(73 days)
Not Found
No
The device description focuses on the material properties and chemical reaction of a bone cement, with no mention of software, algorithms, or data processing that would indicate AI/ML.
No.
This device is intended for structural repair of cranial defects, not for treating a disease or condition.
No
The device is a self-setting calcium phosphate cement intended for the repair of cranial defects, not for diagnosing medical conditions.
No
The device description clearly states it is a self-setting, calcium phosphate cement, which is a physical material, not software.
Based on the provided information, this device is not an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The intended use is for the repair of cranial defects, which is a surgical procedure performed directly on the patient's body.
- Device Description: The device is a self-setting calcium phosphate cement that is implanted into the body.
- Lack of In Vitro Testing: The description focuses on the physical properties of the cement and its performance within the body, not on testing samples taken from the body.
- Clinical Study: The performance study involves evaluating the device's effectiveness and safety in patients through radiographic evaluation and observation of complications and adverse events.
IVD devices are used to examine specimens derived from the human body (like blood, urine, or tissue) to provide information for diagnosis, monitoring, or screening. This device is a therapeutic implant used for structural repair within the body.
N/A
Intended Use / Indications for Use
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.
Product codes (comma separated list FDA assigned to the subject device)
87GXP
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
§ 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).
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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 Road | |
| Richardson, 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
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. 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 | ||
|---|---|---|
| $Ca_4(PO_4)_2 O + CaHPO_4 + [2H_2O]$ | ||
| tetracalcium | ||
| phosphate | → | $Ca_5(PO_4)_3OH + [2H_2O]$ |
| hydroxyapatite | ||
| (BoneSource®) | ||
| dicalcium | ||
| phosphate |
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 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
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.
| COMPARISON OF TECHNOLOGICAL CHARACTERISTICS | ||
|---|---|---|
| FEATURE | BONESOURCE® HAC | CRANIOPLASTICTM (PMMA) |
| Design | Self-setting material intended to | |
| fill, seal and conform to cranial | ||
| defects. | Self-setting material intended to | |
| fill, seal and conform to cranial | ||
| defects. | ||
| Function/ | ||
| Intended Use | For use in the repair of | |
| neurosurgical burr holes, | ||
| contiguous craniotomy cuts and | ||
| other cranial defects with a | ||
| surface area no larger than | ||
| 25cm² per defect. | For repair of cranial defects. | |
| Material | hydroxyapatite cement (HAC) | poly methyl methacrylate |
| (PMMA) | ||
| Chemical | ||
| Composition | tetracalcium phosphate (72.9%) | |
| dicalcium phosphate (27.1%) | methyl methacrylate polymer | |
| (79.6%); | ||
| methyl methacrylate styrene | ||
| copolymer (19.9%); benzoyl | ||
| peroxide (0.5%) | ||
| Setting Time | ~20 minutes at 37°C | |
| (physiologic conditions) | 13-15 minutes at 23°C to 28°C | |
| Chemical | ||
| Reaction | Isothermic | Exothermic (up to 100°C), |
| cooling by water recommended. | ||
| Compressive | ||
| Strength | ≥ 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.