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 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 resorb 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.

AI/ML Overview

This document describes the regulatory submission for Elute, Inc.'s EP Granules™ BVF, a resorbable calcium salt bone void filler. The submission aims to demonstrate substantial equivalence to predicate devices. Here's an analysis of the acceptance criteria and study data:

Unfortunately, the provided document does not contain a table of acceptance criteria and reported device performance for quantitative metrics. Instead, it states that "All necessary verification steps met pre-determined acceptance criteria to confirm safety and effectiveness" and "All data met pre-determined acceptance criteria" for functional/safety testing. This indicates that while acceptance criteria were established and met, the specific values or thresholds are not detailed in this excerpt.

However, based on the provided text, we can infer the types of criteria and studies involved:

Acceptance Criteria and Device Performance (Inferred from Document)

Since specific numerical acceptance criteria and reported performance values are not present, this table will reflect the types of criteria and the general statement of compliance.

Acceptance Criteria Category	Specific Test/Evaluation	Reported Device Performance (as stated in document)
Functional Performance	In-vitro degradation and surface characterizations	Met pre-determined acceptance criteria
	X-ray diffraction (XRD)	Met pre-determined acceptance criteria
	Compressive mechanical testing	Met pre-determined acceptance criteria
	In-vitro pH exposure study	Met pre-determined acceptance criteria
Biocompatibility	Cytotoxicity (ISO 10993-1)	Met pre-determined acceptance criteria
	Sensitization (ISO 10993-1)	Met pre-determined acceptance criteria
	Irritation/ Intracutaneous Toxicity (ISO 10993-1)	Met pre-determined acceptance criteria
	Systemic Toxicity (Material-Mediated pyrogenicity)	Met pre-determined acceptance criteria
	Sub-Acute Toxicity	Met pre-determined acceptance criteria
	Genotoxicity	Met pre-determined acceptance criteria
	Implant Study	Met pre-determined acceptance criteria
	Bacterial Endotoxin (LAL - Pyrogenicity)	Met pre-determined acceptance criteria
Pre-Clinical Safety	Critical size defect model (Large animal models)	Met pre-determined acceptance criteria
Risk Management	Assessment within Elute's Risk Management and Design Controls systems	All necessary verification steps met pre-determined acceptance criteria

Study Details

Sample size used for the test set and the data provenance:
- Test Set Sample Size: Not explicitly stated for any of the individual tests. The document broadly refers to "bench-top testing" and "pre-clinical testing."
- Data Provenance:
  - Bench-top testing: In-vitro (laboratory).
  - Pre-Clinical Testing: "Large animal models." The country of origin for the animal study is not specified. Given the company's location in Salt Lake City, Utah, it is likely the study was conducted in the USA, but this is not confirmed.
  - Biocompatibility testing: In-vitro and in-vivo (animal; e.g., for sensitization, irritation, systemic toxicity, sub-acute toxicity, implant study).
Number of experts used to establish the ground truth for the test set and the qualifications of those experts: Not applicable. This device is a bone void filler, and its performance is evaluated through material science, biological compatibility, and animal model studies, not through expert interpretation of images or other data where "ground truth" is established by human experts. The data are objective measurements or observations from laboratory and animal experiments.
Adjudication method for the test set: Not applicable for this type of device and study. Adjudication methods like 2+1 or 3+1 are typically used for studies involving human interpretation of medical images or data.
If a multi-reader multi-case (MRMC) comparative effectiveness study was done: No. MRMC studies are used for evaluating diagnostic devices, particularly those involving human interpretation (e.g., radiologists reading images). This device is a bone void filler, and its effectiveness is determined by its properties, resorption, and bone regeneration in animal models and clinical use (though clinical data is not detailed in this excerpt).
If a standalone (i.e., algorithm only without human-in-the-loop performance) was done: Not applicable. This is a medical device (bone void filler), not an algorithm or AI system.
The type of ground truth used (expert consensus, pathology, outcomes data, etc.):
- Bench-top Testing: Objective measurements from laboratory equipment (e.g., XRD patterns, compressive strength, pH measurements, degradation rates against known standards).
- Biocompatibility Testing: Standardized biological assays and observations from animal studies (e.g., cell viability, immune response, tissue reaction, pyrogenicity) compared to established toxicity profiles or controls.
- Pre-Clinical Testing (Large animal models): Histological analysis, imaging (if performed), and gross pathology to assess bone regeneration, integration, and resorption in the "critical size defect model" compared to control groups or expected healing patterns. This often involves pathology and outcomes data from the animal models.
The sample size for the training set: Not applicable. This document pertains to a physical medical device, not a machine learning model that requires a training set.
How the ground truth for the training set was established: Not applicable, as there is no training set for this type of device.

