Predicate Devices

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device is a quality control kit for a nucleic acid test and does not describe any analytical or interpretive functions that would typically involve AI/ML.

Therapeutic

No.
This device is a quality control kit for an in vitro diagnostic test, specifically designed to monitor the performance of another diagnostic device. It does not provide any treatment or therapy to a patient.

Diagnostic

No

Explanation: The device is described as an external positive and negative assayed control to monitor the performance of another diagnostic device (Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test). It is a quality control product, not a diagnostic device itself.

SaMD (Software as a Medical Device)

No

The device description explicitly states the product is a "quality control kit consisting of positive and negative controls" and contains "stabilized blood components, blood culture media components, and inactivated, intact microorganisms," which are physical components, not software.

IVD (In Vitro Diagnostic)

Based on the provided text, this device is an IVD (In Vitro Diagnostic).

Here's why:

Intended Use: The intended use explicitly states it's for "use as an external positive and negative assayed control to monitor the performance of the qualitative detection of Gram-Negative bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems." This describes a product used in vitro (outside the body) to assess the performance of another diagnostic test.
Device Description: The description further clarifies that it's a "quality control kit" for a specific diagnostic test. It details the components and how it functions to evaluate the analytical process of the diagnostic test.
Performance Studies: The inclusion of performance studies like precision, stability, and matrix effect are typical for IVD devices to demonstrate their reliability and suitability for their intended purpose.
Predicate Device: The mention of a predicate device (K212576 - MDx-Chex for BCID2) which is also a quality control for an IVD test, further supports its classification as an IVD.

Quality control materials used to monitor the performance of diagnostic tests are considered IVDs themselves because they are used in vitro to provide information about the reliability of a diagnostic procedure.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

MDx-Chex™ for BC-GN is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of Gram-Negative bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GN Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive Control: Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Species: Acinetobacter spe., Citrobacter spp., Enterobacter spp., Proteus spp.; antimicrobial resistance genes: CTX-M, IMP, KPC, NDM, OXA and VIM. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.

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

PMN

Device Description

MDx-Chex™ for BC-GN is a quality control kit consisting of positive and negative controls for the Luminex VERIGENE® Gram-Negative Blood Culture Test (BC-GN). The MDx-Chex™ for BC-GN Positive Control is positive for pathogens and resistance mechanisms in the VERIGENE BC-GN test (See Table 1). The MDx-Chex™ for BC-GN Negative Control is negative for pathogens and resistance mechanisms in the VERIGENE BC-GN test. Each control mix also controls for blood and blood culture media components that have been identified is inhibitors to DNA hybridization assays, namely hemoglobin, leukocyte DNA, and anticoagulants.

The MDx-Chex™ for BC-GN quality control kit contains stabilized blood components, blood culture media components, and inactivated, intact microorganisms resulting in a full-process, cellular-based control for the Luminex VERIGENE BC-GN panel. Use of full-process cellular controls are necessary to evaluate the entire analytical process, including sample lysis, nucleic acid isolation, DNA hybridization detection, and analysis, as well as the impact of inhibitors present in blood culture samples and preanalytical variables. Routine use of full process quality controls can help identify variations in the test system that can lead to incorrect results.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

Not Found

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

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)

Multi-Site Precision (Reproducibility)

Study Type: Multi-site precision (reproducibility) study.
Sample Size: 10 positive control samples and 10 negative control samples per lot for each of 3 lots, total of 30 samples per control type (60 overall per lot). A total of 180 runs (90 positive, 90 negative) were generated.
Key Results:
- All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results.
- Positive Percent Agreement (all sites combined): 99% (89/90) with 95% Confidence Interval of 94% - 100%.
- Negative Percent Agreement (all sites combined): 100% (90/90) with 95% Confidence Interval of 96% - 100%.
- The data supports that there are no significant differences between different operators and different sites (instruments) on different days when testing different control lots.

Single-Site Precision (Repeatability)

Study Type: Single-site precision (repeatability) study.
Sample Size: 20 samples per control type (positive and negative control tubes), 40 samples per MDx-Chex™ for BC-GN lot (for 3 lots), tested over 20 days. A total of 120 runs (20 runs per control type per lot) were generated.
Key Results:
- All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results.
- Repeatability of Positive Control: 98% Positive Percent Agreement (59/60) with 95% Confidence Interval of 91% - 100%.
- Repeatability of Negative Control: 100% Negative Percent Agreement (60/60) with 95% Confidence Interval of 94% - 100%.
- The results support the conclusion that MDx-Chex™ for BC-GN shows repeatability across three separately manufactured control lots when used with the Luminex BC-GN panels.

