Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The description details a standard PCR-based diagnostic test with automated processing and preestablished decision criteria for result determination. There is no mention of AI, ML, or any learning algorithms.

Therapeutic

No.
This device is an in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA, which is used as an aid in determining colonization status. It does not provide therapy or treatment.

Diagnostic

Yes

The "Intended Use / Indications for Use" section explicitly states that the device "is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA." It further clarifies that "Results from the NeuMoDx™ GBS Assay can be used as an aid in determining colonization status in antepartum women," which is a diagnostic purpose. The "Device Description" also refers to it as an "in vitro diagnostic test."

SaMD (Software as a Medical Device)

No

The device is an in vitro diagnostic test that includes reagents, buffers, a microfluidic cartridge, and a fully automated molecular system (hardware) in addition to the software for data analysis and reporting.

IVD (In Vitro Diagnostic)

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

Here's why:

Intended Use/Indications for Use: Explicitly states it is a "qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA".
Device Description: Describes the device as an "automated, qualitative, in vitro diagnostic test for the detection of group B Streptococcus (GBS)".
Intended User/Care Setting: Specifies "Prescription Use (Part 21 CFR 801 Subpart D), Qualified Laboratory Personnel", which is typical for IVD devices used in a clinical laboratory setting.
Performance Studies: The document details clinical performance studies comparing the device to a conventional culture method, which is a standard requirement for demonstrating the performance of an IVD.
Predicate Device(s): Lists a predicate device with a K number (K090191), indicating a comparison to a previously cleared IVD device.

All of these points strongly indicate that the NeuMoDx™ GBS Assay is an In Vitro Diagnostic device.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

The NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from 18-24 hour Lim broth enrichments of vaginal/rectal swabs from pregnant women. The test incorporates automated DNA extraction to isolate the target nucleic acid from the specimen and real-time polymerase chain reaction (PCR) to detect an 88 bp region of the pcsB gene sequence in the Streptococcus agalactiae chromosome. Results from the NeuMoDx™ GBS Assay can be used as an aid in determining colonization status in antepartum women.

The NeuMoDx™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

Product codes (comma separated list FDA assigned to the subject device)

NJR, OOI

Device Description

The NeuMoDx™ GBS Assay (Subject Device) as implemented on the NeuMoDx™ 288 Molecular System is an automated, qualitative, in vitro diagnostic test for the detection of group B Streptococcus (GBS), also known as Streptococcus agalactiae from vaginal/rectal swabs collected from pregnant women at 35 - 37 weeks of gestation and enriched in a commercially available Lim broth medium. An aliquot of an overnight Lim broth culture added to the NeuMoDx™ GBS Assay is used for the testing. All further specimen handling is automated.

The GBS Assay test strip, in combination with required NeuMoDx buffers, extraction reagents, wash and release solutions, as well as the microfluidic cartridge (non-active,) and the fully automated NeuMoDx™ 288 Molecular System (a real time nucleic acid amplification system), utilizes real-time polymerase chain reaction (PCR) for the amplification of GBS DNA and fluorogenic target-specific TaqMan® probes for the detection of the amplified GBS DNA. General use components and the System are packaged and provided separately by NeuMoDx.

After the test is processed, a determination of the presence/absence of GBS DNA in the specimen is automatically made based on the amplification status of GBS and the Sample Process Control using preestablished decision criteria. The test results will be reported as Negative, Positive, Indeterminate or Unresolved based on the amplification status of the target and sample processing control. Results are reported based on the decision algorithm noted in Table 1.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

vaginal/rectal swabs

Indicated Patient Age Range

pregnant women

Intended User / Care Setting

Prescription Use (Part 21 CFR 801 Subpart D)
Moderate Complexity Rx only - Qualified Laboratory Personnel

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

Not Found

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

Clinical Performance Summary
Study Type: Prospective clinical method comparison study.
Sample Size: 1193 specimens with complete, valid, and compliant results.
Data Source: Vaginal/rectal swab specimens collected from pregnant women by health care providers for routine standard of care screening purposes. Specimens were transported to laboratories, inoculated into Lim broth, and incubated for 18-24 hours. Residual Lim broth samples were subcultured to sheep blood agar plates, incubated for up to 48 hours, and inspected for GBS. Suspected colonies were Gram-stained, tested for catalase production, and Gram-positive cocci colonies negative for catalase were identified by streptococcal grouping latex agglutination test to determine GBS presence.
Key Results:
Overall Sensitivity = 96.9% (95% CI: 94.1 - 98.4)
Overall Specificity = 96.0% (95% CI: 94.6 - 97.1)

Precision/Reproducibility
Precision: Qualitative testing on NeuMoDx™ 288 Molecular System using NeuMoDx™ GBS Test Strip. 2 runs per day across 3 systems over 12 non-consecutive days with 2 reagent lots and 2 operators. A run involved 3 replicates for each of 5 levels (True Negative, Low Negative, Moderate Negative, Low Positive, Moderate Positive) for a total of 15 specimens per run per system. Specimens were prepared by spiking cultured GBS into pooled, screened negative clinical remnant Lim broth. A total of 72 runs and 1224 tests were performed.
Inter-Lab Reproducibility: Evaluated at 3 different testing sites by testing 5 replicates of a 4-member panel over 5 days, generating 75 replicates per panel member. Panel samples were prepared by spiking cultured GBS into pooled, negative clinical Lim broth to create Low Negative, Low Positive, and Moderate Positive panel members. True (Blank) Negative samples contained no GBS. Overall, 4 invalid results were obtained (Indeterminate).
Key Results:

