The Cepheid Xpert®Respiratory 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 Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory Syncytial Virus A performed with the Cepheid Xpert® Xpress Flu/RSV assay on the GeneXpert® Instrument System. The controls comprise cultured and inactivated Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory Syncytial Virus A as the positive control and Coxsackie virus B1 as the negative control.

The Cepheid Xpert®Respiratory Control Panel is not intended to replace manufacturer controls provided with the device.

Device Description

The Cepheid Xpert® Respiratory Control Panel is used to monitor RNA extraction, amplification of the Cepheid Xpert® Xpress Flu/RSV assay. The Cepheid Xpert® Respiratory Control Panel contains cultured viruses inactivated by chemical or radiological treatments. Each Cepheid Xpert® Respiratory Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains Influenza A (H1N1) virus, Influenza A (H3N2) virus, Influenza B virus and Respiratory syncytial virus A. Each negative control swab contains Coxsackie B1 virus. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

AI/ML Overview

The acceptance criteria and study proving the device meets them are described below for the Cepheid Xpert® Respiratory Control Panel.

1. Acceptance Criteria and Reported Device Performance

The core acceptance criterion for the Cepheid Xpert® Respiratory Control Panel, as demonstrated by the provided data, is 100% agreement between the expected and observed results for both positive and negative analytes.

Analyte	Acceptance Criteria (Agreement %)	Reported Device Performance (Agreement %)
Positive Analytes
Influenza A (H1N1)	100%	100% (90/90)
Influenza A (H3N2)	100%	100% (90/90)
Influenza B	100%	100% (90/90)
Respiratory Syncytial Virus A	100%	100% (90/90)
Negative Analytes
Coxsackievirus B1	100%	100% (91/91)

It's important to note that the acceptance criteria are inferred from the demonstrated performance, as explicit numerical acceptance criteria for agreement percentages are not directly stated but consistently met at 100%.

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

Positive Controls: The test set included 90 individual tests for each positive analyte (Influenza A (H1N1), Influenza A (H3N2), Influenza B, and Respiratory Syncytial Virus A), resulting in a total of 360 positive control tests. This was broken down into 30 tests per analyte at each of the three sites.
Negative Controls: The test set included 91 individual tests for the negative analyte (Coxsackievirus B1). This was broken down into 30 tests at Site 1, 30 tests at Site 2, and 31 tests at Site 3.
Data Provenance: The study was conducted from three different production lots, at three different sites, using three different GeneXpert® Instrument Systems, and involved six different users. This suggests a prospective, multi-site study design intended to demonstrate real-world performance. The country of origin is not explicitly stated, but the applicant (Microbiologics, Inc.) is based in the United States.

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

The document describes the performance of an assayed quality control material for clinical microbiology assays. For such devices, the "ground truth" is inherent to the known composition of the control material (i.e., presence or absence of specific inactivated viruses). Therefore, no human experts or their qualifications are mentioned for establishing the ground truth of the control panel itself, as it's a manufactured standard. The "ground truth" is defined by the components of the control panel.

4. Adjudication Method for the Test Set

Adjudication methods (like 2+1 or 3+1) are typically used when there is ambiguity or disagreement in human interpretation of results, often in image analysis or diagnostic readings. For a quality control material like the Cepheid Xpert® Respiratory Control Panel, the result is an objective output from the GeneXpert® Instrument System (e.g., positive or negative for a specific virus). Therefore, an adjudication method for the test set is not applicable and not mentioned in the document.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, an MRMC comparative effectiveness study was not done. This type of study assesses how AI assistance impacts human reader performance, which is not relevant for an assayed quality control material designed to objectively monitor instrument performance rather than assist human interpretation of diagnostic images or clinical cases.

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

Yes, the study described is essentially a standalone performance evaluation of the quality control material itself when processed by the GeneXpert® Instrument System. The purpose is to verify that the control panel consistently yields the expected objective results when run through the assay, demonstrating its suitability for monitoring the RNA extraction, amplification, and detection stages of the assay. While humans operate the system and record results, the performance being assessed is that of the QC material and the GeneXpert system, without human "interpretation" of the QC result itself beyond confirming the expected positive/negative output.

7. The Type of Ground Truth Used

The ground truth used is the known composition of the manufactured control panel.

For positive controls, the ground truth is the confirmed presence of specific inactivated viruses (Influenza A (H1N1), Influenza A (H3N2), Influenza B, and Respiratory Syncytial Virus A) at concentrations expected to be detected by the Cepheid Xpert® Xpress Flu/RSV assay.
For the negative control, the ground truth is the confirmed presence of a non-target virus (Coxsackie B1) that should not be detected by the Cepheid Xpert® Xpress Flu/RSV assay.

