Bead Block microspheres are intended to be used for the embolization of hypervascular tumours, including uterine fibroids (UFE) and arteriovenous malformations (AVMs). Bead Block microspheres are also intended for embolization of prostatic arteries (PAE) for symptomatic benign prostatic hyperplasia (BPH).

Device Description

Bead Block, a permanent intravascular implant, is made up of preformed soft, compressible, biocompatible, hydrophilic, non-resorbable and precisely calibrated microspheres that occlude vessels for the purpose of blocking the blood flow to a target tissue. 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 suspended in contrast agents and delivered through microcatheters to the target location. Bead Block is available in bead sizes from 100 – 1200µm and supplied sterile in 20ml syringes which contain 1 or 2 ml of beads suspended in 6 or 5 ml of phosphate buffered saline, respectively. The different bead sizes of the product are differentiated by differently colored labels and syringe end caps. Bead Block is provided as a single use, non-pyrogenic, sterile (steam sterilized) device.

AI/ML Overview

This document is a 510(k) Premarket Notification from the FDA regarding the "Bead Block" device. It attests to the device's substantial equivalence to previously marketed predicate devices for the specified indications for use.

Based on the provided text, the Acceptance Criteria and Device Performance for this medical device (Bead Block) are not defined in terms of typical AI/ML-based image analysis performance metrics (e.g., sensitivity, specificity, AUC). Instead, the document focuses on demonstrating substantial equivalence to existing predicate devices based on safety and effectiveness for its intended use, which is embolization.

The "study" described is a retrospective data review of the clinical outcomes of patients treated with Bead Block for prostatic artery embolization (PAE) for symptomatic benign prostatic hyperplasia (BPH). This is a clinical effectiveness study, not a study of an AI/ML device's diagnostic or analytical performance.

Therefore, many of the requested points related to AI/ML device study parameters (e.g., test set, ground truth experts, MRMC studies, standalone performance) are not applicable to this document.

Here's an attempt to answer the prompt based on the provided text, reinterpreting the "acceptance criteria" and "study" in the context of a medical device submission for substantial equivalence:

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

The "acceptance criteria" for this 510(k) submission are not explicitly stated as quantitative thresholds for clinical performance but rather are implicitly tied to demonstrating safety and effectiveness comparable to predicate devices. The "reported device performance" refers to the clinical outcomes observed in the retrospective study.

Acceptance Criteria (Implicit from 510(k) Process)	Reported Device Performance (from Retrospective Study)
Safety: Device is safe for intended use, with acceptable adverse event profile compared to predicate.	Observed AEs: 149/232 patients (64.2%) reported at least one AE. Most AEs were non-serious and transient. Most common were renal/urinary disorders (15.2%), dysuria (41.4%), pollakiuria (45.3%). Conclusion: "well tolerated treatment."
Effectiveness: Device effectively achieves intended clinical outcome, comparable to predicate.	Clinical Improvements at 12 Months: - 85% of patients: decrease in total IPSS by at least 3 points. - 62% of patients: dropped at least 1 symptom category (severe to moderate to mild). - Statistically significant and clinically relevant improvements in total IPSS, QoL, PSA, and prostate volume (p<0.001). - Improvement tendency in Qmax (p=0.059) and PVR (p=0.1). - PAE did not impair sexual function (IIEF). Conclusion: "effective... with comparable outcomes to Embosphere Microspheres."
Technological Characteristics: Similar to predicate devices, or differences do not raise new safety/effectiveness questions.	Technological Comparison: - Similar size-calibrated spherical microspheres, delivered by microcatheters. - Similar size ranges, steam sterilized, single-use, biocompatible, non-resorbable polymer. - Delivery via microcatheter, visualization via radiographic imaging. - Minor material difference (PVA vs. acrylic/porcine gelatin) "do not raise different questions of safety and effectiveness."
Biocompatibility: Device material is biocompatible for intended use.	Previous Biocompatibility Testing: Genotoxicity, implantation, sensitization, intracutaneous reactivity, acute, subchronic toxicity. Studies showed material is biocompatible.
Material/Device Performance: Physical and chemical properties suitable for intended use.	Previous Bench Testing: Residuals, visual defects, color, solution clarity, catheter delivery (clogging, aggregates, injection ease), particle fiber shedding, pH, packaging integrity, shelf life, sterility, endotoxins.
MR Safety: Demonstration of MR safety/compatibility.	MR Safe: Based on scientific rationale (non-ferrous composition) in alignment with FDA guidance. Labeling updated to reflect MR safety.

