QuadraSphere Microspheres are sterile, biocompatible, hydrophilic, nonresorbable, expandable, acrylic copolymer microspheres. QuadraSphere Microspheres are in vials containing 25 mg of dry microspheres. The expansion rate is dependent on ionic concentration. When in contact with blood, non-ionic contrast media, or normal saline (NaCl 0.9%), QuadraSphere Microspheres expand to approximately 4 times their dry state diameter; equal to 64x volume. They are available in a range of sizes: 30-60 um, 50-100 um, 100-150 um, and 150-200 um. QuadraSphere Microspheres have the following properties: Spherical shape with consistent cross sectional diameter after reconstitution with aqueous-based solutions such as contrast media and 0.9% saline solution for predictable flow directed level of occlusion in the vasculature. Rapidly absorb contrast media and 0.9% saline solution. Conform to vessel lumen, providing more surface contact with vessel intima. Expand up to four times the stated dry diameter when hydrated with non-ionic aqueous solutions, resulting in an increase in surface area contact for a more complete vessel occlusion. The principles of operation for the QuadraSphere Microspheres are the same as the predicate devices K052742 (50-100um, 100-150um and 150-200μm) and K113822 (30-60μm). QuadraSphere Microspheres are permanent implantable devices and are designed for controlled, targeted embolization. The device is provided dry (in a vial) and must be rehydrated before use. The microspheres are injected into the target vessel with an intravascular catheter(s) to selectively occlude blood vessels. Contrast enhancement using commercially available ionic or non-ionic contrast media allows the embolization procedure to be monitored using fluoroscopy. The embolization agents are intended for single use and are provided sterile.

AI/ML Overview

This document is a 510(k) Premarket Notification from BioSphere Medical S.A. for their QuadraSphere Microspheres. It states that the subject device is substantially equivalent to previously cleared predicate devices, K052742 and K113822, with the only change being an update to the indications for use. Therefore, the information provided focuses on the substantial equivalence of the device's technical characteristics and performance to its predicates, rather than presenting a de novo study with acceptance criteria and device performance for a new, unproven device.

Given that this is a 510(k) submission for substantial equivalence based on identical technological characteristics to the predicate devices, a traditional AI/medical device study with specified acceptance criteria and detailed performance reporting (as might be found for a novel AI algorithm) is not present in this document. The document explicitly states: "No new testing was performed since both predicate devices... and the QuadraSphere Microspheres have identical technological subject characteristics, manufacturing, processing and sterilization."

However, I can extract the information related to the device's fundamental attributes and the studies performed on the predicate devices that establish the overall safety and performance.

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

Since this is a 510(k) for substantial equivalence with identical technological characteristics, no new acceptance criteria or reported device performance are provided for the subject device. Instead, the document refers to studies performed on the predicate devices to demonstrate substantial equivalence. The "acceptance criteria" are effectively that the new device is identical to the predicates.

Attribute	Predicate Device Performance (Applicable to Subject Device)
Shelf Life	Three years (36 months)
Material	PVA Acrylic Copolymer (vinyl alcohol-sodium acrylate)
Physical Characteristics	Biocompatible, hydrophilic, non-resorbable, expandable, conformable, and swell upon exposure to aqueous solutions
Sterilization	Radiation Sterilized
Performance	Designed for controlled, targeted embolization when vessel conformity is desired
Volume of Microspheres in Vial (dry)	25 mgs per vial
Biocompatibility	In accordance with ISO 10993-1:2009 for permanent implants in contact with blood
Other Non-Clinical Tests	Chemical analysis, Size range, Catheter compatibility, Density, Packaging performance, Shelf Life, Sterility Safety

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

This document does not describe specific "test sets" for a new study, but rather relies on the equivalency to previously cleared devices. Therefore, these details are not available in this filing. The previous studies on the predicate devices would have encompassed these aspects.

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 provided in this 510(k) submission as it relies on substantial equivalence to predicate devices, not on a new, independent clinical study requiring expert ground truth establishment.

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

Not applicable, as this document does not describe a new test set or clinical study requiring adjudication.

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

Not applicable. This is a medical device (microspheres for embolization), not an AI-based diagnostic or assistive technology.

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

Not applicable. This is a medical device, not an algorithm.

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

For the predicate devices, safety and performance would have been established through a combination of:

Physical and Chemical Testing: Evaluating material composition, size, sterility, expansion characteristics.
Biocompatibility Studies: In vitro and in vivo tests based on ISO 10993-1:2009 (as mentioned).
Pre-clinical Animal Studies: To assess embolization effectiveness and safety in biological systems.
Clinical Data (if available for predicates): Though not explicitly detailed here, general clinical outcomes for embolization procedures would inform the understanding of safe and effective use.

