The HydroPearl® Microspheres are intended for the embolization of arteriovenous malformations and hypervascular tumors, including uterine fibroids, and for embolization of prostatic arteries (PAE) for symptomatic benign prostatic hyperplasia (BPH).

Device Description

The HydroPearl TM Microspheres are a pre-formed, compressible, precisely calibrated, spherical embolic agent consisting of a biocompatible hydrogel. The HydroPearl TM Microspheres are offered in a variety of diameters ranging from 75-1100µm and are provided in a sterile syringe pre-filled with microspheres in phosphate buffered saline. The pre- filled syringe is packaged in a sealed sterile dispenser tray. The HydroPearl TM Microspheres are delivered to the treatment site through a delivery catheter.

AI/ML Overview

The provided document describes the acceptance criteria and study for the HydroPearl Microspheres, specifically for the expanded indication of prostatic artery embolization (PAE) for symptomatic benign prostatic hyperplasia (BPH).

Here's an organized breakdown of the requested information:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state pre-defined acceptance criteria with specific numerical thresholds (e.g., "IPSS score reduction must be X%"). Instead, it reports the observed clinical outcomes and concludes that these results support safe and effective use. The "acceptance criteria" here are implied through the positive clinical outcomes and the comparison to established understanding of PAE effectiveness.

Acceptance Criteria (Implied)	Reported Device Performance (HydroPearl Microspheres)
Primary Endpoint: Reduction in IPSS score during follow-up	Mean baseline IPSS: 20.7 (range; 4-30) Mean IPSS at latest follow-up (8.6 months): 9.1 (range; 2-18) (p<0.05)
Secondary Endpoint: Improvement in Quality of Life (QoL)	Mean baseline QoL score: 3.7 (range; 1-6) Mean QoL score at follow-up: 1.2 (range; 0-3) (p<0.05)
Technical Success: Bilateral prostatic artery embolization	Achieved in all 17 patients (100%)
Clinical Success (based on symptom improvement/medication reduction)	Achieved in 16/17 patients (94%) One patient considered a "clinical failure" (had LUTS well controlled on medication, wanted to cease medication, which was achieved, but symptoms mildly worsened from IPSS 4 to 10). Half of patients on BPH medications at baseline no longer required them after PAE; two additional patients reduced daily medications. Patient relying on CIC: Catheterized 5 times/day before PAE, 0 or 1 time/day after PAE.
Safety: Low rate of adverse events	One major complication: hospitalization for acute prostatitis (n=1), resolved without residual effects. Minor complications: hematuria (n=1), hematospermia (n=1), considered expected for PAE and likely due to mild non-target embolization.
Equivalence to Predicate Device	Comparative mechanical testing showed equivalent performance to Embosphere Microspheres. Pre-clinical animal testing showed similar performance to Embosphere Microspheres with favorable embolization results.

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

Sample Size (Test Set): 17 patients
Data Provenance: Retrospective analysis from a single US center.

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

The document does not specify the number or qualifications of experts for establishing ground truth for the clinical data. The data appears to be derived from standard clinical assessments (IPSS, QoL scores, observation of complications) and procedural records (technical success of embolization), rather than an explicit "ground truth" established by independent expert panel review.

4. Adjudication method for the test set

The document does not describe any specific adjudication method (e.g., 2+1, 3+1) for the clinical outcomes in the retrospective study. Clinical outcomes were reported based on collected patient data.

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

A multi-reader multi-case (MRMC) comparative effectiveness study was not conducted. This study focuses on the device's clinical performance in patients, not on comparing AI assistance to human readers.

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

This is not applicable as the HydroPearl Microspheres are a medical device (embolization agent), not an AI algorithm. The study assesses the performance of the physical device when used by clinicians.

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

The "ground truth" for the clinical study's effectiveness was established through patient-reported outcomes data and objective clinical assessments:

International Prostate Symptom Score (IPSS) and Quality of Life (QoL) scores (patient-reported).
Observation of BPH medication usage reduction/cessation.
Objective assessment of technical success (bilateral PAE).
Adverse event reporting.

8. The sample size for the training set

The document does not describe a "training set" in the context of an AI algorithm. For the clinical performance anaysis, it refers to a retrospective analysis of existing data.

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

Not applicable, as this is not an AI algorithm study requiring a training set with established ground truth in that context.

