Synthecure Synthetic Calcium Sulfate is an implant intended to fill bony voids or gaps of the skeletal system (i.e. 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. Synthecure Synthetic Calcium Sulfate resorbs and is replaced with bone during the healing process.

Synthecure is provided sterile for single use only. Synthecure is biodegradable and biocompatible and may be used at an infected site.

Device Description

Synthecure Synthetic Calcium Sulfate is indicated to be implanted into defects not intrinsic to the structural stability of the skeletal system. Synthecure is biocompatible and may be implanted at an infected site. Synthecure Synthetic Calcium Sulfate is presented as a powder and mixing solution which when mixed together forms a paste which may be injected, digitally implanted or applied to a mold provided to produce pellets.

AI/ML Overview

The provided FDA 510(k) clearance letter pertains to a medical device called "Synthecure Synthetic Calcium Sulfate," a resorbable calcium salt bone void filler. The document focuses on demonstrating substantial equivalence to predicate devices through non-clinical testing.

Based on the provided text, the device is a bone void filler and not a device that would typically have the acceptance criteria in the format requested. The document does not describe a study involving a "test set" with ground truth, expert adjudication, or human reader performance with or without AI assistance, as these are concepts more relevant to diagnostic or AI-powered devices.

Therefore, many of the requested sections (2, 3, 4, 5, 6, 7, 8, 9) are not applicable to the information contained in this FDA clearance letter. The letter focuses on demonstrating the physical, chemical, and biological safety and performance of the bone void filler device through a series of non-clinical tests.

However, I can extract the acceptance criteria as described for the non-clinical tests and the reported performance based on the information provided.

Acceptance Criteria and Study for Synthecure Synthetic Calcium Sulfate

The Synthecure Synthetic Calcium Sulfate is a resorbable calcium salt bone void filler. The provided 510(k) summary outlines non-clinical testing performed to demonstrate its safety and substantial equivalence to predicate devices, rather than a clinical study with a detailed test set and ground truth as might be expected for diagnostic or AI devices.

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

Performance Category	Acceptance Criteria (Implied)	Reported Device Performance
Sterilization Validation	Sterilization must achieve a Sterility Assurance Level (SAL) of $1 \times 10^{-6}$ for the worst-case construct, in compliance with recognized standards.	Sterilization validation has been completed on the worst-case construct to an SAL of $1 \times 10^{-6}$.
Bacterial Endotoxin Testing	Testing must be performed according to ANSI/AAMI ST72:2011 and demonstrate acceptable endotoxin levels.	Testing is performed according to ANSI/AAMI ST72:2011, "Bacterial endotoxins – Test methods, routine monitoring and alternatives to batch testing." (Implies acceptable levels were met).
Packaging Validation	Packaging performance must be validated in accordance with ISO 11607-1:2019 and ISO 11607-2:2019 to ensure product integrity and sterility throughout its shelf life.	Packaging performance validation, in accordance with ISO 11607-1:2019 and ISO 11607-2:2019, was performed on the final packaging and sterilized device. (Implies successful validation).
Biocompatibility	Biological safety evaluation must be completed according to ISO 10993-1 requirements and FDA Guidance Document "Use of International Standard ISO 10993-1," demonstrating all materials are biocompatible for their intended use.	A biological safety evaluation has been completed for Synthecure according to ISO 10993-1 requirements and FDA Guidance Document "Use of International Standard ISO 10993-1." All materials contained in the proposed Synthecure have been evaluated in accordance with recognized standards and are characterized as being biocompatible.
Performance Testing - Bench	Chemical composition and physical properties (e.g., work and setting time) must be equivalent to predicate devices and maintain performance after aging, as per current industry standards and FDA guidance.	The chemical composition and physical properties of the subject and predicate devices were evaluated and demonstrated to be equivalent. Additionally, work and setting time tests were conducted on real-time aged samples to support that the device maintains its performance after aging.
Performance Testing - Animal	An in-vivo implantation study must demonstrate appropriate biological response, resorption, and replacement with bone at specified endpoints (e.g., 3, 6, and 12 weeks) in an animal model, showing performance comparable to expectations for bone void fillers.	An implantation study was conducted using New Zealand White Rabbits with study endpoints at 3, 6, and 12 weeks. (Implies successful outcomes demonstrating expected performance for bone void fillers, leading to substantial equivalence).

