(92 days)
The Cepheid Xpert® CT/NG 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 Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) performed with the Cepheid Xpert® CT/NG assay on the GeneXpert® Instrument System. The controls consist of cultured and inactivated Chlamydia trachomatis and Neisseria gonorrhoeae as the positive control and human cells as the negative control.
The Cepheid Xpert® CT/NG Control Panel is not intended to replace manufacturer controls provided with the device.
The Cepheid Xpert® CT/NG Control Panel is used to monitor the extraction, amplification and detection of the Cepheid Xpert® CT/NG Assay. The Cepheid Xpert® CT/NG Control Panel contains authentic pathogens inactivated by radiological or temperature treatments. Each Cepheid Xpert® CT/NG Control Panel consists of 6 individually packaged positive control swabs and 6 individually wrapped negative control swabs. Each positive control swab contains Chlamydia trachomatis and Neisseria gonorrhoeae as well as preservatives and stabilizers. Each negative control swab contains human cells as well as preservatives and stabilizers. Each swab is individually wrapped with a desiccant in a heat-sealed foil pouch.
The provided text describes the acceptance criteria and performance data for the Cepheid Xpert® CT/NG Control Panel, which is an assayed quality control material for clinical microbiology assays. This is a diagnostic device, not an AI/ML-based device, so many of the requested criteria related to AI/ML studies (such as MRMC studies, training set details, or ground truth establishment by experts for imaging) are not applicable.
Here's an analysis based on the provided document:
1. A table of acceptance criteria and the reported device performance
The acceptance criteria for this device appear to be 100% agreement with expected results for both positive and negative controls. The reported device performance met these criteria.
| Acceptance Criteria | Reported Device Performance |
|---|---|
| Positive Controls: 100% agreement with expected positive results for all analytes (C. trachomatis, N. gonorrhoeae (NG2), N. gonorrhoeae (NG4), SPC) | 100% agreement for all analytes: |
- C. trachomatis: 92/92 (100%)
- N. gonorrhoeae (NG2): 92/92 (100%)
- N. gonorrhoeae (NG4): 92/92 (100%)
- SPC: 92/92 (100%) |
| Negative Controls: 100% agreement with expected negative results for all analytes (SAC, SPC) | 100% agreement for all analytes: - SAC: 97/97 (100%)
- SPC: 97/97 (100%) |
| Consistency in Ct values across sites and operators (implied by %CV data) | Mean Ct and %CV values were reported across sites, demonstrating consistency. (e.g., Overall Mean Ct for C. trachomatis 31.8 (3.8)). |
2. Sample size used for the test set and the data provenance
- Test Set Sample Size:
- Positive Controls: 92 replicates were tested across three sites. (31 from Site 1, 31 from Site 2, 30 from Site 3, with some additional runs for re-tests).
- Negative Controls: 97 replicates were tested across three sites. (33 from Site 1, 34 from Site 2, 30 from Site 3, with some additional runs for re-tests).
- Data Provenance: The data was generated prospectively through a multi-site evaluation. The document does not specify the country of origin of the testing sites, but given it's an FDA submission, it's highly likely to be within the US or under US regulatory guidelines.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is an in vitro diagnostic (IVD) device, specifically a quality control. The "ground truth" is inherent to the control material itself (i.e., the positive control contains the target microbes at a known concentration, and the negative control does not).
Therefore:
- Number of experts: Not applicable in the context of human interpretation for ground truth. The "ground truth" is established by the known composition of the control material (inactivated pathogens for positive, human cells only for negative).
- Qualifications of experts: Not applicable.
4. Adjudication method for the test set
Not applicable for an IVD quality control device. The results are quantitative (Ct values) and qualitative (positive/negative detection) based on the instrument's algorithm, not human interpretation requiring adjudication. Any "ERROR" or "INVALID" results were retested according to the Instructions for Use, which is a standard procedure for IVD testing.
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 an IVD quality control device, not an AI/ML imaging or diagnostic aid for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
This device evaluates the performance of the Cepheid Xpert® CT/NG assay and GeneXpert® Instrument System, which is an automated system. The performance data presented demonstrates the "standalone" or "algorithm only" performance of the control panel interacting with the assay/instrument system as intended, without human interpretation as a variable.
7. The type of ground truth used
The ground truth is based on the known composition of the control materials:
- Positive control: Contains cultured and inactivated Chlamydia trachomatis and Neisseria gonorrhoeae.
- Negative control: Contains human cells.
The "expected results" (positive or negative) are determined by these known compositions.
8. The sample size for the training set
Not applicable. This is a manufactured control material, not an AI/ML algorithm that requires a training set. Its development involves formulation and manufacturing processes, followed by validation and verification studies (which are described as the "performance data").
9. How the ground truth for the training set was established
Not applicable, as there is no "training set" in the AI/ML sense for this type of device. The "ground truth" for the control material itself is established during its design and manufacturing by precisely controlling its components.
§ 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.”