BioSphere Flex is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. BioSphere Flex is indicated to be gently packed into bony voids or gaps of the skeletal system (i.e., the extremities and pelvis). These defects may be surgically created osseous defects created from traumatic injury to the bone. BioSphere Flex must be hydrated with autogenous bone marrow prior to implantation. The product provides a bone void filler that resorbs and is replaced with bone during the healing process.

Device Description

BioSphere Flex is a sterile, single-use resorbable bone void filler that is composed of porous bioactive glass granules suspended in a carrier. BioSphere Flex utilizes 45S5 bioactive glass, which has been shown to be osteoconductive and bioactive. The carrier is composed of a porous scaffold of collagen and sodium hyaluronate. BioSphere Flex has the ability to absorb fluid such as bone marrow aspirate and becomes flexible following hydration. Following implantation into the target site, BioSphere Flex supports bone formation through the porosity of the implant and on the surface of the bioactive glass granules. As the materials resorb, the device is eventually replaced by host bone. BioSphere Flex is provided in a variety of forms.

AI/ML Overview

This document describes the BioSphere Flex, a resorbable bone void filler. The information provided is based on a 510(k) summary, which focuses on demonstrating substantial equivalence to a predicate device rather than presenting a detailed study design with specific acceptance criteria and performance against those criteria in a tabular format as you requested.

Therefore, many of the specific questions you asked about acceptance criteria and study details cannot be directly answered from the provided text. The document primarily discusses the types of tests performed and the conclusions drawn regarding substantial equivalence.

Here's an attempt to extract and infer information relevant to your questions, along with explicit statements where information is not available:

1. A table of acceptance criteria and the reported device performance

No explicit table of acceptance criteria or specific quantitative performance metrics are provided in the regulatory summary. The summary focuses on demonstrating equivalence to predicate devices rather than meeting predefined numerical acceptance criteria against a specific benchmark.

Acceptance Criterion	Reported Device Performance
Biocompatibility	Meets ISO 10993 standards and recommended endotoxin limits.
Bioactivity	Demonstrated hydroxyapatite formation on the surface of bioglass components following exposure to simulated body fluid. (Note: "This has not been correlated to human clinical use.")
Physical/Chemical Stability	Assessed various physical, chemical, and biological characteristics (density, hydration, handling properties, particle distribution, microstructure, particle weight, oxide content, crystallinity).
Osteoconductivity/Bone Formation	Had the same healing characteristics as the BioSphere Putty predicate (K122868) in an in vivo critical-sized sheep femoral defect model. Device is replaced by host bone.
Resorption	The product provides a bone void filler that resorbs and is replaced with bone during the healing process.
Handling Properties (Flexibility/Moldability)	Readily absorbs liquid and becomes flexible and moldable when fully hydrated (with autogenous bone marrow). Differences compared to predicate "do not alter the intended therapeutic/surgical use...and do not affect its safety or effectiveness".
Compositional Similarity	Same component composition (45S5 bioactive glass, collagen, hyaluronic acid), same porous particle size, same carrier, and similar bioactive glass amount as Kinex Bioactive (K130392). Same 45S5 bioactive glass component as BioSphere Putty (K122868).

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

Test Set Sample Size: For the in vivo critical-sized sheep femoral defect study, the exact sample size (number of sheep) is not specified.
Data Provenance: The in vivo animal study was conducted in a critical-sized sheep femoral defect, which can be inferred as a preclinical study. The origin country is not specified but is typically within the country of manufacture or a collaborating research institution. It is a prospective study in the sense that the animal model was specifically used to test the device.

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

This information is not provided. Ground truth in this context would likely be established through histological analysis and radiographic interpretation by veterinary pathologists/radiologists, but the number and qualifications are not detailed.

4. Adjudication method for the test set

This information is not provided.

5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done

No, a multi-reader multi-case (MRMC) comparative effectiveness study was not mentioned or implied. This type of study is more common for diagnostic imaging devices involving interpretation by multiple human readers. The BioSphere Flex is a therapeutic bone void filler.

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

This question is not applicable as the BioSphere Flex is a physical medical device, not an algorithm or AI software, and does not have a "standalone" or "human-in-the-loop" performance in the context of AI. Its performance is inherent in its material properties and biological interaction.

7. The type of ground truth used

For the in vivo animal study, the ground truth was established through:

Histology: Microscopic examination of tissue.
Histomorphometry: Quantitative analysis of tissue structure, likely measuring new bone formation, remaining biomaterial, etc.
Radiographic Analysis: X-ray and micro-CT imaging.

8. The sample size for the training set

This question is not applicable as this is a physical medical device and does not involve AI or machine learning algorithms that require a "training set."

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

This question is not applicable for the same reason as above.

