(103 days)
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.
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.
The Amplichek II is an assayed quality control material for clinical microbiology assays. Its purpose is to monitor the performance of in vitro laboratory nucleic acid testing procedures for the qualitative detection of Methicillin-Resistant Staphylococcus aureus (MRSA), Methicillin-Sensitive Staphylococcus aureus (MSSA), Clostridium difficile (Cdiff), and Vancomycin-resistant Enterococci (VRE) on Cepheid GeneXpert Systems.
Here's an analysis of the acceptance criteria and the study that proves the device meets them:
1. Table of Acceptance Criteria and Reported Device Performance
The primary acceptance criteria for the Amplichek II, as demonstrated by the reproducibility studies, is the percent agreement with the expected result for each analyte at various levels (Negative, Level 1, Level 2, Level 3).
| Acceptance Criteria (Implicit) | Reported Device Performance (Reproducibility Studies) |
|---|---|
| High percent agreement (ideally 100%) for expected positive and negative results across different lots, operators, days, and sites. | Study 1 (Single Lab): 100% agreement for all analytes (SPA, SCCmec, mecA, Binary Toxin, Toxin B, TcdC, Van A) across all Amplichek II levels (Negative, Level 1, Level 2, Level 3) for both product lots (Lot #1 and Lot #2), resulting in 100% total agreement by samples. (e.g., 80/80 agreements) |
| Consistency in Cycle Threshold (Ct) values and low Coefficient of Variation (CV%) across different lots, operators, days, and sites for positive controls. | Study 2 (Three Labs): Ct Mean and Ct %CV provided for positive controls across all analytes and levels for both Lot #1 and Lot #2. The Ct %CV values are generally low, mostly ranging from 1.4% to 9.1%, indicating good consistency. Note that Negative and some Level 1 controls had "N/A" for Ct values as they were expected to be negative. |
| Stability of the material until the expiration date when stored correctly. | An accelerated stability study was performed to establish shelf-life stability claims. Real-time stability studies are ongoing to support product claims. The protocols and acceptance criteria for these studies were reviewed and found acceptable. |
| The labeling is sufficient and satisfies regulatory requirements. | The labeling was deemed sufficient and satisfies the requirements of 21 CFR Parts 801 and 809 and the special controls for this device type. |
2. Sample Size Used for the Test Set and Data Provenance
The document describes two reproducibility studies acting as the test sets:
-
Study 1 (Single Lab):
- Sample Size: For each gene/analyte at each Amplichek II level (Negative, Level 1, Level 2, Level 3), there were 40 tests per lot (2 replicates per run x 2 runs per day x 10 days). With two lots, this totals 80 tests per gene/analyte/level. For instance, for the Cepheid Xpert SA Nasal Complete (MSSA/MRSA), there were 80 tests for SPA, 80 for SCCmec, and 80 for mecA at the Negative level, and similarly for Level 1, Level 2, and Level 3.
- Data Provenance: The data was generated through prospective testing at one laboratory site in the United States (implied by the FDA De Novo application and regulatory context). The study incorporated different operators and different days.
-
Study 2 (Three Labs):
- Sample Size: For each gene/analyte at each Amplichek II level, there were 9 tests per lot (different operators x 3 different days). With two lots, this totals 18 tests per gene/analyte/level.
- Data Provenance: The data was generated through prospective testing at three laboratory sites in the United States (implied by the FDA De Novo application and regulatory context). The study incorporated different operators and different days.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications
The Amplichek II is a quality control material intended to monitor the performance of in vitro laboratory nucleic acid testing. The "ground truth" for the test results (i.e., whether a control should be positive or negative for a specific analyte and its approximate Ct value range) is inherent to the design and composition of the Amplichek II material itself. It is not established by human experts in the way clinical diagnostic ground truth might be (e.g., through pathologist review or clinical outcomes).
Instead, the expected results (positive/negative and Ct range) are predetermined by Bio-Rad Laboratories based on their characterization of the control material's content and concentration of purified intact microorganisms. The studies then verify that the Cepheid GeneXpert Systems accurately detect these known compositions.
Therefore, no external experts were used to establish the ground truth for the test set; the ground truth is defined by the manufacturer's formulation.
4. Adjudication Method for the Test Set
Since the ground truth is defined by the known composition of the control material, and the output is a qualitative (positive/negative) or semi-quantitative (Ct value) result from a machine, there is no adjudication method involving human experts for the test set. The device performance is a direct comparison of the instrument's output against the expected result of the control material.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done
No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This type of study (comparing human readers with and without AI assistance on various cases) is typically applied to diagnostic imaging interpretation or other scenarios where human interpretation is the primary method being evaluated.
