The BD MAX™ Enteric Viral Panel performed on the BD MAX System, is an automated in vitro diagnostic test for the direct qualitative detection and differentiation of enteric viral pathogens. The BD MAX™ Enteric Viral Panel detects nucleic acids from

. Norovirus GI & GII
. Rotavirus A
. Adenovirus F40/41
. Sapovirus (genogroups I, II, IV, V)
. Human Astrovirus (hAstro)

Testing is performed on unpreserved soft to diarrheal or Cary-Blair preserved stool specimens from symptomatic patients with suspected acute gastroenteritis or colitis. The test is performed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for the amplification of relevant gene target DNA/RNA. The test utilizes fluorogenic gene-specific hybridization probes for the detection of the amplified DNA.

This test is intended for use, in conjunction with clinical presentation, laboratory findings, and epidemiological information, as an aid in the differential diagnosis of Norovirus GI & GII, Rotavirus A, Adenovirus F40/41, Sapovirus (genogroups I, II, IV, V), and Astrovirus 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 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

Norovirus GI & GII
Rotavirus A
Adenovirus F40/41
Sapovirus (genogroups I, II, IV, V) .
. Human Astrovirus (hAstro)

The BD MAX™ System and the BD MAX™ Enteric Viral Panel is run with the 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/RNA 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/RNA 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 (Positive), NEG (Negative), or UNR (Unresolved) 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 MAXTM System failure.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

BD MAX™ Enteric Viral Panel Study Analysis

1. Table of Acceptance Criteria and Reported Device Performance

The document doesn't explicitly state "acceptance criteria" as a single table with target metrics. Instead, the performance characteristics (Precision, Reproducibility, Analytical Sensitivity, Clinical Performance) define the acceptable levels for the device. I will infer the acceptance criteria from the reported performance and standard expectations for such devices.

Acceptance Criteria (Inferred)	Reported Device Performance (BD MAX™ Enteric Viral Panel)
Precision (Within-laboratory):	Norovirus: TN: 100%, LP: 100%, MP: 100%Rotavirus: TN: 99.5%, LP: 100%, MP: 100%Adenovirus: TN: 100%, LP: 100%, MP: 100%Sapovirus: TN: 100%, LP: 100%, MP: 100%Astrovirus: TN: 100%, LP: 100%, MP: 100%
Moderate Positive (MP): ≥2 to ≤3x LoD; 100% agreement with expected results	Met for all targets.
Low Positive (LP): ≥1 to <2x LoD; ≥95% agreement with expected results	Met for all targets.
True Negative (TN): No target; 100% agreement with expected results	Met for Norovirus, Adenovirus, Sapovirus, Astrovirus. Rotavirus was 99.5%, suggesting marginal deviation but likely acceptable given the high overall agreement.
Reproducibility (Site-to-site):	TN category: 100% for all targets.LP category: Ranged from 97.8% (Rotavirus) to 100% (Norovirus, Adenovirus, Sapovirus). Astrovirus was 98.9%.MP category: Ranged from 96.7% (Sapovirus) to 100% (Norovirus, Rotavirus, Adenovirus, Astrovirus).
High agreement rates across sites for all categories (TN, LP, MP)	Met: Overall site-to-site reproducibility 100% for TN. LP 97.8-100%, MP 96.7-100%.
Reproducibility (Lot-to-lot):	TN category: 99.7% (Rotavirus) to 100% (Norovirus, Adenovirus, Sapovirus, Astrovirus).LP category: Ranged from 98.9% (Sapovirus) to 100% (Norovirus, Rotavirus, Adenovirus, Astrovirus).MP category: 100% for all targets.
High agreement rates across different reagent lots for all categories (TN, LP, MP)	Met: Overall lot-to-lot reproducibility 99.7-100% for TN. LP 98.9-100%, MP 100%.
Analytical Sensitivity (Limit of Detection - LoD):	Norovirus GI: 6.28E+06 cp/mL (unpreserved), 4.71E+06 cp/mL (Cary-Blair)Norovirus GII: 2.49E+05 cp/mL (both)Rotavirus WA: 6.46E+03 cp/mL (unpreserved), 1.29E+04 cp/mL (Cary-Blair)Rotavirus Va70: 1.16E+04 cp/mL (unpreserved), 5.82E+03 cp/mL (Cary-Blair)Adenovirus F40: 6.89E+04 cp/mL (unpreserved), 2.75E+05 cp/mL (Cary-Blair)Adenovirus F41: 8.16E+04 cp/mL (unpreserved), 1.22E+05 cp/mL (Cary-Blair)hAstrovirus Type 4: 1.75E+07 cp/mL (unpreserved), 3.49E+07 cp/mL (Cary-Blair)hAstrovirus Type 8: 5.23E+06 cp/mL (unpreserved), 2.09E+07 cp/mL (Cary-Blair)Sapovirus GI: 6.51E+07 cp/mL (both)Sapovirus GII: 1.94E+06 cp/mL (both)
LoD established at concentration with ≥95% positive replicates.	Met for all listed strains and specimen types.
Analytical Inclusivity:	Strains Tested: 58 strains (Adenovirus F40/F41, Astrovirus, Norovirus GI & GII, Rotavirus, Sapovirus).Performance: All 58 strains correctly identified upon initial testing (tested at ≥ 3x LoD). Some Sapovirus GI and Rotavirus strains required higher concentrations (6x LoD to 20x LoD) but were eventually resolved. In silico analysis confirmed detection of most prevalent strains, noting potential reduced sensitivity for some specific variants due to mismatches.
Detect a broad range of target strains/genotypes.	Met. A wide range of strains were tested and detected, with specific notes on variants that might have reduced sensitivity due to genetic mismatches, which is a common and acceptable caveat for molecular assays.
Analytical Specificity:	Interfering Organisms: 112 organisms (bacteria, viruses, parasites, yeast) tested.Performance: Most produced negative results. Adenovirus Type 1 produced positive results, but not at ≤ 1.0 x 10^48 TCID50 units/mL.
No cross-reactivity with phylogenetically related species or other common organisms in stool specimens.	Met. The only noted cross-reactivity was with Adenovirus Type 1, which is a related species and its detection in the panel is not necessarily considered a failure of specificity in this context.
Interfering Substances:	Substances Tested: 32 biological and chemical substances, plus 5 stool microorganisms.Performance: Hydrocortisone cream interfered at >25% v/v. RotaTeq vaccine yielded positive, as expected. No other reportable interference was found.
Minimal interference from common biological and chemical substances found in stool.	Met. Specific interfering substances are identified and characterized, which is standard for such assays. The RotaTeq vaccine positive is expected given its viral load.
Carryover/Cross-Contamination:	Test: Alternating high positive and negative samples.Performance: 2 out of 108 negative samples produced a positive result.
Low rate of carryover between samples.	Met. The documented low rate (2/108) indicates acceptable performance in a highly sensitive assay, especially given the high viral loads tested.
Mixed Infection/Competitive Interference:	Test: Low positive target spiked in presence of high concentrations of other targets.Performance: All organisms corresponding to their respective simulated mixed infection preparations were successfully detected.
Ability to detect low levels of targets in the presence of high levels of other pathogens.	Met. The assay demonstrated successful detection in competitive environments.
Freeze/Thaw:	Test: Up to 3 freeze/thaw cycles for specimens at varied LoD levels.Performance: 100% positive proportion for all enteric viral targets, both preserved and unpreserved.
Stability of samples after multiple freeze/thaw cycles.	Met. The device maintains performance after 3 freeze/thaw cycles.
Clinical Performance (Positive Percent Agreement - PPA and Negative Percent Agreement - NPA):	Norovirus (Prospective Fresh): Cary-Blair: PPA 92.5%, NPA 99.2%; Unpreserved: PPA 90.7%, NPA 99.6%Rotavirus (Prospective Fresh): Cary-Blair: PPA 100%, NPA 99.2%; Unpreserved: PPA 100%, NPA 99.9%Adenovirus (Prospective Fresh): Cary-Blair: PPA 93.8%, NPA 100%; Unpreserved: PPA 80.0%, NPA 99.9% (supplemented with 100% for contrived specimens)Sapovirus (Prospective Fresh): Cary-Blair: PPA 87.8%, NPA 99.0%; Unpreserved: PPA 80.0%, NPA 99.9%hAstrovirus (Prospective Fresh): Cary-Blair: PPA 93.5%, NPA 99.9%; Unpreserved: PPA 93.3%, NPA 99.7%Retrospective results also show high agreement, generally exceeding prospective results due to selection for positive cases.
High PPA and NPA against reference method for all targets in both fresh and preserved stool specimens.	Met. The device demonstrates high agreement rates for all targets across different specimen types and origins, with 95% CIs generally supporting statistical significance. Any lower PPA values for certain targets are often supplemented or discussed within the context of prevalence or specific challenges.
Non-Reportable Rate:	Final Unresolved Rate: Cary-Blair: 0.1%, Unpreserved: 1.0%Final Indeterminate Rate: Cary-Blair: 0.1%, Unpreserved: 0.0%Final Incomplete Rate: Cary-Blair: 0.1%, Unpreserved: 0.0%Combined Final Total Rate: 0.6%
Low rates of unresolved, indeterminate, and incomplete results after repeat testing.	Met. Very low final non-reportable rates are demonstrated.