Lot-to-Lot Reproducibility

Study Type: Lot-to-lot reproducibility and within-run precision study.
Sample Size: Lot-to-lot: 10 positive and 10 negative control tubes per lot for 3 lots (30 data points per control type). Within-run: 10 tests for each positive and negative control tube from one lot (total of 20 tests).
Key Results:
- All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results for lot-to-lot and within-run precision.
- Across the three lots tested for Lot-to-Lot precision, all showed 100% agreement for both Positive and Negative Controls (10/10), with 95% Confidence Intervals of 69% - 100%.
- Within-Run precision for the positive and negative controls also showed 100% agreement (10/10) with 95% Confidence Intervals of 69% - 100%.
- The results support that MDx-Chex™ for BC-GN is reproducible across three separately manufactured lots and demonstrates no significant differences in results within a run of a control lot.

Closed-Vial Stability and Shipping Stability

Study Type: Closed-vial stability and shipping stability studies.
Sample Size: Closed-vial: 20 positive and 20 negative control samples per lot (3 lots) at different timepoints and temperatures. Shipping: 20 samples per control type (positive and negative) for each simulated shipping profile.
Key Results:
- All MDx-Chex™ for BC-GN Positive and Negative Control lots passed closed-vial stability, and summer and winter shipping conditions with ≥ 90% agreement with expected results.
- Closed-vial stability results for both positive and negative controls showed 100% agreement (60/60) at Day 0, Day 61+ (2-8°C), and Day 61+ (20-25°C), with 95% Confidence Intervals of 94% - 100%. Some individual lot data for positive control at 20-25C showed slightly lower but acceptable agreement (95% and 90%).
- Shipping study results showed 100% agreement (20/20) for both positive and negative controls under summer and winter conditions, across both 2-8°C and 20-25°C storage temperatures, with 95% Confidence Intervals of 83% - 100%.
- The data supports that MDx-Chex™ for BC-GN Control kit is stable for a minimum of 60 days when stored at 2-25°C and is stable and functional after exposure to extreme summer and winter shipping temperature conditions.

Matrix Effect

Study Type: Matrix effect study.
Sample Size: Triplicate samples for simulated positive MDx-Chex™ for BC-GN matrix, simulated positive clinical sample, simulated negative MDx-Chex™ for BC-GN matrix, and simulated negative clinical sample.
Key Results:
- The simulated positive MDx-Chex™ for BC-GN matrix and simulated positive clinical sample passed with ≥ 90% agreement for positive detection of analyte (100% agreement, 3/3, with 95% Confidence Interval of 29% - 100%).
- The simulated negative MDx-Chex™ for BC-GN matrix and simulated negative clinical sample passed with ≥ 90% agreement for negative detection of analyte (100% agreement, 3/3, with 95% Confidence Interval of 29% - 100%).
- The results demonstrate that MDx-Chex™ for BC-GN matrix has no effect on target detection (no inhibition and/or false negative results) when tested with the Luminex BC-GN panel, and data was consistent with the results of simulated blood culture samples.

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

Not Found

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.

K212576

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

§ 866.3920 Assayed quality control material for clinical microbiology assays.

(a)
Identification. An assayed quality control material for clinical microbiology assays is a device indicated for use in a test system to estimate test precision or to detect systematic analytical deviations that may arise from reagent or analytical instrument variation. This type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
(i) Analyte concentration;
(ii) Expected values;
(iii) Analyte source;
(iv) Base matrix;
(v) Added components;
(vi) Safety and handling information; and
(vii) Detailed instructions for use.
(2) Premarket notification submissions must include detailed documentation, including line data as well as detailed study protocols and a statistical analysis plan used to establish performance, including:
(i) Description of the process for value assignment and validation.
(ii) Description of the protocol(s) used to establish stability.
(iii) Line data establishing precision/reproducibility.
(iv) Where applicable, assessment of matrix effects and any significant differences between the quality control material and typical patient samples in terms of conditions known to cause analytical error or affect assay performance.
(v) Where applicable, identify or define traceability or relationship to a domestic or international standard reference material and/or method.
(vi) Where applicable, detailed documentation related to studies for surrogate controls.
(3) Premarket notification submissions must include an adequate mitigation (e.g., real-time stability program) to the risk of false results due to potential modifications to the assays specified in the device's 21 CFR 809.10 compliant labeling.
(4) Your 21 CFR 809.10 compliant labeling must include the following:
(i) The intended use of your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following:
(A) Assayed control material analyte(s);
(B) Whether the material is intended for quantitative or qualitative assays;
(C) Stating if the material is a surrogate control; and
(D) The system(s), instrument(s), or test(s) for which the quality control material is intended.
(ii) The intended use in your 21 CFR 809.10(a)(2) and (b)(2) compliant labeling must include the following statement: “This product is not intended to replace manufacturer controls provided with the device.”
(iii) A limiting statement that reads “Quality control materials should be used in accordance with local, state, federal regulations, and accreditation requirements.”

