The Gel-Bead embolization spheres (Gel-Bead) consists of biodegradable gelatin spheres pre-filled in a 20 ml syringe. The syringe contains 1 ml of spheres suspended in 5 ml of saline. Gel-Bead is offered in four size ranges: 100-300 µm, 300-500 µm, 500-700 µm and 700-1000 µm. The spheres are intended to be used with a delivery catheter with an inner diameter that is adequate for sphere delivery (not included). The finished product is sterilized by Gamma irradiation and is intended for single use only.

AI/ML Overview

The provided text describes a 510(k) submission for the Gel-Bead embolization spheres device. This is a medical device submission, and the focus of the "study" and "acceptance criteria" is on demonstrating substantial equivalence to existing predicate devices, rather than a clinical trial-style study with direct performance metrics in humans.

Here's a breakdown based on the provided document:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Biocompatibility	Meet ISO 10993-1 recommendations for cytotoxicity, sensitization, irritation/intracutaneous reactivity, acute systemic toxicity, hematology, and genotoxicity.	All listed biocompatibility tests (Cytotoxicity: L929 MEM Elution, Agar Diffusion; Sensitization: Kligman Maximization Sensitization Test (Direct); Irritation/Intracutaneous Reactivity: Intracutaneous Injection (Direct); Acute Systemic Toxicity: Acute Systemic Injection Test, Material Mediated Rabbit Pyrogen (Direct Exposure); Hematology: Hemolysis (Direct), Hemolysis (Indirect), Complement Activation (Direct); Genotoxicity: Bacterial Mutagenicity Test Ames Assay, Mouse Lymphoma Forward Mutation Assay, Rodent Bone Marrow Micronucleus Assay) were performed and their results met the specified acceptance criteria.
Device Functionality	Consistent and reliable implantation in selected target arteries; successful arterial occlusion.	GLP Animal Study: Gel-Bead spheres were consistently and reliably implanted in the selected target arteries of appropriate size and not in additional non-target tissues or regions. All instances of Gel-Bead delivery resulted in successful arterial occlusion at the time of implant, as confirmed by angiography.
Safety (Clinical Pathology)	No clinically significant abnormalities in clinical pathology blood results that negatively reflect on the device.	GLP Animal Study: There were no clinically significant abnormalities identified in the clinical pathology blood results that negatively reflected on either the test (Gel-Bead) or control (Embosphere) devices.
Safety (Systemic)	No systemic abnormalities identified in tissues distant to implantation sites.	GLP Animal Study: Examination of the tissues distant to the implantation sites did not identify any systemic abnormalities.
Clinical Efficacy	Creation of mechanical obstruction to blood flow in the target vessel, as evidenced by disruption in contrast flow rate.	GLP Animal Study: Similar well-demarcated foci of infarction, indicative of successful embolization, were observed in the target organs of both test article animals (Gel-Bead and Embosphere).
Overall Substantial Equivalence	Device design, technological characteristics, and indications for use are substantially equivalent to predicate devices, with no new safety or performance issues raised.	The verification, animal study, and biocompatibility test results met the specified acceptance criteria and did not raise new safety or performance issues. The device is considered substantially equivalent to the predicate devices based on comparisons of device functionality, technological characteristics, and indications for use.

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

Test Set (Animal Study): 12 mature miniature swine.
- 8 animals implanted with Gel-Bead.
- 4 animals implanted with a control (Embosphere Microspheres).
Data Provenance: Prospective animal study (GLP animal study), conducted with animals survived up to 12 weeks following implantation. The country of origin of the data is not specified, but it's typically conducted in a controlled lab environment.

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

The document does not explicitly state the number or qualifications of experts used to establish ground truth. However, given the nature of a GLP animal study, it would typically involve:

Veterinary Pathologists: To interpret tissue examinations and identify foci of infarction.
Veterinarians/Surgeons: For implantation procedures, clinical observation, and interpretation of clinical pathology results.
Radiologists/Interventionalists: To interpret angiographic confirmation of arterial occlusion.

The document states "similar well-demarcated foci of infarction, indicative of successful embolization, observed in the target organs of both test article animals," which implies expert pathological assessment.

4. Adjudication Method for the Test Set

The document does not describe an explicit adjudication method for the animal study (e.g., 2+1 review). The findings related to successful occlusion, infarction, and clinical pathology are presented as observed outcomes of the study. GLP studies inherently have rigorous protocols for data collection and interpretation, but specific adjudication of disagreements is not detailed.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done, and the Effect Size

No, an MRMC comparative effectiveness study was not done. This submission is for a medical device (embolization spheres), not an AI/imaging diagnostic device that would typically involve human readers interpreting cases.

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

No, a standalone (algorithm-only) performance study was not done. This device is not an algorithm; it is a physical medical device. The "study" here refers to the animal study demonstrating the physical device's function and safety.

7. The Type of Ground Truth Used

The ground truth for the animal study was established through a combination of:

Direct Observation/Angiography: Confirmation of successful arterial occlusion at the time of implant.
Pathology: Histopathological examination of target organs to observe "well-demarcated foci of infarction, indicative of successful embolization."
Clinical Pathology: Blood results to assess for systemic toxicity.
Gross Examination: Of tissues distant to implantation sites.

