The Comaneci Embolization Assist Device is indicated for use in the neurovasculature as a temporary endovascular device used to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width ≤ 10 mm. A wide-necked intracranial aneurysm defines the neck width as ≥ 4 mm or a dome-to-neck ratio < 2.

Device Description

The Comaneci Embolization Assist Device consists of three device models: Comaneci, Comaneci Petit, and Comaneci 17 (see Table 1). The Comaneci Embolization Assist Device is intended for temporary use and is introduced through an endovascular approach to the neurovasculature to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width < 10 mm. The device consists of a nitinol fine wire mesh region at the distal end mounted on a flexible shaft that expands and contracts when the physician pulls a core wire that is coated with polytetrafluoroethylene (PTFE) and connected to a handle with a control slider made of a styrene-butadiene copolymer (Figures 1 and 2). The fine wire mesh region on the Comaneci Embolization Assist Device is unique in that it is not self-expandable but is directly controlled by the physician to size this region of the device to the parent vessel. The wires of the mesh are radiopaque, which allows the physician to visualize the mesh under fluoroscopy. The Comaneci and Comaneci Petit models are delivered through a microcatheter with an internal diameter (ID) of 0.021 inches and the Comaneci 17 is delivered through a microcatheter with an ID of 0.017 inches. The devices are packaged in a sterile pouch and are intended for single use only.

AI/ML Overview

The Comaneci Embolization Assist Device is a Class II device (Product Code: PUU, Regulation Number: 21 CFR 882.5955) intended for temporary use in the neurovasculature to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width ≤ 10 mm.

The acceptance criteria for the Comaneci Embolization Assist Device, as derived from the provided text, are multifaceted, encompassing non-clinical bench testing, animal studies, and a retrospective clinical study.

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria are not explicitly presented in a single table with numerical targets, but rather are implicitly defined by the successful outcomes of various tests and the conclusions drawn from them. Below is a structured presentation of the implicit acceptance criteria based on the described studies and the reported device performance.

