(271 days)
Callispheres Embolic Microspheres and 8Spheres Embolic Microspheres are intended to be used for the embolization of arteriovenous malformations (AVMs) and hypervascular tumors, including uterine fibroids.
CalliSpheres and 8Spheres Embolic Microspheres are compressible hydrogel microspheres with a regular shape, smooth surface, and calibrated size, which are formed as a result of chemical modification on polyvinyl alcohol (PVA) materials. CalliSpheres and 8Spheres Embolic Microspheres consist of a macromer derived from polyvinyl alcohol (PVA), and are hydrophilic, non-resorbable, and are available in a range of sizes. The preservation solution is 0.9% sodium chloride solution. The water content of fully polymerized microsphere is 91% ~ 94%. Microspheres can tolerate compression of 30%. CalliSpheres Embolic Microspheres are dyed blue to aid in the visualization of the microspheres in the delivery syringe. 8Spheres Embolic Microspheres are undyed and with natural color. CalliSpheres and 8Spheres Embolic Microspheres are supplied sterile and packaged in sealed glass vials.
CalliSpheres Embolic Microspheres and 8Spheres Embolic Microspheres are intended to be used for the embolization of arteriovenous malformations (AVMs) and hypervascular tumors, including uterine fibroids. By blocking the blood supply to the target area, the tumor or malformation is starved of nutrients and shrinks in size.
CalliSpheres and 8Spheres Embolic Microspheres can be delivered through typical microcatheters in the 1.7- 4 Fr range. At the time of use, CalliSpheres and 8Spheres Embolic Microspheres are mixed with a nonionic contrast agent to form a suspension solution. CalliSpheres and 8Spheres Embolic Microspheres are intended for single use and are supplied sterile and non-pyrogenic.
The provided text describes the acceptance criteria and a study validating the performance of CalliSpheres Embolic Microspheres and 8Spheres Embolic Microspheres, which are vascular embolization devices.
Here's a breakdown of the requested information:
1. Table of acceptance criteria and the reported device performance
The document primarily focuses on non-clinical performance testing (in-vitro bench testing, packaging, shelf-life, sterilization, chemical characterization, and biocompatibility) and an animal study. The "acceptance criteria" are generally implied to be "met predefined acceptance criteria" or "met specifications" for the bench tests, and comparability to a predicate device for the animal study.
| Test Item | Acceptance Criteria (Implied) | Reported Device Performance |
|---|---|---|
| In-Vitro Bench Testing | ||
| Appearance | Met predefined acceptance criteria (e.g., USP & ) | Met predefined acceptance criteria |
| pH test | Met predefined acceptance criteria (e.g., USP ) | Met predefined acceptance criteria |
| Size range confirmation | Met predefined acceptance criteria (e.g., Method adapted from ISO 13322-1:2014) | Met predefined acceptance criteria |
| Compressibility Test | Met predefined acceptance criteria (e.g., retained shape/no breakage after 30% compression for 10s) | Met predefined acceptance criteria |
| Catheter deliverability test | Met predefined acceptance criteria (e.g., no clogging, no breakage/shape change) | Met predefined acceptance criteria |
| Water content test | Met predefined acceptance criteria (e.g., USP ) | Met predefined acceptance criteria |
| Impurities & Residual Solvents Test | Met predefined acceptance criteria (e.g., USP , , , ) | Met predefined acceptance criteria |
| Suspension | Met predefined acceptance criteria (e.g., time to achieve 4 mins) | Met predefined acceptance criteria |
| Sterility Test | Met predefined acceptance criteria (e.g., USP ) | Met predefined acceptance criteria |
| Bacterial Endotoxins | Met predefined acceptance criteria (e.g., USP , not more than 0.5 EU/mL) | Met predefined acceptance criteria |
| Packaging & Shelf Life | ||
| Packaging Integrity | Maintain integrity as per ASTM F1980-16 for 2 years shelf life | All samples met specifications, supported 2-year shelf life |
| Shelf Life | Maintain specifications for 2 years | All samples met specifications after accelerated aging equivalent to 2 years |
| Sterilization | ||
| Sterility Assurance Level (SAL) | 10^-6 (per ANSI/AAMI/ISO 17665-1:2006(R)2013) | Achieved 10^-6 SAL |
| Chemical Characterization | ||
| Risk of Chronic Toxicity & Carcinogenicity | Low risk (based on margins of safety from exhaustive extraction) | Determined to have low risk |
| Biocompatibility | ||
| Cytotoxicity | No evidence of cell lysis or toxicity (grade 2-fold increase in mean mutant frequency) | Not mutagenic |
