Cepheid Xpert SA Nasal Complete Control Panel

K191168 · Microbiologics, Inc. · PMN · Jun 25, 2019 · Microbiology

Device Facts

• Record ID: K191168
• Device Name: Cepheid Xpert SA Nasal Complete Control Panel
• Applicant: Microbiologics, Inc.
• Product Code: PMN · Microbiology
• Decision Date: Jun 25, 2019
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 866.3920
• Device Class: Class 2

Intended Use

The Cepheid Xpert® SA Nasal Complete 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 Methicilin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) performed with the Cepheid Xpert® SA Nasal Complete Assay on the GeneXpert® Dx System. The controls comprise cultured and inactivated Methicillin-Resistant Staphylococcus aureus as the positive control 1: Staphylococcus aureus as the positive control 2; Staphylococcus epidermidis as the negative control. The Cepheid Xpert® SA Nasal Complete Control Panel is not intended to replace manufacturer controls provided with the Cepheid Xpert® SA Nasal Complete Assay.

Device Story

External assayed quality control material; monitors DNA extraction, amplification, and detection processes of Cepheid Xpert SA Nasal Complete Assay. Contains heat-inactivated microorganisms on swabs: MRSA (positive control 1), MSSA (positive control 2), and MSSE (negative control). Used in clinical laboratory settings; processed like patient samples on GeneXpert Dx System. Provides reproducible performance above assay limit of detection. Healthcare providers use results to verify assay performance; ensures reliability of patient test results.

Clinical Evidence

Precision and reproducibility study conducted across 3 sites with 6 operators and 3 lots over 5 days. Total of 90 tests per positive analyte and 90 tests for negative analyte. Results showed 100% agreement (90/90) for MRSA and SA detection. Mean Ct values and %CV reported for target genes (spa, mecA, SCC) and sample processing control. No clinical diagnostic data; bench testing only.

Technological Characteristics

Lyophilized, heat-inactivated microorganisms on swabs. Positive control 1: MRSA; Positive control 2: MSSA; Negative control: MSSE. Designed for use with GeneXpert Dx System. Standards referenced: 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 MRSA and SA detection using the Cepheid Xpert SA Nasal Complete 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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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services seal on the left and the FDA acronym along with the full name of the agency on the right. The FDA part of the logo is in blue, with the acronym in a square and the full name written out to the right of it.

June 25, 2019

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

# Re: K191168

Trade/Device Name: Cepheid Xpert SA Nasal Complete 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 symbol resembling a crescent moon or a partial circle in blue and red. To the right of the symbol, the word "Microbiologics" is written in a bold, blue sans-serif font. Below the word, there is a thin red line, and beneath that, the tagline "A safer, healthier world." is written in a smaller, lighter blue font.

### 510(k) Summary

#### 510(k) Number: K191168

Date: June 10, 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® SA Nasal Complete 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® SA Nasal Complete Control Panel is used to monitor the DNA extraction, amplification and detection processes of the Cepheid Xpert® SA Nasal Complete Assay. The Cepheid Xpert® SA Nasal Complete Control Panel contains cultured microorqanisms inactivated by heat treatments. Each Cepheid Xpert® SA Nasal Complete Control Panel consists of 6 individually packaged Methicillin-Resistant Staphylococcus aureus (MRSA) positive control swabs (positive control 1): 6 individually wrapped Staphylococcus aureus (MSSA) positive controls swabs (positive control 2); and 6 individually wrapped negative control swabs. Each positive control 1 swab contains 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® SA Nasal Complete Assay: Staphylococcal protein A gene spa (SPA), methicillin resistance gene mecA (mec), and the Staphylococcal cassette chromosome (SCC). Each positive control 2 swab contains MSSA at a target level designed to provide reproducible performance above the limit of detection of the spa gene target of the Cepheid Xpert® SA Nasal Complete Assay. Each negative control swab contains Staphylococcus epidermidis (MSSE) which is methicillin susceptible and not detected by the Cepheid Xpert® SA Nasal Complete Assay. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.

## Device Intended Use:

The Cepheid Xpert® SA Nasal Complete 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 Methicilin-Resistant Staphylococcus aureus (MRSA) and Staphylococcus aureus (SA) performed with the Cepheid Xpert® SA Nasal Complete Assay on the GeneXpert® Dx System. The controls comprise cultured and inactivated Methicillin-Resistant Staphylococcus aureus as the positive control 1: Staphylococcus aureus as the positive control 2; Staphylococcus epidermidis as the negative control.

The Cepheid Xpert® SA Nasal Complete Control Panel is not intended to replace manufacturer controls provided with the Cepheid Xpert® SA Nasal Complete Assay.

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Image /page/3/Picture/0 description: The image shows the Microbiologics logo. The logo features a stylized symbol in red and blue, 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.