2. Sample size used for the test set and the data provenance (e.g., country of origin of the data, retrospective or prospective)

Sample Size for Test Set: Not specified in terms typically used for diagnostic or AI studies. For the animal study, the sample size is not explicitly stated number of New Zealand White Rabbits, but it's an animal model.
Data Provenance: The document implies that all testing (bench, animal, etc.) was conducted by or for Austin Medical Ventures, Inc. in support of their 510(k) submission. It's not applicable in terms of "country of origin for human data" as these are non-clinical studies.

3. 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 evaluation relies on physical, chemical, and biological testing, not on expert interpretation of diagnostic images or clinical assessments to establish ground truth in the way a diagnostic device would.

4. Adjudication method (e.g., 2+1, 3+1, none) for the test set

Not applicable. This device does not involve adjudication of expert opinions or interpretations.

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 is not an AI-assisted diagnostic device.

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

Not applicable. This is not a software algorithm or AI device.

7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)

For this type of device, "ground truth" is established through:

Established standards and regulations: e.g., ISO 10993-1 for biocompatibility, ISO 11607 for packaging.
Bench testing methodologies: Measuring physical and chemical properties.
In-vivo animal models: Observing biological response, resorption rates, and bone ingrowth over time (e.g., 3, 6, and 12 weeks endpoints). The "truth" here is the biological reaction within the animal model.

8. The sample size for the training set

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

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

Not applicable. This is not a machine learning or AI device.

Summary

FDA 510(k) Clearance Letter - Synthecure Synthetic Calcium Sulfate

Page 1

U.S. Food & Drug Administration
10903 New Hampshire Avenue Doc ID # 04017.07.05
Silver Spring, MD 20993
www.fda.gov

May 16, 2025

Austin Medical Ventures, Inc.
℅ John J. Smith
Partner
Hogan Lovells US LLP
555 Thirteenth Street NW
Washington, District of Columbia 20004

Re: K250141
Trade/Device Name: Synthecure Synthetic Calcium Sulfate
Regulation Number: 21 CFR 888.3045
Regulation Name: Resorbable Calcium Salt Bone Void Filler Device
Regulatory Class: Class II
Product Code: MQV
Dated: January 17, 2025
Received: April 17, 2025

Dear John J. Smith:

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 (the 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 available 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.

Additional information about changes that may require a new premarket notification are provided in the FDA guidance documents entitled "Deciding When to Submit a 510(k) for a Change to an Existing Device"

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K250141 - John J. Smith Page 2

(https://www.fda.gov/media/99812/download) and "Deciding When to Submit a 510(k) for a Software Change to an Existing Device" (https://www.fda.gov/media/99785/download).

Your device is also subject to, among other requirements, the Quality System (QS) regulation (21 CFR Part 820), which includes, but is not limited to, 21 CFR 820.30, Design controls; 21 CFR 820.90, Nonconforming product; and 21 CFR 820.100, Corrective and preventive action. Please note that regardless of whether a change requires premarket review, the QS regulation requires device manufacturers to review and approve changes to device design and production (21 CFR 820.30 and 21 CFR 820.70) and document changes and approvals in the device master record (21 CFR 820.181).

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 (reporting of medical device-related adverse events) (21 CFR Part 803) for devices or postmarketing safety reporting (21 CFR Part 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reporting-combination-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 Part 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR Parts 1000-1050.

