(108 days)
LC Bead Microspheres & Bead Block Compressible Microspheres is intended for embolization of hypervascular tumors and arteriovenous malformations.
LC Bead/Bead Block are preformed, soft, deformable microspheres that occlude arteries for the purpose of blocking the blood flow to a target tissue, such as a hypervascular tumor or arteriovenous malformations (AVM's). LC Bead/Bead Block consists of a macromer derived from polyvinyl alcohol (PVA). The fully polymerized microsphere is approximately 90% water and is compressible to approximately 20-30% by diameter. Bead Block is dyed blue (LC Bead are available as blue and in natural color) to aid in the visualization of the microspheres in the delivery syringe. The microspheres can be delivered through typical microcatheters in the 1.8-5Fr range.
LC Bead is supplied sterile and packaged in sealed glass vials. Bead Block is supplied sterile and packaged in polycarbonate syringes. The product configurations are described in the table. LC Bead/Bead Block are supplied in several unit sizes covering the range from 100-1200um diameter. At the time of use, LC Bead/Bead Block is mixed with a nonionic contrast agent, e.g. Omnipaque™, to make a 30-50% by weight solution.
The provided text describes the LC Bead/Bead Block Embolic Agent, a vascular embolization device, and includes information relevant to its acceptance criteria and the studies conducted to demonstrate its performance.
Acceptance Criteria and Device Performance
The acceptance criteria for the LC Bead/Bead Block devices are primarily defined by successful outcomes in various biocompatibility tests, in-vitro physical property tests, and pre-clinical animal model performance, all demonstrating substantial equivalence to predicate devices and adherence to relevant standards.
Here's a table summarizing the acceptance criteria and the reported device performance based on the provided document:
| Acceptance Criteria Category | Specific Test/Property | Acceptance Criteria | Reported Device Performance |
|---|---|---|---|
| Biocompatibility (ISO 10993) | Genotoxicity: In Vitro Chromosomal Aberration Study | Pass | Pass |
| Mouse Bone Marrow Micronucleus Study | Pass | Pass | |
| In Vitro Hemolysis Study | Pass | Pass | |
| ISO Muscle Implantation Study (Rabbit) | Pass | Pass | |
| Cytotoxicity Study (ISO Elution Method) | Pass | Pass | |
| ISO Sensitization Study (Guinea Pig) | Pass | Pass | |
| ISO Acute Intracutaneous Reactivity Study (Rabbit) | Pass | Pass | |
| Chronic Toxicity Study (Rat, Subcutaneous, 13 weeks) | Pass | Pass | |
| Subchronic Intravenous Toxicity Study (Rat, 14 days) | Pass | Pass | |
| Genotoxicity: Bacterial Reverse Mutation Study | Pass | Pass | |
| ISO Acute Systemic Toxicity Study (Mouse) | Pass | Pass | |
| ISO Surgical Muscle Implantation (Rabbit, 26 weeks) | Pass | Pass | |
| Pre-clinical (Swine Model) | Recanalization of vessels (comparison to predicate) | Substantially equivalent or better than predicate | LC Bead demonstrated an advantage in having a more durable embolization effect compared to Embospheres. |
| Local and systemic foreign body tissue reactions | Very mild and similar to predicate | Very mild and essentially the same as Embospheres. | |
| Ease of delivery | Easy delivery, minimal catheter clogging | LC Bead delivered easily; only one case of catheter clogging (vs. six for predicate). | |
| Occurrence of blood vessel rupture | No incidents | No incidents. | |
| Non-target embolization/device migration | Minimal incidence, comparable to predicate | One case of unexplained non-target embolization with Embospheres, none with LC Bead. One potential case of device migration with LC Bead, none with Embospheres (overall comparable). | |
| In-Vitro Physical Properties | Size distribution (new 70-150µm LC Bead) | Met specification | All product met specification; graph shows tight distribution for Lots A, B, C. |
| Fibres Specification (new 70-150µm LC Bead) | Pass | Pass | |
| Compressibility | Equivalent to other marketed embolic agents | Equivalent compressibility to other marketed embolic agents. | |
| Catheter Deliverability | Compatible with typical microcatheters | Successfully delivered through various microcatheters ranging from 0.016" to 0.024" ID. | |
| Other Device Attributes | Residual starting materials | Pass | Pass |
| Residual solvents | Pass | Pass | |
| Product visual inspection for presence of fibres | Pass | Pass | |
| Bead Aggregation/Clogging (during catheter delivery) | No unintended aggregation or catheter blockage | Assessed during catheter delivery testing, implied Pass. | |
| Ease of Delivery (during catheter delivery) | "Not difficult" | Assessed as part of catheter delivery testing, must be "not difficult" to pass; implied Pass. | |
| Shape after embolic after injection | Evaluated using optical microscopy; implied acceptable | Evaluated using optical microscopy; implied Pass. | |