Precision (Overall % Positive / % Negative):
- Moderate Positive (MP): 100% (216/216)
- Low Positive (LP): 97.7% (211/216)
- Moderate Negative (MN): 82% (178/216)
- Low Negative (LN): 98.6% (213/216)
- True Negative (TN): 100% (216/216)
Inter-Lab Reproducibility (% Agreement / 95% CI):
- Moderate Positive: 100% (75/75) (95.1 - 100)
- Low Positive: 97.3% (73/75) (90.8 - 99.3)
- Low Negative: 98.7% (74/75) (92.8 - 99.8)
- Blank Negative: 100% (75/75) (95.1 - 100)

Detection Limit
Study Type: Analytical Sensitivity
Sample Size: 60 valid tests at each GBS CFU/mL level tested.
Data Source: Five different levels of GBS (ATCC BAA-611 serotype V) prepared from five independent clinical negative pools.
LoD (Limit of Detection): Determined to be 500 CFU/mL.
Key Results:

1000 CFU/mL: 100% detection rate (60/60)
500 CFU/mL: 100% detection rate (60/60)
200 CFU/mL: 88% detection rate (53/60)
100 CFU/mL: 58% detection rate (35/60)
0 CFU/mL: 0% detection rate (0/60)

Analytical Reactivity (Inclusivity)
Study Type: Inclusivity testing
Sample Size: Twelve different GBS strains spanning various serotypes.
**Key Results:**Detected all major serotypes of group B Streptococcus, including the four most clinically relevant.

Analytical Specificity (Exclusivity)
Study Type: Cross-reactivity screening
Sample Size: 136 organisms common to the urogenital and digestive tract, and species phylogenetically related to GBS.
Key Results: None of the organisms screened demonstrated cross-reactivity.

Interference with Non-Target Organisms
Study Type: Interference testing
Sample Size: The same panel of 136 organisms (Table 6) used for assessing cross-reactivity, pooled into groups of 5-6 in clinical negative Lim broth and spiked with 1200 CFU/mL cultured GBS.
Key Results: Testing validated detection of group B streptococcus in all of the pools tested. No interference due to commensal organisms was observed.

Interference with Exogenous and Endogenous Substances
Study Type: Interference testing
Sample Size: 20 exogenous and 6 endogenous substances.
Data Source: Each substance added to pooled clinical negative Lim broth samples containing GBS at 1200 CFU/mL or 4000 CFU/mL.
Key Results: No adverse effect on detection of GBS at either level tested.

Carry-Over and Cross-Contamination Studies
Study Type: Carry-over and cross-contamination studies
Key Results: No contamination was seen in negative samples integrated with high level samples, or in negative samples that followed samples with high concentrations of GBS, demonstrating the lack of any carry over and / or cross-contamination.

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

Sensitivity = 96.9% (95% CI (94.1 - 98.4))
Specificity = 96.0% (95% CI (94.6-97.1))

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

BD Max™ GBS Assay (K090191)

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 866.3740

Streptococcus spp. serological reagents.(a)
Identification. Streptococcus spp. serological reagents are devices that consist of antigens and antisera (excluding streptococcal exoenzyme reagents made from enzymes secreted by streptococci) used in serological tests to identifyStreptococcus spp. from cultured isolates derived from clinical specimens. The identification aids in the diagnosis of diseases caused by bacteria belonging to the genusStreptococcus and provides epidemiological information on these diseases. Pathogenic streptococci are associated with infections, such as sore throat, impetigo (an infection characterized by small pustules on the skin), urinary tract infections, rheumatic fever, and kidney disease.(b)
Classification. Class I (general controls). The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to § 866.9.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

June 26, 2018

NeuMoDx Molecular, Inc. % Kay Fuller Principal Consultant and Official Correspondent Medical Device Regulatory Solutions, LLC 230 Collingwood Dr. Suite 260 Ann Arbor, Michigan 48103

Re: K173725

Trade/Device Name: NeuMoDx GBS Assay Regulation Number: 21 CFR 866.3740 Regulation Name: Streptococcus spp. serological reagents Regulatory Class: Class I Product Code: NJR, OOI Dated: March 23, 2018 Received: March 29, 2018

Dear Kay Fuller:

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

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may 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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

1

803); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); 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 medical devices and radiation-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,

Ribhi Shawar -S For

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

Enclosure

2

Indications for Use

510(k) Number (if known) K173725

Device Name NeuMoDx™ GBS Assay

Indications for Use (Describe)

The NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from 18-24 hour Lim broth enrichments of vaginal/rectal swabs from pregnant women. The test incorporates automated DNA extraction to isolate the target nucleic acid from the specimen and real-time polymerase chain reaction (PCR) to detect an 88 bp region of the pcsB gene sequence in the Streptococcus agalactiae chromosome. Results from the NeuMoDx™ GBS Assay can be used as an aid in determining colonization status in antepartum women.

The NeuMoDx™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

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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14. 510(k) SUMMARY

NeuMoDx Molecular, Inc.

