TRS CRANIAL BONE VOID FILLER(TRS C-BVF)

• K Number: K123633
• Device Name: TRS CRANIAL BONE VOID FILLER(TRS C-BVF)
• Manufacturer: TISSUE REGENERATION SYSTEMS, INC.
• Date Cleared: 2013-08-16 ( 266 days)
• Product Code: GXR
• Regulation Number: 882.5250

Intended Use

TRS Cranial Bone Void Filler is intended for use in the repair of 13mm neurosurgical cranial burr holes. It should be gently packed into bony voids or gaps of the skeletal system that are not intrinsic to the stability of the bony structure.

Device Description

TRS Cranial Bone Void Filler (TRS C-BVF) is a synthetic, porous, osteoconductive, bone void filler made from PCL polycaprolactone (CaH100-)X which will degrade and resorb fully in vivo by hydrolysis and is subsequently metabolized by the body, and hydroxylapatite (Ca10(PO4)6.(OH)2) with a calcium phosphate bone mineral coating (Hydroxylapatite and Octacalcium phosphate). TRS BVF has an interconnected porous structure that acts as an osteoconductive matrix for the ingrowth of bone. TRS C-BVF is available in single size, which is a 13mm diameter x 5mm "plug" with a 20mm diameter x .90mm thick flange. TRS C-BVF is manufactured using a laser sintering process and is then coated with the calcium phosphate bone mineral coating. The product is shipped to a contract manufacturer who packages, labels and sterilizes the C-BVF devices. They are then returned to TRS and inventoried as Finished Goods.

Predicate Devices

K051093, K071046, K041350, K041611

Reference Devices

Not Found

AI/ML (Artificial Intelligence / Machine Learning)

No
The device description focuses on the material composition and manufacturing process of a bone void filler, with no mention of software, algorithms, or data processing that would indicate AI/ML. The performance studies are based on material properties and animal models, not algorithmic performance.

Therapeutic

No.
The device is a bone void filler intended to repair neurosurgical cranial burr holes, acting as an osteoconductive matrix for bone ingrowth, which is a structural and regenerative function, not a therapeutic one in the sense of treating a disease or condition actively.

Diagnostic

No

The device is a bone void filler intended for structural repair, not for diagnostic purposes.

SaMD (Software as a Medical Device)

No

The device description clearly states it is a synthetic, porous, osteoconductive bone void filler made from physical materials (PCL and hydroxylapatite) and manufactured using a laser sintering process. It is a physical implantable device, not software.

IVD (In Vitro Diagnostic)

No, this device is not an IVD (In Vitro Diagnostic).

Here's why:

• Intended Use: The intended use is for the repair of cranial burr holes and filling bone voids in the skeletal system. This is a surgical procedure performed in vivo (within the body).
• Device Description: The device is a physical implantable material (bone void filler) made of synthetic materials.
• Function: It acts as a scaffold for bone ingrowth within the body.
• IVD Definition: In Vitro Diagnostics are tests performed on samples taken from the human body (like blood, urine, tissue) to detect diseases, conditions, or infections.

This device is a medical device intended for surgical implantation, not for diagnostic testing of samples outside the body.

PCCP (Predetermined Change Control Plan) Authorized

N/A

Overview

Intended Use / Indications for Use

TRS Cranial Bone Void Filler is intended for use in the repair of 13mm neurosurgical cranial burr holes. It should be gently packed into bony voids or gaps of the skeletal system that are not intrinsic to the stability of the bony structure.

Product codes (comma separated list FDA assigned to the subject device)

GXR

Device Description

TRS Cranial Bone Void Filler (TRS C-BVF) is a synthetic, porous, osteoconductive, bone void filler made from PCL polycaprolactone (CaH10O-)X which will degrade and resorb fully in vivo by hydrolysis and is subsequently metabolized by the body, and hydroxylapatite (Ca10(PO4)6.(OH)2) with a calcium phosphate bone mineral coating (Hydroxylapatite and Octacalcium phosphate). TRS BVF has an interconnected porous structure that acts as an osteoconductive matrix for the ingrowth of bone.

TRS C-BVF is available in single size, which is a 13mm diameter x 5mm "plug" with a 20mm diameter x .90mm thick flange.