Acceptance Criterion Category	Specific Acceptance Criterion (Implicit)	Reported Device Performance and Evidence
Biocompatibility	Device components in contact with the patient (e.g., blood) must be biocompatible according to ISO 10993-1, covering hemocompatibility (complement activation, thrombogenicity, indirect/direct hemolysis), cytotoxicity, sensitization, intracutaneous reactivity, acute systemic toxicity, and material-mediated pyrogenicity. (Ref: Section 'BIOCOMPATIBILITY/MATERIALS')	Evaluated as an external communicating device of limited contact duration (< 24 hours), directly blood-contacting. Testing performed per ISO 10993-1:2009/AC:2010 and CDRH Guidance. Specific results are not quantified but the overall conclusion of biological safety is implied by the De Novo grant. (Ref: Section 'BIOCOMPATIBILITY/MATERIALS')
Sterility & Shelf Life	Device must be sterile with a sterility assurance level (SAL) of at least 10^-6, meet endotoxin limits (< 2.15 EU/device), maintain package integrity, and remain functional over its labeled shelf life. (Ref: Section 'SHELF LIFE/STERILITY', Special Control 5 & 6)	Sterility assured by validated EtO sterilization (ISO 11135:2014) achieving SAL of at least 10^-6. Bioburden testing compliant with ISO 11737-1:2006. Bacterial endotoxin testing meets USP <161> (< 2.15 EU/device). Validated for a shelf life of 2.5 years, including package integrity testing (ASTM D4169, F1980, F1929, F2096). (Ref: Section 'SHELF LIFE/STERILITY')
Bench Performance (Non-Clinical)	Device must function adequately under simulated conditions of use, demonstrating: - Adequate tensile strength of joints. - Ability to reach tortuous vasculature without kinking. - Compatibility with recommended microcatheters and delivery through tortuous models. - Resistance to corrosion in simulated physiological environment. - Acceptable tip flexibility. - Verified dimensional attributes. - Minimal particulate generation. - Ability of distal mesh to withstand external forces (coil mass) and retain structural integrity, with safe radial outward forces. - Integrity of PTFE coating on core wire. - Ability to withstand typical tracking forces and procedural torquing. - Performance in simulated in vitro anatomical models as per DFU. (Ref: Section 'PERFORMANCE TESTING - BENCH', Special Control 3)	Comprehensive bench testing performed. Specific quantitative results are not provided, but the successful completion of these tests (under simulated use conditions, post-sterilization) is stated to demonstrate adequate function and mitigation of risks. The De Novo grant implies these acceptance criteria were met. (Ref: Section 'PERFORMANCE TESTING - BENCH', Table 3)
Animal Study Performance	Device must demonstrate acute (4 days) and chronic (28 days) safety and performance in a relevant animal model (rabbit elastase-induced aneurysm), including: - Successful device delivery without major procedural complications (death, artery perforation, flow-limiting dissection/thrombosis). - Absence of embolic coil prolapse in parent artery. - Absence of aneurysm intraluminal filling post-device application. - Overall animal mortality < 15%. - Comparable or better semi-quantitative morphometric analysis in tissue sections vs. control. - Comparable or better histologic indicators of vessel wall healing (injury, inflammation, endothelial loss) vs. control. - Absence of perforations, dissections, erosions, or thrombus. (Ref: Section 'PERFORMANCE TESTING - ANIMAL', Special Control 4)	Acute: Successful coil embolization in 23 aneurysms (20 animals) with no post-procedural mortalities, no angiographically-visible coil protrusions. Absence of morbidity, thrombosis, infection, hemorrhage, downstream ischemia. Chronic: Patent parent vessels, gross/histologic evidence of normal aneurysmal sac embolization. Visible mild coil protrusion in 2 Comaneci cases (1 HyperGlide control). Absence of perforations, dissections, erosions, thrombus formation in contact zones; absence of thrombus in distal skeletal muscles. Overall, performance was deemed comparable or better than control. (Ref: Section 'PERFORMANCE TESTING - ANIMAL')
Clinical Performance & Safety	Device must demonstrate safe and effective performance in a clinical setting, evaluating: - Successful coil embolization without entanglement, ensnarement, or significant prolapse/protrusion. - Acceptable rates of device- and procedure-related serious adverse events (including tissue/vessel damage, thromboembolic events, coil entanglement, coil prolapse). - Ability to be visualized under fluoroscopic guidance (radiopacity). (Ref: Section 'SUMMARY OF CLINICAL INFORMATION', Special Control 1)	Technical Success Rate: 93.65% (59/63 patients) achieved successful coil embolization without entanglement, ensnarement, or prolapse/protrusion. - No coil entanglement/ensnarement. - 4 cases (6.35%) of coil prolapse, none with clinical abnormalities/sequelae. Adverse Events: Total 11.1% (7/63 patients) experienced at least one serious neurological adverse event within 3-months post-procedure. - Symptomatic thrombotic event/ischemic stroke: 2 (3.17%) - Vasospasm: 1 (1.59%) - Contralateral SCA hemorrhage: 1 (1.59%) - Left SCA occlusion: 1 (1.59%) - Other neurological (Cerebellar ataxia, Paresis, Apathy, Mild hemiparesis, Mild aphasia): 5 (1.59% each) - Aneurysm Rupture: 1 (1.59%) (Pre-procedure, patient admitted with ruptured aneurysm). The report notes the AE rate for neurological events is similar to published literature for balloon-assisted coiling and that many AEs may be disease-state related. (Ref: Tables 5, 6, 7; Section 'Results', Section 'Benefit-Risk Determination')
Labeling	Labeling must meet 21 CFR § 801.109 requirements, including instructions for use, technical parameters, clinical testing summary, complications, and shelf life. (Ref: Section 'LABELING', Special Control 7)	Labeling includes instructions for proper device preparation, model/size selection, and use; expertise needed; detailed summary of technical parameters and compatible delivery catheter dimensions; summary of clinical testing results including complications and AEs; and a stated shelf life. (Ref: Section 'LABELING')

Study Proving Device Meets Acceptance Criteria:

The study proving the device meets the acceptance criteria is a multi-faceted approach involving extensive non-clinical bench testing, an animal study, and a retrospective clinical case series. The "Summary of Clinical Information" section specifically details the human study.

2. Sample Size Used for the Test Set and Data Provenance

Test Set Sample Size (Clinical Study): 63 consecutively treated patients with 64 intracranial aneurysms.
Data Provenance:
- Country of Origin: The study was conducted outside the United States (OUS) at two sites: Walton Center in Liverpool, United Kingdom, and University Hospital St. Ivan Rilski in Sofia, Bulgaria.
- Retrospective or Prospective: Retrospective post-market collection.

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

Imaging Data (Technical Success and Safety): Independently analyzed by the Angiography and Noninvasive Imaging Core Lab at University of California - Los Angeles. The number of experts is not specified.
Adverse Events: Adjudicated independently by the Department of Neurology at the University of Southern California. The number of experts is not specified.
Qualifications of Experts: The specific qualifications (e.g., years of experience, subspecialty certification) of the experts for both imaging analysis and AE adjudication are not explicitly detailed beyond their affiliation with known university medical departments/labs.