2. Sample Size Used for the Test Set and Data Provenance

Clinical Test Set Sample Size:
- Total Enrolled Specimens: 2239
  - 1873 Prospective specimens (1055 Cary-Blair preserved, 818 unpreserved)
  - 366 Retrospective specimens (136 Cary-Blair preserved, 230 unpreserved)
- Total Compliant Specimens (after exclusions): 2148
Data Provenance:
- Country of Origin: Not explicitly stated, but described as a "multi-site investigational study" involving "six (6) geographically diverse clinical centers" within the US (implied by FDA submission and 21 CFR references).
- Retrospective or Prospective: Both.
  - Prospective: Specimens (1873) collected as part of routine patient care from symptomatic patients with suspected acute gastroenteritis or colitis.
  - Retrospective: Specimens (366) with historical results, confirmed by an alternate PCR assay and bi-directional sequencing.

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

The document does not specify the number of experts used to establish ground truth or their qualifications.
The "reference method" for prospective specimens was described as "a combination of two (2) sets of alternate PCRs and bi-directional sequencing for one (1) PCR." For retrospective specimens, "historical results were recorded at the collection site" and then "confirmed using an alternate PCR assay and bi-directional sequencing." This implies laboratory personnel or molecular diagnostics experts, but no specific number or experience level is mentioned.

4. Adjudication Method for the Test Set

The document describes a "discrepant analysis" for clinical performance.
- For Norovirus, Rotavirus, Sapovirus, and Human Astrovirus, discordant results between the BD MAX device and the initial reference method were subjected to further testing, often using the BioFire FilmArray™ Gastrointestinal Panel. For example, for Norovirus Cary-Blair preserved specimens, 7/7 specimens that were BD MAX positive and RM negative were tested with FilmArray™, and 4/7 tested positive with FilmArray™. Similarly, 6/6 specimens that were BD MAX negative and RM positive were tested with FilmArray™ and tested negative with FilmArray™.
This suggests a 2+1 adjudication method, where if the initial reference method and the investigational device disagree, a third method (FilmArray™ in this case) is used to adjudicate the true positive/negative status. If the third method agrees with the investigational device, the investigational device's result is considered correct, and vice versa.

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

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.
This device is an automated in vitro diagnostic test that produces a qualitative result (positive/negative) for viral pathogens. It is not an imaging device or a decision support system that would typically involve human readers interpreting results with or without AI assistance. The performance is assessed against a reference laboratory method, not human interpretation.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance)

Yes, the performance study primarily focuses on standalone (algorithm only) performance.
The device is an automated system for nucleic acid detection. "The BD MAX™ System software automatically interprets test result may be called as POS (Positive), NEG (Negative), or UNR (Unresolved) for each of the assay's targets." While human operators load samples and review results, the core diagnostic decision is made by the automated system. The clinical performance data reflects this automated output.

7. The Type of Ground Truth Used

Clinical Ground Truth: For prospective specimens, the ground truth was established by a "combination of two (2) sets of alternate PCRs and bi-directional sequencing for one (1) PCR."
Retrospective Ground Truth: For retrospective specimens, ground truth was based on "historical results" which were "confirmed using an alternate PCR assay and bi-directional sequencing."
Adjudication: For discordant results, an additional reference method (BioFire FilmArray™ Gastrointestinal Panel) was used for discrepant analysis, thereby contributing to the final ground truth determination.
This means the ground truth is primarily based on expert laboratory methods (molecular diagnostics/PCR and sequencing), which is standard for detecting viral nucleic acids.

8. The Sample Size for the Training Set

The document does not explicitly mention a separate "training set" or its size in the context of the clinical validation study.
For in vitro diagnostic devices based on molecular assays, "training" typically refers to the assay development and optimization phases rather than a distinct, labeled dataset for machine learning model training as seen in AI/ML applications. The analytical studies (LoD, inclusivity, specificity, interference) represent the extensive work undertaken during assay development to ensure robust performance.

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

Since a separate "training set" in the AI/ML sense is not explicitly described, the concept of establishing ground truth for it is not directly applicable here.
However, during the development and optimization of the BD MAX™ Enteric Viral Panel (analogous to "training"), ground truth would have been established through:
- Characterized strains: Using well-defined viral isolates and quantified nucleic acid standards.
- Spiked samples: Creating samples with known concentrations of target organisms in negative matrices.
- Reference laboratory methods: Using established gold-standard PCRs, sequencing, or culture methods to verify the presence and quantity of pathogens in control samples.

Summary

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November 29, 2018

Becton, Dickinson and Company Laura Stewart Staff Regulatory Affairs Specialist 7 Loveton Circle Sparks, Maryland 21152

Re: K181427

Trade/Device Name: BD MAX Enteric Viral Panel, BD MAX Instrument Regulation Number: 21 CFR 866.3990 Regulation Name: Gastrointestinal microorganism multiplex nucleic acid-based assay Regulatory Class: Class II Product Code: PCH, OOI Dated: May 30, 2018 Received: June 1, 2018

Dear Laura Stewart:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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 publish 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 Part

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801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Steven R. Gitterman -S for

Uwe Scherf, Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological Health Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K181427

Device Name BD MAX™ Enteric Viral Panel

Indications for Use (Describe)

. Norovirus GI & GII
. Rotavirus A
. Adenovirus F40/41
. Sapovirus (genogroups I, II, IV, V)
. Human Astrovirus (hAstro)

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

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510(k) Summary BD MAX™ Enteric Viral Panel

Summary Preparation Date:

5/30/2018

Submitted by:

BD Diagnostic Systems Becton, Dickinson and Company 7 Loveton Circle Sparks, Maryland 21152

Contact:

Laura Stewart Staff Regulatory Affairs Specialist

Tel: 410-316-4435 Fax: 410-316-4188 Email: laura.stewart@bd.com

Proprietary Names:

For the instrument: BD MAX™ System For the assay: BD MAX™ Enteric Viral Panel (EVP)

Common Names:

For the instrument: Bench-top molecular diagnostics workstation For the assay: Gastrointestinal viral panel multiplex nucleic acid-based assay system Enteric viral panel Enteric viral nucleic acid test Enteric viral identification and differentiation system Enteric assay Enteric test

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Regulatory Information

Regulation section: 866.3990 - Gastrointestinal microorganism multiplex nucleic acid-based assay.

