Tactoset® Injectable Bone Substitute is a synthetic, biocompatible bone graft substitute material that hardens and converts to a poorly crystalline hydroxyapatite at body temperature. It is indicated for filling bone voids or defects of the skeletal system (i.e. extremities and pelvis) that are not intrinsic to the stability of bony structure. These defects may be surgically created osseous defects or defects created from traumatic injury to the bone. The device provides an injectable, self-setting, osteoconductive bone graft substitute that resorbs and is replaced by the growth of new bone during the healing process and may be combined with autogenous bone marrow. Tactoset® Injectable Bone Substitute can augment hardware and support bone fragments during the surgical procedure. The cured paste acts only as a temporary support media and is not intended to provide structural support during the healing process.

Device Description

Tactoset is an injectable osteoconductive calcium phosphate bone graft substitute material. It is provided to the end-user as two components (a dry powder and an aqueous solution in separate pre-loaded syringes) that must be mixed intra-operatively prior to implantation using the supplied mixing system to form a cohesive paste. The dry powder component is composed of the alpha phase of tricalcium phosphate [Ca3(PO4)2], calcium carbonate [CaCO3], and monocalcium phosphate [Ca(H2PO4)2]. The liquid component is composed of sodium phosphate dibasic [Na2HPO4], citric acid [CaHgO7], hyaluronic acid (HA), and water for injection. At a specified volume, the aqueous setting solution can be combined with autogenous bone marrow, i.e., bone marrow aspirate. Tactoset is provided sterile for single use.

AI/ML Overview

The provided text describes a 510(k) premarket notification for a medical device called Tactoset. It focuses on demonstrating substantial equivalence to predicate devices rather than providing specific acceptance criteria and detailed study results for the device itself. Therefore, many of the requested details about acceptance criteria, specific performance metrics, sample sizes, expert qualifications, and ground truth establishment are not present in the provided document.

However, based on the available information, I can extract what is present:

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

The document does not explicitly present acceptance criteria in a quantitative table with specific targets. Instead, it demonstrates "substantial equivalence" to predicate devices through various comparisons, including material composition, physical properties, mechanical testing, and an animal functional study. The closest an explicit performance comparison comes is in the animal study section:

Performance Metric	Subject Device (Tactoset + BMA) Performance	Predicate Device (Tactoset) Performance	Negative Control (Empty Defect) Performance
New Bone Formation (at 12 weeks)	Averages 14.90%	Averages 14.65%	5%
Implant Material Remaining (at 12 weeks)	Approximately 54.3%	Approximately 60.9%	N/A

Other aspects like mixing time, working time, setting time, sterility, and pyrogenicity are presented as characteristics that are equivalent to the predicate device, implying that the predicate's performance in these areas serves as an "acceptance criteria" through analogy.

Characteristic	Subject Device Performance	Primary Predicate Performance
Mixing Time (Min)	1	1
Min Working Time (Min)	7-18	7-18
Setting Time (Min)	10	10
Sterility Method	Single Use, Sterile, SAL 10-6	Single Use, Sterile, SAL 10-6
Pyrogenicity	LAL < 20 EU/device	LAL < 20 EU/device

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

Test Set Sample Size: The document mentions a "rabbit critical sized femoral defect model." It does not specify the number of rabbits or defects used in this study.
Data Provenance: Not specified in the document.

3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)

This information is not provided in the document. The "new bone formation" and "implant material remaining" would likely require expert assessment (e.g., histopathologist), but the details are absent.

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

This information is not provided in the document.

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

No MRMC comparative effectiveness study was done, nor is this an AI-powered device. The study described is an animal functional study comparing the device's performance to a predicate device and a control in terms of bone formation and resorption.

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

This is not an algorithm-only device; it is a bone graft substitute. The standalone performance was assessed in an animal model.

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

For the animal study, the ground truth for "new bone formation" and "implant material remaining" would likely be derived from histopathology analysis of the retrieved bone sections from the rabbit femoral defects.

8. The sample size for the training set

Not applicable/Not provided. The document describes a medical device (bone graft substitute), not a machine learning algorithm that requires a training set.

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

Not applicable/Not provided (as it's not a machine learning algorithm).

Summary

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March 29, 2023

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo is in blue and includes the letters "FDA" in a square and the words "U.S. FOOD & DRUG ADMINISTRATION".

Anika Therapeutics. Inc. % Mehdi Kazemzadeh-Narbat, PhD, PMP, CQA Associate Director, Regulatory Affairs Mcra LLC. 803 7th Street NW Floor 3 Washington, District of Columbia 20001

Re: K223915

Trade/Device Name: Tactoset Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MOV Dated: December 29, 2022 Received: December 29, 2022

Dear Dr. Kazemzadeh-Narbat:

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

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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) 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,

Sara S. Thompson -S

For

Laurence D. Coyne, Ph.D. 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) K223915

Device Name Tactoset

Indications for Use (Describe)

Tactoset® Injectable Bone Substitute is a synthetic, biocompatible bone graft substitute material that hardens and converts to a poorly crystalline hydroxyapatite at body temperature. It is indicated for filling bone voids or defects of the skeletal system (i.e. extremities and pelvis) that are not intrinsic to the stability of bony structure. These defects may be surgically created osseous defects or defects created from traumatic injury to the device provides an injectable, selfsetting, osteoconductive bone graft substitute that resorbs and is replaced by the growth of new ling process and may be combined with autogenous bone marrow. Tactoset® Injectable Bone Substitute can augment hardware and support bone fragments during the surgical procedure. The cured paste acts only as a temporary support media and is not intended to provide structural support during the healing process.