NeuMoDx™ GBS Assay

June 25, 2018

1. GENERAL INFORMATION

| Submitter 1250 Eisenhower Place
Ann Arbor, MI 48108 USA |------------------- | Contact Information: | | Primary Contact: Principal Regulatory Consultant
Medical Device 734-846-7852 | |
| Secondary Contact: Sr. Director Quality Assurance
NeuMoDx Molecular, Inc. | DEVICE INFORMATION | | Device Name: | Proprietary Name: | Common Name: | Classification Name: Streptococcus, | Classification Code: OOI - Secondary | Classification: | FDA Review Panel: | Regulation Number: | PREDICATE DEVICE | DEVICE DESCRIPTION | Information: | NeuMoDx Molecular, Inc.
| |
-----|----------------------------------------------------------------------------------------------------------------|--|
| |
| Kay Fuller, RAC
Regulatory Solutions, LLC
| Dawn Ross
| |
| |
| GBS Assay | |
| NeuMoDx™ GBS Assay | |
| Group B Strep Assay | |
| Nucleic Acid Amplification Assay System, Group B
Direct Specimen Test | |
| NJR - Primary
| |
| Class I | |
| 83 - Microbiology | |
| 21 CFR §866.3740 | |
| BD Max™ GBS Assay (K090191) | |
| |

The NeuMoDx™ GBS Assay (Subject Device) as implemented on the NeuMoDx™ 288 Molecular System is an automated, qualitative, in vitro diagnostic test for the detection of group B Streptococcus (GBS), also

4

known as Streptococcus agalactiae from vaginal/rectal swabs collected from pregnant women at 35 - 37 weeks of gestation and enriched in a commercially available Lim broth medium. An aliquot of an overnight Lim broth culture added to the NeuMoDx™ GBS Assay is used for the testing. All further specimen handling is automated.

The GBS Assay test strip, in combination with required NeuMoDx buffers, extraction reagents, wash and release solutions, as well as the microfluidic cartridge (non-active,) and the fully automated NeuMoDx™ 288 Molecular System (a real time nucleic acid amplification system), utilizes real-time polymerase chain reaction (PCR) for the amplification of GBS DNA and fluorogenic target-specific TaqMan® probes for the detection of the amplified GBS DNA. General use components and the System are packaged and provided separately by NeuMoDx.

After the test is processed, a determination of the presence/absence of GBS DNA in the specimen is automatically made based on the amplification status of GBS and the Sample Process Control using preestablished decision criteria. The test results will be reported as Negative, Positive, Indeterminate or Unresolved based on the amplification status of the target and sample processing control. Results are reported based on the decision algorithm noted in Table 1.

Table 1

Result	GBS Ct	Sample Process Control (SPC1) Ct
Positive	9 3000	N/A
Negative	N/A OR Ct 37	25 2000
Indeterminate	N/A
SYSTEM ERROR NOTED	N/A
SYSTEM ERROR NOTED
Unresolved	Not detected	Not detected

EP = End Point Fluorescence (after baseline correction)

External controls are not provided by NeuMoDx but are recommended to be performed as required by the laboratory's internal procedures.

Standards/Guidance Documents Referenced

CLSI Guideline EP25-A, Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline.

Test Principle - Summary

The amplified targets are detected in real time using hydrolysis probe chemistry (commonly referred to as TaqMan® chemistry) using fluorogenic oligonucleotide probe molecules specific to the amplicons for their respective targets.

TaqMan® probes consist of a fluorophore covalently attached to the 5'-end of the oligonucleotide probe and a quencher at the 3'-end. While the probe

5

is intact, the fluorophore and the quencher are in proximity, resulting in the quencher molecule quenching the fluorescence emitted by the fluorophore via FRET (Förster Resonance Energy Transfer).

TaqMan® probes are designed such that they anneal within a DNA region amplified by a specific set of primers. As the Taq DNA polymerase extends

the primer and synthesizes the new strand, the 5' to 3' exonuclease activity of the Taq DNA polymerase degrades the probe that has annealed to the template. Degradation of the probe releases the fluorophore from it and breaks the close proximity to the quencher, thereby overcoming the quenching effect due to FRET and allowing detecting fluorescence of the fluorophore. The resulting fluorescence signal detected in the quantitative PCR thermal cycler is directly proportional to the fluorophore released and can be correlated to the amount of target DNA present in PCR.

A TaqMan® probe labeled with a fluorophore (Excitation: 490 nm & Emission: 521 nm) at the 5' end, and a dark quencher at the 3' end, is used to detect GBS DNA. For detection of the Sample Process Control, the TaqMan® probe is labeled with an alternate fluorescent dye (Excitation: 535 nm & Emission: 556 nm) at the 5' end, and a dark quencher at the 3' end. The NeuMoDx™ 288 Molecular System monitors the fluorescent signal emitted by the TagMan® probes at the end of each amplification cycle and presents the test result.

5. INDICATIONS FOR USE

The NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System is a qualitative in vitro diagnostic test designed to detect Group B Streptococcus (GBS) DNA from 18-24 hour Lim broth enrichments of vaginal/rectal swabs from pregnant women. The test incorporates automated DNA extraction to isolate the target nucleic acid from the specimen and real-time polymerase chain reaction (PCR) to detect an 88 bp region of the pcsB gene sequence in the Streptococcus agalactiae chromosome. Results from the NeuMoDx™ GBS Assay can be used as an aid in determining colonization status in antepartum women.

