Amplichek II, Negative and Amplichek II, Negative MiniPak, Amplichek II, Level 1 and Amplichek II, Level 1 MiniPak, Amplichek II, Level 2 and Amplichek II, Level 2 MiniPak, Amplichek II, Level 3 and Amplichek II, Level 3 MiniPak

DEN150058 · Bio-Rad Laboratories · PMN · Mar 28, 2016 · Microbiology

Device Facts

• Record ID: DEN150058
• Device Name: Amplichek II, Negative and Amplichek II, Negative MiniPak, Amplichek II, Level 1 and Amplichek II, Level 1 MiniPak, Amplichek II, Level 2 and Amplichek II, Level 2 MiniPak, Amplichek II, Level 3 and Amplichek II, Level 3 MiniPak
• Applicant: Bio-Rad Laboratories
• Product Code: PMN · Microbiology
• Decision Date: Mar 28, 2016
• Decision: DENG
• Submission Type: Post-NSE
• Regulation: 21 CFR 866.3920
• Device Class: Class 2

Intended Use

Amplichek II is intended for use as an external assayed quality control material to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin Resistant Staphylococcus aureus, Methicillin Sensitive Staphylococcus aureus. Clostridium difficile and Vancomycin-resistant Enterococci performed on Cepheid GeneXpert Systems. This product is not intended to replace manufacturer controls provided with the device. This product is only for use with assays and instruments listed in the Representative Results Chart in this labeling.

Device Story

Amplichek II is an external assayed quality control material; used in clinical microbiology laboratories to monitor performance of nucleic acid testing procedures. Input: device acts as a surrogate sample processed through Cepheid GeneXpert Systems; output: qualitative detection results compared against expected values provided in labeling. Device assists laboratory personnel in verifying test precision and detecting systematic analytical deviations (reagent or instrument variation). Does not replace manufacturer-provided controls. Benefits: ensures reliability of diagnostic testing for MRSA, MSSA, C. difficile, and VRE; supports compliance with quality control requirements.

Clinical Evidence

No clinical data. Performance established via bench testing. Reproducibility studies conducted at multiple sites using different operators, lots, and days demonstrated 100% agreement with expected qualitative results for all analytes. Ct mean, SD, and %CV values were reported for positive levels.

Technological Characteristics

Liquid-form control material containing purified, chemically inactivated microorganisms. Buffer solution includes 0.1% 5-chloro-2-methyl-2H-isothiazol-3-one preservative. Three levels (Negative, 1, 2, 3). Designed for use with Cepheid GeneXpert Systems. Storage: 2°C to 8°C.

Indications for Use

Indicated for use as an external assayed quality control material for monitoring in vitro nucleic acid testing procedures (MRSA, MSSA, C. difficile, VRE) on Cepheid GeneXpert Systems. For in vitro diagnostic and prescription use only.

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.”

Submission Summary (Full Text)

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## EVALUATION OF AUTOMATIC CLASS II DESIGNATION FOR Bio-Rad Laboratories Amplichek II

### DECISION SUMMARY

#### A. DEN Number:

DEN150058

#### B. Purpose for Submission:

De novo request for evaluation of automatic Class III designation for the Bio-Rad Laboratories Amplichek II.

#### C. Measurand:

Multi-analyte quality control materials

### D. Type of Test:

Amplichek II is intended for use as an external assayed quality control material to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin Resistant Staphylococcus aureus, Methicillin Sensitive Staphylococcus aureus, Clostridium difficile and Vancomycin-resistant Enterococci performed on Cepheid GeneXpert Systems. This product is not intended to replace manufacturer controls provided with the device. This product is only for use with assays and instruments listed in the Representative Results Chart in this labeling.

### E. Applicant:

Bio-Rad Laboratories

### F. Proprietary and Established Names:

Amplichek II

### G. Regulatory Information:

### 1. Regulation section:

21 CFR 866.3920, Assayed quality control material for clinical microbiology assays

### 2. Classification:

Class II (Special Controls)

{1}------------------------------------------------

### 3. Product code:

PMN

- 4. Panel:
83- Microbiology

## H. Indication(s) for use:

- 1. Indications for use(s):
Amplichek II is intended for use as an external assayed quality control material to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin Resistant Staphylococcus aureus, Methicillin Sensitive Staphylococcus aureus. Clostridium difficile and Vancomycin-resistant Enterococci performed on Cepheid GeneXpert Systems. This product is not intended to replace manufacturer controls provided with the device. This product is only for use with assays and instruments listed in the Representative Results Chart in this labeling.

