(253 days)
Not Found
No
The device description focuses on the physical and chemical properties of the microspheres, and there is no mention of AI or ML in the intended use, device description, or performance studies. The "Mentions AI, DNN, or ML" field is explicitly marked as "Not Found".
Yes
The device is intended for the embolization of hypervascular tumors and arteriovenous malformations, which is a therapeutic intervention to treat these conditions.
No
Explanation: The device, Sunsphere, is described as an embolization device intended to block blood flow to treat hypervascular tumors and AVMs. It is a therapeutic device, not a diagnostic one, as it does not gather or interpret information about a patient's condition for diagnosis.
No
The device description clearly states it is composed of physical microspheres made of polyvinyl alcohol, which are a hardware component.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the embolization of hypervascular tumors and AVMs. This is a therapeutic procedure performed within the body to block blood vessels.
- Device Description: The device is composed of microspheres designed to be injected into blood vessels.
- Input Imaging Modality: DSA is an imaging technique used to visualize blood vessels in vivo.
- Anatomical Site: The anatomical sites are within the body (tumors, AVMs).
- Performance Studies: The performance studies involve animal testing with embolization procedures and evaluation of the effects in vivo.
IVD devices are used to examine specimens (like blood, urine, or tissue) outside of the body to provide information for diagnosis, monitoring, or screening. This device is clearly designed for a therapeutic intervention performed inside the body.
Yes.
The letter explicitly states: "The FDA's substantial equivalence determination also included the review and clearance of your Predetermined Change Control Plan (PCCP)." This sentence directly confirms that the device has an authorized PCCP.
Intended Use / Indications for Use
Sunsphere is intended to be used for the embolization of hypervascular tumors, including uterine fibroids, and arteriovenous malformations (AVMs).
Product codes (comma separated list FDA assigned to the subject device)
KRD, NAJ
Device Description
This proposed device is composed of polyvinyl alcohol embolic microspheres stored in a preservation solution of 0.9% sodium chloride. The proposed devices are compressible hydrogel microspheres with a regular shape, smooth surface, and calibrated size, which are formed as a result of chemical modification on polyvinyl alcohol (PVA) materials. Sunspheres are chemically cross-linked to form the microsphere. Microspheres are round in appearance with uniform size distribution and are available in blue dyed and undyed (colorless) microspheres.
The proposed device available in blue dyed and undyed (colorless) version, which are available in 1 mL and 2 mL volumes, and 6 different calibrated particle sizes from 90 to 1000 um. Different particle sizes are distinguished by the color of the matching vial cap. The proposed device is supplied sterile and packaged in sealed glass vials.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
Not Found
Intended User / Care Setting
Not Found
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Not Found
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Animal Performance Testing Conclusion: This study simulated the clinical use of Sunsphere and performed partial embolization of the right renal artery of healthy domestic pigs by interventional surgical procedures. The test article was Sunsphere, with particle size of 90 um; the control article was the cleared predicate device 8Spheres (polyviny) alcohol embolic microspheres - colorless), with particle size of 100 ~ 300 µm. The efficacy was evaluated by investigating the delivery performance, embolization effect immediate and within the study cycle. The test article in the study cycle was evaluated by investigating the postoperative animal recovery, clinical pathology, local embolization, gross anatomical observation, and systemic histopathological results at postoperative timepoints of 3, 8 and 28 days after embolization.
No clinically relevant intraoperative, postoperative, hematologic, coagulation, or major organ abnormalities other than the right kidney occurred. Among the serum biochemical parameters, the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the test group and the control group were slightly increased in the short term after surgery, but there was no significant difference between the two groups and no physiological abnormality was reached. Histopathology results showed only a small microsphere shift and secondary tissue response in the upper pole of the right kidney on Day 8, but there was no significant difference between the test group and control group, and its severity and extent of involvement were very mild. Overall, the lower pole of the right kidney in the test group and control group presented similar gross lesions and histopathological features. Vascular changes and necrosis were observed to be equivalent in the test group on Day 8 and Day 29, consistent with the equivalent long term embolization performance results of test article. In conclusion, compared with the control article demonstrated efficacy and safety equivalent to the predicate in this animal study.
