OrthoBlast® II is an osteoinductive and osteoconductive bone filling material indicated: OrthoBlast® II is indicated for orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. OrthoBlast" II is included to be packed gently mo bony gapo in the exercial see defects may be surgically created or from the result of traumatic injury to the bone.

Device Description

OrthoBlast® II is derived from selected donated human bone tissue that has been processed into particles. The bone particles are subsequently demineralized using a hydrochloric acid process. The demineralized bone matrix (DBM) is combined with a reverse phase carrier, cancellous bone from the same donor, and formulated to a gel or putty-like consistency.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study information for the IsoTis OrthoBiologics OrthoBlast® II device, based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

The provided text does not explicitly define quantitative "acceptance criteria" in the typical sense (e.g., minimum sensitivity, specificity, or specific numerical outcomes). Instead, it describes performance deemed sufficient for substantial equivalence. The "reported device performance" refers to the outcomes of the tests conducted.

Acceptance Criteria (Implied)	Reported Device Performance
Viral Inactivation	Suitable inactivation potential of processing methods for a wide range of potential human viruses.
Osteoinductive Potential	The in vitro assay (measuring alkaline phosphatase activity) has been validated against the in vivo athymic rat model. It predicts with at least 95% confidence the in vivo osteoinductivity of the test material. 67 out of 67 test lots that passed the in vitro assay passed the in vivo athymic rat assay (intramuscular bone formation confirmed).
Overall Safety & Effectiveness	Data from sheep and rabbit models by histological methods substantiate OrthoBlast II Putty and Paste safety and effectiveness for specified indications.

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

Viral Inactivation Validation: Not specified. A "selected panel of viruses" was used. The study type is not explicitly stated as retrospective or prospective, but it's a validation study of the processing methods.
Osteoinductive Potential:
- In vitro assay: Not specified regarding the number of samples for the in vitro assay validation itself.
- In vivo validation (athymic rat model): 67 individual test lots of DBM.
- Data Provenance: Not specified, but likely from laboratory studies.
Product Performance Testing (Animal Models): Not specified (e.g., number of animals). "Performance of OrthoBlast II DBM has been evaluated in sheep and rabbit models." The study type is likely prospective animal testing.

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

Viral Inactivation: Not applicable. Ground truth is determined by lab tests measuring viral inactivation.
Osteoinductive Potential: Not applicable to human experts. The ground truth for the in vivo validation was "confirmation of intramuscular bone formation" in the athymic rat model, likely assessed by histopathology, which would involve trained histologists, but the number and qualifications are not specified.
Product Performance Testing (Animal Models): Not applicable to human experts in the context of establishing ground truth for the device's performance directly. The performance was evaluated by "histological methods," which would involve trained histologists, but their number and qualifications are not specified.

4. Adjudication Method for the Test Set

Not applicable to the studies described. The studies are laboratory and animal-based, measured against objective endpoints (viral inactivation metrics, alkaline phosphatase activity, confirmation of bone formation via histology), rather than human interpretation requiring adjudication.

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

No. An MRMC comparative effectiveness study involving human readers is not mentioned.

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

Yes, in a conceptual sense. The studies described (viral inactivation, in vitro and in vivo osteoinductivity, animal performance) assess the device's inherent biological and physical properties and performance characteristics in isolation, without human-in-the-loop interaction as would be relevant for diagnostic AI.

7. The Type of Ground Truth Used

Viral Inactivation: Laboratory measurements of viral reduction/inactivation.
Osteoinductive Potential:
- For the in vitro assay: Alkaline phosphatase activity levels compared to controls.
- For the in vivo validation: Histological confirmation of intramuscular bone formation in athymic rats.
Product Performance Testing (Animal Models): Histological assessment of bone healing/ingrowth in sheep and rabbit models.

8. The Sample Size for the Training Set

Viral Inactivation Validation: Not applicable, as this is a validation of processing methods, not a "training set" for an algorithm.
Osteoinductive Potential: Not applicable. While the in vitro assay was "validated against" the in vivo model, it's not a machine learning training set. The 67 test lots mentioned are for validating the in vitro assay's correlation with in vivo results, rather than training an algorithm.
Product Performance Testing (Animal Models): Not applicable. These are performance studies, not training sets.

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

Not applicable, as no machine learning "training set" is described for this device. The studies are evaluating the biological and material properties of the bone void filler.

Summary

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DEC 5 2005

510(k) Summary for IsoTis OrthoBiologic OrthoBlast® II

1. Sponsor

IsoTis OrthoBiologics, Inc. 2 Goodyear, Suite B Irvine, CA 92618 U.S.A

Contact Person:	Paul Doner
Telephone:	(949) 855-7168
Facsimile:	(949) 595-8711

November 11, 2005 Date Prepared:

2. Device Name

Proprietary Name:	OrthoBlast® II Paste and Putty
Common/Usual Name:	Bone Void Filler
Classification Name:	Sec. 888.3045 Resorbable calcium salt bone void fillerdevice.

3. Predicate Devices

DynaGraft II Putty and Gel (K040416)

Device Description 4.

న. Intended Use

OrthoBlast® II is indicated for orthopedic applications as filler for gaps or voids that are not intrinsic to the stability of the bony structure. OrthoBlast® II is indicated to be packed gently into bony gaps in the skeletal system as a bone graft extender and as a bone void filler of the extremities and pelvis. These defects may be surgically created or from the result of traumatic injury to the bone.

Technological Characteristics and Substantial Equivalence 6.

