(1342 days)
The Bio-Seal Lung Biopsy Tract Plug System is indicated to provide accuracy in marking a biopsy location for visualization during surgical resection and to plug pleural punctures associated with percutaneous, transthoracic needle lung biopsies to significantly reduce the risk of pneumothoraces (air leaks).
The Angiotech Bio-Seal Lung Biopsy Tract Plug System is comprised of (1) a pre-formed hydrogel plug and (2) a delivery system, which together are designed for use in conjunction with Fine Needle Aspiration (FNA) biopsy of the lung. During lung biopsy, a 19 gauge coaxial needle is placed at the site to be biopsied, under fluoroscopic guidance. The stylet is removed and a 20 or 22 gauge FNA biopsy needle or biopsy instrument is inserted to obtain the tissue sample. When the FNA biopsy needle or biopsy instrument is removed. the Bio-Seal Lung Biopsy Tract Plug is deployed using the Bio-Seal delivery system through the coaxial needle into the biopsy tract. Upon deployment into the biopsy tract, the hydrogel plug absorbs extracellular fluid and expands to fill the void of the biopsy tract and remains in place for months to mark the biopsy site.
Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:
Acceptance Criteria and Reported Device Performance for Bio-Seal Lung Biopsy Tract Plug System
1. Table of Acceptance Criteria and Reported Device Performance
| Category | Acceptance Criteria (Explicit or Implied from Testing) | Reported Device Performance |
|---|---|---|
| Biocompatibility | Device materials (Bio-Seal Plug and modified delivery system components) must be biocompatible (cytotoxicity, sensitization, intracutaneous reactivity, hemolysis, pyrogenicity, genotoxicity, mutagenicity, chromosomal aberrations, chronic toxicity, implantation, acute systemic toxicity, delayed hypersensitivity, materials-mediated pyrogenicity, LAL). | Bio-Seal Plug: Acceptable for all critical biocompatibility tests (cross-referenced from K041331). Modified Delivery System: All patient-contacting components (Housing, Stylet, Adapter) shown to be biocompatible per ISO 10993-1:2009. |
| Sterility | Achieve a Sterility Assurance Level (SAL) of 10⁻⁶ via Ethylene Oxide (EO) gas sterilization. | Validated in conformance with ISO 11135:1994 and K90-1 Guidance. |
| Shelf Life/Stability | Maintain performance (deployment, protrusion, no premature expansion) for at least three years. The Bio-Seal dimensions must remain within specification, and there should be no premature plug expansion. Plugs must deploy after 60-second hold time and protrude from simulated tissue. Plugs must expand beyond a pre-specified dimension during hydration. | Supported a three-year shelf life. All 10 samples for accelerated aging and 10 samples for real-time aging passed all tests. Bio-Seal dimensions were within specification, no premature expansion. All plugs deployed after 60-second hold time and protruded from simulated tissue. All 15 hydrated plugs expanded beyond the pre-specified dimension. |
| Functional Performance (Bench - Deployment) | Plug must deploy through the coaxial introducer needle. | All 120 devices deployed the plug as intended. |
| Functional Performance (Bench - Protrusion) | Plug must protrude from the simulated lung tissue (pleura). | All 120 devices showed plug protrusion (average protrusion above simulated pleura of (b)(4)). |
| Functional Performance (Bench - Ease of Deployment) | The rating should be acceptable even if not "ideal" as long as the plug deploys correctly. | Average ease of plug deployment rating: (b)(4) (which is likely considered acceptable given the context). |
| Functional Performance (Bench - Deployment Time) | Plug deployment within (b)(4) from attachment to coaxial introducer needle, verified with a (b)(4) hold time. | Average deployment time: (b)(4) after a (b)(4) hold time (meets or exceeds requirement). |
| Dimensional Accuracy (Plug) | Outer diameter (OD) and length must be within acceptable tolerances for housing assembly, coaxial needle fit, and precise positioning. | 1000 sterile plugs dimensionally inspected for OD and length were found to be within acceptable tolerances. |
| Dimensional Accuracy (Adapter/Delivery System) | Main Luer assembly length, nylon tube bond strength, support column length and ID, plunger stylet length, and first laser mark must be within acceptable tolerances. Plunger must seat completely within the adapter hole. | All tested Main Luer assemblies were within acceptable tolerances for critical length. Nylon tube bond strength met or exceeded specification (pull tested (b)(4) assemblies showed bond strength greater than or equal to (b)(4)). All (b)(4) delivery systems tested for support column length, ID, plunger length, and first laser mark were within acceptable measurements. All depths passed. |