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
The FDA's substantial equivalence determination also included the review and clearance of your Predetermined Change Control Plan (PCCP). Under section 515C(b)(1) of the Act, a new premarket notification is not required for a change to a device cleared under section 510(k) of the Act, if such change is consistent with an established PCCP granted pursuant to section 515C(b)(2) of the Act. Under 21 CFR 807.81(a)(3), a new premarket notification is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Accordingly, if deviations from the established PCCP result in a major change or modification in the intended use of the device, or result in a change or modification in the device that could significantly affect the safety or effectiveness of the a new premarket notification would be required consistent with section 515C(b)(1) of the Act and 21 CFR 807.81(a)(3). Failure to submit such a premarket submission would constitute adulteration and misbranding under sections 501(f)(1)(B) and 502(o) of the Act, respectively.
§ 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).
0
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May 30, 2024
Hangzhou Yangshun Medical Technology Co., Ltd. % Diana Hong General Manager Mid-Link Consulting Co., Ltd P.O. Box 120-119 Shanghai, Shanghai 200120 CHINA
Re: K232934
Trade/Device Name: Sunsphere Regulation Number: 21 CFR 870.3300 Regulation Name: Vascular Embolization Device Regulatory Class: II Product Code: KRD, NAJ Received: April 29, 2024
Dear Diana Hong:
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 (the 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 available 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.
The FDA's substantial equivalence determination also included the review and clearance of your Predetermined Change Control Plan (PCCP). Under section 515C(b)(1) of the Act, a new premarket notification is not required for a change to a device cleared under section 510(k) of the Act, if such change is
1
consistent with an established PCCP granted pursuant to section 515C(b)(2) of the Act. Under 21 CFR 807.81(a)(3), a new premarket notification is required if there is a major change or modification in the intended use of a device, or if there is a change or modification in a device that could significantly affect the safety or effectiveness of the device, e.g., a significant change or modification in design, material, chemical composition, energy source, or manufacturing process. Accordingly, if deviations from the established PCCP result in a major change or modification in the intended use of the device, or result in a change or modification in the device that could significantly affect the safety or effectiveness of the a new premarket notification would be required consistent with section 515C(b)(1) of the Act and 21 CFR 807.81(a)(3). Failure to submit such a premarket submission would constitute adulteration and misbranding under sections 501(f)(1)(B) and 502(o) of the Act, respectively.
Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device" (https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).
Your device is also subject to, among other requirements, the Quality System (OS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).
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 Part 803) for devices or postmarketing safety reporting (21 CFR Part 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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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 medical devices and radiation-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-regulatory
2
assistance/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,
Reginald K. Avery -S
for Jason R. Roberts, Ph.D. 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
3
DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration
Indications for Use
510(k) Number (if known) K232934
Device Name Sunsphere
Indications for Use (Describe)
Sunsphere is intended to be used for the embolization of hypervascular tumors, including uterine fibroids, and arteriovenous malformations (AVMs).
| Type of Use (Select one or both, as applicable) | |
|---|---|
| ✓ Prescription Use (Part 21 CFR 801 Subpart D) | Over-The-Counter Use (21 CFR 801 Subpart C) |
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Page 1 of 10
510(k) Summary
Sunsphere
This 510(k) Summary is being submitted in accordance with requirements of Title 21, CFR Section 807.92.