The Amplichek II is a quality control material for an automated molecular diagnostic system (Cepheid GeneXpert Systems). Its function is to verify the correct operation of these automated systems, not to assist human readers in interpreting complex cases. Therefore, the concept of human readers improving with or without AI assistance does not apply here.
6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done
The device itself, Amplichek II, is a physical quality control material, not an algorithm. However, the performance of the Cepheid GeneXpert system when using the Amplichek II control material is effectively a standalone performance evaluation of the GeneXpert system's ability to correctly process and interpret the known control substance. The studies assessed the Cepheid GeneXpert system's output (positive/negative and Ct values) without human intervention in the interpretation of the control material results. The Amplichek II simply serves as the standardized input.
Given that the Amplichek II is designed for automated molecular diagnostic systems, the evaluation of its performance (meaning how effectively it allows monitoring of an automated system) inherently relied on the standalone performance of the GeneXpert system.
7. The Type of Ground Truth Used
The ground truth used is based on the known, pre-defined composition and concentration of microorganisms within the Amplichek II control material. Bio-Rad Laboratories engineers and develops the control material to contain specific analytes (e.g., MRSA, MSSA, Cdiff, VRE) at defined levels (Negative, Level 1, Level 2, Level 3).
Therefore, the expected result for each test (e.g., "Positive" for SCCmec at Level 2, "Negative" for Toxin B at Level 1) is a known characteristic of the manufactured control. The studies verify that the Cepheid GeneXpert Systems produce results that agree with these known characteristics.
8. The Sample Size for the Training Set
The document does not explicitly describe a separate training set for the Amplichek II or the Cepheid GeneXpert System in the context of this submission.
The Amplichek II is a quality control material, not an algorithm that requires a training set. The Cepheid GeneXpert Systems are the devices being monitored by the Amplichek II. The GeneXpert systems themselves would have undergone extensive validation and potentially "training" during their development, but this information is not detailed in the Amplichek II's de novo submission.
The studies described are performance evaluations of the control material and how well it helps monitor the performance of the GeneXpert systems.
9. How the Ground Truth for the Training Set Was Established
As noted above, there is no explicit "training set" for the Amplichek II control material itself. The ground truth for the performance evaluation (test set) is the known, manufactured composition of the control material. This is established through the Bio-Rad Laboratories' internal manufacturing processes, formulation, and characterization of the specific microorganisms and their target concentrations within each level of the Amplichek II product.
{0}------------------------------------------------
EVALUATION OF AUTOMATIC CLASS II DESIGNATION FOR Bio-Rad Laboratories Amplichek II
DECISION SUMMARY
A. DEN Number:
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
-
- Panel:
83- Microbiology
- Panel:
H. Indication(s) for use:
-
- 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.
- Indications for use(s):
-
- Special conditions for use statement(s):
For in vitro diagnostic use only
- Special conditions for use statement(s):
For prescription use only
-
- Special instrument requirements:
The Amplichek II was evaluated on the Cepheid GeneXpert system.
- Special instrument requirements:
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*Lot #1 | % Agreement*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) | |||||
| BinaryToxin | 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) | ||
| BinaryToxin | 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) | ||
| BinaryToxin | 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) | ||
| BinaryToxin | 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 | AmplichekII Level | ExpectedResult | CtMean | Ct SD | Ct%CV | CtMean | CtSD | 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 NasalComplete (MSSA/MRSA) | ||||||||
| SPA/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 | AmplichekII Level | ExpectedResult | CtMean | Ct SD | Ct%CV | CtMean | CtSD | Ct %CV |
| Toxin B/TcdCBinary 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/TcdCBinary 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( C.difficile ) | ||||||||
| 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(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. -
- Comparison studies:
- a. Method comparison with predicate device:
Not applicable.
-
b. Matrix comparison:
Not applicable -
- 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. -
- Clinical cut-off:
Not Applicable.
- Clinical cut-off:
-
- 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.