TRS C-BVF is manufactured using a laser sintering process and is then coated with the calcium phosphate bone mineral coating. The product is shipped to a contract manufacturer who packages, labels and sterilizes the C-BVF devices. They are then returned to TRS and inventoried as Finished Goods.

Mentions image processing

Not Found

Mentions AI, DNN, or ML

Not Found

Input Imaging Modality

Not Found

Anatomical Site

cranial burr holes; bony voids or gaps of the skeletal system

Indicated Patient Age Range

Not Found

Intended User / Care Setting

Not Found

Description of the training set, sample size, data source, and annotation protocol

Not Found

Description of the test set, sample size, data source, and annotation protocol

Not Found

Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)

• Biocompatibility, including Degradation Testing: Comprehensive biocompatibility testing of the TRS C-BVF material demonstrates that it is biocompatible; non-genotoxic, nonpyrogenic, non-toxic and a non-irritant. Results of the degradation testing, which included accelerated and real-time polymer degradation, as well as extreme simulation ceramic degradation, have shown comparable performance between the TRS and chronOS predicate device. Both devices demonstrated a similar PCL degradation mechanism by hydrolysis of the ester linkage to give a carboxylic acid and an alcohol as by products. In addition, similar trace elements were detected for both devices. Molecular ions detected from the extracts from both devices at 90-day real-time test demonstrated similar retention times, and indicate the degraded compounds are similar or related.
• Bench Testing: Bench testing to evaluate the compressive mechanical properties and push out force of the TRS C-BVF, the chronOS and Ostepore devices showed comparable performance and demonstrated that the TRS C-BVF device to possess appropriate performance characteristics for its intended use. In addition, material testing using FTIR demonstrated the same PCL material composition in both the predicate Osteopore PCL Scaffold device and the TRS C-BVF device.
• Animal Testing: Results of the Rabbit Calvarial Defect testing have demonstrated similar performance of the TRS C-BVF and predicate chronOS devices with respect to new bone formation. By 26 weeks, total bone formation in both the subject and predicate devices was approximately equal and by 78 weeks, CT showed bone volumes for both devices to be nearly identical. The data shows that TRS C-BVF facilitates a constant, sustained bony healing response over time.
• Clinical (Literature): The clinical literature summarized utilizes PCL in a number of material forms and indications. Clinical studies reported good outcomes in applied applications, expected absorption rates and with no reported material-mediated complications. No clinical studies have been performed in support of this 510(k) application due to the similarities of the TRS C-BVF to the predicate devices.

Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)

Not Found

Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.

K051093, K071046, K041350, K041611

Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.

Not Found

Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).

Not Found

Regulation Number and Section

§ 882.5250 Burr hole cover.

(a)
Identification. A burr hole cover is a plastic or metal device used to cover or plug holes drilled into the skull during surgery and to reattach cranial bone removed during surgery.(b)
Classification. Class II (performance standards).

Summary

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K123,633

Tissue Regeneration Systems, Inc. 510(k) Premarket Notification TRS CRANIAL BONE VOID FILLER (TRS C-BVF) August 14, 2013

510(k) Summary Tissue Regeneration Systems, Inc TRS Cranial Bone Void Filler Traditional 510(k)

1.0 Manufacturer Name

Tissue Regeneration Systems, Inc. 5400 Carillon Point Kirkland, Washington 98033

AUG 16 2013

2.0 Official Contact

Jim Fitzsimmons Chief Executive Officer

Phone: [phone] Fax: [phone] E-mail: [e-mail]

Alternate Contact

John Garinger Director, Regulatory Affairs and Quality Assurance Phone: [phone] Fax: [phone] E-mail: [e-mail] ·

3.0 Date Prepared: November 16, 2012

4.0 Device Name and Classification

Proprietary Name: Common/Usual Name: Classification Name: Requlation Number: Device Class: Classification Name: Classification Panel:

TRS PCL Cranial Bone Void Filler Bone void filler Burr Hole Cover 8882.5250 Class II GXR

5.0 Indications for Use

TRS Cranial Bone Void Filler is intended for use in the repair of 13mm neurosurgical cranial burr holes. It should be gently packed into bony voids or gaps of the skeletal system that are not intrinsic to the stability of the bony structure.

