EMBOZENE COLOR-ADVANCED MICROSPHERES, EMBOZENE OPAQUE (NON-COLORED) MICROSPHERES, ONCOZENE MICROSPHERES

K141209 · Celonova Biosciences, Inc. · KRD · Aug 7, 2014 · Cardiovascular

Device Facts

• Record ID: K141209
• Device Name: EMBOZENE COLOR-ADVANCED MICROSPHERES, EMBOZENE OPAQUE (NON-COLORED) MICROSPHERES, ONCOZENE MICROSPHERES
• Applicant: Celonova Biosciences, Inc.
• Product Code: KRD · Cardiovascular
• Decision Date: Aug 7, 2014
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 870.3300
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

Embozene® Microspheres are intended for embolization of arteriovenous malformations, and hypervascular tumors, including uterine fibroids and hepatoma. ONCOZENE™ Microspheres are intended for embolization of arteriovenous malformations, and hypervascular tumors, including hepatoma.

Device Story

Embozene and ONCOZENE Microspheres are calibrated, compressible, spherical embolic agents; manufactured from sodium polymethacrylate coated with Polyzene-F. Used for mechanical occlusion of vasculature to block blood flow to target tissues like hypervascular tumors or arteriovenous malformations. Delivered via microcatheter under fluoroscopic visualization by physicians. Embozene available in opaque or color-coded sizes; ONCOZENE available in opaque only. Supplied sterile in syringes or vials. Intended to restrict blood flow to tumors, potentially benefiting patients by reducing tumor vascularity.

Clinical Evidence

No new clinical trials conducted. Evidence consists of a review of published and unpublished data on embolization using various agents over ten years, specifically regarding Embozene use for hypervascular tumors (including hepatoma) outside the U.S., and postmarket experience with the cleared device. No unique safety concerns identified for hepatoma embolization.

Technological Characteristics

Crosslinked polyacrylate hydrogel coated with Polyzene-F. Spherical form factor. Sizes range 40-1300 µm. Mechanical occlusion mechanism. Supplied sterile (SAL 10^-6). Shelf-life 3 years. No software or electronic components.

Indications for Use

Indicated for embolization of arteriovenous malformations and hypervascular tumors, including uterine fibroids (Embozene only) and hepatoma.

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/K132675/K133447)
• ONCOZENE™ Microspheres (K130307)

Submission Summary (Full Text)

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Image /page/0/Picture/1 description: The image shows the seal of the U.S. Department of Health & Human Services. The seal features an abstract design of three human profiles facing right, stacked on top of each other. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the design.

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 7, 2014

CeloNova Biosciences, Inc. Nicole Barber Manager, Regulatory Affairs 18615 Tuscany Stone. Suite 100 San Antonio, TX 78258

Re: K141209

> Trade/Device Name: Embozene Color-Advanced Microspheres; Embozene Opaque (Non-Colored) Microspheres; Oncozene Microspheres Regulation Number: 21 CFR§ 870.3300 Regulation Name: Vascular embolization device Regulatory Class: II Product Code: KRD. NAJ Dated: May 7, 2014 Received: May 9, 2014

Dear Nicole 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.

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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 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 Industry and Consumer Education at its toll-free 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" (21 CFR 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 Industry and Consumer Education at its toll-free number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely vours.

# Herbert P. Lerner -S

for Benjamin R. Fisher, Ph.D. Director Division of Reproductive, Gastro-Renal, and Urological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use Statement

510(k) Number (if known) _____________________________

| Device Name | Embozene® Microspheres |
|---------------------|------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | Embozene® Microspheres are indicated for the embolization of arteriovenous malformations and hypervascular tumors including uterine fibroids and hepatoma. |

_X____________________________________________________________________________________________________________________________________________________________________________ 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)

Herbert P. Lerner -S 2014.08.07 12:57:31 -04'00'

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Indications for Use Statement

510(k) Number (if known) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

| Device Name | ONCOZENE™ Microspheres |
|---------------------|---------------------------------------------------------------------------------------------------------------------------------------------|
| Indications for Use | ONCOZENE™ Microspheres are indicated for the<br>embolization of arteriovenous malformations and<br>hypervascular tumors including hepatoma. |

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)

# Herbert P. Lerner -S 2014.08.07 12:57:50 -04'00'

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# 510(k) Summary of Safety and Effectiveness

| Summary Date: | May 7, 2014 |
|-----------------|------------------------------------------------------------------------------------------------|
| Submitter: | CeloNova BioSciences, Inc.<br>18615 Tuscany Stone, Ste. 100<br>San Antonio<br>Texas 78258, USA |
| Contact: | Nicole C. Barber<br>Manager, Regulatory Affairs |
| | <b>1. Common name, Trade name &amp; Classification of Subject Device</b> |
| Trade Name: | Embozene® Microspheres and ONCOZENET™ Microspheres |
| Common Name(s): | Vascular Embolization device, embolization, arterial |
| Product Code: | KRD, 21 CFR 870.3300 |

