Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description and performance studies focus on real-time PCR technology and automated interpretation based on predefined amplification status, with no mention of AI or ML algorithms.

Therapeutic

No
The device is an in vitro diagnostic test intended to aid in the prevention and control of MRSA and SA infections by detecting their DNA. It is explicitly stated that it is "not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections," which indicates it is not a therapeutic device.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the BD MAX™ StaphSR assay is an "in vitro diagnostic test."

SaMD (Software as a Medical Device)

No

The device description explicitly states that the BD MAX™ System and the BD MAX™ StaphSR assay are 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.

IVD (In Vitro Diagnostic)

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

The "Intended Use / Indications for Use" section explicitly states: "The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization."

This statement directly identifies the device as an in vitro diagnostic test.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymerase chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic target-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

Product codes

NQX, OOI

Device Description

The BD MAX™ System and the BD MAX™ StaphSR assay 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 results. A test result may be called as [SA NEG MRSA NEG (negative)], [SA POS, MRSA POS (MRSA positive)], [SA POS, MRSA NEG (SA positive)] or [SA UNR, MRSA UNR (Unresolved)] 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.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Nasal swabs

Indicated Patient Age Range

Not Found

Intended User / Care Setting

healthcare settings

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

A total of 2451 specimens were enrolled in the study. Of those, 94 specimens were regarded as noncompliant per protocol criteria and three (3) fully compliant specimens gave final non-reportable PCR results. A total of 2354 specimen results were used to determine the clinical performance of the BD MAX™ StaphSR assay in comparison to the Reference Method. The Comparative Reference Method consisted of direct culture complemented by enriched culture. Enriched culture analysis was completed for all specimens that were negative for MRSA or SA by direct culture. Presumptive S. aureus colonies observed on selective (S. aureus) chromogenic medium were subcultured onto Blood Agar (BA). Identification was confirmed with an agglutination test, while methicillin resistance was confirmed by Cefoxitin disk (30 µg) diffusion susceptibility testing. Enrichment in Trypticase Soy Broth with 6.5% NaCI (TSB 6.5% NaCI) was completed in the event that MRSA or SA was not confirmed by the initial direct culture method. Turbid TSB 6.5% NaCl broth was used to inoculate additional chromogenic medium and BA plates; MRSA confirmation was performed as described above.

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

Precision:
Within-laboratory precision was evaluated for the BD MAX™ StaphSR assay at one (1) site. The Precision panel consisted of 4 sample categories near the LoD.
Sample Categories: Moderate Positive (MP) MRSA, Low Positive (LP) MRSA (MREJ Type ii), Low Positive (LP) MRSA (MREJ Type vii), Low Positive (LP) MSSA, High Negative (HN) MRSA (MREJ Type ii), High Negative (HN) MSSA, True negative (TN).
Testing was performed in duplicate, over 12 days, with 2 runs per day, by 2 different technologists.
Results demonstrate 100%, 100%, 97.9%, and 27.1% agreement for TN, MP, LP, and HN MRSA samples respectively. For LP and HN MSSA samples, agreement was 100% and 56.2% respectively.

Reproducibility:
The reproducibility study was performed using the same sample categories as defined for the Precision Study.
Samples in each category were tested in triplicate, on 5 distinct days, with 2 panels tested by 2 different technologists at 3 clinical sites using 1 lot of reagents (Site-to-Site). One site extended the study to test 2 additional lots of reagents (Lot-to-Lot).
Site-to-Site Reproducibility: Overall percent agreement was 100% for MRSA MP and TN categories; 96.7% and 97.8% for MRSA LP and MSSA LP, respectively; and 36.7% and 30.0% for MRSA HN and MSSA HN, respectively.
Lot-to-Lot Reproducibility: Overall percent agreement was 100% for MRSA MP and TN; 96.7% for MRSA LP and MSSA LP; 40.0% and 44.4% for MRSA HN and MSSA HN, respectively.
Second Derivative Peak Abscissa (SDPA) reproducibility was also assessed, showing low %CVs across various target channels, indicating good reproducibility.

Analytical Sensitivity (Limit of Detection or LoD):
Positive specimens were prepared by soaking swabs in MRSA or MSSA bacterial suspensions. The tested strains included 11 MRSA strains (11 MREJ genotypes, 5 SCCmec types) and 2 MSSA strains. Swabs were eluted in simulated nasal matrix. Each strain was tested in replicates of 24 by 2 operators using 3 production lots.
LoD for MRSA strains ranged from 64 to 343 CFU/swab.
LoD for MSSA strains ranged from 174 to 211 CFU/swab.

Analytical Inclusivity:
Evaluated 77 MRSA strains from 27 countries and 51 MSSA strains from 16 countries, including VRSA and VISA.
The assay detected all tested MREJ types (i, ii, iii, iv, v, vi, vii, ix, xiii, xiv and xxi) and SCCmec types (I, II, III, IV, V, VI, VII, VIII, VIII and XI) at 2-3 x LoD. All MRSA displaying vancomycin resistance (VRSA and VISA) were detected, as were all 51 MSSA strains including mecA empty cassette variants.

Evaluation of a Well Characterized Challenge Strain Panel:
Tested 17 MRSA strains (high/low oxacillin MICs, various PFGE types, mecC variant) which showed SA POS, MRSA POS results at 2-3 x LoD.
4 BORSA strains exhibited SA POS, MRSA NEG results at ≥10^6 CFU/swab.
5 MSSA strains exhibited SA POS, MRSA NEG results at ≥10^6 CFU/swab.
1 MRSE strain exhibited SA NEG, MRSA NEG results at ≥10^6 CFU/swab.

Analytical Specificity:
Samples with high levels of non-target organisms and MSSA strains were used.
15 empty cassette variant MSSA strains (≥10^6 CFU/swab) produced SA POS, MRSA NEG results.
57 non-staphylococcal species strains (≥10^6 CFU/mL, except C. neoformans) produced negative results.
45 CoNS and CoPS strains (0.5 McFarland) exhibited negative results.
50 MSSA strains (≥10^6 CFU/swab) produced SA POS, MRSA NEG results.
17 viruses (≥10^5 PFU/mL) produced negative results.

Interfering Substances:
29 microorganisms and chemical substances were evaluated.
Results demonstrated no reportable interference for most substances, except Tobramycin at 4.5 x 10^-3 g/swab.

Microbial Competitive Inhibitory Effect:
MRSE at an MRSA:MRSE ratio of 1: ≥ 1x10^3 showed competition.
MRSE at an MSSA:MRSE ratio of 1: ≥ 1x10^5 showed competition.
MSSA at an MRSA:MSSA ratio of 1: ≥ 1x10^4 showed competition.

