Exactech Resorbable Bone Paste is intended for use as a bone graft extender (extremities, spine, pelvis) and as a bone void filler for bony voids or gaps of the extremities and pelvis that are not intrinsic to the stability of the bony structure. These defects may be surgically created osseous defects or osseous defects created from traumatic injury to the bone.

Exactech Resorbable Bone Paste may be used with rigid fixation systems.

Device Description

Exactech Resorbable Bone Paste is a mixture of demineralized bone matrix (DBM) in a biginert polvethylene divcol (PEG) based polymer and is provided as an aseptic manufacture single use. ready to use implantable device derived from a single donor. DBM resorbs and is replaced with new bone during the healing process.

AI/ML Overview

Acceptance Criteria and Device Performance Study for Exactech Resorbable Bone Paste

This document summarizes the acceptance criteria and the study that demonstrates the Exactech Resorbable Bone Paste meets these criteria, based on the provided 510(k) summary.

1. Table of Acceptance Criteria and Reported Device Performance

The provided 510(k) summary primarily focuses on demonstrating substantial equivalence to predicate devices and establishing safety and biocompatibility. It does not explicitly state quantitative "acceptance criteria" in terms of performance metrics (e.g., specific percentages of bone formation or healing time) for the Exactech Resorbable Bone Paste itself in human subjects. Instead, the "acceptance criteria" are implied through established safety principles, biocompatibility, and qualitative osteoinductivity in an animal model, proving that the device is fit for its intended use as a bone void filler and graft extender.

However, a key "performance" aspect evaluated is the osteoinductivity of the Demineralized Bone Matrix (DBM) component.

Acceptance Criteria (Implied)	Reported Device Performance
Safety and Biocompatibility:
No adverse reactions from the polymer carrier.	Polymer carrier (polyethylene glycol-based) is "bioinert and biocompatible with host tissue and presents no new safety issues."
Human DBM is biocompatible, safe, and effective.	"Human demineralized bone used in Exactech Resorbable Bone Paste is single-donor processed, biocompatible, safe and effective for the repair of bone defects. ...The biocompatibility and efficacy of manufactured demineralized bone matrix has been established through its long history of safe and effective use as a human tissue for transplant without reported incidents of infection or complication."
Effective viral reduction of donor bone.	"This study demonstrates the demineralization process used on donor bone contained in Exactech Resorbable Bone Paste effectively eliminates or reduces the virus responsible for potential infectious disease, which include HIV and Hepatitis... and can reasonably be anticipated to diminish the titers of other viruses."
Device is sterile.	"Exactech Resorbable Bone Paste is aseptic manufactured for single patient use."
Osteoinductivity (DBM Component):
DBM demonstrates osteoinductivity potential.	"Each lot of DBM is screened for osteoinductivity potential, with only acceptable DBM being manufactured into Exactech Resorbable Bone Paste. Osteoinductivity of each lot of Exactech Resorbable Bone Paste is verified using a single test protocol and demonstrates the DBM and the product to be osteoinductive in the athymic mouse." A score of 2 or higher implies some level of endochondral ossification or new bone formation, aligning with osteoinductivity.

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

The primary non-clinical testing described is for osteoinductivity and viral reduction.

Osteoinductivity Test Set:
- Sample Size: 4 samples (implanted bilaterally into the gastrocnemius muscle of 2 animals). This is for each lot of DBM and the final product.
- Data Provenance: Prospective animal study in athymic mice. No country of origin is explicitly stated, but the submission is to the FDA (United States).
Viral Reduction Study Test Set:
- Sample Size: The number of biological samples (e.g., infected bone tissue used in the study) is not specified. However, the study involved testing against four distinct virus models (HAV, HIV-1, PPV, PrV).
- Data Provenance: Prospective in vitro study conducted by a CLIA certified testing laboratory. No country of origin is explicitly stated.

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

Osteoinductivity: The scoring for osteoinductivity (ranging from 1 to 4) is performed "in accordance with the test protocols defined by Schwartz S. Melloniq, Jl. Carnes, Jr. DL. de la Fontaine J. Cochran DL. Dean DD, Boyan BD (1996) Ability of Commercial Demineralized Freeze-dried Bone Allograft to Induce New Bone Formation J. Perio 67:918-926 and the ASTM Draft Standard Guide for the Assessment of Bone Inductive Material." While it's implied that an expert or trained personnel would perform this scoring, the number and qualifications of specific human experts (e.g., pathologists, histologists) involved in the scoring process for this specific device's study are not detailed in the summary. The ground truth is therefore based on established, standardized histological assessment criteria.
Viral Reduction: The study was conducted by a "CLIA certified testing laboratory." This implies that the ground truth (e.g., viral titers, reduction efficiency) was established by qualified laboratory professionals following validated protocols. The number of experts is not specified.