The document implicitly uses the "ground truth" established by the prior clearance of the predicate devices, meaning their safety and effectiveness were already demonstrated.

8. The sample size for the training set

Not applicable. This document is for a physical medical device, not an AI model requiring a training set.

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

Not applicable. This document is for a physical medical device, not an AI model.

Summary

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

July 27, 2015

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

Re: K151187

Trade/Device Name: QuadraSphere Microspheres Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: II Product Code: KRD, HCG Dated: April 30, 2015 Received: May 4, 2015

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. 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

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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 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 at (301) 796-7100 or at its Internet address

http://www.fda.gov/MedicalDevices/Resourcesfor You/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 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 yours.

Benjamin R. Fisher -S

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

Enclosure

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Image /page/2/Picture/1 description: The image contains the logo for BioSphere Medical. The logo consists of a blue circle with white curved lines inside, followed by the text "BioSphere" in a bold, sans-serif font. Below "BioSphere" is the word "Medical" in a smaller, sans-serif font. A registered trademark symbol is present next to the word "BioSphere".

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: January 31, 2017 See PRA Statement below.

510(k) Number (if known)

K151187

Device Name QuadraSphere Microspheres

Indications for Use (Describe)

QuadraSphere Microspheres are indication of hypervascularized tumors including hepatoma, and peripheral arteriovenous malformations.

Type of Use (Select one or both, as applicable)

Prescription Use (Part 21 CFR 801 Subpart D)

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

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.

*DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW."

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

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Image /page/3/Picture/1 description: The image shows the logo for BioSphere Medical. The logo consists of a blue circle with white curved lines inside, followed by the words "BioSphere" in bold black letters and "Medical" in a smaller, lighter font below. A small registered trademark symbol is present next to the word "BioSphere".

Section 5

510(k) Summary

GeneralProvisions	Submitter Name:	BioSphere Medical S.A.
	Address:	383 Rue de la Belle Étoile95700 Roissy-en-France
	Telephone Number:	+33 (0)1 48 17 25 29
	Fax Number:	+33 (0)1 49 38 02 68
	Contact Person:	Alix Fonlladosa
	Registration Number:	9615728
	Correspondent Name:	BioSphere Medical S.A.
	Address:	383 Rue de la Belle Étoile95700 Roissy-en-France
	Telephone Number:	+33 (0)1 48 17 25 30
	Fax Number:	+33 (0)1 49 38 02 68
	Contact Person:	Lionel Ekedi Ngando
	Registration Number:	9615728
SubjectDevice	Trade Name:	QuadraSphere Microspheres
	Common/Usual Name:	Embolization Device
	Classification Name:	Vascular Embolization Device
PredicateDevice		Premarket Notification Predicate Device # 1:
		Trade Name: QuadraSphere Microspheres (Size:50-100μm, 100-150μm, 150-200 μm)
		Common/Usual Name: Embolization Device
		Classification Name: Vascular Embolization Device
		Manufacturer: BioSphere Medical S.A.
		Premarket Notification: K052742, cleared Nov 7, 2006
		Premarket Notification Predicate Device # 2:
		Trade Name: QuadraSphere Microspheres (Size: 30-60μm)
		Common/Usual Name: Embolization Device
		Classification Name: Neurovascular Embolization Device
		Manufacturer: BioSphere Medical S.A.
		Premarket Notification: K113822, cleared Feb 6, 2012
Classification	Class II21 CFR § 870.3300, 21 CFR § 882.5950Product code: KRD, HCGDivision of Cardiovascular Devices
Intended Use	QuadraSphere Microspheres are indicated for embolization ofhypervascularized tumors including hepatoma, and peripheral arteriovenousmalformations.

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Image /page/4/Picture/1 description: The image shows the logo for BioSphere Medical. The logo consists of a blue circle with three white curved lines inside, followed by the text "BioSphere" in a larger, bold font and "Medical" in a smaller font below it. There is a registered trademark symbol next to the word "BioSphere".

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Image /page/5/Picture/1 description: The image shows the logo for BioSphere Medical. The logo consists of a blue circle with three white curved lines inside, followed by the text "BioSphere" in a bold, sans-serif font on the top line and "Medical" in a smaller, sans-serif font on the bottom line. A registered trademark symbol is located to the right of the word "BioSphere".

They are available in a range of sizes.

Reference	Size range (um)
V225QS	30-60
V325QS	50-100
V525QS	100-150
V725QS	150-200

QuadraSphere Microspheres have the following properties:

Device Description

Spherical shape with consistent cross sectional diameter after ● reconstitution with aqueous-based solutions such as contrast media and 0.9% saline solution for predictable flow directed level of occlusion in the vasculature.
. Rapidly absorb contrast media and 0.9% saline solution.
. Conform to vessel lumen, providing more surface contact with vessel intima.
Expand up to four times the stated dry diameter when hydrated with non-ionic aqueous solutions, resulting in an increase in surface area contact for a more complete vessel occlusion.

