Actifuse™ Actifuse™ ABX E-Z-fil Putty, Actifuse™ Shape Actifuse™ is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse is indicated to be packed gently into bony voids or gaps of the skeletal system, i.e., extremities, pelvis, and spine, including use in posterolateral fusion procedures with appropriate stabilizing hardware. 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 by bone during the healing process. Actifuse™ Flow Actifuse™ Flow Bone Graft Substitute is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse™ Flow Bone Graft Substitute can be injected into bony voids or gaps of the skeletal system. i.e., extremities, pelvis, and spine, including use in posterolateral spinal fusion procedures with appropriate stabilizing hardware. 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 by bone during the healing process.

Device Description

Actifuse™ is a bioactive phase-pure silicon-substituted calcium phosphate osteoconductive and osteostimulative bone void filler, comprising a single-phase calcium phosphate scaffold, either granules or granules delivered in a matrix of resorbable polymer. The interconnected and open porous structure of the calcium phosphate phase of Actifuse is similar to human cancellous bone.

AI/ML Overview

This 510(k) summary describes a resorbable calcium salt bone void filler, Actifuse™. It isn't a typical AI/software device that would have specific performance metrics like sensitivity/specificity for diagnosis. Instead, the acceptance criteria and supporting studies focus on the biological and material properties of the bone graft substitute.

Here's an analysis of the provided information:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria	Reported Device Performance
Material Properties:
Composition	Bioactive phase-pure silicon-substituted calcium phosphate osteoconductive and osteostimulative bone void filler. Single-phase calcium phosphate scaffold, either granules or granules delivered in a matrix of resorbable polymer. Interconnected and open porous structure similar to human cancellous bone.
Compliance with relevant standards for Calcium Salt Bone Void Fillers	Testing has shown Actifuse™ to meet the requirements of all relevant standards for Calcium Salt Bone Void Fillers.
Bioactivity:
Induction of an apatite layer in vitro	Induced growth of an apatite layer on the surface of Actifuse following exposure to simulated body fluid.
Rate of apatite layer formation	Time required to form a new apatite layer was reduced by 29% when compared to an identical calcium phosphate material that did not contain 0.8wt% silicate.
Osteostimulation:
Acceleration of cellular responses (metabolic activity, proliferation) in vitro	Cell culture studies showed accelerated cellular responses (metabolic activity and proliferation) compared to an identical material without 0.8wt% silicate.
Functional Outcome:
Scaffold for rapid bone repair via bony infiltration	Confirmed Actifuse™ to be safe and effective in providing a scaffold for rapid bone repair via bony infiltration of the porous scaffold.
Resorption and replacement by bone during healing	The product provides a bone void filler that resorbs and is replaced by bone during the healing process (stated in indications for use and implied by other tests).

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

Sample Size: Not explicitly stated with specific numbers of samples for each test (e.g., number of in-vitro samples, number of cell cultures). The documentation generally refers to "in-vitro studies" and "cell culture studies."
Data Provenance: The studies are described as "in-vitro studies" and "cell culture studies," implying laboratory-based testing. There is no mention of human or animal in-vivo test sets beyond the general assertion that "testing has confirmed Actifuse™ to be safe and effective." The document explicitly states: "The bioactive and osteostimulatory nature of Actifuse has not been correlated with human clinical experience." This indicates the data is from ex vivo (in vitro) experiments rather than in vivo clinical data.

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

This information is not applicable in the context of this submission. The device is a material, not an imaging or diagnostic AI device that requires expert-established ground truth for performance evaluation. The "ground truth" for the material's properties generally comes from validated chemical, biological, and mechanical testing methods.

4. Adjudication Method for the Test Set

Not applicable. As a material, there's no "adjudication method" in the sense of reconciling human expert opinions on a diagnostic outcome. Performance is based on objective scientific measurements.

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 graft substitute, not an AI or software device. Therefore, no MRMC study involving human readers and AI assistance would be relevant or conducted for its approval.

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

Not applicable. This device is a bone graft substitute, not an AI algorithm.

7. The Type of Ground Truth Used

The "ground truth" for the material's performance relies on scientific measurements and established biological assays. This includes:
- Chemical and structural analysis of the material for composition and porous structure.
- In-vitro studies using simulated body fluid to observe apatite layer formation.
- Cell culture studies to measure cellular responses (metabolic activity, proliferation).
- Compliance with "relevant standards for Calcium Salt Bone Void Fillers," which would imply adherence to material and biocompatibility ground truths defined by those standards.

8. The Sample Size for the Training Set

Not applicable. This device is a physical product (a bone graft substitute), not a machine learning model. Therefore, there is no "training set."

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

Not applicable. As there is no training set for an AI model, this question is not relevant. The material's development and characterization would have involved standard scientific research and development procedures to understand its properties.

