(55 days)
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.
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.
The provided document is a 510(k) summary for a medical device called the "Cepheid Xpert SA Nasal Complete Control Panel." This device is an assayed quality control material for clinical microbiology assays. It is not an AI/ML-driven device, diagnostic algorithm, or imaging device, but rather a quality control panel used in laboratory testing.
Therefore, many of the typical acceptance criteria and study aspects you've listed, which are relevant to AI/ML or imaging diagnostics (e.g., sample size for test set, data provenance, number of experts for ground truth, adjudication methods, MRMC studies, standalone performance, ground truth sources like pathology, training set size, etc.), do not apply to this type of medical device.
This document describes a performance study to demonstrate the precision and reproducibility of the quality control panel itself. The acceptance criteria relate to the ability of the control panel to consistently produce the expected results when tested with the target assay.
Here's an attempt to extract and reframe the information based on the document, while acknowledging that many of your requested points are not applicable:
Device: Cepheid Xpert® SA Nasal Complete Control Panel
Device Type: Assayed Quality Control Material for Clinical Microbiology Assays
1. A table of acceptance criteria and the reported device performance
The document does not explicitly state "acceptance criteria" in the format of pass/fail thresholds for a given metric. However, the study aims to demonstrate 100% agreement with expected results for positive and negative controls. The presented performance data shows this agreement was achieved.
Here's the performance data that implicitly represents the desired outcome (100% correct results):
| Analyte Type/Location | Target Mechanism Monitored | Reported Device Performance (Agreement %) | Notes |
|---|---|---|---|
| Positive Control 1 (Methicillin-Resistant Staphylococcus aureus - MRSA) | spa, mec, SCC genes | 100% (90/90 successful tests) | 3 "NO RESULT" responses were observed initially but were retested with new controls, yielding expected results. This suggests that the failures were likely procedural or related to the specific control unit, rather than a fundamental flaw in the control panel's ability to produce the correct result when working as intended. |
| Positive Control 2 (Staphylococcus aureus - MSSA) | spa gene | 100% (90/90 successful tests) | 2 "NO RESULT" responses were observed initially but were retested with new controls, yielding expected results. |
| Negative Control (Staphylococcus epidermidis) | Not detected | 100% (90/90 successful tests) | Multiple "INVALID" and "ERROR" responses were observed across different sites (e.g., 8 INVALID from single user, 1 ERROR, 1 NO RESULT). These were retested with new controls, yielding expected results. This again points to issues with individual control units or testing procedure rather than the overall control type. |
An additional table for quantitative performance (Mean Ct and %CV) is provided for the positive controls and sample processing control, demonstrating reproducibility of the cycle threshold values across sites:
| Analyte/Target Gene | Site 1 Mean Ct (%CV) | Site 2 Mean Ct (%CV) | Site 3 Mean Ct (%CV) | All Sites Mean Ct (%CV) |
|---|---|---|---|---|
| MRSA (SPA) | 27.0 (2.7) | 28.1 (2.3) | 27.8 (2.2) | 27.6 (3.0) |
| MRSA (mec) | 27.3 (2.6) | 28.4 (2.0) | 28.1 (2.1) | 27.9 (2.8) |
| MRSA (SCC) | 28.5 (2.3) | 29.6 (1.9) | 29.3 (2.1) | 29.1 (2.7) |
| MSSA (SPA) | 26.8 (2.7) | 27.8 (2.5) | 27.4 (2.8) | 27.3 (3.0) |
| SPC (Negative Ctrl) | 32.0 (4.2) | 31.8 (3.5) | 32.1 (4.4) | 32.0 (4.0) |
2. Sample size used for the test set and the data provenance
- Test Sample Size:
- For each of the three types of controls (MRSA positive, MSSA positive, negative), there were 90 tests performed in total.
- This was derived from: 3 testing locations x 2 operators/location x 3 lots x (minimum of) 3 tests/lot/operator/day over 5 days (totaling 30 tests per control type per site before accounting for specific retests). The summary table shows 30 tests per site, so 3 sites * 30 tests/site = 90 tests.
- Data Provenance: The document implies the data was collected prospectively as part of a performance study to support the 510(k) submission. Geographic origin is not specified but would typically be within the country of the applicant (USA, based on the address).
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
- Not Applicable: For a quality control material, the "ground truth" is inherent to the known composition of the control and the expected output of the assay it monitors (e.g., a positive control should be positive for specific targets). There is no "expert adjudication" or "radiologist experience" involved in establishing this kind of ground truth. The expected results are defined by the analytical properties of the material.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
- Not Applicable: As there's no subjective interpretation, no adjudication method is needed. The results are quantitative (Ct values) or qualitative (Positive/Negative) based on the instrument's reporting. The document mentions retesting "NO RESULT," "INVALID," or "ERROR" samples, which is a standard laboratory practice for troubleshooting, not an adjudication process.
5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- Not Applicable: This is a quality control material, not an AI/ML diagnostic system. No human readers or AI assistance are involved in interpreting its direct output.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Not Applicable: This is not an algorithm. The "standalone" performance demonstrated is the ability of the control panel itself to reliably elicit the expected response from the GeneXpert Dx System.
7. The type of ground truth used (expert concensus, pathology, outcomes data, etc)
- Analytical Ground Truth: The ground truth is the known composition of the control panel (e.g., contains inactivated MRSA, contains inactivated MSSA, contains inactivated S. epidermidis) and the expected analytical response of the target assay (Cepheid Xpert SA Nasal Complete Assay). For instance, an MRSA positive control should result in detection of SPA, mec, and SCC genes.
8. The sample size for the training set
- Not Applicable: This device is a quality control material, not an algorithm that requires a training set.
9. How the ground truth for the training set was established
- Not Applicable: As above, there is no training set for this type of device. The characteristics of the control panel (contents, concentration) are established during its manufacturing and characterization process, not through a "ground truth establishment" phase for machine learning.
§ 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.”