BioSphere MIS Putty is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. BioSphere MIS Putty is indicated to be gently packed into bony voids or gaps of the skeletal system as a bone void filler in the extremities and pelvis, and as a bone graft extender in the posterolateral spine. These defects may be surgically created osseous defects created from traumatic injury to the bone. The product provides a bone void filler that resorbs and is replaced with bone during the healing process.

Device Description

BioSphere MIS Putty ("BioSphere MIS") is an osteoconductive, bioactive bone void filler that, like its predicate device, is composed primarily of medical-grade 4555 bioactive glass particles. The composition and formula of this material is unchanged and is identical to that used in the BioSphere Putty predicate. The bioactive glass is mixed with an inert, moldable carrier using the exact same composition and formula as used in the predicate device.

The only difference between the two devices is that BioSphere MIS Putty is supplied in a prefilled cannula with a delivery gun to aid with placement into certain types of bony voids that are otherwise difficult to reach. The manner in which the device is delivered to the target site does not play any role in the putty achieving its intended clinical purpose (i.e., supporting bone regeneration).

Upon implantation of BioSphere MIS Putty into the target site, the carrier is absorbed by the site and the remaining bioactive glass particles provide an osteoconductive surface for bone formation. The bioactive glass particles are supplied in a spherical form, and the natural packing of the spheres creates 3-dimensional, interconnected porosity that allows for bone regeneration throughout the defect site. This is the same mechanism of action as with the predicate. In the posterolateral spine, BioSphere MIS Putty can be combined with autograff as a bone graft extender in the same manner as the predicate BioSphere Putty.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called "BioSphere MIS Putty". The purpose of this 510(k) is to modify the existing BioSphere Putty (predicate device) by changing its delivery mechanism from an open bore syringe to a pre-filled cannula with a delivery gun.

Based on the information provided, here's an analysis of the acceptance criteria and the study that proves the device meets those criteria:

1. Table of Acceptance Criteria and Reported Device Performance:

The document does not explicitly state "acceptance criteria" in a quantitative format as would typically be found in a clinical study report. Instead, it describes performance characteristics that were tested to demonstrate the device's functionality with the new delivery system. The goal of these tests was to show that the new delivery mechanism does not negatively impact the device's safety or effectiveness, and that the device remains "substantially equivalent" to its predicate.

Test / Performance Characteristic	Acceptance Criteria (Implied)	Reported Device Performance
Putty Extrusion (Reproducibility)	Consistent and reproducible amount of putty dispensed per trigger pull.	The results showed that the delivery gun was able to extrude a reproducible amount of putty for each trigger pull.
Putty Extrusion (Temperature Effects)	Effective extrusion regardless of putty temperature (room temp, refrigerated).	Extrusion was evaluated with room temperature and refrigerated samples to mimic colder operating room temperatures. The delivery gun was effective in extruding putty from the cannula regardless of putty temperature.
Putty Extrusion (Blocked Cannula)	Effective extrusion even if the cannula is partially blocked.	Extrusion was evaluated with an open and partially blocked cannula end. The delivery gun was able to extrude the putty through a partially blocked end.
Cannula Integrity (3-point bending)	Cannulas should preferentially fail through plastic deformation (buckling/bending) and not critically fail resulting in fracture pieces or broken edges.	A 3-point bending test was used to demonstrate that the cannulas did not critically fail resulting in fracture pieces or broken edges. All cannulas preferentially failed through plastic deformation, as seen by buckling and bending of the cannula.
Delivery Gun Assembly (Stability)	Cannula is easily attached and a stable attachment is maintained during putty extrusion.	A qualitative assessment of the delivery gun assembly showed that the cannula was easily attached and a stable attachment was maintained during putty extrusion.
Biocompatibility (Cytotoxicity)	Non-cytotoxic.	Confirmatory testing of the BioSphere MIS Putty components showed the product was non-cytotoxic.
Biocompatibility (Endotoxin Levels)	Acceptable endotoxin levels.	Confirmatory testing of the BioSphere MIS Putty components showed the product had acceptable endotoxin levels.

2. Sample Size Used for the Test Set and Data Provenance:

The document does not specify exact numerical sample sizes for each test. For example, it says "measuring the dispensed putty amount following each pull of the delivery gun trigger" and "evaluating with room temperature and refrigerated samples". It also refers to "A 3-point bending test" and "Confirmatory testing" but without detailing the number of units tested.

The data provenance is not explicitly stated. However, given that these are performance tests conducted by the manufacturer for regulatory submission, it is assumed to be prospective testing performed in a laboratory setting. There is no information regarding country of origin for the data that would be relevant to clinical studies (e.g., patient data).

