Bead Block™ microspheres are intended to be used for the embolization of hypervascular tumors, including uterine fibroids and arteriovenous malformations (AVMs).

Device Description

Bead Block™ is made up of preformed soft, deformable microspheres that occlude arteries for the purpose of blocking the blood flow to a target tissue, such as a fibroid or a cancerous tumor. Bead Block™ compressible microspheres consist of a macromer derived from polyvinyl alcohol (PVA). The fully polymerized microsphere is approximately 90-95% water and is compressible to approximately 30% by diameter. Bead Block™ microspheres are dyed blue to aid in the visualization of the microspheres in the delivery syringe. The microspheres can be delivered through typical microcatheters in the 1.5-5Fr range.

AI/ML Overview

The provided document is a 510(k) summary for the Bead Block™ device, which is a vascular embolization device. The information requested pertains to the acceptance criteria and the study that proves the device meets the acceptance criteria. The document largely focuses on demonstrating substantial equivalence to a predicate device rather than performance against specific numeric acceptance criteria for the new device.

Here's an analysis based on the available information:

1. Table of acceptance criteria and the reported device performance

The document does not present a table of explicit numeric acceptance criteria. Instead, it relies on demonstrating that Bead Block™ is "as safe and effective as the predicate device" and that its performance is "similar to the predicate device". The "performance" is described qualitatively through the results of non-clinical and animal testing.

Acceptance Criteria Category	Reported Device Performance
Material Properties:
Residual starting material	Specifications met (details not provided)
Residual solvent material	Specifications met (details not provided)
Physical Appearance:
Visual inspection	Visual defects, color, solution clarity evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Delivery & Functionality:
Catheter delivery	Evaluated for catheter clogging, aggregation, ease of injection, and particle shape after injection (results not explicitly stated, but implied to be acceptable for substantial equivalence, and "similar to the predicate device")
Particle size range	Confirmation performed (results not explicitly stated, but implied to be within specified range as per product configurations table, e.g., 100-300μm, 300-500μm, etc.)
Particle fiber shedding	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Biocompatibility:
pH	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Endotoxin	<0.06 EU/ml
Biocompatibility	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence and "minimal tissue necrosis and a common foreign body reaction; however, the intensity of inflammatory reaction is moderate, without humoral response or cytotoxicity" in animal studies)
Sterility & Packaging:
Packaging integrity	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Shelf life	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Sterilization validation	Performed (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Animal Study - UAE:
Short term performance	"similar to the predicate device, with both showing normal, thrombosis and some rupture of the internal elastic lamina"
Side effects	"minimal tissue necrosis and a common foreign body reaction; however, the intensity of inflammatory reaction is moderate, without humoral response or cytotoxicity"
Distribution	Evaluated (results not explicitly stated, but implied to be acceptable for substantial equivalence)
Clinical - Adverse Events:	"Review of the published and unpublished data regarding adverse events associated with Bead Block™ has not identified any unique safety concerns." (This implies a qualitative comparison to expected adverse events for similar devices).

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

Non-clinical testing: No specific sample sizes are mentioned for the non-clinical tests (e.g., material specifications, visual inspection, catheter delivery). These typically involve lab-based testing.
Animal studies:
- Study 1 (sheep penetration model): The sample size is not explicitly stated. The provenance is likely a research lab setting.
- Study 2 (side effects in sheep uteri): The sample size is not explicitly stated. The provenance is likely a research lab setting.
Clinical information: This involved a "review of Bead Block™ published and unpublished data on the use of Bead Block™ for the treatment of leiomyoma uteri (uterine fibroids) [outside the United States] over the last ten years."
- The exact sample size (number of patients/cases) is not provided.
- Provenance: This data is retrospective, collected over "the last ten years," and originated from "outside the United States."