The NeuMoDx™ GBS Assay does not provide susceptibility results. Cultured isolates are needed for performing susceptibility testing as recommended for penicillin-allergic women.

6. COMPARISON OF TECHNOLOGICAL CHARACTERISTICS

The NeuMoDx™ GBS Assay's fundamental technological characteristics are similar to those of the predicate device. The NeuMoDx™ GBS Assay (subject device) is substantially equivalent to the BD Max™ GBS Assay device (predicate device), noted herein. Both the subject device and predicate device assays detect Group B Streptococcus (GBS) DNA from enriched vaginal/rectal swab specimens. Both subject and predicate

6

assays determine the presence of the targetorganisms through real-time PCR amplification and fluorogenic target-specific hybridization detection and utilize a similar instrumentation format.

| Feature
Comparison
Criteria | Subject Device
NeuMoDx™ GBS Assay
K173725 | Predicate Device
BD MAX™ GBS Assay
K090191 | Subject
Device SE
to K090191? |
|------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-------------------------------------|
| 21 CFR Reg #, Product
Code & Classification | 21 CFR §866.3740
NJR
Class I | 21 CFR §866.3740
NJR
Class I | Yes |
| Regulation Name | Nucleic Acid Amplification Assay
System, Group B Streptococcus,
Direct Specimen Test | Nucleic Acid Amplification Assay System,
Group B Streptococcus,
Direct Specimen Test | Yes |
| Prescription Device -
Rx Only | Yes | Yes | Yes |
| Indications for Use | The NeuMoDx™ GBS Assay as implemented
on the NeuMoDx™ 288 Molecular System is a
qualitative in vitro diagnostic test designed
to detect Group B Streptococcus (GBS) DNA
from 18-24 hour Lim broth enrichments of
vaginal/rectal swabs from pregnant women.
The test incorporates automated DNA
extraction to isolate the target nucleic acid
from the specimen and real-time polymerase
chain reaction (PCR) to detect an 88 bp
region of the PcsB gene sequence in the
Streptococcus agalactiae chromosome.
Results from the NeuMoDx™ GBS Assay can
be used as an aid in determining colonization
status in antepartum women.
The NeuMoDx™ GBS Assay does not
provide susceptibility results. Cultured
isolates are needed for performing
susceptibility testing as recommended for
penicillin-allergic women. | The BD MAX™ GBS Assay as implemented on the
BD MAX™ System is a qualitative in vitro
diagnostic test designed to detect Group B
Streptococcus (GBS) DNA in Lim Broth cultures
after incubation for greater than or equal to (>)18
hours, obtained from vaginal and rectal swab
specimens from antepartum pregnant women.
The test incorporates automated DNA extraction
to isolate the target nucleic acid from the
specimen and real-time polymerase chain reaction
(PCR) to detect a 124 bp region of the cfb gene
sequence of the Streptococcus agalactiae
chromosome. Results from the BD MAX™ GBS
Assay can be used as an aid in determining
colonization status in antepartum women.
The BD MAX™ GBS Assay does not provide
susceptibility results. Cultured isolates are
needed for performing susceptibility testing as
recommended for penicillin-allergic women.
Subculture to solidmedia for additional testing
when indicated. | Yes |
| Analyte | Group B Streptococcus DNA | Group B Streptococcus DNA | Yes |
| Specimen Type | Vaginal-rectal swab
(Enriched Lim broth 18-24 hrs) | Vaginal-rectal swab
(Enriched Lim broth > 18 hrs) | Yes |
| Specimen Collection
Media Type | Amies or Stuart | Amies or Stuart | Yes |
| Sample Preparation
Method | Sample Preparation for Nucleic Acid
Extraction is automated on NeuMoDx™
288 Molecular System | Sample Preparation for Nucleic Acid
Extraction is automated on BD MAX System | Yes |
| Sample Matrix | Enriched in overnight LIM | Enriched in overnight LIM | Yes |
| Test Reference
Comparison Method | CDC GBS 2010 Guidelines of Culture
Processing/Identification Procedure | CDC GBS 2002 Guidelines of Culture
Processing/Identification Procedure | Yes |
| Platform | NeuMoDx™ 288 Molecular System
(random access) | BD MAX System (random access) | Yes |
| Assay Format | Amplification: Real Time PCR Detection:
Fluorogenic | Real Time Fluorogenic Detection of PCR
amplification | Yes |
| DNA Target
Sequence | 88 bp region of the PcsB gene sequence
in the Streptococcus agalactiae
chromosome | 124 bp region of the cfb gene sequence of
the Streptococcus agalactiae chromosome | Yes |
| Probes | TaqMan® | Scorpion | Yes |
| Single Use | Yes | Yes | Yes |
| User / skill required | Moderate Complexity
Rx only - Qualified
Laboratory Personnel
Built in protocol
No data interpretation
required | Moderate Complexity
No special skills required
Built in protocol
No data interpretation
required | Yes |
| Automatic Assay | Yes - Built-in Result Interpretation | Yes - Built-in Result Interpretation | Yes |
| Internal Process
Control | Sample process control is extracted and
amplified with each sample as a process
monitor | Extraction and PCR internal process control
is a process monitor | Yes |
| External Control | Not provided by NeuMoDx; commercial
materials available.
Not required to perform testing.
Appropriate controls and testing
intervals must be determined by the
laboratory | Materials available commercially but not
required to run the test | Yes |