The assigned 510(k) Number: K232934
-
- Date of Preparation: May 30, 2024
Sponsor Identification 2.
| Sponsor Name: | Hangzhou Yangshun Medical Technology Co. Ltd. |
|---|---|
| Address: | Room 110, Building 2, No.357 Miaohouwang Road, Xixing Subdistrict |
| Binjiang District, Hangzhou, Zhejiang, China |
| Contact Person: | Dong Hui |
|---|---|
| Position: | Registration Director |
| Phone: | +86-13716835300 |
| Email: | dongh@sunspheremedical.com |
3. Designated Submission Correspondent
Ms. Diana Hong (Primary Contact Person) Ms. Tingting Su (Alternative Contact Person)
Mid-Link Consulting Co., Ltd
P.O. Box 120-119, Shanghai, 200120, China
Phone: +86-21-22815850, Fax: 360-925-3199 Email: info@mid-link.net
4. Identification of Proposed Device
Trade Name: Sunsphere Common Name: Polyvinyl Alcohol Embolic Microspheres
Regulatory Information Regulation Name: Vascular Embolization Device Regulation Number: 21 CFR 870.3300
5
Device Classification: Class II
Product Code: KRD (Device, Vascular, For Promoting Embolization), NAJ (Agents, Embolic, For Treatment Of Uterine Fibroids)
5. Identification of Predicate Device
Device Name: CalliSpheres Embolic Microspheres, 8Spheres Embolic Microspheres 510(k) Number: K173871 Manufacturer: Suzhou Hengrui Callisyn Biomedical Co., Ltd Regulation Number 21 CFR 870.3300 Product Code: KRD, NAJ
The predicate device has not been subject to any design-related recall.
6. Device Description
This proposed device is composed of polyvinyl alcohol embolic microspheres stored in a preservation solution of 0.9% sodium chloride. The proposed devices are compressible hydrogel microspheres with a regular shape, smooth surface, and calibrated size, which are formed as a result of chemical modification on polyvinyl alcohol (PVA) materials. Sunspheres are chemically cross-linked to form the microsphere. Microspheres are round in appearance with uniform size distribution and are available in blue dyed and undyed (colorless) microspheres.
The proposed device available in blue dyed and undyed (colorless) version, which are available in 1 mL and 2 mL volumes, and 6 different calibrated particle sizes from 90 to 1000 um. Different particle sizes are distinguished by the color of the matching vial cap. The proposed device is supplied sterile and packaged in sealed glass vials. The device configurations of Sunspheres are described in Table 1 below.
| Specification | Dye
Color | Calibrated Size (µm) | Size Range (µm) | Quantity |
|---------------|--------------|----------------------|-----------------|--------------------------------------------------------|
| F2B10090 | | 90 | 70 - 120 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B10200 | | 200 | 150 - 250 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B10400 | Blue | 400 | 350 - 450 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B10600 | | 600 | 550 - 650 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B10800 | | 800 | 700 - 900 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| | | | | |
| F2B11000 | | 1,000 | 900 - 1100 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B20090 | | 90 | 70 - 120 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B20200 | | 200 | 150 - 250 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B20400 | | 400 | 350 - 450 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B20600 | | 600 | 550 - 650 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B20800 | | 800 | 700 - 900 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2B21000 | | 1,000 | 900 - 1100 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C10090 | | 90 | 70 - 120 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C10200 | | 200 | 150 - 250 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C10400 | | 400 | 350 - 450 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C10600 | | 600 | 550 - 650 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C10800 | | 800 | 700 - 900 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C11000 | | 1,000 | 900 - 1100 | 1 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C20090 | Colorless | 90 | 70 - 120 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C20200 | | 200 | 150 - 250 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C20400 | | 400 | 350 - 450 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C20600 | | 600 | 550 - 650 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C20800 | | 800 | 700 - 900 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
| F2C21000 | | 1,000 | 900 - 1100 | 2 mL embolic microspheres/7 mL
0.9% sodium chloride |
Table 1. Product specification
6
Page 3 of 10
7. Indications for Use:
Sunsphere is intended to be used for the embolization of hypervascular tumors, including uterine fibroids, and arteriovenous malformations (AVMs).