Class II (special controls)

# 2. 510(k) Numbers and Product Codes of Predicate Devices

Classification:

| Trade Name: | Embozene® Microspheres |
|----------------|----------------------------|
| Manufacturer: | CeloNova BioSciences, Inc. |
| 510(k) Number: | K073417/ K132675/K133447 |
| Product Code: | KRD, NAJ, 21 CFR 870.3300 |
| | |
| Trade Name: | ONCOZENE™ Microspheres |
| Manufacturer: | CeloNova BioSciences, Inc. |
| 510(k) Number: | K130307 |
| Product Code: | KRD, 21 CFR 870.3300 |

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

The modification that is the subject of this 510(k) submission affects two legally marketed CeloNova BioSciences' medical devices; Embozene® Microspheres and ONCOZENE™ Microspheres. The modified indications for use statements for each of these medical devices are as follows:

Embozene® Microspheres are intended for embolization of arteriovenous malformations, and hypervascular tumors, including uterine fibroids and hepatoma.1

ONCOZENE™ Microspheres are intended for embolization of arteriovenous malformations, and hypervascular tumors, including hepatoma.

### 4. Device Description

Embozene® Microspheres and ONCOZENE™ Microspheres are tightly calibrated, compressible microspheres intended to occlude vasculature for the purpose of blocking blood flow to a target tissue such as a hypervascular tumor (HVT) or arteriovenous malformation (AVM). The microspheres are manufactured from sodium polymethacrylate and coated with proprietary Polyzene®F. The microspheres are compressible to enable smooth delivery through the indicated delivery catheter. Embozene® Microspheres are available opaque or color coded by size to allow easy identification of the different sizes; ONCOZENE™ Microspheres are available in opaque only.

Embozene® / ONCOZENE™ Microspheres are supplied sterile and packaged in 20ml polycycloolefin syringes with a standard 7ml fill volume across the range. Embozene® Microspheres syringes or vials are available in 1 ml or 2 ml microsphere volume; ONCOZENE™ Microspheres are available in 2 ml or 3 ml microsphere volume. Product configurations are shown in the following tables.

| Product REF Codes<br>Embozene® Color-Advanced<br>Microspheres | | Volume of Embozene®<br>Color-Advanced<br>Microspheres per Syringe | | Volume of Embozene®<br>Color-Advanced<br>Microspheres 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 |

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

¹ The indications for use statement is different for ONCOZENE™ Microspheres since the sizes available are not applicable to uterine fibroid embolization.

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| 700 um | 700 um ± 50 um | 17010-S1 | 17020-S1 | 17001-V1 | 17002-V1 |
|---------|-----------------|-----------|-----------|----------|-----------------------|
| 900 um | 900 um ± 75 um | 19010-S1 | 19020-S1 | 19001-V1 | 19002-V1 |
| 1100 um | 1100 um ± 75 um | 111010-S1 | 111020-S1 | | 111001-V1 111002-V1 |
| 1300 um | 1300 um ± 75 um | 113010-S1 | 113020-S1 | | 113001-V1 113002-V1 |

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

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

#### ONCOZENE™ Microspheres Specifications

| Product REF Codes<br>ONCOZENE™ Microspheres | | Volume of ONCOZENE™<br>Microspheres per Syringe | |
|---------------------------------------------|----------------|-------------------------------------------------|-----------|
| Nominal<br>Size | Specifications | 2 ml | 3 ml |
| 40 μm | 40 μm ± 10 μm | 10420-US1 | 10430-US1 |
| 75 μm | 75 μm ± 15 μm | 10720-US1 | 10730-US1 |
| 100 μm | 100 μm ± 25 μm | 11020-US1 | 11030-US1 |

#### 5. Similarities and Differences Compared to Predicate Devices

The Embozene® Microspheres that are the subject of this 510(k) are the same as the legally marketed Embozene® Microspheres, previously cleared by FDA, in regard to intended use and technological characteristics. The only difference between the subject of this 510(k) and our legally marketed predicate devices relates to the indications for use statement. The indications for use statement related to this 510(k) includes greater specificity than our predicates by explicitly identifying "hepatoma" as being among the tumors treated with vascular embolization devices, as established by 21 CFR § 870.3300.