All medical devices, including Class I and unclassified devices and combination product device constituent parts are required to be in compliance with the final Unique Device Identification System rule ("UDI Rule"). The UDI Rule requires, among other things, that a device bear a unique device identifier (UDI) on its label and package (21 CFR 801.20(a)) unless an exception or alternative applies (21 CFR 801.20(b)) and that the dates on the device label be formatted in accordance with 21 CFR 801.18. The UDI Rule (21 CFR 830.300(a) and 830.320(b)) also requires that certain information be submitted to the Global Unique Device Identification Database (GUDID) (21 CFR Part 830 Subpart E). For additional information on these requirements, please see the UDI System webpage at https://www.fda.gov/medical-devices/device-advice-comprehensive-regulatory-assistance/unique-device-identification-system-udi-system.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR 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-devices/medical-device-safety/medical-device-reporting-mdr-how-report-medical-device-problems.

For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medical-devices/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-devices/device-advice-comprehensive-regulatory-assistance/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).

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K250141 - John J. Smith Page 3

Sincerely,

JESSE MUIR -S Digitally signed by JESSE MUIR -S Date: 2025.05.16 14:23:08 -04'00'

Jesse Muir, Ph.D.
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

Page 4

DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration

Form Approved: OMB No. 0910-0120
Expiration Date: 07/31/2026
See PRA Statement below.

Indications for Use

Submission Number (if known)
K250141

Device Name
Synthecure Synthetic Calcium Sulfate

Indications for Use (Describe)

Synthecure is provided sterile for single use only. Synthecure is biodegradable and biocompatible and may be used at an infected site.

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)

CONTINUE ON A SEPARATE PAGE IF NEEDED.

This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.

The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:

Department of Health and Human Services
Food and Drug Administration
Office of Chief Information Officer
Paperwork Reduction Act (PRA) Staff
PRAStaff@fda.hhs.gov

"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."

Page 5

Synthecure Synthetic Calcium Sulfate 510(k) Summary

DATE PREPARED
January 17, 2024

MANUFACTURER AND 510(k) OWNER
Austin Medical Ventures, Inc.
3012 Centre Oak Way, Suite 102, Germantown, TN 38138
Ph: (901) 748-2581
Official Contact: Brian Austin, CEO

REPRESENTATIVE/CONSULTANT
Allison Komiyama, Ph.D., RAC
Alexia Haralambous, MS, RAC
RQM+
Ph: (412) 816-8253
Email: akomiyama@rqmplus.com
aharalambous@rqmplus.com

DEVICE INFORMATION
Proprietary Name/Trade Name: Synthecure Synthetic Calcium Sulfate
Common Name: Resorbable Calcium Sulfate Bone Void Filler
Regulation Number: 21 CFR 888.3045
Class: Class II
Product Code: MQV
Review Panel: Orthopedic

PREDICATE DEVICE IDENTIFICATION
The Synthecure Synthetic Calcium Sulfate is substantially equivalent to the following predicates:

510(k) Number	Predicate Device Name / Manufacturer	Predicate/Reference
K141830	Stimulan Kit, Stimulan Rapid Cure / Biocomposites Ltd.	Predicate
K010532	Osteoset BVF Kit / Wright Medical Technology, Inc.	Reference

DEVICE DESCRIPTION
Synthecure Synthetic Calcium Sulfate is indicated to be implanted into defects not intrinsic to the structural stability of the skeletal system. Synthecure is biocompatible and may be implanted at an infected site. Synthecure Synthetic Calcium Sulfate is presented as a powder and mixing solution which when mixed together forms a paste which may be injected, digitally implanted or applied to a mold provided to produce pellets.

