← Product Code [PMN](/submissions/MI/subpart-d%E2%80%94serological-reagents/PMN) · K191172

# Cepheid Xpert MRSA NxG Control Panel (K191172)

_Microbiologics, Inc. · PMN · Jun 20, 2019 · Microbiology · SESE_

**Canonical URL:** https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PMN/K191172

## Device Facts

- **Applicant:** Microbiologics, Inc.
- **Product Code:** [PMN](/submissions/MI/subpart-d%E2%80%94serological-reagents/PMN.md)
- **Decision Date:** Jun 20, 2019
- **Decision:** SESE
- **Submission Type:** Traditional
- **Regulation:** 21 CFR 866.3920
- **Device Class:** Class 2
- **Review Panel:** Microbiology

## Indications for 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).

## Regulatory 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](/device/K182472.md))

## Submission Summary (Full Text)

> This content was OCRed from public FDA records by [Innolitics](https://innolitics.com). If you use, quote, summarize, crawl, or train on this content, cite Innolitics at https://innolitics.com.
>
> Innolitics is a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices, including [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/).

{0}

Food and Drug Administration
10903 New Hampshire Avenue
Silver Spring, MD 20993-0002
www.fda.gov

# 510(k) SUBSTANTIAL EQUIVALENCE DETERMINATION DECISION SUMMARY

ASSAY ONLY

## I Background Information:

A 510(k) Number

K191172

B Applicant

Microbiologics, Inc.

C Proprietary and Established Names

Cepheid Xpert MRSA NxG Control Panel

D Regulatory Information

|  Product Code(s) | Classification | Regulation Section | Panel  |
| --- | --- | --- | --- |
|  PMN | Class II | 21 CFR 866.3920 - Assayed Quality Control Material For Clinical Microbiology Assays | IM - Immunology & MI - Microbiology  |

## II Submission/Device Overview:

A Purpose for Submission:

To obtain a Substantial Equivalence determination for the Cepheid Xpert MRSA NxG Control Panel for use with the Cepheid Xpert MRSA NxG Assay on the GeneXpert Instrument System.

B Measurand:

Nucleic acid quality control material from inactivated Methicillin-Resistant Staphylococcus aureus (MRSA, positive control) and Staphylococcus epidermidis (negative control).

C Type of Test:

The Cepheid Xpert MRSA NxG Control Panel is an external assayed positive and negative quality control material to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin-Resistant Staphylococcus aureus (MRSA) performed with the Cepheid Xpert MRSA NxG Assay on the GeneXpert Instrument System.

K191172 - Page 1 of 7

{1}

K191172 - Page 2 of 7

# III Intended Use/Indications for Use:

## A Intended Use(s):
See Indications for Use below.

## B Indication(s) for 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 Staphylococcus 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.

## C Special Conditions for Use Statement(s):
Rx - For Prescription Use Only

For in vitro diagnostic use only.

This product is not intended to replace the manufacturer controls provided with the Cepheid Xpert MRSA NxG Assay.

## D Special Instrument Requirements:
The Cepheid Xpert MRSA NxG Control Panel is intended for use on the GeneXpert Instrument System.

# IV Device/System Characteristics:

## A 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 a target 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 control swab contains Methicillin-Susceptible Staphylococcus epidermidis (MSSE) that is not targeted/detected by the assay. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

## B Principle of Operation:
The Cepheid Xpert MRSA NxG Control Panel is intended for use as external assayed quality control materials for use in monitoring the DNA extraction, amplification and detection

{2}

processes associated with the Cepheid Xpert MRSA NxG Assay on the GeneXpert Instrument System.

# V Substantial Equivalence Information:

A Predicate Device Name(s):

Cepheid Xpert GBS LB Control Panel

B Predicate 510(k) Number(s):

K182472

C Comparison with Predicate(s):