Summary

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January 22, 2020

MicroVention, Inc. Ms. Analia Staubly Sr. Project Manager, Regulatory Affairs 35 Enterprise Aliso Viejo, California 92656

Re: K192684

Trade/Device Name: HydroPearl Microspheres Regulation Number: 21 CFR 876.5550 Regulation Name: Prostatic Artery Embolization Device Regulatory Class: Class II Product Code: NOY, KRD, NAJ, Dated: September 25, 2019 Received: September 26, 2019

Dear Ms. Staubly:

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 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

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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 (OS) 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 Angel Soler-Garcia, Ph.D. Acting Assistant Director Incontinence and Male Urological Devices Team (THT3B3) DHT3B: Division of Reproductive, Gynecological, and Urological Devices OHT3: Office of Gastrorenal, ObGyn, General Hospital and Urology Devices and Infection Control Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K192684

Device Name HYDROPEARL® Microspheres

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
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Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)

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TRADE NAME:	HydroPearl TM Microspheres
COMMON NAME:	Embolization device
REGULATION NAMES:	Prostatic artery embolization deviceVascular embolization device
CLASSIFICATION:	II, 21 CFR 876.5550 (NOY)II, 21 CFR 870.3300 (KRD/NAJ)
PRODUCT CODE:	NOY/KRD/NAJ
APPLICANT:	MicroVention, Inc.35 EnterpriseAliso Viejo, CA 92656
ESTABLISHMENTREGISTRATION NUMBER:	3013556777
CONTACT:	Analia StaublySr. Project Manager, Regulatory Affairsanalia.staubly@microvention.com
DATE SUMMARY PREPARED:	September 25, 2019
PREDICATE DEVICE:	BioSphere Medical S.A.Embosphere Microspheres (DEN160040)
REFERENCE DEVICE:	HydroPearl TM Microspheres (K150870)
DEVICE DESCRIPTION:	The HydroPearl TM Microspheres are a pre-formed,compressible, precisely calibrated, spherical embolicagent consisting of a biocompatible hydrogel. TheHydroPearl TM Microspheres are offered in avariety of diameters ranging from 75-1100µm and areprovided in a sterile syringe pre-filled with microspheresin phosphate buffered saline. The pre- filled syringe ispackaged in a sealed sterile dispenser tray. TheHydroPearl TM Microspheres are delivered to thetreatment site through a delivery catheter.
INDICATIONS FOR USE:	The HydroPearl TM Microspheres are intended for theembolization of arteriovenous malformations andhypervascular tumors, including uterine fibroids, andfor embolization of prostatic arteries (PAE) forsymptomatic benign prostatic hyperplasia (BPH).

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TECHNOLOGICAL CHARACTERISTICS AND PRODUCT FEATURE COMPARISON:

Characteristics	Predicate Device:Embosphere Microspheres(DEN160040)	Reference Device:HydroPearl Microspheres(K150870)	Subject Device:HydroPearlMicrospheres
Intended Use	Indicated for use in embolizationof arteriovenous malformations,hypervascular tumors, includingsymptomatic uterine fibroids andprostatic arteries forsymptomatic benign prostatichyperplasia (BPH).	Intended for theembolization ofarteriovenousmalformations andhypervascular tumors,including uterine fibroids.	Same asPredicate Device
TECHNICAL
MicrosphereMaterial	Acrylic polymer impregnatedwith porcine delivered gelatin.	Polyethylene glycoldiacrylamide and glycerolmonomethacrylate	Same asReferenceDevice
MicrosphereDiameter	Size Range: 40 – 1200 $\mu$ mLabeled size range:40 - 120 $\mu$ m100 - 300 $\mu$ m300 - 500 $\mu$ m500 - 700 $\mu$ m700 - 900 $\mu$ m900 - 1200 $\mu$ m	Size Range: 75 – 1100 $\mu$ mLabeled size:75 $\mu$ m200 $\mu$ m400 $\mu$ m600 $\mu$ m800 $\mu$ m1100 $\mu$ m	Same asReferenceDevice
MicrosphereContainer	Contained in a sterile, 20 mlpolycarbonate syringe.	Same as Predicate Device	Same asPredicate Device
Microspherevolume persyringe	1.0 or 2.0 ml, in physiologicalsaline.	2.0 ml in phosphatebuffered saline (PBS)	Same asReferenceDevice
RadiopacityMethod	Mixed with contrast media priorto injection.	Same as Predicate Device	Same asPredicate Device
Delivery Method	Via catheter under radiographicimaging.	Same as Predicate Device	Same asPredicate Device
STERILIZATION AND PACKAGING
SterilizationMethod.	Steam sterilization.	Same as Predicate Device	Same asPredicate Device
Packaging	Pre-filled syringe, placed in apolycarbonate tray and sealedwith a peel away Tyvek lid,placed inside bleached sulfatecarton box.	Same as Predicate Device	Same asPredicate Device
Method ofSupply	Sterile and single use.	Same as Predicate Device	Same asPredicate Device

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VERIFICATION AND TEST SUMMARY:

Non-clinical testing was performed on the HydroPearl Microspheres, reference device, to provide reasonable assurance that the proposed device has been designed and tested to assure conformance to special requirements for its intended use. A risk assessment has been performed and demonstrates that the expanded indication did not require additional bench, biocompatibility, packaging or sterilization. All existing testing in the previous HydroPearl Microsphere premarket submission remains applicable.

