Actifuse™ Flow is a bone void filler intended only for orthopedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse™ Flow 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 created from traumatic injury to the bone. The product provides a bone void filler that resorbs and is replaced by bone during process.

Device Description

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 11d 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.

Actifuse™ Flow is phase-pure silicon-substituted calcium phosphate osteoconductive bone void filler, comprising a single-phase calcium phosphate scaffold delivered in a matrix of resorbable polymer. The interconnected and open porous structure inherent of the source material for the mineral phase of Actifuse™ Flow is similar to human cancellous bone.

AI/ML Overview

The medical device described in the provided text is Actifuse™ Flow, a resorbable calcium salt bone void filler. The submission is a 510(k) premarket notification for modifications to the product line, specifically applicator syringe design changes.

Here's an analysis of the acceptance criteria and the study proving the device meets them, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Parameter / Acceptance Criteria	Reported Device Performance and Corresponding Test
1. Chemical and Structural Integrity of Actifuse™ Flow Acceptance Criteria: The modifications to the applicator syringe should have no impact on the chemistry or structure of the Actifuse™ Flow product, ensuring it remains chemically and structurally identical to the predicate device.	Performance Data: The performance of the Actifuse™ Flow device after modifications made to the applicator syringe was assessed by analyzing the Actifuse™ Flow final product for chemical changes relative to the predicate product's specification. Result: "All testing confirmed that the modifications had no impact to the chemistry or structure of the Actifuse™ Flow product."
2. Biocompatibility Acceptance Criteria: The device, including new materials, must meet biocompatibility standards for a permanent duration, implant device, tissue/bone contact.	Performance Data: Biocompatibility assessments were conducted based on ISO-10993-1, "Biological Evaluation of Medical Devices for permanent duration, implant device, tissue/bone contact," and FDA Guidance. Result: "All materials found in these devices that are the subject of this submission have been previously cleared under Baxter's 510(k) premarket notifications K082073 (clearance date September 11, 2008), K130531 (clearance date April 8, 2014) and K071206 (clearance date 31st May, 2007)." This indicates that the materials have already met biocompatibility standards.
3. Sterility and Package Integrity Acceptance Criteria: The product must be sterile (10^-6 SAL) and remain sterile throughout its shelf life, with package integrity maintained.	Performance Data: "The Actifuse™ Flow product line is sterilized with radiation. The minimum sterilizing dose (MSD) required to provide a 10-6 Sterility Assurance Level (SAL) for this (sub) category was established and validated at the manufacturing facility as described in ANSI/AAMI/ISO 11137-2, "Sterilization of health care products- Radiation-Part 2: Establishing the Sterilization Dose."" "Package Verification testing is based on Visual Inspection, Seal Strength, and Bubble Leak testing." Result: "These products are labeled 'Sterile'." The implicit result is that the validation for sterilization and package integrity testing passed, supporting the "Sterile" claim.
4. Shelf Life Stability Acceptance Criteria: The device must maintain its safety and effectiveness for a defined shelf life.	Performance Data: "Baxter has performed aging testing to support a shelf-life claim of two (2) years." Result: The implicit result is that the aging testing successfully demonstrated stability for a two-year shelf life.
5. Overall Safety and Effectiveness (Substantial Equivalence) Acceptance Criteria: The modified device must be as safe and effective as the predicate device.	Performance Data: The entire submission, based on "Discussion of Non-Clinical Data," "Performance Data," "Biocompatibility," "Sterility," and "Shelf Life." Result: "The non-clinical data demonstrate that the subject device is substantially equivalent and performs comparably to the predicate device." "Actifuse™ Flow Bone Graft Substitute is as safe and effective as the predicate Actifuse™ Flow Bone Graft Substitute."

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

The provided text does not specify sample sizes for any of the tests. It broadly mentions "All test results meet the acceptance criteria" and "All testing was performed on the configuration of the devices presented in this premarket notification." This suggests that the testing was conducted on a sufficient number of units to support the conclusions, but the exact count is not given.

The data provenance is pre-market notification testing conducted by Baxter Healthcare Corporation. The location of the testing is not explicitly stated, but Baxter Healthcare Corporation is based in Deerfield, Illinois, USA. The testing appears to be prospective in the sense that it was specifically performed for this 510(k) submission to demonstrate substantial equivalence of the modified device.

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

There is no mention of experts or the establishment of "ground truth" using human experts for this specific submission. This is a non-clinical submission focused on material and design changes to an existing device, not a clinical study involving diagnosis or interpretation where expert consensus on "ground truth" (e.g., disease presence) would be relevant. The "ground truth" for this submission are the established specifications, chemical properties, and performance characteristics of the predicate device, against which the modified device is compared.

