The Cepheid Xpert® MRSA NxG Control Panel is intended for use as an external assayed positive and negative quality control to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin-Resistant Staphylococus aureus performed with the Cepheid Xpert® MRSA NxG Assay on the GeneXpert® Instrument System. The controls comprise cultured and inactivated Methicillin-Resistant Staphylococcus aureus as the positive control and Staphylococcus epidermidis as the negative control.

The Cepheid Xpert® MRSA NxG Control Panel is not intended to replace manufacturer controls provided with the Cepheid Xpert® MRSA NxG Assay.

Device Description

The Cepheid Xpert® MRSA NxG Control Panel is used to monitor the DNA extraction, amplification and detection processes of the Cepheid Xpert® MRSA NxG Assay. The Cepheid Xpert® MRSA NxG Control Panel contains cultured microorganisms inactivated by heat treatments. Each Cepheid Xpert® MRSA NxG Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains cultured and inactivated Methicillin-Resistant Staphylococcus aureus (MRSA) at arget level that is designed to provide reproducible performance above the limit of detection for each of the genes targeted by the Cepheid Xpert® MRSA NxG Assay: methicillin resistance gene mecA (mec) and the Staphylococcal cassette chromosome (SCC). Each negative contains Staphylococcus epidermidis (MSSE) that is not detected by the Cepheid Xpert® MRSA NxG Assay. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

AI/ML Overview

Here's a breakdown of the acceptance criteria and study details for the Cepheid Xpert® MRSA NxG Control Panel, based on the provided text:

Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Acceptance Criteria	Reported Device Performance
Positive Control	100% agreement for Methicillin-Resistant Staphylococcus aureus (mec, SCC) detection across all sites	100% (93/93) overall agreement
Negative Control	100% agreement for Staphylococcus epidermidis (no detection) across all sites	100% (92/92) overall agreement

(Note: The provided text doesn't explicitly state the acceptance criteria as separate from the performance, but the 100% agreement achieved suggests this was the expected outcome for a control panel's precision and reproducibility study.)

Study Details

Sample size used for the test set and the data provenance:
- Sample Size:
  - For Positive Controls: 93 tests (32 at Site 1, 31 at Site 2, 30 at Site 3).
  - For Negative Controls: 92 tests (31 at Site 1, 31 at Site 2, 30 at Site 3).
- Data Provenance: The study was conducted at three different testing locations (referred to as Site 1, Site 2, and Site 3). The document does not specify the country of origin, but it implies a prospective study since it describes "a precision and reproducibility study was conducted."
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The concept of "ground truth" as established by experts (e.g., radiologists) is not applicable here. This is a study for a quality control material for a diagnostic assay, not an AI diagnostic device evaluating patient data. The "ground truth" for the control material is inherently defined by its composition (e.g., inactivated Methicillin-Resistant Staphylococcus aureus for the positive control, Staphylococcus epidermidis for the negative control) and the known expected results from the Cepheid Xpert® MRSA NxG Assay.
Adjudication method for the test set:
- Not applicable. As this is a study for a quality control material, the results are objective (positive/negative detection) based on the performance of the assay with the control. There's no subjective interpretation requiring adjudication among experts. The study reports raw agreement percentages. Any "ERROR" responses were retested with a new control, indicating a procedural re-evaluation rather than expert adjudication of a result.
If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance:
- No. This type of study (MRMC for AI) is not applicable to a quality control panel. This product is a control material for an in-vitro diagnostic assay, not an AI-powered diagnostic device.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- Yes, in essence. The "device performance" refers to the performance of the control panel itself, which is then used by human operators with the GeneXpert® Instrument System and Cepheid Xpert® MRSA NxG Assay. While human operators are involved in running the test, the evaluation of the control material's performance against the assay's expected results is a standalone assessment of the control material's ability to consistently produce those results. This isn't an AI algorithm; rather, it's a quality control for an existing diagnostic system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- The "ground truth" for the control panel is based on its known composition and the expected analytical performance when run on the target assay. For the positive control, the ground truth is the presence of Methicillin-Resistant Staphylococcus aureus (mec, SCC) at a level detectable by the assay. For the negative control, the ground truth is the presence of Staphylococcus epidermidis which should not be detected by the target assay.
The sample size for the training set:
- Not applicable. This study is for a quality control material, not a machine learning or AI algorithm that requires a training set. The "samples" used are the control materials themselves tested on the assay system.
How the ground truth for the training set was established:
- Not applicable. As there is no training set for an AI algorithm, this question is not relevant to the described device and study.

Summary

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June 20, 2019

Microbiologics, Inc. Tina Sobania Director of Corporate Quality 200 Cooper Avenue North St. Cloud, Minnesota 56303

Re: K191172

Trade/Device Name: Cepheid Xpert MRSA NxG Control Panel 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 30, 2019 Received: May 1, 2019

Dear Tina Sobania:

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.

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

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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,

for

Uwe Scherf, M.Sc., Ph.D. Director Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics and Radiological Health Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Image /page/2/Picture/0 description: The image shows the Microbiologics logo. The logo features a stylized blue and red crescent shape on the left, followed by the word "Microbiologics" in blue, with a registered trademark symbol. Below the word, there is a red line and the tagline "A safer, healthier world." in a smaller font.

