(619 days)
WOUNDCHEK Bacterial Status (WCBS) is an in vitro diagnostic chromatographic test for the qualitative detection of bacterial protease activity directly from wound fluid samples collected with a swab. The WCBS test is intended for use in adult patients as an aid in assessing the risk for non-healing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection. The test is intended for use with chronic wounds that are between 21 days and 6 months of age that are
WOUNDCHEK Bacterial Status (WCBS) is a lateral flow assay that qualitatively detects bacterial protease activity in chronic wound fluid. Wound fluid is collected by rolling a swab over the cleansed wound surface until it is saturated. The swab is then incubated in the assay reagent which contains a substrate that can be cleaved by bacterial proteases and human neutrophil elastase (HNE) and an HNE inhibitor. The WCBS test card is used to detect cleavage products of the substrate. It consists of biotinylated bovine serum albumin (BSA) (Test Line (T)), and a control system protein, (Control line (C)), on a nitrocellulose membrane support. Neutravidin, which is conjugated to visualizing particles, binds the biotinylated end of a synthetic peptide and the biotinylated BSA test line. The test result is based on the presence or absence of a pink-to-purple colored Test Line (T) which means bacterial protease activity was detected. A negative test result is defined by the absence of a Test Line (T) which means bacterial protease activity was not detected. If the control line (C) is not present, then the test result is invalid. The device is intended for use on venous leg ulcers (VLU), diabetic foot ulcers (DFU) and pressure ulcers (PU).
A control kit, consisting of negative and positive swabs, is also available for WOUNDCHEK Bacterial Status.
Here's an analysis of the acceptance criteria and the study that proves the WOUNDCHEK Bacterial Status device meets these criteria, based on the provided text:
Acceptance Criteria and Device Performance
1. Table of Acceptance Criteria and Reported Device Performance
| Acceptance Criteria Category | Specific Criteria | Reported Device Performance and Evidence |
|---|---|---|
| Precision | >95% agreement with expected results for moderate positive, low positive, and true negative panel members. Acceptable variability for high negative panel member. No significant differences in detection rate by site, operator, or day. | Met. |
| Results from a three-site, three-operator study (total 9 operators) showed: |
- Moderate Positive: 98.5% (133/135) agreement
- Low Positive: 95.6% (129/135) agreement
- True Negative: 97.8% (132/135) agreement
The high negative panel member had 93.3% (126/135) agreement, acknowledged as variable but acceptable given its nature. No significant differences by site, operator, or day were reported. |
| Sample Stability | Testing of all positive and negative swabs for various storage conditions (up to 9 hours at 2-8°C and 30°C) generated expected results. | Met.
Ten positive and negative swabs were tested for each storage condition (0.5, 1, 1.5, 2, 4, 6, 9 hours at 2-8°C and 30°C). All generated expected results. Interpretations were made by two blinded operators, with a total of (b)(4) determinations per condition. Daily controls met expectations. |
| Detection Limit (LOD) | LOD defined as the level of bacterial protease activity generating a positive result ~95% of the time (C95). C5 level also identified. | Met.
Preliminary and confirmed LODs (C95, C5, C50) were established for individual proteases (V8, GelE, ZapA, LasB) and a pooled mix of these proteases, consistent with the objective of defining these detection levels. (Specific mU/test values are redacted but are reported as being established). |
| Cross-reactivity - Human Proteases | Positive swabs must produce a positive result in the presence of any host protease. Negative swabs must produce a negative result in the presence of any host protease. | Met.
The study identified specific concentrations of human proteases (e.g., MMP-13, MMP-9, HNE, Plasmin) at which no interference was observed with WCBS performance for both positive and negative samples. If initial levels showed interference, dilutions were tested until criteria were met. |
| Interference - Microbial | Positive swabs (with analyte) must produce a positive result in the presence of tested microorganisms. Negative swabs must produce a negative result in the presence of tested microorganisms. | Met.
The study determined specific levels of various fungi, mold, and viruses (e.g., Candida species, Aspergillus fumigatus, Herpes Simplex viruses) at which no interference was observed. If initial levels showed interference with stock solutions, log dilutions were tested until criteria were met. |
| Interference - Healthy Skin Flora | Implied: Device should ideally not react to normal skin flora unless these flora are indicative of bacterial protease activity leading to non-healing. However, the study identified that performance is affected by normal skin flora. This led to a labeling mitigation. | Met (with mitigation).