8. Technological Comparison to Predicate Device
Table 2. General Comparison
7
| Item | Proposed Device
K232934 | Predicate Device
K173871 | Remark |
|---------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|------------|
| Classification | II | II | Same |
| Product Code | KRD, NAJ | KRD, NAJ | Same |
| Regulation
Number | 21 CFR 870.3300 | 21 CFR 870.3300 | Same |
| Indication for Use | The Sunsphere is indicated for
use in the embolization of
hypervascular tumors, including
uterine fibroids, and
arteriovenous malformations
(AVMs). | CalliSpheres Embolic
Microspheres and 8Spheres
Embolic Microspheres are intended
to be used for the embolization of
arteriovenous malformations
(AVMs) and hypervascular tumors,
including uterine fibroids. | Same |
| Polymerization
Method | Suspension polymerization | Suspension polymerization | Same |
| Resorption | Non-resorbable | Non-resorbable | Same |
| Appearance | Hydrogel microspheres with
regular shape. smooth surface
and calibrated size,
Blue dyed or undyed | Hydrogel microspheres with
regular shape. smooth surface and
calibrated size,
CalliSpheres: Blue dyed
8Spheres: Undyed | Same |
| Microsphere
Polymer
Composition | Polyvinyl alcohol (PVA) | PVA | Same |
| Size Range (µm) | Size Range: 70 – 1,100µm
Labeled size range:
70-120
150-250
350-450
550-650
700-900
900-1100 | Size Range: 100 – 1,200µm
Labeled size range:
100-300
300-500
500-700
700-900
900-1200 | Different. |
| Size indicated for
UAE (µm) | 550-650
700-900
900-1100 | 500-700
700-900
900-1200 | Different |
| Storage media | 0.9% sodium chloride solution | 0.9% sodium chloride solution | Same |
| Quantity of
Microspheres | 1 mL (in 7 mL 0.9% sodium
chloride)
2 mL (in 7 mL 0.9% sodium
chloride) | 1 mL (in 7 mL 0.9% sodium
chloride)
2 mL (in 7 mL 0.9% sodium
chloride) | Same |
8
| Packaging | Device are sealed in borosilicate glass vial | Both CalliSpheres and 8Spheres are sealed in borosilicate glass vial | Same |
|---|---|---|---|
| Compressibility | 30% by diameter | 30% by diameter | Same |
| Delivery Method | Delivered to target position by Micro-Catheter under DSA. | Delivered to target position by Micro-catheter under DSA. | Same |
| Compatible Delivery Catheter | 1.7-4.0Fr | 1.7-4.0Fr | Same |
| Radiopacity Method | Mixed with non-ionic contrast agent prior to injection | Mixed with non-ionic contrast agent prior to injection | Same |
| Method of Supply | Sterile and single use | Sterile and single use | Same |
| Shelf Life | 2 years | 2 years | Same |
| Sterilization | Moist heat and non-pyrogenic | Moist heat and non-pyrogenic | Same |
Both devices have the same intended use, and use the same embolization particle composition, vial sizes, and sterilization method. The minimum particle size for the proposed device (70 um) is smaller than the minimum particle size for the predicate device (100 µm). The size ranges indicated for UAE for the proposed device are different from the predicate device size range for UAE. The proposed device range (550-1100 um) is within the range listed for the predicate device (500-1200 um). The differences in the particle sizes does not raise different questions of safety and effectiveness.
9. Non-Clinical Test Conclusion
The device is subject to Guidance for Industry and FDA Staff - Class II Special Controls Guidance Document: Vascular and Neurovascular Embolization Devices issued on December 29, 2004. The safety and effectiveness of the Sunsphere has been evaluated by non-clinical performance testing including:
Performance testing
The following specifications and performance testing were evaluated on the subject device:
- . Appearance
- Microsphere Compressibility .
- Microsphere Quantity in each Vial .
- Microsphere Size ●
- . Time in Suspension
- Catheter Deliverability ●
- Water Content per USP 39 NF 34 (2016) Loss on drying
- pH per USP 39 NF 34 (2016) ●
- Impurities and residual solvents per USP 39 NF 34
Above, all tests were passed and demonstrated the proposed devices can meet the product requirements.