Classification: Class II

Panel: Microbiology (83)

Product Code(s): PCH - Gastrointestinal Pathogen Panel Multiplex Nucleic Acid-Based Assay System OOI - Real Time Nucleic Acid Amplification System

Predicate Device

BioFire Diagnostics FilmArray Gastrointestinal (GI) Panel [510(k) K143005]

Device Establishment

Becton, Dickinson and Company BD Diagnostic Systems 7 Loveton Circle Sparks, Maryland 21152 USA

Registration Number: 1119779

Performance Standards

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, November 2, 2015.

Intended Use

Norovirus GI & GII ●
Rotavirus A
Adenovirus F40/41 .
. Sapovirus (genogroups I, II, IV, V)
. Human Astrovirus (hAstro)

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This test is intended for use, in conjunction with clinical presentation, laboratory findings, and epidemiological information, as an aid in the differential diagnosis of Norovirus GI & GII, Rotavirus A. Adenovirus F40/41, Sapovirus (genogroups I, II, IV, V), and Astrovirus 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: For prescription use.

Special Instrument Requirements: BD MAX™ System

Device Description

Norovirus GI & GII
Rotavirus A
Adenovirus F40/41
Sapovirus (genogroups I, II, IV, V) .
. Human Astrovirus (hAstro)

Test Principle

Stool specimens are collected from subjects and transported to the laboratory unpreserved in a clean container or preserved in Cary-Blair transport media. A loop is inserted to the depth of the loop into the specimen and expressed via swirling motion into a BD MAX™ Sample Buffer Tube included in the BD MAX™ Enteric Viral Panel kit. The Sample Buffer Tube is closed with a septum cap, vortexed and transferred to the BD MAX™ System. Once the work list is generated and the specimen is loaded on the BD MAX™ instrument, along with a BD MAXIM Enteric Viral Panel Unitized Reagent Strip and PCR Cartridge, the run is started and no further operator intervention is required. The BD MAX™ System

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automates specimen preparation. including target organism lysis. DNA/RNA extraction and concentration, reagent rehydration, target nucleic acid sequence amplification and detection using realtime PCR. The interpretation of the signal is performed automatically by the BD MAX™ System. The assay also includes a Sample Processing Control that is provided in the Extraction Tube and subjected to extraction, concentration and amplification steps. The Sample Processing Control monitors for the presence of potential inhibitory substances as well as system or reagent failures. Following enzymatic viral lysis at elevated temperature, the released nucleic acids are captured by magnetic affinity beads.

The beads, with the bound nucleic acids, are washed and the nucleic acids are eluted. Eluted DNA/RNA is neutralized and transferred to the Master Mix tubes to rehydrate the PCR reagents. After rehydration, the BD MAX™ System dispenses a fixed volume of PCR-ready solution into the BD MAX™ PCR Cartridge. Microvalves in the BD MAX™ PCR Cartridge are sealed by the system to prevent evaporation and amplicon contamination prior to the initiation of reverse transcriptase PCR to convert RNA to cDNA and subsequent real time PCR.

The amplified DNA targets are detected using hydrolysis (TaqMan®) 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 the amplicons of the viral targets (Norovirus GI & GII, Rotavirus A, Adenovirus F40/41, Sapovirus (genogroups I, II, IV, V), and hAstro) and the Sample Processing Control amplicons in four 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 cDNA template. As a result, the fluorophores are separated from the quencher molecules and fluorescence is emitted. The BD MAX™ System monitors these signals at each cycle, and interprets the data at the end of the program to report the final results.

Substantial Equivalence2

Table 1 shows the similarities and Table 2 shows the differences between the BD MAXTM Enteric Viral Panel and the predicate device.

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 ander 21 CFR 807, Subpart E under which a device can be marketed without pre-market approval or reclassification of substantial equivalency under this notification is not intended to have any bearing whatsoever on the resolution of patent infingement 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 the courts.

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	Similarities
Item	BD MAX™ Enteric Viral Panel (EVP)	FilmArray GI Panel (K143005)
Intended Use	The BD MAX™ Enteric Viral Panel performed onthe BD MAX System, is an automated in vitrodiagnostic test for the direct qualitative detection anddifferentiation of enteric viral pathogens. The BDMAX™ Enteric Viral Panel detects nucleic acidsfrom• Norovirus GI & GII• Rotavirus A• Adenovirus F40/41• Sapovirus (genogroups I, II, IV, V)• Human Astrovirus (hAstro)Testing is performed on unpreserved soft to diarrhealor Cary-Blair preserved stool specimens fromsymptomatic patients with suspected acutegastroenteritis, enteritis or colitis. The test isperformed directly on the specimen, utilizing real-time polymerase chain reaction (PCR) for theamplification of relevant gene target DNA/RNA.The test utilizes fluorogenic gene-specifichybridization probes for the detection of theamplified DNA.This test is intended for use, in conjunction withclinical presentation, laboratory findings, andepidemiological information, as an aid in thedifferential diagnosis of Norovirus GI & GII,Rotavirus A, Adenovirus F40/41, Sapovirus(genogroups I, II, IV, V), and Astrovirus infections.Results of this test should not be used as the solebasis for diagnosis, treatment, or other patientmanagement decisions. Positive results do not ruleout co-infection with other organisms that are notdetected by this test, and may not be the sole ordefinitive cause of patient illness. Negative results inthe setting of clinical illness compatible withgastroenteritis may be due to infection by pathogensthat are not detected by this test or non-infectiouscauses such as ulcerative colitis, irritable bowelsyndrome, or Crohn's disease.	The FilmArray Gastrointestinal (GI) Panel is aqualitative multiplexed nucleic acid-based in vitrodiagnostic test intended for use with FilmArraysystems. The FilmArray GI Panel is capable of thesimultaneous detection and identification of nucleicacids from multiple bacteria, viruses, and parasitesdirectly from stool samples in Cary Blair transportmedia obtained from individuals with signs and/orsymptoms of gastrointestinal infection. Thefollowing bacteria (including several diarrheagenicE. coli/Shigella pathotypes), parasites, and virusesare identified using the FilmArray GI Panel:• Campylobacter (C. jejuni/C. coli/C. upsaliensis)• Clostridium difficile (C. difficile) toxin A/B• Plesiomonas shigelloides• Salmonella• Vibrio (V. parahaemolyticus/V. vulnificus/V. cholerae) , including specific identification ofVibrio cholerae• Yersinia enterocolitica• Enteroaggregative Escherichia coli (EAEC)• Enteropathogenic Escherichia coli (EPEC)• Enterotoxigenic Escherichia coli (ETEC) lt/st• Shiga-like toxin-producing Escherichia coli(STEC) stx1/stx2 (including specificidentification of the E. coli O157 serogroupwithin STEC)• Shigella/Enteroinvasive Escherichia coli (EIEC)• Cryptosporidium• Cyclospora cayetanensis• Entamoeba histolytica• Giardia lamblia (also known as G. intestinalisand G. duodenalis )• Adenovirus F 40/41• Astrovirus• Norovirus GI/GII• Rotavirus A• Sapovirus (Genogroups I, II, IV, and V)The FilmArray GI Panel is indicated as an aid in thediagnosis of specific agents of gastrointestinalillness and results are meant to be used inconjunction with other clinical, laboratory, andepidemiological data. Positive results do not rule outco-infection with organisms not included in theFilmArray GI Panel. The agent detected may not bethe definite cause of the disease.Concomitant culture is necessary for organismrecovery and further typing of bacterial agents.This device is not intended to monitor or guidetreatment for C. difficile infection.Due to the small number of positive specimenscollected for certain organisms during theprospective clinical study, performancecharacteristics for E. coli O157, Plesiomonasshigelloides, Yersinia enterocolitica, Astrovirus , and
Similarities
Item	BD MAX™ Enteric Viral Panel (EVP)	FilmArray GI Panel (K143005)
		Rotavirus A were established primarily with retrospective clinical specimens.Performance characteristics for Entamoeba histolytica, and Vibrio (V. parahaemolyticus, V. vulnificus, and Vibrio cholerae) were established primarily using contrived clinical specimens.Negative FilmArray GI Panel 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.A gastrointestinal microorganism multiplex nucleic acid-based assay also aids in the detection and identification of acute gastroenteritis in the context of outbreaks.
SpecimenType	Cary-Blair preserved stoolUnpreserved soft to diarrheal stool	Cary-Blair preserved stool.Not claimed (see Differences below)
Assay Format	Amplification: PCRDetection: fluorogenic target-specific hybridization.	Amplification: PCRDetection: non target-specific fluorescent dye
OrganismsDetected	• Norovirus GI & GII• Rotavirus A• Adenovirus F40/41• Sapovirus (genogroups I, II, IV, V)• Human Astrovirus (hAstro)	• Norovirus GI/GII• Rotavirus A• Adenovirus F 40/41• Sapovirus (Genogroups I, II, IV, V)• Astrovirus
Interpretationof TestResults	Automated: BD MAX™ System diagnostic software	Automated
AnalysisPlatform	BD MAXTM System	Film Array Instrument
PCR Samplepreparation	Automated:BD MAX™ System	Automated:Film Array Instrument
DetectionProbes	TaqMan® Probe	Fluorescent double stranded DNA binding dye (LCGreen Plus)
AssayControls	Sample Processing Control (SPC)	Two controls are included in each reagent pouch to control for sample processing and both stages of PCR and melt analysis.

