EP Granules™ BVF

K180853 · Elute, Inc. · MQV · Aug 6, 2018 · Orthopedic

Device Facts

• Record ID: K180853
• Device Name: EP Granules™ BVF
• Applicant: Elute, Inc.
• Product Code: MQV · Orthopedic
• Decision Date: Aug 6, 2018
• Decision: SESE
• Submission Type: Traditional
• Regulation: 21 CFR 888.3045
• Device Class: Class 2
• Attributes: Therapeutic

Intended Use

EP Granules™ BVF is an implant intended to fill bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These osseous defects are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. EP Granules™ BVF resorbs and is replaced with bone during the healing process.

Device Story

EP Granules™ BVF is an osteoconductive bone graft substitute. It consists of hydroxyapatite and calcium carbonate particles bound by a degradable polymer matrix (poly(caprolactone), poly(ethylene glycol), and poly(lactide-co-glycolide)). Supplied as sterile granules, the device is implanted by surgeons in an operating room or surgical suite to fill non-structural bony voids or gaps. Upon implantation, the device provides a scaffold for bone tissue infiltration; the ceramic particles and polymer binder resorb over time, allowing for replacement by new bone and soft tissue. The device benefits patients by facilitating bone healing in osseous defects.

Clinical Evidence

Bench-top testing included in-vitro degradation, surface characterization, X-ray diffraction (XRD), compressive mechanical testing, and pH exposure studies. Pre-clinical testing utilized a large animal critical size defect model under IACUC protocol. Biocompatibility testing was performed per ISO 10993-1 for permanent implant contact (>30 days), including cytotoxicity, sensitization, irritation, systemic toxicity, sub-acute toxicity, genotoxicity, and implant studies. Bacterial endotoxin (LAL) testing was also conducted.

Technological Characteristics

Osteoconductive bone void filler composed of hydroxyapatite and calcium carbonate particles in a poly(caprolactone), poly(ethylene glycol), and poly(lactide-co-glycolide) polymer matrix. Supplied as sterile granules. Sterilization via gamma irradiation. Operates via passive osteoconduction and gradual resorption.

Indications for Use

Indicated for filling surgically created or traumatic osseous defects in the skeletal system (extremities and pelvis) that are not intrinsic to bony structure stability.

Regulatory Classification

Identification

A resorbable calcium salt bone void filler device is a resorbable implant intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure.

Special Controls

*Classification.* Class II (special controls). The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA.” See § 888.1(e) of this chapter for the availability of this guidance.

Predicate Devices

• ProOsteon 500R bone graft substitute (K990131)
• Actifuse Flow bone graft substitute (K082073)

Submission Summary (Full Text)

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Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue.

Elute, Inc. Ashok Khandkar, PhD CEO 417 Wakara Way Suite 3510 Salt Lake City, Utah 84108

Re: K180853

Trade/Device Name: EP Granules™ BVF Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV Dated: June 29, 2018 Received: July 5, 2018

Dear Dr. Khandkar:

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);

U.S. Food & Drug Administration 10903 New Hampshire Avenue Silver Spring, MD 20993 www.fda.gov

August 6, 2018

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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 mediation-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 ([e-mail]) or phone [phone] or 301-796-7100).

Sincerely,

# Melissa Hall -S

For Mark N. Melkerson Director Division of Orthopedic Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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## Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: 06/30/2020 See PRA Statement below.

510(k) Number (if known) K180853

Device Name

EP Granules™ BVF

Indications for Use (Describe)

EP Granules™ BVF is an implant intended to fill bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These osseous defects are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. EP Granules™ BVF resorbs and is replaced with bone during the healing process.

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

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#### K180853 510(k) Summary

| Submitter: | Elute, Inc. |
|----------------------|-----------------------------------------------------------------------------------------------------------------------------------------|
| Contact Person: | AK Khandkar, PhD - CEO<br>417 Wakara Way. Suite 3510<br>Salt Lake City, UT 84108<br>801-696-4716 |
| Date Prepared: | March 29, 2018 |
| Trade Name: | EP Granules™ BVF |
| Classification Name: | Resorbable calcium salt bone void filler device<br>21 CFR §888.3045, Product Code MQV, Class II |
| Predicate Device(s): | K990131, ProOsteon 500R bone graft substitute (1º predicate);<br>K082073, Actifuse Flow bone graft substitute (additional<br>predicate) |

#### Device Description:

EP Granules™ BVF is an osteoconductive device comprising hydroxyapatite (HA) and calcium carbonate (CaCO3) and calcium chloride (CaCl2) particles bound together with a degradable polymer-based binding matrix of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG), and poly(lactide-co-glycolide) (PLGA). The hydroxyapatite and calcium carbonate particles are dispersed throughout the entire structure of the device. Upon implantation, the ceramic hydroxyapatite and calcium carbonate particles resorb over time. The polymer-based binding matrix also resorbs over time. It is supplied sterile in a granulated form of various sizes. When EP Granules™ BVF is placed in direct contact with viable non-infected bone, porous regions form in the device and are infiltrated with bone tissue. Bone formation occurs in apposition to the hydroxyapatite and calcium carbonate surface and within the pores of the device. As the device resorbs, bone and soft tissue grow into the space previously occupied by the device.

## Indications For Use:

EP Granules™ BVF is an implant intended to fill bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These osseous defects are surgically created or the result of traumatic injury to the bone and are not intrinsic to the stability of the bony structure. EP Granules™ BVF resorbs and is replaced with bone during the healing process.