9
Biocompatibility testing
The biocompatibility evaluation for the proposed device was conducted in accordance with FDA Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process", issued September 8, 2023. The following tests were conducted for Sunsphere, for a permanent implant device in contact with blood:
| Biological Endpoint | Test Method | Results |
|---|---|---|
| MTT Cytotoxicity Test | ISO 10993-5:2009 | Non-cytotoxic |
| ISO Guinea Pig Maximization | ||
| Sensitization Test | ISO 10993-10:2010 | Non-sensitizer |
| ISO Intracutaneous Study in | ||
| Rabbits | ISO 10993-10:2010 | Non-irritant |
| ISO Acute Systemic Toxicity | ||
| Study in Mice | ISO 10993-11:2017 | No mortality or evidence of systemic |
| toxicity | ||
| ASTM Hemolysis Study | ISO 10993-4:2017 | |
| ASTM F756:2017 | Non-hemolytic | |
| ASTM Partial Thromboplastin | ||
| Time | ASTM F2382:2018 | Non-activator |
| SC5b-9 Complement Activation | ||
| Assay | ISO 10993-4:2017 | Both the test article and the sponsor |
| provided control were considered to be | ||
| potential activators of the complement | ||
| system. | ||
| The test article was compared | ||
| statistically to the control and the test | ||
| article was lower than the control and | ||
| was statistically different. | ||
| USP Rabbit Pyrogen Study, | ||
| Material Mediated | ISO 10993-11:2017 | Non-pyrogenic |
| Genotoxicity Mouse | ||
| Lymphoma Assay | ISO 10993-3:2014 | Non-mutagenic |
| Biological Endpoint | Test Method | Results |
| Bacterial Reverse Mutation | ||
| Study | ISO 10993-3:2014 | Non-mutagenic |
| ISO Systemic Toxicity Study in | ||
| Rats Following | ||
| Subcutaneous Implantation, | ||
| 13 Weeks | ISO 10993-6:2016 | |
| ISO 10993-11:2017 | There was no evidence of systemic | |
| toxicity from the test article following | ||
| subcutaneous implantation in the rat. | ||
| Microscopically, the test article was | ||
| classified as causing minimal to no | ||
| reaction. | ||
| ISO Muscle Implantation Study | ||
| in Rabbits, 1 Week | ISO 10993-6:2016 | The macroscopic reaction was not |
| significant as compared to the negative | ||
| control article. | ||
| Microscopically, the test article caused a | ||
| minimal to no reaction as compared to | ||
| the negative control article. | ||
| ISO Muscle Implantation Study | ||
| in Rabbits, 4 Weeks | ISO 10993-6:2016 | The macroscopic reaction was not |
| significant as compared to the negative | ||
| control article. | ||
| Microscopically, the test article caused a | ||
| minimal to no reaction as compared to | ||
| the negative control article. | ||
| ISO Muscle Implantation Study | ||
| in Rabbits, 13 Weeks | ISO 10993-6:2016 | The macroscopic reaction was not |
| significant as compared to the negative | ||
| control article. | ||
| Microscopically, the test article caused a | ||
| minimal reaction as compared to the | ||
| negative control article. | ||
| ISO Muscle Implantation Study | ||
| in Rabbits, 26 weeks | ISO 10993-6:2016 | The macroscopic reaction was not |
| significant as compared to the negative | ||
| control article. | ||
| Microscopically, the test article caused | ||
| no reaction as compared to the negative | ||
| control article. | ||
| Biological Endpoint | Test Method | Results |
| Chronic Systemic Toxicity and | ||
| Carcinogenicity Evaluation | ISO 10993-18:2023 | A chemical characterization study and |
| toxicological risk assessment were used | ||
| to support chronic systemic toxicity and | ||
| carcinogenicity endpoints. The study was | ||
| based on chemical characterization | ||
| results and supported by information on | ||
| the Sunsphere materials of construction, | ||
| gathered toxicological data on these | ||
| materials. A toxicological risk | ||
| assessment was completed based on the | ||
| results from the chemical | ||
| characterization. |
10
11
Page 8 of 10
Chemical Characterization
Chemical characterization testing was conducted on Sunsphere in accordance with ISO 10993-18:2022. The testing consisted of exhaustive extraction of the microspheres in purified water, ethanol, and hexane. Extracts and normal saline were analyzed per Direct Injection Gas Chromatography Mass Spectrometry (DI-GCMS), Headspace Gas Chromatography Mass Spectrometry (HS-GC-MS), Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) and Inductively Coupled Plasma Mass Spectrometry (ICP-MS) screening analysis.