Carryover / Cross-Contamination:
A study investigated potential carry-over/cross-contamination between high MRSA (≥10^6 CFU/swab) and negative specimens.
3 false positive results were obtained out of 203 reportable expected negative samples (1.5%) due to carry-over contamination.

Clinical Performance Studies:
Multi-site prospective investigational study with 3 centers.
Total of 2354 specimen results compared to Reference Method (Direct/Enriched Culture).
MRSA performance: Sensitivity 93.1%, Specificity 97.5%.
SA performance: Sensitivity 92.0%, Specificity 93.1%.
Compared to Direct Culture (2393 specimens):
MRSA performance: Positive Percent Agreement 96.5%, Negative Percent Agreement 96.9%.
SA performance: Positive Percent Agreement 95.1%, Negative Percent Agreement 90.9%.
Initial Unresolved Rate: 0.6% (15/2399). After repeat testing: 0.04% (1/2399).
Empty Cassette Variants: 10 specimens out of 2354 fit the empty cassette profile, all verified true negative MRSA and true positive SA.

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

MRSA (compared to Reference Method - Direct/Enriched Culture):
Sensitivity: 93.1% (149/160) (95% CI: 88.1%, 96.1%)
Specificity: 97.5% (2140/2194) (95% CI:96.8%, 98.1%)
PPV: 73.2% (95% CI: 67.8%, 78.3%)
NPV: 99.5% (95% CI: 99.1%, 99.7%)

SA (compared to Reference Method - Direct/Enriched Culture):
Sensitivity: 92.0% (599/651) (95% CI: 89.7%, 93.9%)
Specificity: 93.1% (1585/1703) (95% CI: 91.8%, 94.2%)
PPV: 83.4% (95% CI: 81.9%, 85.8%)
NPV: 96.8% (95% CI: 96.0%, 97.6%)

MRSA (compared to Direct Culture):
Positive Percent Agreement: 96.5% (137/142) (95% CI: 92.0%, 98.5%)
Negative Percent Agreement: 96.9% (2182/2251) (95% CI: 96.1%, 97.6%)

SA (compared to Direct Culture):
Positive Percent Agreement: 95.1% (564/593) (95% CI: 93.1%, 96.6%)
Negative Percent Agreement: 90.9% (1636/1800) (95% CI: 89.5%, 92.1%)

Unresolved Rates:
Initial Unresolved Rates: 0.6% (15/2399) (95% CI: 0.4%, 1.0%)
Unresolved Rates After Repeat: 0.04% (1/2399) (95% CI: 0%, 0.2%)

Predicate Device(s)

K120138, K071026

Reference Device(s)

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information

Not Found

Regulation Number and Section

§ 866.1640 Antimicrobial susceptibility test powder.

(a)
Identification. An antimicrobial susceptibility test powder is a device that consists of an antimicrobial drug powder packaged in vials in specified amounts and intended for use in clinical laboratories for determining in vitro susceptibility of bacterial pathogens to these therapeutic agents. Test results are used to determine the antimicrobial agent of choice in the treatment of bacterial diseases.(b)
Classification. Class II (performance standards).

Summary

0

K132822.

510(k) Summary

November 19, 2013

BD Diagnostics BD MAX™ StaphSR

Submitted by:

GeneOhm Sciences Canada Inc. (BD Diagnostics) 2555 Boul. Parc-Technologique Quebec (Quebec), Canada G1P 4S5

Contact:

Device:

NOV 2 6 2013

510(k) Number:

Trade Name:

BD MAX™ StaphSR

K132822

Patricia Dionne, Ph.D.

Common Name:

Type of Test:

Staphylococcus aureus and Methicillin-resistant Staphylococcus aureus Qualitative Nucleic Acid Amplification Test from nasal swab specimens

Staphylococcus aureus and Methicillin-resistant

Staphylococcus aureus detection assay

Classification:

Antimicrobial susceptibility test powder Requlation Name:

ll

866.1640 Requiation Number:

Product Code: NQX: OOI

Microbiology (83) Panel:

Predicate Devices: BD MAX™ MRSA and BD GeneOhm™ StaphSR Assay

Predicate 510(k) Numbers: K120138 and K071026

Intended Use:

The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes realtime polymerase chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic tarqet-specific hybridization probes for the detection of the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negative result does

1

not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

Indication for Use:

The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes realtime polymerase chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic target-specific hybridization probes for the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negative result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

Special Conditions for Use Statement:

For prescription use

Special Instrument Requirements:

The BD MAX™ System

Device Description:

The BD MAX™ System and the BD MAX™ StaphSR assay 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 results. A test result may be called as [SA NEG MRSA NEG (negative)], [SA POS, MRSA POS (MRSA positive)], [SA POS, MRSA NEG (SA positive)] or [SA UNR, MRSA UNR (Unresolved)] 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™ StaphSR assay performed on the BD MAX™ System is an automated in vitro diagnostic test for the direct, qualitative detection and differentiation of the Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization.

A nasal specimen is collected and transported to the laboratory using the recommended swab. The swab is placed in a BD MAX™ StaphSR Sample Buffer Tube. The Sample

2

Buffer Tube is closed with a septum cap and vortexed. A worklist is created and the Sample Buffer Tube, the BD MAX™ StaphSR unitized reagent strip 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 i 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 a specific amplicon in the SCCmec right-extremity junction (MREJ), the genes for methicillin resistance mecA and mecC, the nuc gene encoding a thermostable nuclease of S. aureus and SPC amplicons in four different optical channels of the BD MAX™ System: MREJ amplicons are detected in the FAM channel, mecA and mecC amplicons are detected in the ROX channel, nuc amplicons are detected in the VIC channel and SPC amplicons are detected in the Cy5.5 channel. 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 four optical channels used for the BD MAX™ StaphSR assay 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.

Substantial Equivalence:

Table 1 shows the similarities and differences between the BD MAX™ StaphSR assay and the predicate devices.