Neurology

6.0 Device Description

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Tissue Regeneration Systems. Inc. 510(k) Premarket Notification TRS CRANIAL BONE VOID FILLER (TRS C-BVF) August 14, 2013

TRS Cranial Bone Void Filler (TRS C-BVF) is a synthetic, porous, osteoconductive, bone void filler made from PCL polycaprolactone (CaH100-)X which will degrade and resorb fully in vivo by hydrolysis and is subsequently metabolized by the body, and hydroxylapatite (Ca10(PO4)6.(OH)2) with a calcium phosphate bone mineral coating (Hydroxylapatite and Octacalcium phosphate). TRS BVF has an interconnected porous structure that acts as an osteoconductive matrix for the ingrowth of bone.

TRS C-BVF is available in single size, which is a 13mm diameter x 5mm "plug" with a 20mm diameter x .90mm thick flange.

TRS C-BVF is manufactured using a laser sintering process and is then coated with the calcium phosphate bone mineral coating. The product is shipped to a contract manufacturer who packages, labels and sterilizes the C-BVF devices. They are then returned to TRS and inventoried as Finished Goods.

7.0 Predicate Devices

Osteopore PCL Scaffold Bone Void Filler (BVF), (K051093, product code GXP cleared on March 17, 2006) Note: This device would be cleared under product code GXR if it were reviewed using today's more product specific product codes.

Synthes chronOS Composite resorbable bone void filler (K071046, product code MQV, cleared on October 23, 2007).

Synthes chronOS, porous, osteoconductive, resorbable bone void filler (K041350, product code GXP, cleared on July 8, 2004).

Synthes Rapid Resorbable Cranial Clamp burr hole cover (K041611, product code GXR, cleared on September 8, 2004.

8.0 Comparison to Marketed Devices

Tissue Regeneration Systems, Inc. purports the information contained in this 510(k) Submission demonstrates that the TRS Cranial Bone Void Filler is substantially equivalent to Osteopore PCL Scaffold Bone Void Filler cleared under K051093. Synthes chronOS Composite cleared under K071046, Synthes chronOS, cleared under K041350 and Synthes Rapid Resorbable Cranial Clamp cleared under K041611.

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510(k) Premarket Notification
CRANIAL BONE VOID FILLER (TRS C-BV
August 14, 20

Table 6-1 Predicate Device Regulatory Comparisor

Information	Subject Device	Predicate Device	Predicate Device	Predicate Device	Predicate Device
Manufacturer	Tissue Regeneration Systems, Inc.	Synthes	Synthes chronOS	Osteopore	Synthes
Trade Name	TRS C-BVF	Synthes chronOS Composite	Synthes chronOS	Osteopore PCL Scaffold Bone Void Filler	CranioClamp - Bioabsorbable Cranial Bone Flap Fixation System
510(k) #	To Be Determined	K071046	K041350	K051093	K071138
Product Code	GXR	MQV	GXP	GXP	GXR
Regulation Number	882.55250	888.3045	882.5300	882.5300	882.5250
Classification Name	Burr Hole Cover	Resorbable Calcium Salt Bone Void Filler	Methylmethacrylate for Cranioplasty	Methylmethacrylate for Cranioplasty	Burr Hole Cover
Device Class	Class II	Class II	Class II	Class II	Class II
Classification Panel	Neurology	Orthopedic and Rehabilitation Devices	Neurology	Neurology	Neurology