Summary

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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 (DICE@fda.hhs.gov) or phone (1-800-638-2041 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)

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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K180853 510(k) Summary

Submitter:	Elute, Inc.
Contact Person:	AK Khandkar, PhD - CEO417 Wakara Way. Suite 3510Salt Lake City, UT 84108801-696-4716
Date Prepared:	March 29, 2018
Trade Name:	EP Granules™ BVF
Classification Name:	Resorbable calcium salt bone void filler device21 CFR §888.3045, Product Code MQV, Class II
Predicate Device(s):	K990131, ProOsteon 500R bone graft substitute (1º predicate);K082073, Actifuse Flow bone graft substitute (additionalpredicate)

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:

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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(K990131)	Additional Predicate(K082073)
Device Name	EP Granules™ BVF	Pro Osteon 500 R BoneGraft Substitute	Actifuse Flow BoneGraft Substitute
Intended Use	Bone Graft Substitute	Bone Graft Substitute	Bone Graft Substitute
Indicationsfor use	EP Granules™ BVF is animplant intended to fillbony voids or gaps of theskeletal system (i.e., theextremities and pelvis).These osseous defectsare surgically created orthe result of traumaticinjury to the bone and arenot intrinsic to the stabilityof the bony structure. EPGranules™ BVF resorbsand is replaced with boneduring the healingprocess.	Pro Osteon 500 RResorbable Bone GraftSubstitute is indicated onlyfor bony voids or gaps thatare not intrinsic to thestability of the bonystructure. Pro Osteon 500R is indicated to be gentlypacked into bony voids orgaps of the skeletalsystem (i.e., theextremities and pelvis).These defects may besurgically created osseousdefects or osseousdefects created fromtraumatic injury to thebone. The productprovides a bone graftsubstitute that resorbs andis replaced with boneduring the healingprocess.	Actifuse Flow is intendedonly for orthopaedicapplications as filler forgaps and voids that arenot intrinsic to the stabilityof the bony structure.Actifuse Flow Bone GraftSubstitute can be injectedinto bony voids or gaps ofthe skeletal system, i.e.,extremities and pelvis withappropriate stabilizinghardware. These defectsmay be surgically createdosseous defects orosseous defects createdfrom traumatic injury to thebone. The productprovides bone void fillerthat resorbs and isreplaced by bone duringthe healing process.
Prescription(Rx Only)	Yes	Yes	Yes
Classification	Orthopedic Devices-Resorbable Calcium SaltBone Void Filler21 CFR §888.3045,Product code: MQVClass II	Orthopedic Devices-Resorbable Calcium SaltBone Void Filler21 CFR §888.3045,Product code: MQVClass II	Orthopedic Devices-Resorbable Calcium SaltBone Void Filler21 CFR §888.3045,Product code: MQVClass II
Anatomicalsite	Within voids or gaps thatare not intrinsic to thestability of the bonystructure.	Within voids or gaps thatare not intrinsic to thestability of the bonystructure.	Within voids or gaps thatare not intrinsic to thestability of the bonystructure.
Where Used	Operating Room orSurgical Suite	Operating Room orSurgical Suite	Operating Room orSurgical Suite
Morphology	Granules and croutons ofcalcium salts withresorbable polymer binder	Particles, granules &blocks of calcium salts	Hydrated putty of calciumsalt granules withresorbable polymer binder
FundamentalScientificTechnology	Once implantation, theceramic hydroxyapatiteand calcium carbonateparticles slowly resorbover time, allowing for newbone growth.	Once implanted, thecalcium phosphate outerlayer will slowly resorb,delaying exposure of theunderlying and fasterresorbing calciumcarbonate	Once implantedresorbable polymers bindand deliver osteo-conductive calcium saltparticles to be used as abone void filler
Sterilization	Gamma irradiation	Gamma irradiation	Provided Sterile, MethodUnknown
Bioactivity	Osteo-conductive	Osteo-conductive	Osteo-conductive &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.

Regulation Number and Section

§ 888.3045 Resorbable calcium salt bone void filler device.

(a)
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.(b)
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.