The Cepheid Xpert® C. difficile/Epi Control Panel is intended for use as external assayed positive and negative quality controls to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Clostridioides (Clostridium) difficile performed with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The controls comprise cultured and inactivated Clostridioides (Clostridium) difficile 027-NAP1-B1 as the positive control and Clostridium sordellii as the negative control.

The Cepheid Xpert® C. difficile/Epi Control Panel is not intended to replace manufacturer controls provided with the device.

Device Description

The Cepheid Xpert® C. difficile/Epi Control Panel to monitor DNA extraction, amplification and detection of the Cepheid Xpert® C. difficile/Epi assay. The Cepheid Xpert® C. difficile/Epi Control Panel contains cultured microorqanisms inactivated by heat treatments. Each Cepheid Xpert® C. difficile/Epi 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 Clostridioides difficile at a target level that is designed to provide reproducible performance above the limit of detection of the Cepheid Xpert® C. difficile/Epi assay. The positive control swab is expected to produce positive results for each of the genes targeted by the Cepheid Xpert® C. difficile/Epi assay: toxin B (tcdB), binary toxin (CDT) and the variant requlator gene, tcdC. Each negative control swab contains Clostridium sordelli. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

AI/ML Overview

Here's an analysis of the provided text to fulfill your request regarding acceptance criteria and the study proving device performance:

Device Name: Cepheid Xpert C. difficile/Epi Control Panel

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a codified manner for a diagnostic accuracy study (e.g., target sensitivity, specificity). Instead, it presents the results of a precision and reproducibility study to demonstrate the performance of the control panel itself. The implicit acceptance criterion for a control panel is 100% agreement with the expected result (positive controls yield positive results, negative controls yield negative results).

Acceptance Criteria (Implied)	Reported Device Performance
Positive Controls: 100% agreement with expected positive results	Clostridioides difficile: 91/91 (100%) agreement
Negative Controls: 100% agreement with expected negative results	Clostridium sordellii: 91/91 (100%) agreement
Consistent Ct values (low %CV) across sites and operators	Mean Ct (%CV) for tcdB: 29.5 (2.2)
	Mean Ct (%CV) for Binary Toxin: 28.9 (2.2)
	Mean Ct (%CV) for tcdC: 28.8 (2.2)
	Mean Ct (%CV) for SPC (Negative Controls): 32.5 (2.0)

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size: 91 positive control tests and 91 negative control tests.
- For the positive control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
- For the negative control: 30 at Site 1, 31 at Site 2, 30 at Site 3.
Data Provenance: The document does not specify the country of origin. The study was conducted as a "precision and reproducibility study," which is typically prospective, designed to evaluate product consistency.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts

Not applicable. This study evaluates a quality control panel, not a diagnostic device's ability to identify disease in patient samples. The "ground truth" for the test set is established by the known composition of the control panel itself (i.e., the positive control contains C. difficile, and the negative control contains C. sordellii). There are no human experts classifying images or results for ground truth in this context.

4. Adjudication Method for the Test Set

Not applicable. As noted above, the "ground truth" is inherent in the design of the control panel. The performance is assessed against the expected molecular detection profile of the contained microorganisms.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, If So, What Was the Effect Size of How Much Human Readers Improve with AI vs Without AI Assistance

Not applicable. This is a study for a quality control panel, not an AI-powered diagnostic device. No human readers or AI assistance are involved in interpreting the results beyond standard laboratory procedures for running the GeneXpert® Dx System.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

The study inherently evaluates the "standalone" performance of the control panel in conjunction with the Cepheid Xpert® C. difficile/Epi assay on the GeneXpert® Dx System. The control panel is a reagent designed to monitor the assay's performance. The results (presence/absence of targets, Ct values) are generated directly by the GeneXpert system without further human interpretation beyond confirming the system's output.

7. The Type of Ground Truth Used

The ground truth is based on the known composition of the manufactured control materials. The positive control contains cultured and inactivated Clostridioides difficile, and the negative control contains Clostridium sordellii. The expected results are therefore known beforehand based on the microbial content.

8. The Sample Size for the Training Set

Not applicable. This device is a quality control panel, not an algorithm or AI system that requires a "training set." The study evaluated the performance of the manufactured controls.

9. How the Ground Truth for the Training Set Was Established

Not applicable (as described in point 8).