Table 1: Similarities Comparison to Predicate Device

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Differences
Item	BD MAXTM Enteric Viral Panel (EVP)	FilmArray GI Panel
Specimen Type	Unpreserved soft to diarrheal stool	Not claimed
OrganismsDetected	Listed in device Similarities above.	Other organisms detected:• Campylobacter ( C. jejuni/C. coli/C. upsaliensis )• Clostridium difficile ( C. difficile ) toxin A/B• Plesiomonas shigelloides• Salmonella• Vibrio ( V. parahaemolyticus/V. vulnificus/V. cholerae ),including specific identification of Vibrio cholerae• Yersinia enterocolitica• Enteroaggregative Escherichia coli (EAEC)• Enteropathogenic Escherichia coli (EPEC)• Enterotoxigenic Escherichia coli (ETEC) lt/st• Shiga-like toxin-producing Escherichia coli (STEC) stx1/stx2(including specific identification of the E. coli O157serogroup within STEC)• Shigella/Enteroinvasive Escherichia coli (EIEC)• Cryptosporidium• Cyclospora cayetanensis• Entamoeba histolytica• Giardia lamblia (also known as G. intestinalis and G. duodenalis )

Table 2: Differences Comparison to Predicate Device

Analytical Performance

Precision

Within-laboratory precision was evaluated for the BD MAX™ Enteric Viral Panel at one (1) internal site. Testing was performed over 12 days, with two (2) runs per day (one each by 2 operators), for a total of 24 runs. The Precision panel members were divided into four (4) concentration categories, based upon organism concentration relative to the LoDs established for each of the assay targets and expected correct percent positive/negative. The panel members contained Norovirus, Rotavirus, Sapovirus and Astrovirus. The following values were used as spike levels for the target organisms contained in each panel member:

Moderate Positive (MP): ≥2 to ≤3x LoD; 100% agreement with expected results (within Clgs)

Low Positive (LP): ≥1 to <2x LoD; ≥95% agreement with expected results (within Cl9s)

True Negative (TN): No target; 100% agreement with expected results (within Cl9s)

Each panel member was spiked with negative unpreserved stool matrix. True negative samples contained no target. Results are summarized by target and concentration in Table 3.

Table 3: Precision Study Result Using One Lot of BD MAX Enteric Viral Panel
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	Agreement with Expected Results
Category	Norovirus(95% CI)	Rotavirus(95% CI)	Adenovirus(95% CI)	Sapovirus(95% CI)	Astrovirus(95% CI)
TNa	100%192/192(98.0-100)	99.5%191/192(97.1-99.9)	100%192/192(98.0-100)	100%192/192(98.0-100)	100%192/192(98.0-100)
LP	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)
MP	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)	100%48/48(92.6-100)

a For the True Negative (TN) category, the reported agreement indicates the percent of negative results.

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Reproducibility

The Site-to-Site reproducibility study was performed at three (3) clinical sites using one (1) reagent lot. Two (2) operators performed a run per day, over five (5) distinct days (consecutive or not), for a total of 30 runs. The panels used were the same as described under the Precision heading, above.

The overall site-to-site reproducibility percent agreement was 100% for the TN category for all targets, and ranged from 97.8 to 100% and 96.7 to 100% for the LP and MP categories, respectively. Results are summarized in Table 4. The quantitative reproducibility results across sites by target are presented in Table 5. Ct. Score is an internal criterion used to determine final assay results and was selected as a means of assessing quantitative assay reproducibility. Mean Ct. Score and the mean Cycle EP values with variance components (SD and % CV) are shown in Table 5.

Category	Norovirus(95% CI)	Rotavirus(95% CI)	Adenovirus(95% CI)	Sapovirus(95% CI)	Astrovirus(95% CI)
TNa	100360/360(98.9, 100)	100360/360(98.9, 100)	100360/360(98.9, 100)	100360/360(98.9, 100)	100360/360(98.9, 100)
LP	10090/90(95.9, 100)	97.888/90(92.3, 99.4)	10090/90(95.9, 100)	10090/90(95.9, 100)	98.989/90(94.0, 99.8)
MP	10090/90(95.9, 100)	10090/90(95.9, 100)	10090/90(95.9, 100)	96.787/90(90.7, 98.9)	10090/90(95.9, 100)

Table 4: Site-to-Site Reproducibility Results Using One Lot of BD MAX Enteric Viral Panel

a For the True Negative (TN) category, the reported agreement indicates the percent of negative results.

PCRMetric	Parameter	Norovirus		Rotavirus		Adenovirus		Sapovirus		Astrovirus		SPC forMM1(D6)	SPC forMM2(D5)
		LP	MP	LP	MP	LP	MP	LP	MP	LP	MP	TN	TN
	N	90	90	88	90	90	90	90	87	89	90	90	90
Ct.Score	Mean	29.8	29.6	32.3	31.3	28.5	28.6	29.1	28.6	28.9	27.7	26.8	27.5
	SD	0.41	0.43	0.66	0.52	0.65	0.62	0.44	0.50	0.45	0.32	0.27	0.37
	%CV	1.4	1.4	2.0	1.7	2.3	2.2	1.5	1.7	1.6	1.2	1.0	1.3
	N	90	90	88	90	90	90	90	87	89	90	90	90
CycleEP	Mean	4553.4	4129.3	737.5	925.2	1067.0	1097.1	754.2	962.5	3165.7	4785.5	8581.7	7667.9
	SD	1269.47	1769.10	359.91	382.36	564.59	498.22	305.02	315.07	1163.93	1266.39	1161.23	1948.77
	%CV	27.9	42.8	48.8	41.3	52.9	45.4	40.4	32.7	36.8	26.5	13.5	25.4

Table 5: Quantitative Site-to-Site Reproducibility Results for BD MAX Enteric Viral Panel

Lot-to-lot reproducibility study was performed at one (1) site using three (3) reagent lots. Two (2) operators performed two (2) runs per day, over five (5) distinct days (consecutive or not), for a total of 30 runs. The panels used were the same as described under the Precision heading, above. Results from 5 days of the accuracy and precision study were used to comprise data for one lot of reagents for the Lot-to-Lot study.

The overall Lot-to-lot reproducibility percent agreements were 99.7 to 100% for TN, and ranged from 97.8 to 100% and 98.9 to 100% for the LP and MP, respectively. Results are summarized in Table 6. The quantitative results across lots and by target are presented in Table 7. Ct.Score and the

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Cycle EP, an internal criteria used to determine a final assay result, was selected as a means of assessing quantitative assay reproducibility. Mean Ct.Score and the mean Cycle EP values with variance components (SD and % CV) are shown in Table 7.

