreserved specimens initially reported as Unresolved. Following a valid repeat test, 0.1% of the Cary-Blair preserved and 1.0% of the unpreserved specimens remained Unresolved. Of the 783 retrospective specimens initially evaluated with the BD MAX™ Enteric Bacterial Panel, 2.2% of the Cary-Blair preserved and 4.1% of the unpreserved specimens initially reported as Unresolved. Following a valid repeat test, 0.2% of the Cary-Blair preserved and 0.6% of the unpreserved specimens remained Unresolved (Table 27). The total numbers provided in Table 27 are based on compliant specimens and BD MAX™ Enteric Bacterial Panel results.

| | | Initial Unresolved Rates | | Unresolved Rates After
Repeat | |
|------------------|---------------------------|--------------------------|--------------|----------------------------------|--------------|
| Specimen
Type | Specimen
Origin | Percent | 95% Cl | Percent | 95% Cl |
| Cary-Blair | Prospective
(Fresh) | 4.0% (77/1905) | (3.2%, 5.0%) | 0.1% (2/1897) | (0.0%, 0.4%) |
| | Retrospective
(Frozen) | 2.2% (10/464) | (1.2%, 3.9%) | 0.2% (1/463) | (0.0%, 1.2%) |
| Unpreserved | Prospective
(Fresh) | 7.8%
(100/1278) | (6.5%, 9.4%) | 1.0% (13/1251) | (0.6%, 1.8%) |
| | Retrospective
(Frozen) | 4.1% (13/319) | (2.4%, 6.8%) | 0.6% (2/317) | (0.2%, 2.3%) |

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BD MAX™ Enteric Bacterial Panel

Of the 3183 prospective specimens initially evaluated with the BD MAX™ Enteric Bacterial Panel, 1.7% of the Cary-Blair preserved and 1.6% of the unpreserved specimens initially reported as Indeterminate. Following a valid repeat test, 0% of the Cary-Blair preserved and 0.2% of the unpreserved specimens remained Indeterminate. Of the 783 retrospective specimens initially evaluated with the BD MAX™ Enteric Bacterial Panel, 1.5% of the Cary-Blair preserved and 1.9% of the unpreserved specimens initially reported as Indeterminate. Following a valid repeat test, 0% of the Cary-Blair preserved and 0% of the unpreserved specimens remained Indeterminate (Table 28). The total numbers provided in Table 28 are based on compliant specimens and BD MAX ™ Enteric Bacterial Panel results.

| | | Initial Indeterminate
Rates | | Final Indeterminate Rates After
Repeat | |
|------------------|---------------------------|--------------------------------|-----------------|-------------------------------------------|--------------|
| Specimen
Type | Specimen
Origin | Percent | 95% Cl | Percent | 95% Cl |
| Cary-Blair | Prospective
(Fresh) | 1.7%
(33/1905) | (1.2%,
2.4%) | 0.0% (0/1897) | (0.0%, 0.2%) |
| | Retrospective
(Frozen) | 1.5% (7/464) | (0.7%,
3.1%) | 0.0% (0/463) | (0.0%, 0.8%) |
| Unpreserved | Prospective
(Fresh) | 1.6%
(20/1278) | (1.0%,
2.4%) | 0.2% (2/1251) | (0.0%, 0.6%) |
| | Retrospective
(Frozen) | 1.9% (6/319) | (0.9%,
4.0%) | 0.0% (0/317) | (0.0%, 1.2%) |

Table 28: Indeterminate Rates

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Of the 3183 prospective specimens initially evaluated with the BD MAX™ Enterio Bacterial Panel. 1,3% of the Carv-Blair preserved and 2.0% of the unpreserved specimens initially reported as Incomplete. Following a valid repeat test, 0% of the Cary-Blair preserved and 0% of the unpreserved specimens remained Incomplete. Of the 783 retrospective specimens initially evaluated with the BD MAX™ Enteric Bacterial Panel, 1.3% of the Cary-Blair preserved and 0% of the unpreserved specimens initially reported as Unresolved. Following a valid repeat test, 0% of the Cary-Blair preserved specimens remained Incomplete (Table 29). The total numbers provided in Table 29 are based on remainou moomplete (Table 20). The tetail hambers provided in Panel results.