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Table 6-2: Device Characteristic Comparison
Characteristic	TRS C-BVF
(subject device)	Synthes chronOS
Composite
(predicate/reference)	Synthes chronOS
(predicate device)	Osteopore PCL
Scaffold
(predicate device)	Synthes
CranioClamp -
Bioabsorbable
Cranial Bone
Flap Fixation
System (predicate
device)	Similar	Different
Materials	PCL (poly-ε-
caprolactone),
Hydroylapatite,
Octacalcium
Phosphate
Bone contacting
surface:
Hydroxyapatite and
Calcium Phosphate
PCL Matrix
Ceramic Particles	PCL (polylactide-co-ε-
caprolactone) matrix
with imbedded β-
Tricalcuim Phosphate
granules.
Bone contacting
surface:
Calcium Phosphate
PCL Matrix
Ceramic Particles	β-Tricalcuim
Phosphate
granules.
Bone contacting
surface:
Calcium Phosphate	PCL (poly-ε-
caprolactone)
Bone contacting
surface: PCL (poly-
ε-caprolactone)
PCL Matrix
No Ceramic
Particles	85:15 Poly (L-lactide-
co-glycolide)
Bone contacting
surface:85:15 Poly
(L-lactide-co-
glycolide)
No PCL
No Ceramic Particles	X
	Not intended to be
trimmed	Can be trimmed with a
scalpel or molded	Can be trimmed
with a scalpel or
molded	Can be trimmed
with a scalpel	Not intended to be
trimmed	X
Biocompatible	Resorbable
materials
Meets ISO 10993
Interconnected
macroporous
structure
PCL Matrix
Ceramic Particles	Resorbable materials
Meets ISO 10993
Interconnected
macroporous structure
PCL Matrix
Ceramic Particles	Resorbable
materials
Meets ISO 10993
Interconnected
macroporous
structure
No PCL
Ceramic Particles	Resorbable
materials
Meets ISO 10993
Interconnected
macroporous
structure
PCL Matrix
No Ceramic
Particles	Resorbable materials
Meets ISO 10993
Smooth surface
No PCL
No Ceramic Particles	X
Design	Not intended to be
trimmed
Cylindrical plug with
flange	Can be trimmed with a
scalpel or molded
Various forms/sizes	Can be trimmed
with a scalpel or
molded
Various forms/sizes	Can be trimmed
with a scalpel
Various forms/sizes	Not intended to be
trimmed
18 mm diameter disc	X
Characteristic	TRS CBVF
(subject device)	Synthes chronOS Composite
(predicate/reference)	chronOS
(predicate device)	Osteopore PCL Scaffold
(predicate device)	CranioClamp - Bioabsorbable
Cranial Bone
Flap Fixation
System	Similar	Different
Intended Use	Is intended to be gently packed or placed into bony voids or gaps of the skeletal system.	Is intended to be gently packed or placed into site.	Is intended to be gently packed or placed into site.	Is intended to be gently packed or placed into bony voids or gaps of the skeletal system.	Is intended for covering burr holes and for fixation of cranial bone flaps, in pediatric and adult patients.	X
Indications for Use	Is indicated for use in the repair of neurosurgical cranial burr holes.	Is indicated for bony voids or gaps that are not intrinsic to the stability of the bony structure. Synthes chronOS Composite is indicated for use in the treatment of bony defects created surgically or through traumatic injury.	Is intended for the repair or filling of craniofacial defects and craniotomy cuts with a surface area no larger than 25 cm². It is also indicated for the restoration or augmentation of bony contours of the craniofacial skeleton; including the fronto-orbital, malar and mental areas.	Is indicated for use in the repair of neurosurgical burr holes, craniotomy cuts and other cranial defects. It is also for use in the augmentation or restoration of bony contour in the craniofacial skeleton.	Is intended for covering burr holes and for fixation of cranial bone flaps, in pediatric and adult patients.		X
Function	Fill bony voids or gaps of the skeletal system until the device is replaced by bone during the healing process.	Fill bony voids or gaps of the skeletal system until the device is replaced by bone during the healing process.	Fill bony voids or gaps of the skeletal system until the device is replaced by bone during the healing process.	Fill bony voids or gaps of the skeletal system until the device is replaced by bone during the healing process.	Covering burr holes and for fixation of cranial bone flaps	X
Sterilization	Sterile Ethylene Oxide	Sterile Irradiation	Sterile Irradiation	Sterile Irradiation	Sterile		X

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Tissue Regeneration Systems, Inc. 510(k) Premarket Notification TRS CRANIAL BONE VOID FILLER (TRS C-BVF) August 14, 2013

Comparison to Marketed Devices continued: The subject device and the predicate devices have the same intended use, are of similar design, perform the same function and are composed of similar resorbable materials. The subject and predicate devices are osteoconductive and both provide an interconnected, porous scaffold and an environment for new bone ingrowth. Both devices are available in similar forms and are provided sterile. Both the subject and predicate devices are shown to be biocompatible, perform similarly in in-vitro and animal testing and are composed of component materials with a history of use in implantable medical devices.