3

	DEVICE	PREDICATE
ITEM	BD MAX™ StaphSR
(K132822)	BD GeneOhm StaphSR
Assay (K071026)	BD MAX MRSA Assay
(K120138)
Intended Use	The BD MAX™ StaphSR assay
performed on the BD MAX ™
System is an automated
qualitative in vitro diagnostic test
for the direct detection and
differentiation of Staphylococcus
aureus (SA) and methicillin-
resistant Staphylococcus aureus
(MRSA) DNA from nasal swabs
in patients at risk for nasal
colonization. The test utilizes
real-time polymerase chain
reaction (PCR) for the
amplification of MRSA/SA DNA
and fluorogenic target-specific
hybridization probes for the
detection of the amplified DNA.
The BD MAX™ StaphSR assay
is intended to aid in the
prevention and control of MRSA
and SA infections in healthcare
settings. It is not intended to
diagnose MRSA or SA infections
nor guide or monitor treatment
for MRSA/SA infections. A
negative result does not
preclude nasal colonization.
Concomitant cultures are
necessary to recover organisms
for epidemiological typing or for
further susceptibility testing.	The BD GeneOhm™ StaphSR
Assay is a qualitative in vitro
diagnostic test for the rapid
detection of Staphylococcus
aureus (SA) and methicillin-
resistant Staphylococcus
aureus (MRSA) directly from
positive blood culture. The
assay utilizes polymerase
chain reaction (PCR) for the
amplification of specific targets
and fluorogenic target-specific
hybridization probes for the
real-time detection of the
amplified DNA. The assay is
performed on Gram positive
cocci, identified by Gram stain,
from positive blood cultures.
The BD GeneOhm™ StaphSR
Assay is not intended to
monitor treatment for
MRSA/SA infections.
Subculturing of positive blood
cultures is necessary for
further susceptibility testing.	The BD MAX™ MRSA Assay
performed on the BD MAX ™
System is an automated
qualitative in vitro diagnostic
test for the direct detection of
Methicillin-resistant
Staphylococcus aureus (MRSA)
DNA from nasal swabs in
patients at risk for nasal
colonization. The test utilizes
real-time polymerase chain
reaction (PCR) for the
amplification of MRSA DNA and
fluorogenic target-specific
hybridization probes for the
detection of the amplified DNA.
The BD MAX™ MRSA Assay is
intended to aid in the prevention
and control of MRSA infections
in healthcare settings. It is not
intended to diagnose, guide or
monitor MRSA infections. A
negative result does not
preclude nasal colonization.
Concomitant cultures are
necessary to recover organisms
for epidemiological typing or for
further susceptibility testing.
Specimen type	Nasal swabs	Positive blood culture	Nasal swabs
Assay Format	Amplification: PCR
Detection: Fluorogenic target-
specific hybridization	Same	Same
Mode of Detection
for Methicillin
Resistance in
S.aureus	Presence of SCCmec cassette
at orfX junction and mecA or
mecC genes	Presence of SCCmec cassette
at orfX junction (specific to S.
aureus)	Presence of SCCmec cassette
at orfX junction (specific to S.
aureus)
Mode of Detection
for SA	Presence of nuc gene specific
for SA	Same	Not detected
Interpretation of
Test Results	Automated (Diagnostic software
of BD MAX™ System)	Automated (Diagnostic
software of SmartCycler®
System)	Automated (Diagnostic software
of BD MAX™ System)
Analysis Platform	BD MAX™ System	SmartCycler® System	BD MAX™ System
PCR Sample
Preparation	Automated by the BD MAX TM
System	Manual	Automated by the BD MAX TM
System
Detection Probes	TaqMan® Probe	Molecular Beacon Probe	TaqMan® Probe
ITEM	DEVICE	PREDICATE
	BD MAX™ StaphSR
(K132822)	BD GeneOhm StaphSR
Assay (K071026)	BD MAX MRSA Assay
(K120138)
Assay Controls	Specimen Processing Control
(SPC)	Positive PCR control (DNA
from S.aureus ATCC 43300).
Negative control (DNA from
S.epidermidis ATCC 14990).
Internal Control	Specimen Processing Control
(SPC)

Table 1: Substantial Equivalence Information

4

Analytical Performance:

Precision

Within-laboratory precision was evaluated for the BD MAX™ StaphSR assay at one (1) site. The Precision panel consisted of 4 sample categories near the LoD. Each specimen contained simulated nasal matrix. MRSA and MSSA strains were tested as follows:

Moderate Positive (MP) MRSA (MREJ Type ii): ≥ 2 and ≤ 5 x LoD .
Low Positive (LP) MRSA (MREJ Type ii): ≥ 1 and mecA or mecC 2
(MREJ types
pooled, ROX
Channel) | N | 33 | 174 | 90 | 35 | 174 | 90 |
| | Mean | 35.1 | 31.8 | 31.1 | 35.0 | 31.7 | 31.1 |
| | SD | 1.16 | 1.42 | 0.78 | 1.15 | 1.36 | 0.54 |
| | %CV | 3.3% | 4.5% | 2.5% | 3.3% | 4.3% | 1.7% |
| | | HN MREJ
Type ii | HN MSSA | LP MSSA | HN MREJ
Type ii | HN MSSA | LP MSSA |
| nuc 3
(VIC Channel) | N | 24 | 63 | 88 | 19 | 50 | 87 |
| | Mean | 34.9 | 34.8 | 32.0 | 35.2 | 34.8 | 32.0 |
| | SD | 1.78 | 1.69 | 1.12 | 1.85 | 1.57 | 0.78 |
| | %CV | 5.1% | 4.9% | 3.5% | 5.2% | 4.5% | 2.4% |
| | | HN MREJ
Type ii | HN MSSA | TN | HN MREJ
Type ii | HN MSSA | TN |
| SPC4
(Cy5.5 Channel) | N | 33 | 27 | 90 | 36 | 40 | 90 |
| | Mean | 30.0 | 30.3 | 30.2 | 29.9 | 30.0 | 30.0 |
| | SD | 0.79 | 0.68 | 0.63 | 0.49 | 0.43 | 0.45 |
| | %CV | 2.6% | 2.2% | 2.1% | 1.7% | 1.4% | 1.5% |

Table 4. Site-to-Site and Lot-to-Lot Reproducibility Study Underlying Numerical SDPA
Overall Results

'Values shown are those obtained for the MREJ target in the samples that gave a SA POS, MRSA POS result

2Values shown are those obtained for the mech or mec target in the samples that gave a SA POS, MRSA POS result

3Values shown are those obtained for the nuc target in the samples that gave a SA POS, MRSA NEG result 4 Calculated for the Specimen Processing Control of the samples that gave a SA NEG, MRSA NEG result

Sample Storage

Specimens can be stored at25 ±2°C for a maximum of 48 hours or at 2-8 °C for a maximum of 120 hours (5 days) before testing. In case of repeat testing from the Sample Buffer Tube, the following storage conditions apply:

within 36 hours of the steps covered in the Specimen Preparation section of the . package insert, when stored at 25 ±2℃ or
up to 120h (5 days) after the end of the initial run when stored at 2-8°C. .