- 2. Special conditions for use statement(s):
For in vitro diagnostic use only

For prescription use only

- 3. Special instrument requirements:
The Amplichek II was evaluated on the Cepheid GeneXpert system.

# I. Device Description:

Amplichek II (Assayed Microbiology Control) is manufactured at three levels, Levels 1, 2 and 3, for each analyte indicated in the package insert. Individual analyte values are listed in the package insert and are specific for the instrument system or method utilized.

Each control is prepared in liquid form in a buffer solution with preservatives including 5chloro-2-methyl-2H-isothiazol-3-one at a concentration of 0.1%, stabilizers and added preparations of purified intact microorganisms grown in microbial culture. Source materials are chemically treated and processed to inactivate infectious agents. However, no known test or inactivation method can assure that this product will not transmit infection. Thus, the package insert recommends that this product and all human specimens be handled in accordance with Biosafety Level 2 practices as described in the United States Department of Health and Human Services Centers for Disease Control and Prevention (CDC) and National Institutes of Health (NIH), Biosafety in Microbiological and Biomedical Laboratories, or other equivalent guidelines.

{2}------------------------------------------------

## J. Standard/Guidance Document Referenced (if applicable):

None was referenced

### K. Test Principle:

Not applicable

### L. Performance Characteristics (if/when applicable):

### 1. Analytical performance:

### a. Precision/Reproducibility:

Two reproducibility studies were performed with the Amplichek II on Cepheid Xpert test kits and GeneXpert systems. Assay reproducibility was evaluated for all Amplichek II levels: Negative (Methicillin Sensitive Staphylococcus epidermidis (MSSE)), Level 1 (Methicillin Sensitive Staphylococcus aureus (MSSA)), Level 2 and Level 3 (Methicillin Resistant Staphylococcus aureus (MRSA), Clostridium difficile (Cdiff), and Vancomycin-resistant Enterococci (VRE). Testing on Cepheid Xpert test kits and GeneXpert systems incorporated a range of potential testing variables including different operators, different lots, and different days.

The first reproducibility study was performed at one laboratory site and was assessed using two product lots on the Cepheid Xpert test kits by two operators performed for ten different days, two replicates per run, and two runs per day for a total of 40 test results for each lot. Summary of qualitative results from the first reproducibility study (percent agreement with the expected result) for each control is provided in the Table 1 below.

| Table 1. Amplichek II Summary of Reproducibility Result using Cepheid Xpert test kits | | | | | |
|---------------------------------------------------------------------------------------|--------------------|-----------------|------------------------|------------------------|------------------------------|
| Gene | Amplichek II Level | Expected Result | % Agreement*<br>Lot #1 | % Agreement*<br>Lot #2 | % Total Agreement by Samples |
| Cepheid Xpert SA Nasal Complete (MSSA/MRSA) | | | | | |
| SPA | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SCCmec | Negative | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| mecA | | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SPA | | Positive | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SCCmec | Level 1 | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| mecA | | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SPA | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SCCmec | Level 2 | Positive | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| mecA | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SPA | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| SCCmec | Level 3 | Positive | 100% (40/40) | 100% (40/40) | 100% (80/80) |

{3}------------------------------------------------

| Table 1. Amplichek II Summary of Reproducibility Result using Cepheid Xpert test kits | | | | | |
|---------------------------------------------------------------------------------------|----------|----------|--------------|--------------|--------------|
| mecA | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Cepheid Xpert C. difficile/Epi (C.Difficile) | | | | | |
| Binary<br>Toxin | | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| | Toxin B | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| | TcdC | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Binary<br>Toxin | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| | Toxin B | Level 1 | Negative | 100% (40/40) | 100% (40/40) |
| | TcdC | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Binary<br>Toxin | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| | Toxin B | Level 2 | Positive | 100% (40/40) | 100% (40/40) |
| | TcdC | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Binary<br>Toxin | | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| | Toxin B | Level 3 | Positive | 100% (40/40) | 100% (40/40) |
| | TcdC | | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Cepheid Xpert vanA (VRE) | | | | | |
| Van A | Negative | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Van A | Level 1 | Negative | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Van A | Level 2 | Positive | 100% (40/40) | 100% (40/40) | 100% (80/80) |
| Van A | Level 3 | Positive | 100% (40/40) | 100% (40/40) | 100% (80/80) |

