Cepheid Xpert MRSA NxG Control Panel

K191172 · Microbiologics, Inc. · PMN · Jun 20, 2019 · Microbiology

Device Facts

• Record ID: K191172
• Device Name: Cepheid Xpert MRSA NxG Control Panel
• Applicant: Microbiologics, Inc.
• Product Code: PMN · Microbiology
• Decision Date: Jun 20, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3920
• Device Class: Class 2

Intended Use

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 Story

External quality control material for clinical microbiology assays; monitors DNA extraction, amplification, and detection processes of Cepheid Xpert® MRSA NxG Assay. Input: heat-inactivated cultured microorganisms (MRSA positive control; S. epidermidis negative control) on lyophilized swabs. Process: swabs processed like patient samples on GeneXpert® Instrument System. Output: qualitative detection results (positive/negative) and Ct values for target genes (mecA, SCC) and sample processing control (SPC). Used in clinical laboratories; operated by laboratory personnel. Output used by clinicians to verify assay performance and ensure reliability of patient test results; benefits patient by reducing risk of false results in MRSA diagnostic testing.

Clinical Evidence

No clinical data. Bench testing only. Reproducibility study conducted across three sites, five days, two operators, using three lots (≥90 replicates per control). Results showed 100% correct results for both positive and negative controls. Stability established via accelerated study (43°C, 53°C, 63°C) supporting 9-month shelf life at 2°C-25°C and 5-hour in-use stability post-rehydration.

Technological Characteristics

Lyophilized, heat-inactivated microbial swabs. Positive control: MRSA; Negative control: MSSE. Compatible with GeneXpert Instrument System. Standards: CLSI EP25-A (stability), CLSI EP05-A3 (precision), ANSI/ASQ Z1.4-2003 (sampling).

Indications for Use

Indicated for use as external quality control material for laboratory personnel performing nucleic acid testing for Methicillin-Resistant Staphylococcus aureus (MRSA) using the Cepheid Xpert MRSA NxG Assay on the GeneXpert Instrument 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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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 ([e-mail]) or phone [phone] 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 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® 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:

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.

#### Device Intended Use:

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.

#### 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 vitro<br>laboratory nucleic acid testing procedures<br>for the qualitative detection of Methicillin-<br>Resistant Staphylococcus aureus performed<br>with the Cepheid Xpert® MRSA NxG Assay<br>on the GeneXpert® Instrument System. The<br>controls comprise cultured and inactivated<br>Methicillin-Resistant Staphylococcus aureus<br>as the positive control and Staphylococcus<br>epidermidis as the negative control. | materials to monitor the performance of in<br>vitro laboratory nucleic acid testing<br>procedures for the qualitative detection of<br>Group B Streptococcus (GBS) performed<br>with the Cepheid Xpert® GBS LB Assay on<br>the GeneXpert® Instrument System. The<br>controls comprise cultured and inactivated<br>Streptococcus agalactiae as the positive<br>control and Lactobacillus acidophilus as<br>the 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 the<br>Cepheid Xpert® MRSA NxG Assay. | controls provided with the device. |
| Physical Format | Lyophilized swab | Lyophilized swab |
| Composition | Inactivated microorganisms | Inactivated microorganisms |
| Analytes | Methicillin-Resistant Staphylococcus aureus<br>Staphylococcus epidermidis | 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® 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.

| Positive<br>Analyte | Agreement (%) by Test Site/GeneXpert® System | | | |
|-----------------------------------------------------------|----------------------------------------------|----------------|----------------|----------------|
| | Site 11 | Site 2 | Site 3 | Overall |
| Methicillin-Resistant Staphylococcus aureus<br>(mec, SCC) | 32/32<br>(100) | 31/31<br>(100) | 30/30<br>(100) | 93/93<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 11 | Site 21 | Site 3 | Overall |
| Staphylococcus epidermidis | 31/31<br>(100) | 31/31<br>(100) | 30/30<br>(100) | 92/92<br>(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.