(60 days)
Embosphere Microspheres are indicated for use in the embolization of:
• Hypervascular tumors, including symptomatic uterine fibroids
• Prostatic arteries for symptomatic benign prostatic hyperplasia (BPH)
• Arteriovenous malformations
• Blood vessels to occlude blood flow to control bleeding/hemorrhaging in the peripheral vasculature (subject of this Traditional 510(k))
Embosphere Microspheres are small, compressible, hydrophilic, biocompatible spheres made of acrylic polymer and porcine-derived gelatin. The microspheres are packaged in 0.9% saline and are provided sterile and non-pyrogenic in a vial or in a syringe.
The product is provided in seven size ranges to allow physicians to choose the calibration necessary for the vessel being embolized. The size ranges available are:
- 50-100 microns
- 40-120 microns
- 100-300 microns
- 300-500 microns
- 500-700 microns
- 700-900 microns
- 900-1200 microns .
The principles of operation for the subject device Embosphere Microspheres are the same as the predicate device Embosphere Microspheres (K021397) and reference devices Embosphere Microspheres (K991549, DEN160040). Embosphere Microspheres are permanent implantable devices and are designed for controlled, targeted embolizations for Embosphere Microsphere Microspheres involve arterial embolization; embolization of uterine fibroids, arteriovenous malformations, hypervascular tumors and benign prostatic hyperplasia involve an embolization of the arteries supplying those areas. The procedure of arterial embolization is similar for all arteries. Appropriately sized microspheres for target vessel occlusion are chosen by the trained interventional radiologist. The delivery procedure involves arterial access through an artery, using a quidewire and microcatheter under fluoroscopic guidance. Once the catheter tip is placed in the artery(ies) supplying the targeted tissue Embosphere Microspheres mixed with a non-ionic contrast agent are delivered in a controlled manner under visualization to occlude the feeding vessel(s) to stop blood flow to the targeted area. The device is intended for single use.
The provided document is a 510(k) Summary for Embosphere Microspheres, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting detailed acceptance criteria and a study to prove a device meets those criteria directly.
Given the context of a 510(k) submission, the "acceptance criteria" and "device performance" are framed in terms of substantial equivalence to a previously cleared predicate device. The primary "study" is a literature review of clinical data to support the safety and effectiveness of the existing device for a new indication.
Here's an attempt to extract and synthesize the information based on your request, understanding that the document is not an efficacy study report in the traditional sense for a novel AI device:
Acceptance Criteria and Reported Device Performance
The "acceptance criteria" for the subject device (Embosphere Microspheres with an expanded indication) are effectively demonstrating substantial equivalence to the predicate Embosphere Microspheres (K021397) and reference devices (K991549, DEN160040) in terms of intended use, design, technological characteristics, and safety/performance. The new indication itself needed to be supported by existing safety and effectiveness data.
Table of Acceptance Criteria (Implied by Substantial Equivalence) and Reported Device Performance:
| Acceptance Criteria (Implied for Substantial Equivalence to Predicate) | Reported Device Performance and Characteristics (Subject Device) |
|---|---|
| Intended Use: Similar fundamental purpose as predicate. | Intended Use: Embolization of: Hypervascular tumors (including symptomatic uterine fibroids), Prostatic arteries for symptomatic BPH, Arteriovenous malformations, AND Blood vessels to occlude blood flow to control bleeding/hemorrhaging in the peripheral vasculature (new Indication For Use). The function of both the subject and predicate device is to occlude blood vessel(s) to stop blood flow to a targeted area. |
| Technological Characteristics: Identical to predicate device. | Technological Characteristics: Identical to predicate. Includes: - Shelf Life (single use): Three years (36 months) - Material (spheres): Acrylic polymer and porcine-derived gelatin - Physical Characteristics: Biocompatible, hydrophilic, compressible, non-resorbable - Microspheres Size: Seven size ranges (50-100 to 900-1200 microns) - Sterilization: Steam sterilized - Pyrogenicity: Non-pyrogenic - Performance: Designed for controlled, targeted embolization at the desired level of vessel occlusion - Principle of Operation: Microspheres administered with contrast medium into artery via catheter - Volume of microspheres per container: 1ml or 2ml in 0.9% saline - Packaging: 8-mL glass vial or 20-mL plastic syringe |
| Safety and Effectiveness: Demonstrate safety and effectiveness for the proposed indication, not raising new safety/effectiveness issues. | Safety and Effectiveness: Extensive clinical data from 40 publications (8 prospective, 32 retrospective, 2000-2018) with 662+ patients reviewed. Embolization with Embosphere was found to be an effective method to control bleeding/hemorrhaging in the peripheral vasculature, with a low complication rate. Adverse events (catheterization complications, post-embolization syndrome, non-targeted embolization) are known and addressed in the predicate device's IFU. No new safety/effectiveness issues were identified with the expanded indication. |
Study Details: Clinical Literature Review (Not a direct device performance study)
-
Sample Size Used for the Test Set and Data Provenance:
- Sample Size (Patients): At least 662 patients in the reviewed literature.