4. Adjudication Method for the Test Set

Imaging Data: Independent analysis by a core lab (UCLA). No specific "2+1" or "3+1" consensus method is described, implying independent interpretation rather than a multi-reader consensus process for a single finding.
Adverse Events: Independently adjudicated by a department (USC Neurology). Similar to imaging, a specific multi-expert consensus method (e.g., 2+1) is not explicitly stated.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not explicitly done to evaluate how human readers improve with AI vs. without AI assistance. The clinical study was a retrospective case series focused on device performance and safety with standard human intervention. The device is a mechanical assist device, not an AI-powered diagnostic or assistive tool for human readers (e.g., radiologists interpreting images). Therefore, this type of MRMC study is not applicable to the Comaneci device's function.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

Not applicable. The Comaneci device is a physical, mechanical embolization assist device, not an algorithm. Its performance is inherently tied to human use in a medical procedure. Standalone performance for a device of this type would refer to bench testing (which was performed) or animal studies (which were performed), demonstrating the device's mechanical integrity and biological interaction. It does not relate to an algorithm's performance without human interaction.

7. The Type of Ground Truth Used

Clinical Study: The ground truth for clinical outcomes (technical success and adverse events) was established through a combination of:
- Independent analysis of imaging data (angiography) by a core lab for technical success (e.g., aneurysm occlusion, coil prolapse).
- Independent adjudication of adverse events by a neurology department based on collected CRF data.
- Patient follow-up data (up to 3 months post-procedure) to assess clinical abnormalities or sequelae related to events like coil prolapse.
- For the purposes of this device, the "ground truth" concerning the clinical outcomes is defined by these independent expert evaluations and the observed clinical course.
Animal Study: Ground truth was established by:
- Angiographic evaluations at termination to assess blood flow, aneurysm filling, and coil presence.
- Gross and histological evaluations (light microscopy, SEM) of tissue sections for injury, inflammation, and endothelial loss.
- Clinical observation of animals (morbidity, thrombosis, infection, hemorrhage).

8. The Sample Size for the Training Set

The document does not mention a "training set" in the context of device development or evaluation, as this pertains more to AI/machine learning models. For a physical medical device, development involves iterative design, bench testing, and animal studies, which collectively inform and "train" the design, but not in the sense of a data science training set. The clinical study was a retrospective data collection for validation, not a dataset used for iterative model training.

9. How the Ground Truth for the Training Set Was Established

As a "training set" in the data science sense is not explicitly mentioned or used for this mechanical device, the concept of establishing ground truth for it is not applicable here. The development and verification process relied on engineering principles, bench testing standards, animal models, and human clinical experience.

Summary

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DE NOVO CLASSIFICATION REQUEST FOR COMANECI EMBOLIZATION ASSIST DEVICE

REGULATORY INFORMATION

FDA identifies this generic type of device as:

Temporary coil embolization assist device. A temporary coil embolization assist device is a prescription device intended for temporary use in the neurovasculature to mechanically assist in the embolization of intracranial aneurysms with embolic coils. The device is delivered into the neurovasculature with an endovascular approach. This device is not intended to be permanently implanted and is removed from the body when the procedure is completed.

NEW REGULATION NUMBER: 21 CFR 882.5955

CLASSIFICATION: Class II

PRODUCT CODE: PUU

BACKGROUND

DEVICE NAME: Comaneci Embolization Assist Device

SUBMISSION NUMBER: DEN170064

DATE DE NOVO RECEIVED: September 28, 2017

SPONSOR INFORMATION:	Rapid-Medical Ltd.Carmel Building, POB 337Yokneam, Yokneam 2069205Israel
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INDICATIONS FOR USE

LIMITATIONS

The sale, distribution, and use of the Comaneci Embolization Assist Device are restricted to prescription use in accordance with 21 CFR 801.109.

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PLEASE REFER TO THE LABELING FOR A COMPLETE LIST OF WARNINGS. PRECAUTIONS AND CONTRAINDICATIONS.

DEVICE DESCRIPTION

Figure 1. Comaneci Embolization Assist Device mesh region in both the expanded and contracted positions.

Figure 2. Comaneci Embolization Assist Device with Handle.

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	Comaneci	Comaneci Petit	Comaneci 17
Weight	36 g	36 g	36 g
Contracted MeshLength	32 mm	24 mm	22 mm
Expanded MeshLength	25 mm (4.0 mmsimulated vessel)	21 mm (3.0 mmsimulated vessel)	16 mm (3.0 mmsimulated vessel)
Total Length (NotIncluding Handle)	1825 mm	1827 mm	1787 mm

Table 1. Comaneci Embolization Assist Device Dimensions

SUMMARY OF NONCLINICAL/BENCH STUDIES

BIOCOMPATIBILITY/MATERIALS

The Comaneci Embolization Assist Device is classified as an external communicating device of limited contact duration (< 24 hours) and is directly blood-contacting. Table 2 shows the device components and materials of construction that were evaluated for biocompatibility. The applicable biocompatibility endpoints evaluated are hemocompatibility (complement activation, thrombogenicity, indirect hemolysis and direct hemolysis), cytotoxicity, sensitization, intracutaneous (intradermal) reactivity. acute systemic toxicity, and material-mediated pyrogenicity testing per International Standard Organization (ISO) 10993-1:2009/AC:2010 (Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing) and the Center for Devices and Radiological Health (CDRH) Guidance for Industry and Food and Drug Administration Staff, "Use of International Standard ISO 10993-1. 'Biological Evaluation of Medical Devices - Part 1: Evaluation and Testing within a Risk Management Process"", issued on June 16, 2016.