Summary

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Premarket Notification [510(k)] Summary (per 21 CFR 807.92)

K081979

NOV - 6 2008

Submitter:	ApaTech Limited370 Centennial AvenueCentennial ParkElstree, Hertfordshire WD6 3TJUnited Kingdom
Contact Person:	James J. Cassidy, Ph.D.(320) 355-2679 (phone)(320) 355-3206 (fax)
Date Prepared:	October 27, 2008
Classification:	Resorbable calcium salt bone void filler devices have been classified bythe Orthopedics Device Panel as Class II Special Controls per 21 CFR888.3045, Product Code MQV.
Trade Name:	Actifuse™ Bone Graft SubstituteActifuse ™ ABX E-Z-fil Bone Graft SubstituteActifuse™ Shape Bone Graft SubstituteActifuse™ Flow Bone Graft Substitute
Common Name:	Bone Void Filler

Intended use:

Actifuse™ Actifuse™ ABX E-Z-fil Putty, Actifuse™ Shape

Actifuse™ is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse is indicated to be packed gently into bony voids or gaps of the skeletal system, i.e., extremities, pelvis, and spine, including use in posterolateral fusion procedures with appropriate stabilizing hardware. 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 by bone during the healing process.

Actifuse™ Flow

Actifuse™ Flow Bone Graft Substitute is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse™ Flow Bone Graft Substitute can be injected into bony voids or gaps of the skeletal system. i.e., extremities, pelvis, and spine, including use in posterolateral spinal fusion procedures with appropriate stabilizing hardware. 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 by bone during the healing process.

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Device Description

Technological Characteristics and Substantial Equivalence

Actifuse™ is composed of a porous calcium salt equivalent to that contained in the predicate device and to that in routine clinical use. The technologies employed in Actifuse™ and its predicate device are therefore substantially equivalent. Actifuse™ has the same indications, risks and potential adverse events as the predicate device and thus substantial equivalence is claimed for the device.

Testing

Testing has shown Actifuse™ to meet the requirements of all relevant standards for Calcium Salt Bone Void Fillers. Testing has confirmed Actifuse™ to be safe and effective in providing a scaffold for rapid bone repair via bony infiltration of the porous scaffold.

Actifuse is bioactive based on in-vitro studies in which growth of an apatite layer was induced on the surface of Actifuse following exposure to simulated body fluid. The time required to form a new apatite layer on the surface of Actifuse was reduced by 29% when compared to an identical calcium phosphate material that did not contain 0.8wt% silicate.

Actifuse is found to be osteostimulatory based on cell culture studies that showed that cellular responses, such as metabolic activity and proliferation, were accelerated when compared to an identical that did not contain 0.8wt% silicate.

These results demonstrate that Actifuse is a scaffold supporting rapid bone formation. The bioactive and osteostimulatory nature of Actifuse has not been correlated with human clinical experience.

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Image /page/2/Picture/1 description: The image is a black and white logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle-like symbol with flowing lines, representing the department's mission. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the symbol. The text is in all caps and is evenly spaced around the circle.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

FEB 5 - 2009

Apatech Ltd % Ms. Candace F. Cederman 15058 Armel Drive Oregon City, Oregon 97045

Re: K081979

Trade Name: Actifuse™ Bone Graft Substitute, Actifuse™ ABX E-Z-FIL, Actifuse™ Shape Bone Graft and Actifuse™ Flow Bone Graft Substitute Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: II Product Code: MQV Dated: July 10, 2008 Received: July 11, 2008

Dear Ms. Cederman:

This letter corrects our substantially equivalent letter of November 6, 2008.

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 (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.

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 mav 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); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 - Ms. Candace F. Cederman

This letter will allow you to continue marketing your device as described in your Section 510(k) premarket notification. The FDA finding of substantial equivalence of your device to a legally marketed predicate device results in a classification for your device and thus, permits your device to proceed to the market.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Center for Devices and Radiological Health's (CDRH's) Office of Compliance at (240) 276-0120. Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding postmarket surveillance, please contact CDRH's Office of Surveillance and Biometric's (OSB's) Division of Postmarket Surveillance at (240) 276-3474. For questions regarding of device adverse events (Medical Device Reporting (MDR)), please contact the Division of Surveillance Systems at (240) 276-3464. You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers. International and Consumer Assistance at toll-free number (800) 638-2041 or (240) 276-3150 or the Internet address http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,
Mark A. Mikkelson

Mark N. Melkerson Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

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510(k) Number (if known): K081979

Device Name: Actifuse™ Flow Bone Graft Substitute

Indications for Use:

Actifuse™ Flow Bone Graft Substitute is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse™ Flow Bone Graft Substitute can be injected into bony voids or gaps of the skeletal system, i.e., extremities, pelvis, and spine, induding use in posterolateral spinal fusion procedures with appropriate stabilizing hardware. 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 by bone during the healing process.

Prescription Use _ × (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

(Division Sign-Off)

Division of General, Restorative, and Neurological Devices

510(k) Number 16871779

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510(k) Number (if known): K081979

Device Name: Actifuse™ Shape Bone Graft Substitute

Indications for Use:

Actifuse™ Shape is a bone void filler intended only for orthopaedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse is indicated to be packed gently into bony voids or gaps of the skeletal system, i.e., extremities, pelvis, and spine, including use in posterolateral fusion procedures with appropriate stabilizing harchware. 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 by bone during the healing process

Prescription Use _____________________________________________________________________________________________________________________________________________________________ (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

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510(k) Number (if known): K081979

Device Name: Actifuse™ ABX E-Z-fil Putty

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR

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

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

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510(k) Number (if known): K081979

Device Name: Actifuse™ Bone Graft Substitute

Indications for Use:

Prescription Use X (Part 21 CFR 801 Subpart D)

AND/OR -

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

(PLEASE DO NOT WRITE BELOW THIS LINE - CONTINUE ON ANOTHER PAGE IF NEEDED) Concurrence of CDRH, Office of Device Evaluation (ODE)

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.