510(k) Summary

510(k) Number: K191172

Date: June 12, 2019

Applicant Information:

Applicant:	Microbiologics, Inc.
Address:	200 Cooper Avenue NorthSt. Cloud, MN 56303
Primary Contact:	Tina Sobania, Director of Corporate Quality
Phone:	320-229-7050
Email:	tsobania@microbiologics.com

Device:

Device Trade Name:	Cepheid Xpert® MRSA NxG Control Panel
Common Name:	Assayed quality control material for clinical microbiology assays
Classification:	Class II
Regulation:	21 CFR 866.3920
Panel:	83-Microbiology
Product Code:	PMN

Predicate Device:

Cepheid Xpert® GBS LB Control Panel

Device Description:

Device Intended Use:

The Cepheid Xpert® MRSA NxG Control Panel is not intended to replace manufacturer controls provided with the Cepheid Xpert® MRSA NxG Assay.

Substantial Equivalence:

Characteristic	Cepheid Xpert® MRSA NxG Control Panel	Cepheid Xpert® GBS LB Control Panel (K182472)
Intended Use	The Cepheid Xpert® MRSA NxG Control Panel is intended for use as an external assayed positive and negative quality	The Cepheid Xpert® GBS LB Control Panel is intended for use as external assayed positive and negative quality control

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Image /page/3/Picture/0 description: The image shows the Microbiologics logo. The logo features a stylized symbol resembling a crescent shape, with the left side in blue and the right side in red. To the right of the symbol is the word "Microbiologics" in blue, with a registered trademark symbol. Below the word is the tagline "A safer, healthier world".

	control to monitor the performance of in vitrolaboratory nucleic acid testing proceduresfor the qualitative detection of Methicillin-Resistant Staphylococcus aureus performedwith the Cepheid Xpert® MRSA NxG Assayon the GeneXpert® Instrument System. Thecontrols comprise cultured and inactivatedMethicillin-Resistant Staphylococcus aureusas the positive control and Staphylococcusepidermidis as the negative control.	materials to monitor the performance of invitro laboratory nucleic acid testingprocedures for the qualitative detection ofGroup B Streptococcus (GBS) performedwith the Cepheid Xpert® GBS LB Assay onthe GeneXpert® Instrument System. Thecontrols comprise cultured and inactivatedStreptococcus agalactiae as the positivecontrol and Lactobacillus acidophilus asthe negative control.
	The Cepheid Xpert® MRSA NxG Control	The Cepheid Xpert® GBS LB Control Panel
	Panel is not intended to replace	is not intended to replace manufacturer
	manufacturer controls provided with theCepheid Xpert® MRSA NxG Assay.	controls provided with the device.
Physical Format	Lyophilized swab	Lyophilized swab
Composition	Inactivated microorganisms	Inactivated microorganisms
Analytes	Methicillin-Resistant Staphylococcus aureusStaphylococcus epidermidis	Streptococcus agalactiaeLactobacillus acidophilus
Test System	Cepheid GeneXpert® System	Cepheid GeneXpert® System
Directions for Use	Process like patient sample	Process like patient sample
Assay Steps	Extraction, amplification, and detection	Extraction, amplification, detection
Monitored

Summary of Performance Data:

A precision and reproducibility study was conducted to determine device performance. Three different testing locations were used. Six different operators (2 at each facility) and 3 different lots of the Cepheid Xpert® MRSA NxG Control Panel were tested over five days. Each operator performed a minimum of 3 tests (1 per lot) on 5 different days. All testing was performed on a GeneXpert® Instrument System using the Cepheid Xpert® MRSA NxG Assay.

PositiveAnalyte	Agreement (%) by Test Site/GeneXpert® System
	Site 11	Site 2	Site 3	Overall
Methicillin-Resistant Staphylococcus aureus(mec, SCC)	32/32(100)	31/31(100)	30/30(100)	93/93(100)

1 One ERROR response was observed; a new control was retested and the expected results were obtained.

NegativeAnalyte	Agreement (%) by Test Site/GeneXpert ® System
	Site 11	Site 21	Site 3	Overall
Staphylococcus epidermidis	31/31(100)	31/31(100)	30/30(100)	92/92(100)

1 ERROR responses were observed; a new control was retested and the expected results were obtained.

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Image /page/4/Picture/0 description: The image shows the Microbiologics logo. The logo consists of a blue and red circular shape on the left, followed by the word "Microbiologics" in blue, with a registered trademark symbol. Below the word, there is a red line and the text "A safer, healthier world." in a smaller font.

Site	6047 Mean Ct (%CV)		6048 Mean Ct (%CV)
	mec	SCC	SPC
1	28.0 (3.5)	29.5 (3.3)	32.4 (3.1)
2	29.2 (3.8)	30.8 (3.7)	32.2 (2.0)
3	29.1 (4.9)	30.6 (4.6)	32.6 (3.2)
All Sites	28.7 (4.5)	30.3 (4.3)	32.4 (2.8)
%CV: Percent Coefficient of Variation; SPC: Sample Processing Control
%CV: Percent Coefficient of Variation; SPC: Sample Processing Control

Conclusion

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

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.”