The Osteogenics BoneSource® Hydroxyapatite Cement (HAC) is a self-setting, calcium phosphate cement intended for use in the repair of neurosurgical burr holes, contiguous craniotomy cuts and other cranial defects with a surface area no larger than 25cm per defect.

Device Description

The Osteogenics BoneSource® Hydroxyapatite Cement (HAC) is a self-setting, calcium phosphate cement that hardens in an aqueous environment at body temperature and consists solely of calcium phosphate compounds. The cement is mixed freshly at the time of implantation and can be applied directly into the defect to fill the void. BoneSource® remains malleable for approximately 20 minutes during which time it can be contoured to custom-fit the defect. The setting reaction is complete after four hours. BoneSource® is fabricated by combining two phosphates of calcium (i.e., dicalcium phosphate and tetracalcium phosphate). At the time of use, BoneSource® is combined with sterile water which results in an isothermic setting reaction yielding pure HAC after four hours. Under in-vitro conditions (37°C), the product hardens in approximately 20 minutes. After four hours, the reaction is complete, yielding pure hydroxyapatite with no significant dimensional changes and no by-products. The compressive strength of BoneSource® is ≥ 50 MPa. The BoneSource® paste during the setting reaction has been determined to be in the range of 6.5 to 8.5. As a consequence of its apatitic nature, the product is highly compatible with both soft and hard tissue. Approximately 45% of the implant volume consists of micropores (the remainder is solid) with an average pore size of <1 micron in diameter. This small pore diameter serves to inhibit the passage of infection-causing microorganisms. BoneSource® is supplied sterile and is intended for single use only.

AI/ML Overview

Here's an analysis of the provided text, focusing on acceptance criteria and supporting studies for the BoneSource® Hydroxyapatite Cement:

1. Table of Acceptance Criteria and Reported Device Performance

The document does not explicitly state "acceptance criteria" in a bulleted or numbered list with corresponding "reported performance." Instead, it describes various tests and their outcomes, implying that successful outcomes from these tests constituted the basis for acceptance. I have inferred the acceptance criteria based on the described testing and conclusions.