X Prescription Use (Part 21 CFR 801 Subpart D)

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

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510(k) SUMMARY

Device Trade Name:	Tactoset
Manufacturer:	Anika Therapeutics, Inc.32 Wiggins AvenueBedford, MA 01730
Contact:	Wei ZhaoExecutive Director, Regulatory AffairsMobile: (978)888-5948E-Mail: wzhao@anika.com
Prepared by:	Mehdi Kazemzadeh-Narbat, PhD, PMP, CQADirector, Regulatory Affairs,MCRA, LLC803 7th Street NW, Floor 3Washington, DC 20001Office: 202.552.6011mkazemzadeh@mcra.com
Date Prepared:	Mar 23, 2023
Classifications:	21 CFR §880.3045, Resorbable calcium salt bone void filler device
Class:	II
Product Codes:	MQV
Primary Predicate:	Tactoset (K212083)
Additional Predicates:	Tactoset (K173008)MasterGraft Putty (K051386)MagnetOs Granules (K213111)

Indications For Use:

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Device Description:

Predicate Device:

Anika Therapeutics, Inc. submits the following information in this Premarket Notification to demonstrate that, for the purposes of FDA's regulation of medical devices. Tactoset is substantially equivalent in indications, design principles, and performance to the following predicate devices, which have been determined by FDA to be substantially equivalent to pre-amendment devices:

Primary Predicate:	Tactoset (K212083)
Additional Predicates:	Tactoset (K173008)MasterGraft Putty (K051386)MagnetOs Granules (K213111)

Performance Testing Summary:

Bench testing data including analytical characterization, chemical composition, physical properties, mechanical testing (Pull-Out, Compressive Strength, Bone Alignment) and animal functional study were conducted for the subject Tactoset and the predicate devices. The results of the study demonstrate substantial equivalence to the predicate devices.

Substantial Equivalence:

The subject device is substantially equivalent to the Tactoset (K212083) in terms of material composition, manufacturing process, sterilization, and packaging and both are manufactured in the same facility.

The subject device and the predicate devices (primary and additional) have the same intended uses, the same product classification and product code (MQV) and have similar "Indications for Use" statements in the extremities and pelvis. The subject device and the predicate devices are bone void fillers that are intended for bony voids or gaps that are not intrinsic to the stability of the bony structure. The subject device and the primary predicate incorporate the same basic design, incorporates similar materials, have identical manufacturing process, identical packaging and are both provided sterile for single-patient, single-use in the same device volume.

The performance of Tactoset + BMA was compared to Tactoset in a rabbit critical sized femoral defect model. At the 12-week timepoint, animal study data demonstrated new bone formation averages of 14.90% in the Tactoset + BMA group, 14.65% in the Tactoset predicate group, and 5% in the empty defect negative control group. Animal study data demonstrated that

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approximately 54.3% of implant material remained in the Tactoset + BMA group and 60.9% remained in the Tactoset group 12 weeks following implantation. Clinical performance has not been evaluated.

No clinical data were required to support the substantial equivalence.

	Table 1. Substantial Equivalence of the Subject and Predicate Devices.
Information	Subject Device	Primary Predicate
	(Tactoset with Bone Marrow Aspirate)
Manufacturer	Anika Therapeutics, Inc.	Anika Therapeutics, Inc.
Trade Name	Tactoset	Tactoset
510(k) Number	TBD	K212083
Product Code	MQV	MQV
Classification	Resorbable calcium salt bone void filler device	Resorbable calcium salt bone void filler device
Materials	Powder: 4g	Powder: 4g
	- α-Tricalcium phosphate	- α-Tricalcium phosphate
	- Calcium carbonate	- Calcium carbonate
	- Monocalcium phosphate	- Monocalcium phosphate
	Liquid: 4mL setting solution, as supplied	Liquid: 4mL setting solution
	- Sodium hyaluronate	- Sodium hyaluronate
	- Citric acid	- Citric acid
	- Sodium phosphate dibasic	- Sodium phosphate dibasic

	3mL of the supplied setting solution may be
	combined with 1 mL of autogenous bone marrow
Physical Form	Injectable Paste/Putty	Injectable Paste/Putty
Dimension (CC)	4	4
Mixing Time (Min)	1	1
Min Working Time	7-18	7-18
(Min)
Setting Time (Min)	10	10
Sterility Method	Single Use, Sterile, SAL 10-6	Single Use, Sterile, SAL 10-6
	Setting Solution: Autoclave and VHP	Setting Solution: Autoclave and VHP
	Powder Component: Gamma Irradiation	Powder Component: Gamma Irradiation
Pyrogenicity	LAL < 20 EU/device	LAL < 20 EU/device
Packaging	The liquid syringe is double packaged in Tyvek	The liquid syringe is double packaged in heat-sealed
	pouches. The cement powder is provided in a mixing	Tyvek pouches. The cement powder is provided in a
	syringe packaged in a foil pouch. The foil pouch is	mixing syringe packaged in a foil pouch. The foil pouch
	then packaged in a plastic tray with a Tyvek lid.	is then packaged in a plastic tray with a Tyvek lid.

Table 1, Substantial Fauivalanaa of the Subject and Prodicete Device

Conclusion:

The subject device and the predicate devices have intended use, have similar technological characteristics, and are made of similar materials. The subject and predicate devices are packaged in similar materials and are sterilized using similar methods. The data included in this submission demonstrate substantial equivalence to the predicate devices listed above. Tactoset is as safe, as effective, and performs as well as, or better, than 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.