| ISO Muscle Implantation Study | Macroscopic reaction not significant compared to negative control; microscopic reaction minimal to slight | Macroscopic reaction not significant; microscopic reaction slight |
| Systemic Toxicity (13 weeks) | No changes in hematology/clinical chemistry related to implantation; no evidence of systemic response; local tissue response comparable to control | No systemic toxicity; minimal to no reaction in tissue |
| Chronic Systemic Toxicity & Carcinogenicity (Biological Risk Assessment) | Not considered to have chronic systemic toxicity and carcinogenicity risk | Not considered to have chronic systemic toxicity and carcinogenicity risk |
| Animal Performance Testing | ||
| Recanalization/Durability of Occlusion | Comparable to predicate device (Embosphere) | Complete embolization effectively achieved |
| Local/Systemic Foreign Body Reactions | Mild and comparable to predicate device | Mild and comparable |
| Embolization Effectiveness | Comparable to predicate device | Complete embolization effectively achieved |
| Ease of Delivery | Easily delivered to target vessels, comparable to predicate | Easily delivered to target vessels |
| Rupture/Puncture of Blood Vessels | No rupture or perforation | No vascular rupture or perforation |
| Non-target Embolization/Device Migration | Comparable to predicate device | Comparable non-target embolization |
| Clinicopathological Examination | No significant difference in adverse reactions compared to predicate | No significant difference |
2. Sample sized used for the test set and the data provenance
- In-vitro Bench Testing: The specific sample sizes for each bench test are not explicitly provided, but it's stated that for Packaging Integrity and Shelf Life, "3 batches of each tested for all device specifications."
- Animal Performance Testing:
- Sample Size: 24 swine (12 for CalliSpheres Embolic Microspheres, 12 for Embosphere microspheres).
- Data Provenance: The study was an "animal study... intended to simulate the clinical application... A pig model was chosen." This indicates prospective animal data, conducted to support the device's substantial equivalence. The country of origin for the study is not explicitly stated in the provided text.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts
This document describes a pre-market notification (510(k)) for a medical device (embolic microspheres). It does not describe a study involving human experts establishing ground truth for AI model testing. The ground truth for the non-clinical tests is based on established laboratory standards, and for the animal study, it's based on clinical observations, histopathological results, and standard measurements.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
Not applicable, as this is not a human expert-based ground truth adjudication for an AI device.
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 document is for a medical device (embolic microspheres), not an AI-assisted diagnostic or triaging tool.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
Not applicable. This document is for a medical device, not a software algorithm.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)
- In-vitro Bench Testing: Ground truth is based on established international and national standards (e.g., USP, ISO, ASTM guidelines) and predefined acceptance criteria for physical, chemical, and biological properties.
- Animal Performance Testing: Ground truth was established through:
- Direct observation and measurement: Ease of delivery, presence of rupture/perforation, non-target embolization.
- Clinical tests: Blood routine, coagulation function, renal function, liver function.
- Imaging: DSA angiography.
- Pathology/Histopathology: Evaluation of local and systemic foreign body reactions, and assessment of embolization effectiveness after necropsy.
8. The sample size for the training set
Not applicable. This document describes the validation of a physical medical device (embolic microspheres), not an AI model requiring a training data set.
9. How the ground truth for the training set was established
Not applicable, as there is no training set for an AI model.
§ 870.3300 Vascular embolization device.
(a)
Identification. A vascular embolization device is an intravascular implant intended to control hemorrhaging due to aneurysms, certain types of tumors (e.g., nephroma, hepatoma, uterine fibroids), and arteriovenous malformations. This does not include cyanoacrylates and other embolic agents, which act by polymerization or precipitation. Embolization devices used in neurovascular applications are also not included in this classification, see § 882.5950 of this chapter.(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 § 870.1(e).