Acceptance Criteria (Inferred)	Reported Device Performance
In-Vitro Characterization
Complete setting reaction to pure hydroxyapatite within 4 hours (X-ray Diffraction)	X-ray diffraction patterns taken before hardening and after hardening demonstrate that the setting reaction is complete after four hours. The device becomes totally apatitic with no by-products present.
pH of paste during setting range 6.5 to 8.5	The pH of the BoneSource® paste during setting has been determined to be in the range of 6.5 to 8.5, verified by laboratory testing and consistent with published literature.
No significant dimensional changes upon hardening	Under in-vitro conditions (37°C), BoneSource® hardens in approximately 20 minutes with no significant dimensional changes. Measurements of molds vs. specimens, and 50g samples in acrylic cylinders, showed negligible change.
Compressive strength ≥ 50 MPa	The compressive strength of BoneSource® is ≥ 50 MPa.
Biocompatibility (Inferred: Must be non-toxic, non-irritant, non-mutagenic, non-pyrogenic, and well-tolerated at implant site)
In Vitro Cytotoxicity (Agarose Overlay) - Non-toxic to L-929 cells	Non-toxic
Guinea Pig Delayed Contact Sensitization Test - Non-irritant	Non-irritant: none of the animals in the study showed abnormal clinical signs.
Salmonella Mammalian Mutagenicity Assessment/Ames Assay - Non-mutagenic	Non-mutagenic
Limulus Amebocyte Lysate (LAL) Endotoxin Test - Non-pyrogenic	Non-pyrogenic: no detectable level of endotoxin.
USP Intramuscular Implant Test - Non-toxic effect at implant site	Non-toxic effect: difference between average encapsulation score for BoneSource® and negative control implants was zero for each animal and overall.
30-Day HAC Cranial Implant Test (dogs) - Good tissue integration, no infection/toxicity, osteogenesis	Defects filled with fibrin, fibrous tissue, and new bone. New bone extended from edges. Osteogenesis evident at all sites. No evidence of infection or toxicity of surrounding bone.
Animal Studies (Inferred: Demonstrate safety, effectiveness, bone integration, and resorption/replacement)
Hydroxyapatite Cement: Basic Chemistry and Histologic Properties (cats) - No toxicity, extrusion, migration, infection, fibrous encapsulation; bone growth into and replacement of implant	No toxic reactions, extruded implants, disk migrations, wound infections, nor fibrous encapsulation found. Bone growth occurred into implants; disks resorbed and replaced by bone.
Obliteration and Reconstruction of the Cat Frontal Sinus - Progressive replacement by bone, no complications, good integration, no volume loss/contour change, infection resistance	Progressive replacement with bone over time (CT/radiographs). No postoperative mortalities, complications, wound infections, or extrusions. Excellent integration, no loss of volume or significant change in implant contour. Ability to resist infection demonstrated.
Experimental Hydroxyapatite Cement Cranioplasty (cats) - No wound infections, structural failures; well-tolerated; progressive replacement by new bone/soft tissue without shape/volume change	No wound infections or structural failures observed; implants well tolerated histologically. Progressive replacement of cement by new bone and soft tissue without change in shape or volume. New bone comprised 77.3% (HAC) and 64.7% (HAC/autogenous bone) of replacement tissue.
Clinical Effectiveness (Inferred: Acceptable implant survival rate, minimal volume loss, device-related explants)
Implant survival rate (based on volume loss > 10% or explantation as failure)	Cumulative survival rate of 81.32% (with 11 implants not yet evaluated at 24 months and 31 not yet due for 24-month follow-up). This reflects incidences of volume loss in excess of 10% for four implants and all explants as failures (though none were considered device-related by investigators).
Clinical Safety (Inferred: Laboratory values within normal/clinically non-significant ranges, acceptable complication/adverse event rates)
Laboratory Values (Ca, Cl, Na, K, Bicarbonate, Phosphate) - Maintain within clinically normal ranges or demonstrate non-significant changes	Calcium: statistically significant changes at 12 and 24 months, but mean within-patient percent change averaged only 3.21% and 4.21% respectively, not clinically significant. Min/max levels well within handbook range. Sodium: statistically significant change at 24 months, but mean within-patient change averaged 1.01%, not clinically significant. Min/max levels well within handbook range. Potassium: statistically significant changes at 12 and 24 months, but none clinically significant. Chloride, bicarbonate, phosphate: no statistical significance. Six patients had slightly high chloride early post-op, but dropped to non-significant levels.
Complications (defect-specific & patient-specific) - Favorable rates, non-device related	Majority of implants presented no defect-specific complications. Majority of patients presented with no patient-related complications.
Adverse Events/Death - Not device-related	Five adverse events reported: two deaths from cancer (not device-related); one stroke after tumor removal with pneumonia (not device-related); one hematoma (not specified if device-related, but overall conclusion states adverse events not device-related when administered as intended); one CSF leak with BoneSource® injected through nostril (protocol violation), resulting in explantation. Overall conclusion: None device-related when administered as intended.
Substantial Equivalence	Demonstrated substantial equivalence to CranioPlastic™ (PMMA) in design and function.

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

Clinical Test Set:
- Sample Size: 103 patients presenting 175 cranial defects.
- Data Provenance: Prospective, non-randomized clinical investigational study conducted under an approved Investigational Device Exemption. Country of origin is not explicitly stated but implied to be the US, given the FDA 510(k) submission.
Animal Studies Test Set:
- Hydroxyapatite Cement: Basic Chemistry and Histologic Properties: 9 cats.
- Hydroxyapatite Cement: Obliteration and Reconstruction of the Cat Frontal Sinus: 9 cats.
- Experimental Hydroxyapatite Cement Cranioplasty: 6 cats for primary study, plus 3 additional cats for controls.
- 30-Day HAC Cranial Implant Test (Biocompatibility): 2 dogs (10 defects total, 8 with BoneSource®, 2 controls).
- Data Provenance: Prospective animal studies. No country of origin specified.
In-Vitro Testing: Sample sizes for specific in-vitro tests (e.g., number of specimens for dimensional verification, compressive strength) are not explicitly detailed, but implied to be sufficient for scientific assessment.