Substantial Equivalence Summary

7. NON-CLINICAL TESTING SUMMARY

Analytical Performance

a. Precision/Reproducibility

Precision

Qualitative testing was performed on the NeuMoDx™ 288 Molecular System using the NeuMoDx™ GBS Test Strip where 2 runs per day were performed across 3 systems over a period of 12 non-consecutive days. This within-lab precision testing included 2 reagent lots and was performed by 2 operators.

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A run was defined as three replicates tested for each of the five different levels shown in Table 2 (True Negative, Low Negative, Moderate Negative, Low Positive and Moderate Positive) for a total of 15 specimens per run Specimens were prepared by spiking cultured GBS into per system. pooled, screened negative clinical remnant Lim broth. For each run performed, a positive and a negative external control were processed in addition to the 15 specimens. A total of 72 runs and 1224 tests were performed in this study, including the external controls. Table 3 shows comparison across instruments. Table 4 shows precision across operators.

			Table 2: Within Lab Precision Pane
--	--	--	------------------------------------	--

Panel Member	Level Tested	GBS (CFU/mL)
Moderate Positive (MP)	3-4x LoD	1600
Low Positive (LP)	1-2x LoD	600
Moderate Negative (MN)	>10-fold dilution of 1x LoD	40
Low Negative (LN)	>100-fold dilution of 1x LoD	4
True (Blank) Negative (TN)	0	0

	Instrument 1	Instrument 2	Instrument 3	Overall
Level	Percent Positive	Percent Positive	Percent Positive	Percent Positive
MP	100% (72/72)	100%(72/72)	100%(72/72)	100% (216/216)
LP	100% (72/72)	95.8% (69/72)	97.2% (70/72)	97.7% (211/216)
	Percent Negative	Percent Negative	Percent Negative	Percent Negative
MN	77.7% (56/72)	86.1% (62/72)	83.3% (60/72)	82% (178/216)
LN	97.2% (70/72)	100% (72/72)	98.6% (71/72)	98.6% (213/216)
TN	100% (72/72)	100% (72/72)	100% (72/72)	100% (216/216)

		Table 4: Quantitative GBS Parameter Analysis from Within Lab Precision (Across Operators)
--	--	--------------------------------------------------------------------------------------------	--	--	--	--	--

	First Operator				Second Operator				Combined Data Set
Level	Detected
Pos/Total	%
Positive	Ave Ct	Std
Dev	% CV*	Detected
Pos/Total	%
Positive	Ave Ct	Std
Dev	% CV	Detected
Pos/Total	%
Positive	Ave Ct	Std
Dev	% CV
MP	108/108	100.0%	31.61	0.54	1.7%	108/108	100.0%	32.22	0.51	1.6%	216/216	100.0%	31.91	0.61	1.9%
LP	106/108	98.1%	34.16	0.68	2.0%	105/108	97.2%	34.39	0.72	2.1%	211/216	97.7%	34.27	0.71	2.1%
MN	20/108	18.5%	35.00	0.53	1.5%	18/108	16.7%	35.28	0.40	1.1%	38/216	17.6%	35.10	0.49	1.4%
LN	2/108	1.9%	35.49	0.12	0.3%	1/108	0.9%	35.03	N/A	N/A	3/216	1.4%	35.33	0.28	0.8%
TN	0/108	0.0%	N/A	N/A	N/A	0/108	0.0%	N/A	N/A	N/A	0/216	0.0%	N/A	N/A	N/A

%CV: The coefficient of variation, 100* standard deviation/Ave Ct.

Reproducibility

Inter-Lab Reproducibility

The reproducibility of the NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System using the NeuMoDx™ GBS Test Strip was evaluated at 3 different testing sites by testing 5 replicates of a 4member panel over 5 days, which generated a total of 75 replicates per panel member. Panel samples were prepared by spiking cultured GBS into pooled, negative clinical Lim broth to create Low Negative, Low Positive and

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Moderate Positive panel members, whereas the True (Blank) Negative samples contained no GBS. Concentrations of the panel members correspond to the same levels listed in Table 8 above used for Precision (minus the Moderate Negative sample). A positive and a negative external control were were were were were were were were were were were were were were were were were werken in die werken in die werken in die were were were were were were were were were we also processed o on each day of of testing.