## Substantial Equivalence:

| Characteristic | Cepheid Xpert® SA Nasal Complete | Cepheid Xpert® GBS LB Control |
|--------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Control Panel | Panel (K182472) |
| Intended Use | The Cepheid Xpert® SA Nasal Complete<br>Control Panel is intended for use as an<br>external assayed positive and negative<br>quality control to monitor the performance of<br>in vitro laboratory nucleic acid testing<br>procedures for the qualitative detection of<br>Methicillin-Resistant Staphylococcus aureus<br>(MRSA) and Staphylococcus aureus (SA)<br>performed with the Cepheid Xpert® SA<br>Nasal Complete Assay on the GeneXpert®<br>Dx System. The controls comprise cultured<br>and inactivated Methicillin-Resistant<br>Staphylococcus aureus as the positive<br>control 1; Staphylococcus aureus as the<br>positive control 2; Staphylococcus<br>epidermidis as the negative control.<br>The Cepheid Xpert® SA Nasal Complete<br>Control Panel is not intended to replace<br>manufacturer controls provided with the<br>Cepheid Xpert® SA Nasal Complete Assay. | The Cepheid Xpert® GBS LB Control<br>Panel is intended for use as external<br>assayed positive and negative quality<br>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.<br>The controls comprise cultured and<br>inactivated Streptococcus agalactiae<br>as the positive control and<br>Lactobacillus acidophilus as the<br>negative control.<br>The Cepheid Xpert® GBS LB Control<br>Panel is not intended to replace<br>manufacturer controls provided with<br>the device. |
| Physical Format | Lyophilized swab | Lyophilized swab |
| Composition | Inactivated microorganisms | Inactivated microorganisms |
| Analytes | Methicillin-Resistant Staphylococcus aureus<br>Staphylococcus aureus<br>Staphylococcus epidermidis | Streptococcus agalactiae<br>Lactobacillus acidophilus |
| Test System | Cepheid GeneXpert® Dx System | Cepheid GeneXpert® Instrument<br>System |
| Directions for Use | Process like patient sample | Process like patient sample |
| Assay Steps<br>Monitored | Extraction, amplification, and detection | Extraction, amplification, detection |

## 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® SA Nasal Complete 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® SA Nasal Complete Assay.

| Positive<br>Analyte<br>Location | Agreement (%) by Test Site/GeneXpert® System | | | | |
|-------------------------------------------------------------------|----------------------------------------------|-----------------------------|------------------------------|-------------------------|------------------------------|
| Assay Response | Site 1<br>Correct<br>Result | Site 2<br>Correct<br>Result | Site 31<br>Correct<br>Result | Site 31<br>NO<br>RESULT | Overall<br>Correct<br>Result |
| Methicillin-Resistant<br>Staphylococcus aureus<br>(SPA, mec, SCC) | 30/30<br>(100) | 30/30<br>(100) | 30/30<br>(100) | 1 | 90/90<br>(100) |
| Staphylococcus aureus<br>(SPA) | 30/30<br>(100) | 30/30<br>(100) | 30/30<br>(100) | 2 | 90/90<br>(100) |

1 Three NO RESULT responses were observed; new controls were 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 stylized symbol to the left, resembling a blue and red crescent shape. To the right of the symbol is the word "Microbiologics" in a bold, dark blue font, with a registered trademark symbol. Below the word is the tagline "A safer, healthier world." in a smaller, lighter font.

| Negative<br>Analyte | Agreement (%) by Test Site/GeneXpert® System | | | | | | | | |
|-------------------------------|----------------------------------------------|-----------|-------------------|---------|-----------|-------------------|---------|--------------|-------------------|
| Location | Site 11 | Site 21,3 | | | Site 31,2 | | Overall | | |
| Assay<br>Response | Correct<br>Result | INVALID | Correct<br>Result | INVALID | ERROR | Correct<br>Result | INVALID | NO<br>RESULT | Correct<br>Result |
| Staphylococcus<br>epidermidis | 30/30<br>(100) | 84 | 30/30<br>(100) | 2 | 1 | 30/30<br>(100) | 4 | 1 | 90/90<br>(100) |

1 Multiple INVALID responses were observed; new controls were retested and the expected results were obtained.

2 One NO RESULT response was observed; a new control was retested and the expected results were obtained. 3 One ERROR response was observed; a new control was retested, and the expected results were obtained.

4 Eight INVALID responses from single user.

| Site | 6027 Mean Ct (%CV) | | |
|-----------|--------------------|------------|------------|
| | SPA | mec | SCC |
| 1 | 27.0 (2.7) | 27.3 (2.6) | 28.5 (2.3) |
| 2 | 28.1 (2.3) | 28.4 (2.0) | 29.6 (1.9) |
| 3 | 27.8 (2.2) | 28.1 (2.1) | 29.3 (2.1) |
| All Sites | 27.6 (3.0) | 27.9 (2.8) | 29.1 (2.7) |

%CV: Percent Coefficient of Variation

| Site | 6028 Mean Ct<br>(%CV)<br>SPA |
|-----------|------------------------------|
| 1 | 26.8 (2.7) |
| 2 | 27.8 (2.5) |
| 3 | 27.4 (2.8) |
| All Sites | 27.3 (3.0) |

| %CV: Percent Coefficient of Variation | |
|---------------------------------------|--|
|---------------------------------------|--|

| Site | 6029 Mean Ct<br>(%CV) |
|-----------|-----------------------|
| | SPC |
| 1 | 32.0 (4.2) |
| 2 | 31.8 (3.5) |
| 3 | 32.1 (4.4) |
| All Sites | 32.0 (4.0) |

%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.