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

Clinical Study:
- Effectiveness (Radiographic Evaluation): The assessment was done by "radiographic evaluation (x-ray or CAT Scan)." The number and qualifications of the readers or experts who performed these evaluations are not specified within this summary.
- Safety (Complications/Adverse Events): "Considered by the Investigator and Medical Monitor." This implies at least two experts (Investigator, Medical Monitor). Their specific qualifications (e.g., number of years experience) are not provided, but they would be medical professionals overseeing the clinical trial.
- Histopathology (30-Day HAC Crania Implant Test in dogs): A "blinded histopathological evaluation" was performed. The number and qualifications of the histopathologist(s) are not specified.
Animal Studies: The histological and radiographic evaluations in the cat studies were conducted, but the specific number and qualifications of the experts (e.g., veterinary pathologists, radiologists) who established the ground truth are not mentioned.

4. Adjudication Method for the Test Set

Clinical Study: Not explicitly stated. For "Effectiveness" evaluation (volume loss), the method for combining or adjudicating multiple radiographic interpretations (if more than one reader was used) is not described. For "Safety" related to device-relatedness of outcomes, it states "considered by the Investigator and Medical Monitor," implying a consensus or adjudicated decision between at least these two individuals.
30-Day HAC Cranial Implant Test (dogs): A "blinded histopathological evaluation" was performed, but the adjudication method (e.g., if multiple pathologists disagreed) is not detailed.

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, an MRMC comparative effectiveness study involving AI assistance for human readers was not done. This document describes the safety and effectiveness of a medical device (a bone cement), not an AI diagnostic tool. Therefore, the concept of human readers improving with AI assistance is not applicable here.

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

Not Applicable. This document describes a physical medical device (bone cement), not a diagnostic algorithm.

7. The Type of Ground Truth Used

Clinical Study:
- Effectiveness: Based on radiographic evaluation (x-ray or CAT Scan) for implant stability (volume loss) and evaluation of explants (physical assessment).
- Safety: Based on laboratory data (blood chemistry) and direct clinical observations and records of postoperative complications and adverse events, interpreted by medical professionals.
Animal Studies:
- Histology: Direct examination of tissue samples for bone growth, resorption, tissue reactions, etc. (e.g., "Examination of decalcified and undecalcified sections," "blinded histopathological evaluation").
- Imaging: Computed tomography and radiographs.
- Gross observation: Direct visual assessment of implant site, wound, etc.
In-Vitro Tests: Based on laboratory measurements and analytical techniques (e.g., X-ray Diffraction, pH meter, micrometers for dimensional changes, mechanical testing for compressive strength).

8. The Sample Size for the Training Set

Not Applicable. This document describes the testing of a physical medical device, not a machine learning model. There is no concept of a "training set" in this context. The animal and in-vitro studies could be analogized to preclinical foundational research, but not a dataset for training an algorithm.

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

Not Applicable. As there is no training set for an algorithm, this question is not relevant to the provided text.

Summary

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K964557

JAN 24 1997

SUMMARY OF SAFETY AND EFFECTIVENESS BONESOURCE® HYDROXYAPATITE CEMENT (HAC)

I. GENERAL INFORMATION

Classification Name:	Methyl methacrylate for cranioplasty
Common Name:	Hydroxyapatite Cement (HAC)
Device Trade Name:	BoneSource® Hydroxyapatite Cement (HAC)
Classification Code:	87GXP
Submitter's Name & Address:	Osteogenics Inc.250 East Arapaho RoadRichardson, Texas 75081(214) 918-8361
Establishment Registration No:	2183449

Contact Person: Mary Biggers, Senior Regulatory Affairs Specialist

Summary Preparation Date: November 8, 1996

II. PREDICATE DEVICE

BoneSource® is claimed to be substantially equivalent in design and function to CranioPlastic™, manufactured by L.D. Caulk Company of Milford, Delaware and distributed by Codman and Shurtleff, Inc. of Randolph, Massachusetts. CranioPlastic™ was cleared by FDA under 510(k) K873689 on October 26, 1987.