K250141
Page 1 of 3

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Synthecure Synthetic Calcium Sulfate
K250141

510(k) Summary

DATE PREPARED
January 17, 2024

MANUFACTURER AND 510(k) OWNER
Austin Medical Ventures, Inc.
3012 Centre Oak Way, Suite 102, Germantown, TN 38138
Ph: (901) 748-2581
Official Contact: Brian Austin, CEO

REPRESENTATIVE/CONSULTANT
Allison Komiyama, Ph.D., RAC
Alexia Haralambous, MS, RAC
RQM+
Ph: (412) 816-8253
Email: akomiyama@rqmplus.com
aharalambous@rqmplus.com

PREDICATE DEVICE IDENTIFICATION
The Synthecure Synthetic Calcium Sulfate is substantially equivalent to the following predicates:

510(k) Number	Predicate Device Name / Manufacturer	Predicate/Reference
K141830	Stimulan Kit, Stimulan Rapid Cure / Biocomposites Ltd.	Predicate
K010532	Osteoset BVF Kit / Wright Medical Technology, Inc.	Reference

Page 1 of 3

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Synthecure Synthetic Calcium Sulfate

INDICATIONS FOR USE
Synthecure Synthetic Calcium Sulfate is an implant intended to fill bony voids or gaps of the skeletal system (i.e. 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. Synthecure Synthetic Calcium Sulfate resorbs and is replaced with bone during the healing process.

Synthecure is provided sterile for single use only. Synthecure is biodegradable and biocompatible and may be used at an infected site.

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
Austin Medical Ventures, Inc. believes that the Synthecure Synthetic Calcium Sulfate is substantially equivalent to the predicate devices based on the information summarized here: Synthecure Synthetic Calcium Sulfate is identical in function and intended use to the predicate device. The subject and predicate devices are intended to be implanted into defects not intrinsic to the structural stability of the skeletal system. Additionally, the subject device has a similar design and uses similar materials to the predicate. The subject device and the predicate device are presented as a powder, manufactured from medical grade calcium sulfate, and a mixing solution which, when mixed, form a paste which may be digitally implanted or applied to a mold provided to produce beads. Both are biocompatible and may be implanted at an infected site which resorbs and is replaced by bone during the healing process. These technological characteristics have undergone testing to ensure the device is as safe and effective as the predicates.

SUMMARY OF NON-CLINICAL TESTING
Austin Medical Ventures, Inc. has conducted testing per FDA Guidance Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device (issued on June 2, 2003). The following tests were performed to demonstrate safety based on current industry standards:

Performance Category	Testing
Sterilization Validation	Sterilization validation has been completed on the worst-case construct to an SAL of 1x10-6.
Bacterial Endotoxin Testing	Testing is performed according to ANSI/AAMI ST72:2011, Bacterial endotoxins – Test methods, routine monitoring and alternatives to batch testing.
Packaging Validation	Packaging performance validation, in accordance with ISO 11607-1:2019 and ISO 11607-2:2019, was performed on the final packaging and sterilized device.
Biocompatibility	A biological safety evaluation has been completed for Synthecure according to ISO 10993-1 requirements and FDA Guidance Document Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation

K250141
Page 2 of 3

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Synthecure Synthetic Calcium Sulfate

Performance Category	Testing
	and testing within a risk management process" (issued on September 8, 2023). All materials contained in the proposed Synthecure have been evaluated in accordance with recognized standards and are characterized as being biocompatible.
Performance Testing - Bench	The chemical composition and physical properties of the subject and predicate devices were evaluated and demonstrated to be equivalent. Additionally, work and setting time tests were conducted on real-time aged samples to support that the device maintains its performance after aging.
Performance Testing - Animal	An implantation study was conducted using New Zealand White Rabbits with study endpoints at 3, 6, and 12 weeks.

The results of these tests indicate that the Synthecure Synthetic Calcium Sulfate is substantially equivalent to the predicate devices.

CONCLUSION
Based on the testing performed, including sterilization validation, packaging validation, biocompatibility, bench testing and an animal study, it can be concluded that the subject device does not raise new issues of safety or effectiveness compared to the predicate devices. The similar indications for use, technological characteristics, and performance characteristics for the proposed Synthecure Synthetic Calcium Sulfate are assessed to be substantially equivalent to the predicate devices.

K250141
Page 3 of 3

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.