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.

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.

AI/ML Overview

The provided text describes the NeuMoDx™ GBS Assay, an in vitro diagnostic test for Group B Streptococcus (GBS), and its performance data to establish substantial equivalence to a predicate device. This is a molecular diagnostic test, not an AI/imaging device, so many of the requested elements pertaining to AI and imaging studies (e.g., number of experts, adjudication methods, MRMC studies, effect size of human readers improving with AI) are not applicable. However, I will detail the available information relevant to acceptance criteria and performance as presented in the document.

Here's a breakdown of the acceptance criteria and study proving the device meets them, based on the provided FDA 510(k) summary:

Acceptance Criteria and Reported Device Performance

Note: For molecular diagnostic devices, acceptance criteria are typically defined by performance characteristics such as sensitivity, specificity, Limit of Detection (LoD), inclusivity, and exclusivity. The document doesn't explicitly state "acceptance criteria" for clinical performance in a table, but it presents the results of a comparative study against a reference method, which implicitly serves as the standard for acceptance. For analytical performance, criteria are demonstrated through detailed studies (e.g., 100% detection rate at LoD).

Clinical Performance:

Performance Metric	Acceptance Criteria (Implied/Expected)	Reported Device Performance (NeuMoDx™ GBS Assay)
Sensitivity	High detection rate of true positives	96.9% (253/261) 95% CI (94.1 - 98.4)
Specificity	High detection rate of true negatives	96.0% (895/932) 95% CI (94.6-97.1)

Analytical Performance:

Performance Metric	Acceptance Criteria (Implied/Expected)	Reported Device Performance (NeuMoDx™ GBS Assay)
Limit of Detection (LoD)	Concentration at which 95% or 100% of replicates are detected.	500 CFU/mL (100% detection at 500 CFU/mL)
Precision/Reproducibility	Consistent results across instruments, operators, and sites, with low variability.	Demonstrated with high percent positive/negative rates across runs, operators, and sites (e.g., 97.7% for Low Positive, 98.7% for Low Negative in Inter-Lab Reproducibility).
Analytical Reactivity (Inclusivity)	Detection of all major GBS serotypes.	Detected all 12 tested GBS strains/serotypes at 100% detection (concentrations 400-1500 CFU/mL).
Analytical Specificity (Exclusivity)	No cross-reactivity with common urogenital/digestive organisms or related species.	None of 136 screened organisms demonstrated cross-reactivity.
Interference	No adverse effect on detection in presence of exogenous/endogenous substances.	No adverse effect on GBS detection observed in the presence of 20 exogenous and 6 endogenous interfering substances.
Carry-Over/Cross-Contamination	No contamination in negative samples adjacent to/following high positive samples.	No contamination observed.

Study Details:

A table of acceptance criteria and the reported device performance: Done in the table above.
Sample size used for the test set and the data provenance:
- Clinical Performance Test Set: 1193 specimens with complete, valid, and compliant results were included in the study.
- Data Provenance: The study was a "prospective clinical method comparison study" conducted at "three (3) geographically diverse laboratory locations." The data were collected from pregnant women in the US (implied by FDA submission to US authority). Specimens were collected for "routine standard of care screening purposes."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- This is a molecular diagnostic test. The "ground truth" for clinical performance was established by "conventional culture methods recommended by the Center for Disease Control (CDC) to identify GBS from subcultures of enriched Lim broth." This involves laboratory procedures and standard microbiological protocols rather than expert human interpretation of images. Therefore, the concept of "experts" as in radiologists for imaging is not directly applicable here.
- The document implies that "qualified laboratory personnel" were involved in processing samples and establishing the ground truth via culture.
Adjudication method (e.g., 2+1, 3+1, none) for the test set:
- Not applicable as this is a molecular diagnostic test where the ground truth is established by a predefined laboratory culture method, not human adjudication of ambiguous cases. Discordant results between the device and the reference culture method would be analyzed, but not "adjudicated" in the sense of multiple human readers coming to a consensus.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- Not applicable. This is a standalone diagnostic device (an automated in vitro diagnostic test) and not an AI-assisted imaging device. There are no "human readers" in the context of interpreting the primary test output or "AI assistance" provided to human readers.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, the performance characteristics (sensitivity, specificity, LoD, inclusivity, exclusivity, etc.) described for the NeuMoDx™ GBS Assay are "standalone" performance, meaning they relate directly to the output of the automated system. The device automatically determines "Positive, Negative, Indeterminate or Unresolved" results based on pre-established decision criteria (Table 1).
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Clinical Performance Ground Truth: "Conventional culture methods recommended by the Center for Disease Control (CDC) to identify GBS from subcultures of enriched Lim broth" (specifically the 2010 CDC guidelines). This is a laboratory-based reference method, considered the "gold standard" for GBS colonization status.
- Analytical Performance Ground Truth: Established through prepared spiked samples with known concentrations (CFU/mL) of GBS and other organisms.
The sample size for the training set:
- The document describes a 510(k) submission for substantial equivalence, not a de novo premarket submission that typically details a separate training set for a machine learning algorithm.
- For a molecular diagnostic test like this, "training" often refers to the internal development and optimization of the assay parameters using characterized samples, rather than a distinct "training set" in the machine learning sense. The document does not specify a formal "training set" size.
How the ground truth for the training set was established:
- As noted above, a formal machine learning "training set" is not explicitly defined. Assay development and optimization would have relied on internally validated methods and known concentrations of GBS and non-GBS organisms to establish parameters such as Ct thresholds and call criteria (Table 1). This process implicitly establishes the "ground truth" for the test's internal logic.