Summary

0

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 and Human Services logo. To the right of that 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.

July 27, 2023

Streck Cody Janssen Regulatory Affairs Coordinator 7002 S. 109th Street La Vista, Nebraska 68128

Re: K231223

Trade/Device Name: MDx-Chex for BC-GN Regulation Number: 21 CFR 866.3920 Regulation Name: Assayed Quality Control Material For Clinical Microbiology Assays Regulatory Class: Class II Product Code: PMN Dated: April 26, 2023 Received: April 28, 2023

Dear Cody Janssen:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

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

1

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

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

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/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely. Digitally signed by Bryan M. Bryan M. Grabias -S Grabias -S -S Date: 2023.07.27 for Noel J. Gerald, Ph. D. Branch Chief Bacterial Respiratory and Medical Countermeasures Branch Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

2

Indications for Use

510(k) Number (if known) K231223

Device Name MDx-Chex™ for BC-GN

Indications for Use (Describe)

MDx-Chex™ for BC-GN is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of Gram-Negative bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GN Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive Control: Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Species: Acinetobacter spe., Citrobacter spp., Enterobacter spp., Proteus spp.; antimicrobial resistance genes: CTX-M, IMP, KPC, NDM, OXA and VIM. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.

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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3

| 510(k) Submitter: | Streck
7002 S. 109th Street
La Vista, NE 68128 |
|--------------------------------------------|-----------------------------------------------------------------------------------------------|
| Official Correspondent:
Address: | Cody Janssen
7002 S. 109th Street
La Vista, NE 68128 |
| Phone:
Fax:
Email:
Date Prepared: | 402-537-5216
402-537-5317
CJanssen@Streck.com
July 24, 2023 |
| Names
Trade Name:
Common Name: | MDx-Chex™ for BC-GN
Quality Control Material for Microbiology
Assays |
| Device Type: | Assayed external control material for microbiology
nucleic acid amplification (NAT) assays |
| Product Code:
Panel: | PMN (21 CFR 866.3920)
Microbiology |
| Predicate Device: | K212576 - MDx-Chex for BCID2 |

Device Description

MDx-Chex™ for BC-GN is a quality control kit consisting of positive and negative controls for the Luminex VERIGENE® Gram-Negative Blood Culture Test (BC-GN). The MDx-Chex™ for BC-GN Positive Control is positive for pathogens and resistance mechanisms in the VERIGENE BC-GN test (See Table 1). The MDx-Chex™ for BC-GN Negative Control is negative for pathogens and resistance mechanisms in the VERIGENE BC-GN test. Each control mix also controls for blood and blood culture media components that have been identified is inhibitors to DNA hybridization assays, namely hemoglobin, leukocyte DNA, and anticoagulants.

4

Table 1 - Pathogens and antimicrobial resistance genes detected by MDx-Chex™ for BC-GN Control Kit.

Gram-negative bacteria and resistance genes
Pathogen/Resistance gene	Positive Control	Negative Control
Acinetobacter spp.	Detected	Not Detected
Citrobacter spp.	Detected	Not Detected
Enterobacter spp.	Detected	Not Detected
Escherichia coli	Detected	Not Detected
Klebsiella oxytoca	Detected	Not Detected
Klebsiella pneumoniae	Detected	Not Detected
Proteus spp.	Detected	Not Detected
Pseudomonas aeruginosa	Detected	Not Detected
CTX-M	Detected	Not Detected
IMP	Detected	Not Detected
KPC	Detected	Not Detected
NDM	Detected	Not Detected
OXA	Detected	Not Detected
VIM	Detected	Not Detected

The MDx-Chex™ for BC-GN quality control kit contains stabilized blood components, blood culture media components, and inactivated, intact microorganisms resulting in a full-process, cellular-based control for the Luminex VERIGENE BC-GN panel. Use of full-process cellular controls are necessary to evaluate the entire analytical process, including sample lysis, nucleic acid isolation, DNA hybridization detection, and analysis, as well as the impact of inhibitors present in blood culture samples and preanalytical variables. Routine use of full process quality controls can help identify variations in the test system that can lead to incorrect results.