Comparative mechanical testing was conducted to compare the performance of the HydroPearl Microspheres to that of legally marketed devices for the same indication. The HydroPearl Microspheres performed equivalently to the Embosphere Microspheres, predicate device, in comparative mechanical testing. Pre-clinical animal testing was also performed in animal models representing the renal and prostatic vasculature. The HydroPearl performed similarly to the Embosphere Microspheres and had favorable embolization results in both studies.

CLINICAL INFORMATION:

Existing real-world data from a single, US center was analyzed retrospectively for the purpose of expanding the existing indication for the HydroPearl Microspheres to include embolization of prostatic artery embolization (PAE) for symptomatic benign prostatic hyperplasia (BPH). The retrospective analysis consisted of 17 patients that underwent prostatic artery embolization (PAE) using HydroPearl Microspheres for the treatment of symptomatic benign prostatic hyperplasia (BPH). The primary objective was to collect data of the procedure safety and efficacy, which included age, prostate volume baseline International Prostate Symptom Score + Quality of Life score (IPSS+QoL), unilateral embolization, size of particles used, complications and follow-up IPSS+OoL. The primary endpoint was reduction in IPSS score during the follow-up period.

Demographics and Baseline Characteristics:

Twenty-three patients were identified. 17 patients returned consent forms and their data was included in this study.

The mean age of the patients included was 70 (range; 55-85) and their mean prostate volume was 63 ml (range; 27-140). One of the patients relied on clean intermittent catheterization (CIC) for voiding and the rest were able to void without a catheter. Fourteen of seventeen patients were on BPH medications at the time of PAE.

All 17 patients underwent bilateral prostatic artery embolization was performed with either 75 um HydroPearl (n=2), 200 um HydroPearl (n=3) or 75 um followed by 200 um HydroPearl (n=12).

Primary Endpoint Results:

Mean follow up period was 8.6 months (range; 1-12). Mean baseline International Prostate Symptom Score was 20.7 (range; 4-30) at baseline and 9.1 (range; 2-18) at latest follow-up (p<0.05). Mean Quality of Life Score was 3.7 (range; 1-6) at baseline and 1.2 (range; 0-3) at follow-up (p<0.05). The single patient who relied on CIC for voiding catheterized 5 times a day before PAE and 0 or 1 time a day after PAE. Seven of the 14 patients on BPH medications at

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baseline no longer took these medications at their latest follow-up and two additional patients were able to reduce their daily medications.

Technical and Clinical Success Results :

Technical success, defined as bilateral prostate artery embolization, was achieved in all 17 patients. Clinical success was achieved in 16/17 patients (94%). The single patient that was considered a clinical failure underwent PAE with the goal of no longer requiring BPH medication after the procedure because of the side-effects that he experienced. His LUTS were well controlled on the medication prior to PAE (IPSS of 4). Post-PAE, he was able to cease taking medication, but his symptoms did mildly worsen (IPSS of 10).

Safety Results:

One major complication was reported that involved hospitalization of one subject 2 days after PAE to treat acute prostatitis. The patient was discharged after a 4-day admission without any residual effects. Additional minor complications that were reported included hematuria (n=1) and hematospermia (n=1). These two adverse events were likely the result of mild non-target embolization and are expected complications of PAE.

Study Conclusion:

PAE performed with HydroPearl Microspheres resulted in clinical success in nearly all the patients included in this analysis. The single exception was a patient who already had his LUTS well controlled on alpha-blocker medication. but who desired to no longer take this medication, which was accomplished after PAE. Additionally, half of the patients who presented at baseline on BPH medication, no longer required them after PAE.

In addition to the retrospective analysis, MicroVention Inc. conducted a comprehensive review of relevant clinical literature to assess whether any issues of safety or effectiveness were raised using microparticle embolic devices for prostatic artery embolization (PAE) for symptomatic benign hyperplasia (BPH). The literature review concludes that PAE is a safe, minimally invasive, and efficacious procedure with low rate of adverse events, particularly those related to the embolic agent.

CONCLUSION:

Based on the indications for use, technological characteristics, safety and performance testing, and clinical evidence, the HydroPearl Microspheres have been shown to support safe effective use in humans for prostatic artery embolization for symptomatic benign hyperplasia (BPH) and are substantially equivalent to Embosphere Microspheres

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

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.