*For Negative samples, % Agreement = (#negative/total samples run); for positive samples, % Agreement = (#positive/total samples run).

> The second study was performed at three laboratory sites and was assessed using two product lots on the Cepheid Xpert test kits by different operators performed for three different days for a total of 9 test results for each lot. A summary of qualitative results from the second reproducibility study (percent agreement with the expected result) for each control is provided in the Table 2 below.

| Table 2. Amplichek II Summary of Performance Evaluation using Cepheid Xpert test kits | | | | | | | | |
|---------------------------------------------------------------------------------------|-----------------------|---------------------------|------------|--------|-----------|------------|----------|--------|
| | Lot #1 | | | Lot #2 | | | | |
| Test | Amplichek<br>II Level | Expected<br>Result | Ct<br>Mean | Ct SD | Ct<br>%CV | Ct<br>Mean | Ct<br>SD | Ct %CV |
| Cepheid Xpert MRSA (MRSA) | | | | | | | | |
| SCCmec | Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| SCCmec | Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| SCCmec | Level 2 | Positive | 28.7 | 0.9 | 3.3 | 30.1 | 1.6 | 5.5 |
| SCCmec | Level 3 | Positive | 23.6 | 0.6 | 2.7 | 24.2 | 1.2 | 4.8 |
| Cepheid Xpert SA Nasal<br>Complete (MSSA/MRSA) | | | | | | | | |
| SPA/<br>SCCmec/ | Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| Table 2. Amplichek II Summary of Performance Evaluation using Cepheid Xpert test kits | | | | | | | | |
| | | Lot #1 | | | Lot #2 | | | |
| Test | Amplichek II Level | Expected Result | Ct Mean | Ct SD | Ct %CV | Ct Mean | Ct SD | Ct %CV |
| mecA | Level 1 | Positive | 30.2 | 1.5 | 4.8 | 29.7 | 0.4 | 1.4 |
| SPA | | | | | | | | |
| SCCmec/mecA | | | | | | | | |
| Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 2 | Positive | 28.4 | 0.7 | 2.5 | 30.4 | 1.1 | 3.7 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 2 | Positive | 30.9 | 0.7 | 2.4 | 32.0 | 1.2 | 3.7 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 3 | Positive | 29.9 | 0.7 | 2.3 | 30.9 | 1.3 | 4.1 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 3 | Positive | 23.3 | 0.6 | 2.4 | 24.5 | 0.8 | 3.1 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 3 | Positive | 25.6 | 0.6 | 2.3 | 26.0 | 0.8 | 2.9 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Level 3 | Positive | 24.6 | 0.6 | 2.3 | 24.8 | 0.8 | 3.2 | |
| | | SPA | | | | | | |
| | | SCCmec/mecA | | | | | | |
| Cepheid Xpert MRSA/SA Blood Culture MRSA (MSSA/MRSA) | | | | | | | | |
| Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 1 | Positive | 31.9 | 1.5 | 4.7 | 31.2 | 1.7 | 5.4 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 30.5 | 0.7 | 2.3 | 30.7 | 1.4 | 4.5 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 33.1 | 0.7 | 2.1 | 32.1 | 1.2 | 3.8 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 31.9 | 0.7 | 2.1 | 31.1 | 1.2 | 4.0 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 24.2 | 1.0 | 4.1 | 25.6 | 0.8 | 3.0 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 27.0 | 0.9 | 3.3 | 27.2 | 0.7 | 2.8 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 25.8 | 0.9 | 3.5 | 26.2 | 0.8 | 3.1 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Cepheid Xpert MRSA/SA SSTI (MSSA/MRSA) | | | | | | | | |
| Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 1 | Positive | 30.8 | 1.4 | 4.4 | 29.5 | 1.3 | 4.4 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 29.1 | 1.6 | 5.6 | 30.4 | 0.9 | 2.9 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 31.7 | 1.5 | 4.6 | 31.7 | 0.9 | 2.7 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 2 | Positive | 30.6 | 1.6 | 5.1 | 30.5 | 0.8 | 2.7 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 23.6 | 0.8 | 3.5 | 25.6 | 2.1 | 8.1 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 25.9 | 0.8 | 3.2 | 26.3 | 1.5 | 5.7 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Level 3 | Positive | 24.9 | 0.9 | 3.7 | 25.3 | 1.5 | 5.9 | |
| | | SPA/SCCmec/mecA | | | | | | |
| | | SPA | | | | | | |
| Cepheid Xpert C. difficile/Epi (C.difficile) | | | | | | | | |
| Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | Binary Toxin/Toxin B/TcdC | | | | | | |
| | | Binary Toxin/ | | | | | | |
| Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A | |
| | | Binary Toxin/Toxin B/TcdC | | | | | | |
| | | Binary Toxin/ | | | | | | |
| Table 2. Amplichek II Summary of Performance Evaluation using Cepheid Xpert test kits | | | | | | | | |
| | | | Lot #1 | | | Lot #2 | | |
| Test | Amplichek<br>II Level | Expected<br>Result | Ct<br>Mean | Ct SD | Ct<br>%CV | Ct<br>Mean | Ct<br>SD | Ct %CV |
| Toxin B/<br>TcdC<br>Binary Toxin | | | 28.4 | 2.0 | 7.2 | 28.1 | 1.1 | 3.8 |
| Toxin B | Level 2 | Positive | 29.1 | 2.2 | 7.4 | 28.9 | 1.1 | 3.8 |
| TcdC | | | 29.7 | 2.2 | 7.5 | 29.5 | 1.2 | 4.1 |
| Toxin B/<br>TcdC<br>Binary Toxin | | | 24.2 | 2.2 | 9.1 | 24.2 | 1.2 | 4.8 |
| Toxin B | Level 3 | Positive | 25.1 | 2.1 | 8.4 | 25.1 | 1.2 | 4.9 |
| TcdC | | | 25.4 | 2.3 | 9.1 | 25.9 | 1.3 | 5.1 |
| Cepheid Xpert C. difficile<br>( <i>C.difficile</i> ) | | | | | | | | |
| Toxin B | Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| Toxin B | Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| Toxin B | Level 2 | Positive | 29.0 | 0.8 | 2.9 | 29.6 | 0.9 | 3.0 |
| Toxin B | Level 3 | Positive | 24.3 | 0.8 | 3.1 | 24.8 | 1.1 | 4.5 |
| Cepheid Xpert vanA<br>(VRE) | | | | | | | | |
| Van A | Negative | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| Van A | Level 1 | Negative | N/A | N/A | N/A | N/A | N/A | N/A |
| Van A | Level 2 | Positive | 28.6 | 1.9 | 6.8 | 30.1 | 1.2 | 4.0 |
| Van A | Level 3 | Positive | 21.1 | 1.7 | 8.0 | 25.1 | 1.2 | 4.8 |

{4}------------------------------------------------

{5}------------------------------------------------

N/A: Negative Ct recovery observed

These results establish the variance in testing of the control material when tested by multiple users, multiple sites on different days. Reproducibility study data are acceptable.

- b. Linearity/assay reportable range:
Not applicable

- c. Traceability, Stability, Expected values (controls, calibrators, or methods):
Traceability:

Not applicable

Stability:

An accelerated stability study was performed to establish the shelf life stability claims for Amplichek II. Based on this study, Amplichek II Levels Negative, 1, 2, and 3 is expected to be stable until the expiration date when stored unopened between 2°C to 8°C. This product is for single use.

{6}------------------------------------------------

Real-Time Stability Program: Real-time stability studies are ongoing to support product claims and to monitor potential assay modifications for which the Amplicheck II is indicated for use. Real-time stability study protocols and acceptance criteria were reviewed and found to be acceptable.