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

Sample Size: 232 patients.
Data Provenance: Retrospective data review. The country of origin is not explicitly stated in this document but implied to be from a clinical setting where Bead Block was used.

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

Not applicable. This was a retrospective clinical outcomes study, not a study involving expert readers establishing ground truth for image interpretation by an AI device. The "ground truth" here is the observed clinical outcomes in patients.

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

Not applicable, as this was a clinical outcomes study, not an imaging study requiring reader adjudication. Clinical outcomes (IPSS, QoL, prostate volume, Qmax, PVR, IIEF, AEs) were measured directly.

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 document describes a PMA (pre-market approval) or 510(k) submission for a physical medical device (embolization microspheres), not an AI/ML-based diagnostic or assistive device. Therefore, no MRMC study or AI assistance comparison was performed.

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

Not applicable, as this is not an AI/ML algorithm.

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

The ground truth for the effectiveness portion of the study was clinical outcomes data (e.g., International Prostate Symptom Score (IPSS), erectile function (IIEF), Quality of Life (QoL), Prostate volume (PV), objective measures of urinary flow (Qmax, PVR)) and adverse events (AEs) reported by patients or clinicians over the course of the study.

8. The sample size for the training set

Not applicable. This is not an AI/ML device that requires a training set. The "study" described is a retrospective clinical review, which would be analogous to a "test set" in an AI/ML context, if at all.

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

Not applicable, as there is no training set for an AI/ML algorithm. The clinical data collected was used to demonstrate the performance of the device itself.

Summary

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April 20, 2021

Biocompatibles UK Ltd (part of Boston Scientific Corporation) % Christina Fischer Principal Regulatory Affairs Specialist Boston Scientific Medizintechnik GmbH Daniel-Goldbach-Straße 17 - 27 Ratingen, 40880 GERMANY

Re: K203276

Trade/Device Name: Bead Block (100 - 300um, 1ml), Bead Block (300 - 500um, 1ml), Bead Block (500 - 700um, 1ml), Bead Block (700 - 900μm, 1ml), Bead Block (900 - 1200μm, 1ml), Bead Block (100 - 300um, 2ml), Bead Block (300 - 500um, 2ml), Bead Block (500 - 700μm, 2ml), Bead Block (700 - 900μm, 2ml), Bead Block (900 - 1200um, 2ml) Regulation Number: 21 CFR 876.5550 Regulation Name: Prostatic Artery Embolization Device Regulatory Class: II Product Code: NOY Dated: March 3, 2021 Received: March 4, 2021

Dear Christina Fischer:

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

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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 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/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). 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 (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely,

for Mark Antonino, M.S. Assistant Director DHT3B: Division of Reproductive. Gynecology and Urology Devices OHT3: Office of GastroRenal, ObGyn, General Hospital and Urology Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

Submission Number (if known)

K203276
Device Name
Bead Block (100 - 300μm, 1 ml) (EB1S103);
Bead Block (300 - 500μm, 1 ml) (EB1S305);
Bead Block (500 - 700μm, 1 ml) (EB1S507);
Bead Block (700 - 900μm, 1 ml) (EB1S709);
Bead Block (900 - 1200μm, 1 ml) (EB1S912);
Bead Block (100 - 300μm, 2 ml) (EB2S103);
Bead Block (300 - 500μm, 2 ml) (EB2S305);
Bead Block (500 - 700μm, 2 ml) (EB2S507);
Bead Block (700 - 900μm, 2 ml) (EB2S709);
Bead Block (900 - 1200μm, 2 ml) (EB2S912)

Indications for Use (Describe)

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.