III. DEVICE DESCRIPTION

BoneSource® is fabricated by combining two phosphates of calcium (i.e., dicalcium phosphate and tetracalcium phosphate). At the time of use, BoneSource® is combined with sterile water which results in an isothermic setting reaction yielding pure HAC after four hours. This reaction is illustrated below:

Premarket Notification: BoneSource® HAC Modification: Removal of Sinus-Communicating Warning Osteogenics Inc. November 8, 1996

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HAC Setting Reaction
$Ca_4(PO_4)_2 O + CaHPO_4 + [2H_2O]$tetracalciumphosphate	→	$Ca_5(PO_4)_3OH + [2H_2O]$hydroxyapatite(BoneSource®)
dicalciumphosphate

Under in-vitro conditions (37°C), the product hardens in approximately 20 minutes. After four hours, the reaction is complete, yielding pure hydroxyapatite with no significant dimensional changes and no by-products. The compressive strength of BoneSource® is ≥ 50 MPa. The BoneSource® paste during the setting reaction has been determined to be in the range of 6.5 to 8.5. As a consequence of its apatitic nature, the product is highly compatible with both soft and hard tissue. Approximately 45% of the implant volume consists of micropores (the remainder is solid) with an average pore size of <1 micron in diameter. This small pore diameter serves to inhibit the passage of infection-causing microorganisms. BoneSource® is supplied sterile and is intended for single use only.

IV. INDICATIONS FOR USE

V. IN-VITRO TESTING

In-vitro testing was performed using BoneSource® Hydroxyapatite Cement in order to demonstrate substantial equivalence to polymethylmethacrylate and to define safety and effectiveness parameters. In addition to fundamental device characterization, the following testing was performed. A summary is presented below:

X-ray Diffraction

X-ray diffraction was utilized to demonstrate the BoneSource® HAC reaction setting time. X-ray diffraction patterns taken before hardening and after hardening demonstrate that the setting reaction is complete after four hours. In addition, these x-ray diffraction patterns also demonstrate that the device becomes totally apatitic with no by-products present.

pH Value Determination

The pH of the BoneSource® paste during setting has been determined to be in the range of 6.5 to 8.5. This pH range was verified by laboratory testing in which pH values were measured both during and after setting, and are also consistent with values previously reported in published scientific literature.

Dimensional Verification

Under in-vitro conditions (37°C), BoneSource® hardens in approximately 20 minutes with no significant dimensional changes. Dimensional changes of HAC after setting were evaluated by measuring the dimensions of the molds used in the preparation of the diametral tensile strength and compressive strength samples and comparing these dimensions with the HAC specimens prepared from the same molds. Additionally, 50

Premarket Notification: BoneSource® HAC Modification: Removal of Sinus-Communicating Warning Osteogenics Inc. November 8, 1996

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gram samples were prepared and placed in an acrylic cylinder utilizing a high frequency vibrating table to eliminate air inclusions. After 24 hours storage, the length of acrylic mold was measured, as well as, five measurements of the center of the set cement rod using a digital micrometer. The results show negligible change

VI. ANIMAL TESTING

Well controlled animal studies were conducted to further verify safety and effectiveness parameters of BoneSource® Hydroxyapatite Cement. Summaries of these studies are presented below:

Hydroxyapatite Cement: Basic Chemistry and Histologic Properties

Nine cats were implanted with hydroxyapatite cement disks, applied directly to the surface of the calvarium. The animals were sacrificed at three, six and nine months after implantation, with no toxic reactions, extruded implants, disk migrations, wound infections nor fibrous encapsulation found. When in direct contact with viable bone, bone growth occurred into the implants, and over time, the disks were resorbed and replaced at a rate in direct proportion to surface area. Implant replacement by bone is postulated to occur through a combination of implant resorption coupled with osteoconduction.