Expected Values:

- d. Detection limit:
Not applicable

- e. Analytical Reactivity (Inclusivity):
Not applicable

- f. Cross Reactivity:
Not applicable

- Interference: g.
Not applicable

- Assay cut-off: h.
Not applicable.

- 2. Comparison studies:
- a. Method comparison with predicate device:

Not applicable.

- b. Matrix comparison:
Not applicable

- 3. Clinical Studies:
- a. Clinical Sensitivity:

Not applicable

- b. Clinical specificity:

{7}------------------------------------------------

Not applicable

- Other clinical supportive data (when a. and b. are not applicable): C.
Not applicable.

- 4. Clinical cut-off:
Not Applicable.

- 5. Expected values/Reference range:
This product does not have assigned values. Representative results from testing control material using Cepheid Xpert commercially marketed test kits presented in the Representative Results Chart below were obtained by testing one lot of this product in the same manner as used for unknown specimens. Each data set was obtained by testing this product at three different locations on three different days. The results were tabulated and are presented in the chart directly below. Results may vary depending on the use of different lots of the same test kit and different laboratories. Performance characteristics for Amplichek II have not been evaluated for use with other laboratory tests.

| Representative Results Chart | | | | | |
|-------------------------------------------|---------------|----------|-------------------------------------|--------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------|
| Analytes | *PPA | Negative | Level 1 | Level 2 | Level 3 |
| MRSA/ MSSA | | | | | |
| Cepheid Xpert<br>MRSA | 100%<br>(9/9) | Negative | Negative | Positive<br>(SCCmec Ct. 25.1 - 35.0) | Positive<br>(SCCmec Ct. 20.7 - 27.7) |
| Cepheid Xpert<br>SA Nasal<br>Complete | 100%<br>(9/9) | Negative | Positive<br>(SPA Ct. 28.5 - 30.9) | Positive<br>(SPA Ct. 27.0 - 33.8)<br>(mecA Ct. 27.1- 34.6 )<br>(SCCmec Ct.28.5 - 35.6) | Positive<br>(SPA Ct. 22.3 - 26.8)<br>(mecA Ct. 22.4 - 27.2 )<br>(SCCmec Ct. 23.7 - 28.0 ) |
| Cepheid Xpert<br>MRSA/SA Blood<br>Culture | 100%<br>(9/9) | Negative | Positive<br>(SPA Ct. 26.1 - 36.2) | Positive<br>(SPA Ct. 26.6 - 34.8)<br>(mecA Ct. 27.4 - 34.8)<br>(SCCmec Ct. 28.4 - 35.7) | Positive<br>(SPA Ct. 23.3-27.8)<br>(mecA Ct. 23.7- 28.7)<br>(SCCmec Ct. 24.39 - 29.4) |
| Cepheid Xpert<br>MRSA/SA SSTI | 100%<br>(9/9) | Negative | Positive<br>(SPA Ct.25.5-<br>33.4 ) | Positive<br>(SPA Ct. 25.6-34.5)<br>(mecA Ct.28.1-33.0)<br>(SCCmec Ct.29.1-34.3) | Positive<br>(SPA Ct.19.4 - 31.8 )<br>(mecA Ct. 20.8 - 29.8 )<br>SCCmec Ct. 21.9 - 30.8) |
| Clostridium<br>difficile | | | | | |
| Cepheid Xpert<br>C. difficile | 100%<br>(9/9) | Negative | Negative | Positive<br>(Toxin B Ct. 26.9 - 32.2) | Positive<br>(Toxin B Ct. 21.4 - 28.2 ) |
| Cepheid Xpert<br>C. difficile/Epi | 100%<br>(9/9) | Negative | Negative | Positive<br>(BinaryToxin Ct. 25.0-<br>31.3)<br>(Toxin B Ct. 25.6-32.2 )<br>(Tcd C Ct. 25.9-33.2) | Positive<br>BinaryToxin Ct. 20.8 -<br>27.7)<br>(Toxin B Ct. 21.4 - 28.7)<br>(TcdC Ct. 21.9 - 29.8) |
| Vancomycin-<br>resistant<br>Enterococci | | | | | |
| Cepheid Xpert | 100% | Negative | Negative | Positive | Positive |

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| Representative Results Chart | | | | | |
|------------------------------|-------|----------|---------|-----------------------|-----------------------|
| Analytes | *PPA | Negative | Level 1 | Level 2 | Level 3 |
| vanA | (9/9) | | | (van A Ct. 26.5-33.7) | (van A Ct. 21.5-28.6) |

*PPA = positive percent agreement

# M. Proposed Labeling:

The labeling is sufficient and it satisfies the requirements of 21 CFR Parts 801 and 809 and the specials controls for this device type.