Table 1. Comparison with the Predicate

|  Device & Predicate Device(s): | K191172 | K182472  |
| --- | --- | --- |
|  Device Trade Name | Cepheid Xpert MRSA NxG Control Panel | Cepheid Xpert GBS LB Control Panel  |
|  General Device Characteristic Similarities  |   |   |
|  Intended Use/Indications for Use | 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 Staphylococcus aureus (MRSA) 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. | External assayed positive and negative quality control materials to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Group B Streptococcus (GBS) performed with the Cepheid Xpert GBS LB Assay on the GeneXpert Instrument System. The controls comprise cultured and inactivated Streptococcus agalactiae as the positive control and Lactobacillus acidophilus as the negative control. The Cepheid Xpert GBS LB Control Panel is not intended to replace the manufacturer controls provided with the device.  |
|  Composition | Inactivated microorganisms | Same  |
|  Test System | Cepheid GeneXpert System | Same  |
|  Directions for Use | Process like a patient sample | Same  |

K191172 - Page 3 of 7

{3}

K191172 - Page 4 of 7

|  Assay Steps Monitored | Extraction, amplification, and detection | Same  |
| --- | --- | --- |
|  Physical Format | Lyophilized swab | Lyophilized swab  |
|  General Device Characteristic Differences  |   |   |
|  Analytes | • Positive Control: (MRSA) Methicillin-resistant Staphylococcus aureus
• Negative Control: Staphylococcus epidermidis | • Positive Control: Streptococcus agalactiae
• Negative Control: Lactobacillus acidophilus  |
|  Assay Compatibility | Cepheid Xpert MRSA NxG Assay (K162444) | Cepheid Xpert GBS LB Assay (K121539)  |

## VI Standards/Guidance Documents Referenced:

CLSI. Evaluation of Stability of In Vitro Diagnostic Reagents; Approved Guideline. CLSI Document EP25-A. Wayne, PA: Clinical and Laboratory Standards Institute; 2009.

CLSI. Evaluation of Precision of Quantitative Measurement Procedures: Approved Guideline – Third Edition. CLSI Document EP05-A3. Wayne, PA: Clinical and Laboratory Standards Institute; 2014.

ANSI. Sampling Procedures and Tables for Inspection by Attributes. ANSI/ASQ Z1.4-2003; 2013.

## VII Performance Characteristics (if/when applicable):

### A Analytical Performance:

1. Precision/Reproducibility:

A study was performed to determine the reproducibility of the Cepheid Xpert MRSA NxG Control Panel using the Cepheid Xpert MRSA NxG Assay on the GeneXpert Instrument System. Testing was done at three different locations over five days. At each location, two operators each tested three lots of control material for a total of at least 90 test results for each control swab (3 sites x 5 days x 2 operators x ≥3 replicates = ≥90 replicates in total). Summaries of the results for both the positive and negative controls are provided in Table 2 and Table 3. On initial testing one positive control and three negative controls were reported as "ERROR" due to system failure. In each case, retesting was performed with new control swabs and all positive and negative controls produced the expected results.

Table 2. Summary of results from the Reproducibility Study (qualitative)

|  Positive Control (Methicillin-Resistant Staphylococcus aureus)  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Test location | Total Tests Performed | ERROR^{1} | Correct Result^{2} | Incorrect Result | Percent Correct^{3}  |
|  1 | 33 | 1 | 32 | 0 | 100%  |
|  2 | 31 | 0 | 31 | 0 | 100%  |
|  3 | 30 | 0 | 30 | 0 | 100%  |
|  All sites | 94 | 1 | 93 | 0 | 100%  |

{4}

K191172 - Page 5 of 7

|  Negative Control (Staphylococcus epidermidis)  |   |   |   |   |   |
| --- | --- | --- | --- | --- | --- |
|  Test location | Total Tests Performed | ERROR¹ | Correct Result² | Incorrect Result | Percent Correct³  |
|  1 | 33 | 2 | 31 | 0 | 100%  |
|  2 | 32 | 1 | 31 | 0 | 100%  |
|  3 | 30 | 0 | 30 | 0 | 100%  |
|  All sites | 95 | 3 | 92 | 0 | 100%  |

¹ Number of ERROR responses observed; in each case new controls were tested and the expected results were obtained.
² As indicated in the test protocol, both positive and negative controls were retested in the event of an ERROR response.
³ Data from the test runs with the ERROR response were not included in the Percent Correct analysis.

