Embozene Microspheres are intended for embolization of arteriovenous malformations and hypervascular tumors, including uterine fibroids (UFE) and hepatoma, and for embolization of prostatic arteries (PAE) for symptomatic benien prostatic hyperplasia (BPH).

This device is not intended for neurovascular use.

Device Description

Embozene™ Color-Advanced Microspheres (hereafter referenced as Embozene or Embozene Microspheres) are spherical, tightly calibrated, biocompatible, hydrogel microspheres coated with proprietary polymer (Polyzene®-F). The microspheres are compressible to enable smooth delivery through the indicated delivery catheter and color-coded by size to allow for easy identification.

Microspheres are supplied sterile and packaged in 20 ml syringes with an approximate 7ml fill volume across the range. Embozene microspheres syringes are available in 2 ml microsphere volume for 40 -1300 µm.

AI/ML Overview

Acceptance Criteria and Device Performance for Embozene Color-Advanced Microspheres

This information is extracted from the provided 510(k) Summary for Embozene Color-Advanced Microspheres (K180102).

1. Table of Acceptance Criteria and Reported Device Performance

The acceptance criteria for the Embozene Color-Advanced Microspheres for the expanded indication of prostatic artery embolization (PAE) for symptomatic benign prostatic hyperplasia (BPH) are implicitly derived from the primary endpoints of the prospective clinical study, which focused on safety and symptomatic improvement. Specific quantitative acceptance criteria are not explicitly stated in the provided document, but the results demonstrate successful outcomes relative to baseline.

Acceptance Criteria (Implied from Study Endpoints)	Reported Device Performance (Embozene Prospective Data)
Safety: No serious adverse events or device-related events.	- No serious adverse events reported. - No device-related events reported. - No post-prostatic artery embolization syndrome events reported. - Total adverse events in 39.5% of subjects, none of which were serious or device-related.
Symptomatic Improvement of BPH (at 6 and 12 months) as measured by IPSS: - Improvement in average IPSS score over baseline. - Proportion of subjects with at least 3 IPSS points improvement.	IPSS: - Average 6-month IPSS score demonstrated 46% improvement over baseline. - Average 12-month IPSS score demonstrated 47% improvement over baseline. - 81.8% of subjects improved at least 3 IPSS points at 12 months.
Improvement in Quality of Life (QoL): - Improvement in average QoL score over baseline.	QoL: - Baseline QoL score of 4.4 (mostly dissatisfied) improved to 2.3 (mostly satisfied) at 3 months, maintained through 12 months.
Physiological Improvements: - Prostate volume reduction. - Increase in peak flow rates (Qmax).	Physiological Parameters: - Prostate volume reduction maintained through follow-up. - Increase of peak flow rates (Qmax) maintained through follow-up.
Procedural Success: - High success rate of embolization procedures. - No non-targeted embolization.	Procedural Success: - 100% (38/38) successful embolization procedures. - No cases of non-targeted embolization.

The document also refers to non-clinical tests for biocompatibility and performance for the Embozene Microspheres (which were previously cleared). The acceptance criteria for these tests were "All tests passed, indicating that the device materials are biocompatible for its intended use" and "All tests passed demonstrating the device meets the predetermined performance requirements." These include:

Biocompatibility: Cytotoxicity, Sensitization, Sub-Acute and Sub-Chronic Systemic Toxicity, Systemic Toxicity- Material Mediated Pyrogenicity, Genotoxicity (Bacterial Mutagenicity, In-vitro Chromosome Aberration, In-Vivo Micronucleous Assay), Implantation, Hemocompatibility (hemolysis, partial thromboplastin time, platelet/leukocyte counts).
Performance: Microsphere size distribution, visual inspection, pH of transport solution, Osmolality of transport solution, Microsphere suspension, Catheter compatibility, and Elution Test: Determination of leachable substances by UV-Vis, HPLC, and ICP-MS.