Intended Use

MDx-Chex™ for BC-GN is intended for use as an external positive and negative assayed control to monitor the performance of the qualitative detection of Gram-negative bacteria and associated antimicrobial resistance genes, by the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) on Luminex VERIGENE® systems. The MDx-Chex™ for BC-GN Positive and Negative Controls are composed of a buffered solution with stabilized erythrocytes and leukocytes in a matrix of blood culture media components. Positive Control: Gram-negative bacteria: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Species: Acinetobacter spp., Citrobacter spp., Enterobacter spp., Proteus spp.; antimicrobial resistance genes: CTX-M, IMP, KPC, NDM, OXA, and VIM. Negative Control: buffered solution only. This product is not intended to replace manufacturer controls provided with the device.

5

Comparison to Predicate Device

Device and Predicate Device:	K231223	K212576
Device Trade Name	Candidate Device: MDx-Chex™ for BC-GN	Predicate Device: Streck MDx-Chex for BCID2
General Device Characteristic Similarities
Intended use	MDx-Chex™ for BC-GN is
intended for use as an external
positive and negative assayed
control to monitor the
performance of the qualitative
detection of Gram-negative
bacteria and associated
antimicrobial resistance genes,
by the Luminex VERIGENE®
Gram-Negative Blood Culture
Nucleic Acid Test (BC-GN) on
Luminex VERIGENE® systems.
The MDx-Chex™ for BC-GN
Positive and Negative Controls
are composed of a buffered
solution with stabilized
erythrocytes and leukocytes in a
matrix of blood culture media
components. Positive Control:
Gram-negative bacteria:
Escherichia coli, Klebsiella
pneumoniae, Klebsiella oxytoca,
Pseudomonas aeruginosa,
Species: Acinetobacter spp.,
Citrobacter spp., Enterobacter
spp., Proteus spp.; antimicrobial
resistance genes: CTX-M, IMP,
KPC, NDM, OXA, and VIM.
Negative Control: buffered
solution only. This product is not
intended to replace
manufacturer controls provided
with the device.	MDx-Chex for BCID2 is
intended for use as an external
positive and negative assayed
control to monitor the
performance of the qualitative
detection of yeast, Gram-
positive and Gram-negative
bacteria, as well as associated
antimicrobial resistance genes,
by the BIOFIRE® Blood Culture
Identification 2 (BCID2) Panel
on BIOFIRE FilmArray®
systems. Control 1-GN: Gram-
negative bacteria:
Acinetobacter calcoaceticus-
baumannii complex,
Bacteroides fragilis,
Enterobacter cloacae complex,
Escherichia coli, Klebsiella
aerogenes, Klebsiella oxytoca,
Klebsiella pneumoniae group,
Proteus spp., Salmonella spp.,
Serratia marcescens,
Haemophilus influenzae,
Neisseria meningitidis,
Pseudomonas aeruginosa,
Stenotrophomonas maltophilia;
antimicrobial resistance genes:
KPC, CTX-M, IMP, NDM, OXA-
48-like, VIM, mcr-1. Control 2-
GPY: Gram-positive bacteria:
Enterococcus faecalis,
Enterococcus faecium, Listeria
monocytogenes,
Staphylococcus aureus,
Staphylococcus epidermidis,
Staphylococcus lugdunensis,
Streptococcus agalactiae,
Streptococcus pneumoniae,
Streptococcus pyogenes;
yeast: Candida albicans
		Candida auris, Candida
glabrata, Candida krusei,
Candida parapsilosis, Candida
tropicalis, Cryptococcus
neoformans/gatti; antimicrobial
resistance genes: mecA/C and
MREJ, vanA/B. This product is
not intended to replace
manufacturer controls provided
with the device.
Physical Format	Ready-to-Use Liquid	Same
Direction for Use	Process like a patient sample	Same
Composition	Intact inactivated bacteria,
human erythrocytes and
leukocytes, and relevant
components of blood culture
media	Same
General Device
Characteristic
Differences
Assay Steps Monitored	Lysis, nucleic acid
isolation/purification/inhibitor
removal, DNA hybridization,
detection, identification/data
reporting	Lysis, nucleic acid
isolation/purification/PCR
inhibitor removal, amplification,
detection, identification/data
reporting
Number of targets
monitored in one assay	Multiple, 14 targets	Multiple, >30 targets
(22 gram-negative)

6

Discussion of Tests and Test Results

To substantiate the product performance claims for MDx-Chex™ for BC-GN, Streck collected product performance data for the following studies:

· Multi-Site Precision (Reproducibility),
· Single-Site Precision (Repeatability),
Lot-to-Lot Reproducibility
Closed-Vial Stability and Shipping Stability
Matrix Effect

7

Multi-Site Precision (Reproducibility)

Testing was completed at three (3) sites and consisted of 10 positive control samples and 10 negative control samples for each MDx-Chex™ for BC-GN lot for a total of 30 samples per control type (positive and negative control tubes), 60 samples per lot, tested on different days (2 vials x 1 lot x 1 day, for 10 days and 3 different lots). A total of 180 runs (90 runs per MDx-Chex™ for BC-GN control type: control type = positive or negative control) were generated for data analysis from all testing sites and all MDx-Chex™ for BC-GN lots.