Comaneci Embolization Assist Device.
Name of Component	Materials used in Finished Devices
Distal Mesh	Nitinol Wire
Tip	(b) (4) and Nitinol
Core Wire	Nitinol with PTFE Coating
Markers	(b) (4)

Table 2. Patient Contacting Materials of Construction of the

SHELF LIFE/STERILITY

The Comaneci Embolization Assist Device is sterilized with ethylene oxide (EtO). The sterility of the Comaneci Embolization Assist Device was assured by using the validated (b) (4) sterilization method qualified in accordance with ISO 11135:2014. Based on the validation results, a sterility assurance level (SAL) of at least 10-6 was achieved. The sterilization validation included (D) (4)

The surveillance of the sterilization results was performed using biological indicators and complies with the requirements in ISO 11138-2:2006. Bioburden testing was performed on packaged devices using the validation test method according to ISO 11737-1:2006. "Sterilization of Medical Devices

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Microbiological Methods - Part 1: Determination of a Population of Microorganisms on Product."

Bacterial endotoxin testing using the limulus amebocyte lysate (LAL) test method was also evaluated for the Comaneci Embolization Assist Device to meet the endotoxin limit of less than 2.15 endotoxin units (EU)/device according to United States Pharmacopeia (USP) <161> Transfusion and Infusion Assemblies and Similar Medical Devices. This evaluation is important because there is the risk of vessel dissection with the subject device, which can result in direct contact with cerebrospinal fluid (CSF) and introduce the risk of infection in the brain if there are bacterial endotoxins remaining on the device.

The Comaneci Embolization Assist Device is packaged inside a (b) (4)

blister box. The blister box is closed by a cover to prevent device movement during handling and shipment. The blister box is placed inside a heatsealed Tyvek® pouch. The seal is designed for EtO sterilization providing a microbiological barrier and allowing the passage of moisture and EtO to enable the sterilization of the packaged contents.

The Comaneci Embolization Assist Device and its packaging has been validated for a shelf life of 2.5 years. The test units for shelf-life testing contained a blister box with hoop and tube that simulated the device and handle to represent the packaged device configuration and weight. The test units were also packaged in Tyvek pouches and underwent two EtO sterilization cycles. The Comaneci Embolization Assist Device also underwent additional package integrity testing in accordance with the following standards:

ASTM D4169:2009 - Standard Practice for Performance Testing of Shipping Containers and Systems
ASTM F1980:2011 Standard Guide for Accelerated Aging of Sterile Barrier ● Systems for Medical Devices
. ASTM F1929:2004 - Standard Test Method for Detecting Seal Leaks in Porous Medical Packaging by Dye Penetration
ASTM F2096:2011 – Standard Test Method for Detecting Gross Leaks in Packaging by Internal Pressurization (Bubble Test)

PERFORMANCE TESTING - BENCH

Non-clinical bench testing was provided to demonstrate that the device would function adequately under simulated conditions of use and mitigate risks to health associated with device breakage and failure. The non-clinical bench testing is described in Table 3 based on the device risk analysis, FDA guidances for embolization devices and guidewires, and the following standards:

ISO 10555-1 (2013): Intravascular Catheters Sterile and Single-use Catheters -. Part 1: General Requirements.

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ISO 11070 (2014): Sterile Single-use Intravascular Introducers, Dilators and . Guidewires.
ISO 25539-2 (2012): Cardiovascular Implants Endovascular Devices Part 2: . Vascular Stents.

Before non-clinical bench testing, the final finished Comaneci Embolization Assist Device underwent 2 full cycles of EtO sterilization followed by inspection to ensure the devices met specifications.