Controls

External Control materials are not provided by BD. Various types of External Controls are recommended to allow the user to select the most appropriate for their laboratory quality control program:

Commercially available control materials [e.g. a reference MRSA strain (ATCC -43300), and Methicillin-susceptible Staphylococcus aureus strain (e.g. ATCC 29213) can be used as positive controls. Staphylococcus epidermidis strain (e.g. ATCC 12228) can be used as negative control.].

7

Previously characterized specimens known to be positive or negative for S. aureus or MRSA.
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.

Analytical Sensitivity

The analytical sensitivity (Limit of Detection or LoD) for the BD MAX™ StaphSR assay was determined as follows: positive specimens were prepared by soaking swabs in a wide range of MRSA or MSSA bacterial suspensions prepared and quantified from cultures. The tested strains included 11 MRSA strains representing 11 MREJ genotypes (i, ii, iii, iv, v, vi, vii, ix, xiii, xiv and xxi) corresponding to 5 SCCmec types (1, II, III, IV and XI) as well as 2 MSSA strains. The swabs were then eluted in simulated nasal matrix. Each MRSA and MSSA strain was tested in replicates of 24 per concentration by 2 different operators using 3 different production lots of the BD MAX™ StaphSR assay. Analytical sensitivity (LoD), defined as the lowest concentration at which at least 95% of all replicates tested positive, ranged from 64 to 343 CFU/swab (Table 5) for the detection of MRSA strains and from 174 to 211 CFU/swab (Table 6) for the detection of MSSA strains.

| MRSA Strain | MREJ Genotype | SCCmec type | LoD Concentration
[CFU/swab (95% CI²)] |
|-------------|---------------|-------------|-------------------------------------------|
| 1 | Type i | I | 84 (49, 142) |
| 2 | Type ii | II | 103 (64, 167) |
| 3 | Type iii | III | 160 (93, 278) |
| 4 | Type iv | III | 68 (42, 109) |
| 5 | Type v | IV | 128 (73, 225) |
| 6 | Type vi | ND³ | 343 (186, 632) |
| 7 | Type vii | II | 219 (110, 439) |
| 8 | Type ix | ND³ | 144 (82, 255) |
| 9 | Type xiii | ND³ | 64 (36, 114) |
| 10 | Type xiv | ND³ | 78 (48, 127) |
| 11 | Type xxi | XI | 112 (64, 197) |

Table 5: Limit of Detection of MRSA Genotypes by the BD MAX™ StaphSR Assay

SCCmec type does not correlate to the MREJ type as these are two different typing methods. CI: Confidence Intervals

ND = not determined

mecc-containing MRSA strains (Also known as mecAuga25; strain)

		Table 6: Limit of Detection of MSSA by the
		BD MAX™ StaphSR Assay

| MSSA Strain | LoD Concentration [CFU/swab
(95% CI)] |
|-------------|------------------------------------------|
| 1 | 174 (89, 341) |
| 2 | 211 (105, 428) |

1Cl: Confidence Intervals

Analytical Inclusivity

An analytical inclusivity study was performed using a variety of MRSA and MSSA strains, taking into account geographic origin, MREJ genotype (wild type and mutant), SCCmec type. Pulsed-Field Gel Electrophoresis (PFGE) type, temporal diversity and susceptibility pattern. Seventy-seven (77) MRSA strains from 27 countries (see Table 7) and 51 MSSA strains from 16 countries were tested in this study, including strains

8

from public collections and from well-characterized clinical isolates, including Vancomycin-Resistant Staphylococcus aureus (VRSA) and Vancomycin Intermediate Staphylococcus aureus (VISA) strains.

The BD MAX™ StaphSR assay detected MREJ types i, ii, iii, iv, v, vi, vii, ix, xiii, xiv and xxi when tested at low bacterial load (2-3 x LoD). The BD MAX™ StaphSR assay detected MRSA SCCmec types 1, II, III, IV, V, VI, VII, VIII, VIII and XI as well as MRSA PFGE types USA 100 to 800, 1000 and 1100 at 2-3 x LoD. All MRSA strains displaying additional resistance to vancomycin (VRSA and VISA) were also detected. The BD MAX™ StaphSR assay detected all 51 MSSA strains tested including mecA empty cassette variants.

| Collection Number | MREJ
Type | SCCmec
typing / PFGE
type |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------- | ATCC | ATCC BAA-1770 | | ATCC BAA-421 | | ATCC BAA-38 | | ATCC BAA-41 | | ATCC BAA-39 | | ATCC BAA-40 | | ATCC 43300 | | ATCC 33592 | Harmony
collection of
European
epidemic
MRSA | 62305 | ii mut36 | IV | | 97S99 | | 3717 | | 9805-01937 | LSPQ | ID-61882 | | ID-61880 | NARSA | NRS383 | | NRS385 | | NRS715 | | NRS386 | | NRS686 | | NRS234 | | VRS53 | | NRS14 | | NRS44 | | VRS23 | | VRS41,3 | | NRS382 | | NRS384 | | NRS387 | | NRS484 | | NRS645 | | NRS123 | NA | NA | | NA | | 5599 | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------
Collection | Reference | | SCCmed
voing / P
type |
| | 7909 | | 7916 | | 7917 | | 7921 | | 7922 | | 7913 | | NA | | 1555 | | MAH 305 | | CCRI-11840 | | JCSC6082 | | 92 | | 2100 | | CCRI-12480 | | CCRI-12496 | | CCRI-12640 ² | | CCRI-9866 2 | | 48 | | 347101 | | CCRI-12503 | | CCRI-12790 | | CCRI-12608 | | CCRI-8895 | (R523) | V | IV |
| | CCRI-12767 | | 571 | 47.3.270206 MJS | Vi | ND |
| | CCRI-12425 2 | | CCRI-12763 | | CCRI-9583 | | CCRI-9711 | | 521 | | CCRI-9681 | | 494 | | ST2011 11005 | | 126 | | CCRI-8894 | | MAH 20° | | MAH 15 | | CCRI-1262 | | CCRI-2025 | | CCRI-9773 | | CCRI-9624 | Reference,
-------------------------|--------------|---------------------------------|
| iii | USA1000 |
| ii | VI |
| i | I |
| ii | II |
| iii | III |
| iv | III |
| ii | II |
| iv | III |
|
| ii mut45 | IV |
| iii | III |
| iii mut45 | ND |
| iii | III / CMRSA-3 |
| vii | II / CMRSA-1 |
| ii | II / USA200 |
| ii | IV / USA500 |
| ii | II/USA600 |
| ii | IV / USA700 |
| i | IV/IBERIAN |
| ii | II |
| ii | ND |
| ii | II |
| ii | II |
| ii | ND |
| ii | ND |
| ii | II / USA100 |
| ii | IV / USA300 |
| ii | IV / USA800 |
| ii | IV / USA1100 |
| ii | IV/IBERIAN |
| ii mut36 | IV / USA400 |
| ii | II / USA 100 |
| iii | II / USA 100 |
| ii | II / USA100 |
| li | IV / USA300 |
| ii | IV / USA300 |
| ii | IV / USA300 |
| li | IV / USA300 |
| li | IV / USA300 |
| ii mut36 | IV / USA400 |
| ll | IV / USA 800 |
| XXI | ND |
| xxi | ND |
| i | VIII · |
| iii | VII |
| xili | ND |
| xiv | ND |
| li | ND |
| li | ND |
| li | ND |
| ii mut36 | ND |
| iiii | V |
| iii | V |
| lli | ND |
| lii | ND |
| iv | ND |
| IV | 111 |
| CCRI-1263
| V | ND |
| VI | ND |
| MLST 22 HOS
| Vii | ND |
| vii | ND |
| VII | ll |
| VII | ND |
| Vi | ND |
| ix | ND |
| xiiii | ND |
| xxi | ND |
| xiv | ND |
| İ | l |
| xxi | ND |
| xxi | ND |
| ili | III |
| V | IV |
| vii | == |
| ii mut36 | ND |