Three lots were used for this study, (#22343, #22353, #22355), at least three Luminex BC-GN panel lots, three locations and at least three operators were included in the study. The data supports that there are no significant differences between different operators and different sites (instruments) on different days when testing different control lots. All samples were prepared and analyzed on the Luminex VERIGENE System Instrument per the control Instructions for Use.

All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results. The results support the conclusion that MDx-Chex™ for BC-GN shows reproducibility across three separately manufactured control lots between sites, days, and operators when used with the Luminex BC-GN panels on different Luminex VERIGENE systems.

	Site #1		Site #2		Site #3
Category	#
Observed
Results/#
Expected
Results¹	Positive
Percent
Agreement	#
Observed
Results/#
Expected
Results¹	Positive
Percent
Agreement	#
Observed
Results/#
Expected
Results¹	Positive
Percent
Agreement	Percent
Agreement
(all sites
combined)	95%
Confidence
Interval
MDx for
BC-GN
Positive
Control	29/30*	97%	30/30	100%	30/30	100%	99%
(89/90)	94%

100% |

Multi-site Precision (Reproducibility) Positive Percent Agreement

"One Positive Control gave initial false negative expected result upon a single relest. The relest un is not included in total number of tests included in this study

ted result for the Positive Control is positive

Multi-site Precision (Reproducibility) Negative Percent Agreement

	Site #1		Site #2	Site #3
Category	#
Observed
Results/#
Expected
Results 1	Negative
Percent
Agreement	#Observed
Results/#
Expected
Results 1	Negative
Percent
Agreement	#
Observed
Results/#
Expected
Results 1	Negative
Percent
Agreement	Percent
Agreement
(all sites
combined)	95%
Confidence
Interval
MDx for
BC-GN
Negative
Control	30/30	100%	30/30	100%	30/30	100%	100%
(90/90)	96%
100% -

Expected Results for the Negative Control is negative

Single-Site Precision (Repeatability)

The repeatability of MDx-Chex™ for BC-GN was evaluated using three separately manufactured lots of control. Each lot was tested using the Luminex VERIGENE System. A minimum of three Luminex BC-GN panel lots were used.

8

Three MDx-Chex™ for BC-GN lots (#22343, #22353, #22355), at least three Luminex BC-GN panel lots and a minimum of two operators were included in the study. Testing consisted of 20 samples per control type (positive and negative control tubes), 40 samples per MDx-Chex™ for BC-GN lot, tested over 20 days. A total of 120 runs (20 runs per MDx-Chex™ for BC-GN control type; control type = positive or negative control) were generated for data analysis for all MDx-Chex™ for BC-GN lots.

Samples were prepared according to MDx-Chex™ for BC-GN control instructions. Samples were analyzed on the Luminex VERIGENE System per the Instructions for Use. All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results. The results support the conclusion that MDx-Chex™ for BC-GN shows repeatability across three separately manufactured control lots when used with the Luminex BC-GN panels.

Table 1: Repeatability of MDx-Chex™ for BC-GN Positive Control: Positive Percent Agreement

| Category | # Observed Results/

Expected Results 1 | Positive Percent

Agreement | 95% Confidence
Interval |
|-----------------------------------------|---------------------------------------------|-------------------------------|----------------------------|
| MDx-Chex TM for BC-GN, Positive Control | 59/60* | 98% | 91% - 100% |

One Positive Control gave initial false negative result upon a single retest. The retest un is not included in the above calculation. Expected result for the Positive Control is positive.

Table 2: Repeatability of MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement

| Category | # Observed Results/

Expected Results 1 | Negative Percent

Agreement | 95% Confidence
Interval |
|----------------------------------------------|---------------------------------------------|-------------------------------|----------------------------|
| MDx-Chex™ for BC-
GN, Negative
Control | 60/60 | 100% | 94% - 100% |

1 Expected result for the Negative Control is negative

Lot-to-Lot Reproducibility

The reproducibility of MDx-Chex™ for BC-GN was evaluated using three separately manufactured lots (#22343, #22353, #22355) manufactured lots of control. Samples were prepared per the control Instructions for Use (IFU) prior to testing with the same Luminex BC-GN panel lot tested on one Luminex VERIGENE System over multiple days.

The within-run precision study was performed to assess performance of one MDx-Chex™ for BC-GN lot (#22343), using the same Luminex BC-GN panel lot tested on the same day with one Luminex VERIGENE System.