OrthoBlast® II and its predicate device are similar in design, materials of construction and function. The proposed and predicate device are osteoconductive

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and osteoinductive. The OrthoBlast II product and its predicate device provide interconnected, porous scaffold and an environment for new bone ingrowth and stimulate bone growth. All products are provided sterile and for single patient use.

The only differences between the proposed device and its predicate are the addition of cancellous bone to the formulation and a lower concentration of DBM in the product. The donor bone in the OrthoBlast II product meets the requirements of the AATB. Product safety and effectiveness is adequately supported by the substantial equivalence information, materials data and test results provided in this Premarket Notification.

Viral Inactivation Validation

The methods for processing DBM contained in OrthoBlast® II were evaluated for their viral inactivation potential. A selected panel of viruses representing various virus types, sizes, shapes and genomes were evaluated. The viral inactivation testing demonstrated suitable inactivation potential of the processing methods for a wide range of potential human viruses.

Osteoinductive Potential

The osteoinductive potential of the DBM used in OrthoBlast® II is determined via an in vitro assay. The assay measures the alkaline phosphatase activity of myoblast cells. The level of alkaline phosphatase induction is compared to positive and negative DBM controls. Results from the assay were correlated with results from implantation of DBM into an athymic rat muscle pouch. Analysis of these results shows that the in vitro assay has been validated against the in vivo athymic rat model and predicts with at least 95% confidence the in vivo osteoinductivity of the test material. 67 out of 67 test lots that passed the in vitro assay passed the in vivo athymic rat assay via confirmation of intramuscular bone formation.

Each lot of DBM incorporated in OrthoBlast® II Putty and Paste is evaluated for osteoinductive potential using an in vitro assay. Testing each lot of DBM assures that only DBM with osteoinductive potential is used in OrthoBlast® II Putty and Paste. Although DBM used in the final product has been shown to be osteoinductive using an in vitro assay, the combination of DBM, cancellous bone chips and inert carrier has not been evaluated for osteoinductivity; therefore, it is unknown to what extent the formulation components may alter the osteoinductivity of the DBM. Additionally, it is unknown how osteoinductivity of the DBM component, measured via the in vitro assay, will correlate with human clinical performance of OrthoBlast II.

Product Performance Testing

Performance of OrthoBlast II DBM has been evaluated in sheep and rabbit models by histological methods for the indication specified in this Premarket Notification.

These data substantiate OrthoBlast II Putty and Paste safety and effectiveness for the indications presented in the Premarket Notification.

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Image /page/2/Picture/1 description: The image shows the seal of the Department of Health and Human Services, USA. The seal features a circular border with the text "DEPARTMENT OF HEALTH AND HUMAN SERVICES, USA" arranged around the perimeter. Inside the circle is a stylized emblem resembling an eagle or bird in flight, composed of three curved lines.

Food and Drug Administration 9200 Corporate Boulevard Rockville MD 20850

DEC 5 2005

Paul Doner Director of Regulatory Affairs and Quality Assurance IsoTis OrthoBiologics, Inc. 2 Goodyear, Suite B Irvine, California 92618

Re: K050642

Trade/Device Name: OrthoBlast® II Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: II Product Code: MBP, MQV Dated: November 13, 2005 Received: November 14, 2005

Dear Mr. Doner:

We have reviewed your Section 510(k) premarket notification of intent to market the device we nave reviewed your becaren or (2) fee device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate for use stated in the encreated of the enactment date of the Medical Device Amendments, or to commerce provide to May 20, 1978, the ennounce with the provisions of the Federal Food, Drug, devices mat have been roomstilled in assee approval of a premarket approval application (PMA). and Cosmetic Act (11ct) that as novice, subject to the general controls provisions of the Act. The r ou may, merciole, market are as act include requirements for annual registration, listing of general controls provision gractice, 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 If your device is elassified (over a controls. Existing major regulations affecting your device can may be subject to saterial Regulations, Title 21, Parts 800 to 898. In addition, FDA may be found in the Ood of reans concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean I Toase oc acrisou that I Drimination that your device complies with other requirements of the Act that I DA has made a sond regulations administered by other Federal agencies. You must of any i-cocraf statutes and regaraments, including, but not limited to: registration and listing (21 Comply with an the Not 6 require Part 801); good manufacturing practice requirements as set CFR in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic form in the qualify of the provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

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Page 2 - Paul Doner

This letter will allow you to begin marketing your device as described in your Section 510(k) I his letter will anow you to oogin manteally your antial equivalence of your devertits your devertis prematication. The PDA micing of east in 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 If you desire specific advice for your acrise of the career note the regulation entitled, colliati the Office of Comphalled as (2 + + + + + + + 807.97). You may obtain Milsoranung by reference to premaintenensibilities under the Act from the Division of Small other general information on your responser Assistance at its toll-free number (800) 638-2041 or Manufacturers, International and Octisa.http://www.fda.gov/cdrh/industry/support/index.html.

Sincerely yours,

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

Enclosure

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Indications for Use Statement

K050642 510(k) Number (if known):

. OrthoBlast® li Device Name:

Indications for Use:

OrthoBlast® II is an osteoinductive and osteoconductive bone filling material indicated:

OrthoBlast® II is indicated for orthopedic applications as filler for gaps or voids that are Offhoblast "If is Indicated for of the bony structure. OrthoBlast" II is included to be packed not filthisic to the stablily of the bony craft extender and as a bone void as a bone void gently mo bony gapo in the exercial see defects may be surgically created or from the result of traumatic injury to the bone.

Prescription Use	X
(Part 21 CFR 801 Subpart D

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_Lo 5064 C

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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.