3. Number of Experts Used to Establish the Ground Truth for the Test Set and Their Qualifications:

This submission does not involve clinical data or "ground truth" established by experts in the context of diagnostic accuracy. The tests described are engineering and material characterization tests of the device's physical and biological properties. Therefore, there were no experts used to establish ground truth in this context. The "ground truth" for these tests would be the measured physical and chemical properties themselves against predefined specifications.

4. Adjudication Method for the Test Set:

Not applicable. As noted above, this submission involves engineering and material characterization tests, not human-based assessments requiring adjudication.

5. 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 device is a bone void filler and does not involve "human readers" or "AI assistance". It's a medical implant/material.

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

Not applicable. This is not an AI/algorithm-based device.

7. The Type of Ground Truth Used:

The "ground truth" for the performance tests described is based on engineering specifications, material science standards, and established biocompatibility testing protocols. For example, the non-cytotoxicity test would have a defined standard (e.g., ISO 10993) that dictates what constitutes a "non-cytotoxic" result. Similarly, "reproducible amount," "effective extrusion," and "preferentially failed through plastic deformation" would be evaluated against internal design specifications and industry best practices for device performance.

8. The Sample Size for the Training Set:

Not applicable. This is not an AI/machine learning device that requires a training set.

9. How the Ground Truth for the Training Set was Established:

Not applicable, as there is no training set.

Summary

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January 19, 2018

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

Re: K173301

Trade/Device Name: BioSphere MIS Putty (BioSphere MIS) Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV Dated: December 22, 2017 Received: December 22, 2017

Dear Mr. Prebula:

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

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manufacturing practice requirements as set forth in the quality systems (OS) regulation (21 CFR Part 820); 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 the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

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.

Katherine D. Kavlock -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: January 31, 2017 See PRA Statement on last page

510(k) Number (if known)

K173301

Device Name:

BioSphere MIS Putty (BioSphere MIS)

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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FORM FDA 3881 (8/14)

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510(k) Summary BioSphere® MIS Putty

1. Submitter Information:

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

Date Prepared: December 22, 2017

2. Contact Information:

Randy Prebula Hogan Lovells US LLP 555 Thirteenth Street, NW Washington, DC 20004

3. Device Name and Classification:

Product Name:	BioSphere MIS Puttv
Common Name:	Bone Void Filler
Classification Regulation:	21 CFR § 888.3045
Classification Name:	Resorbable Calcium Salt Bone Void Filler Device
Classification Panel:	Orthopedic
Product Code:	MQV
Device Class:	Class II

4. Predicate Device:

BioSphere Putty (K140844, K122868)

5. Device Description and Summary of Technological Characteristics:

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6. Intended Use / Indications for Use:

BioSphere MIS Putty is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. BioSphere MIS Putty is indicated to be gently packed into bony voids or gaps of the skeletal system as a bone void filler in the extremities and pelvis, and as a bone graft extender in the posterolateral spine. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone. The product provides a bone void filler that resorbs and is replaced with bone during the healing process.

7. Purpose of 510(k):

The purpose of this 510(k) is to modify the BioSphere Putty (K140844) by supplying the final putty formulation pre-filled in a cannula, with a delivery qun, instead of in an open bore syringe. This modification is being made to enhance access of the device to bony voids or gaps that are within the cleared predicate's indications for use, but were previously difficult to reach - namely, deep graft sites and graft sites resulting from minimally invasive surgery.

8. Performance Data:

BioSphere MIS Putty was characterized by a variety of quantitative tests and qualitative assessments.

. Putty extrusion was evaluated by measuring the dispensed putty amount following each pull of the delivery gun trigger. The results showed that the delivery gun was able to extrude a reproducible amount of putty for each trigger pull.
- o Assessments of putty extrusion were also conducted using room temperature and refrigerated samples to mimic colder operating room temperatures. Additionally, extrusion was evaluated with an open and partially blocked cannula end. The delivery gun was effective in extruding putty from the cannula regardless of putty temperature, and was able to extrude the putty through a partially blocked end.
. A 3-point bending test was used to demonstrate that the cannulas did not critically fail resulting in fracture pieces or broken edges. All cannulas preferentially failed through plastic deformation, as seen by buckling and bending of the cannula.
. A qualitative assessment of the delivery gun assembly showed that the cannula was easily attached and a stable attachment was maintained during putty extrusion.
o Confirmatory testing of the BioSphere MIS Putty components showed the product was non-cytotoxic and had acceptable endotoxin levels.

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9. Conclusion:

BioSphere MIS Putty is as safe and effective as the predicate device. BioSphere MIS Putty has the same intended uses and similar indications, technological characteristics, and principles of operation as its predicate device. The only difference between the modified device and the cleared predicate (change in delivery mechanism from an open bore syringe to a cannula with delivery gun) does not impact its function as a bone void filler and raise no new issues of safety or effectiveness. Thus, BioSphere MIS Putty is substantially equivalent to the predicate.

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.