| Bead Deliverability (whole vial through catheter) | Successful delivery of whole vial | Ability to deliver the whole vial of beads mixed with contrast agent through a catheter as described in the IFU; implied Pass. | |
| Levels of broken or bead fragments after catheter delivery | Minimal/acceptable | Evaluated after catheter delivery using optical microscopy; implied Pass. | |
| Time to Suspension Studies | Stable homogeneous suspension within specified time | Time taken for beads to form a stable homogeneous suspension when mixed with contrast and saline/water; implied Pass. | |
| Bead aspiration from vial | Easy removal using standard syringes and needles | Ease of removing beads from primary packaging using standard syringes and needles as described in IFU; implied Pass. | |
| Bead sizing (after packaging and sterilization) | Met specification | Size of beads after packaging and sterilization; implied Pass. | |
| pH Testing (of final packing solution) | Met specification | pH of the final packing solution after sterilization; implied Pass. |
Study Details
The primary study mentioned to demonstrate device performance is a pre-clinical evaluation in a swine model and various in-vitro and biocompatibility tests.
2. Sample Size and Data Provenance
- Test Set (Pre-clinical Swine Model):
- Sample Size: LC Bead Embolic Agent (n=36) and Embosphere® microspheres (n=36). Total of 72 cases.
- Data Provenance: Prospective animal study (swine model), likely conducted in a controlled laboratory setting. The country of origin is not specified but assumed to be within the regulatory framework of the submitting company (UK) or a contracted research organization.
3. Number of Experts and Qualifications for Ground Truth (Test Set)
The document does not specify the number or qualifications of experts used to establish a "ground truth" in the clinical sense for the animal study. The evaluation appears to be based on direct observations and pathological analyses rather than expert consensus on diagnostic images. Outcomes assessed include recanalization, tissue reactions, ease of delivery, rupture, and migration. These would typically be evaluated by a team of veterinary surgeons, pathologists, and potentially radiologists, but their specific qualifications are not detailed.
4. Adjudication Method (Test Set)
The document does not describe a formal adjudication method (like 2+1 or 3+1 consensus) for the pre-clinical swine study outcomes. The assessment appears to be based on direct measurement and observation by the study investigators.
5. Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study
No MRMC comparative effectiveness study involving human readers or AI assistance is described. This device is a physical embolization device, not an AI software or diagnostic tool that would typically involve such a study with human readers interpreting images.
6. Standalone Performance Study
The "pre-clinical testing in a large animal model" and the "in-vitro testing" sections describe studies of the device's standalone performance. These are intended to demonstrate the device's intrinsic characteristics and biological safety without human interaction beyond its intended use (delivery by a clinician).
7. Type of Ground Truth Used for Test Set
- Pre-clinical Swine Model: The ground truth was established through direct observation during procedures (e.g., ease of delivery, vessel rupture), gross pathological examination (e.g., non-target embolization, device migration), and histological analysis of explanted tissues (e.g., recanalization, local and systemic foreign body tissue reactions).
- Biocompatibility Tests: Laboratory assays and animal studies according to ISO standards, providing biological and toxicological endpoints.
- In-vitro testing: Direct physical measurements and observations of device properties (e.g., size distribution, compressibility, catheter deliverability, residual materials).
8. Sample Size for the Training Set
The document does not mention a training set. This is because the device is a physical medical device, not a machine learning or AI algorithm that requires a training set. The performance data presented are from verification and validation studies.
9. How the Ground Truth for the Training Set Was Established
Not applicable, as no training set for an AI/ML algorithm is described.
§ 882.5950 Neurovascular embolization device.
(a)
Identification. A neurovascular embolization device is an intravascular implant intended to permanently occlude blood flow to cerebral aneurysms and cerebral ateriovenous malformations. This does not include cyanoacrylates and other embolic agents, which act by polymerization or precipitation. Embolization devices used in other vascular applications are also not included in this classification, see § 870.3300.(b)
Classification. Class II (special controls.) The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices.” For availability of this guidance document, see § 882.1(e).