EmboCube Embolization Gelatin is a hydrophilic medical device which consists of pre-cut, dry cubes of resorbable gelatin sponge packaged in a syringe. The device is available in 2 cube sizes and 3 weight configurations. Once rehydrated, the deformable cubes can be injected into the target vessel with an intravascular catheter or a micro-catheter (depending on the size range) to provide a mechanical barrier to blood flow. Contrast enhancement may be used to monitor the embolization procedure using fluoroscopy. The device is intended for single use and is provided sterile.

AI/ML Overview

The provided text is a 510(k) summary for the EmboCube Embolization Gelatin and does not contain information about the acceptance criteria and study proving a device meets acceptance criteria related to AI/algorithm performance, multi-reader multi-case (MRMC) studies, or ground truth establishment for a test or training set.

The document describes a medical device, EmboCube Embolization Gelatin, and its substantial equivalence to a predicate device based on various non-AI performance tests and an animal study. Therefore, I cannot address most of the points in your request based on the provided text.

However, I can extract information related to the device itself and the general summary of testing:

Device Information:

Trade/Device Name: EmboCube Embolization Gelatin
Regulation Name: Vascular Embolization Device
Regulatory Class: Class II
Product Code: KRD
Intended Use: For use in embolization of hypervascular tumors.
Device Description: Hydrophilic medical device consisting of pre-cut, dry cubes of resorbable gelatin sponge packaged in a syringe. Available in 2 cube sizes and 3 weight configurations. Once rehydrated, deformable cubes can be injected to provide a mechanical barrier to blood flow.

Study Information (Non-AI related):

A table of acceptance criteria and the reported device performance:
The document lists the types of tests performed to demonstrate that the device meets "critical design specifications" and "clinical performance attributes," but it does not provide a table of
specific quantitative acceptance criteria (e.g., "rehydration time must be < X minutes") nor the specific reported performance values for each test. Instead, it states that these tests were "successfully completed."

Types of Performance Attributes Tested:
- Macroscopic appearance (visual inspection)
- Pepsin digestibility
- Size range
- Density
- Moisture content (H2O analysis)
- Hydration test
- Effect on pH variation
- Sterility
- Pyrogenicity (Bacterial endotoxins)
- Deliverability with the recommended catheters and radiopaque contrast agents
- Flush test
Biocompatibility Testing:
- Cytotoxicity
- Sensitization
- Irritation
- Acute Systemic Toxicity
- Material-Mediated Pyrogenicity
- Genotoxicity
- Hemolysis
- Complement Activation
- Chemical characterization and toxicological risk assessment for Subacute/Subchronic Systemic Toxicity, Chronic Systemic Toxicity, and Carcinogenicity.
Sample size used for the test set and the data provenance:
- Animal Study: "An animal study was conducted on eight test (EmboCube Embolization Gelatin) and four control (Gel-Block 10x Embolization Pledgets, K143038) adult female sheep in the renal arteries over a period of 4 weeks."
- Data Provenance: Conducted in sheep (animal study). No information on country of origin or retrospective/prospective nature. (Animal studies for device approval are typically prospective).
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):
Not applicable (N/A) as this is not an AI/algorithm study involving human expert review for ground truth. The animal study evaluated "vascular safety, local tissue effects, and in vivo degradation."
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
N/A, as this is not an AI/algorithm study that would involve expert interpretation requiring adjudication.
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:
N/A. This document describes a physical medical device, not an AI/algorithm.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
N/A. This document describes a physical medical device, not an AI/algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
For the animal study, the "ground truth" was established by the observed "vascular safety, local tissue effects, and in vivo degradation" in the sheep. These are direct biological and physiological outcomes, not expert consensus on images or pathology as typically understood in AI studies.
The sample size for the training set:
N/A. This document describes a physical medical device, not an AI/algorithm with a training set.
How the ground truth for the training set was established:
N/A. This document describes a physical medical device, not an AI/algorithm with a training set.