Test	Test Purpose and Description
Tensile Strength	To verify that the tensile strength of each joint of the device complied with the requirements. Testing was performed with a calibrated tensile machine. The following joints were inspected: proximal connection, core wire to handle, shaft to handle, and distal connection.
Kink Resistance	To evaluate the ability of the device to reach tortuous vasculature without being kinked. Testing was performed with a calibrated kink measurement jig.
Functional andMicrocatheterCompatibility	To evaluate the ability of the device to be delivered in the recommended compatible microcatheter through the tortuous vessels of a silicone neurovasculature tortuosity model to the target site.
Corrosion	To evaluate the susceptibility of the device components to corrosion in a simulated physiological environment.
Tip Flexibility	To measure the maximum force deflected by the device tip. Testing was performed with a calibrated tensile machine.
DimensionalVerification	To verify various device dimensional attributes.
ParticulateEvaluation	To measure the total quantity and size of particulates that the device may generate in a simulated use neurovascular model.
Radial Force/Crush	To demonstrate the ability of the distal mesh portion of the device to withstand external forces and to retain its structural integrity while being compressed from the embolic coil mass. Additionally, this testing was performed to measure the radial outward forces from the device to ensure the forces exhibited from the device will not cause serious vessel damage.
Coating Integrity	To evaluate the coating integrity of the core wire, which has a PTFE coating.
Tracking Force/Torque	To demonstrate the device can withstand typical tracking forces and procedural torqueing of the device as the device is intended to be used in the neurovasculature which can have significant tortuosity.
Simulated Use	To demonstrate device performance in a simulated in vitro anatomical model from entry through the femoral artery to the
Test	Test Purpose and Description
	target neurovasculature. The testing followed the procedural instructions outlined in the Directions for Use.

Table 3. Summary of Non-Clinical Bench Testing for the Comaneci Embolization Assist Device.

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PERFORMANCE TESTING - ANIMAL

An animal study was conducted in accordance with Good Laboratory Practice (GLP) in a rabbit model of an elastase-induced aneurysm to evaluate the acute (4 days) and chronic (28 days) safety and performance of the Comaneci Embolization Assist Device compared to a control device (HyperGlide™ Balloon Catheter). The study characterized aneurysmal healing by light microscopy and en face assessment of the luminal surface by scanning electron microscopy (SEM). The animal study also assessed overall performance and handling of the device, in-life health, systemic biological tolerance, vascular injury and in-vivo thrombogenicity.

For the gross, histological, and clinical chemistry evaluations at both the acute and chronic time points, the objectives of the study were:

. Successfully create elastase-induced saccular aneurysms in rabbits to compare test and control devices.
Compare test and control devices with respect to tissue response, degree of . aneurysm healing, and safety.

Angiographic evaluations were conducted at the time of termination in both test and control animals for both acute and chronic time points to assess blood flow through the treated region, presence or absence of intra-luminal filling of the embolized aneurysm, and presence or absence of embolic coils in the parent artery. Success criteria for this assessment included:

Successful delivery of the test and control devices to the target location without . major procedural device-related complications such as death, artery perforation or flow-limiting dissection or thrombosis.
Absence of embolic coil prolapse in the parent artery. .
Absence of aneurysm intraluminal filling following device application. .
. Less than 15% overall animal mortality.
. Comparable or better performance by semi-quantitative morphometric analysis in tissue sections treated with the subject device test articles when compared to tissue sections treated with the control test articles.
Comparable or better histologic indicators of vessel wall healing such as: injury. . inflammation and extent of endothelial loss as determined by light microscopy and SEM in tissue sections exposed to the subject device test articles when compared to tissue sections exposed to the control test articles at 28 ± 2 days follow-up.

The non-clinical animal study concluded for the acute time point assessment that the parent artery was patent during coil embolization of aneurysms with both the control

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device (HyperGlide Balloon Catheter) and the subject Comaneci Embolization Assist Device. There were 23 aneurysms created in 20 animals and all of these animals underwent successful coil embolization with no post-procedural mortalities and no angiographically-visible coil protrusions into the parent vessels. Recovery of the animals in both groups was associated with absence of morbidity, thrombosis, infection, hemorrhage, or downstream ischemia.

The non-clinical animal study concluded for the terminal assessments at the chronic time point that there were patent parent vessels with gross and histologic evidence of normal aneurysmal sac embolization. Upon explant using high-resolution radiographical assessment, visible mild embolic coil protrusion was observed in two aneurysms treated with the Comaneci Embolization Assist Device and one aneurysm treated with the HyperGlide Balloon Catheter. Light microscopic and SEM evaluations of adjacent. proximal, and distal regions of the device vessel contact zones showed an absence of perforations, dissections, erosions, or thrombus formation. The distal skeletal muscles were also observed to be absent of any thrombus formation.

SUMMARY OF CLINICAL INFORMATION

Clinical data from an outside the United States (US) post-market retrospective collection of intracranial aneurysms treated with the subject device was used to support the safety and effectiveness of the Comaneci Embolization Assist Device in the subject De Novo request. The clinical study design and results are further summarized below.

Design:

The Comaneci Embolization Assist Device was evaluated in an outside the US post-market retrospective study from 63 consecutively treated patients with 64 intracranial aneurysms between March to December 2017 at two sites: Walton Center in Liverpool, United Kingdom and University Hospital St. Ivan Rilski in Sofia, Bulgaria. The patients were followed for up to 3-months post-procedure. Table 4 below summarizes the patient demographic and baseline intracranial aneurysm characteristics.

Imaging data for technical success and safety were independently analyzed by the Angiography and Noninvasive Imaging Core Lab at University of California - Los Angeles in Los Angeles, California. Adverse events were adjudicated independently by the Department of Neurology at the University of Southern California.

