The Cepheid Xpert® CT/NG 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 Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) performed with the Cepheid Xpert® CT/NG assay on the GeneXpert® Instrument System. The controls consist of cultured and inactivated Chlamydia trachomatis and Neisseria gonorrhoeae as the positive control and human cells as the negative control.

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

Device Description

The Cepheid Xpert® CT/NG Control Panel is used to monitor the extraction, amplification and detection of the Cepheid Xpert® CT/NG Assay. The Cepheid Xpert® CT/NG Control Panel contains authentic pathogens inactivated by radiological or temperature treatments. Each Cepheid Xpert® CT/NG Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains Chlamydia trachomatis and Neisseria gonorrhoeae as well as preservatives and stabilizers. Each negative control swab contains human cells as well as preservatives and stabilizers. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

AI/ML Overview

The provided text describes the acceptance criteria and performance data for the Cepheid Xpert® CT/NG Control Panel, which is an assayed quality control material for clinical microbiology assays. This is a diagnostic device, not an AI/ML-based device, so many of the requested criteria related to AI/ML studies (such as MRMC studies, training set details, or ground truth establishment by experts for imaging) are not applicable.

Here's an analysis based on the provided document:

1. A table of acceptance criteria and the reported device performance

The acceptance criteria for this device appear to be 100% agreement with expected results for both positive and negative controls. The reported device performance met these criteria.

Acceptance Criteria	Reported Device Performance
Positive Controls: 100% agreement with expected positive results for all analytes (C. trachomatis, N. gonorrhoeae (NG2), N. gonorrhoeae (NG4), SPC)	100% agreement for all analytes: - C. trachomatis: 92/92 (100%)- N. gonorrhoeae (NG2): 92/92 (100%)- N. gonorrhoeae (NG4): 92/92 (100%)- SPC: 92/92 (100%)
Negative Controls: 100% agreement with expected negative results for all analytes (SAC, SPC)	100% agreement for all analytes: - SAC: 97/97 (100%)- SPC: 97/97 (100%)
Consistency in Ct values across sites and operators (implied by %CV data)	Mean Ct and %CV values were reported across sites, demonstrating consistency. (e.g., Overall Mean Ct for C. trachomatis 31.8 (3.8)).

2. Sample size used for the test set and the data provenance

Test Set Sample Size:
- Positive Controls: 92 replicates were tested across three sites. (31 from Site 1, 31 from Site 2, 30 from Site 3, with some additional runs for re-tests).
- Negative Controls: 97 replicates were tested across three sites. (33 from Site 1, 34 from Site 2, 30 from Site 3, with some additional runs for re-tests).
Data Provenance: The data was generated prospectively through a multi-site evaluation. The document does not specify the country of origin of the testing sites, but given it's an FDA submission, it's highly likely to be within the US or under US regulatory guidelines.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This is an in vitro diagnostic (IVD) device, specifically a quality control. The "ground truth" is inherent to the control material itself (i.e., the positive control contains the target microbes at a known concentration, and the negative control does not).

Therefore:

Number of experts: Not applicable in the context of human interpretation for ground truth. The "ground truth" is established by the known composition of the control material (inactivated pathogens for positive, human cells only for negative).
Qualifications of experts: Not applicable.

4. Adjudication method for the test set

Not applicable for an IVD quality control device. The results are quantitative (Ct values) and qualitative (positive/negative detection) based on the instrument's algorithm, not human interpretation requiring adjudication. Any "ERROR" or "INVALID" results were retested according to the Instructions for Use, which is a standard procedure for IVD testing.

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 an IVD quality control device, not an AI/ML imaging or diagnostic aid for human readers.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This device evaluates the performance of the Cepheid Xpert® CT/NG assay and GeneXpert® Instrument System, which is an automated system. The performance data presented demonstrates the "standalone" or "algorithm only" performance of the control panel interacting with the assay/instrument system as intended, without human interpretation as a variable.

7. The type of ground truth used

The ground truth is based on the known composition of the control materials:

Positive control: Contains cultured and inactivated Chlamydia trachomatis and Neisseria gonorrhoeae.
Negative control: Contains human cells.

The "expected results" (positive or negative) are determined by these known compositions.

8. The sample size for the training set

Not applicable. This is a manufactured control material, not an AI/ML algorithm that requires a training set. Its development involves formulation and manufacturing processes, followed by validation and verification studies (which are described as the "performance data").

9. How the ground truth for the training set was established

Not applicable, as there is no "training set" in the AI/ML sense for this type of device. The "ground truth" for the control material itself is established during its design and manufacturing by precisely controlling its components.

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 is the Department of Health & Human Services USA seal. To the right of that is the FDA logo, with the letters "FDA" in a blue square. To the right of the square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

May 8, 2019

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

Re: K190223

Trade/Device Name: Cepheid Xpert CT/NG 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 4, 2019 Received: February 5, 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/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 mediation-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, 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 symbol resembling a crescent shape or an incomplete circle on the left. To the right of the symbol is the company name "Microbiologics" in a bold, blue, sans-serif font, with a registered trademark symbol. Below the company name, there is a thin red line, and underneath that, the tagline "A safer, healthier world." is written in a smaller, italicized font.