| | | Initial Incomplete Rates | | Final Incomplete Rates After
Repeat | |
|------------------|---------------------------|--------------------------|-----------------|----------------------------------------|--------------|
| Specimen
Type | Specimen
Origin | Percent | 95% Cl | Percent | 95% Cl |
| Cary-Blair | Prospective
(Fresh) | 1.3%
(24/1905) | (0.8%,
1.9%) | 0.0% (0/1897) | (0.0%, 0.2%) |
| | Retrospective
(Frozen) | 1.3% (6/464) | (0.6%,
2.8%) | 0.0% (0/463) | (0.0%, 0.8%) |
| Unpreserved | Prospective
(Fresh) | 2.0%
(26/1278) | (1.4%,
3.0%) | 0.0% (0/1251) | (0.0%, 0.3%) |
| | Retrospective
(Frozen) | 0.0% (0/319) | (0.0%,
1.2%) | 0.0% (0/317) | (0.0%, 1.2%) |

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Expected Values

In the BD MAX Enteric Bacterial Panel clinical study, reportable results from compliant specimens, were obtained from 8 geographically diverse sites and compared to the reference methods. The study population was grouped based on specimen type. The number and percentage of positive cases by target, as determined by the BD MAX Enteric Bacterial Panel during the prospective segment of the clinical trial, are presented below in Table 30.

Prevalence
Specimen TypeSiteSalmonellaShigella/EIECCampylobacterShiga toxins
Cary-Blair Preserved10.0% (0/186)0.0% (0/186)1.1% (2/188)0.0% (0/185)
20.8% (3/377)0.3% (1/377)1.6% (6/368)0.8% (3/391)
30.9% (5/548)0.2% (1/548)0.8% (4/528)0.2% (1/551)
43.9% (6/152)11.2% (17/152)2.0% (3/152)0.0% (0/135)
50.3% (1/339)0.0% (0/339)1.5% (5/340)0.3% (1/320)
61.4% (6/431)0.0% (0/431)1.9% (8/431)0.7% (3/411)
Total1.0% (21/2033)0.9% (19/2033)1.4% (28/2007)0.4% (8/1993)
Unpreserved11.6% (6/376)0.3% (1/376)0.8% (3/376)0.0% (0/176)
71.6% (5/305)0.0% (0/305)2.0% (6/304)0.0% (0/229)
81.4% (4/284)0.0% (0/284)1.1% (3/284)0.4% (1/265)
42.9% (9/314)6.7% (21/314)3.5% (11/314)0.4% (1/266)
Total1.9% (24/1279)1.7% (22/1279)1.8% (23/1278)0.2% (2/936)

Table 30: Observed Prevalence by Target and Specimen Type

BD Diagnostic Systems Becton, Dickinson and Company

31

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food und Drug Administra 10903 New Hampshire Aven Document Control Center - WO Silver Spring, MD 20993-0007

BECTON, DICK INSON AND COMPANY PAUL SWIFT REGULATORY AFFAIRS PROJECT MANAGER 7 LOVETON CIRCLE SPARKS MD 21152

May 06, 2014

Re: K140111

Trade/Device Name: BD MAX™ Enteric Bacterial Panel Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal microorganism multiplex nucleic acid-based assay Regulatory Class: II Product Code: PCI, PCH, OOI Dated: April 25, 2014 Received: April 28, 2014

Dear Mr. Swift:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may oublish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Parts 801 and 809); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

32

Page 2-Mr. Swift

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Industry and Consumer Education at its toll-free number (800) 638 2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to promarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Industry and Consumer Education at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

John Hobson -S for

Sally Hojvat, M.Sc., PhD Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

33

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement on last page.

510(k) Number (if known)

K140111

Device Name

BD MAX™ Enteric Bacterial Panel

Indications for Use (Describe)

The BD MAX™ Enteric Bacterial Panel performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct oualitative detection and differentiation of enterial pathogens. The BD MAX Enteric Bacterial Panel detects nucleic acids from:

  • Salmonella spp. ●
  • . Campylobacter spp. (jejuni and coli)
  • Shigella spp. / Enteroinvasive E. coll (EIEC) .
  • Shiga toxin 1 (stx1) / Shiga toxin 2 (stx2) genes (found in Shiga toxin-producing E. coli [STEC]) as well as Shigello . dysenterioe, which can possess a Shiga toxin gene (stx) that is identical to the stx1 gene of STEC.

Testing is performed on unpreserved 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 SpoO, a Campylobocter specific tufgene sequence, ipoH 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/EEC, Compylobacter and Shiga toxin-producing E. coll (STEC) infections. Results of this test should not be used as tor 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 of cinical 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.

Type of Use (Select one or both, as applicable) 2 Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C)

  • ☐ Over-the-Counter use (21 CFR 301) Sunpain C

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON A SEPARATE PAGE IF NEEDED.

ੰ , ਹੁੰ , ਹੁੰ , ਕੁ , ਮੁ , ਮੁ FOR FDA USE ONLY :

Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

John Hobson-S
2014.05.06-11:33:07-04'00'

34

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