SIGNAFUSE Bioactive Bone Graft is a bone graft substitute intended for use in bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure. These osseous defects may be surgically created or result from traumatic injury to the bone. SIGNAFUSE Bioactive Bone Graft is indicated to be combined with autologous bone marrow aspirate and packed into osseous defects of the extremities, pelvis and posterolateral spine. When used in the posterolateral spine, SIGNAFUSE Bioactive Bone Graft is to be used as an autograft extender. The device resorbs and is replaced by host bone during the healing process.

Device Description

SIGNAFUSE Bioactive Bone Graft is a bioactive bone graft substitute comprising biphasic mineral granules and 4555 bioactive glass suspended in a porous type I collagen matrix. The device is provided sterile and is to be combined with autologous bone marrow aspirate prior to use to facilitate packing into bony defects. The device provides an osteoconductive scaffold that resorbs and guides host bone regeneration during the healing process.

AI/ML Overview

The provided text describes the regulatory clearance of a medical device, SIGNAFUSE Bioactive Bone Graft, and not a software-driven AI/ML medical device. Therefore, the information required to answer the specific questions about acceptance criteria, study design for AI/ML performance (e.g., sample size for test/training sets, expert adjudication, MRMC studies, standalone performance, ground truth establishment) is not present in the provided document.

The document focuses on the substantial equivalence of the SIGNAFUSE Bioactive Bone Graft to existing predicate devices based on its intended use, materials, and performance in a rabbit model.

However, I can extract the information that is relevant to the device's performance assessment as described in the document, which pertains to its biological and physical characteristics rather than an AI/ML algorithm.

Here's what can be inferred about the "acceptance criteria" and "study that proves the device meets the acceptance criteria" in the context of this specific bone graft device:

Acceptance Criteria and Device Performance (for SIGNAFUSE Bioactive Bone Graft - a physical device)

The acceptance criteria for this physical device are primarily related to its biocompatibility, sterility, shelf-life, and in vivo performance (osteoconductivity and resorption) comparable to a predicate device.

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria Category	Specific Criteria	Reported Device Performance
Biocompatibility	Meets ISO 10993 requirements.	SIGNAFUSE Bioactive Bone Graft has met the ISO 10993 biocompatibility requirements.
Bacterial Endotoxin	Meets ANSI/AAMI ST72 bacterial endotoxin requirements.	SIGNAFUSE Bioactive Bone Graft has met the ANSI/AAMI ST72 bacterial endotoxin requirements relevant to bone void filler devices.
Raw Material Sourcing (Bovine Collagen)	Controls on sourcing, collection, and handling meet ISO 22442-2 and ISO 22442-3.	Identical to MCP Bone Putty, meeting ISO 22442-2 and ISO 22442-3 requirements.
Sterilization	Terminal sterilization via gamma irradiation; validated to SAL of 10^-6 according to ANSI/AMMI/ISO 11137-2 (Method VDmax).	Terminally sterilized via gamma irradiation and validated to a sterility assurance level (SAL) of 10^-6 according to ANSI/AMMI/ISO 11137-2 (Method VDmax).
Shelf-life	3 years.	Shelf-life of 3 years.
In Vivo Performance (Osteoconductivity & Resorption)	Biological safety and normal osteoconductive healing characteristics; substantially equivalent in vivo performance to primary predicate (MCP Bone Putty) in an established posterolateral spine fusion rabbit defect model.	Results confirm biological safety and normal osteoconductive healing characteristics; demonstrate substantially equivalent in vivo performance to the primary predicate MCP Bone Putty (K160446) in an established posterolateral spine fusion rabbit defect model (Boden, ASTM F2307-17).
Physical/Chemical Characterization	Fully characterized to meet current MCP Bone Putty specifications (other than strip dimensions and HA/B-TCP content).	SIGNAFUSE Bioactive Bone Graft formulation has been fully characterized to meet the current MCP Bone Putty specifications other than strip dimensions and HA/B-TCP content.
Compositional Ratio	Overall collagen to particulate ratio remains the same as MCP Bone Putty.	The overall collagen to particulate ratio remains the same between the subject device and the MCP Bone Putty.

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

Test Sample Size: Not explicitly stated for the rabbit model. The document mentions "a posterolateral spine fusion rabbit model" and "testing performed in K160446," implying a set of rabbits were used, but no specific count is provided.
Data Provenance: The study was an in vivo animal study based on a "posterolateral spine fusion rabbit model," indicating animal data. The location/country of the study is not specified in the provided text. It was a comparative study ("in comparison to the MCP Bone Putty predicate device, as well as a control group").

3. Number of Experts Used to Establish Ground Truth and Qualifications:

Not applicable / Information not provided. This device is a physical bone graft, not an AI/ML algorithm requiring human expert review for ground truth establishment. The ground truth for its performance is based on in vivo animal histology, imaging, or physical outcomes (e.g., fusion success), evaluated by researchers/veterinarians, not by human radiologists/experts determining image-based diagnoses for an AI.