Summary

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Image /page/0/Picture/0 description: The image contains the logos of the Department of Health and Human Services (HHS) and the Food and Drug Administration (FDA). The HHS logo is on the left and features a stylized human figure. The FDA logo is on the right and includes the agency's acronym in a blue square, followed by the words "U.S. FOOD & DRUG ADMINISTRATION" in blue text.

September 27, 2018

Biosphere Medical, S.A. Alix Fonlladosa Regulatory Affairs Manager Parc des Nations - Paris Nord 2, 383 rue de la Belle Etoile Roissy en France, 95700 Fr

Re: K181021

Trade/Device Name: EmboCube Embolization Gelatin Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: Class II Product Code: KRD Dated: September 4, 2018 Received: September 4, 2018

Dear Alix Fonlladosa:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.htm); good manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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 comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/) and CDRH Learn (http://www.fda.gov/Training/CDRHLearn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (http://www.fda.gov/DICE) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

Misti L. Malone -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

510(k) Number (if known) K181021

Device Name EmboCube Embolization Gelatin

Indications for Use (Describe)
EmboCube Embolization Gelatin is indicated for use in embolization of hypervascular tumors.

Type of Use (Select one or both, as applicable)X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) Summary

September 27, 2018
General Provisions	Submitter Name:Address:Telephone Number:Fax Number:Contact Person:Registration Number:			Biosphere Medical, S.A.Parc des Nations - Paris Nord 2383, rue de la Belle Etoile95700 Roissy-en-France, France+33 (0)1 48 17 25 29+33 (0)1 49 38 02 68Alix Fonlladosa9615728
Subject Device	Trade Name: EmboCube Embolization GelatinCommon/Usual Name: Embolization deviceClassification Name: 21 CFR § 870.3300 Vascular Embolization Device
Predicate and ReferenceDevices	Primary Predicate Device:Trade Name: Gel-Block 10x Embolization PledgetsClassification Name: 21 CFR § 870.3300 Vascular Embolization DevicePremarket Notification: K143038Manufacturer: Vascular SolutionsReference Device:Trade Name: Embosphere MicrospheresClassification Name: 21 CFR 870.3300 - Vascular Embolization DevicePremarket Notification: K021397Manufacturer: Biosphere Medical, S.A.
Classification	Class II21 CFR § 870.3300FDA Product Code: KRDDivision of Cardiovascular Devices
Intended Use	EmboCube Embolization Gelatin is indicated for use in embolization ofhypervascular tumors.
Device Description	Reference code	Cube size (mm)	Quantity of dry cubes per syringe	EmboCube Embolization Gelatin is a hydrophilic medical device which consists of pre-cut, dry cubes of resorbable gelatin sponge packaged in a syringe. The device is available in 2 cube sizes and 3 weight configurations. Once rehydrated, the deformable cubes can be injected into the target vessel with an intravascular catheter or a micro-catheter (depending on the size range) to provide a mechanical barrier to blood flow. Contrast enhancement may be used to monitor the embolization procedure using fluoroscopy. The device is intended for single use and is provided sterile.
	EC2525	2.5x2.5x2.5	25 mg
	EC2550	2.5x2.5x2.5	50 mg
	EC25100	2.5x2.5x2.5	100 mg
	EC5025	5.0x5.0x5.0	25 mg
	EC5050	5.0x5.0x5.0	50 mg
	EC50100	5.0x5.0x5.0	100 mg
Comparison to Predicate	EmboCube Embolization Gelatin is similar in design to the Primary Predicate Device, Gel-Block 10x Embolization Pledgets (K143038) and the Reference Device, Biosphere Embosphere Microspheres (K021397), as all of them provide a mechanical barrier to blood flow in the vasculature and are delivered using catheters. The subject device is available in six sizes, as the Reference Device, Biosphere Embosphere Microspheres (K021397), while the Primary Predicate Device, Gel-Block 10x Embolization Pledgets, K143038 is available in three