N	64 intracranial aneurysms in 63 patients
Ruptured/Unruptured (N=64)	Ruptured - 51/64 (80%)
	Unruptured- 13/64 (20%)
Age (N=63)	57 (34-73) years
Gender (N=63)	34 Female, 29 Male
Mean Neck Size (N=64)	4.2 mm (Range 1.9-11.5 mm)

Table 4. Patient Demographics and Baseline Intracranial Aneurysm Characteristics Treated with the Comaneci Embolization Assist Device

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Aneurysm Location (N=64)	Anterior Communicating Artery (AComm) - 17 (26.6%)
	Anterior Cerebral Artery (ACA) - 1 (1.5%)
	Anterior Choroidal Artery - 1 (1.5%)
	Anterior Inferior Cerebellar Artery (AICA) - 1 (1.5%)
	Basilar Tip - 3 (4.7%)
	Middle Cerebral Artery (MCA) - 10 (15.6%)
	Ophthalmic - 6 (9.4%)
	Posterior Communicating Artery (PComm) - 17 (26.6%)
	Superior Cerebellum Artery (SCA) - 4 (6.2%)
	Internal Carotid Artery (ICA) - 4 (6.2%)
Mean Number of Coils per Aneurysm (N=64)	6.09 (Range 1-19)

Data was collected using a pre-specified case report form (CRF) that was designed to collect technical procedural related information regarding the use of the subject device and devicerelated serious adverse events (AEs). Data collected in the CRF included:

Whether the Comaneci Embolization Assist Device was used as a first-choice device.
Number of device attempts.
Intracranial aneurysm neck coverage. ●
Number of embolization coils deployed.
Number of re-expansions of the Comaneci Embolization Assist Device during the ● procedure.
Intracranial aneurysm occlusion using the Raymond-Roy scale.
Alternative treatment(s) used. ●
Time the Comaneci Embolization Assist Device was left inside the target vessel while ● opened.
Incidences of rupture, hemorrhage, thrombotic events, deaths, coil prolapse, and coil entanglement.

The clinical study also evaluated radiopacity of the device to verify it can be visualized under fluoroscopic guidance. No pre-specified inclusion or exclusion criteria were used in the retrospective study analysis, and the treating physician used their own judgment to determine if a patient was eligible for treatment with the subject device. In the De Novo request, the training plan for the use of the device with the novel adjustment feature of the mesh region was provided as part of the review.

Results:

No mortality or subject device-coil entanglements were reported in the outside the US retrospective study of the Comaneci Embolization Assist Device. Table 5 shows the ten (10) serious AEs reported from the retrospective study and an additional one AE of intracranial

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aneurysm rupture associated with the patient. A limitation of the retrospective study was that the data was only collected at 2 sites outside the US and the AE data reported was limited to devicerelated serious AEs including intracranial aneurysm or vessel rupture or hemorrhage, death, thrombotic events, and technical success data such as coil entanglement and prolapse into the parent artery. Therefore, this retrospective data is not a full representation of the safety profile of the Comaneci Embolization Assist Device.

Adverse Event	Numberof Events	IncidenceRate (%)N=63Patients	Time of EventOnset	95%UnadjustedConfidenceIntervals (%)1
Symptomatic thromboticevent/ischemic stroke	2	3.17	24 and 4 hourspost-procedure	(0.39, 11.0)
Vasospasm	1	1.59	Duringprocedure	(0.04, 8.53)
Contralateral SCAhemorrhage	1	1.59	Duringprocedure	(0.04, 8.53)
Left SCA occlusion	1	1.59	3 months post-procedure	(0.04, 8.53)
Cerebellar ataxia	1	1.59	24 hours post-procedure	(0.04, 8.53)
Paresis for right leg	1	1.59	48 hours post-procedure	(0.04, 8.53)
Apathy, memory disorder,personality changes	1	1.59	48 hours post-procedure	(0.04, 8.53)
Mild hemiparesis	1	1.59	48 hours post-procedure	(0.04, 8.53)
Mild aphasia	1	1.59	48 hours post-procedure	(0.04, 8.53)
Aneurysm Rupture*	1	1.59	Pre-procedure	(0.04, 8.53)

Table 5. Adverse Events Reported in Retrospective Study of the Comaneci Embolization Assist Device

(*) Patient admitted with ruptured intracranial aneurysm.

(1) All 95% confidence intervals (CIs) are unadjusted. As such. The CI is provided to show the variability only and should not be used to draw any statistical conclusions.

Table 6 shows the post-hoc analysis using descriptive statistics of the total incidence of treated patients experiencing at least one AE from the retrospective post-market case series from 2 outside the US sites of 63 patients recorded within 3-months post-procedure.

