EMBOZENE MICROSPHERES

K132675 · Celonova Biosciences, Inc. · KRD · Oct 3, 2013 · Cardiovascular

Device Facts

• Record ID: K132675
• Device Name: EMBOZENE MICROSPHERES
• Applicant: Celonova Biosciences, Inc.
• Product Code: KRD · Cardiovascular
• Decision Date: Oct 3, 2013
• Decision: SESE
• Submission Type: Special
• Regulation: 21 CFR 870.3300
• Device Class: Class 2
• Attributes: Therapeutic, Real-World Evidence

Real-World Evidence

Submission	Device	Sponsor	RWD Sources	RWE Use Summary	Key Tags
K132675 · Oct 3, 2013	EMBOZENE MICROSPHERES	Celonova Biosciences, Inc.	Scientific literature; Unpublished clinical data; Post-market surveillance	The sponsor conducted a review of clinical experience, including literature and post-market surveillance of Transarterial Embolization (TAE) procedures, to support the safety and effectiveness of the expanded size range of the Embozene® Microspheres.	Transarterial Embolization; Post-market surveillance; Literature review

Clinical Evidence

Study Design	Population	Comparator	Key Endpoints
Review of Transarterial Embolization (TAE) clinical experience; Retrospective review of scientific literature, unpublished data, and post-market surveillance; Follow-up/Duration: Last ten years; Study Period: Last ten years	Patients treated with embolic agents for hypervascular tumors and arteriovenous malformations	Not applicable for this study	Safety and effectiveness of Embozene® Microspheres

Indications for Use

Embozene® Microspheres are indicated for the embolization of hypervascular tumors and arteriovenous malformations.

Device Story

Embozene® Microspheres are calibrated, compressible, spherical embolic agents; manufactured from sodium polymethacrylate coated with Polyzene®-F. Used to occlude vasculature; block blood flow to target tissues like hypervascular tumors (HVT) or arteriovenous malformations (AVM). Supplied sterile in polycycloolefin syringes or vials; color-coded by size (40 μm to 1300 μm) for identification. Delivered via catheter by physicians in clinical settings. Compression allows smooth delivery through catheters. Occlusion of target vessels reduces blood flow to lesions, providing therapeutic benefit for hypervascularized conditions.

Clinical Evidence

No new clinical trials conducted. Evidence based on literature review of Transarterial Embolization (TAE) using various embolic agents over ten years, unpublished data, and post-market surveillance. Concluded that Embozene® Microspheres, including the new 1100 μm and 1300 μm sizes, are safe and effective for the indicated use.

Technological Characteristics

Materials: Sodium polymethacrylate core, Polyzene®-F coating. Form factor: Compressible microspheres, 40-1300 μm diameter. Delivery: Syringe or vial, sterile, pyrogen-free. Connectivity: None. Energy source: None (mechanical).

Indications for Use

Indicated for embolization of hypervascular tumors and arteriovenous malformations in patients requiring vascular occlusion.

Regulatory Classification

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.

Special Controls

*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).

Predicate Devices

• Embozene® Microspheres (K073417)

Submission Summary (Full Text)

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### 510(k) Summary of Safety and Effectiveness

| Summary Date: | August 23, 2013 |
|------------------|---------------------------------------------------------------|
| Submitter: | CeloNova BioSciences, Inc. |
| | 18615 Tuscany Stone, Ste. 100 |
| | San Antonio |
| | Texas 78258, USA |
| | ОСТ 0 3 2013 |
| Contact : | Nicole C. Barber |
| | Manager, Regulatory Affairs |
| | 1. Common name, Trade name & Classification of Subject Device |
| Trade Name : | Embozene® Microspheres |
| Common Name(s) : | Vascular Embolization device, embolization, arterial |
| Product Code: | KRD, 21 CFR 870.3300 |
| Classification: | Class II |
| | 2. 510(k) Number and Product Code of Predicate Device |
| Trade Name: | Embozene® Microspheres |
| Manufacturer: | CeloNova BioSciences, Inc. |
| 510(k) Number: | K073417 |
| Product Code: | KRD, 21 CFR 870.3300 |
| | 3. Indications for Use and Intended Purpose |

#### 3. Indications for Use and Intended Purpose

Embozene® Microspheres are intended for embolization of hypervascular tumors and arteriovenous malformations.

