EMBOSPHERE® Microspheres are spherical microbeads for arterial embolization, made of acrylic polymer impregnated with gelatin. They are delivered with the help of a microcatheter in an amount appropriate to the area to be embolized. Six ranges of EMBOSPHERE® Microspheres are available in order to allow the physician to choose the calibration necessary for the vessel being embolized:

40-120 microns
100-300 microns
300-500 microns
500-700 microns
700-900 microns
900-1200 microns

AI/ML Overview

The provided text describes a 510(k) summary for Biosphere Medical, Inc. EMBOSPHERE® Microspheres, an artificial embolization device. The document focuses on demonstrating substantial equivalence to predicate devices rather than providing a detailed study design with acceptance criteria and device performance metrics in the typical format of a clinical trial for a standalone AI device.

Therefore, many of the requested elements for describing acceptance criteria and a study that proves the device meets them, especially those pertaining to AI/ML device evaluation (like sample size for test sets, data provenance, number of experts, adjudication methods, MRMC studies, standalone performance, and training set details), are not applicable or cannot be extracted from this document.

However, I can extract information related to the performance testing employed to demonstrate substantial equivalence for the EMBOSPHERE® Microspheres.

1. Table of Acceptance Criteria and Reported Device Performance

The document does not present specific quantitative acceptance criteria or a direct comparison of device performance against such criteria in a table format. Instead, it lists types of performance testing that support substantial equivalence. The "performance" in this context refers to the device's characteristics and its comparable behavior to predicate devices and established clinical practice, rather than specific performance metrics (e.g., accuracy, sensitivity, specificity) typically associated with AI/ML device evaluations.

Acceptance Criteria (Implied by Substantial Equivalence Claim)	Reported Device Performance (Summary)
Biocompatibility	Tested in accordance with ISO 10993.
Bench Testing (developmental)	Conducted during product development.
Ease of Injection (in-vivo)	Examined in animal testing.
Depth of Penetration (in-vivo)	Examined in animal testing.
Tissue Reaction (in-vivo)	Examined in animal testing.
Clinical Safety and Efficacy (for intended use)	Supported by European clinical experience in treating hypervascular tumors and arteriovenous malformations.
Comparative Efficacy (e.g., against predicate)	Clinical study comparing EMBOSPHERE® Microspheres to PVA for preoperative embolization of meningiomas was conducted.

2. Sample size used for the test set and the data provenance

Sample Size:
- Animal Testing: The document does not specify the sample size (number of animals) used.
- Clinical Data (European experience): The specific sample size for the European clinical data (referenced as "clinical data describing the European experience") is not provided in this summary.
- Comparative Clinical Study: The specific sample size for the "clinical study comparing EMBOSPHERE® Microspheres to PVA for preoperative embolization of meningiomas" is not provided in this summary.
Data Provenance:
- Animal Testing: Implied to be laboratory-based (likely in a controlled research setting).
- Clinical Data: "European experience." This is retrospective in the sense that it relies on past clinical use.
- Comparative Clinical Study: The citation indicates a study by Bendszus M, Klein R, Burger R, et al.: "Efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the prooperative embolization of meningiomas." This was published in AJNR in Feb 2000, suggesting a prospective clinical trial.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts

This information is not provided in the document. For device evaluations like this (medical products, not AI), the concept of "ground truth" and expert consensus as used in AI/ML performance testing is not directly applicable in the same way. Clinical outcomes and imaging results would be assessed by medical professionals, but their number and specific qualifications for establishing a "ground truth" for a test set are not detailed.

4. Adjudication method

This information is not provided and is not typically relevant for the type of device evaluation described in this 510(k) summary. Adjudication methods (like 2+1 or 3+1) are common in AI/ML studies where multiple human readers' interpretations need to be reconciled to establish a ground truth.

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

MRMC Study: No, a multi-reader multi-case (MRMC) comparative effectiveness study involving human readers with and without AI assistance was not done. This is not an AI/ML device.
The document mentions a "clinical study comparing EMBOSPHERE® Microspheres to PVA for preoperative embolization of meningiomas." This is a comparative effectiveness study between two embolization materials, not an MRMC study related to AI. Therefore, there is no effect size related to AI assistance.