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Safety & Performance Tests	sizes. The subject and predicate devices differ in shape: EmboCubeEmbolization Gelatin is a cubic embolic while the Primary Predicate Device, Gel-Block 10x Embolization Pledgets, K143038 are cylindrical and the ReferenceDevice, Biosphere Embosphere Microspheres (K021397) are spherical particles.Both the subject device and the Primary Predicate Device, Gel-10x BlockEmbolization Pledgets, K143038 are made from resorbable porcine gelatin. TheReference Device, Biosphere Embosphere Microspheres (K021397) consists ofa non-resorbable acrylic polymer impregnated with porcine gelatin.
	The technological differences between the subject and predicate deviceshave been evaluated through biocompatibility, bench and animal testing toprovide evidence of substantial equivalence of the EmboCube EmbolizationGelatin to the Primary Predicate Device, Gel-Block 10x Embolization Pledgets,K143038.
	No performance standards have been established under Section 514 of theFood, Drug and Cosmetic Act for these devices. However, vascular embolizationdevices are subject to the special controls specified in "Guidance for Industryand FDA Staff - Class II Special Controls Guidance Document: Vascular andNeurovascular Embolization Devices", issued on December 29, 2004. Inaddition, the subject device follows the FDA Draft Guidance on Medical DevicesContaining Materials Derived from Animal Sources (Except for In VitroDiagnostic Devices), issued on January 23, 2014.
	A battery of tests performed on EmboCube Embolization Gelatin were designedto demonstrate that the device meets critical design specifications as well asclinical performance attributes for its intended use. Where appropriate, the testswere based on the requirements of the following documents:• FDA Guidance Class II Special Controls Guidance Document: Vascular andNeurovascular Embolization Devices (December 29, 2004)• ASTM F2096-11, Standard Test Method for Detecting Gross Leaks in MedicalPackaging by Internal Pressurization (Bubble Test)• ASTM F1140/F1140M-13, Standard Test Methods for Internal PressurizationFailure Resistance of Unrestrained Packages for Medical Applications• ASTM F88/F88M-09, Standard Test Method for Seal Strength of FlexibleBarrier Materials• ASTM D4332-14, Standard Practice for Conditioning Containers, Packages, orPackaging Components for Testing• ASTM D4169-16, Standard Practice for Performance Testing of ShippingContainers and Systems• ASTM F1980-16, Standard Guide for Accelerated Aging of Sterile BarrierSystems for Medical Devices• ISO 11137-1:2016, Sterilization of health care products -- Radiation - Part 1:Requirements for development, validation and routine control of a sterilizationprocess for medical devices• ISO 10993-1:2009, Biological Evaluation of Medical Devices Part 1:Evaluation and Testing within a risk management process, and the FDAModified ISO 10993 Test Profile FDA Memo G95-1

	EmboCube Embolization Gelatin was evaluated for various performanceattributes to demonstrate the substantial equivalence of the device to thepredicate. The following is a list of all testing that was successfully completed:• Macroscopic appearance (visual inspection)• Pepsin digestibility• Size range• Density• Moisture content (H20 analysis)• Hydration test• Effect on pH variation• Sterility• Pyrogenicity (Bacterial endotoxins)• Deliverability with the recommended catheters and radiopaque contrast agents• Flush test
Safety & Performance Tests(Continued)	Biocompatibility testing included• Cytotoxicity• Sensitization• Irritation• Acute Systemic Toxicity• Material-Mediated Pyrogenicity• Genotoxicity• Hemolysis• Complement ActivationChemical characterization and toxicological risk assessment were used toassess Subacute/Subchronic Systemic Toxicity, Chronic Systemic Toxicity, andCarcinogenicity
	An animal study was conducted on eight test (EmboCube Embolization Gelatin)and four control (Gel-Block 10x Embolization Pledgets, K143038) adult femalesheep in the renal arteries over a period of 4 weeks. The animal study evaluatedvascular safety, local tissue effects, and in vivo degradation of the EmboCubeEmbolization Gelatin.
Summary ofSubstantialEquivalence	Based on the indications for use, design and performance testing, the subjectEmboCube Embolization Gelatin is substantially equivalent to the PrimaryPredicate Device, the currently marketed Gel-Block 10x Embolization Pledgets,manufactured by Vascular Solutions, 510(k) K143038.

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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).