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N(Patients)	Number of Patients ThatExperienced Any AEEvent	AE Rate(%)	95% UnadjustedLower Bound CI(%)*	95% UnadjustedUpper Bound CI(%)*
63	7	11.1%	5.55	23.15

				Table 6. Post-hoc Safety Analysis
--	--	--	--	-----------------------------------	--	--

All 95% CIs are unadjusted. As such. the CI is provided to show the variability only and should not be used to draw any statistical conclusions.

Table 7 shows the technical success rate defined post-hoc as the successful coil embolization of the target intracranial aneurysm without the incidence of embolic coil entanglement. ensnarement, prolapse, or protrusion into the parent vessel was observed in 93.65% (59/63) of the patients treated in the retrospective case series study. No cases of coil entanglement or ensnarement were observed, and 4 cases (6.35% (4/63)) of coil prolapse were noted. None of the four events were associated with any clinical abnormalities or sequelae with the known followup data collected within 3-months post-procedure.

N(Patients)	Technical Success Rate (%)	95% UnadjustedLower Bound CI(%)*	95% UnadjustedUpper Bound CI(%)*
63	93.65	84.53	98.24

Table 7 Post-hoc Technical Success Analysis

All 95% CIs are unadjusted. As such, the CI is provided to show the variability only and should not be used to draw any statistical conclusions.

Pediatric Extrapolation

In this De Novo request, existing clinical data were not leveraged to support the use of the device in a pediatric patient population.

POSTMARKET EVALUATION

A post-market study will be conducted to collect data on the safety of the Comaneci Embolization Assist Device in US patients. This is a post-market, prospective, multi-center study of US patients with wide-necked intracranial aneurysms that requires adjunctive assistance with coil embolization during the surgical procedure. This post-market study will evaluate the safety of the subject device used in the real-world clinical setting in the US to assess how well US physicians are trained on the use of the subject device based on the novel adjustment feature of the mesh region of the Comaneci Embolization Assist Device.

LABELING

The labeling includes instructions for use for the physician and satisfies the requirements of 21 CFR § 801.109 for prescription devices. The labeling includes:

. Detailed instructions on proper device preparation, appropriate model and size selection, and use to assist in the coil embolization of intracranial aneurysms.
Expertise needed for the safe use of the device. .

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. A detailed summary of the device technical parameters including compatible delivery catheter dimensions.
Summary of the clinical testing results, including a detailed summary of the device- and procedure-related complications and adverse events.
A shelf life. ●

RISKS TO HEALTH

The table below identifies the risks to health that may be associated with use of a temporary coil embolization assist device and the measures necessary to mitigate these risks.

Identified Risks to Health	Mitigation Measures
Infection	Sterilization validationPyrogenicity testingShelf life testingLabeling
Adverse tissue reaction	Biocompatibility evaluation
Tissue or vessel damage:• Dissection• Perforation• Hemorrhage• Vasospasm	Non-clinical performance testingClinical performance testingLabeling
Thromboembolic event	Non-clinical performance testingClinical performance testingLabeling
Coils ensnarement	Non-clinical performance testingClinical performance testingLabeling

Table 8. Identified Risks to Health and Mitigation Measures

SPECIAL CONTROLS

In combination with the general controls of the FD&C Act. the temporary coil embolization assist device is subject to the following special controls:

1. Clinical performance testing of the device must demonstrate the device performs as intended for temporary use as an endovascular device to assist in the coil embolization of intracranial aneurysms and must evaluate all adverse events, including tissue or vessel damage that could lead to dissection, perforation, hemorrhage, or vasospasm, thromboembolic events, and coil entanglement.
1. The patient-contacting components of the device must be demonstrated to be biocompatible.
1. Non-clinical performance testing must demonstrate the device performs as intended under anticipated conditions of use, including:
- a. Mechanical testing to demonstrate the device can withstand anticipated tensile, torsional, compressive, and tip deflection forces;

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b. Mechanical testing to evaluate the radial forces exerted by the device;
c. Simulated use testing to demonstrate the device can be delivered to the target location in the neurovasculature and is compatible with embolic coils;
d. Dimensional verification testing;
e. Radiopacity testing; and
f. Performance testing to evaluate the coating integrity and particulates under simulated use conditions.
1. Animal testing under anticipated use conditions must evaluate all adverse events, including damage to vessels or tissues.
1. Performance data must support the sterility and pyrogenicity of the device.
1. Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
1. The labeling must include:
- a. Instructions for use;
- b. A detailed summary of the device technical parameters, including compatible delivery catheter dimensions and device sizing information;
- c. A summary of the clinical testing results. including a detailed summary of the deviceand procedure-related complications and adverse events; and
- d. A shelf life.