8. The Sample Size for the Training Set

The concept of a "training set" is not applicable here because this is a physical medical device submission, not an AI/machine learning algorithm that requires training data. The animal study described is a verification and validation study for the device's performance and safety.

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

As there is no training set in the context of this device submission, this question is not applicable.

Summary

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510(k) Summary [As required by 21 CFR 807.92] Date Prepared: April 25, 2014 510(k) Number: K133237

Submitter's Name / Contact Person

Manufacturer Vascular Solutions, Inc. 6464 Sycamore Court North Minneapolis, MN 55369 USA Establishment Registration # 2134812 Contact Person Ellie Gillespie Sr. Regulatory Product Specialist Tel: 763-656-4300 Fax: 763-656-4253

General Information

Trade Name	Gel-Bead embolization spheres
Common / Usual Name	embolization spheres
Classification Name	870.3300, KRD - Device, vascular, for promoting embolization, Class I
Predicate Device(s)	K021397 – Embosphere Microspheres (Biosphere Medical, Inc./MeritMedical Systems, Inc.)K113266 - Gel-Block Embolization Pledgets (Vascular Solutions, Inc.)

Device Description

Intended Use / Indications

Gel-Bead embolization spheres is intended for use in embolization of hypervascular tumors.

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Technological Characteristics

Gel-Bead has the same intended use as both predicate devices but Embosphere and Gel-Block are also intended for use in arteriovenous malformations and Embosphere is also intended for use in symptomatic uterine fibroids. Gel-Bead is similar in design to the predicate devices as they are gelatincontaining embolization devices delivered through a catheter with the same principle of operation (create a mechanical obstruction to blood flow in the target vessel, as evidenced by disruption in the contrast flow rate). Gel-Bead size ranges are within the range of Embosphere Microspheres (Embosphere). Gel-Bead is biodegradable like Gel-Block embolization pledgets (Gel-Block). The only technological difference between the subject device and the predicate devices is the materials of construction.

Substantial Equivalence and Summary of Studies

The subject device design was evaluated through biocompatibility and animal tests to provide evidence of safe and effective use of Gel-Bead. Gel-Bead is substantially equivalent to the specified predicate devices based on comparisons of device functionality, technological characteristics, and indications for use. The subject device design has been verified through an animal study and the following biocompatibility tests performed as recommended by ISO 10993-1:

· Cytotoxicity
- o L929 MEM Elution
- Agar Diffusion o
· Sensitization
- Kligman Maximization Sensitization Test (Direct) o
· Irritation/Intracutaneous Reactivity
- o Intracutaneous Injection (Direct)
· Acute Systemic Toxicity
- o Acute Systemic Injection Test
- 0 Material Mediated Rabbit Pyrogen (Direct Exposure)
· Hematology
- o Hemolysis (Direct)
- Hemolysis (Indirect) 0
- Complement Activation (Direct) O
· Genotoxicity
- Bacterial Mutagenicity Test Ames Assay O
- o Mouse Lymphoma Forward Mutation Assay
- Rodent Bone Marrow Micronucleus Assay O

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A GLP animal study was conducted on twelve mature miniature swine, with animals survived up to 12 weeks following implantation. Eight animals were implanted with Gel-Bead and four animals implanted with a control (Embosphere). Gel-Bead spheres were consistently and reliably implanted in the selected target arteries of appropriate size and not in additional non-target tissues or regions. All instances of Gel-Bead delivery resulted in successful arterial occlusion at the time of implant, as confirmed by angiography. There were similar well-demarcated foci of infarction, indicative of successful embolization, observed in the target organs of both test article animals. There were no clinically significant abnormalities identified in the clinical pathology blood results that negatively reflected on either the test or control devices. Examination of the tissues distant to the implantation sites did not identify any systemic abnormalities.

Verification, animal study, and biocompatibility test results met the specified acceptance criteria and did not raise new safety or performance issues. Therefore, Gel-Bead is substantially equivalent to the predicate devices.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

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

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April 25, 2014

Vascular Solutions, Inc. Ellie Gillespie Senior Regulatory Product Specialist 6464 Sycamore Court North Minneapolis, MN 55369

K133237 Re:

Trade/Device Name: Gel-Bead™ Embolization Spheres Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: Class II Product Code: KRD Dated: March 18, 2014 Received: March 20, 2014

Dear Ms. Gillespie:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave rove 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 conimered prices 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 I ou may, morely manso 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), II your device is blassified (oos aothols. 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 ulal FDA has made a determination that your istered by other Federal agencies. You must comply of of all the Act's requirements, including, but not limited to: registration and listing (21 CFR

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Page 2 - Ellie Gillespie

Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical devicerelated 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/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Kenneth J. Cavanaugh -S

for

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

Enclosure

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Indications for Use

K133237 510(k) Number (if known): _

Device Name: Gel-Bead embolization spheres

Indications for Use:

Gel-Bead embolization spheres is intended for use in embolization of hypervascular tumors.

Prescription Use _ X (Part 21 CFR 801 Subpart D)

Over-The-Counter Use AND/OR (21 CFR 801 Subpart C)

(Please DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

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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).