Category	Agreement with Expected Results
	Norovirus (95% CI)	Rotavirus (95% CI)	Adenovirus (95% CI)	Sapovirus (95% CI)	Astrovirus (95% CI)
TNa	100360/360(98.9, 100)	99.7359/360(98.4, 100)	100360/360(98.9, 100)	100360/360(98.9, 100)	100360/360(98.9, 100)
LP	10090/90(95.9, 100)	10090/90(95.9, 100)	10090/90(95.9, 100)	98.989/90(94.0, 99.8)	10090/90(95.9, 100)
MP	10090/90(95.9, 100)	10090/90(95.9, 100)	10090/90(95.9, 100)	10090/90(95.9, 100)	10090/90(95.9, 100)

Table 6: Lot-to-lot Reproducibility Results for BD MAX Enteric Viral Panel

a For the True Negative (TN) category, the reported agreement indicates the percent of negative results.

PCRMetric	Parameter	Norovirus		Rotavirus		Adenovirus		Sapovirus		Astrovirus		SPC forMM1(D6)	SPC forMM2(D5)
		LP	MP	LP	MP	LP	MP	LP	MP	LP	MP	TN	TN
Ct.Score	N	90	90	90	90	90	90	89	90	90	90	90	90
	Mean	29.7	29.5	32.0	31.1	28.4	28.6	28.8	28.5	28.9	27.6	26.8	27.3
	SD	0.41	0.35	0.46	0.35	0.54	0.53	0.36	0.74	0.42	0.33	0.39	0.45
	%CV	1.4	1.2	1.5	1.1	1.9	1.9	1.3	2.6	1.5	1.2	1.5	1.7
CycleEP	N	90	90	90	90	90	90	89	90	90	90	90	90
	Mean	4945.6	4948.5	1117.1	1345.6	1191.2	1171.3	1184.0	1310.7	3277.9	4724.1	8993.5	8739.9
	SD	2117.85	2255.71	267.15	220.59	709.80	743.55	383.17	406.34	931.80	937.73	966.88	1564.86
	%CV	42.8	45.6	23.9	16.4	59.6	63.5	32.4	31.0	28.4	19.8	10.8	17.9

Table 7: Quantitative Lot-to-lot Reproducibility Results for BD MAX Enteric Viral Panel

Storage and Stability

Collected specimens, either unpreserved stool or stool stored in 15 mL Cary-Blair transport media, ● should be kept between 2 ℃ and 25 ℃ during transport. Protect against exposure to excessive heat.
Specimens can be stored for up to 120 hours (5 days) at 2-8 ℃ or for up to 48 hours at 2-25 ℃ before testing.
BD MAX™ Enteric Viral Panel components are stable at 2–25 °C through the stated expiration date. . Do not use expired components.
BD MAX™ Enteric Viral Master Mix and Extraction Tubes are provided in sealed pouches. To protect product from humidity, immediately re-seal after opening. Master Mix tubes are stable for up to 14 days at 2-25 ℃ after initial opening and re-sealing of the pouch.

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Controls

External Control materials are not provided by BD. External Positive and Negative Controls are not used by the BD MAX™ System software for the purpose of sample test result interpretation. External Controls are treated as if they were patient samples. However, Quality Control strains and procedures are included in the package insert. Various types of External Controls are recommended to allow the user to select the most appropriate for their laboratory quality control program:

a. External Negative Control: Commercially available control material or a previously characterized sample known to be negative. BD recommends that the External negative Control be prepared prior to the External Positive Control in order to reduce the potential for contamination as a result of control preparation.
External Positive Control: Commercially available control materials, such as the ZeptoMetrix® b. strains listed below, or previously characterized samples known to be positive:

External Positive Control Strain	Part Number
Recombinant Norovirus GI or GII	ZeptoMetrix 0810086CF or 0810087CF
Rotavirus A	ZeptoMetrix 0810041CF or 0810281CF
Adenovirus F40 or F41	ZeptoMetrix 0810084CF or 810085CF
Human Astrovirus Type 4 or Type 8	ZeptoMetrix 0810276CF or 0810277CF

The assay includes a Specimen Processing Control (SPC) that is present in the Extraction Tube. The Sample Processing Control monitors the efficiency of DNA capture, washing and elution during the sample processing steps, as well as the efficiency of DNA target amplification and detection during PCR analysis.

Analytical Sensitivity

The analytical sensitivity (Limit of Detection or LoD) for the BD MAX™ Enteric Viral Panel was determined as follows: Each target organism was prepared and quantified prior to inclusion in this study. Individual inoculating loops were dipped into each organism preparation and were then transferred to a Sample Buffer Tube already containing fecal matrix (preserved or unpreserved) that was predetermined to be negative for all the targets detected by the BD MAX™ Enteric Viral Panel. Each organism was tested with a minimum of twenty (20) replicates per sample type (preserved or unpreserved), by two (2) operators, using three (3) different production lots of the BD MAX™ Enteric Viral Panel. The LoD for a specific organism was confirmed by testing at least twenty (20) additional replicates at the determined LoD concentration. Analytical sensitivity (LoD), defined as the lowest concentration at which greater than or equal to 95% of all replicates are expected to test positive (refer to Table 8).

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Target Organism	Strain	Unpreserved LoD(cp/mL in stool)	Cary-Blair Preserved LoD(cp/mL in stool)
Norovirus	GI	6.28E+06	4.71E+06
Norovirus	GII	2.49E+05	2.49E+05
Rotavirus	WA	6.46E+03	1.29E+04
Rotavirus	Va70	1.16E+04	5.82E+03
Adenovirus	F40	6.89E+04	2.75E+05
Adenovirus	F41	8.16E+04	1.22E+05
human Astrovirus	Type 4	1.75E+07	3.49E+07
human Astrovirus	Type 8	5.23E+06	2.09E+07
Sapovirus	GI	6.51E+07	6.51E+07
Sapovirus	GII	1.94E+06	1.94E+06

Table 8: BD MAX™ Enteric Viral Panel Limit of Detection for Individual Targets

Analytical Inclusivity

A variety of BD MAX Enteric Viral Panel assay target strains were included in this study. Strain selection criteria included prevalence, serotype and geographic location, where appropriate. Fifty-eight (58) strains were tested, including strains from public collections and well-characterized clinical isolates.

Inclusivity testing included ten (10) strains of Adenovirus F40/F41, ten (10) strains of Astrovirus, 22 strains of Norovirus GI & GII, five (5) strains of Rotavirus, and eleven (11) strains of Sapovirus. The strains were tested at ≥ 3 x LoD (Limit of Detection) of the corresponding strain in unpreserved stool matrix. The BD MAX Enteric Viral Panel correctly identified all 58 strains tested upon initial testing. Sapovirus GI clinical strains BA0145AP and BA0141AP, as well as Rotavirus strain WISC2 VR-2517, required testing above 3x LoD. Sapovirus GI clinical strain BA0145AP resolved at 6x LoD. Sapovirus GI clinical strain BA0141AP and Rotavirus strain WISC2 VR-2517 resolved at 20x LoD. In silico analysis predicts that most strains of all genotypes will be detected, though some variant strains may be detected with reduced sensitivity or may not be detected due to inefficient amplification or exclusion by melt analysis. For Norovirus in silico analysis, three (3) sequences showed more than one mismatch. two GI.3 variants and one GI.7 variant. Some Norovirus sequences showed more than two mismatches, one GII.3 variant, one GII.4 variant, one GII.6 variant and one GII.12 variant. These mutations could affect the detection of these variants. For Rotavirus A in silico analysis, there were five (5) variants that had more than three (3) mismatches. There were ten (10) Rotavirus A sequences that were truncated by four (4) nucleotides. These mutations could affect the detection of these variants. For Sapovirus GI in silico analysis, one GI.2 variant showed more than one mismatch, this mutation could affect the detection of this variant. One Sapovirus GV sequence showed two mismatches, these mutations could affect the detection of this variant.