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510(k) Summary		K203276Page 1 of 3
Contact Details		21 CFR 807.92(a)(1)
Applicant Name	Biocompatibles UK Ltd (part of Boston Scientific Corporation)
Applicant Address	Chapman House, Weydon Lane Surrey Farnham GU9 8QL UnitedKingdom of Great Britain and Northern Ireland
Applicant Contact Telephone	+491621788391
Applicant Contact	Mrs. Christina Fischer
Applicant Contact Email	christina.fischer@bsci.com
Device Name	21 CFR 807.92(a)(2)
Device Trade Name	Bead Block (100 - 300µm, 1 ml) (EB1S103);Bead Block (300 - 500µm, 1 ml) (EB1S305);Bead Block (500 - 700µm, 1 ml) (EB1S507);Bead Block (700 - 900µm, 1 ml) (EB1S709);Bead Block (900 - 1200µm, 1 ml) (EB1S912);Bead Block (100 - 300µm, 2 ml) (EB2S103);Bead Block (300 - 500µm, 2 ml) (EB2S305);Bead Block (500 - 700µm, 2 ml) (EB2S507);Bead Block (700 - 900µm, 2 ml) (EB2S709);Bead Block (900 - 1200µm, 2 ml) (EB2S912)
Common Name	Prostatic artery embolization device
Classification Name	Agents, Embolic, For Treatment Of Benign Prostatic Hyperplasia
Regulation Number	876.5550
Product Code	NOY
Legally Marketed Predicate Devices	21 CFR 807.92(a)(3)
Predicate #	Predicate Trade Name (Primary Predicate is listed first)		Product Code
DEN160040	Embosphere Microspheres		NOY
K150876	Bead Block		KRD
21 CFR 807.92(a)(4)
Device Description Summary
Bead Block, a permanent intravascular implant, is made up of preformed soft, compressible, biocompatible, hydrophilic, non-resorbableand precisely calibrated microspheres that occlude vessels for the purpose of blocking the blood flow to a target tissue. Bead Blockcompressible microspheres consist of a macromer derived from polyvinyl alcohol (PVA). The fully polymerized microsphere isapproximately 90-95% water and is compressible to approximately 30% by diameter. Bead Block microspheres are dyed blue to aid inthe visualization of the microspheres in the delivery syringe. The microspheres can be suspended in contrast agents and deliveredthrough microcatheters to the target location.Bead Block is available in bead sizes from 100 – 1200µm and supplied sterile in 20ml syringes which contain 1 or 2 ml of beadssuspended in 6 or 5 ml of phosphate buffered saline, respectively. The different bead sizes of the product are differentiated by differentlycolored labels and syringe end caps.

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Bead Block is provided as a single use, non-pyrogenic, sterile (steam sterilized) device.

Intended Use/Indications for Use

Indications for Use Comparison

The subject device Bead Block and the predicate device Embospheres have the same intended use and indications for use. They are both intended for the embolization of hypervascular tumors, including uterine fibroids and for prostatic artery embolization for benign prostate hyperplasia. The subject device Bead Block has the same intended use (embolization of vessels) compared to the reference device, Bead Block (K150876) with an extension of the indication for use to include prostatic artery embolization.

Technological Comparison

The subject device Bead Block and the predicate device Embospheres are size calibrated spherical microspheres delivered by microcatheters to occlude a target blood vessel. They have similar technological characteristics including the following: - Size callbrated microspheres for embolization in similar size ranges (Bead Block 100 - 1200um). The Bead Block size intended to be used for PAE (100 - 300μm) are identically available for the primary predicate device

Steam sterilized, single use device
Biocompatible, non-resorbable polymer
Delivery via microcatheter to the site of desired embolization
Visualization of the embolization process using radiographic imaging

Bead Block and the predicate device have minor different technological characteristics, as the subject device is made of polyvinyl alcohol and the predicate device is made of acrylic polymer and porcine delatin. However, the difference in technological characteristics between the subject and predicate device do not raise different questions of safety and effectiveness.

The Bead Block microspheres (subject device) are identical to the reference device, Biocompatible's Bead Block (K150876) in design / technological characteristics, manufacturing, material, packaging, sterilization method and principle of operation. MR safety is added to the labeling for Bead Block based on a scientific rational referring to the non-ferrous composition of the device.

Non-Clinical and/or Clinical Tests Summary & Conclusions 21 CFR 807 92(b)

The determination of substantial equivalence, for the Indication for Use to include prostatic artery embolization, did not require non-clinical performance testing performance testing, which includes bench testing, biocompatibility testing and animal studies, submitted in previous premarket submissions remain valid for Bead Block microspheres.

Previous bench testing of Bead Block included determination of residuals (starting material, solvents), visual defects, color, solution clarity), catheter delivery, including catheter clogging, formation of aggregates, ease of injection, and shape of embolization particle after injection of size range, particle fiber shedding, pH, packaging integrity, shelf life, sterility and endotoxins.

Previous biocompatibility testing for Bead Block included genotoxicity, implantation, sensitization, intracutaneous reactivity as well as acute, subchronic toxicity testing. The studies have shown that the Bead Block material is biocompatible for its intended use.

Six animal studies were previously performed for Bead Block to demonstrate the safety and effectiveness of Bead in its intended use as an embolic agent. These studies were conducted employing a swine arteriovenous malformation model, rabit, swine, and sheep renal and uterus embolization model in sheep uterus. Comparison to the predicate device Embosphere was studied in the swine model and similar behavior of the embolic devices was shown.

