Who is the manufacturer of MDx-Chex for BC-GN?

Streck filed the 510(k) submission for MDx-Chex for BC-GN (K231223).

What is the FDA product code for MDx-Chex for BC-GN?

PMN. It is classified under 21 CFR 866.3920 as a Class 2 device in the Microbiology panel.

What is the regulatory pathway for MDx-Chex for BC-GN?

510(k) clearance (submission type: Traditional).

What are the predicate devices for MDx-Chex for BC-GN?

Streck MDx-Chex for BCID2 (K212576).

Who can help prepare an FDA 510(k) submission like MDx-Chex for BC-GN?

Innolitics — a medical-device software consultancy — provides regulatory and engineering support for FDA 510(k) submissions. See https://innolitics.com/services/510ks/ or contact https://innolitics.com/contact.

MDx-Chex for BC-GN

K231223 · Streck · PMN · Jul 27, 2023 · Microbiology

Device Facts

Record ID	K231223
Device Name	MDx-Chex for BC-GN
Applicant	Streck
Product Code	PMN · Microbiology
Decision Date	Jul 27, 2023
Decision	SESE
Submission Type	Traditional
Regulation	21 CFR 866.3920
Device Class	Class 2

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.

Device Story

MDx-Chex™ for BC-GN is a ready-to-use liquid quality control kit; contains stabilized human erythrocytes, leukocytes, blood culture media components, and inactivated intact microorganisms. Used as an external control for the Luminex VERIGENE® BC-GN test; processed by laboratory technicians like a patient sample. The device monitors the entire analytical process: sample lysis, nucleic acid isolation, DNA hybridization, detection, and data reporting. It specifically controls for the presence of common blood culture inhibitors (hemoglobin, leukocyte DNA, anticoagulants). By verifying the performance of the test system, it helps identify preanalytical variables or system variations that could lead to incorrect clinical results, thereby ensuring the reliability of pathogen and resistance gene identification for clinicians.

Clinical Evidence

No clinical data. Bench testing only. Reproducibility study (n=180 runs) across three sites, seven operators, and three lots showed 99% PPA and 100% NPA. Repeatability study (n=120 runs) showed 98% PPA and 100% NPA. Lot-to-lot reproducibility (n=60) confirmed performance consistency. Shipping stability studies confirmed functionality after exposure to extreme temperature profiles. Matrix equivalency study confirmed the simulated matrix does not inhibit target detection compared to clinical blood culture matrix.

Technological Characteristics

Ready-to-use liquid control; contains stabilized human erythrocytes, leukocytes, blood culture media, and inactivated microorganisms. Functions as a full-process control for nucleic acid amplification/hybridization assays. No energy source; standalone product. Stability validated for 60+ days at 2-25°C.

Indications for Use

Indicated for use as an external positive and negative assayed control to monitor the performance of the Luminex VERIGENE® Gram-Negative Blood Culture Nucleic Acid Test (BC-GN) for the qualitative detection of Gram-negative bacteria and associated antimicrobial resistance genes. Intended for professional use in clinical laboratory settings.

Regulatory Classification

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.

Special Controls

An assayed quality control material for clinical microbiology assays must comply with the following special controls: (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; Expected values: (ii) Analyte source: (iii) (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., realtime 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 in your 21 CFR 809.10(a)(2) and 21 CFR 809.10(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; (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 21 CFR 809.10(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."

*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.”

Predicate Devices

Streck MDx-Chex for BCID2 (K212576)

Related Devices

K231221 — MDx-Chex for BC-GP · Streck · Jul 27, 2023
K254166 — MDx-Chex for BCN · Streck · Mar 23, 2026

Submission Summary (Full Text)

{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) | #### CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. #### *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {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. {9}------------------------------------------------ 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 {10}------------------------------------------------ #### 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). {11}------------------------------------------------ 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. {12}------------------------------------------------ | 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 {13}------------------------------------------------ ### 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.