#### 4. Device Description

Embozene® Microspheres are tightly calibrated, compressible microspheres intended to occlude vasculature for the purpose of blocking blood flow to a target tissue such as hypervascular tumor (HVT) or arteriovenous malformation (AVM). Embozene® Microspheres are manufactured from sodium polymethacrylate and coated with proprietary Polyzene®-F. The

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microspheres are compressible to enable smooth delivery through the indicated delivery catheter. Embozene® Microspheres are color coded by size to allow easy identification of different sizes.

Embozene® Microspheres are supplied sterile and packaged in 20ml polycycloolefin syringes with a standard 7ml fill volume across the range. Embozene® Microspheres syringes and vials are available with 1 ml or 2 ml microsphere volume per syringe or vial. Product configurations are shown in the Tables below.

| Product REF Codes<br>Embozene® Color-Advanced<br>Microspheres | | Volume of Color Embozene®<br>Microspheres per Syringe | | Volume of Color<br>Embozene Microspheres<br>per Vial | |
|---------------------------------------------------------------|-----------------|-------------------------------------------------------|-----------|------------------------------------------------------|-----------|
| Nominal Size | Specifications | 1ml | 2ml | 1ml | 2ml |
| 40 μm | 40 μm ±10 μm | 10410-S1 | 10420-S1 | 10401-V1 | 10402-V1 |
| 75 μm | 75 μm ±15 μm | 10710-S1 | 10720-S1 | 10701-V1 | 10702-V1 |
| 100 μm | 100 μm ±25 μm | 11010-S1 | 11020-S1 | 11001-V1 | 11002-V1 |
| 250 μm | 250 μm ± 50 μm | 12010-S1 | 12020-S1 | 12001-V1 | 12002-V1 |
| 400 μm | 400 μm ± 50 μm | 14010-S1 | 14020-S1 | 14001-V1 | 14002-V1 |
| 500 μm | 530 μm ± 50 μm | 15010-S1 | 15020-S1 | 15001-V1 | 15002-V1 |
| 700 μm | 700 μm ± 50 μm | 17010-S1 | 17020-S1 | 17001-V1 | 17002-V1 |
| 900 μm | 900 μm ± 75 μm | 19010-S1 | 19020-S1 | 19001-V1 | 19002-V1 |
| 1100 μm | 1100 μm ± 75 μm | 111010-S1 | 111020-S1 | 111001-V1 | 111002-V1 |
| 1300 μm | 1300 μm ± 75 μm | 113010-S1 | 113020-S1 | 113001-V1 | 113002-V1 |

Product REF Codes for Embozene Color-Advanced Microspheres in Syringe and Vial

#### Product REF Codes for Embozene Opaque (Non-Colored) Microspheres in Syringe and Vial

| Product REF Codes<br>Embozene® Opaque<br>Microspheres | | Volume of Opaque<br>Embozene® Microspheres<br>per Syringe | | Volume of Opaque<br>Embozene Microspheres<br>per Vial | |
|-------------------------------------------------------|-----------------|-----------------------------------------------------------|-----------|-------------------------------------------------------|-----------|
| Nominal Size | Specifications | 1ml | 2ml | 1ml | 2ml |
| 40 μm | 40 µm ±10 µm | 10410-S0 | 10420-S0 | 10401-V0 | 10402-VO |
| 75 μm | 75 µm ±15 µm | 10710-S0 | 10720-S0 | 10701-V0 | 10702-VO |
| 100 μm | 100 µm ±25 µm | 11010-S0 | 11020-S0 | 11001-V0 | 11002-VO |
| 250 μm | 250 µm ± 50 μm | 12010-S0 | 12020-50 | 12001-V0 | 12002-VO |
| 400 μm | 400 μm ± 50 μm | 14010-S0 | 14020-50 | 14001-V0 | 14002-V0 |
| 500 μm | 530 μm ± 50 μm | 15010-50 | 15020-50 | 15001-V0 | 15002-V0 |
| 700 μm | 700 μm ± 50 μm | 17010-50 | 17020-50 | 17001-V0 | 17002-V0 |
| 900 μm | 900 μm ± 75 μm | 19010-50 | 19020-50 | 19001-V0 | 19002-VO |
| 1100 μm | 1100 µm ± 75 µm | 111010-50 | 111020-50 | 111001-V0 | 111002-V0 |
| 1300 µm | 1300 µm ± 75 µm | 113010-50 | 113020-50 | 113001-VO | 113002-V0 |

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#### 5. Similarities and Differences to Predicate device

The intended use of the subject device remains unchanged as compared to the predicate. The subject device and the predicate have the same design, specifications, fundamental scientific technology, and packaging. The only change is the addition of 1100 um and 1300 µm sizes of Embozene® Microspheres. The additional sizes are available in gray and pink colors, respectively. The colorants used to create those colors are the same as those used in the predicate.