9.0 Performance Testing

TRS Cranial Bone Void Filler has undergone a comprehensive battery of non-clinical testing, including chemical, physical, animal and biocompatibility. Testing has provided reasonable assurance of safety and effectiveness for its intended use and supports a determination of substantial equivalence.

9.1 Biocompatibility, including Degradation Testing:

Comprehensive biocompatibility testing of the TRS C-BVF material demonstrates that it is biocompatible; non-genotoxic, nonpyrogenic, non-toxic and a non-irritant. See Table 6-3 for the specific tests performed including the results and conclusions.

Results of the degradation testing, which included accelerated and real-time polymer degradation, as well as extreme simulation ceramic degradation, have shown comparable performance between the TRS and chronOS predicate device. Both devices demonstrated a similar PCL degradation mechanism by hydrolysis of the ester linkage to give a carboxylic acid and an alcohol as by products. In addition, similar trace elements were detected for both devices. Molecular ions detected from the extracts from both devices at 90-day real-time test demonstrated similar retention times, and indicate the degraded compounds are similar or related. These results provide further evidence that the TRS C-BVF is substantially equivalent to the chronOS predicate device.

While degradation testing was not performed on the OsteoPore PCL Scaffold predicate device, an infrared analysis of both the TRS C-BVF device and the OsteoPore PCL Scaffold device was undertaken using Fourier Transform Infrared Spectroscopy (FTIR) to qualitatively establish similarity of PLC polymeric material components between these devices. FTIR results for both TRS device and Osteopore PCL Scaffold showed strong peaks

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Tissue Regeneration Systems, Inc. 510(k) Premarket Notification TRS CRANIAL BONE VOID FILLER (TRS C-BVF) August 14, 2013

consistent with traditional peaks found in the infrared spectra of PCL indicated that PCL is a major component for these devices. (See Section 11.4 of this 510(k) submission and Appendix B, Tab B-5 for a summary of this testing.) Given that both the TRS C-BVF device and the OsteoPore PCL Scaffold predicate are composed of Poly-E-caprolactone material, degradation results for the OsteoPore material are presumed substantially similar to the TRS C-BVF device.

In conclusion, the TRS C-BVF device is biocompatible and demonstrates comparable degradation performance to the predicate devices, supporting a claim of substantial equivalence to the predicate chronOS and OsteoPore PCL Scaffold devices.