2. Sample Size Used for the Test Set and Data Provenance

Sample Size: 38 patients (male evaluable subjects).
Data Provenance: Prospective clinical study at a single center. The country of origin is not explicitly stated, but the submission is to the U.S. FDA by a U.S.-based company (Boston Scientific Corporation).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts

The document does not specify the number or qualifications of experts used to establish a "ground truth" for the test set. The clinical study collected patient-reported outcomes (IPSS, QoL, IIEF) and objective clinical measurements (Qmax, PVR, PV, PSA) which serve as the primary evaluation metrics for efficacy and safety. These are standard clinical assessments rather than expert-adjudicated ground truth in a diagnostic sense.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the test set. The data presented are reported clinical outcomes and adverse events collected directly from patients and clinical assessments.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was Done

No, a Multi-Reader Multi-Case (MRMC) comparative effectiveness study was not done. This study is a prospective single-arm study evaluating the device's performance directly in patients, not assessing human reader performance with or without AI assistance.

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

This question is not applicable. The device, Embozene Color-Advanced Microspheres, is a medical device (embolization microspheres) used in a medical procedure performed by a physician, not an algorithm or AI system. Therefore, standalone algorithm performance is not relevant.

7. The Type of Ground Truth Used

The "ground truth" for the clinical study's primary endpoints was based on:

Patient-reported outcomes: International Prostate Symptom Score (IPSS), Quality of Life (QoL) questionnaires, and International Index of Erectile Function (IIEF).
Objective clinical measurements: Peak flow rate (Qmax), Post Void Residual (PVR), Prostate Volume (PV), and Prostate Specific Antigen (PSA) levels.
Safety assessment: Reported adverse events.
Procedural success: Radiographic evidence.

8. The Sample Size for the Training Set

No training set is mentioned as this is a medical device and not an AI/ML algorithm.

9. How the Ground Truth for the Training Set Was Established

Not applicable, as no training set was used for an AI/ML algorithm.

Summary

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April 19, 2018

Boston Scientific Corporation Heidi Shearer Regulatory Affairs Specialist 3 Scimed Place Maple Grove, MN 55311

Re: K180102

Trade/Device Name: Embozene Color-Advanced Microspheres Regulation Number: 21 CFR& 876.5550 Regulation Name: Prostate Artery Embolization Device Regulatory Class: II Product Code: NOY, KRD, NAJ Dated: January 18, 2018 Received: January 19, 2018

Dear Heidi Shearer:

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.

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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); 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.

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.

For comprehensive regulatory information about medical devices and radiation-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,

Charles Viviano -S

Benjamin R. Fisher, Ph.D. For 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) K180102

Device Name Embozene Color-Advanced Microspheres

Indications for Use (Describe)

This device is not intended for neurovascular use.

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)

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510(k) Summary per 21 CFR §807.92

Sponsor	Boston Scientific Corporation300 Boston Scientific WayMarlborough, Massachusetts 01752USA
Contact Name andInformation	Heidi ShearerThree Scimed PlaceMaple Grove, MN 55311-1566Phone:763-255-0056Fax: 763-494-2222e-mail: Heidi.Shearer@bsci.com
Prepared	12 January 2018
Proprietary Name	EmbozeneTM Color-Advanced Microspheres
Common Name	Prostatic Artery Embolization DeviceVascular Embolization Device
Product Code	NOYKRD, NAJ
Classification	Class II, 21 CFR Part 876.5550 (NOY) and 21 CFRPart 870.3300 (KDR, NAJ)
Predicate Device	Embosphere® Microspheres (Embosphere PROTMProstatic Artery Embolization Kit), Merit MedicalSystems Inc.DEN160040 (21-Jun-2017)
Reference Device	EmbozeneTM Color-Advanced Microspheres, BostonScientific CorporationK141209 (07-Aug-2014)

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Device Description

Indications for Use/ Intended Use

This device is not intended for neurovascular use.

Comparison of Technological Characteristics

The Embozene Microspheres are substantially equivalent to the legally marketed Merit Medical Systems Inc. Embosphere® Microspheres, cleared by FDA (DEN160040), in regard to indications for use and similar in technological characteristics. Both devices are spherical, non-resorbable polymer microspheres which are delivered through a microcatheter to embolize the target vessel. There are differences in actual material composition; however, the materials of the Embozene Microspheres are well-known and widely used in the medical environment and are biocompatible for their intended use. The devices are available in similar sizes, Embozene (40-1300 µm) vs Embosphere (40-1200 µm). While Embozene is available in a slightly larger diameter, the size ranqe typically used to treat the prostatic artery are the same between both devices. The differences in materials and size range of these devices do not affect overall safety or effectiveness as demonstrated by clinical data. The Embozene Microspheres are identical to the reference device, Boston Scientific's Embozene Microspheres (K141209), in design, function, device materials, packaging, sterilization method, operating principle, and fundamental technology.