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

The document does not detail the use of "experts" to establish a ground truth in the typical sense of a diagnostic device. The evaluation of non-clinical tests would be performed by qualified lab personnel. For animal studies, the assessment of tissue necrosis, inflammation, and vascular effects would be done by veterinary pathologists or other trained researchers, but no specific number or qualifications are given. For the clinical data review, it's not described as an adjudication process by experts to establish ground truth for a test set, but rather a review of existing clinical outcomes/adverse events.

4. Adjudication method for the test set

There is no mention of an adjudication method (like 2+1 or 3+1) for establishing ground truth from multiple readers/experts. This type of adjudication is typically relevant for diagnostic imaging studies where agreement on subtle findings is crucial. The studies described are primarily performance and safety assessments of an embolic device.

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

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not reported. The device (Bead Block™) is an embolic agent, not an AI-powered diagnostic or assistive tool for human readers. Therefore, the question of human reader improvement with or without AI assistance is not applicable to this device submission.

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

This question is not applicable. Bead Block™ is a physical medical device (microspheres for embolization), not an algorithm or AI system. Its performance is inherent to its physical properties and interaction with biological systems when used by a clinician, not a standalone software performance metric.

7. The type of ground truth used

Non-clinical testing: Ground truth is established by standard laboratory test methods, specifications, and physical measurements (e.g., chemical analysis for residual materials, microscopy for particle size, functional testing for catheter delivery).
Animal studies: Ground truth is established by histological examination and pathological assessment of tissue samples from the embolized animals, comparing observed effects to normal physiology and effects seen with the predicate device.
Clinical data review: Ground truth is the documented adverse events and clinical outcomes collected in real-world use outside the US, reviewed descriptively (not as a systematically adjudicated "ground truth" for a specific test set, but rather a summary of real-world safety data).

8. The sample size for the training set

The concept of a "training set" is not applicable here. This is a medical device submission based on non-clinical, animal, and existing clinical data, not a machine learning model developed with training data.

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

Not applicable, as there is no training set for an algorithm/AI in this submission.

Summary

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

March 7, 2016

Biocompatibles UK Ltd % Simon Leppard Director of Regulatory Affairs BTG International, Inc. Lakeview, Riverside Way, Watchmoor Park Camberley, Surrey, GU15 3YL, GB

Re: K150876

Trade/Device Name: Bead Block™ Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: Class II Product Code: NAJ Dated: February 2, 2016 Received: February 4, 2016

Dear Simon Leppard,

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

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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 (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/ResourcesforYou/Industry/default.htm.

Sincerely yours,

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

Enclosure

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Indications for Use

510(k) Number (if known) K150876

Device Name Bead Block™

Indications for Use (Describe)

Bead Block™ microspheres are intended to be used for the embolization of hypervascular tumors, including uterine fibroids and arteriovenous malformations (AVMs).

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 for the Biocompatibles UK Ltd. Bead Block™ (per 21CFR 807.92)

1. SUBMITTER/510(K) HOLDER

Biocompatibles UK Ltd. Weydon Lane Chapman House Weydon Lane, Farnham, Surrey, GU9 8QL, UK

Contact Person: Simon Leppard Telephone: +44 (0) 1276 902 020 Fax: +44 (0) 1276 537 162 Email: simon.leppard@btgplc.com

March 4, 2016 Date Prepared:

2. DEVICE NAME

Proprietary Name: Bead Block™ Common/Usual Name: Embolic Agents Regulation: 870.3300, vascular embolization device Regulatory Class: II Product Code: NAJ, uterine artery embolization

3. PREDICATE DEVICES

The primary predicate device has been identified as listed below:

. Predicate Device: Embosphere Microspheres, Biosphere Medical, Inc. (K021397)

4. DEVICE DESCRIPTION

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Bead Block™ Product Configurations
Product Code	Size Range	QuantityBead Block	QuantitySaline	Intended for*UFE
EB1S103	100-300μm	1 ml	6 ml	No
EB1S305	300-500μm	1 ml	6 ml	No
EB1S507	500-700μm	1 ml	6 ml	No
EB1S709	700-900μm	1 ml	6 ml	Yes
EB1S912	900-1200μm	1 ml	6 ml	Yes
EB2S103	100-300μm	2 ml	5 ml	No
EB2S305	300-500μm	2 ml	5 ml	No
EB2S507	500-700μm	2 ml	5 ml	No
EB2S709	700-900μm	2 ml	5 ml	Yes
EB2S912	900-1200μm	2 ml	5 ml	Yes

Bead Block™ is available in the configurations shown in the table below.