| Hydration Rate | Sterilization should not adversely affect hydration rate. Plugs must expand to prespecified dimensions within 1998 seconds and fit the ID of the coaxial needle. | Sterilization did not adversely affect hydration rate. Post-sterilization, plugs expanded to prespecified dimensions within 1998 seconds. Time needed to reach a predetermined diameter where the plug would no longer fit the ID of the coaxial needle was also measured, implying it was within acceptable limits for physician deployment time. |
| Pneumothorax Rate Reduction (Effectiveness) | Significantly reduce the risk of pneumothoraces (air leaks) post-lung biopsy compared to standard procedure. | Statistically and clinically significant reduction: ITT population: 75% success (no pneumothorax) with device vs. 57% without (p=0.0008). PP population: 85% success with device vs. 69% without (p=0.0022). |
| Safety | Comparable or improved safety profile regarding adverse events for procedure-related and non-procedure related events compared to control group. No clinical harm from device malfunction events. | Non-procedure related events comparable. Device/procedure-related events higher in control group (44% vs. 25%). 7 device malfunction events reported, but none resulted in clinical harm. 3 deaths (2 control, 1 Bio-Seal) were unrelated to device or procedure. |
| Resorption Characteristics | Minimal inflammation in lung tissue for up to 6 months. Essentially resorbed at 20 months. | Swine studies showed minimal inflammation comparable to absorbable sutures at 7, 14, 90, and 180 days. In vitro studies at 37°C indicated theoretical degradation within 15-18 months with two-thirds degradation within 6-9 months (consistent with "essentially resorbed at 20 months" inference from previous animal data). |
2. Sample Size Used for the Test Set and Data Provenance
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Clinical Trial Test Set:
- Intent-to-Treat (ITT) Population: 339 total patients (170 Bio-Seal, 169 Control)
- Per Protocol (PP) Population: 287 total patients (150 Bio-Seal, 137 Control)
- Data Provenance: Multi-centered (15 US centers), prospective, randomized controlled trial.
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Bench Testing Test Set:
- Shelf Life: 10 samples for accelerated aging, 10 samples for real-time aging (2 samples at each time point: 1, 1.5, 2, 2.5, 3 years).
- Hydration Rate: 15 Bio-Seal plugs.
- Dimensional (Plug): 1000 sterile plugs.
- Dimensional (Main Luer assembly): (b)(4) assemblies (number redacted but plural).
- Nylon Tube Bond Strength: (b)(4) assemblies (number redacted but plural).
- Dimensional (Delivery System): (b)(4) delivery systems (number redacted but plural).
- Functional (Deployment, Protrusion, Ease, Time): 120 devices.
- Data Provenance: Bench (laboratory) setting.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of those Experts
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Clinical Trial: The primary effectiveness endpoint (incidence rate of pneumothorax) was "measured by chest x-rays at 0-60 minutes after procedure, 24 hours after discharge and 30 days post discharge. A blinded, independent reader analyzed the x-rays, whose opinion was used in evaluating the primary endpoint."
- Number of Experts: One (a single "blinded, independent reader").
- Qualifications: "Independent reader" implies they are qualified to interpret chest x-rays for pneumothorax, likely a radiologist, but specific qualifications (e.g., years of experience) are not provided. The term "blinded" is a critical qualification ensuring objectivity.
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Animal Studies (Pathology/Inflammation): Not explicitly stated, but for the chronic GLP animal study involving histological evaluation, it can be inferred that veterinary pathologists or similar experts established the ground truth regarding inflammation. The text doesn't specify the number.
4. Adjudication Method for the Test Set
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Clinical Trial (Pneumothorax Endpoint): None explicitly mentioned as an adjudication method where multiple readers disagree. It states a "blinded, independent reader analyzed the x-rays, whose opinion was used in evaluating the primary endpoint." This suggests the single reader's opinion was the definitive determination, rather than a consensus or adjudication process among multiple readers.