Table 7: MRSA Strains Tested in the Inclusivity Study of the BD MAX™ StaphSR Assay.

9

The initial result was negative for MRSA. Both samples (ATCC BAA42 and VRS4) were repeated from the SBT and assay results are
conforming (SA+, MRSA+).

10

2These are the results for the repeats as the initial run gave an IND result due to a PCR heater warning. 3VRSA strains (http://www.narsa.net/control/member/repositories) 4VISA strains (http://www.narsa.net/control/member/repositories) أmecC variant strains

Evaluation of a Well Characterized Challenge Strain Panel

An additional analytical study was carried out to evaluate the analytical performance of the BD MAX™ StaphSR assay using a well characterized challenge strain panel:

Seventeen (17) out of 17 MRSA strains with high and low oxacillin minimum . inhibitory concentrations (MICs), including PFGE types USA 100 to 800, 1000, PFGE type IV/IBERIAN and mecC variant (mecA-containing S. aureus strain LGA251) tested at a concentration of 2-3 x LoD, exhibited SA POS, MRSA POS results.
Four (4) out of 4 BORSA strains (Borderline Oxacillin-Resistant S. aureus) . tested at ≥10° CFU/swab, exhibited SA POS, MRSA NEG results.
Five (5) out of 5 MSSA strains tested at ≥10° CFU/swab, exhibited SA POS, . MRSA NEG results
. One (1) out of 1 Methicillin-Resistant Staphylococcus epidermidis (MRSE) strains tested at ≥10° CFU/swab, exhibited a negative result (SA NEG, MRSA NEG).

Analytical Specificity

The BD MAX™ StaphSR assay was performed on samples containing high levels of non-target organisms and MSSA strains (Table 8), using the BD MAX™ System, to demonstrate the specificity of the assay for detection of MRSA and SA.

Fifteen (15) out of 15 empty cassette variant MSSA strains tested at ≥10° . CFU/swab produced SA POS, MRSA NEG results.
Fifty-seven (57) out of 57 strains of various non-staphylococcal species tested . at a concentration of at least ≥10° CFU/mL (except for Cryptococcus neoformans which was tested at 3x10* CFU/swab) produced negative results (SA NEG, MRSA NEG).
Forty-five (45) Coagulase-Negative staphylococcal strains (CoNS) and � Coagulase-Positive staphylococcal strains (CoPS) representing 28 species were tested at a concentration of 0.5 McFarland with the BD MAX™ StaphSR assay. Forty-five (45) of the 45 strains tested exhibited negative results (SA NEG, MRSA NEG).
Fifty (50) out of 50 MSSA strains tested at high concentrations ≥10° . CFU/swab), produced SA POS, MRSA NEG results.
Seventeen (17) viruses representing 12 different viral species were tested at ≥ o 105 PFU/mL. All 17 viruses produced negative results (SA NEG, MRSA NEG).

11

Table 8: Microorganisms Tested for the Analytical Specificity Study
Non-Staphylococcal Species
Acinetobacter
baumannii	Corynebacterium
bovis	Escherichia coli
(3 strains)	Neisseria
meningitidis	Pasteurella
aerogenes
Acinetobacter
haemolyticus	Corynebacterium
flavescens	Haemophilus
influenzae	Streptococcus
anginosus	Proteus mirabilis
Bacillus cereus	Corynebacterium
genitalium	Klebsiella oxytoca	Streptococcus
agalactiae	Proteus vulgaris
Bordetella
pertussis	Cryptococcus
neoformans	Klebsiella
pneumoniae	Streptococcus
mitis	Providencia stuartii
Candida albicans
(2 strains)	Enterobacter
aerogenes	Lactobacillus
crispatus	Streptococcus
mutans	Pseudomonas
aeruginosa
Candida
guilliermondii	Enterobacter
cloacae	Lactobacillus
reuteri	Streptococcus
pneumoniae	Pseudomonas
fluorescens
Candida tropicalis	Enterococcus
faecalis	Lactobacillus
acidophilus	Streptococcus
pyogenes	Salmonella
enterica subsp.
Enterica
Candida glabrata	Enterococcus
faecium	Listeria
monocytogenes	Streptococcus
salivarius	Serratia
marcescens
Citrobacter freundii	Enterococcus
flavescens	Micrococcus luteus	Streptococcus
sanguinis	Shigella sonnei
Citrobacter koseri	Enterococcus hirae	Moraxella
catarrhalis	Streptococcus suis	Yersinia
enterocolitica
Corynebacterium
aquaticus	Enterococcus
gallinarum	Neisseria
gonorrhoeae	Streptococcus sp.
Various Coagulase Positive Staphylococcus Species
Staphylococcus
intermedius	Staphylococcus
lutrae (2 stains)	Staphylococcus
pseudointermedius	Staphylococcus
schleiferi	Staphylococcus
schleiferi subsp.
coagulans
Staphylococcus
delphini
Various Coagulase Negative Staphylococcus Species
Staphylococcus
arlettae	Staphylococcus
chromogenes	Staphylococcus
gallinarum	Staphylococcus
lentus	Staphylococcus
sciuri
Staphylococcus
auricularis	Staphylococcus
cohnii subsp.
urealyticum	Staphylococcus
haemolyticus
(3 strains)	Staphylococcus
lugdunensis	Staphylococcus
simulans
Staphylococcus
capitis	Staphylococcus
epidermidis
(9 strains)	Staphylococcus
hominis (3 strains)	Staphylococcus
pasteuri	Staphylococcus
warneri (2 strains)
Staphylococcus
caprae	Staphylococcus
equorum	Staphylococcus
hominis subsp.
hominis	Staphylococcus
pulvereri	Staphylococcus
xylosus (2 strains)
Staphylococcus
carnosus	Staphylococcus
felis	Staphylococcus
kloosii	Staphylococcus
saprophyticus	Staphylococcus
xylosus
Virus
Adenovirus
(type 1 and 7A)	Enterovirus	Human
parainfluenza (type
1, 2, 3)	Measles	Respiratory
syncytial virus
Human
coronavirus (2)	Epstein Barr Virus	Human
metapneumovirus	Mumps virus	Rhinovirus
Cytomegalovirus	Human influenza
virus (type A and
B)