4. Adjudication Method for the Test Set

As this is a non-clinical submission, there is no adjudication method described. Adjudication methods (e.g., 2+1, 3+1) are typically used in clinical studies, especially those involving human interpretation of medical images or other subjective data, to resolve discrepancies among readers/experts. These are not applicable to the chemical, physical, and sterility tests described.

5. Multi Reader Multi Case (MRMC) Comparative Effectiveness Study

No, a Multi Reader Multi Case (MRMC) comparative effectiveness study was not done. This type of study is relevant for AI or imaging devices where human readers' performance with and without AI assistance is compared. This submission pertains to a physical medical device (bone void filler) with modifications to its applicator syringe, not an AI or imaging diagnostic device.

6. Standalone (Algorithm Only Without Human-in-the-Loop Performance) Study

Not applicable. This question typically applies to AI algorithms. The device described is a physical medical product, not an algorithm. The "performance" assessment here relates to chemical, physical, and biological properties of the device itself, not an algorithm's output.

7. Type of Ground Truth Used

The "ground truth" used for this submission is based on established specifications, validated test methods, and existing regulatory clearances for the predicate device and the materials used. Specifically:

Chemical/Structural Integrity: Ground truth is the defined chemical and structural properties of the predicate Actifuse™ Flow and its components.
Biocompatibility: Ground truth is established biocompatibility standards (e.g., ISO-10993-1) and the successful prior clearance of the materials in other Baxter devices.
Sterility: Ground truth is a 10^-6 Sterility Assurance Level (SAL) as established by international standards (ANSI/AAMI/ISO 11137-2).
Shelf Life: Ground truth is the stability of a product over time, which is confirmed by specific aging tests.

Essentially, the ground truth is the established and acceptable performance of the predicate device and known standards, against which the modified device is compared.

8. Sample Size for the Training Set

There is no mention of a "training set" in this submission. Training sets are relevant for machine learning algorithms. This is a traditional medical device submission based on a direct comparison to a predicate device and engineering/material testing, not machine learning.

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

As there is no training set, this question is not applicable.

Summary

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August 17, 2018

Baxter Healthcare Corporation Daniel Davis Senior Manager, Global Regulatory Affairs 32650 North Wilson Road Round Lake, Illinois 60073

Re: K181306

Trade/Device Name: Actifuse™M Flow Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MOV Dated: July 18, 2018 Received: July 20, 2018

Dear Mr. Davis:

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/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, 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

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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/CombinationProducts/GuidanceRegulatoryInformation/ucm597488.html; good manufacturing practice requirements as set forth in the quality systems (OS) 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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Form Approved: OMB No. 0910-0120

Expiration Date: January 31, 2017

See PRA Statement below.

Indications for Use

510(k) Number (if known) K181306

Device Name Actifuse TM Flow

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
X 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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Section 5. 510(k) Summary

May 22, 2018

OWNER:

Baxter Healthcare Corporation One Baxter Parkway Deerfield, Illinois 60015

CONTACT PERSON:

Daniel Davis Senior Manager, Global Regulatory Affairs 32650 N. Wilson Road Round Lake, IL 60073 Telephone: (224) 948-3775 Fax: (224) 270-4119

IDENTIFICATION OF THE DEVICE:

Common Name: Filler, bone void, calcium compound Trade Name: Actifuse™ Flow Bone Graft Substitute Classification Panel: Orthopaedic and Rehabilitation Devices Panel Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MQV

Model Number	Name
506005078076	Actifuse Flow Bone Graft Substitute, 1.5ml
506005078077	Actifuse Flow Bone Graft Substitute, 3.0ml
506005078078	Actifuse Flow Bone Graft Substitute, 5.0ml

Table 1. Model Numbers for Actifuse™ Flow

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PREDICATE DEVICE:

Table 2. Predicate Device

Device	Company	Predicate 510(k)	Clearance Date
ActifuseTM Flow BoneGraft Substitute	ApaTech Limited370 Centennial AvenueElstree, HertfordshireWD6 3TJUnited Kingdom.1	K082073	September 11, 2008