*Uterine Fibroid Embolization

5. INDICATION FOR USE/INTENDED USE

Bead BlockTM microspheres are intended to be used for the embolization of hypervascular tumors, including uterine fibroids and arteriovenous malformations (AVMs).

6. SUMMARY OF TECHNOLOGICAL CHARACTERISTICS COMPARED TO THE PREDICATE DEVICE/S

Bead BlockTM and the proposed predicate device are size calibrated spherical particles delivered by microcatheters to occlude a target blood vessel. Bead Block™ and the predicate device (K021397) have the same intended use and similar technological characteristics including the following:

Intended for the embolization of hypervascular tumors and arteriovenous ● malformations
Size calibrated microspheres for embolization
Delivery via microcatheter to the site of desired embolization ●
Visualization of the embolization process using radiographic imaging ●
A range of sizes permits selection of the most appropriate size for target vessels ●

The indications for use of Bead Block™ are comparable to the predicate device. However, Bead Block™ and the predicate device have different technological characteristics, as the subject device is made of polyvinyl alcohol and the predicate device is made of acrylic polymer and porcine derived gelatin. However, the difference in technological characteristics between the subject and predicate device do not raise different questions of safety and effectiveness.

7. SUMMARY OF NON-CLINICAL PERFORMANCE TESTING AS BASIS FOR SUBSTANTIAL EQUIVALENCE

The device is subject to Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices issued on 29 December 2004.

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The safety and effectiveness of Bead Block™ has been confirmed by non-clinical testing including:

Residual starting material specifications
Residual solvent material
Visual inspection (visual defects, color, solution clarity) ●
Catheter delivery, including catheter clogging, formation of ● aggregates, ease of injection, and shape of embolization particle after injection
Confirmation of particle size range
Particle fiber shedding
pH
Packaging integrity ●
Shelf life
Sterilization validation
Endotoxin (<0.06 EU/ml) ●
Biocompatibility ●

No additional testing was conducted since the predicate and subject devices have equivalent technical characteristics, manufacturing, processing, and sterilization.

8. SUMMARY OF ANIMAL PERFORMANCE TESTING AS A BASIS FOR SUBSTANTIAL EQUIVALENCE

The animal studies used to assess uterine artery embolization included a sheep penetration model to evaluate the short term performance of Bead Block™ when compared to the predicate device; specifically local effects of the embolization and the distribution of microspheres in the vasculature. The second study assessed the possible side effects of embolization in sheep uteri (e.g., tissue necrosis and inflammation) when using Bead Block™. The results of the first study demonstrate that the performance of Bead Block™ is similar to the predicate device, with both showing normal, thrombosis and some rupture of the internal elastic lamina. The results of the second study demonstrate that Bead Block™ is associated with minimal tissue necrosis and a common foreign body reaction; however, the intensity of inflammatory reaction is moderate, without humoral response or cytotoxicity.

SUMMARY OF CLINICAL TESTING AS A BASIS FOR SUBSTANTIAL EQUIVALENCE 9.

The clinical information submitted included a review of Bead Block™ published and unpublished data on the use of Bead Block™ for the treatment of leiomyoma uteri (uterine fibroids) [outside the United States] over the last ten years. Review of the published and unpublished data regarding adverse events associated with Bead BlockTM has not identified any unique safety concerns.

10. CONCLUSION

The results of the testing described above provide reasonable assurance that Bead Block™ is as safe and effective as the predicate device and supports a determination of substantial equivalence.

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).