Table 8: Microorganisms Tested for the Analytical Specificity Study

12

Interfering Substances

Twenty nine (29) microorganisms and chemical substances occasionally used in the nares or found in nasal swab specimens were evaluated for potential interference with the BD MAX™ StaphSR assay (Table 9). MRSA negative samples and MRSA positive samples at 2-3 x LoD were tested with the highest amount of each compound or microorganism likely to be found at the sampling site or on the nasal swab sample. Results demonstrated no reportable interference with any microorganisms or chemical substance except for Tobramycin that showed inhibition in the BD MAX™ StaphSR assay when tested at a concentration of 4.5 x 10-3 g/swab.

Table 9: Endogenous and Commercial Exogenous Substances Tested with the
BD MAX™ StaphSR Assay

Substance'	Result'
Mucin, from bovine submaxillary glands	NI
Dexamethasone Sodium Phosphate Ophtalmic
Solution	NI
USP, 0.1% Dexamethasone Phosphate Equivalent
Chloraseptic™	NI
Taro-Mupirocin, Mupirocin Ointment USP, 2%	NI
Long Lasting Dristan™ Nasal Mist	NI
Neo-Synephrine™	NI
Equate® Nasal Spray Decongestant	NI
Beconase AQ™	NI
Flunisolide Nasal Solution USP, 0.025%	NI
Nasacort™ AQ	NI
Nasonex™	NI
Relenza™	NI
Tobramycin	I
Blood	NI
Flumist®	NI
Substance	Result
Rhinocort aqua™	NI
Zicam® No-Drip Liquid™ Nasal
Gel™ Extreme Congestion
Relief	NI
Fluticasone Propionate	NI
Luffeel™	NI
Staphylococcus epidermidis	NI
Micrococcus luteus	NI
Enterococcus faecium	NI
Enterococcus faecalis	NI
Escherichia coli	NI
Corynebacterium flavescens	NI
Moraxella catarrhalis	NI
Staphylococcus hominis subsp
hominis	NI
Haemophilus influenzae	NI
Streptococcus pneumoniae	NI

NI: No reportable interference with the BD MAX™ StaphSR assay.

I: Reportable interference with the BD MAX™ StaphSR assay.

Microbial Competitive Inhibitory Effect

A study was conducted to determine the potential competitive inhibitory effect of:

an increasing concentration of MRSE when co-spiked with a low concentration । (1-2 x LoD) of MRSA or MSSA, and
an increasing concentration of MSSA when co-spiked with a low concentration -(1-2 x LoD) of MRSA.

Results demonstrated competition from:

MRSE at an MRSA:MRSE ratio of 1: ≥ 1x103 で
MRSE at an MSSA:MRSE ratio of 1: ≥ 1x105 -
MSSA at an MRSA:MSSA ratio of 1: ≥ 1x104. ー

Carryover / Cross-Contamination

A study was conducted to investigate the potential for carry-over/cross-contamination between high MRSA (≥10' CFU/swab) specimens and negative specimens throughout the BD MAX™ StaphSR workflow. Twelve (12) replicates of the high

13

positive sample and 12 replicates of the negative sample were tested in each run by alternating negative and positive replicates. Four (4) operators performed a total of 18 runs of 24 samples. Overall, from 203 reportable results out of 216 expected negative samples, 3 false positive results were obtained (3/203; 1.5%) due to carry-over contamination.

Clinical Performance Studies

Clinical performance characteristics of the BD MAX™ StaphSR assay were determined in a multi-site prospective investigational study. Three (3) investigational centers participated in the study. To be enrolled in the study, patients had to be eligible for MRSA or SA testing according to institutional policies. Eligibility requirements for targeted screening as per clinical site policies included, but were not limited to: patients admitted into the particular healthcare system; patients admitted to the Intensive Care Unit; patients transferred to the Intensive Care Unit; pre-elective surgery patients; and patients being admitted from long-term care facilities. Specimens from patients previously enrolled in the study were excluded.

The Comparative Reference Method consisted of direct culture complemented by enriched culture. Enriched culture analysis was completed for all specimens that were negative for MRSA or SA by direct culture. Presumptive S. aureus colonies observed on selective (S. aureus) chromogenic medium were subcultured onto Blood Agar (BA). Identification was confirmed with an agglutination test, while methicillin resistance was confirmed by Cefoxitin disk (30 µg) diffusion susceptibility testing. Enrichment in Trypticase Soy Broth with 6.5% NaCI (TSB 6.5% NaCI) was completed in the event that MRSA or SA was not confirmed by the initial direct culture method. Turbid TSB 6.5% NaCl broth was used to inoculate additional chromogenic medium and BA plates; MRSA confirmation was performed as described above.

Results Obtained with the BD MAX™ StaphSR Assay in Comparison to the Reference Method

A total of 2451 specimens were enrolled in the study. Of those, 94 specimens were regarded as noncompliant per protocol criteria and three (3) fully compliant specimens gave final non-reportable PCR results. A total of 2354 specimen results were used to determine the clinical performance of the BD MAX™ StaphSR assay in comparison to the Reference Method (Tables 10 to 13).

Compared to the Reference Method (Direct/Enriched Culture), the BD MAX™ StaphSR assay identified 93.1% of the MRSA positive specimens and 97.5% of the MRSA negative specimens (Table 10). For the population tested, this resulted in a Negative Predictive Value (NPV) of 99.5% and a Positive Predictive Value (PPV) of 73.2%.