Hydroxyapatite Cement: Obliteration and Reconstruction of the Cat Frontal Sinus

Nine cats underwent unilateral removal of the frontal sinus followed by a reconstruction of the area with non-sterile hydroxyapatite cement. The non-operated side of each cat was used as the control. The animals were sacrificed at six, 12 and 18 months postoperatively. Computed tomography and radiographs confirmed progressive replacement of the implants with bone over time. There were no postoperative mortalities, complications, wound infections or wound related complications. No implants were infected or extruded and no depressions were detected in the reconstruction areas. Examination revealed excellent integration of the implant to the surrounding bone and differed little in appearance from the surrounding non-operated frontal bone. There was no loss of volume or significant change in implant contour. Its use in this study without sterilization supports HAC's ability to resist infection unlike most other alloplastic implants.

Experimental Hydroxyapatite Cement Cranioplasty

Six cats underwent bilateral reconstruction of 2.5 cm diameter full thickness criticalsized parietal skull defects with hydroxyapatite cement. In these animals, one side was reconstructed with 100% hydroxyapatite and the other side was reconstructed with a mixture of 50% hydroxyapatite/50% ground autogenous bone. The animals were sacrificed at six and 12 months with no wound infections or structural failures observed, and the implants were well tolerated histologically. Examination of decalcified and undecalcified sections revealed progressive replacement of the cement by new bone and soft tissue without a change in the shape or volume of the hydroxyapatite reconstructed areas. New bone comprised 77.3% of the tissue replacing the hydroxyapatite implants and 64.7% of the tissue replacing the hydroxyapatite/ground autogenous bone implants. Replacement of the hydroxyapatite cement implants by new bone is postulated to occur by a continuation of osteoconduction and implant resorption.

Premarket Notification: BoneSource® HAC Modification: Removal of Sinus-Communicating Warning November 8, 1996 Osteogenics Inc.

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Three additional cats were prepared as positive and negative controls. The control animals underwent unilateral reconstruction with methyl methacrylate; the opposite sides received no reconstruction. The control animals were sacrificed at six months. None of the unreconstructed control defects was completely filled with repair bone. All methyl methacrylate reconstructed defects demonstrated foreign body giant cell formation and fibrous encapsulation of the implants and no new bone growth.

VII. BIOCOMPATIBILITY TESTING

Biocompatibility testing was conducted and performed in accordance with the Good Laboratory Practice regulation in order to assess the microbiological and toxicological impact of BoneSource® Hydroxyapatite Cement. A summary of these tests is presented below:

In Vitro Cytotoxicity Using Agarose Overlay: Non-toxic: non-toxic to L-929 cells

Guinea Pig Delayed Contact Sensitization Test

Non-irritant: none of the animals in the study showed abnormal clinical signs during the test period.

Salmonella Mammalian Mutagenicity Assessment/Ames Assay Non-mutagenic

Limulus Amebocyte Lysate (LAL) Endotoxin Test Non-pyrogenic: no detectable level of endotoxin.

USP Intramuscular Implant Test

the difference between the average encapsulation score for Non-toxic effect: BoneSource® implants and negative control implants was zero for each animal. The overall score difference for all implantation sites was also zero.

30-Dav HAC Cranial Implant Test

Ten, 4.0 mm diameter cranial defects were successfully created in the parietal bone of two dogs (i.e., five defects in each dog). Four of the five defects in each dog were filled with BoneSource® Hydroxyapatite Cement; the fifth defect in each dog was left empty to serve as a control. At the end of 30 days, a blinded histopathological evaluation of the defects was performed. Histopathology revealed that the defects were filled with fibrin, fibrous tissue and new bone. Much of the new bone extended from the edges of the defect. Osteogenesis was evident at all sites in both animals. There was no evidence of infection and no toxicity of the bone surrounding any of the defects.

VIII. CLINICAL TESTING

In order to assess the safety and effectiveness of BoneSource® Hydroxyapatite Cement for use in the repair of cranial burr holes, contiguous craniotomy cuts and other cranial defects, a non-randomized clinical investigational study was conducted under an approved Investigational Device Exemption. The study involved three sites and a total enrollment of 103 patients presenting 175 cranial defects. The clinical investigation postoperative evaluation period is 24 months.