4. Adjudication Method for the Test Set:

Not applicable / Information not provided. Adjudication methods (like 2+1, 3+1) are typically used in clinical studies for diagnostic accuracy, especially with human readers or AI outputs, where there might be disagreement in interpretations. This is not relevant for the in vivo animal study described for a physical bone graft.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, and its effect size:

No. An MRMC study is designed to assess the diagnostic performance of human readers, often with and without AI assistance, across multiple cases. This is irrelevant for evaluating a physical medical device like a bone graft.

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

No. This refers to AI algorithm performance. SIGNAFUSE Bioactive Bone Graft is a physical device, so this question is not applicable.

7. The Type of Ground Truth Used:

Animal study outcomes: The performance was evaluated using an "established posterolateral spine fusion rabbit defect model (Boden, ASTM F2307-17)." This implies that the ground truth for in vivo performance was based on biological outcomes observed in the rabbits, likely through histological analysis, radiography, or other methods specific to bone fusion assessment in animal models. It is a biological/physiological ground truth.

8. The Sample Size for the Training Set:

Not applicable. This device is not an AI/ML algorithm, therefore, there is no "training set" in the context of machine learning.

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

Not applicable. As above, there is no "training set" for an AI/ML algorithm.

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.

Bioventus % Christine Scifert Exec VP MRC-X, LLC 6075 Poplar Ave Memphis, Tennessee 38119

Re: K193513

Trade/Device Name: SIGNAFUSE Bioactive Bone Graft Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV Dated: May 20, 2020 Received: May 22, 2020

Dear Ms. Scifert:

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. 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/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.

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

June 18, 2020

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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/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 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 https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-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-regulatoryassistance/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,

Jesse Muir, Ph.D. Acting Assistant Director DHT6C: Division of Restorative, Repair, and Trauma Devices OHT6: Office of Orthopedic Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known)

K193513

Device Name SIGNAFUSE Bioactive Bone Graft

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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510(k) Summary

SIGNAFUSE Bioactive Bone Graft December 16, 2019

Company:	Bioventus4721 Emperor Blvd, Suite 100Durham, NC 27700USA
Primary Contact:	Christine Scifert, Exec VP of MRC-X, LLC
Company Contact:	Kim Patterson Kelly, Senior Director, Regulatory & Clinical Affairs
Trade Name:	SIGNAFUSE Bioactive Bone Graft
Common Name:	Filler, Bone Void, Calcium Compound
Classification:	Class II
Regulation Number:	21 CFR 888.3045 (Resorbable calcium salt bone void filler device)
Panel:	Orthopedic
Product Code:	MOV

Device Description:

Indications for Use:

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Substantial Equivalence:

The subject device is substantially equivalent to the following predicate devices:

Primary Predicate:

MCP Bone Putty, Bioventus, K160446 (S.E 11/7/2016)
Secondary Predicate:
Interface Bone Void Filler, Bioventus, K112857 (S.E 12/13/2011)
The subject device is for filling of bony voids or gaps of the skeletal system not intrinsic to the stability of the bony structure, like the predicate devices. The subject device is identical in indications and principle of operation to both predicate devices. The subject device contains the same materials used in the predicate devices, but the materials are present in different ratios than in the predicate devices. However, the overall collagen to particulate ratio remains the same between the subject device and the MCP Bone Putty. The geometrical differences between the subject device and the MCP Bone Putty result in more choices of graft volume to allow treatment of different size defects, but do not change the ratio of components within the device.

Performance Testing:

SIGNAFUSE Bioactive Bone Graft is a change to the manufacturer's (Bioventus) own predicate device, MCP Bone Putty (K160446, S.E 11/7/2016) to add bioactive glass (Interface Bone Void Filler, K112857, S.E. 12/13/2011) to the formulation. The SIGNAFUSE Bioactive Bone Graft formulation has been fully characterized to meet the current MCP Bone Putty specifications other than strip dimensions and HA/B-TCP content.

SIGNAFUSE Bioactive Bone Graft has met the ISO 10993 biocompatibility requirements and ANSI/AAMI ST72 bacterial endotoxin requirements relevant to bone void filler devices. The controls on sourcing, collection, and handling of the bovine collagen raw materials used in the manufacture of the SIGNAFUSE are identical to MCP Bone Putty and meet requirements of ISO 22442-2 and ISO 22442-3.

SIGNAFUSE Bioactive Bone Graft is terminally sterilized via gamma irradiation and validated to a sterilityassurance level (SAL) of 10 • according to ANSI/AMMI/ISO 11137-2 (Method VDwax) with a shelf-life of 3 years.

To ensure that the device still functions as intended, SIGNAFUSE Bioactive Bone Graft was evaluated in a posterolateral spine fusion rabbit model in comparison to the MCP Bone Putty predicate device, as well as a control group. The model and method used was identical to the testing performed in K160446 to gain clearance for MCP Bone Putty. Results confirm the biological safety and normal osteoconductive healing characteristics associated with the SIGNAFUSE Bioactive Bone Graft and demonstrate substantially equivalent in vivo performance to the primary predicate MCP Bone Putty (K160446, 11/7/2016) in an established posterolateral spine fusion rabbit defect model (Boden, ASTM F2307-17).

Conclusion:

Performance testing and technological comparisons presented in this 510(k) indicate SIGNAFUSE Bioactive Bone Graft is substantially equivalent to the predicate devices.

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.