14

	All Sites	Reference Method
		MRSA Positive	Negative	Total
BD MAX TM StaphSR Assay	Positive	149	54	203
	Negative	11	2140	2151
	Total	160	2194	2354
Sensitivity: 93.1% (149/160) (95% CI: 88.1%, 96.1%)
Specificity: 97.5% (2140/2194) (95% CI:96.8%, 98.1%)
PPV: 73.2% (95% CI: 67.8%, 78.3%)
NPV: 99.5% (95% CI: 99.1%, 99.7%)

Table 10: Results Obtained for MRSA with the BD MAX ™ StaphSR Assay in Comparison to the Reference Method

the Reference Method and the BD MAX ™ StaphSR assay.

· 12 of 54 MRSA False Positive BD MAX™ StaphSR specimens were also found to be positive after repeat of Reference Method

· 5 of 11 MRSA False Negative BD MAX™ StaphSR specimens were also found to be negative after repeat of Reference Method

	Table 11: Site-by-Site Performance Obtained for MRSA with the BD MAX™
	StaphSR Assay in Comparison to the Reference Method

Clinical Sites	Prevalence	Sensitivity (95% CI)
Site 1	4.3% (41/960)	92.7% (38/41)
(80.6%, 97.5%)	98.9% (908/918)
(98.0%, 99.4%)
Site 2	5.8% (38/650)	86.8% (33/38)
(72.7%, 94.2%)	98.5% (583/592)
(97.1%, 99.2%)
Site 3	10.6% (81/765)	96.3% (78/81)
(89.7%, 98.7%)	94.9% (649/684)
(93.0%, 96.3%)
Overall	6.7% (160/2375)	93.1% (149/160)
(88.1%, 96.1%)	97.5% (2140/2194)
(96.8%, 98.1%)

. Prevalence based on reference method only

b Confidence interval

° 2375 specimens were reference method compliant

Compared to the Reference Method (Direct/Enriched Culture), the BD MAX™ StaphSR assay identified 92.0% of the SA positive specimens and 93.1% of the SA negative specimens (Tables 12 and 13). For the population tested, this resulted in a NPV of 96.8% and a PPV of 83.4%.

	Table 12: Results Obtained for SA with the BD MAX™
	StaphSR Assay in Comparison to the Reference Method

	Reference Method
All Sites	SA	Positive	Negative	Total
	Positive	599	118	717
BD MAXTM StaphSR Assay	Negative	52	1585	1637
	Total	651	1703	23541
Sensitivity: 92.0% (599/651) (95% CI: 89.7%, 93.9%)
Specificity: 93.1% (1585/1703) (95% CI: 91.8%, 94.2%)
PPV: 83.4% (95% CI: 81.9%, 85.8%)
NPV: 96.8% (95% CI: 96.0%, 97.6%)
1Further investigation was performed on specimens with discordant results between
the Reference Method and the BD MAXTM StaphSR assay.
28 of 118 SA False Positive BD MAXTM StaphSR specimens were also

found to be positive after repeat of Reference Method

23 of 52 SA False Negative BD MAX™ StaphSR specimens were also � found to be negative after repeat of Reference Method

15

Clinical Sites	Prevalence	Sensitivity with 95% CI
Site 1	27.2% (261/960)	90.0% (235/261)
(85.8%, 93.1%)	96.3% (672/698)
(94.6%, 97.4%)
Site 2	27.5% (179/650)	91.5% (162/177)
(86.5%, 94.8%)	90.9% (412/453)
(88.0%, 93.3%)
Site 3	27.8% (213/765)	94.8% (202/213)
(91.0%, 97.1%)	90.8% (501/552)
(88.1%, 92.9%)
Overall	27.5% (653/2375)	92.0% (599/561)
(89.7%, 93.9%)	93.1% (1585/1703)
(91.8%, 94.2%)

Table 13: Site-by-Site Performance Obtained for SA with the BD MAX™ StaphSR Assay in Comparison to the Reference Method

a Prevalence based on reference method only

6 Confidence interval

€ 2375 specimens were reference method compliant

Results Obtained with the BD MAX™ StaphSR Assay in Comparison to Direct Culture

A total of 2451 specimens were enrolled in the study. Of those, 54 specimens were regarded as noncompliant per protocol criteria and four (4) fully compliant specimens gave non reportable PCR results. A total of 2393 specimen results were used to determine the positive and negative percent agreement of the BD MAX™ StaphSR assay in comparison to Direct Culture (Tables 14 to 17).

Compared to Direct Culture, the BD MAX™ StaphSR assay identified 96.5% of the MRSA positive specimens and 96.9% of the MRSA negative specimens (Tables 14 and 15).

		Direct Culture
All Sites		Positive	Negative	Total
BD MAX™ StaphSR Assay	Positive	137	69	206
	Negative	5	2182	2187
	Total	142	2251	2393
Positive Percent Agreement: 96.5% (137/142) (95% CI: 92.0%, 98.5%)
Negative Percent Agreement: 96.9% (2182/2251) (95% CI: 96.1%, 97.6%)

Table 14: Results Obtained for MRSA with the BD MAX™ StaphSR Assay in Comparison to Direct Culture

Table 15: Site-by-Site Performance Obtained for MRSA with the BD MAX™ StaphSR Assay in Comparison to Direct Culture

| Clinical
Sites | Positive Percent
Agreement with 95%
CI | Negative Percent
Agreement with 95%
CI |
|-------------------|----------------------------------------------|----------------------------------------------|
| Site 1 | 100% (35/35)
(90.1%, 100%) | 98.6% (911/924)
(97.6%, 99.2%) |
| Site 2 | 93.5% (29/31)
(79.3%, 98.2%) | 97.8% (586/599)
(96.3%, 98.7%) |
| Site 3 | 96.1% (73/76)
(89.0%, 98.6%) | 94.1% (685/728)
(92.1%, 95.6%) |
| Overall | 96.5% (137/142)
(92.0%, 98.5%) | 96.9% (2182/2251)
(96.1%, 97.6%) |

8 Confidence interval

16

Compared to Direct Culture, the BD MAX™ StaphSR assay identified 95.1% of the SA positive specimens and 90.9% of the SA negative specimens (Tables 16 and 17).