For the Lot-to-lot study, data from 10 positive and negative control tubes, tested on the same VERIGENE System, were used for data analysis for each control tube per MDx-Chex™ for BC-GN lot (30 data points per control type) for a total of 60 data points from three MDx-Chex™ for BC-GN lots.

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The within-run precision study consisted of 10 tests for each positive and negative control tube generated from one MDx-Chex™ for BC-GN lot (total of 20 tests per control kit). For this study, Day 60 (2C) closed-vial stability data were used to demonstrate the within-run precision.

All MDx-Chex™ for BC-GN Positive and Negative Control lots passed with ≥ 90% agreement with expected results. The results support that MDx-Chex™ for BC-GN is reproducible across three separately manufactured lots when used with the Luminex VERIGENE BC-GN panel. The results also demonstrate that there are not significant differences in results within run of a control lot.

Table 1: Lot-to-Lot Precision Summary for MDx-Chex™ for BC-GN Positive Control: Positive Percent Agreement

| Category | # Lot | # Observed Results/#
Expected Results1 | Positive Percent
Agreement | 95% Confidence
Interval |
|-----------------------------------------------|-------|-------------------------------------------|-------------------------------|----------------------------|
| MDx-ChexTM for BC-
GN,
Positive Control | 22343 | 10/10 | 100% | 69% - 100% |
| MDx-ChexTM for BC-
GN,
Positive Control | 22353 | 10/10 | 100% | 69% - 100% |
| MDx-ChexTM for BC-
GN,
Positive Control | 22355 | 10/10 | 100% | 69% - 100% |

1 Expected result for the Positive Control is positive.

Table 2: Lot-to-Lot Precision Summary for MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement

| Category | # Lot | # Observed Results/

Expected Results 1 | Negative

Percent
Agreement | 95% Confidence
Interval |
|-------------------------------------------|-------|---------------------------------------------|----------------------------------|----------------------------|
| MDx-Chex™ for BC-
GN, Negative Control | 22343 | 10/10 | 100% | 69% - 100% |
| MDx-Chex™ for BC-
GN, Negative Control | 22353 | 10/10 | 100% | 69% - 100% |
| MDx-Chex™ for BC-
GN, Negative Control | 22355 | 10/10 | 100% | 69% - 100% |

1 Expected result for the Negative Control is negative.

Table 3: Within-Run Precision Summary for MDx-Chex™ for BC-GN Positive Control: Positive Percent Agreement

| Category | # Lot | # Observed
Results/# Expected
Results 1 | Positive Percent
Agreement | 95% Confidence
Interval |
|-------------------------------------------|-------|-----------------------------------------------|-------------------------------|----------------------------|
| MDx-Chex™ for BC-
GN, Positive Control | 22343 | 10/10 | 100% | 69% - 100% |

Expected result for the Positive Control is positive.

Table 4: Within-Run Precision Summary for MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement

| Category | # Lot | # Observed Results/

Expected Results 1 | Negative Percent

Agreement | 95% Confidence
Interval |
|-------------------------------------------|-------|---------------------------------------------|-------------------------------|----------------------------|
| MDx-Chex™ for BC-
GN, Negative Control | 22343 | 10/10 | 100% | 69% - 100% |

pected result for the Negative Control is negative

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Closed-Vial Stability and Shipping Stability

A closed-vial stability study was conducted to assess performance of three MDx-Chex™ for BC-GN lots (#22343, #22353, #22355) with the Luminex BC-GN panel using Luminex VERIGENE systems. Testing consisted of 20 positive and 20 negative control samples, per MDx-Chex™ for BC-GN lot, collected at different data collection timepoints and stored at room (25C) and at refrigerated (2°C) temperatures.

For the shipping stability study, one of the MDx-Chex™ for BC-GN lots (RPL #22355) from each storage temperature (2°C and 25°C) was subjected to simulated winter and summer shipping temperature profiles over 5 days. Data was collected from 20 samples per control type (i.e., positive and negative), for each simulated shipping profile, within the 61-day CVS testing period.

Samples were prepared and analyzed on the Luminex VERIGENE systems per MDx-Chex™ for BC-GN assay Instructions for Use. All MDx-Chex™ for BC-GN Positive and Neqative Control lots passed closed-vial stability, and summer and winter shipping conditions with ≥ 90% agreement with expected results. The data supports that MDx-Chex™ for BC-GN Control kit is stable for a minimum of 60 days for use with the Luminex BC-GN panel lot when stored at 2-25°C. The data also supports that the Control kit is stable and functional after exposure to extreme summer and winter shipping temperature conditions.

| Shelf-Life | Storage
Temperature | #Observed Results/
#Expected Results 1 | Positive
Percent
Agreement | 95% Confidence
Interval | PPA ≥ 90%
Acceptance |
|------------|------------------------|-------------------------------------------|----------------------------------|----------------------------|-------------------------|
| Day 0 | NA | 60/60 | 100% | 94% - 100% | Pass |
| Day 61+ | 2-8°C | 60/60 | 100% | 94% - 100% | Pass |
| | 20-25°C | 60/60 | 100% | 94% - 100% | Pass |

Table 1 Closed-vial stability of MDx-Chex™ for BC-GN Negative Control: Positive Percent Agreement.

