K Number
K132675
Date Cleared
2013-10-03

(36 days)

Product Code
Regulation Number
870.3300
Reference & Predicate Devices
Predicate For
AI/MLSaMDIVD (In Vitro Diagnostic)TherapeuticDiagnosticis PCCP AuthorizedThirdpartyExpeditedreview
Intended Use

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

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 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.

AI/ML Overview

This document is a 510(k) summary for Embozene® Microspheres, describing their intended use, device description, and a comparison to a predicate device. It does not describe a study involving an AI device or a direct performance evaluation against acceptance criteria in the context of AI/ML. Instead, it focuses on demonstrating substantial equivalence to a previously cleared device.

Therefore, many of the requested elements for an AI device study are not present in the provided text. I will answer based on the information available and indicate when information is not extractable from the provided text.


1. A table of acceptance criteria and the reported device performance

The provided text describes a submission for demonstrating substantial equivalence for an existing device, Embozene® Microspheres, with the addition of new sizes (1100 µm and 1300 µm). It does not present acceptance criteria for a "device performance" in the typical sense of accuracy, sensitivity, or specificity as might be seen for an AI/ML device.

Instead, the "performance" here relates to demonstrating that the new sizes of the Embozene® Microspheres maintain the same characteristics and safety profile as the predicate device. The implicit acceptance criteria are that the new sizes are substantially equivalent to the cleared predicate device.

Acceptance Criterion (Implicit)Reported Device Performance
Same Indications for UseUnchanged: Embolization of hypervascular tumors and arteriovenous malformations.
Same Design, Specifications, Fundamental Scientific TechnologyThe subject device and predicate have the same design, specifications, fundamental scientific technology, and packaging. The only change is the addition of 1100 µm and 1300 µm sizes.
Chemical CompositionUnchanged
Osmolarity of Transport SolutionUnchanged
pH of Transport SolutionUnchanged
Shelf LifeSame (3 years)
SterilitySame (Pyrogen-free, sterile)
PackagingSame (Syringe or vial)
Syringe Total Fill VolumeSame (7ml)
Microsphere Volume per SyringeSame (1 or 2 ml)
Catheter CompatibilityTesting conducted on the subject device and concluded to be equivalent to the predicate.
Size DistributionTesting conducted on the subject device and concluded to be equivalent to the predicate. Specific sizes and tolerances for the new sizes (1100 µm ± 75 µm and 1300 µm ± 75 µm) are provided, consistent with the predicate's sizing methodology.
Overall Safety and Effectiveness (Clinical Review)Clinical evaluation included a review of scientific literature, unpublished data, and post-market surveillance over ten years. "Concluded that the benefits of TAE with Embozene microspheres family including the additional 1100 and 1300 µm microspheres for the treatment of hypervascular tumors and arteriovenous malformations outweigh the potential risk."

2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)

This information is not applicable in the context of the provided document. The submission is for a medical device (microspheres), not an AI/ML diagnostic or prognostic tool that would typically use a test set of data. The "clinical evaluation" mentioned in Section 8 refers to a review of existing literature and post-market surveillance, not a specific prospective or retrospective study with a defined sample size for the purpose of validating an algorithm.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not applicable. The document describes a medical device, not an AI/ML algorithm that requires expert-established ground truth on a test set. The clinical evaluation process relies on existing scientific literature, a broad assessment by medical professionals, and regulatory review processes, rather than a specific number of experts labeling data for a test set.

4. Adjudication method (e.g. 2+1, 3+1, none) for the test set

This information is not applicable for the same reasons as points 2 and 3.

5. If a multi reader multi case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance

This information is not applicable. This document is a 510(k) summary for a medical device (microspheres), not an AI/ML device, and thus no MRMC study or AI assistance evaluation was conducted or reported here.