| ISO
10993

Standard	Test	Results	Conclusions
10993-5	Cytotoxicity (ISO Elution
Method- 1X MEM
Extract)	No cytoxicity or cell lysis was noted in any of the test wells. No
pH shift was observed at 48 hours. Reactivity grade was 0
(none).	Non-cytotoxic
10993-10	Sensitization (Guinea
pig maximization
sensitization test)	All Animals were clinically normal throughout the study. Test
article extracts showed no evidence of causing delayed dermal
contact sensitization in guinea pig.	Non-sensitizer
10993-10	Intracutaneous
Reactivity	There was no erythema and no edema from the 0.9% sodium
chloride solution test extract. There was very slight erythema
and very slight edema from the sesame oil test extract.
However, the difference from the control was 1.0 or less.	Non-irritant
10993-11	Systemic Toxicity (Acute
systemic toxicity in mice)	There was no mortality or evidence of systemic toxicity from
the test extracts. Body weight data were acceptable.	No acute systemic
toxicity
10993-3	Genotoxicity (Gene
mutation): Bacterial
Reverse Mutation study	The DMSO and saline extracts from TRS device were
considered to be non-mutagenic to Salmonella typhimurium
tester strains TA98, TA100, TS1535, and TA1537, and to
Escherichia coli tester strain WP2uvrA.	Non-mutagenic
10993-3	Genotoxicity (in-vivo;
Mouse Peripheral Blood
Micronucleus Study)	The saline and sesame oil test extracts did not induce
micronuclei in mice. There were no statistically significant
differences between the test and negative control groups.	Non-clastogenic
10993-3	Genotoxicity (Mouse
Lymphoma Assay)	The undiluted RPMI₀ and 1.0% DMSO TRS device extracts did
not cause any positive increase in the mean mutant frequency
in the L5178Y/TK⁺/⁻ cell line either in the presence or absence
of metabolic activation.	Non-mutagenic
10993-6	Local effects after
Implantation (Muscle
implantation study in
rabbits-2 weeks)	The macroscopic reaction of TRS device was not significant as
compared to the ChronOS and negative control (HDPE).
Microscopically, TRS device was classified as a non-irritant as
compared to ChronOS and HDPE.	Non-irritant as
compared to the
negative control
(HDPE) and
predicate device
(ChronOS)
ISO
10993	Test Description	Results	August 14, 2013
Conclusions
10993-6	Local effects after
Implantation (Muscle
implantation study in
rabbits-6 weeks)	The macroscopic reaction of TRS device was not significant as
compared to the ChronOS and negative control (HDPE).
Microscopically, TRS device was classified as a non-irritant as
compared to ChronOS and a slight irritant when compared to
HDPE.	Non-irritant as
compared to the
predicate device
(ChronOS) and a
slight irritant when
compared to the
negative control
(HDPE)
10993-11	Systemic toxicity (USP
Pyrogen study)	One (out of 3) of the animals showed a rise of 0.5°Cabove its
baseline temperature. The result was inconclusive and the
protocol required 5 additional animals to be injected.	Inconclusive - retest
required
10993-11	Systemic toxicity (USP
Pyrogen study-retest)	A total of 3 out of 8 rabbits had a temperature rise of ≥ 0.5°C,
and the total temperature rise of the 8 animals did not exceed
3.3°C. The USP test requirement was met. TRS device was
considered non-pyrogenic.	Non-pyrogenic
10993-11	Systemic toxicity: Sub-
chronic toxicity (13 week
study in rats following
subcutaneous
implantation)	No evidence of systemic toxicity from TRS device following
subcutaneous implantation in the rat. Daily clinical
observations, body weights, necropsy findings, organ weights
and organ/body weight ratios were within acceptable limits and
were similar between TRS device and control (HDPE)
treatment group. There were no changes in histopathology,
hematology values or clinical chemistry values in either male
or female rats. Microscopic evaluation of the selected tissues
revealed no evidence of a treatment related response.
Microscopic evaluation of the implant sites revealed that the
test implant site scores were higher than control implant site
scores.	No evidence of
systemic toxicity,
local macroscopic
tissue reaction not
significant as
compared to HDPE
control,
microscopically
classified as slight
irritant as compared
to HDPE control
10993-11	Systemic toxicity:
Chronic toxicity (26
week study in rats
following subcutaneous
implantation)	No evidence of systemic toxicity from TRS device following
subcutaneous implantation in the rat. Daily clinical
observations, body weights, necropsy findings, organ weights
and organ/body weight ratios were within acceptable limits and
were similar between TRS device and control (HDPE)
treatment group. There were no changes in histopathology,
hematology values or clinical chemistry values in either male
or female rats that were considered to be biologically
significant or related to treatment with TRS device. Microscopic
evaluation of the selected tissues revealed no evidence of a
treatment related response. Microscopic evaluation of the