Table 16: Results Obtained for SA with the BD MAX™ StanhSR Assay in Comparison to Direct Culture

All Sites		Direct Culture
		Positive	Negative	Total
BD MAX TM StaphSR Assay	Positive	564	164	728
	Negative	29	1636	1665
	Total	593	1800	2393
Positive Percent Agreement: 95.1% (564/593) (95% CI: 93.1%, 96.6%)
Negative Percent Agreement: 90.9% (1636/1800) (95% CI: 89.5%, 92.1%)

Table 17: Site-by-Site Performance Obtained for SA with the BD MAX™ StaphSR Assay in Comparison to Direct Culture

| Clinical
Sites | Positive Percent
Agreement with
95% CIa | Negative Percent
Agreement with 95%
CIa |
|-------------------|-----------------------------------------------|-----------------------------------------------|
| Site 1 | 93.0% (213/229)
(89.0%, 95.7%) | 93.4% (682/730)
(91.4%, 95.0%) |
| Site 2 | 94.9% (149/157)
(90.3%, 97.4%) | 88.6% (419/473)
(85.4%, 91.1%) |
| Site 3 | 97.6% (202/207)
(94.5%, 99.0%) | 89.6% (535/597)
(86.9, 91.8%) |
| Overall | 95.1% (564/593)
(93.1%, 96.6%) | 90.9% (1636/1800)
(89.5%, 92.1%) |

8 Confidence interval

Out of 2399 nasal swab specimens tested with the BD MAX™ StaphSR assay that were compliant at the specimen and PCR level, 15 (0.6%) were reported as Unresolved after initial testing. The Unresolved Rate after repeat testing is 0.04% (1/2399) (Table 18).

Initial Unresolved Rates	Unresolved Rates After Repeat
0.6% (15/2399)* (95% CI: 0.4%, 1.0%)	0.04% (1/2399) (95% CI: 0%, 0.2%)
*Total number based on compliant specimens and BD MAX™ StaphSR assay results

*Total number based on compliant specimens and BD MAX™ StaphSR assay results

Out of the same 2399 nasal swab specimens tested with the BD MAX™ StaphSR assay, 14 (0.6%) were initially reported as Indeterminate. No result remained Indeterminate upon repeat (two specimens were not retested). Eight (8) (0.3%) were initially reported as Incomplete. No result remained Incomplete upon repeat (one specimen was not retested).

Empty Cassette Variants

Among the 2354 eligible specimens included in the clinical performance determination, a total of 10 specimens fit the empty cassette profile resulting in detection of MREU, without mecA or mecC gene detection. All of the 10 specimens were verified true negative MRSA and true positive SA relative to the Reference Method.

17

Expected Values

In the BD MAX™ StaphSR assay clinical study a total of 2395 reportable results, from specimens compliant at the specimen and PCR levels, were obtained from 3 geographically diverse sites and compared with Direct and Enriched culture. The study population was grouped into in-patient and unknown categories. The number and percentage of positive cases, as determined by the BD MAX™ StaphSR assay, are presented in the table below:

| Group | Total Number
of
Specimens¹ | BD MAX™ StaphSR Assay | | Positive
MRSA
Percentage | Positive SA
Percentage |
|-------------|----------------------------------|-------------------------------|--------------------------|--------------------------------|---------------------------|
| | | Number of
MRSA
Positive | Number of SA
Positive | | |
| In-patient | 1685 | 178 | 548 | 10.6%
(178/1685) | 32.5%
(548/1685) |
| Out-patient | 710 | 28 | 182 | 3.9%
(28/710) | 25.6%
(182/710) |
| Total¹ | 2395 | 206 | 730 | 8.6%
(206/2395) | 30.5%
(730/2395) |

1Total specimens based on compliant PCR results.

18

Image /page/18/Picture/0 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo consists of a circular seal with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES USA" around the perimeter. Inside the seal is a stylized symbol resembling an eagle or bird with three curved lines representing its wings or feathers.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Humpshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

GENEOHM SCIENCE CANADA. INC. (BD DIAGNOSTICS) PATRICIA DIONNE, PH.D, MBA DIRECTOR. REGULATORY AFFAIRS 2555 BOUL. DU PARC-TECHNOLOGIQUE QUEBEC, QUEBEC, GIP 4S5 CANADA

Re: K132822

Trade/Device Name: BD MAXTM StaphSR Regulation Number: 21 CFR 866.1640 Regulation Name: Antimicrobial Susceptibility Test Powder Regulatory Class: II Product Code: NQX, OOI Dated: September 16, 2013 Received: September 17, 2013

November 26, 2013

Dear Dr. Dionne:

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 10 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. Ilisting 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 11 (Special Controls) or class 111 (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 Parts 801 and 809); medical device 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.

19

Page 2-Dr. Dionne

If you desire specific advice for your device on our labeling regulations (21 CFR Parts 801 and 809), please contact the Division of Small Manufacturers. International and Consumer Assistance 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 premarket 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 Small Manufacturers. International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.hum.

Sincerely yours.

Sally A. Hojvat -S

Sally A. Hojvat, M.Sc., Ph.D. Director Division of Microbiology Devices Office of In Vitro Diagnostics and Radiological l-lealth Center for Devices and Radiological Health

Enclosure

20

DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: December 31, 2013 See PRA Statement on last page.

510(k) Number (if known) K132822

Device Name BD MAX™ StaphSR

Indications for Use (Describe)

The BD MAX™ StaphSR assay performed on the BD MAX™ System is an automated qualitative in vitro diagnostic test for the direct detection and differentiation of Staphylococus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) DNA from nasal swabs in patients at risk for nasal colonization. The test utilizes real-time polymense chain reaction (PCR) for the amplification of MRSA/SA DNA and fluorogenic arget-specific hybridization probes for the amplified DNA. The BD MAX™ StaphSR assay is intended to aid in the prevention and control of MRSA and SA infections in healthcare settings. It is not intended to diagnose MRSA or SA infections nor guide or monitor treatment for MRSA/SA infections. A negalive result does not preclude nasal colonization. Concomitant cultures are necessary to recover organisms for epidemiological typing or for further susceptibility testing.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

] Over-The-Counter Use (21 CFR 807 Subpart C)

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

. SEAR . . . . . . . . . . . . . . . . . . . . . FOR FOR FOR FOR FOR . . . . . . . . . . . . . - • Concurrence of Center for Devices and Radiological Health (CDRH) (Signature)

Ribhi Shawar-S 2013.11.25 08:19:23 -05'00'

Image /page/20/Picture/17 description: The image shows a logo with the letters "FDA" in a stylized, geometric design. The letters are formed by a series of parallel lines, creating a layered effect. The logo is black and white and appears to be a simplified or abstract representation of the Food and Drug Administration logo.

FORM FDA 3881 (6/13)