6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done

This information is not applicable. This document is a 510(k) summary for a medical device (microspheres), not an AI/ML device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc)

For the purpose of this 510(k) submission, the "ground truth" concerning the safety and effectiveness of the Embozene® Microspheres (including the new sizes) is established through:

  • Engineering and material characterization: In-vitro testing for size distribution and catheter compatibility (Section 7). This confirms the physical properties.
  • Scientific literature review: A comprehensive review of Transarterial Embolization (TAE) using various embolic agents, including the existing Embozene® Microspheres, over the last ten years (Section 8). This constitutes a form of aggregated "outcomes data" and medical consensus from the broader scientific community.
  • Unpublished data and post-market surveillance: This also contributes to the "outcomes data" and real-world evidence confirming the safety and effectiveness of the existing device family (Section 8).

There is no "ground truth" established for an AI algorithm's performance.

8. The sample size for the training set

This information is not applicable. This is not an AI/ML device.

9. How the ground truth for the training set was established

This information is not applicable. This is not an AI/ML device.

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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 CodesEmbozene® Color-AdvancedMicrospheresVolume of Color Embozene®Microspheres per SyringeVolume of ColorEmbozene Microspheresper Vial
Nominal SizeSpecifications1ml2ml1ml2ml
40 μm40 μm ±10 μm10410-S110420-S110401-V110402-V1
75 μm75 μm ±15 μm10710-S110720-S110701-V110702-V1
100 μm100 μm ±25 μm11010-S111020-S111001-V111002-V1
250 μm250 μm ± 50 μm12010-S112020-S112001-V112002-V1
400 μm400 μm ± 50 μm14010-S114020-S114001-V114002-V1
500 μm530 μm ± 50 μm15010-S115020-S115001-V115002-V1
700 μm700 μm ± 50 μm17010-S117020-S117001-V117002-V1
900 μm900 μm ± 75 μm19010-S119020-S119001-V119002-V1
1100 μm1100 μm ± 75 μm111010-S1111020-S1111001-V1111002-V1
1300 μm1300 μm ± 75 μm113010-S1113020-S1113001-V1113002-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 CodesEmbozene® OpaqueMicrospheresVolume of OpaqueEmbozene® Microspheresper SyringeVolume of OpaqueEmbozene Microspheresper Vial
Nominal SizeSpecifications1ml2ml1ml2ml
40 μm40 µm ±10 µm10410-S010420-S010401-V010402-VO
75 μm75 µm ±15 µm10710-S010720-S010701-V010702-VO
100 μm100 µm ±25 µm11010-S011020-S011001-V011002-VO
250 μm250 µm ± 50 μm12010-S012020-5012001-V012002-VO
400 μm400 μm ± 50 μm14010-S014020-5014001-V014002-V0
500 μm530 μm ± 50 μm15010-5015020-5015001-V015002-V0
700 μm700 μm ± 50 μm17010-5017020-5017001-V017002-V0
900 μm900 μm ± 75 μm19010-5019020-5019001-V019002-VO
1100 μm1100 µm ± 75 µm111010-50111020-50111001-V0111002-V0
1300 µm1300 µm ± 75 µm113010-50113020-50113001-VO113002-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 ComparisonEmbozene®SubjectEmbozene®Predicate
Chemical compositionunchangedunchanged
Osmolarity of transport solutionunchangedunchanged
pH of transport solutionunchangedunchanged
Size Range and Colors40 ± 10 µmBlack40 ± 10 µmBlack
75 ± 15 µmBurgundy75 ± 15 µmBurgundy
100 ± 25 µmOrange100 ± 25 µmOrange
250 ± 50 µmYellow250 ± 50 µmYellow
400 ± 50 µmBlue400 ± 50 µmBlue
500 ±50 µmRed500 ±50 µmRed
700 ± 50 µmGreen700 ± 50 µmGreen
900 ± 75 µmPurple900 ± 75 µmPurple
1100 ± 75 µmGray
1300 ± 75 µmPink
Color AvailabilityColor or opaqueColor or opaque
SterilityPyrogen-free, sterilePyrogen-free, sterile
PackagingSyringe or vialSyringe or vial
Syringe total fill volume7ml7ml
Microsphere volume per syringe1 or 2 ml1 or 2 ml
Shelf life3 years3 years
Indication for UseHypervascularized Tumors,Arteriovenous MalformationsHypervascularized Tumors,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.

  1. 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 (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" (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 (800) 638-2041 or (301) 796-7100 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

§ 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).