Embozene® Microspheres are indicated for the embolization of arteriovenous malformations and hypervascular tumors including uterine fibroids and hepatoma.

ONCOZENE™ Microspheres are indicated for the embolization of arteriovenous malformations and hypervascular tumors including hepatoma.

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.

AI/ML Overview

The provided document is a 510(k) Summary of Safety and Effectiveness for CeloNova BioSciences' Embozene® Microspheres and ONCOZENE™ Microspheres. This document focuses on demonstrating substantial equivalence to existing predicate devices, rather than establishing acceptance criteria and proving new device performance against those criteria as would be typical for a novel device.

The core of this submission is an expanded indication for use to explicitly include "hepatoma" among the hypervascular tumors treated with these embolization devices. Therefore, the "acceptance criteria" here are implicitly related to the safety and effectiveness for this expanded indication, demonstrated by comparison to predicate devices and existing clinical data.

Here's an analysis based on your requested information:

1. Table of Acceptance Criteria and Reported Device Performance

Since this is a 510(k) for an expanded indication and not a de novo submission, there are no explicit, quantifiable "acceptance criteria" presented in the document in the format of a novel device performance study. Instead, the "acceptance criteria" are implied to be demonstration of substantial equivalence to legally marketed predicate devices, particularly regarding the safety and effectiveness for the embolization of hypervascular tumors, specifically hepatoma.

The "device performance" is primarily the finding that the subject devices are substantially equivalent to the predicate devices and that existing clinical data supports their safety and effectiveness for the expanded indication.

Acceptance Criteria (Implied for Substantial Equivalence)	Reported Device Performance
Maintain identical technological characteristics to predicate devices.	The subject devices (Embozene® and ONCOZENE™ Microspheres) have identical technological characteristics, manufacturing, processing, and sterilization as their predicate counterparts (K073417/K132675/K133447 and K130307).
Existing clinical data demonstrates safety and effectiveness for embolization of hypervascular tumors, including hepatoma.	A review of published and unpublished data on the use of Embozene® for hypervascular tumors (including hepatoma outside the US) and postmarket experience with cleared devices did not identify any unique safety concerns regarding hepatoma embolization. The data were deemed "sufficient to support the safety and effectiveness" for this indication.
No new performance standards applicable.	There are no new performance standards applicable to the device beyond existing guidance.

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

Test Set Sample Size: Not explicitly stated as a defined "test set" with a specific sample size. The clinical information reviewed included "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." The exact number of patients or cases in this cumulative "test set" is not provided.
Data Provenance: The data provenance mentioned is "outside the United States" for the use of Embozene® for hepatoma, and general "postmarket experience" with the cleared devices. This suggests a mix of retrospective (published studies, postmarket reports) and potentially some prospective data if "unpublished data" includes ongoing registries or smaller studies.

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

The document does not specify the number or qualifications of experts used to establish a "ground truth" for a specific test set. The clinical information reviewed was "published and unpublished data" and "postmarket experience," implying that the assessment of safety and effectiveness relied on existing medical literature and real-world usage data, which inherently includes diagnoses and outcomes established by medical professionals in various clinical settings.

4. Adjudication Method for the Test Set

No explicit adjudication method is mentioned. The review seems to be a synthesis of existing literature and postmarket surveillance rather than a specific study with a defined adjudication process.

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

No, an MRMC comparative effectiveness study was not done. This submission is for an expanded indication based on substantial equivalence and a review of existing data, not for a comparative effectiveness study of human readers with or without AI assistance.

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

This question is not applicable. The device is a medical product (microspheres for embolization), not an algorithm or AI.

7. The Type of Ground Truth Used

The "ground truth" for demonstrating safety and effectiveness for hepatoma embolization was based on the outcomes data and findings reported in published and unpublished clinical studies, as well as postmarket surveillance data. This includes diagnoses by clinicians, treatment effectiveness, and adverse events.

8. The Sample Size for the Training Set

This question is not applicable. The device is a medical product, not an AI or algorithm that requires a "training set." The submission relies on existing clinical evidence, not a machine learning model.

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

This question is not applicable for the reasons mentioned above.

Summary

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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 (800) 638-2041 or (301) 796-7100 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 (800) 638-2041 or (301) 796-7100 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 theembolization of arteriovenous malformations andhypervascular 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.18615 Tuscany Stone, Ste. 100San AntonioTexas 78258, USA
Contact:	Nicole C. BarberManager, Regulatory Affairs
	1. Common name, Trade name & Classification of Subject Device
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

Product REF CodesEmbozene® Color-AdvancedMicrospheres		Volume of Embozene®Color-AdvancedMicrospheres per Syringe		Volume of Embozene®Color-AdvancedMicrospheres 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 CodesEmbozene® OpaqueMicrospheres		Volume of Embozene®Opaque Microspheres perSyringe		Volume of Embozene®Opaque Microspheres perVial
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 CodesONCOZENE™ Microspheres		Volume of ONCOZENE™Microspheres per Syringe
NominalSize	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®and ONCOZENETM Microspheres	Predicate Embozene®and ONCOZENETM Microspheres
Administrative Elements
Manufacturer	CeloNova BioSciences, Inc.	CeloNova BioSciences, Inc.Same
Premarket Notification	To be assigned by FDA	K073417 andK132675
Classification	Class II (special controls)	Class II (special controls)
ClassificationRegulation	21 CFR 870.3300	21 CFR 870.3300
Product Code	KRD - Device, Vascular,For Promoting Embolization	KRD - Device, Vascular, ForPromoting Embolization
	NAJ- Agents, Embolic, ForTreatment Of Uterine Fibroids(Embozene only)	NAJ- Agents, Embolic, ForTreatment Of Uterine Fibroids(Embozene only)
Intended Use
Indications for UseStatement	Embozene® Microspheres are intendedfor embolization of arteriovenousmalformations and hypervasculartumors, including uterine fibroids andhepatoma.*	Embozene® Microspheres are intendedfor embolization of arteriovenousmalformations and hypervasculartumors, including uterine fibroids.
	ONCOZENETM Microspheres areintended for embolization ofarteriovenous malformations andhypervascular tumors includinghepatoma.*	ONCOZENETM Microspheres areintended for embolization ofarteriovenous malformations andhypervascular tumors.
Method of Delivery	Microcatheter underfluoroscopic visualization withcontrast	Same
OTC or Rx	Rx	Same
Technological Characteristics
Mechanism of Action	Mechanical Occlusion	Same
Material Class	Crosslinked polyacrylatehydrogel	Same
Material Design	Spherical	Same
Material Composition	Crosslinked polyacrylatehydrogelwith Polyzene-F	Same
Sizes [µm]			Same
40 ± 10
75 ± 15
100 ± 25
250 ± 50
400 ± 50
530 ± 50
700 ± 50	Sizes 250 - 1300 areavailable forEmbozene Only
900 ± 75
1100 ± 75
1300 ± 75

Biocompatibility ofpatient-contactingmaterials	Yes		Same
Microsphere Volume[ml]	Embozene: 1 or 2ONCOZENE: 2 or 3		Same
Sterility AssuranceLevel	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.

Regulation Number and Section

§ 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).