Summary of Bench Tests

Non-clinical tests performed on the Embozene Microspheres, reference device, provide reasonable assurance that the proposed device has been designed and tested to assure conformance to the requirements for its intended use. A risk assessment was performed and demonstrates that the expanded indication did not require additional bench, biocompatibility, sterilization, or pre-clinical animal testing beyond what was required for the reference device. All existing provided in the previous Embozene Microspheres premarket submissions remains applicable.

Biocompatibility testing provided in the previous Embozene Microspheres premarket notification included: Cytotoxicity, Sensitization, Sub-Acute and Sub-Chronic Systemic Toxicity, Systemic Toxicity- Material Mediated Pyrogenicity, Genotoxicity (Bacterial Mutagenicity, In-vitro Chromosome Aberration, In-Vivo Micronucleous Assay), Implantation, Hemocompatibility (hemolysis, partial thromboplastin time, platelet/leukocyte counts). All tests passed, indicating that the device materials are biocompatible for its intended use.

Performance testing provided in the previous Embozene Microspheres premarket notification included: Microsphere size distribution, visual inspection, pH of transport solution, Osmolality of transport solution, Microsphere suspension, Catheter compatibility, and Elution Test: Determination of leachable substances by UV-Vis, HPLC, and ICP-MS. All tests passed demonstrating the device meets the predetermined performance requirements.

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Published literature on four (4) preclinical animal studies assessed the biocompatibility, safety, and efficacy of Embozene Microspheres in comparison with the Embosphere predicate and other embolization devices. The devices were evaluated in a porcine kidney model to determine arterial distribution characteristics, inflammation and recanalization, impact on inflammatory tissue and foreign body reaction, and immunohistochemical inflammatory reactions. The results demonstrate a similar biological tissue response between the Embozene Microsphere predicate device which supports substantial equivalence.

Additionally, for labeling with MR compatibility, the proposed Embozene Microspheres were assessed and met 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.

Clinical Data Summary

Clinical data from a prospective clinical study along with literature on the Embozene Microspheres supports the expanded indication for use and is considered to be substantially equivalent in safety and effectiveness to the predicate Merit Medical's Embosphere Microspheres.

A prospective clinical study at a single center evaluated 38 patients that underwent a prostatic artery embolization (PAE) using Embozene Microspheres for the treatment of symptomatic benign prostatic hyperplasia (BPH). The primary endpoints included safety and the symptomatic improvement of BPH symptoms through follow-up as measured by the International Prostate Symptom Score (IPSS) and the peak flow rate (Qmax). Safety was assessed from the reported adverse events. At baseline, patients underwent a clinical assessment for Qmax, post void residual (PVR), prostate volume (PV) and prostate specific antigen (PSA) levels. All patients also completed the validated symptom and quality of life (QoL) questionnaires. Clinical assessments included the validated IPSS, International Index of Erectile Function (IIEF) and quality of life (QOL) questionnaires.

Results

Thirty-eight male evaluable subjects have been enrolled in the study with a mean age of 64.6±8.4 years. Bilateral embolization procedures were performed in 94.7% (36/38). Post procedural radiographic evidence demonstrated that the embolization procedures were 100% (38/38) successful without any cases of non-targeted embolization. Table 1 summarizes the baseline characteristics.

