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

Device Description

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

AI/ML Overview

The provided document is a 510(k) summary for a medical device (Exactech Resorbable Room Temperature Bone Paste) and does not describe software or an AI/ML powered medical device. Therefore, many of the requested categories for AI/ML device studies are not applicable.

However, I can extract the relevant information regarding the device's acceptance criteria and the studies performed to demonstrate its safety and effectiveness based on the content available.

Here's a breakdown of the information that can be extracted, and where the requested AI/ML specific information is not applicable:

Acceptance Criteria and Device Performance for Exactech Resorbable Room Temperature Bone Paste

This device is a bone void filler and bone graft extender. The safety and effectiveness information is based on its components, manufacturing processes, and biological testing, rather than an AI/ML algorithm.

1. Table of Acceptance Criteria and Reported Device Performance

| Acceptance Criteria Category | Specific Criterion | Reported Device Performance |
|:--------------------------------------|:-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| Sterility | Each lot must undergo microbiologic testing for sterility in conformance with 21CFR610.12. | Performed and in conformance. (Each lot of Exactech Resorbable Room Temperature Bone Paste undergoes microbiologic testing for sterility in conformance with 21CFR610.12.) |
| Biocompatibility (DBM carrier) | Human demineralized bone (DBM) is known to be biocompatible. | Demonstrated biocompatible based on long history of use without adverse reactions or complications. |
| Biocompatibility (Polymer carrier)| The polyethylene divcol (PEG) based polymer carrier must be demonstrated to be biocompatible. | Demonstrated biocompatible in accordance with ISO 10993 testing and other in vivo testing. |
| Osteoinductive Potential | A minimum of two implanted samples per lot must demonstrate osteoinductive potential, assessed by histological evidence of endochondral bone formation (cartilage/chondrocytes, osteoblasts, osteoid, newly formed/mineralized bone, marrow/fat cells) in an athymic nude mouse model, in accordance with the ASTM Draft Standard Guide for the Assessment of Bone Inductive Material. | Test samples from each lot were implanted bilaterally into the gastrocnemius muscle of 2 athymic nude mice and demonstrated successful osteoinductive potential. (Note: Osteoinduction assay results in the athymic mouse model should not be interpreted to predict clinical performance in human subjects). |
| Viral Inactivation | The demineralization process used on donor bone must significantly diminish model viruses (HAV, HIV-1, PPV, PrV) to reasonably be anticipated to diminish titers of other viruses. | A viral reduction study demonstrated significant diminution of all four model viruses by the demineralization process. |

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

Osteoinductive Potential Test:
- Sample Size: 2 athymic nude mice for each lot tested. Each mouse had samples implanted bilaterally (total of 4 implant sites per lot).
- Data Provenance: In vivo animal study (athymic nude mice). The country of origin of the data is not specified. This is a prospective animal study for each lot.
Viral Inactivation Validation Study:
- Sample Size: Not specified in terms of number of samples, but the study used four virus models directly: Hepatitis A Virus (HAV), Human immunodeficiency virus type 1 (HIV-1), Porcine parvovirus (PPV), and Pseudorabies virus (PrV).
- Data Provenance: This was a laboratory study conducted by a CLIA certified testing laboratory using virus models. The country of origin of the data is not specified. This is a prospective laboratory study.

(Note: Data provenance for human clinical data is not applicable as this is not a clinical study involving human patients for effectiveness data, but rather a device relying on material properties and established biocompatibility/safety of its components.)

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

Osteoinductive Potential: The assessment was based on "histological evidence of endochondral bone formation." This implies evaluation by a qualified histopathologist, but the specific number and qualifications of experts are not provided in this summary.
Viral Inactivation Validation: Conducted by a "CLIA certified testing laboratory." The specific experts involved are not detailed.

4. Adjudication Method for the Test Set

The document does not describe an adjudication method for the test sets as it pertains to human interpretation/consensus, which is common in AI/ML studies. The assessments are based on laboratory testing and histological criteria.

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 a physical medical device (bone paste), not an AI/ML powered device. No MRMC study was conducted.

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

Not Applicable. This is a physical medical device (bone paste), not an AI/ML powered device. No standalone algorithm performance study was conducted.

7. The type of ground truth used

Osteoinductive Potential: Histological evidence of endochondral bone formation as defined by specific biological markers (cartilage/chondrocytes, osteoblasts, osteoid, newly formed/mineralized bone, marrow/fat cells). This is a biological ground truth established through scientific observation and defined criteria.
Viral Inactivation Validation: Measurement of viral titers before and after the demineralization process, comparing the reduction against established criteria for viral inactivation. This is a laboratory-based, quantitative ground truth.
Biocompatibility (DBM): Long history of clinical use without adverse reactions or complications serves as the "ground truth" for biocompatibility.
Biocompatibility (Polymer): ISO 10993 testing and other in vivo testing results (standardized, objective measures).