Overall, there were 4 invalid results obtained during the Reproducibility study - one replicate of each of the 4 concentrations yielded an "Indeterminate" and all occurred on the same day of testing (Day 2) at Site B. Upon repeat testing, 2 of the 4 samples yielded a valid, correct result; the remaining two samples yielded an "Indeterminate" result a second time before yielding a valid, correct result. The percent agreement with the expected result for the panel members for all sites combined is presented in Table 5.

| Panel Member
Concentration | Site 1 (A) | Site 2 (B) | Site 3 (D) | Total Agreement
(CI 95%) a |
|-------------------------------|------------|------------|------------|--------------------------------|
| Moderate Positive | 25/25 | 25/25 | 25/25 | 100% (75/75)
(95.1 - 100) |
| Low Positive | 24/25 | 25/25 | 24/25 | 97.3% (73/75)
(90.8 - 99.3) |
| Low Negative | 25/25 | 25/25 | 24/25 b | 98.7% (74/75)
(92.8 - 99.8) |
| Blank Negative | 25/25 | 25/25 | 25/25 | 100% (75/75)
(95.1 - 100) |

Table 5: Inter-Lab Reproducibility Performance Summary of the NeuMoDx™ GBS Assay

d The lower and upper limits of the presented 95% confidence interval (CI) were calculated using the 95% score confidence interval method.

b The Low Negative sample concentration is anticipated to be detected as positive ~5% of the time.

b. Linearity/Assay Reportable Range

Not applicable. The NeuMoDx™ GBS Assay is a qualitative test

c. Traceability, Stability, Expected Values

Traceability

Traceability to a certified control or calibrator is not applicable as there are no certified external controls or calibrators available for use with GBS assays. NeuMoDx developed internal sample processing controls, included in the assay reagents, to assure test methods were properly executed. The NeuMoDx™ GBS Assay Instructions for Use (IFU) contains a recommendation for external controls.

Product Lot and Serial Number traceability has been implemented through the use of Unique Device Identifier (UDI) and GS1 compatible 2D and 1D barcodes within the unit labeling. The GBS Test Strip as used for the GBS Assay contains a (device) serial number for each unit/piece.

Stability

Stability studies were performed to assess the in-use stability of the reagents and the shelf-life stability of the packaged NeuMoDx™ GBS Test Strip and the Lysis Buffer 4.

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d. Detection Limit

The Analytical Sensitivity of the NeuMoDx™ GBS Assay using the NeuMoDx™ GBS Test Strip was characterized by testing five different levels of GBS (ATCC BAA-611 serotype V) prepared from five independent clinical negative pools on the NeuMoDx™ 288 Molecular System.

The study was performed over non-consecutive days across multiple systems with each system processing ten replicates at each level per day. A unique lot of each of the following: NeuMoDx™ GBS Test Strip. NeuMoDx™ Extraction Plate and NeuMoDx™ Lysis Buffer 4 was tested on each System. Detection rates are depicted in the following table. The LoD was determined to be 500 CFU/mL.

| GBS CFU/mL | Number of
Valid Tests | Number of
Positives | Number of
Negatives | Detection
Rate |
|------------|--------------------------|------------------------|------------------------|-------------------|
| 1000 | 60 | 60 | 0 | 100% |
| 500* | 60 | 60 | 0 | 100% |
| 200 | 60 | 53 | 7 | 88% |
| 100 | 60 | 35 | 25 | 58% |
| 0 | 60 | 0 | 60 | 0% |

Positive percent detection rates for samples used to determine LoD of the NeuMoDx™ GBS Assay

*equivalent to 20 CFU/test

e. Analytical Reactivity (Inclusivity)

The NeuMoDx™ GBS Assay as implemented using the NeuMoDx™ GBS Test Strip detected all major serotypes of group B Streptococcus, including the four most clinically relevant. The twelve different strains of GBS bacteria spanning the serotypes that were tested using the NeuMoDx™ GBS Test Strip are shown in Table 6.

	Table 6: GBS Serotypes Tested

GBS Serotype	GBS Strain	ATCC/BEI#	Concentration (CFU/mL) with 100% Detection
Ia	A909	ATCC: BAA-1138	1500
Ib	H36b	ATCC: BAA-1174	1000
II	MNZ933	BEI: NR-43896	400
III	MNZ938	BEI: NR-43897	400
Ic	CDC SS700	ATCC: 27591	800
IV	2011201884	ATCC: BAA-2673	800
VI	2010228816	ATCC: BAA-2671	800
VII	4832-06	ATCC: BAA-2670	800
VIII	5030-08	ATCC: BAA-2669	800
IX	7509-07	ATCC: BAA-2668	800
Non-hemolytic	NCTC 8181	ATCC: 13813	800
TX Clinical Isolate 2012	SGBS030	BEI: NR-44144	800

f. Analytical Specificity (Exclusivity)

Analytical Specificity and Cross-reactivity

Analytical specificity was demonstrated by screening 136 organisms common to the urogenital and digestive tract, as well as species phylogenetically related to GBS for cross-reactivity on the NeuMoDx™ 288 Molecular System using the NeuMoDx™ GBS Test Strip. Organisms were prepared in pools of 5-6 and tested at a high concentration (bacteria 6 -9x106 CFU/mL; viruses 1x106-1x107 copies/mL).

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None of the organisms screened demonstrated cross-reactivity when implementing the NeuMoDx™ GBS Assay. The organisms tested are shown in Table 7.