Characteristic	Embozene Prospective DataMean±SD (n)
Age Yrs	64.6±8.4 (38)
IPSS	21.2±6.7 (37)
Quality of Life	4.4±1.1 (38)
Qmax (ml/s)	10.9±6.9 (30)
Prostate Volume (ml)	79.0±55.7 (38)
PSA (ng/ml)	3.7±3.4 (38)

Table 1 Baseline Data

The average 6 month and 12 month IPSS scores demonstrated a symptomatic improvement over baseline at 46% and 47%, respectively. Additionally, 81.8% of the subjects improved at least 3 IPSS points at 12 months (Table 3). The baseline QoL score of 4.4 (mostly dissatisfied) improved to a 2.3 (mostly satisfied) at 3 months which was maintained through 12 months. A prostate volume reduction was also maintained through the follow up with an increase of the peak flow rates (Qmax).

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Table 2 Mean Results for Baseline, 3 Months, 6 Months and 12 Months
	Embozene Prospective Data
Characteristic	Baseline	3 months	6 months	12 months
	Mean±SD(n)	Mean±SD (n)	Mean±SD (n)	Mean±SD (n)
IPSS	21.2±6.7 (37)	10.8±7.7 (36)	11.5±8.1 (37)	11.3±6.3 (23)
Quality of Life	4.4±1.1 (38)	2.3±1.2 (33)	2.1±1.3 (36)	2.3±1.4 (23)
Qmax (ml/s)	10.9±6.9 (30)	17.6±16.8 (12)	15.4±7.7 (23)	18.5±10.2 (10)
Prostate Volume (ml)	79.0±55.7 (38)	69.3±35.1 (7)	65.1±41.4 (33)	56.8±24.3 (5)

Table 3 Proportion of Patients with at least 1 and 3 point IPSS Improvement

	Embozene Prospective Data
IPSS Points	3 months% (n/N)95% CI	6 months% (n/N)95% CI	12 months% (n/N)95% CI
At least 1 pointimprovement	85.7% (30/35)[69.7%, 95.2%]	88.9% (32/36)[73.9%, 96.9%]	95.5% (21/22)[77.2%, 99.9%]
At least 3 pointsimprovement	82.9% (29/35)[66.4%, 93.4%]	80.6% (29/36)[64.0%, 91.8%]	81.8% (18/22)[59.7%, 94.8%]

The adverse events are presented in Table 4 by system organ class (SOC) and Preferred Term (PT). There were no serious adverse events or device related events reported. The investigative site did not report any post-prostatic artery embolization syndrome events.

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System/Organ Class	Preferred Term	TotalEvents(Subjects)	Rate ofSubjectswith Event
Total	Total	22 (15)	39.5%
Renal and urinarydisorders	Total	12 (9)	23.7%
	Hematuria	3 (3)	7.9%
	Dysuria	2 (2)	5.3%
	Micturition urgency	2 (2)	5.3%
	Urine flow decreased	2 (2)	5.3%
	Pollakiuria	1 (1)	2.6%
	Urinary incontinence	1 (1)	2.6%
	Urinary retention	1 (1)	2.6%
Infections andinfestations	Total	3 (3)	7.9%
	Cystitis	2 (2)	5.3%
	Penile infection	1 (1)	2.6%
Nervous systemdisorders	Total	2 (2)	5.3%
	Paraesthesia	2 (2)	5.3%
Reproductive system andbreast disorders	Total	2 (2)	5.3%
	Penis disorder	1 (1)	2.6%
	Spermatic cord pain	1 (1)	2.6%
Blood and lymphaticsystem disorders	Total	1 (1)	2.6%
	Leukocytosis	1 (1)	2.6%
Musculoskeletal andconnective tissuedisorders	Total	1 (1)	2.6%
	Muscle tightness	1 (1)	2.6%
Psychiatric disorders	Total	1 (1)	2.6%
	Sleep disorder	1 (1)	2.6%

Conclusion

Based on the indications for use, technological characteristics, safety and performance testing, and clinical evidence, the Embozene Color-Advanced Microspheres have been shown to support safety and effectiveness and are considered to be substantially equivalent to Embosphere Microspheres when indicated for embolization of prostatic arteries for symptomatic benign hyperplasia (BPH),

The Embozene Microspheres demonstrates compliance with the Special Controls under 21 CFR 876.5550 for the expanded indication for use and 21 CFR 870.3300.

In addition, the MR Compatability meets the requirements of the Guidance Document Establishing Safety and Compatibility of Passive Implants in the Magnetic Resonance (MR) Environment.

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.