Summary

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September 12, 2018

Synergy Biomedical % Randy Prebula Partner Hogan Lovells U.S. LLP 555 Thirteenth Street N.W. Washington, District of Columbia 20004

Re: K173424

Trade/Device Name: BioSphere Flex Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV Dated: August 10, 2018 Received: August 10, 2018

Dear Mr. Prebula:

We have reviewed vour Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrl/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal

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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) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; 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 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to 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,

Laurence D. Coyne -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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DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Indications for Use

Form Approved: OMB No. 0910-0120 Expiration Date: June 30, 2020 See PRA Statement on last page

510(k) Number (if known)

K173424

Device Name

BioSphere Flex

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)

区 Prescription Use (Part 21 CFR 801 Subpart D)

_ Over-The-Counter Use (21 CFR 801 Subpart C)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

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510(k) SUMMARY BioSphere Flex

Submitter

Synergy Biomedical, LLC 100 Springhouse Drive, Suite 108 Collegeville, PA 19426

Phone: 484-902-8141 Facsimile: 484-902-8179

Contact Person

Randy Prebula Hogan Lovells U.S. LLP 555 Thirteenth Street, NW Washington, DC 20004

Date Prepared: September 10, 2018

Name of Device: BioSphere Flex Common or Usual Name: Bioactive Bone Graft Classification Requlation: 21 C.F.R. § 888.3045, Bone Void Filler Device Class: Class II Product Code: MQV 510(k) Review Panel: Orthopedic

Predicate/Reference Devices

Primary Predicate: K122868 – BioSphere Putty (Synergy Biomedical, LLC) Reference Device: K130392 - Kinex Bioactive (Globus Medical, Inc)

Device Description

Intended Use / Indications for Use

BioSphere Flex is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. BioSphere Flex is indicated to be gently packed into bony voids or gaps of the

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skeletal system (i.e., the extremities and pelvis). These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. BioSphere Flex must be hydrated with autogenous bone marrow prior to implantation. The product provides a bone void filler that resorbs and is replaced with bone during the healing process.

The only difference between the BioSphere Flex indications for use and those cleared for the BioSphere Putty predicate is the requirement for hydration with autogenous bone marrow, obtained by aspiration, prior to implantation. This difference has no impact on the device's therapeutic purpose or ability to achieve its function as a bone void filler; it also does not affect the device's safety or effectiveness when used as labeled, because it merely serves to ensure that BioSphere Flex, which has a slightly different composition and configuration than the predicate, will still be sufficiently moldable/flexible to fit various sizes and shapes of bony Moreover. the reference device, Kinex Bioactive (K130392), has identical defects. indications for use to BioSphere Flex.

Summary of Technological Characteristics

BioSphere Flex is composed of the same 45S5 bioactive glass component as the predicate device, mixed with an inert carrier. In BioSphere Flex, the bioactive glass is in the form of porous granules composed of thermally bonded 45S5 bioactive glass spheres. The bioactive glass granules are suspended in a 3-dimensional, porous scaffold carrier composed of freezedried collagen and sodium hyaluronate. BioSphere Flex is designed to be mixed with autogenous bone marrow. The structure readily absorbs liquid and becomes flexible and moldable when fully hydrated.

BioSphere Flex and its predicates rely on the same technological principles for bone healing, When implanted, the device provides an osteoconductive environment for new bone formation. The porosity of BioSphere Flex allows it to support new bone formation throughout its structure and on the surface of the device. As natural healing progresses, the new bone remodels and the device is eventually replaced by host bone.

Performance Data

The device's physical characteristics and ability to function as intended were evaluated in bench and animal testing. In addition, BioSphere Flex was subjected to ISO 10993 biocompatibility testing and was shown to be biocompatible, including testing which demonstrated that the device meets recommended endotoxin limits.

Bench testing assessed various physical, chemical, and biological characteristics of the device, including density, hydration, handling properties, particle distribution, microstructure, particle weight, oxide content, crystallinity, and bioactivity. Bioactivity was assessed through demonstration of hydroxyapatite formation on the surface of the bioglass components following exposure to simulated body fluid. This has not been correlated to human clinical use. The results of Bioactive glass testing were compared against those from BioSphere Putty (K122868). Additionally, BioSphere Flex was determined to have the same component composition (45S5 bioactive glass, collagen, hyaluronic acid), same porous particle size, same carrier (porous collagen/hyaluronic acid), and a similar bioactive glass amount as Kinex Bioactive (K130392).

The ability of the device to support new bone formation was confirmed through in vivo testing in a critical-sized sheep femoral defect. In vivo testing, including x-ray and micro-CT

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radiographic analysis, histology, and histomorphometry, demonstrated that BioSphere Flex had the same healing characteristics as the BioSphere Putty predicate (K122868).

Conclusions

BioSphere Flex is as safe and effective as the predicate devices. BioSphere Flex has the same intended use and similar indications for use, technological characteristics, and principles of operation as its predicate devices. The minor differences in indications do not alter the intended therapeutic/surgical use of the device and do not affect its safety or effectiveness when used as labeled. Similarly, the minor technological differences between BioSphere Flex and the primary predicate, Biosphere Putty, raise no new issues of safety or effectiveness and are supported by similarities to the Kinex Bioactive reference device. Performance data further demonstrate that BioSphere Flex is as safe and effective as the identified predicates. Thus, BioSphere Flex is substantially equivalent.

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.