4. Adjudication Method for the Test Set

Osteoinductivity: The summary does not describe a formal "adjudication" method (like 2+1 or 3+1 expert consensus) for the osteoinductivity scoring. The scoring is done "in accordance with the test protocols." This suggests a standardized, objective assessment criterion rather than a subjective human opinion requiring adjudication.
Viral Reduction: As a laboratory test, adjudication would typically involve internal quality control and validation procedures based on quantitative scientific data, rather than expert consensus on subjective interpretations. No specific adjudication method similar to those used for image interpretative tasks is described.

5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study Was Done

No, an MRMC comparative effectiveness study was not done for this device. The submission is for a bone void filler/graft extender and focuses on demonstrating substantial equivalence, safety, and basic biological function (osteoinductivity) rather than comparing human reader performance with and without AI assistance. The device itself is biological/biomaterial, not an AI diagnostic tool.

6. If a Standalone (i.e., algorithm only without human-in-the-loop performance) Was Done

This question is not applicable. Exactech Resorbable Bone Paste is a physical medical device (bone void filler), not an algorithm or AI system. Therefore, standalone algorithm performance is not relevant.

7. The Type of Ground Truth Used

Osteoinductivity: Histological analysis of explanted muscle tissue from athymic mice, scored against defined criteria for endochondral ossification and new bone formation. This is a pathology-based ground truth (histological assessment).
Viral Reduction: Quantitative viral assays (e.g., plaque assays, PCR) measuring viral titers before and after the demineralization process. This is a laboratory-based, quantitative ground truth.
Biocompatibility & Safety: Based on established literature ("long history of safe and effective use as a human tissue for transplant") and in vitro testing for the carrier. This is a combination of historical evidence and laboratory testing.

8. The Sample Size for the Training Set

The concept of "training set" is not applicable as this is not an AI/machine learning device. The studies described are for verification and validation of the product's properties for regulatory submission, not for training a model.

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

Not applicable, as there is no training set for an AI model. For the development of the DBM processing and the PEG carrier, extensive biological research and material science principles would have guided their design and selection, but these are not referred to as "training sets" in this context.

Summary

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FEB 27 2004

510(k) Summary of Safety and Effectiveness

This 510(k) Summary for Exactech Resorbable Bone Paste is provided as required per Section 513(1)(3) of the Food, Drug and Cosmetic Act.

1. Submitter:	Exactech Inc.2320 NW 66th CourtGainesville, Florida 32653Telephone 352-377-1140Fax 352-378-2617
Contact person:	Steve Lin, D.ScVice President, Advanced Technology & Business DevelopmentExactech Inc.Telephone 352-377-1140Fax 352-378-2617
Date of original submission:	01-08-2001
FDA Establishment Number	1038671

1. Proprietary Name: Exactech Resorbable Bone Paste Common Name: Bone void filler Product Code: MQV Device Class: Not classified Classification Panel: Orthopaedic

3. Legally Marketed Devices for Substantial Equivalence Comparison:

Product Code	Manufacturer	510(k) Number	Product
MQV	Wright	K963562	Wright Plaster of Paris Pellets
MQV	EBI	K011386	EBI Osteostim Granules –Resorbable Bone Graft Substitute
MQV	Neu Coll Laboratories	K000122	Collagraft Strip Bone Graft Matrix

Comparison to the Predicate Device(s): 4.

Exactech Resorbable Bone Paste shares the same function and intended use and therefore is substantially equivalent to Wright Medical - Plaster of Paris (Osteoset), Neu Coll Laboratories -Collagraft Strip and EBI - EBI OsteoStim Granules - Resorbable Bone Graft Substitute as a bone void filler.

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510(k) Summary of Safety and Effectiveness

The polymer carrier used in Exactech Resorbable Bone Paste absorbs in-vivo and is used solely for the ease of handling and delivery of DBM.

Device Description: 5.

Indications for Use 6.

Exactech Resorbable Bone Paste may be used with rigid fixation systems.

7. Contraindications:

Exactech Resorbable Bone Paste is not intended to provide structural support during the healing process, therefore, Exactech Resorbable Bone Paste is contraindicated in cases where structural support of the skeletal system is required by the graft during healing.

This allograft should not be implanted into sites with an active infection.

Polymixin Sulfate B and Bacytracin are used in processing this graft and trace amounts remain. Since it is impossible to quantify the levels at which any individual may have an allergic response, this product is contraindicated in patients with known sensitivity.

8. Safety and Effectiveness Information:

Human demineralized bone used in Exactech Resorbable Bone Paste is single-donor processed. biocompatible, safe and effective for the repair of bone defects. Exactech Resorbable Bone Paste is aseptic manufactured for single patient use.

The polymer carrier used in Exactech Resorbable Bone Paste is bioinert and biocompatible with host tissue and presents no new safety issues.