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

This is not applicable as the EMBOSPHERE® Microspheres are a medical device (microspheres for embolization), not an algorithm or AI system. Their performance is inherently tied to their physical and biological interaction within the patient and their delivery by a physician.

7. The type of ground truth used

For the clinical and animal studies, the "ground truth" would implicitly be derived from:

Clinical Outcomes Data: Observed patient outcomes (e.g., successful embolization, tumor reduction, AVM occlusion, complications, tissue reaction) as assessed by clinicians and confirmed through imaging or other diagnostic methods.
Pathology: Potentially from tissue samples in animal studies to assess tissue reaction and depth of penetration.
Imaging Data: Radiographic imaging results (e.g., visualization of embolization process, extent of embolization).

8. The sample size for the training set

This is not applicable as the EMBOSPHERE® Microspheres are a physical medical device, not an AI/ML model that requires a training set. The development of the device involved bench testing and iterative design, but not "training data" in the AI sense.

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

This is not applicable for the reason stated above (not an AI/ML model requiring a training set).

Summary

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Image /page/0/Picture/1 description: The image shows a series of numbers and letters written in a stylized, calligraphic font. The characters appear to be 'K961549'. The font is bold and the characters are closely spaced, giving the impression of a continuous, flowing design. The image is in black and white, with the characters standing out against a white background.

510(k) Summary for Biosphere Medical, Inc. EMBOSPHERE® Microspheres

1. SPONSOR

Biosphere Medical, Inc. 1050 Hingham Street Rockland, MA 02370 (781) 681-7900 Telephone: (781) 681-5093 Fax:

Contact Individual: Jon McGrath

2. DEVICE NAME ·

EMBOSPHERE® Microspheres Proprietary Name: Artificial embolization device Common/Usual Name: Artificial embolization device Classification Name:

3. PREDICATE DEVICES

ITC Contour Emboli (K944354) .
ITC Radiopaque Spherical Emboli (RSE) (K871047) �
Target Therapeutics Berenstein Coil (K961923, K964112) .

DEVICE DESCRIPTION 4.

40-120 microns
100-300 microns
300-500 microns
500-700 microns
700-900 microns · 1
900-1200 microns -

Biosphere Medical, Inc.
EMBOSPHERE® Microspheres

April 24, 2000

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ಳು INTENDED USE

EMBOSPHERE® Microspheres are indicated for embolization of hypervascular tumors and arteriovenous malformations.

TECHNOLOGICAL CHARACTERISTICS AND SUBSTANTIAL EQUIVALENCE હ.

The method of application for EMBOSPHERE® Microspheres and all of the predicate devices is the same. All are intended to be delivered to selected sites through catheters with a diameter appropriate for the vascular target and the size of the emboli. Accurate placement of all of the embolization devices is assured through visualization of the embolization process using radiographic imaging. The RSE silicone elastomer microspheres and the Berenstein Coils are both radiopaque, while the PVA particles and EMBOSPHERE® Microspheres are mixed with a radiopacity agent prior to injection to permit visualization. The EMBOSPHERE® Microspheres, like the predicate devices, are available in a range of sizes to permit selection of the most appropriate size for target vessels. EMBOSPHERE Microspheres and all of the substantially equivalent embolization devices are intended for single use. The ITC RSE silicone microspheres are supplied non-sterile, while the EMBOSPHERE® Microspheres, and all of the other predicate devices, are supplied sterile.

7. PERFORMANCE TESTING

The substantial equivalence of EMBOSPHERE® Microspheres was supported by both in-vitro and in-vivo performance testing, which included the following:

biocompatibility testing conducted in accordance with ISO 10993 .
bench testing conducted during the development of the product ●
animal testing to examine ease of injection, depth of penetration, and 0 tissue reaction"
. clinical data describing the European experience with using EMBOSPHERE® Microspheres to treat a variety of hypervascular tumors and arteriovenous malformations'
the results of a clinical study comparing EMBOSPHERE® Microspheres . to PVA for preoperative embolization of meningiomas.4

Biosphere Medical, Inc. EMBOSPHERE® Microspheres

:5 :00 :00 :00 :00 :

AMERICA (1) 2017-1917 (1978) 1997-1999

April 24, 2000

1 Laurent A, Beaujeux R, Wassef M, et al.: Trisacryl gelatin microspheres for the therapeutic embolization, I: Development and in vitro evaluation. AJNR, 17:533-40, Mar 1996.