Out of (b)(4) apparently healthy skin swab samples, 20 were positive by both operators, and an additional 4 by one operator, totaling 44 false positives out of 102 readings. While the device is affected, this finding is acknowledged as expected due to skin flora secreting proteases. The mitigation is a prominent instruction in the IFU: "Do not swab intact skin." |
| Interfering Substances | Positive swabs must produce a positive result in the presence of the interfering substance. Negative swabs must produce a negative result in the presence of the interfering substance. | Met.
The study identified specific concentrations for a wide range of wound-related substances (e.g., acetic acid, silver dressings, Manuka honey, mupirocin, blood, various antibiotics, skin substitutes, iodine, antifungals) at which no interference was observed. If a substance failed at the initial level, it was diluted twofold until criteria were met. |
| Clinical Performance (Risk Assessment for Non-Healing) | Provide Positive Likelihood Ratio (PLR) and Negative Likelihood Ratio (NLR) for indication. | Met (with caveats).
For the intended use population (wounds
§ 866.3231 Device to detect bacterial protease activity in chronic wound fluid.
(a)
Identification. A device to detect bacterial protease activity in chronic wound fluid is a lateral flow prescription in vitro diagnostic device that may include a sterile swab. The device is intended for use in patients as an aid in assessing the risk for non-healing of chronic venous, diabetic foot, and pressure ulcers associated with wounds where there are no signs of wound infection and where patients are asymptomatic for clinical signs of infection.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Any swab used to collect a patient specimen must be FDA-cleared, -approved, or -classified as 510(k) exempt (standalone or as part of a test system) for the collection of wound fluid specimens; alternatively, the sample collection device must be cleared in a premarket submission as a part of this device.
(2) The labeling required under § 809.10(b) of this chapter must include:
(i) An intended use that includes the following statements:
(A) A statement that the device detects and measures bacterial proteases from a swab saturated with wound fluid.
(B) A statement that the device provides a qualitative output to aid the user in assessing the risk for non-healing of wounds (
e.g., chronic venous, diabetic foot and pressure ulcers).(C) A description of the clinical indications for test use.
(D) The specific population(s) for which the device is intended.
(E) A description of the recommended training (
e.g., knowledge and experience) for safe and effective use of the device and to minimize the risks of incorrect results and misinterpretation.(ii) A detailed description of the performance characteristics of the device from the analytical and clinical studies required under paragraphs (b)(3)(ii) and (iii) of this section.
(iii) A detailed explanation of the interpretation of results.
(iv) A warning statement describing situations where the device has not been validated or may not perform as identified in the labeling (
e.g., not for use with wounds which are ≥6 months of age and ≥1 cm2 in size).(v) The following limiting statements:
(A) That the device is not intended to provide a risk assessment of chronic wound infection status or aid in the diagnosis of infection in chronic wounds, nor is the device intended for monitoring the effectiveness of anti-infective therapy.
(B) That a negative result does not exclude the presence of bacterial proteases. Therefore, the results should be used in conjunction with clinical findings to make an accurate assessment of risk of nonhealing. The test result should be interpreted in conjunction with other risk factors, along with clinical and laboratory data available to the clinician.
(C) That the device has been validated using wound fluid samples only. Other sample types (
e.g., whole blood from venous or capillary draws, other body fluids) have not been evaluated.(D) That skin flora may secrete bacterial proteases therefore, swab contact with intact skin should be avoided as this may yield false positive results.
(vi) Labeling must include a brief reference sheet for healthcare professionals that includes the intended use, summary of clinical performance, results from analytical testing on normal skin and human proteases, and warning and limiting statements.
(3) Design verification and validation must include the following:
(i) A detailed device description (
e.g., all device parts, control elements incorporated into the test procedure, reagents required but not provided, and the principle of device operation and test methodology).(ii) Detailed documentation and results from analytical studies, including the limit of detection, inclusivity, cross-reactivity, microbial interference, analytical sensitivity for normal skin flora and human proteases, interfering substances, specimen stability, within-lab precision, and reproducibility.
(iii) Detailed documentation and results from a clinical study that includes prospective (sequentially collected) samples for the intended specimen type that are representative of the intended use population(s). The clinical study must compare the device performance to results obtained from a reference or comparator method that FDA has determined is appropriate.