implant sites revealed that the test implant site scores were
higher than control implant site scores	No evidence of
systemic toxicity,
local macroscopic
tissue reaction not
significant as
compared to HDPE
control,
microscopically
classified as
moderate irritant as
compared to HDPE
control.
The degrading
sample elicited an
expected mild
macrophage/giant
cell response.
10993-4	ASTM F756 Hemolysis
Test - Direct contact
and extract test	The hemolytic index of the test article in direct contact with
blood was 0.4% and the hemolytic index for the test article
extract was 0.1%. The test article in direct contact with blood
and the test article extract were both non-hemolytic.	Non-hemolytic
ASTM
F2382	Partial Thromboplastin
Time (PTT)	Average clotting time of the test article was 77% of the
negative control	Passed as a minimal
activator of the
intrinsic coagulation
pathway
(ASTM F2382
defines the test
result of > 50% of the
negative control as a
passing result)
ISO
10993	Test Description	Results	Conclusions
10993-4	C3a Complement
Activation Assay	C3a concentration of the test article was statistically
significantly higher than the activated NHS (normal human
serum) control and negative control (low density polyethylene).	Complement
activation by a
device is primarily a
surface related
phenomenon. As
TRS is not a direct
blood-contacting
device, there is no
direct interaction of
the blood with the
surface of the
device.
10993-4	SC5b-9 Complement
Activation Assay	SC5b-9 concentration of the test article was statistically
significantly higher than the activated NHS (normal human
serum) control and negative control (low density polyethylene).	Complement
activation by a
device is primarily a
surface related
phenomenon. As
TRS is not a direct
blood-contacting
device, there is no
direct interaction of
the blood with the
surface of the
device.
10993-13	Identification and
quantification of
degradation products
from polymeric devices
(Real time polymer
degradation
Polymer:
30,90,180,365,540, and
730 days)	After incubation in phosphate buffered saline (PBS) at 37 °C,
TRS C-BVF lost 10% and 23% of its molecular weight and
0.26% and 0.47% of its initial mass at 365 and 730 days,
respectively. Extracts of TRS device revealed one compound
(2-hexenoic acid, butyl ester, (E)-) at 30, 90, 180, and 365 day
at a concentration in the range of 2-6 ppm. ChronOS
composite resulted in one compound (di-n-octyl phthalate)
detected in the 30 day replicate 2 extract. The average
molecular weight (Mw) shows that TRS devices were
unchanged after 30 days, but did exhibit degradation by 90
days with approximately 5% reduction in average molecular
weight. Mw at 365 days showed a decrease of approximately
5%with a similar trend for the later time points. The ChronOS
composite, on the other hand, exhibited a 57% reduction in
average molecular weight by 30 days and a considerable 90%
reduction by 90 days, 95% at 180 days, 98% by 365 days, and
was completely degraded prior to the 540 day time point. The
decrease in pH of the solution of ChronOS composite, may
have affected the degradation profile. The number average
molecular weight (Mn) showed that the Mn of TRS device
decreased approximately 10% over 365 days and further
decreased to 23% after 730 days. No other compounds were
detected at any other time point above the quantitation limit.	TRS device real time
degradation results
demonstrated that
the device is in the
first stage of
degradation with the
decrease in
molecular weight
without mass loss
and deformation.
(Additional detail to
following in
Executive Summary)
10993-14	Identification and
quantification of
degradation products
from ceramics
(extreme/simulation)	The extreme solution test caused approximately 26-27% of the
ceramic and hydroxylapatite to dissolve from both the coated
and uncoated discs. After the testing had been performed, the
buffer solutions showed the presence of calcium, magnesium,
phosphorus, sulfur, and in some cases aluminum, barium, and
iron.
The simulation solution test caused a mass loss of less than
1% for both coated and uncoated discs. The solutions after
the simulation test contained calcium and phosphorus for both
sample types. In the case of the coated discs, magnesium
and sodium were also observed. The SEM images for the
coated samples after the simulation test still showed the flake-
like structure, but some erosion was apparent. After the
simulation test, no significant differences in the EDS data were
observed, as compared to the coated samples that had not
been subjected to the simulation test.	Both extreme and
simulation test
demonstrated that
the ceramic
component of TRS
device is composed
of calcium and
phosphate ceramic.
Quantitative analysis
of four individual
heavy metal
elements (As, Cd,
Pb, Hg) was within
acceptable limit as
stated in ISO 13779.
(Additional detail to
following in
Executive Summary)

