(344 days)
The PAXgene Blood DNA Tube is intended to collect, anticoagulate, stabilize, transport, and store a venous whole blood sample for preparation of human DNA for use with molecular diagnostic test methods that require DNA.
The performance characteristics of this device have not been established for molecular diagnostic assays in general. Users must validate use of product for their specific molecular diagnostic assay.
The PAXgene® Blood DNA Tube is a sterile, single use, plastic, evacuated blood collection tube with a BD Hemogard™ closure assembly and a measured quantity of K2EDTA additive. The additive quantity dispensed into each tube is designed to match the nominal blood draw volume of 2.5 mL. The tube is made of polyethylene terephthalate (PET) plastic which functions to maintain vacuum within the tube, allowing for accurate and consistent blood draw for the duration of the shelf life of the tube. A predetermined vacuum is drawn inside the tube that is sealed with a BD Hemogard™ closure which consists of a rubber stopper plus BD Hemogard™ shield. The tube is intended to be placed inside a tube holder or an adaptor that contains a needle designed to pierce the tube closure and allow blood to flow into the tube. Once the vein has been penetrated (using either a standard blood collection needle or a blood collection set), the tube is pushed into the holder, and the blood enters the tube. Once a tube has drawn the appropriate amount of blood, it is disengaged from the holder and inverted the recommended number of times (8–10) to mix the additive with the blood. The DNA in whole blood collected in the PAXgene® Blood DNA Tube has been shown to be suitable for molecular diagnostic testing for 14 days at room temperature (18–25°C), 28 days refrigerated (2–8°C), 3 days at 35°C, up to 52 weeks frozen (–20°C), or when subjected to up to three freeze-thaw cycles. The PAXgene® Blood DNA Tube is robust with respect to mishandling including reduced inversions and partial blood draw. The product shelf life is one year from the date of manufacture including limited storage temperature excursions which simulate shipping conditions from –20°C to 45°C. The PAXgene® Blood DNA Tube is available as a 13 x 75 mm tube with a 2.5 mL nominal blood draw. The referenced first dimension represents the diameter of the tube and the second dimension represents the length of the tube.
The provided document describes the PAXgene® Blood DNA Tube, a blood collection device, and its performance characteristics as part of a 510(k) premarket notification. The study aims to demonstrate substantial equivalence to a legally marketed predicate device.
Here's an analysis of the acceptance criteria and study findings based on the provided text, while noting the limitations of the document regarding certain specific study parameters that are often found in AI/ML performance studies:
1. Table of Acceptance Criteria and Reported Device Performance
The document does not explicitly state formal "acceptance criteria" in a typical table format with pre-defined thresholds. Instead, it presents performance data for DNA yield, concentration, purity, and concordance with FDA-cleared molecular diagnostic assays to demonstrate the device's suitability for its intended use and substantial equivalence to the predicate device.
However, based on the summary results and the nature of this submission, which is for a blood collection tube rather than an AI/ML diagnostic algorithm, the acceptance criteria are implicitly met if the device consistently yields high-quality DNA that produces 100% correct calls in various molecular diagnostic assays, and if its stability and robustness are demonstrated.
Here's a synthesized table based on the various performance summaries:
| Performance Metric | Implicit Acceptance Criteria (based on reported results) | Reported Device Performance (PAXgene® Blood DNA Tube) |
|---|---|---|
| DNA Yield (µg DNA / 200 µl blood) | Consistent yield for downstream applications | Magnetic Bead: Mean 6.05 ± 1.61 µg; Median 5.77 µg; 95% samples > 3.64 µg. |
| Silica Membrane: Mean 4.89 ± 2.48 µg; Median 4.49 µg; 95% samples ≥ 1.86 µg. | ||
| DNA Concentration (ng DNA / µl eluate) | Sufficient concentration for downstream applications | Magnetic Bead: Mean 30.2 ± 8.0 ng/µl; Median 28.9 ng/µl; 95% samples > 18.2 ng/µl. |
| Silica Membrane: Mean 48.85 ± 24.75 ng/µl; Median 44.90 ng/µl; 95% samples ≥ 18.56 ng/µl. | ||
| DNA Purity (A260/A280) | Optimal range (typically 1.7-2.0) | Magnetic Bead: Mean 1.85 ± 0.04; Median 1.86; 95% samples 1.75-1.93. |
| Silica Membrane: Mean 1.86 ± 0.08; Median 1.88; 95% samples 1.67-2.06. | ||
| Interference/Handling: 1.7-1.9 or 1.8-1.9. | ||
| Assay Concordance (with FDA-cleared MDx assays) | 100% correct calls / High concordance | Primary Testing: 100% correct calls in all assessed assays (CF Assay, HLA Assay 1, Thrombophilia, HLA Assay 2, HLA Assay 3) across multiple sites, with 95% CI lower bounds generally >90%, and for large sample sets >99%. One exceptional case of 97.3% for CF Assay at Site B with one "No Call" due to degraded enzyme, which was not attributed to the device itself. |
| Device Shelf-Life: 100% concordance. | ||
| DNA Stability (Blood in Tube): 100% concordance across various storage conditions. | ||
| Interference: 100% concordance with interfering substances. | ||
| Sample Handling (Underfilling/Mixing): 100% concordance. | ||
| Product Shelf Life | At least 12 months at room temperature | Supported for up to 12 months at room temperature, including temperature cycling (45°C and -20°C). |
| Blood Stability in Tube | Up to 14 days (RT), 28 days (refrigerated), 52 weeks (frozen), 3 freeze-thaw cycles | As stated: 14 days at 18-25°C; 28 days at 2-8°C; 1, 6, 12 months at -20°C; 1, 2, 3 freeze-thaw cycles; up to 3 days at 35°C. |
| Robustness (Underfilling/Mixing) | Consistent performance under mishandling | Demonstrated consistent DNA concentration, purity, and 100% assay concordance for underfilling (2.5ml, 1.25ml, 0.70ml) and mixing (0, 1, 5, 8 inversions). |
| Interference | No impact on assay performance | No effect on FDA-cleared assay performance (HLA Assay 3) with tested interfering substances (Hemoglobin, Bilirubin, Triglycerides, Albumin). |
2. Sample sizes used for the test set and the data provenance
The "test set" here refers to the samples used for performance evaluation, as this is not an AI/ML device in the traditional sense that uses training/test splits.