- Expected values/Reference range:
| Representative Results Chart | |||||
|---|---|---|---|---|---|
| Analytes | *PPA | Negative | Level 1 | Level 2 | Level 3 |
| MRSA/ MSSA | |||||
| Cepheid XpertMRSA | 100%(9/9) | Negative | Negative | Positive(SCCmec Ct. 25.1 - 35.0) | Positive(SCCmec Ct. 20.7 - 27.7) |
| Cepheid XpertSA NasalComplete | 100%(9/9) | Negative | Positive(SPA Ct. 28.5 - 30.9) | Positive(SPA Ct. 27.0 - 33.8)(mecA Ct. 27.1- 34.6 )(SCCmec Ct.28.5 - 35.6) | Positive(SPA Ct. 22.3 - 26.8)(mecA Ct. 22.4 - 27.2 )(SCCmec Ct. 23.7 - 28.0 ) |
| Cepheid XpertMRSA/SA BloodCulture | 100%(9/9) | Negative | Positive(SPA Ct. 26.1 - 36.2) | Positive(SPA Ct. 26.6 - 34.8)(mecA Ct. 27.4 - 34.8)(SCCmec Ct. 28.4 - 35.7) | Positive(SPA Ct. 23.3-27.8)(mecA Ct. 23.7- 28.7)(SCCmec Ct. 24.39 - 29.4) |
| Cepheid XpertMRSA/SA SSTI | 100%(9/9) | Negative | Positive(SPA Ct.25.5-33.4 ) | Positive(SPA Ct. 25.6-34.5)(mecA Ct.28.1-33.0)(SCCmec Ct.29.1-34.3) | Positive(SPA Ct.19.4 - 31.8 )(mecA Ct. 20.8 - 29.8 )SCCmec Ct. 21.9 - 30.8) |
| Clostridiumdifficile | |||||
| Cepheid XpertC. difficile | 100%(9/9) | Negative | Negative | Positive(Toxin B Ct. 26.9 - 32.2) | Positive(Toxin B Ct. 21.4 - 28.2 ) |
| Cepheid XpertC. difficile/Epi | 100%(9/9) | Negative | Negative | Positive(BinaryToxin Ct. 25.0-31.3)(Toxin B Ct. 25.6-32.2 )(Tcd C Ct. 25.9-33.2) | PositiveBinaryToxin Ct. 20.8 -27.7)(Toxin B Ct. 21.4 - 28.7)(TcdC Ct. 21.9 - 29.8) |
| Vancomycin-resistantEnterococci | |||||
| 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 theBenefit(s) | The Amplichek II (Multi-Analyte controls) serves an external control for usewith Cepheid Xpert MRSA/SA Blood Culture Assay, Cepheid Xpert MRSA,Cepheid Xpert SA Nasal Complete, Cepheid Xpert MRSA/SA SSTI,Cepheid Xpert C. difficile, Cepheid Xpert C. difficile/Epi and Cepheid XpertvanA. It may identify false positive or false negative results produced bythese assays in association with decreased laboratory performance. TheAmplichek II (Multi-Analyte controls) are part of overall laboratory qualityassurance, and are not directly used with patient samples. It may producebenefits by confirming accurate device results, but does not provide directbenefit to individual patients. |
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| Summary of theRisk(s) | There is minimal potential risk associated with use of the Amplichek II(Multi-Analyte controls), given the combination of required general controlsand the special controls established for this device. If both the Amplichek IIand Cepheid Xpert assays simultaneously 'malfunctioned' (i.e., theAmplichek II did not meet specification in some respect and this was notdetected by the Cepheid GeneXpert Systems), patient samples could thenpotentially have incorrect results generated by a GeneXpert system withoutthis being recognized. However, given that positive and negative controls areused and Cepheid GeneXpert System assays incorporate internal controls, itis not anticipated that patients would experience harm due to 'failure' of theAmplichek II. The Special Controls will sufficiently assist in managing risksassociated with incorrect results and/or failure to correctly operate the deviceby insuring proper performance and use of the device. |
|---|---|
| Summary ofOther Factors | Not applicable. |
| ConclusionsDo the probablebenefitsoutweigh theprobable risks? | Yes, the probable benefits outweigh the potential risks, given thecombination of required general controls and the special controls establishedfor this device. It is unlikely that a patient would be harmed by use of theAmplichek II (Multi-Analyte controls) since it is not intended for use onpatient samples. However, this control material could provide benefit byproviding an external source of quality control material to identify problemswith laboratory systems. Therefore, Amplichek II (Multi-Analyte controls)are likely to improve laboratory performance without negatively impactingpatient 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
- (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:
- (1) Premarket notification submissions must include detailed device description documentation and information concerning the composition of the quality control material, including, as appropriate:
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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."
§ 866.3920 Assayed quality control material for clinical microbiology assays.
(a)
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.(b)
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.”