BENEFIT-RISK DETERMINATION

The risks of the device are based on nonclinical laboratory and animal studies as well as data collected in a clinical study described above. Device-related risks or adverse events could include thrombo-embolic events, tissue or vessel damage including dissection, perforation, hemorrhage, or vasospasm, entanglement of the device with embolic coils, coil prolapse into the parent vessel, death, infection, adverse tissue reaction. Based on the results of the retrospective case series submitted in support of this De Novo request with complete CRFs provided for all subjects, 11.1% (7/63) of treated subjects experienced a serious neurological adverse event within 3-months post-procedure. This serious adverse event rate is not all deemed to be deviceor procedure-related because many of the subjects treated had ruptured intracranial aneurysms and these adverse events may occur because of the disease state of these subjects. In addition, this adverse event rate is similar to that published in the scientific literature for balloon assisted coiling of intracranial aneurysms with cleared balloon occlusion catheters.

The probable benefits of the device are also based on nonclinical laboratory and animal studies as well as data collected in a clinical study as described above. The benefit of the subject device is that it is not permanently implanted and allows for blood to be supplied to the distal vasculature during the coil embolization procedure unlike balloon occlusion catheters. The osthoc analysis of the retrospective case series showed that 93.65% (59/63) of treated subjects experienced successful coil embolization of their target intracranial aneurysm without the incidence of embolic coil entanglement, ensnarement, prolapse, or protrusion into the parent vessel.

One of the limitations of the submitted clinical data is the uncertainty associated with study design (retrospective case series) and limited number of subjects (64). Only the neurological

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adverse events that could be attributed to the device or procedure were specified in the CRF. The majority of patients had ruptured intracranial aneurysms (51/64 = 79.7%) and many of the neurological adverse effects may be attributed to the underlying disease state of these patients with ruptured intracranial aneurysms. The neurological AE profile in the real world may change with a greater variety of patients to assist in the coil embolization of unruptured intracranial aneurysms. The neurological AE profile was obtained from only two sites, both of which are located outside the US. Thus, there may be additional uncertainty as to how well the submitted clinical data will predict the safety of this device in US clinical use in a broader patient population. Due to these limitations, a planned postmarket study will supplement existing evidence and gather additional experience on the safety profile of this device in the US.

Patient Perspectives

This submission did not include specific information on patient perspectives for this device.

Benefit/Risk Conclusion

In conclusion, given the available information above, for the following indication statement:

The Comaneci Embolization Assist Device is indicated for use in the neurovasculature as a temporary endovascular device used to assist in the coil embolization of wide-necked intracranial aneurysms with a neck width < 10 mm. A wide-necked intracranial aneurysm defines the neck width as ≥ 4 mm or a dome-to-neck ratio < 2.

The probable benefits outweigh the probable risks for the Comaneci Embolization Assist Device. The device provides benefits and the risks can be mitigated by the use of general controls and the identified special controls.

CONCLUSION

The De Novo request for the Comaneci Embolization Assist Device is granted and the device is classified as follows:

Product Code: PUU Device Type: Temporary coil embolization assist device Regulation Number: 21 CFR 882.5955 Class: II

Regulation Number and Section

§ 882.5955 Temporary coil embolization assist device.

(a)
Identification. A temporary coil embolization assist device is a prescription device intended for temporary use in the neurovasculature to mechanically assist in the embolization of intracranial aneurysms with embolic coils. The device is delivered into the neurovasculature with an endovascular approach. This device is not intended to be permanently implanted and is removed from the body when the procedure is completed.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Clinical performance testing of the device must demonstrate the device performs as intended for temporary use as an endovascular device to assist in the coil embolization of intracranial aneurysms and must evaluate all adverse events, including tissue or vessel damage that could lead to dissection, perforation, hemorrhage, or vasospasm, thrombo-embolic events, and coil entanglement.
(2) The patient-contacting components of the device must be demonstrated to be biocompatible.
(3) Non-clinical performance testing must demonstrate the device performs as intended under anticipated conditions of use, including:
(i) Mechanical testing to demonstrate the device can withstand anticipated tensile, torsional, compressive, and tip deflection forces;
(ii) Mechanical testing to evaluate the radial forces exerted by the device;
(iii) Simulated use testing to demonstrate the device can be delivered to the target location in the neurovasculature and is compatible with embolic coils;
(iv) Dimensional verification testing;
(v) Radiopacity testing; and
(vi) Performance testing to evaluate the coating integrity and particulates under simulated use conditions.
(4) Animal testing under anticipated use conditions must evaluate all adverse events, including damage to vessels or tissues.
(5) Performance data must support the sterility and pyrogenicity of the device.
(6) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the labeled shelf life.
(7) The labeling must include:
(i) Instructions for use;
(ii) A detailed summary of the device technical parameters, including compatible delivery catheter dimensions and device sizing information;
(iii) A summary of the clinical testing results, including a detailed summary of the device- and procedure-related complications and adverse events; and
(iv) A shelf life.