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#### Comparative Analysis:

lt has been demonstrated that the EP Granules™ BVF device is comparable to the predicate devices in intended use, fundamental scientific technology, design, principles of operation and functional performance evaluations. The EP Granules™ BVF device has been fully assessed within Elute's Risk Management and Design Controls systems. All necessary verification steps met pre-determined acceptance criteria to confirm safety and effectiveness.

| Technology Comparison of EP Granules™ BVF with Predicate Device: | | | |
|------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| | Subject Device – | 1° Predicate<br>(K990131) | Additional Predicate<br>(K082073) |
| Device Name | EP Granules™ BVF | Pro Osteon 500 R Bone<br>Graft Substitute | Actifuse Flow Bone<br>Graft Substitute |
| Intended Use | Bone Graft Substitute | Bone Graft Substitute | Bone Graft Substitute |
| Indications<br>for use | EP Granules™ BVF is an<br>implant intended to fill<br>bony voids or gaps of the<br>skeletal system (i.e., the<br>extremities and pelvis).<br>These osseous defects<br>are surgically created or<br>the result of traumatic<br>injury to the bone and are<br>not intrinsic to the stability<br>of the bony structure. EP<br>Granules™ BVF resorbs<br>and is replaced with bone<br>during the healing<br>process. | Pro Osteon 500 R<br>Resorbable Bone Graft<br>Substitute is indicated only<br>for bony voids or gaps that<br>are not intrinsic to the<br>stability of the bony<br>structure. Pro Osteon 500<br>R is indicated to be gently<br>packed into bony voids or<br>gaps of the skeletal<br>system (i.e., the<br>extremities and pelvis).<br>These defects may be<br>surgically created osseous<br>defects or osseous<br>defects created from<br>traumatic injury to the<br>bone. The product<br>provides a bone graft<br>substitute that resorbs and<br>is replaced with bone<br>during the healing<br>process. | Actifuse Flow is intended<br>only for orthopaedic<br>applications as filler for<br>gaps and voids that are<br>not intrinsic to the stability<br>of the bony structure.<br>Actifuse Flow Bone Graft<br>Substitute can be injected<br>into bony voids or gaps of<br>the skeletal system, i.e.,<br>extremities and pelvis with<br>appropriate stabilizing<br>hardware. These defects<br>may be surgically created<br>osseous defects or<br>osseous defects created<br>from traumatic injury to the<br>bone. The product<br>provides bone void filler<br>that resorbs and is<br>replaced by bone during<br>the healing process. |
| Prescription<br>(Rx Only) | Yes | Yes | Yes |
| Classification | Orthopedic Devices-<br>Resorbable Calcium Salt<br>Bone Void Filler<br>21 CFR §888.3045,<br>Product code: MQV<br>Class II | Orthopedic Devices-<br>Resorbable Calcium Salt<br>Bone Void Filler<br>21 CFR §888.3045,<br>Product code: MQV<br>Class II | Orthopedic Devices-<br>Resorbable Calcium Salt<br>Bone Void Filler<br>21 CFR §888.3045,<br>Product code: MQV<br>Class II |
| Anatomical<br>site | Within voids or gaps that<br>are not intrinsic to the<br>stability of the bony<br>structure. | Within voids or gaps that<br>are not intrinsic to the<br>stability of the bony<br>structure. | Within voids or gaps that<br>are not intrinsic to the<br>stability of the bony<br>structure. |
| Where Used | Operating Room or<br>Surgical Suite | Operating Room or<br>Surgical Suite | Operating Room or<br>Surgical Suite |
| Morphology | Granules and croutons of<br>calcium salts with<br>resorbable polymer binder | Particles, granules &<br>blocks of calcium salts | Hydrated putty of calcium<br>salt granules with<br>resorbable polymer binder |
| Fundamental<br>Scientific<br>Technology | Once implantation, the<br>ceramic hydroxyapatite<br>and calcium carbonate<br>particles slowly resorb<br>over time, allowing for new<br>bone growth. | Once implanted, the<br>calcium phosphate outer<br>layer will slowly resorb,<br>delaying exposure of the<br>underlying and faster<br>resorbing calcium<br>carbonate | Once implanted<br>resorbable polymers bind<br>and deliver osteo-<br>conductive calcium salt<br>particles to be used as a<br>bone void filler |
| Sterilization | Gamma irradiation | Gamma irradiation | Provided Sterile, Method<br>Unknown |
| Bioactivity | Osteo-conductive | Osteo-conductive | Osteo-conductive &<br>Osteo-stimulatory |

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#### Functional/Safety Testing:

The following functional tests were performed. All data met pre-determined acceptance criteria.

## · Bench-top Testing:

- In-Vitro degradation and surface characterizations of EP Granules™ BVF O formulation
- o X-ray diffraction (XRD) and compressive mechanical testing of EP Granules™ BVF formulation from an Accelerated Shelf-Life Study
- In-vitro pH exposure study of EP Granules™ BVF o
- Pre-Clinical Testing –Large animal models, i.e. as critical size defect model, under an IACUC approved protocol
- · Biocompatibility Per ISO 10993-1 for Implant Devices, Tissue/bone Contact, Permanent contact (> 30 days) including:
- Cytotoxicity ●
- Sensitization
- Irritation/ Intracutaneous Toxicity ●
- Systemic Toxicity (Material ● Mediated pyrogenicity)
- Sub-Acute Toxicity ●
- Genotoxicity
- Implant Study ●
- Bacterial Endotoxin (LAL -Pyrogenicity) ●

## Conclusion:

The EP Granules BVF device is substantially equivalent to the cited predicate devices. Additionally, the EP Granules BVF device met all acceptance criteria to confirm safety and effectiveness.