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# 6. Summary of Technological Characteristics

Comparison between the Subject Devices (Embozene® and ONCOZENE™) and the Predicate Devices (Embozene® and ONCOZENE™)

| | Subject Embozene®<br>and ONCOZENETM Microspheres | Predicate Embozene®<br>and ONCOZENETM Microspheres | |
|--------------------------------------------------------|---------------------------------------------------------------------------------------------------------------------------------------------------------------------|----------------------------------------------------------------------------------------------------------------------------------------------------|------|
| Administrative Elements | | | |
| Manufacturer | CeloNova BioSciences, Inc. | CeloNova BioSciences, Inc.Same | |
| Premarket Notification | To be assigned by FDA | K073417 and<br>K132675 | |
| Classification | Class II (special controls) | Class II (special controls) | |
| Classification<br>Regulation | 21 CFR 870.3300 | 21 CFR 870.3300 | |
| Product Code | KRD - Device, Vascular,<br>For Promoting Embolization | KRD - Device, Vascular, For<br>Promoting Embolization | |
| | NAJ- Agents, Embolic, For<br>Treatment Of Uterine Fibroids<br>(Embozene only) | NAJ- Agents, Embolic, For<br>Treatment Of Uterine Fibroids<br>(Embozene only) | |
| Intended Use | | | |
| Indications for Use<br>Statement | Embozene® Microspheres are intended<br>for embolization of arteriovenous<br>malformations and hypervascular<br>tumors, including uterine fibroids and<br>hepatoma.* | Embozene® Microspheres are intended<br>for embolization of arteriovenous<br>malformations and hypervascular<br>tumors, including uterine fibroids. | |
| | ONCOZENETM Microspheres are<br>intended for embolization of<br>arteriovenous malformations and<br>hypervascular tumors including<br>hepatoma.* | ONCOZENETM Microspheres are<br>intended for embolization of<br>arteriovenous malformations and<br>hypervascular tumors. | |
| Method of Delivery | Microcatheter under<br>fluoroscopic visualization with<br>contrast | Same | |
| OTC or Rx | Rx | Same | |
| Technological Characteristics | | | |
| Mechanism of Action | Mechanical Occlusion | Same | |
| Material Class | Crosslinked polyacrylate<br>hydrogel | Same | |
| Material Design | Spherical | Same | |
| Material Composition | Crosslinked polyacrylate<br>hydrogel<br>with Polyzene-F | Same | |
| Sizes [µm] | | | Same |
| 40 ± 10 | | | |
| 75 ± 15 | | | |
| 100 ± 25 | | | |
| 250 ± 50 | | | |
| 400 ± 50 | | | |
| 530 ± 50 | | | |
| 700 ± 50 | Sizes 250 - 1300 are<br>available for<br>Embozene Only | | |
| 900 ± 75 | | | |
| 1100 ± 75 | | | |
| 1300 ± 75 | | | |
| | | | |
| Biocompatibility of<br>patient-contacting<br>materials | Yes | | Same |
| Microsphere Volume<br>[ml] | Embozene: 1 or 2<br>ONCOZENE: 2 or 3 | | Same |
| Sterility Assurance<br>Level | Supplied sterile to SAL 10-6 | | Same |
| Pyrogen-free | Yes | | Same |
| Packaging | Syringe or vial (vial for Embozene only) | | Same |
| Shelf-life | 3 years | | Same |

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## 7. Summary of Non-Clinical Performance Testing

There are no performance standards applicable to the device is subject Guidance for Industry and FDA Staff – Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices issued on December, 29 2004. Non-clinical performance testing conducted on the predicate device includes:

- Chemical analysis
- Size range
- Catheter compatibility ●
- Density ●
- . Packaging performance
- Shelf Life
- Sterility ●
- Biocompatibility ●

No new testing was conducted since the predicate device and the subject device have identical technological characteristics, manufacturing, processing, and sterilization.

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#### 8. Summary of Clinical Experience

The clinical information submitted included a review of embolization using various embolic agents to physically occlude vessels to restrict blood flow over the last ten years, published and unpublished data on the use of Embozene® for the treatment of hypervascular tumor including hepatoma (outside the United States) and postmarket experience with the cleared device.

Review of published and unpublished data regarding adverse events associated with Embozene® Microspheres and ONCOZENE™ Microspheres did not identify any unique safety concerns regarding use of Embozene® Microspheres and ONCOZENE™ Microspheres for hepatoma embolization.

#### 9. Conclusion

The Embozene® Microspheres and ONCOZENE™ Microspheres that are the subject of this 510(k) submission are substantially equivalent to the two predicate devices (Embozene® Microspheres K073417/K132675/K133447 and ONCOZENE™ Microspheres K130307) when indicated for the more general intended use of embolization of hypervascular tumors. The data on hepatoma embolization are sufficient to support the safety and effectiveness of Embozene Microspheres and ONCOZENE™ Microspheres for embolization of hepatoma.