1 Expected result for the Negative Control is negative. Indicates that lots stored at 2-8°C were tested for at least 61 days; Lot 22353 (74 days), and Lot 2255 (78 days). Lots stored at 20-25"C were also tested for at least 61 days; Lot 22343 (72 days), Lot 22353 (76 days), and Lot 22355 (80 days).

Table 2. Closed-vial stability of MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement.

| Shelf-Life | Storage
Temperature | #Observed
Results/
#Expected
Results 1 | Negative
Percent
Agreement | 95%
Confidence
Interval | NPA ≥
90%
Acceptanc
e |
|------------|------------------------|-------------------------------------------------|----------------------------------|-------------------------------|--------------------------------|
| Day 0 | NA | 60/60 | 100% | 94% - 100% | Pass |
| Day 61+ | 2-8°C | 60/60 | 100% | 94% - 100% | Pass |
| 20-25°C | 60/60 | 100% | 94% - 100% | Pass | |

1 Expected result for the Negative Control is negative.

t indicates that lots stored at 2-8°C were test 61 days; of 22343 70 days), and Lot 22355 (78 days), Lots stored at 20-25°C were also tested for at least 61 days; Lot 22343 (72 days), Lot 22353 (76 days), and Lot 22355 (80 days).

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Table 3. Closed-vial stability of MDx-Chex™ for BC-GN Positive Control: Positive Percent Agreement for each MDx-Chex Lot.

| Shelf-
Life | Storage
Temperature | # Lot | #Observed
Results/
#Expected
Results 1 | Positive
Percent
Agreement | 95%
Confidence
Interval | PPA ≥ 90%
Acceptance |
|----------------|------------------------|-------|-------------------------------------------------|----------------------------------|-------------------------------|-------------------------|
| Day 0 | NA | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22353 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22355 | 20/20 | 100% | 83% - 100% | Pass |
| Day 61+ | 2-8°C | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | | 22353 | 20/20 | 100% | 83% - 100% |
| | | | 22355 | 20/20 | 100% | 83% - 100% |
| | 20-25°C | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | | 22353 | 19/20* | 95% | 75% - 100% |
| | | | 22355 | 18/20** | 90% | 68% - 99% |

1 Expected result for the Positive Control is positive.

One Positive Control gave initial false negative results which produced the expected result upon a single retest.
Two Positive Controls gave initial false negative results upon a single retest. Note: The retest runs are not included in the above calculations for this study.

t indicates that lots stored at 2-8'C were tested for at 2234 (70 days), and Lot 22355 (78 days), Lots stored at 20-25'C were also tested for at least 61 days; Lot 22343 (72 days), Lot 22353 (76 days), and Lot 22355 (80 days).

Table 4 Closed-vial stability of MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement for each MDx-Chex Lot

| Shelf-Life | Storage
temperature | # Lot | #Observed Results/
#Expected Results 1 | Negative
Percent
Agreement | 95%
Confidence
Interval | NPA ≥ 90%
Acceptance |
|------------|------------------------|-------|-------------------------------------------|----------------------------------|-------------------------------|-------------------------|
| Day 0 | NA | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22353 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22355 | 20/20 | 100% | 83% - 100% | Pass |
| Day 61+ | 2-8°C | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22353 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22355 | 20/20 | 100% | 83% - 100% | Pass |
| | 20-25°C | 22343 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22353 | 20/20 | 100% | 83% - 100% | Pass |
| | | 22355 | 20/20 | 100% | 83% - 100% | Pass |

1 Expected result for the Negative Control is negative.

Indicates that lots stored at 2-8°C were lested for at 22343 (71 days), Lot 22353 (75 days), and Lot 22355 (79 days). Lots stored at 20-25°C were also tested for at least 61 days; Lot 22343 (73 days), Lot 22353 (77 days), and Lot 22355 (81 days).