Toxicological Risk Assessment
The toxicological risk assessment was performed to address the chronic systemic toxicity and carcinogenicity end point. For each detected compound, a toxicological risk assessment was conducted in accordance with ISO 10993-17: 2002 and ISO/TS 21726: 2019. The toxicological risk assessment was conducted on the detected compounds from the chemical characterization study. The amount of each detected compound is below the threshold of toxicological concern (TTC) value. The appropriate uncertainty factors are used to derive the tolerable intake (TI) limit as recommended in ISO 10993-17:2002. The results demonstrated that the margins of safety (MoS) for potential chemical exposures represented a low risk of chronic toxicity and carcinogenicity. The Sunsphere is not expected to raise an unacceptable toxicity risk to the exposed patients when used as intended.
Sterility, Shipping, and Shelf -life
The proposed device is sterilized by moist heat steam which under validated parameters (121°C, 30 minutes) after sealing the vials to achieve a sterility assurance level (SAL) of 106 in accordance with USP and
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ISO 17665:2015. Bacterial Endotoxin Levels were below the level of 0.5 EU/ml in accordance with USP . Both baseline and accelerated shelf life testing were conducted demonstrating the device will perform as intended to support the proposed 2 year shelf-life.
- Package integrity test after environmental conditioning, simulated transportation testing in accordance . to ASTM D4169-22 on final, packaged, and sterile device.
- . Sterile Barrier Packaging performed on the proposed device:
- Dye penetration ASTM F1929-15 O
- Shelf-life of 2-years is validated using FDA recognized standard ASTM F1980 -21 Standard Guide for ● Accelerated Aging of Sterile Barrier Systems for Medical Devices.
Animal Performance Testing Conclusion
This study simulated the clinical use of Sunsphere and performed partial embolization of the right renal artery of healthy domestic pigs by interventional surgical procedures. The test article was Sunsphere, with particle size of 90 um; the control article was the cleared predicate device 8Spheres (polyviny) alcohol embolic microspheres - colorless), with particle size of 100 ~ 300 µm. The efficacy was evaluated by investigating the delivery performance, embolization effect immediate and within the study cycle. The test article in the study cycle was evaluated by investigating the postoperative animal recovery, clinical pathology, local embolization, gross anatomical observation, and systemic histopathological results at postoperative timepoints of 3, 8 and 28 days after embolization.
No clinically relevant intraoperative, postoperative, hematologic, coagulation, or major organ abnormalities other than the right kidney occurred. Among the serum biochemical parameters, the alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the test group and the control group were slightly increased in the short term after surgery, but there was no significant difference between the two groups and no physiological abnormality was reached. Histopathology results showed only a small microsphere shift and secondary tissue response in the upper pole of the right kidney on Day 8, but there was no significant difference between the test group and control group, and its severity and extent of involvement were very mild. Overall, the lower pole of the right kidney in the test group and control group presented similar gross lesions and histopathological features. Vascular changes and necrosis were observed to be equivalent in the test group on Day 8 and Day 29, consistent with the equivalent long term embolization performance results of test article. In conclusion, compared with the control article demonstrated efficacy and safety equivalent to the predicate in this animal study.
10. Conclusion
As described above, the subject devices have intended use as the predicate device. The differences in technological characteristics between the subject devices and the predicate do not raise different questions of safety and effectiveness. To evaluate the impact of the technological differences, performance testing was conducted as described above. The testing demonstrate that the subject devices, Sunsphere, is
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as safe and effective as the predicate device and supports a determination of substantial equivalence.