510(k) Summary

510(k) Number: K190223

Date: May 1, 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® CT/NG 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 (K182472)

Device Description:

Device Intended Use:

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

Substantial Equivalence:

Characteristic	Cepheid Xpert® CT/NG Control Panel	Predicate Device -Cepheid Xpert® GBS LB Control Panel(K182472)
Intended Use	The Cepheid Xpert® CT/NG Control Panel isintended for use as an external assayedpositive and negative quality control to monitor	The Cepheid Xpert® GBS LB Control Panel isintended for use as external assayed positiveand negative quality control materials to monitor

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Image /page/3/Picture/0 description: The image shows the Microbiologics logo. The logo features a 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 and the text "A safer, healthier world."

	the performance of in vitro laboratory nucleicacid testing procedures for the qualitative	the performance of in vitro laboratory nucleicacid testing procedures for the qualitative
	detection of Chlamydia trachomatis (CT) and	detection of Group B Streptococcus (GBS)
	Neisseria gonorrhoeae (NG) performed with	performed with the Cepheid Xpert® GBS LB
	the Cepheid Xpert® CT/NG assay on theGeneXpert® System. The controls comprise	Assay on the GeneXpert® Instrument System.
	cultured and inactivated Chlamydia trachomatis	The controls comprise cultured and inactivatedStreptococcus agalactiae as the positive control
	and Neisseria gonorrhoeae as the positive	and Lactobacillus acidophilus as the negative
	control and human cells as the negative	control.
	control.
	The Cepheid Xpert® CT/NG Control Panel is	The Cepheid Xpert® GBS LB Control Panel isnot intended to replace manufacturer controls
	not intended to replace manufacturer controls	provided with the device.
	provided with the device.
Physical Format	Lyophilized swab	Lyophilized swab
Composition	Inactivated microorganisms	Inactivated microorganisms
Analytes	Chlamydia trachomatis	Streptococcus agalactiae
	Neisseria gonorrhoeae	Lactobacillus acidophilus
	Human epithelial cells
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:

The Cepheid Xpert CT/NG Control Panel was evaluated at three testing sites with two operators at each site (total of six operators). Three lots of the control material were tested with the Cepheid Xpert CT/NG assay on the Cepheid Xpert Instrument, over five days. Each positive control was tested in three replicates on each day. There were seven ERROR results (assay aborted due to instrument or reagent problem) and one INVALID result (failure of the internal control/s). Those samples were retested using a new control swab according to the Instructions for Use. All testing utilized the Xpert Vaginal/Endocervical Swab Specimen Collection kit.

PositiveTarget	Site 1 1,4	Site 2 2,4	Site 3	Overall
C. trachomatis	31/31(100)	31/31(100)	30/30(100)	92/92(100)
N. gonorrhoeae(NG2)	31/31(100)	31/31(100)	30/30(100)	92/92(100)
N. gonorrhoeae(NG4)	31/31(100)	31/31(100)	30/30(100)	92/92(100)
SPC3	31/31(100)	31/31(100)	30/30(100)	92/92(100)

1 Three ERROR results were observed; in all cases a new control was retested and the expected results were obtained.

2 Two ERROR results and one INVALID result were obtained; in all cases a new control was retested and the expected results were obtained. 3 SPC: Sample Processing Control

4 More than 30 measurements were taken as extra positive controls were ran during re-tests of negative controls.

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Image /page/4/Picture/0 description: The image shows the logo for "Microbiologics". The logo features a stylized symbol resembling a crescent shape in blue and red, followed by the word "Microbiologics" in a bold, dark blue font. Below the word, there is a thin red line and the tagline "A safer, healthier world." in a smaller, lighter font.

NegativeTarget	Agreement (%) with Expected Results, by Test Site
	Site 11,2,3	Site 22,3	Site 3	Overall
SAC	33/33(100)	34/34(100)	30/30(100)	97/97(100)
SPC	33/33(100)	34/34(100)	30/30(100)	97/97(100)

1 Two ERROR results were observed at Site 1; in all cases a new control was retested and the expected results were obtained. 2 One Negative Control at Site 1 and two Negative Controls at Site 2 generated a positive result for NG2 target, however the qualitative results were negative in each case because the Xpert® CT/NG Assays requires both NG4 targets to be positive in order to return a positive result for NG. In accordance with the assay protocol, the work area was cleaned and the controls were retested.

3 More than 30 measurements were taken as extra negative controls were ran during re-tests of positive controls.

Site	Mean Ct (%CV) Positive Control
	CT1	NG2	NG4
1	31.3 (1.3)	31.2 (1.4)	30.6 (1.5)
2	31.2 (2.6)	31.8 (2.1)	31.1 (2.6)
3	33.0 (3.9)	33.4 (4.1)	32.5 (4.0)
AllSites	31.8 (3.8)	32.1 (4.0)	31.4 (3.9)

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

Site	Mean Ct (%CV) NegativeControl
	SAC	SPC
1	27.3 (1.8)	31.6 (0.9)
2	27.7 (1.8)	31.4 (0.7)
3	28.8 (4.1)	31.5 (0.5)
AllSites	27.9 (3.5)	31.5 (0.7)

%CV: Percent Coefficient of Variation; SAC: Sample Adequacy Control; 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.”