- Data Provenance: Clinical data from 40 publications (2000-2018). These included 8 prospective trials and 32 retrospective trials. The document does not specify the country of origin for the data, but it's reasonable to assume a mix of international and potentially US-based studies given the FDA review. The data consists of both retrospective and prospective studies.
-
Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts:
- This section is not applicable in the traditional sense of an AI device's test set. The "ground truth" here is the clinical outcomes reported in published literature regarding the safety and effectiveness of Embosphere Microspheres for embolization. The ground truth was established by the clinical judgment and findings of the physicians and researchers who conducted the studies included in the literature review. The qualifications of these clinicians would implicitly be interventional radiologists or other specialists performing embolization procedures. The FDA, through its review process, acts as the ultimate body verifying the acceptability of the evidence presented.
-
Adjudication Method for the Test Set:
- Not applicable for a literature review. The clinical outcomes were observed and reported in the individual studies. The FDA's review process then evaluated the aggregated evidence.
-
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 is for a medical device (microspheres for embolization), not an AI/CADe device that assists human readers.
-
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done:
- Not applicable. This is a medical device, not an algorithm.
-
The type of ground truth used:
- Clinical Outcomes Data: The ground truth used was the reported clinical outcomes, safety profiles, and effectiveness data derived from published clinical studies (prospective and retrospective trials) on the use of Embosphere Microspheres for embolization procedures, specifically for controlling bleeding/hemorrhaging in the peripheral vasculature.
-
The Sample Size for the Training Set:
- Not applicable. This is not an AI/machine learning device. The "training data" in a conceptual sense would be the cumulative clinical experience and data that formed the basis for previous clearances of Embosphere Microspheres and the general understanding of embolization procedures.
-
How the Ground Truth for the Training Set Was Established:
- Not applicable. As above, not an AI device with a distinct training set.
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July 16, 2018
BioSphere Medical, S.A. Rosène Amossé Senior Regulatory Affairs Specialist Parc des Nations - Paris Nord 2 383 Rue de la Belle Etoile 95700 Roissy en France France
Re: K181300
Trade/Device Name: Embosphere Microspheres Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: Class II Product Code: KRD. NAJ. NOY. HCG Dated: May 15, 2018 Received: May 17, 2018
Dear Rosène Amossé:
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 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);
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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 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.
Brian D. Pullin -S
for Bram D. Zuckerman, M.D. Director Division of Cardiovascular Devices Office of Device Evaluation Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K181300
Device Name Embosphere Microspheres
Indications for Use (Describe)
Embosphere Microspheres are indicated for use in the embolization of:
- · Hypervascular tumors, including symptomatic uterine fibroids
- · Prostatic arteries for symptomatic Benign Prostatic Hyperplasia (BPH)
- · Arteriovenous malformations
- · Blood vessels to occlude blood flow to control bleeding/hemorrhaging in the peripheral vasculature
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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Change in Indication for use
K181300 510(k) Summary
July 13, 2018
| GeneralProvisions | Submitter Name: | Biosphere Medical, S.A. |
|---|---|---|
| Address: | Parc des Nations - Paris Nord 2383, rue de la Belle Etoile95700 Roissy-en-France, France | |
| Telephone Number:Fax Number:Contact Person:Registration Number: | +33 (0)1 48 17 25 29+33 (0)1 49 38 02 68Alix Fonlladosa9615728 | |