The biocompatibility and effically manufactured demineralized bone matrix has been established through its long history of safe and effective use as a human tissue for transplant without reported incidents of infection or complication. A viral reduction study was conducted by a CLIA certified testing laboratory using four virus models representing RNA, DNA,

Rev. 2-26-2004

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510(k) Summary of Safety and Effectiveness

envelope and non-envelope virus, which included: 1) Hepatitis A Virus (HAV), non-enveloped, RNA-containing picornavirus 2) Human immunodeficiency virus type 1 (HIV-1) enveloped, RNA-containing retrovirus. 3) Porcine parvovirus (PPV) non-enveloped. DNA-containing parvovirus, which serves as a model for other parvovirus such as human parvovirus B19 and 4) Pseudorabies virus (PrV), enveloped. DNA-containing virus belonging to the Herpesviridae family and serves as a model for other herpesviruses such as Cytomegalovirus (CMV). This study demonstrates the demineralization process used on donor bone contained in Exactech Resorbable Bone Paste effectively eliminates or reduces the virus responsible for potential infectious disease, which include HIV and Hepatitis.

Non-Clinical Testing: ഴി

Each lot of DBM is screened for osteoinductivity potential, with only acceptable DBM being manufactured into Exactech Resorbable Bone Paste. Osteoinductivity of each lot of Exactech Resorbable Bone Paste is verified using a single test protocol and demonstrates the DBM and the product to be osteoinductive in the athymic mouse. Osteoinduction assay results in the athymic mouse model should not be interpreted to predict clinical performance in human subjects.

Test samples are implanted bilaterally into the castrocnemius muscle of 2 animals (total of 4 samples of each lot), explanted at day 35 and scored for osteoinductivity in accordance with the test protocols defined by Schwartz S. Melloniq, Jl. Carnes, Jr. DL. de la Fontaine J. Cochran DL. Dean DD, Boyan BD (1996) Ability of Commercial Demineralized Freeze-dried Bone Allograft to Induce New Bone Formation J. Perio 67:918-926 and the ASTM Draft Standard Guide for the Assessment of Bone Inductive Material. A score of 1-4 is assigned with:

1 = implant present no new bone or cartilage present
2 = endochondral ossification <25% implant site and/or new bone covering <25% of implant
3 = endochondral ossification 26-50% implant site and/or new bone covering 26-50% of implant
4 = >50% endochondral ossification and/or new bone covering > 50% of implant

A viral reduction study was conducted by a CLIA certified testing laboratory using four virus models representing RNA, DNA, envelope and non-envelope virus, which included: 1) Hepatitis A Virus (HAV), non-enveloped, RNA-containing picornavirus 2) Human immunodeficiency virus type 1 (HIV-1) enveloped, RNA-containing retrovirus, 3) Porcine parvovirus (PPV) non-enveloped, DNA-containing parvovirus, which serves as a model for other parvovirus such as human parvovirus B19 and 4) Pseudorabies virus (PrV), enveloped, DNA-containing virus belonging to the Herpesviridae family and serves as a model for other herpesviruses such as Cytomegalovirus (CMV). This study demonstrates the demineralization process used on donor bone contained in Exactech Resorbable Bone Paste significantly diminishes these model viruses and can reasonably be anticipated to diminish the titers of other viruses.

Rev. 2-26-2004

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Image /page/3/Picture/1 description: The image shows the seal of the Department of Health & Human Services (HHS) of the United States. The seal features the department's name encircling a symbol. The symbol consists of three stylized human profiles facing right, stacked on top of each other, with flowing lines beneath them, possibly representing water or movement.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

FEB 2 7 2004

Ms. Rebecca S. Roberts CTBS Sr. Regulatory Representative Tissue Bank Director Exactech 2320 NW 66th Court Gainesville, Florida 32653

Re: K020078

Trade Name: Exactech Resorbable Bone Paste Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MOV, MBP Dated: November 25, 2003 Received: December 1, 2003

Dear Ms. Roberts:

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. 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 such 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

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Page 2 - Ms. Rebecca S. Roberts CTBS

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.

This letter will allow you to begin 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 Office of Compliance at (301) 594-4659. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers, International and Consumer Assistance at its toll-free number (800) 638-2041 or (301) 443-6597 or at its Internet address http://www.fda.gov/cdrh/dsma/dsmamain.html

Sincerely yours,

L. Mark N. Milkman

Celia M. Witten, Ph.D. M.D. Director Division of General, Restorative and Neurological Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Exactech Resorbable Bone Paste

Indications for Use

510(k) Number (if known):

K020078

Device Name:

Indications for Use:

Exactech Resorbable Bone Paste may be used with rigid fixation systems.

Prescription Use X Over-The-Counter Use AND/OR (Part 21 CFR 801 Subpart D) (21 CFR 807 Subpart C) (PLEASE DO NOT WRITE BELOW THIS LINE-CONTINUE ON ANOTHER PAGE OF NEEDED)

Concurrence of CDRH, Office of Device Evaluation (ODE)

l. Mark M. Millerson

Division of General, Restorative, and Neurological Devices

510(k) Number K020078

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.