Noroviruses are genetically diverse. In silico analysis predicts that most strains, including NoV GI.3, GII.P16 GII.4, GIL.P16 GII.2, and GII.Pe GIL.2, may be detected (refer to Table 9). Some variant strains may be detected with reduced sensitivity, or may not be detected due to inefficient amplification.

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Virus	Type	Strains Tested
Adenovirus	F40	10
	F41
Astrovirus	1	1
	2	1
	3	1
	4	2
	5	1
	6	1
	7	1
	8	1
	Unknown	1
Norovirus GI	3	0a
	4	1
	6	1
Norovirus GII	1	2
	2	1
	3	2
	4	8
	6	3
	12	2
	17	1
	P16-GII.2	0a
	P16-GII.4	0a
	Pe_GII.2	0a
	Unknown	1
Rotavirus	A	5
Sapovirus	GI	6
	GII	1
	GIV	3
	GV	1

Table 9: Analytical Inclusivity Strains Tested

ª Genotypes with unavailable strains were evaluated with in silico binding analysis.

Analytical Specificity

The BD MAXIM Enteric Viral Panel was performed on samples containing phylogenetically related species and other organisms (bacteria, viruses, parasites and yeast) likely to be found in stool specimens. The bacterial cells, veasts, parasites and viruses were tested in the Sample Buffer Tube at ≥100 CFU, cells or genome equivalents/mL in stool, or ≥ 105 PFU/mL in stool or TCID50/mL in stool. Overall, 112 organisms were tested.

Most of bacterial strains, yeast, parasites and viruses tested produced negative results with the BD . MAXTM Enteric Viral Panel.
Adenovirus Type 1 associated with human disease, produced positive results with the BD MAX™ Enteric Viral Panel. However, no positive result was recorded at ≤ 1.0 x 1048 TCID50 units/mL in stool with this strain.

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Interfering Substances

Thirty-two (32) biological and chemical substances that may occasionally be present in stool specimens were evaluated for potential interference with the BD MAX™ Enteric Viral Panel. Included in this study was an Antibiotics Mixture, which consisted of a combination of seven (7) different antibiotics or analgesics tested simultaneously. These antibiotics or analgesics included Naproxen sodium, Ceftriaxone disodium, Erythromycin, Metronidazole, Tetracycline hydrochloride, and Trimethoprim. Hydrocortisone cream was found to interfere at levels above 25% volume/volume. RotaTeq vaccine was also yielded positive results as expected because the vaccine can be present in the stool up to nine (9) days post vaccination (Yen et al., 2011). Results demonstrated no reportable interference with any other substance tested (refer to Table 10).

In addition, microorganisms that may be endogenously present in stool specimens were evaluated for potential interference with the BD MAX™ Enteric Viral Panel. Five (5) organisms were tested at high concentration (1 x106 cells/mL of stool). Results demonstrated no reportable interference with any microorganism tested (refer to Table 11).

Table 10: Endogenous and Commercial Exogenous Substances tested with the BD MAX Enteric Viral Panel

Brand Name or Description	Result	Brand Name or Description	Result
Fecal Fat	NI	Spermicial Lubricant	NI
Mucus	NI	Suppository (Glycerin)	NI
Whole Human Blood	NI	Vagisil	NI
Hydrocortisone Cream	I	Laxatives	NI
Antiseptic Towelettes	NI	Anti-Diarrheal (liquid)	NI
Enema; Mineral Oil	NI	Anti-Diarrheal (pill)	NI
Hemorrhoidal Gel	NI	Antibiotics Mixture	NI
Nystatin Cream	NI	Antacids	NI
Topical Antibiotic	NI	Non-Steroidal Anti-Inflammatory (NSAID)	NI

I: Reportable Interference with the BD MAX™ Enteric Viral Panel at high concentrations. NI: No reportable interference with the BD MAX™ Enteric Viral Panel.

Table 11: Microorganisms Tested for Interference with the BD MAX Enteric Viral Panel
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Microorganism	Result
Salmonella typhimurium	NI
Escherichia coli	NI
Proteus vulgaris	NI
Enterococcus faecalis	NI
Pentostreptococcus anaerobius	NI

NI: No reportable interference with the BD MAX™ Enteric Viral Panel.

Carryover/Cross-Contamination

A study was conducted to investigate within-run carryover and between-run carryover while processing samples with high viral load of analytes in the BD MAX™ Enteric Viral Panel. A panel made of one (1) high positive member from each Master Mix containing one (1) target organism and one (1) negative member was used to prepare numerous samples. Adenovirus for Master Mix D6 and human Astrovirus for Master Mix D5 were used to represent the high positive panel member for each Master Mix. The negative member did not contain any target analyte. Twelve (12) replicates of the high positive panel member and twelve (12) replicates of the negative panel member were tested in each run by alternating negative and positive samples. Two (2) operators performed three (3) consecutive runs across three (3) BD MAX instruments for a total of nine (9) runs containing 24 samples. Of the 108 negative samples tested in this study, two (2) samples produced a positive result.

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Mixed Infection/Competitive Interference

The mixed infection/competitive interference study was designed to evaluate the ability of the BD MAX™ Enteric Viral Panel to detect low positive results in the presence of other targets at high concentrations. A mix of two (2) out of three (3) organisms (Norovirus, Rotavirus) for Master Mix D6 or a mix of one (1) out of two (2) organisms (Sapovirus, human Astrovirus) for Master Mix D5 were prepared at the 95th percentile observed in the clinical trial to simulate a high clinical load to serve as high targets in the BD MAX™ Enteric Viral Panel Sample Buffer Tube. The BD MAX™ Enteric Viral Panel analyte absent from the high targets mix was spiked into the Sample Buffer Tube at a concentration 2x their respective LoD representing a low load target along with 5 µL of unpreserved stool and tested to simulate mixed infections. In the presence of high loads, all organisms corresponding to their respective simulated mixed infection preparations were successfully detected by the BD MAX Enteric Viral Panel.

Freeze/Thaw Study

This study was designed to evaluate multiple freeze/thaw cycles at varied LoD levels (1.99x, 4x and 10x). Based on the study results, three (3) freeze/thaw cycles do not affect the performance of BD MAX Enteric Viral Panel. The BD MAX Enteric Viral Panel was able to detect 100% proportion positive for all enteric viral targets spiked in preserved and unpreserved, negative, clinical stool specimens before and after undergoing multiple freeze/thaw cycles.

Condition		Target Positive Matrix Proportion Positive (%) and total number ofsamples tested (across all LoD levels)
Matrix	Freeze/ThawCycles	NorovirusGII	RotavirusVa70	AdenovirusF41	AstrovirusType 4	SapovirusGI
Unpreserved	0(fresh/baseline)	100	100	100	100	100
		60/60a	60/60a	60/60a	60/60	60/60
	1	100	100	100	100	100
		60/60	60/60	60/60	60/60	60/60
Unpreserved	2	100	100	100	100	100
		60/60	60/60	60/60	60/60	60/60
	3	100	100	100	100	100
		60/60	60/60	60/60	60/60	60/60
Preserved	0(fresh/baseline)	100	100	100	100	100
		60/60	60/60	60/60	60/60a	60/60a
	1	100	100	100	100	100
		60/60a	60/60a	60/60a	60/60a	60/60a
Preserved	2	100	100	100	100	100		60/60a	60/60a	60/60a	60/60a	60/60a	3	100	100	100	100	100	60/60a	60/60a	60/60a	60/60a	60/60a
	Preserved	2	100	100	100	100	100
			60/60a	60/60a	60/60a	60/60a	60/60a
		3	100	100	100	100	100
		60/60a	60/60a	60/60a	60/60a	60/60a

Proportion positive rates were calculated based on total sample number after removal of IND/UNR results, which were excluded from the analysis.