- DNA Yield, Concentration, and Purity Summary:
- Magnetic Bead based DNA extraction kit: 581 specimens from approximately 200 consented subjects.
- Silica Membrane based DNA extraction kit: 540 specimens from 152 consented subjects.
- Molecular Diagnostic Test Methods (Assay Concordance):
- Individual assays varied: CF Assay (40 samples per site, total 117 after retest); HLA Assay 1 (40 samples per site, total 120 after retest); Thrombophilia Assay (80 samples); HLA Assay 2 (698 samples after retest); HLA Assay 3 (100 samples).
- Reproducibility studies: 20 donors for site-to-site and lot-to-lot.
- Device Shelf-Life Study: Tested with 24 subjects (12 per time point/group) for 12, 13 months, and with temperature cycling.
- DNA Stability (Whole Blood Storage in Tube): Sample sizes of 12 or 60 for various storage conditions and time points.
- Interference Study: 10 samples per interfering substance for both magnetic bead and silica membrane purification methods.
- Sample Handling (Underfilling and Mixing): 10 subjects for each handling condition.
Data Provenance: The document states that blood was drawn from "consented subjects" and mentions testing at "four (4) external clinical test sites and one (1) internal test site". This strongly indicates prospective data collection from human subjects. The document does not specify the country of origin of the data, but given the FDA submission, it likely includes data from the US or regions compliant with FDA standards.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This is not applicable in the context of this device. The ground truth for this device (a blood collection tube) is objectively measured through DNA quantification (yield, concentration, purity) and the concordance of results with established, FDA-cleared molecular diagnostic assays. The "ground truth" for the molecular diagnostic assays themselves would be derived from clinical diagnosis or confirmed genetic status, not expert consensus on image interpretation. No human experts are used for establishing ground truth for device performance in this manner.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable. This is not a study requiring reader adjudication of ambiguous cases, as it measures objective biochemical and molecular assay outcomes.
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 not an AI/ML medical device, and no human readers are involved in interpreting results that would be enhanced by AI assistance. The performance is assessed on the ability of the tube to collect and preserve DNA for downstream molecular diagnostic tests.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Yes, in a sense, the primary studies are "standalone" performance evaluations of the device itself (the blood collection tube) to ensure it performs its function of preserving DNA for analysis. The "algorithm" here is the device's mechanism (anticoagulation, stabilization) and the subsequent molecular diagnostic assays. The results presented (DNA metrics and assay concordance) are direct outputs of using the PAXgene Blood DNA Tube in conjunction with standard laboratory procedures and FDA-cleared assays, without human interpretation as part of the 'device's' output.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
The ground truth used for evaluating the PAXgene Blood DNA Tube's performance is multi-faceted:
- Quantitative DNA metrics: Measured values (yield, concentration, purity) obtained through standard laboratory equipment (e.g., UV absorbance).
- Concordance with FDA-cleared Molecular Diagnostic Assays: The "ground truth" for the assay results themselves is that the assay should correctly identify the genetic markers it is cleared to detect. The study establishes that DNA collected in the PAXgene tube yields results (e.g., genotypes) that are 100% concordant with those obtained from control (predicate or EDTA) tubes, demonstrating that the sample preparation did not alter the diagnostic outcome.
8. The sample size for the training set
Not applicable. This is a blood collection device, not an AI/ML algorithm that requires a training set.
9. How the ground truth for the training set was established
Not applicable. No training set is used for this device.
§ 862.1675 Blood specimen collection device.
(a)
Identification. A blood specimen collection device is a device intended for medical purposes to collect and to handle blood specimens and to separate serum from nonserum (cellular) components prior to further testing. This generic type device may include blood collection tubes, vials, systems, serum separators, blood collection trays, or vacuum sample tubes.(b)
Classification. Class II.