Premarket Notification: BoneSource® HAC Modification: Removal of Sinus-Communicating Warning Osteogenics Inc. November 8, 1996

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Effectiveness

The effectiveness of BoneSource® Hydroxyapatite Cement, for its intended use, is assessed by radiographic evaluation (x-ray or CAT Scan) of the implant's stability as determined by volume loss at each postoperative interval. Effectiveness is also assessed by an evaluation of all device explants and the relation of the explantation to the device.

Statistical analysis was performed on effectiveness data based upon an implant survival analysis utilizing the Life-Table Method. The cumulative survival rate of BoneSource® Hydroxyapatite Cement is 81.32% with 11 implants not yet evaluated at the 24 Month interval and 31 implants not yet due for 24 Month follow-up. NOTE: this survival rate of 81.32% reflects incidences of volume loss in excess of 10% for four implants due to inadequate drainage of excess wound fluid present at the implant site; and reflects all explants as failures though none are considered by the Investigator and Medical Monitor to be device-related, but attributable to patient-related conditions such the reoccurrence of tumor formation.

Based upon the survival analysis and resulting survival rate of 81.32%, BoneSource® Hydroxyapatite Cement is demonstrated to be effective regardless of the demographic characteristics of age, gender, race and medical history, and more importantly, to be effective regardless of the clinical characteristics of the implants such as cause, type, location and dimensions of the defects presenting in this investigation.

Safety

The safety of BoneSource® Hydroxyapatite Cement is evaluated for all patients at all postoperative intervals throughout the duration of the 24-month follow-up and is assessed by the observations of laboratory data, postoperative complications and adverse events.

Laboratory Values

Laboratory data were collected at all postoperative intervals in order to monitor the subject's levels of calcium, chloride, sodium, potassium, bicarbonate and phosphate. The mean laboratory values, as well as, mean within-patient changes were identified for each blood chemistry parameter at each interval and presented against baseline to the Month 12 and to the Month 24 interval. Additionally, each blood chemistry parameter was assessed against the normal laboratory range for each site. Those values which fell outside these normal ranges were further reviewed as compared to clinical panic ranges as defined by Wolfson, W.L., Eds., Laboratory Test Handbook.

Calcium levels demonstrated slight hemodilution during the interval immediately postoperatively, and in the follow-up period there is a statistical difference among baseline and Month 12 and among baseline and Month 24. However, the mean withinpatient percent change averaged only 3.21% and 4.21 at each respective interval. These percent changes are not considered clinically significant. Furthermore, the minimum and maximum calcium levels are well within the Laboratory Test Handbook range.

Sodium demonstrated statistical significance among baseline and Month 24 only; however, it should be noted that the mean within-patient change from baseline averaged only 1.01%. Additionally, the minimum and maximum sodium levels are well within the

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handbook range. Potassium demonstrated a statistical significance among baseline and Month 12 and among baseline and Month 24. However, none of the values for potassium are considered to be clinically significant.

Chloride, bicarbonate and phosphate demonstrated no statistical significance among baseline, Month 12 and Month 24 values. Although six patients demonstrated chloride levels slightly above the handbook "high", these levels presented at early postoperative intervals and dropped to clinically non-significant levels during the remainder of the follow-up intervals. Of the six patients, four underwent intradural surgery; abnormal electrolyte levels are commonly observed in this type of surgery.

Complications

Complications are divided into two groups: defect-specific complications and patientspecific complications. Defect-specific complications include edema, redness, tenderness, seroma, hematoma, tissue thinning, sinusitis, surgical site infection and "other", and were tabulated according to relation to the device and to the interval in which the complication occurred. The majority of the implants enrolled in this investigation presented no complications at any postoperative or follow-up interval.

Patient-specific complications include headache, fever, systemic infection, dizziness, GI symptoms, seizures and diplopia, and are tabulated according to relation to the device and to the interval in which the complication occurred. Of the 103 patients enrolled in this clinical investigation, the majority presented with no patient-related complications at any postoperative or follow-up interval.