Summary

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Indications for Use

510(k) Number (if known)

Device Name

Indications for Use (Describe)

Prescription Use (Part 21 CFR 801 Subpart D)

| Over-The-Counter Use (21 CFR 801 Subpart C)

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April 19, 2019

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

Re: K190463

Trade/Device Name: Cepheid Xpert C. difficile/Epi 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: February 25, 2019 Received: February 26, 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 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR

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for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); 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 http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for

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

Enclosure

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Image /page/3/Picture/0 description: The image is the logo for "Microbiologics". The logo consists of a red and blue circular graphic on the left, followed by the word "Microbiologics" in blue, with a red line underneath. To the right of the word "Microbiologics" is a circled R, indicating a registered trademark. Below the red line is the text "A safer, healthier world."

510(k) Summary

510(k) Number: K190463

Date: March 25, 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® C. difficile/Epi 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® C. difficile/Epi Control Panel is not intended to replace manufacturer controls provided with the device.

Substantial Equivalence:

Characteristic	Cepheid Xpert® C. difficile/Epi Control Panel	Cepheid Xpert® GBS LB Control Panel (K182472)
Intended Use	The Cepheid Xpert® C. difficile/Epi Control Panel is intended for use as external	The Cepheid Xpert® GBS LB Control Panel is intended for use as external assayed positive and negative quality

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Image /page/4/Picture/0 description: The image shows the Microbiologics logo. The logo features a stylized blue and red circular design on the left, followed by the word "Microbiologics" in blue, with a registered trademark symbol. Below the word, there is a red line under "Microbio" and a blue line under "logics", and the tagline "A safer, healthier world" is written in a smaller font.

	assayed positive and negative qualitycontrols to monitor the performance of invitro laboratory nucleic acid testingprocedures for the qualitative detection ofClostridioides (Clostridium) difficileperformed with the Cepheid Xpert® C.difficile/Epi assay on the GeneXpert® DxSystem. The controls comprise culturedand inactivated Clostridioides (Clostridium)difficile 027-NAP1-B1 as the positivecontrol and Clostridium sordellii as thenegative control.The Cepheid Xpert® C. difficile/Epi ControlPanel is not intended to replacemanufacturer controls provided with thedevice.	control materials to monitor theperformance of in vitro laboratorynucleic acid testing procedures for thequalitative detection of Group BStreptococcus (GBS) performed withthe Cepheid Xpert® GBS LB Assay onthe GeneXpert® Instrument System. Thecontrols comprise cultured andinactivated Streptococcus agalactiae asthe positive control and Lactobacillusacidophilus as the negative control.The Cepheid Xpert® GBS LB ControlPanel is not intended to replacemanufacturer controls provided with thedevice.
Physical Format	Lyophilized swab	Lyophilized swab
Composition	Inactivated microorganisms	Inactivated microorganisms
Analytes	Clostridioides difficile (tcdB, binary toxin,tcdC)Clostridium sordellii	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® C. difficile/Epi 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® Dx System using the Cepheid Xpert® C. difficile/Epi assay.

PositiveAnalyte	Agreement (%) by Test Site/GeneXpert® System
	Site 1	Site 21	Site 3	Overall
Clostridioides difficile(tcdB/binary toxin/tcdC)	30/30(100)	31/31(100)	30/30(100)	91/91(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 1	Site 21	Site 3	Overall
Clostridium sordellii	30/30(100)	31/31(100)	30/30(100)	91/91(100)

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

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Image /page/5/Picture/0 description: The image shows the Microbiologics logo. The logo features a stylized symbol to the left of the word "Microbiologics" in a bold, blue font. Below the word, there is a red line and the text "A safer, healthier world." in a smaller, sans-serif font.

Site	Mean Ct (%CV)
	tcdB	Binary Toxin	tcdC	SPC 1
1	29.5 (2.6)	29.0 (2.5)	28.8 (2.5)	32.7 (2.1)
2	29.7 (2.2)	29.2 (2.1)	29.1 (2.1)	32.3 (1.6)
3	29.3 (1.5)	28.7 (1.6)	28.6 (1.6)	32.5 (2.0)
All Sites	29.5 (2.2)	28.9 (2.2)	28.8 (2.2)	32.5 (2.0)

%CV: Percent Coefficient of Variation; SPC: Sample Processing Control

%CV: Percent Coefficient of Variation; SPC: Sample Processing Control
¹ The values shown for the SPC are only for testing performed with Negative Controls

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.”