Table 7: Pathogens Used to Demonstrate Analytical Specificity
---------------------------------------------------------------	--	--

Table 7: Pathogens Used to Demonstrate Analytical Specificity	Bacteria, Yeast and Parasites
Streptococcus pyogenes	Salmonella enterica (serovar Minnesota)	Cryptococcus neoformans
Streptococcus salivarius	Alcaligenes faecalis	Candida glabrata
Streptococcus sanguinis	Staphylococcus saprophyticus	Achromobacter xerosis
Moraxella (Branhamella) catarrhalis	Eikenella corrodens	Rhodospirillum rubrum
Neisseria gonorrhoeae	Enterococcus avium	Neisseria subflava
Streptococcus pyogenes	Micrococcus luteus	Pseudomonas putida
Streptococcus mitis	Citrobacter freundii	Bacillus subtilis
Lactococcus lactis;	Gemella haemolysans	Corynebacterium xerosis
Listeria monocytogenes	Kingella kingae	Mycobacterium smegmatis
Morganella morganii	Rahnella aquatilis	Legionella pneumophila
Plesiomonas shigelloides	Bacillus cereus	Moraxella lacunata
Proteus vulgaris	Aeromonas hydrophila	Streptomyces griseus
Salmonella enterica (serovar Typhi)	Enterobacter cloacae	Gardnerella vaginalis
Staphylococcus aureus	Brevibacterium linens	Clostridium perfringens
Staphylococcus epidermidis	Candida parapsilosis	Peptostreptococcus anaerobius
Streptococcus mutans	Lactobacillus brevis	Bifidobacterium adolescentis
Yersinia enterocolitica	Deinococcus radiodurans	Derxia gummosa
Providencia stuartii	Pseudomonas protegens	Veillonella parvula
Pseudomonas aeruginosa	Acinetobacter calcoaceticus	Mycoplasma pneumoniae
Acinetobacter Iwoffii	Lactobacillus acidophilus	Bacteroides fragilis
Proteus mirabilis	Vibrio parahaemolyticus	Acinetobacter baumannii
Klebsiella pneumoniae	Corynebacterium genitalium	Corynebacterium, strain HFH0082
Aerococcus viridans	Enterococcus faecalis	Enterobacter aerogenes
Enterococcus faecium	Salmonella enterica	Klebsiella oxytoca
Neisseria lactamica	Lactobacillus jensenii	Escherichia coli
Neisseria meningitidis	Lactobacillus delbrueckii	Streptococcus canis
Streptococcus pneumoniae	Serratia marcescens	Streptococcus dysgalactiae
Kingella denitrificans	Candida albicans	Streptococcus oralis
Haemophilus influenzae	Candida tropicalis	Streptococcus uberis
Neisseria perflava	Chromobacterium violaceum	Streptococcus suis
Moraxella osloensis	Candida krusei
Neisseria meningitidis Sero C	Saccharomyces cerevisiae
Neisseria meningitidis Sero A	Corynebacterium urealyticum
Streptococcus anginosus (Grp C)	MRSA	Viruses
Streptococcus bovis	Chlamydia trachomatis	CMV*
Streptococcus intermedius	Bifidobacterium breve	EBV (HHV-4)
Neisseria meningitidis M158 group D	Mobiluncus mulieris*	HSV1*
Neisseria flavescens	Propionibacterium acnes	HSV2*
Streptococcus parasanguinis	Campylobacter jejuni	VZV (HHV 3)*
Lactobacillus casei	Haemophilus ducreyi	HPV-16*
Lactobacillus lactis	Mycoplasma hominis	JC virus*
Haemophilus influenzae type B	Mycoplasma genitalium	BK virus
Salmonella newport	Trichomonas vaginalis	HHV-6A
Shigella flexneri	Pseudomonas fluorescens	HHV-6B
Shigella sonnei	Enterococcus dispar	HHV-7
Enterococcus durans	Ureaplasma urealyticum	HHV-8
Enterococcus sp. (ATCC® 202155™)	Chlamydia pneumoniae*

*Tested at 10 ng/ml

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g. Interference with Non-Target Organisms

The NeuMoDx™ GBS Assay was tested for interference in the presence of non-target organisms (co-habiting in the urogenital tract) by evaluating the performance of the assay at low levels of GBS on the NeuMoDx™ 288 Molecular System. The same panel of 136 organisms (Table 6) used for assessing cross-reactivity was used for this study. The organisms were pooled into groups of 5-6 in clinical negative Lim broth and spiked with 1200 CFU/mL cultured GBS. Testing validated detection of group B streptococcus in all of the pools tested. No interference due to commensal organisms was observed.

h. Interference with Exogenous and Endogenous Substances

The performance of the NeuMoDx™ GBS Assay was assessed on the NeuMoDx™ 288 Molecular System in the presence of exogenous and endogenous interfering substances which may typically be encountered in GBS clinical specimens. Each of the endogenous and exogenous substances listed, in Table 8, were added to pooled clinical negative Lim broth samples containing GBS at 1200 CFU/mL or 4000 CFU/mL. The 20 exogenous and 6 endogenous substances that were tested for interference using the NeuMoDx™ GBS Test Strip resulted in no adverse effect on detection of GBS at either level tested further demonstrating the robustness of the NeuMoDx™ GBS Assay.