Adverse Events/Death

During the course of this clinical investigation, unanticipated adverse events were reported for five patients. Of the five patients presenting with adverse events two died from cancer, but neither are considered to be device-related. Of the remaining three patients presenting adverse events, one patient suffered a stroke following deep brain tumor removal with postoperative refractory pneumonia requiring a tracheotomy. Another developed a hematoma formation beneath the implant; and the last patient (protocol violation) presented with a life-threatening cerebral spinal fluid leak and was injected with BoneSource® through the nostril in an emergency situation. Subsequently, extrusion of hydroxyapatite cement fragments was observed, resulting in a 95% explantation of the device. The Investigator reports, however, that the remaining 5% of implant has plugged the defect and is functioning properly. None of the adverse events reported during the course of this investigation are considered to be related to BoneSource® Hydroxyapatite Cement when administered as intended.

Conclusion

The safety of BoneSource® Hydroxyapatite Cement was assessed by the evaluation of laboratory data, postoperative complications and adverse events. Based upon evaluation of blood chemistry levels (i.e., calcium, chloride, sodium, potassium, bicarbonate and phosphate), with the exception of those values identified, all laboratory values are within clinically normal ranges. Therefore, the presence of BoneSource® Hydroxyapatite Cement is not expected to adversely effect laboratory values. The incidence of complications and adverse events are not occurring at a rate considered to be untoward for the patient population. Therefore, based upon these clinical data, BoneSource®

Premarket Notification: BoneSource® HAC Modification: Removal of Sinus-Communicating Warning November 8, 1996 Osteogenics Inc.

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Hydroxyapatite Cement is considered to be safe and effective for the stated indication and performs as well as, or better than, CranioPlastic™ (PMMA).

IX. STERILIZATION

BoneSource® is provided sterile and is for single use only. Sterilization is achieved by gamma irradiation in compliance with ANSI/AAMI ST32-1991, Method I.

X. SUBSTANTIAL EQUIVALENCE

COMPARISON OF TECHNOLOGICAL CHARACTERISTICS
FEATURE	BONESOURCE® HAC	CRANIOPLASTICTM (PMMA)
Design	Self-setting material intended tofill, seal and conform to cranialdefects.	Self-setting material intended tofill, seal and conform to cranialdefects.
Function/Intended Use	For use in the repair ofneurosurgical burr holes,contiguous craniotomy cuts andother cranial defects with asurface area no larger than25cm² per defect.	For repair of cranial defects.
Material	hydroxyapatite cement (HAC)	poly methyl methacrylate(PMMA)
ChemicalComposition	tetracalcium phosphate (72.9%)dicalcium phosphate (27.1%)	methyl methacrylate polymer(79.6%);methyl methacrylate styrenecopolymer (19.9%); benzoylperoxide (0.5%)
Setting Time	~20 minutes at 37°C(physiologic conditions)	13-15 minutes at 23°C to 28°C
ChemicalReaction	Isothermic	Exothermic (up to 100°C),cooling by water recommended.
CompressiveStrength	≥ 50 MPa	70 MPa

XI. CONCLUSION

BoneSource® is claimed to be substantially equivalent in design and function to CranioPlastic™. The conclusions drawn from in-vitro, animal, biocompatibility and clinical testing demonstrate that BoneSource® Hydroxyapatite Cement is safe and effective and performs as well as or better than CranioPlasticTM (polymethylmethacrylate) for the stated indication. In addition, these tests demonstrate that BoneSource® Hydroxyapatite Cement is well accepted by host tissue with no evidence of local or systemic adverse effects related to the device.

Regulation Number and Section

§ 882.5300 Methyl methacrylate for cranioplasty.

(a)
Identification. Methyl methacrylate for cranioplasty (skull repair) is a self-curing acrylic that a surgeon uses to repair a skull defect in a patient. At the time of surgery, the surgeon initiates polymerization of the material and forms it into a plate or other appropriate shape to repair the defect.(b)
Classification. Class II (performance standards).