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Bench/Animal Studies: Not applicable in the context of human reader adjudication.
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
- No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done.
- This device is a physical medical device (lung biopsy tract plug), not an AI algorithm. Therefore, there is no AI component, and no study measuring human reader improvement with or without AI assistance was conducted.
6. If a Standalone (i.e. algorithm only without human-in-the loop performance) was done
- No, this device is a physical medical device. It does not involve an algorithm and is not intended for standalone algorithmic performance evaluation. Its use is hands-on by a physician.
7. The Type of Ground Truth Used
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Clinical Trial:
- Effectiveness (Pneumothorax): Expert interpretation of chest x-rays by an independent, blinded reader. This is a form of expert consensus/interpretation of imaging.
- Safety (Adverse Events): Clinically observed adverse events documented in Case Report Forms (CRFs), including pneumothorax, coughing with blood, infections, etc.
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Animal Studies:
- Resorption/Inflammation: Histological evaluation in swine sacrificed at various time points (7, 14, 90, 180 days). This is based on pathology.
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Bench Studies:
- Dimensional, Functional, Hydration, Sterility, Shelf-life: Physical measurements, visual inspection, timed observations, and standardized laboratory tests with defined specifications/tolerances.
8. The Sample Size for the Training Set
- Training Set for a Physical Device: This concept generally doesn't apply to a physical medical device in the same way it does to an AI algorithm.
- However, the text mentions "Research and development acute studies included demonstrating expansion characteristics of a prototype plug under inflation, air leakage in the presence of blood, varying depth placements of the plug, physician preference, and techniques for maneuvering the marker, photographic documentation of placement and extension beyond pleura, and feedback for physician training." This iterative R&D likely involved numerous prototypes and tests (a form of "training" for the device's design and manufacturing process), but a specific "training set" sample size for the final product is not applicable in the AI sense.
- The Bio-Seal Plug itself "was previously cleared as a lung biopsy site marker device under K041331." This prior clearance and continued use/manufacturing would involve a vast dataset of material characterization and performance data that iteratively refined the design and manufacturing processes, but it's not a discrete "training set."
9. How the Ground Truth for the Training Set Was Established
- As above, for a physical device, a "training set" ground truth isn't established in the AI sense. Instead, the design and manufacturing process is refined through:
- Bench Testing: Extensive iterative testing and characterization of materials, dimensions, and functional performance with defined engineering specifications and physics-based outcomes.
- Animal Studies: Acute and chronic animal studies provided in-vivo data on tissue reaction, expansion characteristics, and resorption.
- Physician Feedback: Early prototype evaluations and preference studies guided the design for usability and effectiveness.
- Prior Regulatory Clearances: Previous successful clearances (e.g., K041331) established a foundational understanding of the device's behavior and safety, confirming ground truth for its core components.
Essentially, the "ground truth" for developing the device was derived from a combination of scientific principles, engineering validated measurements, and biological responses observed in preclinical models.
§ 878.4755 Absorbable lung biopsy plug.
(a)
Identification. A preformed (polymerized) absorbable lung biopsy plug is intended to provide accuracy in marking a biopsy location for visualization during surgical resection and closure of pleural punctures associated with percutaneous, transthoracic needle lung biopsies. Upon deployment into the biopsy tract, the plug expands to fill the biopsy void and remains in place until resorbed.(b)
Classification. Class II (special controls). The special controls for this device are:(1) The design characteristics of the device must ensure that the geometry and material composition are consistent with the intended use.
(2) Performance testing must demonstrate deployment as indicated in the accompanying labeling, including the indicated introducer needles, and demonstrate expansion and resorption characteristics in a clinically relevant environment.
(3) In vivo evaluation must demonstrate performance characteristics of the device, including the ability of the plug to not prematurely resorb or migrate and the rate of pneumothorax.
(4) Sterility testing must demonstrate the sterility of the device and the effects of the sterilization process on the physical characteristics of the plug.
(5) Shelf-life testing must demonstrate the shelf-life of the device including the physical characteristics of the plug.
(6) The device must be demonstrated to be biocompatible.
(7) Labeling must include a detailed summary of the device-related and procedure-related complications pertinent to the use of the device and appropriate warnings. Labeling must include identification of compatible introducer needles.