Exogenous Substances			Endogenous Substances
Monistat® Cream			Human Amniotic Fluid
Yeast Gard Advanced™
(Douche)			Human Whole Blood
Metamucil® Fiber
Supplement			Human Urine
Ex-lax® (Chocolate
Pieces)			Human Fecal Sample
Phillips'® Milk of
Magnesia			Mucus
Pepto-Bismol™			Human Genomic DNA
Kaopectate®
	Dulcolax®
Suppositories	K-Y™ Jelly
	Fleet® Enema	McKesson Gel
	Preparation H®
Cream	Contraceptive Foam
	Vagisil™ Powder	Moisturizing Lotion
	Norforms®
Suppositories	Neutrogena® Body
oil
	FDS® Deodorant
Spray	Gold Bond® Powder
	New Mama
Bottom Spray

Table 8: Exogenous and Endogenous Interfering Agents tested

i. Carry-Over and Cross-Contamination Studies

Potential sample carry-over and cross-contamination studies were performed on the NeuMoDx™ 288 Molecular System using the NeuMoDx™ GBS Test Strip. The two-part study first evaluated the impact on GBS negative samples by being interspersed with samples containing high GBS target (at 1x107 CFU/mL). The positive and negative samples were loaded such that each negative sample was adjacent to a high positive sample. The second part of this study processed all negative samples immediately following a run which had processed all high GBS concentration samples.

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No contamination was seen in negative samples integrated with high level samples, or in negative samples that followed samples with high concentrations of GBS demonstrating the lack of any carry over and / or cross-contamination.

8. COMPARISON STUDIES

a. Method Comparison with Predicate Device Not Applicable
b. Matrix Comparison Not Applicable

9. CLINICAL PERFORMANCE SUMMARY

Clinical Performance

Performance characteristics were determined during a prospective clinical method comparison study conducted at three (3) geographically diverse laboratory locations to evaluate the comparative performance of the of the NeuMoDx™ GBS Assay as implemented on the NeuMoDx™ 288 Molecular System compared conventional to culture methods recommended by the Center for Disease Control (CDC) to identify GBS from subcultures of enriched Lim broth. Specimens eligible for enrollment were collected from pregnant women by health care providers for routine standard of care screening purposes recommended by the CDC between 35-37 weeks gestation.

The collected vaginal / rectal swab specimens were transported to the various laboratories in appropriate transport medium and then inoculated into a selective Lim broth medium by laboratory personnel in preparation to undergo an 18 - 24 hour incubation period. Following the incubation period and routine care testing, the residual Lim broth samples were subcultured to a sheep blood agar plate as recommended by the 2010 published CDC procedures for processing clinical specimens for culture of GBS. The agar plates were incubated for up to 48 hours and inspected for organisms suggestive of GBS. Suspected colonies were Gram-stained and the Gram-positive cocci colonies were tested for catalase production: Gram positive cocci colonies that tested negative for catalase production were worked-up for further identification by a streptococcal grouping latex agglutination test to determine the presence of GBS. Clinical performance is based on 1193 specimens with complete, valid, and compliant results included in the study and summarized in the tables below. The lower and upper limits of the presented 95% confidence interval (CI) were calculated using the 95% score confidence interval method.

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NeuMoDx™ GBS Assay Clinical Performance Summary

Clinical Site Summary		Culture / Reference Method
		Positive	Negative	Total
	Positive	253	37	290	Sensitivity = 96.9%
95% CI (94.1 - 98.4)
NeuMoDx
TM
GBS	Negative	8	895	903	Specificity = 96.0%
95% CI (94.6-97.1)
	Total	261	932	1193

Site Specific Clinical Performance of the NeuMoDx™ GBS Assay

| Site | n | Sensitivity
(95% CI) a | Specificity
(95% CI) a | Prevalence b
(95% CI) a |
|-------|------|---------------------------------|---------------------------------|----------------------------------|
| A | 351 | 92.4%
73/79
(84.4-96.5) | 96.7%
263/272
(93.8-98.3) | 22.5%
79/351
(15.1-22.2) |
| B | 400 | 98.4%
62/63
(91.5-99.7) | 94.4%
318/337
(91.4-96.4) | 15.8%
63/400
(10.8-17.0) |
| C | 442 | 99.2%
118/119
(95.4-99.9) | 97.2%
314/323
(94.8-98.5) | 26.9%
119/442
(18.2-24.7) |
| Total | 1193 | 96.9%
253/261
(94.1-98.4) | 96.0%
895/932
(94.6-97.1) | 21.9%
261/1193
(19.6-24.3) |

a The lower and upper limits of the presented 95% confidence interval (CI) were calculated using the 95% score confidence interval method.

b Prevalence calculations based on reference method results obtained by following the CDC-recommended procedures for processing clinical specimens for culture of group B Streptocccus. (Published 2010)

INSTRUMENT NAME

NeuMoDx™ 288 Molecular System

1. SYSTEM SOFTWARE
  FDA has reviewed applicant's Hazard Analysis and software development processes for this line of product types:

Yes X No __

11. CONCLUSIONS DRAWN FROM NON-CLINICAL AND CLINICAL TESTS

The subject device and the predicate device are substantially equivalent, with respect to intended use, instructions for use, design features, technological characteristics, manufacturing methods, performance criteria, special controls, and safety and effectiveness. The subject device is substantially equivalent to the predicate device (K090191).

CONCLUSION Based on the information contained herein, we conclude the NeuMoDx™ GBS Assay (subject device) when implemented on the NeuMoDx™ 288 Molecular System is substantially equivalent to the legally marketed predicate device (K090191), and is safe and effective for its labeled intended use.