8. The Sample Size for the Training Set

The document does not provide information about a "training set" because this device is a quality control material, not a machine learning algorithm that requires training data. Its performance is evaluated based on its ability to produce expected results when tested, not by learning from a dataset.

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

As mentioned above, there is no training set for this type of device. The ground truth for the performance evaluation (test set) is intrinsically defined by the known biological composition and manufacturing specifications of the control panel itself.

Summary

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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there is a symbol representing the Department of Health & Human Services. To the right of the symbol, there is the FDA logo in blue, followed by the words "U.S. FOOD & DRUG" in a larger font and "ADMINISTRATION" in a smaller font below it, also in blue.

October, 7 2019

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

Re: K190086

Trade/Device Name: Cepheid Xpert Respiratory 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: September 12, 2019 Received: September 13, 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/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 mediation-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,

Tamara Feldblyum, M.S., Ph.D. Chief. Viral Respiratory and STI Branch 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 symbol 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: K190086

Date: September 19, 2019

Applicant Information:

Email:

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

Device:

Device Trade Name:	Cepheid Xpert® Respiratory 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

tsobania@microbiologics.com

Predicate Device:

Cepheid Xpert® GBS LB Control Panel (K182472)

Device Description:

Device Intended Use:

The Cepheid Xpert®Respiratory Control Panel is not intended to replace manufacturer controls provided with the device.

Substantial Equivalence:

Characteristic	Cepheid Xpert® Respiratory ControlPanel	Predicate DeviceCepheid Xpert® GBS LB ControlPanel (K182472)
Intended Use	The Cepheid Xpert® RespiratoryControl Panel is intended for us as anexternal assayed positive and negativequality control to monitor the	The Cepheid Xpert® GBS LB ControlPanel is intended for use as externalassayed positive and negative qualitycontrol materials to monitor the

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Image /page/3/Picture/0 description: The image shows the logo for "Microbiologics". The logo consists of a blue and red circular graphic on the left, followed by the word "Microbiologics" in blue, with a registered trademark symbol. Underneath the word "Microbiologics" is the text "A safer, healthier world".

	performance of in vitro laboratorynucleic acid testing procedures for thequalitative detection of Influenza A(H1N1) virus, Influenza A (H3N2) virus,Influenza B virus and RespiratorySyncytial Virus A performed with theCepheid Xpert® Xpress Flu/RSV assayon the GeneXpert® Instrument System.The controls comprise cultured andinactivated Influenza A (H1N1) virus,Influenza A (H3N2) virus, Influenza Bvirus and Respiratory Syncytial Virus Aas the positive control and Coxsackievirus B1 as the negative control.The Cepheid Xpert® RespiratoryControl Panel is not intended toreplace manufacturer controls providedwith the device.	performance 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.The controls comprise cultured andinactivated Streptococcus agalactiaeas the positive control andLactobacillus acidophilus as thenegative control.The Cepheid Xpert® GBS LB ControlPanel is not intended to replacemanufacturer controls provided withthe device.
Physical Format	Lyophilized swab	Lyophilized swab
Composition	Inactivated microorganisms	Inactivated microorganisms
Analytes	Influenza A (H1N1) virusInfluenza A (H3N2) virusInfluenza B virusRespiratory Syncytial Virus ACoxsackie virus B1	Streptococcus agalactiaeLactobacillus acidophilus
Test System	Cepheid GeneXpert® System	Cepheid GeneXpert® System
Directions for Use	Process like patient sample	Process like patient sample
Assay StepsMonitored	Extraction, amplification, and detection	Extraction, amplification, detection

Summary of Performance Data:

The performance of the Cepheid Xpert® Respiratory Control Panel was evaluated in a study that was performed using three different production lots, three sites, using three different GeneXpert® Instrument Systems and six different users. The results of the study are summarized below.

PositiveAnalyte	Agreement (%) by Test Site/GeneXpert® System
	Site 1	Site 2	Site 31	Overall
Influenza A (H1N1)	30/30(100)	30/30(100)	30/30(100)	90/90(100)
Influenza A (H3N2)	30/30(100)	30/30(100)	30/30(100)	90/90(100)
Influenza B	30/30(100)	30/30(100)	30/30(100)	90/90(100)
Respiratory Syncytial Virus A	30/30(100)	30/30(100)	30/30(100)	90/90(100)

1 One NO RESULT response was 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 logo for "Microbiologics". The logo consists of a stylized symbol resembling a partially closed circle with red and blue sections, followed by the word "Microbiologics" in a bold, blue font. Below the word, there is a tagline that reads "A safer, healthier world."

NegativeAnalyte	Site 1	Site 2	Site 3	Overall
Coxsackievirus B1	30/30(100)	30/30(100)	31/31(100)	91/91(100)

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.”