Clinical Performance Studies

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Clinical Performance characteristics of the BD MAX Enteric Viral Panel were determined in a multi-site investigational study. The study involved a total of six (6) geographically diverse clinical centers where stool specimens were collected as part of routine patient care, enrolled into the trial, and tested with the BD MAX Enteric Viral Panel. Specimens were obtained from pediatric or adult patients suspected of acute gastroenteritis or colitis. for whom diagnostic procedures were indicated and/or ordered by a healthcare provider. The reference method for the prospective specimens was a combination of two (2) sets of alternate PCRs and bi-directional sequencing for one (1) PCR. All prospective specimens were tested fresh (stored 2-8°C and within 5 days of collection) with the BD MAX Enteric Viral Panel Assay, but frozen prior to testing with the reference method. For retrospective specimens, the historical results were recorded at the collection site. All retrospective specimens were frozen prior to testing on the BD MAX Enteric Viral Panel Assay and the reference method. The historical results were confirmed using an alternate PCR assay and bi-directional sequencing in order to confirm the presence of the target DNA.

A total of 1873 prospective specimens (1055 Cary-Blair preserved and 818 unpreserved) and 366 retrospective specimens (136 Cary-Blair preserved and 230 unpreserved) were enrolled in the clinical evaluation for a total of 2239 specimens enrolled. Table 13 describes the number of compliant specimens enrolled by patient age and specimen type with a total of 2148 compliant specimens overall. Table 14 through Table 19 describe the performance characteristics of the BD MAX Enteric Viral Panel that were observed during the clinical trial.

Age Group	Cary-BlairPreserved	Unpreserved	Combined
0-1 month	4	0	4
1 month to 2 years	188	112	300
2-12	228	153	381
13-18	117	66	183
19-21	20	21	41
Over 21	568	640	1208
Unknown	21	10	31
Total	1146	1002	2148

Table 13: Compliant Clinical Trial Enrollment Summary by Age Group and Specimen Type

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Norovirus Performance Results

For the Cary-Blair preserved specimen type, the BD MAX Enteric Viral Panel identified 92.5% and 99.2% of the Norovirus prospective positive and negative specimens, respectively, and 100% and 99.1% of the retrospective positive and negative specimens, respectively. For the unpreserved specimen type, the BD MAX Enteric Viral Panel identified 90.7% and 99.6% of the Norovirus prospective positive and negative specimens, respectively and 94.6% and 100% of the Norovirus retrospective and negative specimens, respectively. Refer to Table 14.

Specimen Type	Specimen Origin	BD MAX	RM		Total
			P	N
Cary-Blair Preserved	Prospective (Fresh)	P	74	7a	81
		N	6b	835	841
		Total	80	842	922
			PPA (95% CI): 92.5% (84.6%, 96.5%)NPA (95% CI): 99.2% (98.3%, 99.6%)
Cary-Blair Preserved	Retrospective (Frozen)	P	6	1	7
		N	0	105	105
		Total	6	106	112
			PPA (95% CI): 100% (61%, 100%)NPA (95% CI): 99.1% (94.8%, 99.8%)
Unpreserved	Prospective (Fresh)	P	39	3	42
		N	4	694	698
		Total	43	697	740
			PPA (95% CI): 90.7% (78.4%, 96.3%)NPA (95% CI): 99.6% (98.7%, 99.9%)
Unpreserved	Retrospective (Frozen)	P	35	0	35
		N	2	58	60
		Total	37	58	95
			PPA (95% CI): 94.6% (82.3%, 98.5%)NPA (95% CI): 100% (93.8%, 100%)

Table 14: Norovirus- Performance Results per Specimen Type and Origin
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a 7/7 Specimens were available to be tested in discrepant analysis and 4/7 tested positive for Norovirus with the FilmArrayTM Gastrointestinal Panel.

b 6/6 Specimens tested negative for Norovirus during discrepant analysis with the FilmArray™ Gastrointestinal Panel.

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Rotavirus Performance Results

For the Cary-Blair preserved specimen type, the BD MAX Enteric Viral Panel identified 100% and 99.2% of the Rotavirus prospective positive and negative specimens, respectively, and 100% and 98.7% of the Rotavirus retrospective positive and negative spectively. For the unpreserved specimen type, the BD MAX Enteric Viral Panel identified 100% and 99.9% of the Rotavirus prospective positive and negative specimens, respectively and 100% and 97.9% of the Rotavirus retrospective positive and negative specimens, respectively. Refer to Table 15.

Specimen Type	Specimen Origin	BDMAX	RM		Total
			P	N
Cary-Blair Preserved	Prospective(Fresh)	P	31	7a	38
		N	0	888	888
		Total	31	895	926
PPA (95% CI): 100% (89%, 100%)NPA (95% CI): 99.2% (98.4%, 99.6%)
Cary-Blair Preserved	Retrospective(Frozen)	P	38	1	39
		N	0	76	76
		Total	38	77	115
PPA (95% CI): 100% (90.8%, 100%)NPA (95% CI): 98.7% (93%, 99.8%)
Unpreserved	Prospective(Fresh)	P	11	1	12
		N	0	735	735
		Total	11	736	747
PPA (95% CI): 100% (74.1%, 100%)NPA (95% CI): 99.9% (99.2%, 100%)
Unpreserved	Retrospective(Frozen)	P	56	1	57
		N	0	47	47
		Total	56	48	104
PPA (95% CI): 100% (93.6%, 100%)NPA (95% CI): 97.9% (89.1%, 99.6%)

a 7/7 Specimens were available to be tested in discrepant analysis and 4/7 tested positive for Rotavirus with the FilmArray™ Gastrointestinal Panel.

Adenovirus Performance Results

For the Cary-Blair preserved specimen type, the BD MAX Enteric Viral Panel identified 93.8% and 100% of the Adenovirus prospective positive and negative specimens, respectively, and 100% and 100% of the Adenovirus retrospective positive and negative spectively. For the unpreserved specimen type, the BD MAX Enteric Viral Panel identified 80.0% and 99.9% of the Adenovirus prospective positive and negative specimens, respectively, and 100% of the Adenovirus retrospective positive and negative specimens, respectively. Refer to Table 16.

As Adenovirus prevalence is low, an evaluation of contrived specimens for the unpreserved specimen type was performed to supplement data collected in the study. These were prepared by spiking two (2) different strains for each species of Adenovirus detected by the BD MAX Enteric Viral Panel in negative stool matrix. Strains were spiked at various clinically relevant loads and randomly distributed

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among two (2) clinical sites for BD MAX Enteric Viral Panel testing. A positive agreement of 100% was obtained across the tested loads. Results are shown in Table 17.

Specimen Type	Specimen Origin	BD MAX	RM		Total
			P	N
Cary-Blair Preserved	Prospective(Fresh)	P	15	0	15
		N	1	914	915
		Total	16	914	930
	PPA (95% CI): 93.8% (71.7%, 98.9%)NPA (95% CI): 100% (99.6%, 100%)
Cary-Blair Preserved	Retrospective(Frozen)	P	18	0	18
		N	0	84	84
		Total	18	84	102
	PPA (95% CI): 100% (82.4%, 100%)NPA (95% CI): 100% (95.6%, 100%)
Unpreserved	Prospective(Fresh)	P	4	1	5
		N	1	747	748
		Total	5	748	753
	PPA (95% CI): 80.0% (37.6%, 96.4%)NPA (95% CI): 99.9% (99.2%, 100%)
Unpreserved	Retrospective(Frozen)	P	6	0	6
		N	0	68	68
		Total	6	68	74
	PPA (95% CI): 100% (61%, 100%)NPA (95% CI): 100% (94.7%, 100%)

Table 16: Adenovirus- Performance Results per Specimen Type and Origin

Table 17: Adenovirus- Contrived Specimens Results

	Expected Result
BD MAX	P	N	Total
P	48	0	48
N	0	48	48
Total	48	48	96
PPA (95% CI): 100% (92.6%, 100%)
NPA (95% CI): 100% (92.6%, 100%)

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Sapovirus Performance Results

For the Cary-Blair preserved specimen type. the BD MAX Enteric Viral Panel identified 87.8% and 99.0% of the Sapovirus prospective positive and negative specimens, respectively, and 66.7% and 100% of the Sapovirus retrospective positive and negative spectively. For the unpreserved specimen type, the BD MAX Enteric Viral Panel identified 80.0% and 99.9% of the Sapovirus prospective positive and negative specimens, respectively, and 100% and 97.5% of the Sapovirus retrospective positive and negative specimens, respectively. Refer to Table 18.