Bead Block is MR Safe, based on scientific rationale as per the requirements in the Guidance for Industry and Food and Drug Administration Staff Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) environment (Dec 2014). Bead Block's materials are non-ferrous therefore supporting the conclusion of MR Safe in the MR environment.

A retrospective data review was designed to collect data on the effects of Bead Block on safety as well as effectiveness. The data review assessed International Prostate Symptom Score (IPSS), erectile function (IIEF), Quality of Life (QoL), Prostate volume (PV) and objective measures of urinary flow in male patients with moderate to severe lower urinary tract symptoms (LUTS) due to BPH who underwent PAE procedure.

Overall, 232 patients were included in this study. Bead Block 100-300 um was used in 3 patients (1%), 300-500 um in 220 patients (95%) and unknown bead size in 9 patients (4%).

21 CFR 807.92(a)(5)

21 CFR 807.92(a)(6)

FR 807.92(a)(5)

K203276

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K203276

Page 3 of 3

Baseline Characteristics (no of patients) Age (years) 65.2 ± 8.2 (226) IPSS 21.8 ± 7.0 (167) Quality of Life (QoL) 4.3 ± 1.0 (168) Prostate Volume (ml) 86.4 ± 47.4 (180) Qmax (peak urinary flow) (ml/s) 10.4 ± 6.5 (154) PVR (Post-void residual volume) (ml) 105.2 ± 116.7 (154)

The results show that at 12 months post-embolization, 85% of patients treated with Bead Block reported a decrease in their total IPSS by at least 3 points, and 62% patients dropped at least 1 symptom category, from severe to moderate to mild. Statistically significant and clinically relevant in total IPSS, QoL, PSA and prostate volume at 12 months (p<0.001) has been observed. Maximum urine flow (Qmax) and post-void residual (PVR) also showed improvement tendency at 12 months (p = 0.059 and 0.1). PAE using Bead Block did not impair sexual function as measured by IIEF.

Observed adverse events (AEs) were generally non-serious and transient. Overall, 149/232 patients (64.2%) reported at least one AE over the course of the study, most commonly renal and urinary disorders which were reported by 128 patients (15.2%). Dysuria (reported by 96/232 patients (41.4%)) and pollakiuria (reported by 105/232 patients (45.3%)) were the most common AEs.

Based on the technological characteristics and intended use along with the non-clinical and clinical data for Bead or referenced in this submission, it has been demonstrated that Bead Block used for the prostatic artery for treatment of benign prostatic hyperplasia is an effective and well tolerated treatment in the study population, with comparable outcomes to Embosphere Microspheres. Bead Block is considered substantially equivalent to the predicate Embospheres in safety and effectiveness for the embolization of the prostatic artery for treatment of benign prostatic hyperplasia.

Bead Block demonstrates compliance with the Special Controls under 21 CFR876.5550 for the expanded indication for use to include prostatic artery embolization. In addition, Bead Block is demonstrated to be MR safe ial characteristics in alignment with the requirements of the Guidance Document Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment. The expansion of the indication for use and the addition of MR compatibility information to not raise new questions of safety or effectiveness.

Regulation Number and Section

§ 876.5550 Prostatic artery embolization device.

(a)
Identification. A prostatic artery embolization device is an intravascular implant intended to occlude the prostatic arteries to prevent blood flow to the targeted area of the prostate, resulting in a reduction of lower urinary tract symptoms related to benign prostatic hyperplasia. This does not include cyanoacrylates and other embolic agents which act by in situ polymerization or precipitation, or embolization devices used in neurovascular applications (see 21 CFR 882.5950).(b)
Classification. Class II (special controls). The special controls for this device are:(1) The device must be demonstrated to be biocompatible.
(2) Non-clinical performance testing must demonstrate that the device performs as intended under anticipated conditions of use. The following performance characteristics must be tested:
(i) Evaluation of suitability for injection through catheters intended for use in embolization; and
(ii) Evaluation of the size distribution of the device.
(3) Performance data must support the sterility and pyrogenicity of the device.
(4) Performance data must support the shelf life of the device by demonstrating continued sterility, package integrity, and device functionality over the identified shelf life.
(5) Clinical data must evaluate post-embolization damage due to non-target embolization under anticipated use conditions.
(6) The labeling must include:
(i) Specific instructions on safe device preparation and use;
(ii) The device shelf life;
(iii) Data regarding urinary retention; and
(iv) Data regarding post-prostatic artery embolization syndrome.