1 ApaTech Limited was acquired by Baxter Healthcare Corporation in 2010

Device	Company	Reference 510(k)	Clearance Date
Actifuse™ Flow BoneGraft Substitute,Actifuse™ Shape BoneGraft Substitute,Actifuse™ ABX E-Z filPutty, Actifuse™ BoneGraft Substitute	ApaTech Limited370 Centennial AvenueElstree, HertfordshireWD6 3TJUnited Kingdom.1	K081979	November 6, 2008
Altapore™ Bone GraftSubstitute	ApaTech Limited370 Centennial AvenueElstree, HertfordshireWD6 3TJUnited Kingdom.1	K130531	April 8, 2014
Actifuse™ ABX E-Z filPutty Bone GraftSubstitute	ApaTech Limited370 Centennial AvenueElstree, HertfordshireWD6 3TJUnited Kingdom.1	K071206	May 31, 2007
Actifuse™ Bone GraftSubstituteActifuse™Microgranules BoneGraft SubstituteActifuse™ E-Z-PrepActifuse™ ABX BoneGraft SubstituteActifuse™ MISActifuse™ Shape BoneGraft SubstituteActifuse™ Flow BoneGraft Substitute	ApaTech Limited370 Centennial AvenueElstree, HertfordshireWD6 3TJUnited Kingdom.1	K090850	July 30, 2009
1 ApaTech Limited was acquired by Baxter Healthcare Corporation in 2010

Table 3. Reference 510(k)

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DESCRIPTION OF THE DEVICE:

INDICATIONS FOR USE:

Actifuse™ Flow is a bone void filler intended only for orthopedic applications as a filler for gaps and voids that are not intrinsic to the stability of the bony structure. Actifuse™ Flow 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.

PURPOSE OF SUBMISSION:

The basis for this premarket notification is modifications to the Actifuse™ Flow product line. The modifications consist of applicator syringe design changes (both material and dimensional changes) to create a ready-to-use version of the Actifuse™ Flow device. The proposed new applicator syringe materials are currently used in Baxter's Altapore and Actifuse™ ABX Bone Graft substitute product lines and have been previously cleared under 510(k) premarket notifications K130531 (cleared date 8th Apr, 2014) and K071206 (cleared date 31st May, 2007) respectively. The hydroxyapatite granules used in Actifuse ABX. Actifuse Flow, and Altapore are all chemically identical. These modifications do not impact the intended use or the fundamental technology of the devices.

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TECHNOLOGICAL CHARACTERISTICS AND SUBSTANTIAL EQUIVALENCE:

The proposed devices have equivalent technological characteristics as Baxter's currently cleared Actifuse™ Flow product line, cleared under 510(k) premarket notification K082073 (cleared September 11, 2008).

DISCUSSION OF NON-CLINICAL DATA:

Baxter Healthcare Corporation conducts risk analyses and design verification tests based on the result of these analyses. All test results meet the acceptance criteria, and support that the proposed devices are appropriately designed for their intended use. All testing was performed on the configuration of the devices presented in this premarket notification.

Performance Data

The performance of the Actifuse™ Flow device after modifications made to the applicator syringe was assessed by analyzing the Actifuse™ Flow final product for chemical changes relative to the predicate product's specification. All testing confirmed that the modifications had no impact to the chemistry or structure of the Actifuse™ Flow product.

Biocompatibility

All materials found in these devices that are the subject of this submission have been previously cleared under Baxter's 510(k) premarket notifications K082073 (clearance date September 11, 2008), K130531 (clearance date April 8, 2014) and K071206 (clearance date 31st May, 2007).

Biocompatibility assessments were conducted based on ISO-10993-1, Biological Evaluation of Medical Devices for permanent duration, implant device, tissue/bone contact, and FDA Guidance, Use of International Standard ISO 10993-1, "Biological evaluation of medical devices - Part 1: Evaluation and testing within a risk management process", as recommended in the "Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device: Guidance for Industry and FDA".

Sterility

The Actifuse The Flow product line is sterilized with radiation. The minimum sterilizing dose (MSD) required to provide a 10-6 Sterility Assurance Level (SAL) for this (sub) category was established and validated at the manufacturing facility as described in

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ANSI/AAMI/ISO ISO 11137-2, "Sterilization of health care products- Radiation-Part 2: Establishing the Sterilization Dose."

These products are labeled "Sterile". Package Verification testing is based on Visual Inspection, Seal Strength, and Bubble Leak testing.

Shelf Life

Baxter has performed aging testing to support a shelf-life claim of two (2) years.

CONCLUSION:

Actifuse™ Flow Bone Graft Substitute is as safe and effective as the predicate Actifuse™ Flow Bone Graft Substitute. Both devices share indications for use, technological characteristics, and principles of operation. The only differences between the two devices are the changes to the dimensions and materials of the syringes housing the devices. The non-clinical data demonstrate that the subject device is substantially equivalent and performs comparably to the predicate device.

Regulation Number and Section

N/A