Cepheid Xpert C. difficile/Epi Control Panel

K190463 · Microbiologics, Inc. · PMN · Apr 19, 2019 · Microbiology

Device Facts

• Record ID: K190463
• Device Name: Cepheid Xpert C. difficile/Epi Control Panel
• Applicant: Microbiologics, Inc.
• Product Code: PMN · Microbiology
• Decision Date: Apr 19, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3920
• Device Class: Class 2

Intended Use

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 Story

External assayed quality control material; lyophilized positive and negative control swabs. Positive control contains heat-inactivated Clostridioides difficile 027/NAP1/B1 strain; negative control contains heat-inactivated Clostridium sordellii. Used in clinical laboratories to monitor DNA extraction, amplification, and detection processes of Cepheid Xpert C. difficile/Epi assay on GeneXpert Dx System. Operators rehydrate swabs in sample reagent; process on GeneXpert instrument. Output consists of qualitative positive/negative results for toxin B (tcdB), binary toxin genes, and tcdC gene deletion. Ensures assay performance and validity of patient test results.

Clinical Evidence

No clinical data. Bench testing only. Reproducibility study conducted at three sites over five days with three lots of controls (n ≥ 90 replicates per control). All replicates produced expected qualitative results. Mean cycle threshold (Ct) and endpoint fluorescence values were consistent across sites, operators, and lots. Stability studies support 18-month shelf-life at 2-25°C and 5-hour in-use stability at 20°C.

Technological Characteristics

Lyophilized swab format; heat-inactivated microbial organisms. Positive control: Clostridioides difficile 027/NAP1/B1. Negative control: Clostridium sordellii. Compatible with GeneXpert Dx System. Standards referenced: CLSI EP25-A (stability), CLSI EP05-A3 (precision).

Indications for Use

Indicated for use as external quality control material for laboratory personnel performing nucleic acid testing for Clostridioides difficile using the Cepheid Xpert C. difficile/Epi assay on the GeneXpert Dx System.

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

• Cepheid Xpert® GBS LB Control Panel (K182472)

Submission Summary (Full Text)

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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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Image /page/1/Picture/0 description: The image contains the logos of the U.S. Food and Drug Administration (FDA) and the Department of Health & Human Services. The FDA logo features the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text. The Department of Health & Human Services logo is a symbol with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" surrounding it.

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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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 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 ([e-mail]) or phone [phone] 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 North<br>St. Cloud, MN 56303 |
| Primary Contact: | Tina Sobania, Director of Corporate Quality |
| Phone: | 320-229-7050 |
| Email: | [e-mail] |

#### 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:

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.

## Device Intended Use:

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.

#### 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 quality<br>controls to monitor the performance of in<br>vitro laboratory nucleic acid testing<br>procedures for the qualitative detection of<br>Clostridioides (Clostridium) difficile<br>performed with the Cepheid Xpert® C.<br>difficile/Epi assay on the GeneXpert® Dx<br>System. The controls comprise cultured<br>and inactivated Clostridioides (Clostridium)<br>difficile 027-NAP1-B1 as the positive<br>control and Clostridium sordellii as the<br>negative control.<br>The Cepheid Xpert® C. difficile/Epi Control<br>Panel is not intended to replace<br>manufacturer controls provided with the<br>device. | control materials to monitor the<br>performance of in vitro laboratory<br>nucleic acid testing procedures for the<br>qualitative detection of Group B<br>Streptococcus (GBS) performed with<br>the Cepheid Xpert® GBS LB Assay on<br>the GeneXpert® Instrument System. The<br>controls comprise cultured and<br>inactivated Streptococcus agalactiae as<br>the positive control and Lactobacillus<br>acidophilus as the negative control.<br>The Cepheid Xpert® GBS LB Control<br>Panel is not intended to replace<br>manufacturer controls provided with the<br>device. |
|--------------------|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Physical Format | Lyophilized swab | Lyophilized swab |
| Composition | Inactivated microorganisms | Inactivated microorganisms |
| Analytes | Clostridioides difficile (tcdB, binary toxin,<br>tcdC)<br>Clostridium sordellii | Streptococcus agalactiae<br>Lactobacillus 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.

| Positive<br>Analyte | Agreement (%) by Test Site/GeneXpert® System | | | |
|------------------------------------------------------|----------------------------------------------|----------------|----------------|----------------|
| | Site 1 | Site 21 | Site 3 | Overall |
| Clostridioides difficile<br>(tcdB/binary toxin/tcdC) | 30/30<br>(100) | 31/31<br>(100) | 30/30<br>(100) | 91/91<br>(100) |

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

| Negative<br>Analyte | Agreement (%) by Test Site/GeneXpert® System | | | |
|------------------------------|----------------------------------------------|----------------|----------------|----------------|
| | Site 1 | Site 21 | Site 3 | Overall |
| <i>Clostridium sordellii</i> | 30/30<br>(100) | 31/31<br>(100) | 30/30<br>(100) | 91/91<br>(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.