Table 6-3: Biocompatibility Tests, Results and Conclusions

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Tissue Regeneration Systems, Inc.

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Tissue Regeneration Systems, Inc. 10 - 10 - 10 - 2010 - 10 - 510 (K) Premarket Notification

TRS CRANIAL BONE VOID FILLER (TRS C-BVF)
TRS CRANIAL BONE VOID FILLER (TRS C-BVF)

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9.2 Bench Testing:

Bench testing to evaluate the compressive mechanical properties and push out force of the TRS C-BVF, the chronOS and Ostepore devices showed comparable performance and demonstrated that the TRS C-BVF device to possess appropriate performance characteristics for its intended use. In addition, material testing using FTIR demonstrated the same PCL material composition in both the predicate Osteopore PCL Scaffold device and the TRS C-BVF device. These results provide further technical evidence supporting a claim of substantial equivalence between the subject and predicate devices.

9.3 Animal Testing:

Results of the Rabbit Calvarial Defect testing have demonstrated similar performance of the TRS C-BVF and predicate chronOS devices with respect to new bone formation. By 26 weeks, total bone formation in both the subject and predicate devices was approximately equal and by 78 weeks, CT showed bone volumes for both devices to be nearly identical. The data shows that TRS C-BVF facilitates a constant, sustained bony healing response over time. Results of this testing demonstrate that the TRS C-BVF performs in a similar manner to the predicate chronOS device in a cranial defect in an animal model. This testing provides further technical evidence that the TRS C-BVF device performs comparably to the predicate chronOS device and provides additional support to a claim of substantial equivalence to the predicate devices.

0.4 Clinical (Literature):

The clinical literature summarized utilizes PCL in a number of material forms and indications. Clinical studies reported good outcomes in applied applications, expected absorption rates and with no reported material-mediated complications.

No clinical studies have been performed in support of this 510(k) application due to the similarities of the TRS C-BVF to the predicate devices. Further, the constituent materials of the subject device have a long history of safe and successful clinical use in numerous implantable medical applications as identified above. The PCL containing materials and material combinations referenced in this literature are comparable to that utilized in the TRS C-BVF. As such, the reported successful clinical history provides evidence of PCL's safety profile in clinical use and is representative of the expected safety profile for TRS C-BVF.

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10.0 Conclusion

Product characterization and testing on the TRS Cranial Bone Void Filler when compared to its predicate devices demonstrate that it is substantially equivalent to the Osteopore PCL Scaffold Bone Void Filler, Synthes chronOS, Synthes chronOS Composite and Synthes Rapid Resorbable Cranial Clamp devices, commercially available cranial burr hole covers.

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Image /page/11/Picture/0 description: The image shows the logo for the U.S. Department of Health and Human Services. The logo features a stylized depiction of an eagle or bird-like figure with three curved lines forming its body and wings. The text "DEPARTMENT OF HEALTH & HUMAN SERVICES - USA" is arranged in a circular pattern around the bird symbol.

DEPARTMENT OF HEALTH & HUMAN SERVICES

Public Health Service

Food and Drug Administration 10903 New Hampshire Avenue Document Control Center - WO66-G609 Silver Spring, MD 20993-0002

August 16, 2013

Tissue Regeneration Systems, Inc. Mr. William J. Fitzsimmons President and Chief Executive Officer 5400 Carillon Point Kirkland, WA 98033

Re: K123633

Trade/Device Name: Tissue Regeneration Systems Cranial Bone Void Filler (TRS C-BVF) Regulation Number: 21 CFR 882.5250 Regulation Name: Burr Hole Cover Regulatory Class: Class II Product Code: GXR Dated: July 10, 2013 Received: July 18, 2013

Dear Mr. Fitzsimmons:

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 10 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. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you; however, that device labeling must be truthful and not misleading.

If your device is classified (see above) into either class II (Special Controls) or class III (PMA). it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations. Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.

Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); medical device reporting (reporting of medical

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Page 2 – Mr. William J. Fitzsimmons

device-related adverse events) (21 CFR 803); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820); and if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

If you desire specific advice for your device on our labeling regulation (21 CFR Part 801), please contact the Division of Small Manufacturers, International and Consumer Assistance at its tollfree number [phone] or [phone] or at its Internet address

http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm. Also, please note the regulation entitled. "Misbranding by reference to premarket notification" (21CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to

http://www.fda.gov/MedicalDevices/Safety/ReportaProblem/default.htm for the CDRH's Office of Surveillance and Biometrics/Division of Postmarket Surveillance.

You may obtain other general information on your responsibilities under the Act from the Division of Small Manufacturers. International and Consumer Assistance at its toll-free number [phone] or [phone] or at its Internet address http://www.fda.gov/MedicalDevices/ResourcesforYou/Industry/default.htm.

Sincerely yours,

Joyce M. Whang -S

for Victor Krauthamer, Ph.D. Acting Director Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known): K123633

Device Name: Tissue Regeneration Systems Cranial Bone Void Filler (TRS C-BVF))

Indications For Use:

TRS C-BVF is intended for use in the repair of 13 mm neurosurgical cranial burr holes. It should be gently packed into bony voids or gaps of the skeletal system that are not intrinsic to the stability of the bony structure.

V Prescription Use (Part 21 CFR 801 Subpart D)

AND/OR

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)

lovce M. Whana -

Division Sign Off) Division of Neurological and Physical Medicine Devices (DNPMD)

510(k) Number K123633

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