Table 3. Summary of results from the Reproducibility Study (quantitative)

|   | Mean Ct (%CV)  |   |   |
| --- | --- | --- | --- |
|  Test location | Positive Control |   | Negative Control  |
|   |  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)  |

SPC: Sample processing control
Ct: Cycle Threshold; %CV: Percent Coefficient of Variation;

The reproducibility of the Cepheid Xpert MRSA NxG Control Panel within and between test locations, GeneXpert Instruments, operators, and lots was determined to be acceptable.

2. Linearity:
Not applicable.

3. Analytical Specificity/Interference:
Not applicable.

4. Assay Reportable Range:
Not applicable.

5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):

Traceability:
Not applicable.

Stability:
1. Shelf-life was established through an Accelerated Stability Study that was performed with three lots of the Cepheid Xpert MRSA NxG Control Panel placed at elevated temperatures (43°C, 53°C and 63°C). Four replicates of the positive control were tested at each of the four time points (Day 0, Day 14, Day 28 and Day 42). The negative control was tested in duplicate at two time points (Day 0 and Day 42). At each time point, each replicate of both the positive and negative controls produced the expected results with the Cepheid Xpert

{5}

MRSA NxG Assay on the GeneXpert Instrument System. Together with regression analysis of Ct values, these results were used to support assignment of 9 month expiration dating from the date of manufacture when the Cepheid Xpert MRSA NxG Control Panel is held at 2°C - 25°C.

2. A Real-Time, Shelf-Life Stability Study is in process. Under a 14-point regression design, three lots of each control will be incubated at two temperatures (2-8°C and 25°C). Regression analysis will be performed at the end of the study to evaluate performance and determine if the acceptance criteria are met. At that time, the expiration date will be updated to the time point at which all criteria are met.

3. An In-Use Stability Study was done to determine how long the positive and negative controls would remain stable after reconstitution. Controls from a single lot were rehydrated and kept at room temperature for different time periods prior to testing. All results were as expected and indicate that Cepheid Xpert MRSA NxG Control Panel swabs may be used up to five hours following rehydration.

6. Detection Limit:
Not applicable.

7. Assay Cut-Off:
Not applicable.

B. Comparison Studies:

1. Method Comparison with Predicate Device:
Not applicable.

2. Matrix Comparison:
Not applicable.

C. Clinical Studies:

1. Clinical Sensitivity:
Not applicable.

2. Clinical Specificity:
Not applicable.

3. Other Clinical Supportive Data (When 1. and 2. Are Not Applicable):
Not applicable.

D. Clinical Cut-Off:
Not applicable.

K191172 - Page 6 of 7

{6}

# E Expected Values/Reference Range:

The Cepheid Xpert MRSA NxG Control Panel is a qualitative control expected to produce the results described in Table 4 when tested with the Cepheid Xpert MRSA NxG Assay using the GeneXpert Instrument System.

Table 4: Expected values

|  Control | Analyte | Expected Assay Result | Interpretation  |
| --- | --- | --- | --- |
|  Positive Control | Methicillin-Resistant S. aureus(MRSA) | MRSA DETECTED | MRSA DNA is detected. MRSA targets, mec (mecA/mecC) and SCCmec, have a cycle threshold (Ct) within the valid range.  |
|  Negative Control | Methicillin-Susceptible S. epidermidis | MRSA NOT DETECTED | MRSA DNA is detected. Target DNA for SCCmec and/or mec (mecA/mecC) is not detected.  |

# VIII Proposed Labeling:

The labeling supports the finding of substantial equivalence for this device.

# IX Conclusion:

The submitted information in this premarket notification is complete and supports a substantial equivalence decision.

K191172 - Page 7 of 7

---

**Source:** [https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PMN/K191172](https://fda.innolitics.com/submissions/MI/subpart-d%E2%80%94serological-reagents/PMN/K191172)

**Published by [Innolitics](https://innolitics.com)** — a medical-device software consultancy. We help companies design, build, and clear FDA-regulated software and AI/ML devices. If you're preparing [a 510(k)](https://innolitics.com/services/510ks/), [a De Novo](https://innolitics.com/services/regulatory/), [a SaMD](https://innolitics.com/services/end-to-end-samd/), [an AI/ML medical device](https://innolitics.com/services/medical-imaging-ai-development/), or [an FDA regulatory strategy](https://innolitics.com/services/regulatory/), [get in touch](https://innolitics.com/contact).

**Cite:** Innolitics at https://innolitics.com