| Correspondent Name:Address:Telephone Number:Fax Number:Contact Person:Registration Number: | Biosphere Medical, S.A.Parc des Nations - Paris Nord 2383, rue de la Belle Etoile95700 Roissy-en-France, France+33 (0)1 48 17 25 29+33 (0)1 49 38 02 68Alix Fonlladosa9615728 | |
| SubjectDevice | Trade Name:Common/Usual Name:Classification Name: | Embosphere® MicrospheresEmbolization device21 CFR 870.3300 - Vascular Embolization Device |
| PredicateDevice | Predicate Device:Trade Name:Classification Name:Premarket Notification:Manufacturer: | Embosphere® Microspheres21 CFR 870.3300 - Vascular Embolization DeviceK021397Biosphere Medical, S.A. |
| Reference devices:Trade Name:Classification Name: | Embosphere® Microspheres21 CFR 882.5950 - Neurovascular embolization device21 CFR 876.5550 - Prostatic artery embolization device | |
| Premarket Notification:Manufacturer: | K991549, DEN160040Biosphere Medical, S.A. | |
| Classification | Class II21 CFR § 870.3300FDA Product Code: KRDFDA Secondary Product Codes: HCG, NAJ, NOYDivision of Cardiovascular Devices |
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| Intended Use | Embosphere Microspheres are indicated for use in the embolization of:• Hypervascular tumors, including symptomatic uterine fibroids• Prostatic arteries for symptomatic benign prostatic hyperplasia (BPH)• Arteriovenous malformations• Blood vessels to occlude blood flow to control bleeding/hemorrhaging inthe peripheral vasculature (subject of this Traditional 510(k)) |
|---|---|
| -------------- | ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- |
Embosphere Microspheres are small, compressible, hydrophilic, biocompatible spheres made of acrylic polymer and porcine-derived gelatin. The microspheres are packaged in 0.9% saline and are provided sterile and non-pyrogenic in a vial or in a syringe.
The product is provided in seven size ranges to allow physicians to choose the calibration necessary for the vessel being embolized. The size ranges available are:
- 50-100 microns ●
- 40-120 microns ●
- 100-300 microns
- 300-500 microns ●
- 500-700 microns
- 700-900 microns ●
- 900-1200 microns .
Device Description
The principles of operation for the subject device Embosphere Microspheres are the same as the predicate device Embosphere Microspheres (K021397) and reference devices Embosphere Microspheres (K991549, DEN160040). Embosphere Microspheres are permanent implantable devices and are designed for controlled, targeted embolizations for Embosphere Microsphere Microspheres involve arterial embolization; embolization of uterine fibroids, arteriovenous malformations, hypervascular tumors and benign prostatic hyperplasia involve an embolization of the arteries supplying those areas. The procedure of arterial embolization is similar for all arteries. Appropriately sized microspheres for target vessel occlusion are chosen by the trained interventional radiologist. The delivery procedure involves arterial access through an artery, using a quidewire and microcatheter under fluoroscopic guidance. Once the catheter tip is placed in the artery(ies) supplying the targeted tissue Embosphere Microspheres mixed with a non-ionic contrast agent are delivered in a controlled manner under visualization to occlude the feeding vessel(s) to stop blood flow to the targeted area. The device is intended for single use.
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The technological characteristics of the subject device Embosphere Microspheres are identical to the predicate Embosphere Microspheres (K021397) and the reference devices Embosphere Microspheres (K991549, DEN160040). Only the indications for use change between the subject device and the legally marketed predicate device Embosphere Microspheres (K021397) and reference devices Embosphere Microspheres (K991549, DEN160040). The indications for use statement of the subject Embosphere Microspheres includes a specific indication by identifying "control bleeding / hemorrhaging in the peripheral vasculature" as being the result of embolization since embolization stops arterial blood flow, as established by 21 CFR § 870.3300.