## N. Identified Risks and Required Mitigations:

| Identified Risks to Health | Required Mitigations |
|---------------------------------------------------------------------------------------------|------------------------------------|
| Incorrect use of the instrument for non-indicated samples resulting in a delay in diagnosis | Special Controls (1), (3), and (4) |
| Assessment performance error (false negative) | Special Control (1) |
| Incorrect results due improper or unexpected performance | Special Control (2) and (4)(iii) |
| Failure to correctly operate the instrument | Special Control (1) |

## O. Benefit/Risk Analysis:

| Summary | |
|------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Summary of the<br>Benefit(s) | The Amplichek II (Multi-Analyte controls) serves an external control for use<br>with Cepheid Xpert MRSA/SA Blood Culture Assay, Cepheid Xpert MRSA,<br>Cepheid Xpert SA Nasal Complete, Cepheid Xpert MRSA/SA SSTI,<br>Cepheid Xpert C. difficile, Cepheid Xpert C. difficile/Epi and Cepheid Xpert<br>vanA. It may identify false positive or false negative results produced by<br>these assays in association with decreased laboratory performance. The<br>Amplichek II (Multi-Analyte controls) are part of overall laboratory quality<br>assurance, and are not directly used with patient samples. It may produce<br>benefits by confirming accurate device results, but does not provide direct<br>benefit to individual patients. |

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| Summary of the<br>Risk(s) | There is minimal potential risk associated with use of the Amplichek II<br>(Multi-Analyte controls), given the combination of required general controls<br>and the special controls established for this device. If both the Amplichek II<br>and Cepheid Xpert assays simultaneously 'malfunctioned' (i.e., the<br>Amplichek II did not meet specification in some respect and this was not<br>detected by the Cepheid GeneXpert Systems), patient samples could then<br>potentially have incorrect results generated by a GeneXpert system without<br>this being recognized. However, given that positive and negative controls are<br>used and Cepheid GeneXpert System assays incorporate internal controls, it<br>is not anticipated that patients would experience harm due to 'failure' of the<br>Amplichek II. The Special Controls will sufficiently assist in managing risks<br>associated with incorrect results and/or failure to correctly operate the device<br>by insuring proper performance and use of the device. |
|-------------------------------------------------------------------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Summary of<br>Other Factors | Not applicable. |
| Conclusions<br>Do the probable<br>benefits<br>outweigh the<br>probable risks? | Yes, the probable benefits outweigh the potential risks, given the<br>combination of required general controls and the special controls established<br>for this device. It is unlikely that a patient would be harmed by use of the<br>Amplichek II (Multi-Analyte controls) since it is not intended for use on<br>patient samples. However, this control material could provide benefit by<br>providing an external source of quality control material to identify problems<br>with laboratory systems. Therefore, Amplichek II (Multi-Analyte controls)<br>are likely to improve laboratory performance without negatively impacting<br>patient care. |

## P. Conclusion:

The information provided in this de novo submission is sufficient to classify this device into class II under regulation 21 CFR 866.3950. FDA believes that the stated special controls, and applicable general controls, including design controls, provide reasonable assurance of the safety and effectiveness of the device type. The device is classified under the following:

| Product Code: | PMN |
|---------------|--------------------------------------------------------------------|
| Device Type: | Assayed quality control material for clinical microbiology assays. |
| Class: | II (special controls) |
| Regulation: | 21 CFR 866.3920 |

- (a) Identification. An assayed quality control material for clinical microbiology 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

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type of device consists of single or multiple microbiological analytes intended for use with either qualitative or quantitative assays.

- (b) Classification. Class II (special controls). 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

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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."