8. The sample size for the training set

This device does not involve an AI/ML model, so there is no concept of a "training set" in the context of machine learning. The "training" for this device would be analogous to continuous quality control and material sourcing, which are ongoing processes.

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

Not Applicable. As there is no AI/ML training set, this question is not relevant.

Summary

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K04-0755

JUN 1 7 2004

Special 510(k) Summary of Safety and Effectiveness

This 510(k) Summary for Exactech Resorbable Room Temperature 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:	03-19-2004
	FDA Establishment Number	1038671
2.	Proprietary Name:	Exactech Resorbable Room Temperature BonePaste
	Common Name:	Bone void filler
	Product Code:	MQV, MBP
	Device Class:	Class II
	Classification Panel:	Orthopaedic
3.	Legally Marketed Devices for Substantial Equivalence Comparison:

ਦ

Product Code	Manufacturer	510(k) Number	Product
MQV, MBP	Exactech Inc.	K020078	Exactech Resorbable Bone Past

Comparison to the Predicate Device(s): 4.

Exactech Resorbable Room Temperature Bone Paste shares the same components, function and intended use as the predicate device, Exactech Resorbable Bone Paste. Modifications to this device do not affect safety and efficacy of the device and is therefore substantially equivalent to predicate device.

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Special 510(k) Summary of Safety and Effectiveness

Device Description: 5.

6. Indications for Use

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

7. Contraindications:

Exactech Resorbable Room Temperature Bone Paste is not intended to provide structural support during the healing process; therefore. Exactech Resorbable Room Temperature 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:

Exactech Resorbable Room Temperature Bone Paste is aseptically manufactured for single patient use. Each lot of Exactech Resorbable Room Temperature Bone Paste undergoes microbiologic testing for sterility in conformance with 21CFR610.12.

Human demineralized bone used in Exactech Resorbable Room Temperature Bone Paste is known to be biocompatible based on its long history of use without adverse reactions or complications.

The polymer carrier used in Exactech Resorbable Room Temperature Bone Paste was demonstrated to be biocompatible in accordance with ISO 10993 biocompatibility testing and other in vivo testing.

Rev 06-14-2004

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Special 510(k) Summary of Safety and Effectiveness

Osteoinductive Potential a.

Test samples from each lot of Exactech Resorbable Room Temperature Bone Paste are implanted bilaterally into the gastrocnemius muscle of 2 athymic nude mice in accordance with the ASTM Draft Standard Guide for the Assessment of Bone Inductive Material. A minimum of two implanted samples must demonstrate osteoinductive potential as assessed by histological evidence of endochondral bone formation, including the presence of cartilage or chondrocytes, active osteoblasts, osteoid, newly formed and mineralized bone and/or marrow and associated fat cells. Osteoinduction assay results in the athymic mouse model should not be interpreted to predict clinical performance in human subjects.

Viral Inactivation Validation b.

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 Room Temperature Bone Paste significantly diminishes these model viruses and can reasonably be anticipated to diminish the titers of other viruses.

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Image /page/3/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo is a circular seal with the words "DEPARTMENT OF HEALTH & HUMAN SERVICES • USA" around the perimeter. Inside the circle is an emblem of an eagle with its wings spread, clutching a staff with a snake wrapped around it, which is a symbol of medicine and healing.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

JUN 1 7 2004

Ms. Rebecca S. Roberts CTBS Regulatory Affairs Representative - Biologics Exactech Inc. 2320 NW 66th Court Gainesville, Florida 32653

Re: K040755

Exactech Resorbable Room Temperature Bone Paste Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler devices Regulatory Class: Class II Product Code: MQV, MBP Dated: May 17, 2004 Received: May 19, 2004

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 Eederal 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

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Page 2 - Ms. Rebecca S. Roberts CTBS

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) This iction will anow you to organ made of substantial equivalence of your device to a premarket notification. - The PDF intilation 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), if you desire specific advice to: Jour are 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 may obtain 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,
O. Merle A. Melkersen

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 Room Temperature Bone Paste

Indications for Use

510(k) Number (if known):

K040155

Exactech Resorbable Room Temperature Bone Paste

Indications for Use:

Device Name:

Exactech Resorbable Bone Paste is intended for use as a bone graft extender (extremities, spine, Exacted Resorbable Bone it asie is intended for acc a benefit es and pelvis that are not pelvis) and as a bone vold finer for borry volus of gape of the may be surgically created osseous infirmsic to the stabliky of the won't from traumatic injury to the bone.

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

Prescription Use X(Part 21 CFR 801 Subpart D)	AND/OR	Over-The-Counter Use(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)

(Division Sign-Off)

Division of General, Restorative, and Neurological Devices

510(k) Number	K040753
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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.