Table 1. Shipping Study of MDx-Chex™ for BC-GN Positive Control: Positive Percent Agreement.

| Category | Storage
Temperature* | #Observed Results/
#Expected Results1 | Positive
Percent
Agreement | 95% Confidence
Interval | PPA ≥ 90%
Acceptance |
|----------|-------------------------|------------------------------------------|----------------------------------|----------------------------|-------------------------|
| Summer | 2-8°C | 20/20 | 100% | 83% - 100% | Pass |
| | 20-25°C | 20/20 | 100% | 83% - 100% | Pass |
| Winter | 2-8°C | 20/20 | 100% | 83% - 100% | Pass |
| | 20-25°C | 20/20 | 100% | 83% - 100% | Pass |

Samples were stored at each respective to exposure to simulated summer or winter conditions and, following the shipping simulation, relumed to each respective storage temperature prior to testing on the Luminex VERIGENE System.

1 Expected result for the Positive Control is positive.

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| Category | Storage
Temperature* | #Observed Results/
#Expected Results 1 | Negative
Percent
Agreement | 95% Confidence
Interval | PPA ≥ 90%
Acceptance |
|----------|-------------------------|-------------------------------------------|----------------------------------|----------------------------|-------------------------|
| Summer | 2-8°C | 20/20 | 100% | 83% - 100% | Pass |
| Summer | 20-25°C | 20/20 | 100% | 83% - 100% | Pass |
| Winter | 2-8°C | 20/20 | 100% | 83% - 100% | Pass |
| Winter | 20-25°C | 20/20 | 100% | 83% - 100% | Pass |

Table 2. Shipping Study of MDx-Chex™ for BC-GN Negative Control: Negative Percent Agreement.

Samples were stored at each respective prior to exposure to simulated summer or winter conditions and, following the shipping simulation, returned back at each respective storage temperature prior to testing on the Luminex VERIGENE System.

1 Expected result for the Negative Control is negative.

Matrix Effect

A matrix effect study was completed to demonstrate that the matrix of the MDx-Chex™ for BC-GN has no effect on target detection by the VERIGENE® Gram Negative Blood Culture (BC-GN) panel and produces results consistent with contrived positive blood culture samples.

To verify that the simulated blood culture matrix does not impact performance of the Luminex BC-GN panel, one lot (#23026) of Enterobacter cloacae (1.4E8 cells/mL final concentration) was spiked into MDx-Chex™ for BC-GN matrix and also into BD BACTEC Plus Aerobic/F culture medium supplemented with negative whole blood to simulate a clinical sample (note: spike-in concentration is within the clinical bottle positivity range of approximately 1E7-1E9 CFU/mL).

The simulated samples (i.e., Positive Control) were tested in triplicate using Luminex BC-GN panel. Additionally, non-spiked simulated samples were tested in triplicate using Luminex BC-GN panel serving as negative controls.

The simulated positive MDx-Chex™ for BC-GN matrix and simulated positive clinical sample passed with ≥ 90% agreement for positive detection of analyte. The simulated negative MDx-Chex™ for BC-GN matrix and simulated negative clinical sample passed with ≥ 90% agreement for negative detection of analyte. The results demonstrate that MDx-Chex™ for BC-GN matrix has no effect on target detection (no inhibition and/or false negative results) when tested with the Luminex BC-GN panel. Data was consistent with the results of simulated blood culture samples.

Table 1: Effect of MDx-Chex™ for BC-GN and clinical sample matrices, spiked with Enterobacter cloacae, tested on Luminex Gram-Negative Blood Culture (BC-GN) Test

| Matrix type | # Observed Results/#
Expected Results 1 | Positive
Percent
Agreement | 95% Confidence
Interval |
|----------------------------------------------------|--------------------------------------------|----------------------------------|----------------------------|
| MDx-Chex™ for BC-GN
Matrix,
Positive Control | 3/3 | 100% | 29% - 100% |
| Clinical Matrix, Positive
Control | 3/3 | 100% | 29% - 100% |

Expected result for the Spiked-in matrices are positive for Enterobacter cloacae

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Table 2: Effect of negative MDx-Chex™ for BC-GN and clinical sample matrices tested on Luminex Gram-Negative Blood Culture (BC-GN) Test

| Matrix type | # Observed Results/ #
Expected Results 1 | Negative
Percent
Agreement | 95% Confidence
Interval |
|-------------------------------------------------|---------------------------------------------|----------------------------------|----------------------------|
| MDx-Chex™ for BC-GN
Matrix, Negative Control | 3/3 | 100% | 29% - 100% |
| Clinical Matrix, Negative
Control | 3/3 | 100% | 29% - 100% |

1 Expected result for non-spiked matrices are negative.

Conclusions Drawn from Tests

Study results demonstrate MDx-Chex™ for BC-GN to be consistently reproducible, substantially equivalent to the predicate product, and stable for the product dating. MDx-Chex™ for BC-GN is a safe and effective product, which fulfills its intended use when used as instructed in the Instructions for Use.