Summary

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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

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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

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Indications for Use

510(k) Number (if known) K173725

Device Name NeuMoDx™ GBS Assay

Indications for Use (Describe)

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 Information:	NeuMoDx Molecular, Inc.1250 Eisenhower PlaceAnn Arbor, MI 48108 USA
Contact Information:
Primary Contact:	Kay Fuller, RACPrincipal Regulatory ConsultantMedical Device Regulatory Solutions, LLC734-846-7852
Secondary Contact:	Dawn RossSr. Director Quality AssuranceNeuMoDx Molecular, Inc.
DEVICE INFORMATION
Device Name:	GBS Assay
Proprietary Name:	NeuMoDx™ GBS Assay
Common Name:	Group B Strep Assay
Classification Name:	Nucleic Acid Amplification Assay System, Group BStreptococcus, Direct Specimen Test
Classification Code:	NJR - PrimaryOOI - Secondary
Classification:	Class I
FDA Review Panel:	83 - Microbiology
Regulation Number:	21 CFR §866.3740
PREDICATE DEVICE	BD Max™ GBS Assay (K090191)
DEVICE DESCRIPTION

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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.

Table 1

Result	GBS Ct	Sample Process Control (SPC1) Ct
Positive	9 < Ct < 37And EP > 3000	N/A
Negative	N/A OR Ct < 9 OR > 37	25 < Ct < 35And EP > 2000
Indeterminate	N/ASYSTEM ERROR NOTED	N/ASYSTEM 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

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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 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

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

FeatureComparisonCriteria	Subject DeviceNeuMoDx™ GBS AssayK173725	Predicate DeviceBD MAX™ GBS AssayK090191	SubjectDevice SEto K090191?
21 CFR Reg #, ProductCode & Classification	21 CFR §866.3740NJRClass I	21 CFR §866.3740NJRClass I	Yes
Regulation Name	Nucleic Acid Amplification AssaySystem, 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 implementedon the NeuMoDx™ 288 Molecular System is aqualitative in vitro diagnostic test designedto detect Group B Streptococcus (GBS) DNAfrom 18-24 hour Lim broth enrichments ofvaginal/rectal swabs from pregnant women.The test incorporates automated DNAextraction to isolate the target nucleic acidfrom the specimen and real-time polymerasechain reaction (PCR) to detect an 88 bpregion of the PcsB gene sequence in theStreptococcus agalactiae chromosome.Results from the NeuMoDx™ GBS Assay canbe used as an aid in determining colonizationstatus in antepartum women.The NeuMoDx™ GBS Assay does notprovide susceptibility results. Culturedisolates are needed for performingsusceptibility testing as recommended forpenicillin-allergic women.	The BD MAX™ GBS Assay as implemented on theBD MAX™ System is a qualitative in vitrodiagnostic test designed to detect Group BStreptococcus (GBS) DNA in Lim Broth culturesafter incubation for greater than or equal to (>)18hours, obtained from vaginal and rectal swabspecimens from antepartum pregnant women.The test incorporates automated DNA extractionto isolate the target nucleic acid from thespecimen and real-time polymerase chain reaction(PCR) to detect a 124 bp region of the cfb genesequence of the Streptococcus agalactiaechromosome. Results from the BD MAX™ GBSAssay can be used as an aid in determiningcolonization status in antepartum women.The BD MAX™ GBS Assay does not providesusceptibility results. Cultured isolates areneeded for performing susceptibility testing asrecommended for penicillin-allergic women.Subculture to solidmedia for additional testingwhen 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 CollectionMedia Type	Amies or Stuart	Amies or Stuart	Yes
Sample PreparationMethod	Sample Preparation for Nucleic AcidExtraction is automated on NeuMoDx™288 Molecular System	Sample Preparation for Nucleic AcidExtraction is automated on BD MAX System	Yes
Sample Matrix	Enriched in overnight LIM	Enriched in overnight LIM	Yes
Test ReferenceComparison Method	CDC GBS 2010 Guidelines of CultureProcessing/Identification Procedure	CDC GBS 2002 Guidelines of CultureProcessing/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 PCRamplification	Yes
DNA TargetSequence	88 bp region of the PcsB gene sequencein the Streptococcus agalactiaechromosome	124 bp region of the cfb gene sequence ofthe Streptococcus agalactiae chromosome	Yes
Probes	TaqMan®	Scorpion	Yes
Single Use	Yes	Yes	Yes
User / skill required	Moderate ComplexityRx only - QualifiedLaboratory PersonnelBuilt in protocolNo data interpretationrequired	Moderate ComplexityNo special skills requiredBuilt in protocolNo data interpretationrequired	Yes
Automatic Assay	Yes - Built-in Result Interpretation	Yes - Built-in Result Interpretation	Yes
Internal ProcessControl	Sample process control is extracted andamplified with each sample as a processmonitor	Extraction and PCR internal process controlis a process monitor	Yes
External Control	Not provided by NeuMoDx; commercialmaterials available.Not required to perform testing.Appropriate controls and testingintervals must be determined by thelaboratory	Materials available commercially but notrequired 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	DetectedPos/Total	%Positive	Ave Ct	StdDev	% CV*	DetectedPos/Total	%Positive	Ave Ct	StdDev	% CV	DetectedPos/Total	%Positive	Ave Ct	StdDev	% 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 MemberConcentration	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 ofValid Tests	Number ofPositives	Number ofNegatives	DetectionRate
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® FiberSupplement			Human Urine
Ex-lax® (ChocolatePieces)			Human Fecal Sample
Phillips'® Milk ofMagnesia			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® Bodyoil
	FDS® DeodorantSpray	Gold Bond® Powder
	New MamaBottom 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)
NeuMoDxTMGBS	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.

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.