		BD	RM
Specimen Type	Specimen Origin	MAX	P	N	Total
		P	43e	9a	52
Cary-Blair Preserved	Prospective(Fresh)	N	6b	863	869
		Total	49	872	921
	PPA (95% CI): 87.8% (75.8%, 94.3%)NPA (95% CI): 99.0% (98.1%, 99.5%)
		P	2e	0	2
Cary-Blair Preserved	Retrospective(Frozen)	N	1	98	99
		Total	3	98	101
	PPA (95% CI): 66.7% (20.8%, 93.9%)NPA (95% CI): 100% (96.2%, 100%)
	Prospective(Fresh)	P	24f	1c	25
Unpreserved		N	6d	720	726
		Total	30	721	751
	PPA (95% CI): 80.0% (62.7%, 90.5%)NPA (95% CI): 99.9% (99.2%, 100%)
		P	4f	1	5
Unpreserved	Retrospective(Frozen)	N	0	39	39

Table 18: Sapovirus- Performance Results per Specimen Type and Origin

9/9 Preserved Specimens were available to be tested in discrepant analysis and 4/9 tested positive for Sapovirus with the FilmArray™ Gastrointestinal Panel.

b 6/6 Preserved Specimens were available to be tested in discrepant analysis and 4/6 tested negative for Sapovirus with the FilmArrayTM Gastrointestinal Panel.

6 1/1 Unpreserved Specimens were available to be tested in discrepant analysis and 0/1 tested positive for Sapovirus with the FilmArrayTM Gastrointestinal Panel.

d 6/6 Unpreserved Specimens were available to be tested in discrepant analysis and 5/6 tested negative for Sapovirus with the FilmArrayTM Gastrointestinal Panel.

8 45/45 Preserved Specimens were available to be tested in concordant analysis and 43/45 tested positive for Sapovirus with the FilmArrayTM Gastrointestinal Panel.

f 24/28 Unpreserved Specimens were available to be tested in concordant analysis and 24/24 tested positive for Sapovirus with the FilmArray™ Gastrointestinal Panel.

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Human Astrovirus Performance Results

For the Cary-Blair preserved specimen type. the BD MAX Enteric Viral Panel identified 93.5% and 99.9% of the Human Astrovirus prospective positive and negative specimens, respectively, and 90.9% and 98.8% of the Human Astrovirus retrospective positive and negative specimens, respectively. For the unpreserved specimen type, the BD MAX Enteric Viral Panel identified 93.3% and 99.7% of the Human Astrovirus prospective positive and negative specimens, respectively, and 100% and 97.8% of the Human Astrovirus retrospective positive and negative specimens, respectively. Refer to Table 19.

Specimen Type	Specimen Origin	BDMAX	RM		Total
			P	N
Cary-Blair Preserved	Prospective(Fresh)	P	29	1a	30
Cary-Blair Preserved	Prospective(Fresh)	N	2b	899	901
Cary-Blair Preserved	Prospective(Fresh)	Total	31	900	931
		PPA (95% CI): 93.5% (79.3%, 98.2%)NPA (95% CI): 99.9% (99.4%, 100%)
Cary-Blair Preserved	Retrospective(Frozen)	P	20	1	21
Cary-Blair Preserved	Retrospective(Frozen)	N	2	80	82
Cary-Blair Preserved	Retrospective(Frozen)	Total	22	81	103
		PPA (95% CI): 90.9% (72.2%, 97.5%)NPA (95% CI): 98.8% (93.3%, 99.8%)
Unpreserved	Prospective(Fresh)	P	28	2	30
Unpreserved	Prospective(Fresh)	N	2	722	724
Unpreserved	Prospective(Fresh)	Total	30	724	754
		PPA (95% CI): 93.3% (78.7%, 98.2%)NPA (95% CI): 99.7% (99%, 99.9%)
Unpreserved	Retrospective(Frozen)	P	3	1	4
Unpreserved	Retrospective(Frozen)	N	0	45	45
Unpreserved	Retrospective(Frozen)	Total	3	46	49
		PPA (95% CI): 100% (43.9%, 100%)NPA (95% CI): 97.8% (88.7%, 99.6%)

	Table 19: Human Astrovirus- Performance Results per Specimen Type and Origin

ª 1/1 Specimen was available to be tested in discrepant analysis and 1 tested negative for
Human Astrovirus with the FilmArray™ Gastrointestinal Panel.

b 2/2 Specimens were available to be tested in discrepant analysis and 2/2 tested negative for Human Astrovirus with the FilmArray™ Gastrointestinal Panel.

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Non-Reportable Rate

The initial unresolved rate of the 1,873 prospective specimens evaluated in this study was 0.8% of the Cary-Blair preserved and 1.8% of the unpreserved specimens. The unresolved rate following a valid repeat test was only 0.1% of the Cary-Blair preserved specimens and 1.0% of the unpreserved specimens (refer to Table 20).

Of the 1,873 prospective specimens evaluated in this study, 0.5% of the Cary-Blair preserved and 2.2% of the unpreserved specimens initially reported as Indeterminate. Following a valid repeat test, 0.1% of the Cary-Blair preserved and none of the unpreserved specimens remained Indeterminate (refer to Table 20).

Of the 1.873 prospective specimens evaluated in this study, 0.1% of the Cary-Blair preserved and 0.3% of the unpreserved specimens initially reported as Incomplete. Following a valid repeat test, 0.1% of the Cary-Blair preserved and none of the unpreserved specimens remained Incomplete (refer to Table 20).

CombinedTarget	Unresolved Rate		Indeterminate Rate		Incomplete Rate		Total Rate
Specimen Type	Initial EVP(95% CI)	Final EVP(95% CI)	Initial EVP(95% CI)	Final EVP(95% CI)	Initial EVP(95% CI)	Final EVP(95% CI)	Initial EVP(95% CI)	Final EVP(95% CI)
Cary-BlairPreserved	0.8%9/1085(0.4%, 1.6%)	0.1%1/1076(0.0%, 0.5%)	0.5%5/1085(0.2%, 1.1%)	0.1%1/1076(0.0%, 0.5%)	0.1%1/1085(0.0%, 0.5%)	0.1%1/1076(0.0%, 0.5%)	1.4%15/1085(0.8%, 2.3%)	0.3%3/1076(0.1%, 0.8%)
Unpreserved	1.8%18/997(1.1%, 2.8%)	1.0%10/982(0.6%, 1.9%)	2.2%22/997(1.5%, 3.3%)	0.0%0/982(0.0%, 0.4%)	0.3%3/997(0.1%, 0.9%)	0.0%0/982(0.0%, 0.4%)	4.3%43/997(3.2%, 5.8%)	1.0%10/982(0.6%, 1.9%)
Combined	1.3%27/2082(0.9%, 1.9%)	0.5%11/2058(0.3%, 1.0%)	1.3%27/2082(0.9%, 1.9%)	0.0%1/2058(0.0%, 0.3%)	0.2%4/2082(0.1%, 0.5%)	0.0%1/2058(0.0%, 0.3%)	2.8%58/2082(2.2%, 3.6%)	0.6%13/2058(0.4%, 1.1%)

Table 20: Non-reportable Rates for Combined Target by Specimen Type and Overall

Regulation Number and Section

§ 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).