2 Derdeya CP, Graves VB, Salamat MS, et al .: Collagen-coated acrylic microspheres for embolotherapy: In vivo and in vitro characteristics. AINR, 18:647-53, Apr 1997.

3 Beaujeux R, Laurent A, Wassef M, et al.: Trisacryl gelain microspheres for therapeutic embolization, II: Preliminary clinical evaluation in tumors and arteriovenous malformations. AJNR, 17:541-48, Mar 1998

4 Bendszus M, Klein R, Burger R, et al .: Efficacy of trisacryl gelatin microspheres versus polyvinyl alcohol particles in the prooperative embolization of meningiomas. AJNR, 21(2):255-61, Feb 2000.

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Image /page/2/Picture/1 description: The image is a black and white seal for the Department of Health & Human Services - USA. The seal is circular with the text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" around the perimeter. Inside the circle is an abstract image of an eagle with three stripes above it.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

Biosphere Medical, Inc. c/o Ms. Sheila Hemeon-Hever, J.D., R.A.C. Senior Staff Consultant Medical Device Consultants, Inc. 49 Plain Street North Attleboro, Massachusetts 02760

APR 26 2000

K991549 Re: Trade Name: EMBOSPHERE® Microspheres Regulatory Class: III Product Code: HCG

Dated: January 26, 2000 Received: January 27, 2000

Dear Ms.Hemeon-Heyer:

We have reviewed your Section 510(k) notification of intent to market the device referenced above and we have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to 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). 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.

If your device is classified (see above) into either class II (Special Controls) or class III (Premarket Approval), it may be subject to such additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 895. A substantially equivalent determination assumes compliance with the current Good Manufacturing Practice requirement, as set forth in the Quality System Regulation (QS) for Medical Devices: General regulation (21 CFR Part 820) and that, through periodic (QS) inspections, the Food and Drug Administration (FDA) will verify such assumptions. Failure to comply with the GMP regulation may result in regulatory action. In addition, FDA may publish further announcements concerning your device in the Federal Register. Please note: this response to your premarket notification submission does not affect any obligation you might have under sections 531 through 542 of the Act for devices under the Electronic Product Radiation Control provisions, or other Federal laws or regulations.

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Page 2 - Ms. Sheila Hemeon-Heyer, J.D., R.A.C.

This letter will allow you to begin marketing your device as described in your 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits vour device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801 and additionally 809.10 for in vitro diagnostic devices), please contact the Office of Compliance at (301) 594-4595. Additionally, for questions on the promotion and advertising of your device, please contact the Office of Compliance at (301) 594-4639. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 807.97). Other general information on your responsibilities under the Act may be obtained from the Division of Small Manufacturers Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its internet address "http://www.fda.gov/cdrh/dsmamain.html".

Sincerely yours.

s R lehner.

Celia M. Witten, Ph.D., M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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510(k) Number (if known): K991G45

Device Name: _BioSepra EMBOSPHERE® Microspheres

Indications For Use:

EMBOSPHERE® Microspheres are indicated for embolization of hypervascular tumors and arteriovenous malformations.

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NECESSARY)

Concurrence of CDRH, Office of Device Evaluation (ODE)

Dulles R. lochner.
(Divi
Devices
K991549
510(k) Number

Prescription Use (Per 21 CFR 801.109)

Over-The-Counter Use

Regulation Number and Section

§ 882.5950 Neurovascular embolization device.

(a)
Identification. A neurovascular embolization device is an intravascular implant intended to permanently occlude blood flow to cerebral aneurysms and cerebral ateriovenous malformations. This does not include cyanoacrylates and other embolic agents, which act by polymerization or precipitation. Embolization devices used in other vascular applications are also not included in this classification, see § 870.3300.(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 § 882.1(e).