The principles of operation for the QuadraSphere Microspheres are the same as the predicate devices K052742 (50-100um, 100-150um and 150-200μm) and K113822 (30-60μm). QuadraSphere Microspheres are permanent implantable devices and are designed for controlled, targeted embolization. The device is provided dry (in a vial) and must be rehydrated before use. The microspheres are injected into the target vessel with an intravascular catheter(s) to selectively occlude blood vessels. Contrast enhancement using commercially available ionic or non-ionic contrast media allows the embolization procedure to be monitored using fluoroscopy. The embolization agents are intended for single use and are provided sterile.

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Image /page/6/Picture/1 description: The image shows the logo for BioSphere Medical. The logo consists of a blue circular graphic on the left, followed by the text "BioSphere" in a larger, bolder font, and "Medical" in a smaller font below it. A registered trademark symbol is present next to the word "BioSphere".

The technological characteristics of the subject of this Traditional 510(k) are identical to the predicate QuadraSphere Microspheres, K052742 (50-100µm, 100-150µm and 150-200µm) cleared on November 7, 2006 and K113822 (30-60µm) cleared on February 6, 2012. Only the indications for use change between the subject device and the legally marketed QuadraSphere Microspheres, K052742 and K113822. The indications for use statement of the subject QuadraSphere Microspheres includes a specific indication by identifying "hepatoma" as being a subset of hypervascularized tumors treated with vascular embolization devices, as established by 21 CFR § 870.3300.

Technological Characteristics Comparison Table
	Attribute	PredicateDeviceQuadraSphereMicrospheres50-100μm100-150μm150-200 μm	PredicateDeviceQuadraSphereMicrospheres30-60μm	SubjectDeviceQuadraSphereMicrospheres30-60μm50-100μm100-150μm150-200 μm	Comment
Comparisonto Predicate	Shelf Life(single use)	Three years(36 months)	Three years(36 months)	Three years(36 months)	Same
	Material	PVA AcrylicCopolymer(vinyl alcohol-sodiumacrylate)	PVA AcrylicCopolymer(vinyl alcohol-sodiumacrylate)	PVA AcrylicCopolymer(vinyl alcohol-sodiumacrylate)	Same
	PhysicalCharacteristics	Biocompatible,hydrophilic,non-resorbable,expandable,conformableand swell uponexposure toaqueoussolutions	Biocompatible,hydrophilic,non-resorbable,expandable,conformableand swell uponexposure toaqueoussolutions	Biocompatible,hydrophilic,non-resorbable,expandable,conformableand swell uponexposure toaqueoussolutions	Same
	Sterilization	RadiationSterilized	RadiationSterilized	RadiationSterilized	Same
	Performance	Designed forcontrolled,targetedembolizationwhen vesselconformity isdesired	Designed forcontrolled,targetedembolizationwhen vesselconformity isdesired	Designed forcontrolled,targetedembolizationwhen vesselconformity isdesired	Same
	Volume ofMicrospheresin Vial (dry)	25 mgs per vial	25 mgs per vial	25 mgs per vial	Same

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Image /page/7/Picture/1 description: The image shows the logo for BioSphere Medical. The logo consists of a blue circle with white curved lines inside, followed by the text "BioSphere" in a bold, sans-serif font. Below "BioSphere" is the word "Medical" in a smaller, sans-serif font.

No performance standards applicable to this device have been adopted under Section 514 of the Act. However, vascular embolization devices are subject to the special controls specified in "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 Safety · Biocompatibility Performance Tests Biocompatibility evaluation was performed in accordance with ISO 10993-1:2009 for permanent implants in contact with blood for the predicate devices K052742 (50-100μm, 100-150μm and150-200μm) and K113822 (30-60um), and is being adopted for this subject device based upon the fact that all devices are made from the same materials using the same manufacturing and sterilization processes. No new testing was performed since both predicate devices, K052742 (50-100μm, 100-150μm and150-200μm) and K113822 (30-60μm), and the QuadraSphere Microspheres have identical technological subject characteristics, manufacturing, processing and sterilization. Based on the same intended use (other than the requested change that is the objective of this submission), design, fundamental scientific technological characteristics, fundamental operational characteristics and safety and Summary of performance testing, the BioSphere Medical subject QuadraSphere Substantial Microspheres device meets the requirements that are considered essential Equivalence for its intended use and is substantially equivalent to the predicate devices, QuadraSphere Microspheres K052742 (50-100µm, 100-150µm and 150-200um) and K113822 (30-60µm).

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).