| Technological Characteristics Comparison Table | ||||
|---|---|---|---|---|
| Attribute | Predicate DeviceEmbosphereMicrospheres(K021397) andReference devicesEmbosphereMicrospheres(K991549,DEN160040) | Subject DeviceEmbosphereMicrospheres | Comment | |
| Comparison toPredicate | Shelf Life(single use) | Three years(36 months) | Three years(36 months) | Same |
| Material(spheres) | Acrylic polymer andporcine-derived gelatin | Acrylic polymer andporcine-derived gelatin | Same | |
| PhysicalCharacteristics | Biocompatible,hydrophilic,compressible, non-resorbable | Biocompatible,hydrophilic,compressible, non-resorbable | Same | |
| MicrospheresSize | • 50-100 microns• 40-120 microns• 100-300 microns• 300-500 microns• 500-700 microns• 700-900 microns• 900-1200 microns | • 50-100 microns• 40-120 microns• 100-300 microns• 300-500 microns• 500-700 microns• 700-900 microns• 900-1200 microns | Same | |
| Sterilization | Steam sterilized | Steam sterilized | Same | |
| Pyrogenicity | Non-pyrogenic | Non-pyrogenic | Same | |
| Performance | Designed for controlled,targeted embolization atthe desired level ofvessel occlusion | Designed for controlled,targeted embolization atthe desired level ofvessel occlusion | Same | |
| Principle ofOperation | The microspheres areadministered withcontrast medium into thepatient's artery via acatheter | The microspheres areadministered withcontrast medium into thepatient's artery via acatheter | Same | |
| Volume ofmicrospheres percontainer | 1 ml or 2 ml ofmicrospheresin 0.9% saline solution | 1 ml or 2 ml ofmicrospheresin 0.9% saline solution | Same | |
| Packaging | 8-mL glass vial, or 20-mL plastic syringeMicrobial barrier: Blistertray sealed by aTyvek® peel-away lid | 8-mL glass vial, or 20-mL plastic syringeMicrobial barrier: Blistertray sealed by aTyvek® peel-away lid | Same |
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No performance standards have been established under Section 514 of the Food, Drug and Cosmetic Act for these devices. However, vascular and neurovascular embolization devices are subject to the special controls specified in "Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices", issued on December 29, 2004. In addition, the subject device follows the FDA Draft Guidance on "Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices)", issued on January 23, 2014.
Non-clinical performance testing conducted on the predicate device includes:
- · Chemical analysis
- · Size range
- Catheter compatibility
- Packaging performance
- · Shelf Life
- · Sterilitv
- · Biocompatibility
Biocompatibility evaluation was performed in accordance with ISO 10993-1:2009 for permanent implants in contact with blood for the predicate device Embosphere Microspheres (K021397) and the reference devices Embosphere Microspheres (K991549, DEN160040), and is being adopted for this subject device based upon the fact that all devices are made from the same materials using the same manufacturing and sterilization processes.
Safety & Performance Tests
No new testing was performed since predicate device Embosphere Microspheres (K021397) / reference devices Embosphere Microspheres (K991549. DEN160040), and subject device Embosphere Microspheres have identical technological characteristics, manufacturing, processing and sterilization.
Clinical data from the literature were reviewed on the use of Embosphere Microspheres for embolization of blood vessels to occlude blood flow to control bleeding / hemorrhaging in the peripheral vasculature. The retrieved clinical data consisted of 40 publications from 2000 to 2018, including eight prospective trials and thirty-two retrospective trials. The total number of patients treated with Embosphere Microspheres was 662 (at least). The majority of patients were adults of both genders. Some publications listed age ranges below adult (from 1 to 17 years).
The extensive clinical data provide relevant information about the safety and effectiveness of the subject Embosphere Microspheres in the proposed indication for use. Embolization of arteries with Embosphere was found to be an effective method to control bleeding / hemorrhaging in the peripheral vasculature, with a low complication rate.
Adverse events that were found related to the procedure are mostly complications related to catheterization, post-embolization syndrome and non- targeted embolization. The raised events found are addressed in the predicate device Embosphere Microspheres (K021397) and the reference devices Embosphere Microspheres (K991549, DEN160040) IFU as warnings or potential complications.
The proposed indication for use does not raise a safety or effectiveness issue that was not raised by the predicate device, or have the potential to significantly increase a safety or effectiveness concern raised by the predicate device. The
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function of both the subject device and predicate device (K021397) is to occlude blood vessel(s) in order to stop blood flow to a targeted area, which is the clinical endpoint for both devices. The safety and effectiveness of the device are related to size, shape, compressibility and biocompatibility for both general and specific indications. These characteristics do not change from the predicate to the subject Embosphere Microspheres.
Based on the same intended use (other than the requested change that is the objective of this submission), design, fundamental scientific technological Summary of characteristics, fundamental operational characteristics and safety and Substantial performance testing, the BioSphere Medical subject Embosphere Microspheres device meets the requirements that are considered essential for its intended use Equivalence and is substantially equivalent to the predicate device Embosphere Microspheres (K021397).
§ 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).