#### 6. Summary of Technological Characteristics

| Point of Comparison | Embozene®<br>Subject | Embozene®<br>Predicate |
|----------------------------------|----------------------------------------------------------|----------------------------------------------------------|
| Chemical composition | unchanged | unchanged |
| Osmolarity of transport solution | unchanged | unchanged |
| pH of transport solution | unchanged | unchanged |
| Size Range and Colors | 40 ± 10 µm<br>Black | 40 ± 10 µm<br>Black |
| | 75 ± 15 µm<br>Burgundy | 75 ± 15 µm<br>Burgundy |
| | 100 ± 25 µm<br>Orange | 100 ± 25 µm<br>Orange |
| | 250 ± 50 µm<br>Yellow | 250 ± 50 µm<br>Yellow |
| | 400 ± 50 µm<br>Blue | 400 ± 50 µm<br>Blue |
| | 500 ±50 µm<br>Red | 500 ±50 µm<br>Red |
| | 700 ± 50 µm<br>Green | 700 ± 50 µm<br>Green |
| | 900 ± 75 µm<br>Purple | 900 ± 75 µm<br>Purple |
| | 1100 ± 75 µm<br>Gray | |
| | 1300 ± 75 µm<br>Pink | |
| Color Availability | Color or opaque | Color or opaque |
| Sterility | Pyrogen-free, sterile | Pyrogen-free, sterile |
| Packaging | Syringe or vial | Syringe or vial |
| Syringe total fill volume | 7ml | 7ml |
| Microsphere volume per syringe | 1 or 2 ml | 1 or 2 ml |
| Shelf life | 3 years | 3 years |
| Indication for Use | Hypervascularized Tumors,<br>Arteriovenous Malformations | Hypervascularized Tumors,<br>Arteriovenous Malformations |

Comparison between the Subject Device (Embozene®) and the Predicate Device (Embozene®)

#### 7. Summary of In-Vitro Testing

Size distribution and catheter compatibility testing were conducted on the subject device and concluded to be equivalent to the predicate.

8. Summary of Clinical Experience

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The clinical evaluation included in the 510(k) reviews Transarterial Embolization (TAE) using various embolic agents to physically occlude vessels to restrict blood flow over the last ten years. The overall review of the scientific literature, unpublished data and post market surveillance, indicate that Embozene® Microspheres including 1100 um are reasonably safe and effective for the treatment of hypervascular tumors and arteriovenous malformations. Therefore, it could be concluded that the benefits of TAE with Embozene microspheres family including the additional 1100 and 1300 um microspheres for the treatment of hypervascular tumors and arteriovenous malformations outweigh the potential risk when used within their labeled application.

#### 9. Summary

The subject device and the predicate have the same indications for use, design, and fundamental scientific technology. The subject device Embozene® Microspheres with the addition of 1100 um and 1300 um sizes are substantially equivalent to the cleared Embozene® Microspheres (K073417).

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DEPARTMENT OF HEALTH & HUMAN SERVICES

October 3, 2013

CeloNova BioSciences, Inc. C/O Nicole C. Barber, RAC Manager, Regulatory Affairs 18615 Tuscany Stone Suite 100 San Antonio, TX 78258

Re: K132675

Trade/Device Name: Embozene® Microspheres Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: Class II Product Code: KRD Dated: September 2, 2013 Received: September 4, 2013

Dear Ms. Barber:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G605 Silver Spring MD 20993-0002

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Page 2 - Nicole C. Barber]

forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

## Bram D. Zury Berman -S

Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health

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K132675

Indications for Use Statement

| 510(k) Number (if known) | |
|--------------------------|--|
|--------------------------|--|

Device Name Vascular Embolization Device

Indications for Use Embozene® Microspheres are indicated for the embolization of hypervascular tumors and arteriovenous malformations.

Prescription Use × (Per 21 CFR 801. 109) AND/ OR

Over-The-Counter Use_

PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED

Concurrence of CDRH, Office of Device Evaluation (ODE)

# Bram 2013.1