Bicera™ Resorbable Bone Substitute is intended for use as a bone void filler for voids or gaps that are not intrinsic to the stability of the bony structure. Bicera™ Resorbable Bone Substitute is indicated for use in the treatment of surgically created osseous defects or osseous defects resulting from traumatic injury to the bone. Bicera™ Resorbable Bone Substitute is intended to be packed into bony voids or gaps of the skeletal system as a bone void filler (i.e., extremities and pelvis). This product provides a bone void filler that resorbs and is replaced by bone during the healing process.

Device Description

Bicera™ Resorbable Bone Substitute is a bioceramic medical device that its composition of crystalline phase contains 60% hydroxyapatite (HAP) and 40% beta-tricalcium (B-TCP). Bicera™ is a bone void filler for orthopedic surgery. It is indicated for use in the treatment of surgically created osseous defects or osseous defects resulting from traumatic injury to the bone. This composite material is acretts resumity in vivo and is replaced by new bone. Bicera™ Resorbable Bone Substitute is supplied sterile in various shapes and sizes.

AI/ML Overview

Here's a breakdown of the acceptance criteria and the study that proves the device meets them, based on the provided text:

Acceptance Criteria and Device Performance

The core of the "acceptance criteria" for Bifcera™ Resorbable Bone Substitute is demonstrating substantial equivalence to an existing predicate device, MBCPTM Bone Graft Substitute (K032268). This is achieved by comparing several technological characteristics and demonstrating similar performance in biological and in-vivo settings.

Table of Acceptance Criteria and Reported Device Performance:

Characteristic	Acceptance Criteria (Predicate Device: MBCPTM)	Reported Device Performance (Bicera™)	Notes
Composition (wt%)	60% HAP and 40% β-TCP	60% HAP and 40% β-TCP	Identical composition
Porosity (%)	70	79.22 ± 1.04	Bicera™ has slightly higher porosity. The submission implies this is acceptable for substantial equivalence, likely due to similar intended function and in-vivo performance.
Pore size (µm)	450 ± 49	442.65 ± 80.31	Very similar pore size, within the reported range of the predicate.
Ca/P	1.60 ± 0.02	1.61	Very similar Ca/P ratio, indicating similar mineralization properties.
Density (g/cm³)	0.87 ± 0.04	0.64 ± 0.03	Bicera™ has a lower density. This correlates with its higher porosity. Accepted due to other factors demonstrating substantial equivalence.
Pore structure	Interconnected pores	Interconnected pores	Identical pore structure, crucial for bone ingrowth.
Specific surface area (m²/g)	1.8 ± 0.1	1.57	Similar specific surface area.
Compressive strength (MPa)	3.04 ± 0.79	1.80 ± 0.24	Bicera™ has lower compressive strength. This difference is accepted likely because the device is "not intrinsic to the stability of the bony structure" and is a bone void filler.
Biocompatibility	Acceptable as per ISO 10993, ASTM F-1408-97, USP, FDA guidelines (implied from predicate)	Acceptable results for cytotoxicity, sensitization, irritation, acute systemic toxicity, pyrogen, and subcutaneous implantation study.	Demonstrated good affinity with surrounding tissue with no inflammatory or adverse reaction.
Resorption Profile & New Bone Formation	Substantially equivalent to predicate (implied from predicate's established performance)	Substantially equivalent to predicate in a long bone animal critical-sized defect model.	Demonstrated over time at multiple post-op evaluations.

Study Details

The provided document describes studies conducted to demonstrate substantial equivalence, primarily focusing on non-clinical tests.

Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective):
- Test Set (Animal Study): The document mentions a "long bone animal critical sized defect model." It does not specify the exact sample size (number of animals or defects) used in this model.
- Data Provenance: The study was conducted by the submitter, Wiltrom Corporation (Taiwan). The provenance for the animal study is therefore prospective as it was specifically conducted for this submission.
Number of experts used to establish the ground truth for the test set and the qualifications of those experts:
- The document does not specify the number of experts or their qualifications for establishing ground truth in the animal study. The evaluation likely involved veterinary pathologists or histologists specializing in bone healing, but this is not explicitly stated.
Adjudication method (e.g. 2+1, 3+1, none) for the test set:
- The document does not describe any adjudication method used for the animal study results. The evaluation of resorption and new bone formation would typically involve histological assessment, often by one or more trained pathologists, but formal adjudication is not mentioned.
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 was not done. This device is a bone substitute material, not an AI-powered diagnostic tool. Therefore, the concept of "human readers improve with AI" is not applicable here.
If a standalone (i.e. algorithm only without human-in-the-loop performance) was done:
- No, this is not applicable. The device is a physical medical implant, not an algorithm.
The type of ground truth used (expert consensus, pathology, outcomes data, etc):
- For the animal study comparing resorption and new bone formation, the ground truth was based on histopathological evaluation (pathology) of the bone defect sites at multiple post-operative evaluations. This is a standard method for assessing bone graft performance in animal models.
- For the biocompatibility tests (cytotoxicity, sensitization, etc.), the ground truth was established by standardized laboratory test methods (e.g., cell viability assays, skin irritation tests) which have defined endpoints for acceptability.
The sample size for the training set:
- Not applicable. This device is a physical product, not a machine learning algorithm, so there is no "training set."
How the ground truth for the training set was established:
- Not applicable, as there is no training set for this device.

Summary

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110949 AGE I OF 4

SEP 1 8 2012

510(K) Summary

1. Submitter's Identification

Address: No.221, Sec.1, Chung Hsing Rd., Chutung, Hsinchu, Taiwian 31053, R.O.C.

TEL: (886) 3-582-8999 FAX: (886) 3-582-6859 Contact: Yung-Chih Wu

US Representative:

Address: 5025 Collwood Way, Unit 19 San Diego, CA 92115, USA TEL: 1-808-277-1579 Email: mhanb20012001@gmail.com Contact: Yi-An Lai

1. Proprietary Name
  Bicera™ Resorbable Bone Substitute

3. Common Name

Bone Void Filler

4. Classification Name

21 CFR 888.3045 – Resorbable Calcium Salt Bone Void Filler Device – Class II

5. Device Code/Panel Code

Orthopedics/MQV

1. Predicate Device

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MBCPTM Bone Graft Substitute, K032268

7. Mandatory Performance Standard

Class II Special Controls Guidance Document: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA (Document # 855)

8. Voluntary Performance Standards

ISO 11137-2:2006 ISO 9001:2000 ISO 10993-1,3,5,6,10,11,12,14 ISO/IEC 17025:2005 21 CFR 58 ASTM F2150-02 ASTM D695-02a ASTM D1621-04a ASTM D3576-4 ASTM F1185-03 ASTM F1185-87. ASTM D4332 ASTM F1140-07 ASTM F88-07a ASTM F1929-98 ASTM F1608-00 ASTM F895 ASTM F1408-97 ASTM F1980-07

9. Device Description

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available shapes and sizes.

Table 1. Product Form
Form	Size
Stick, ≤ 5 mm width or height≤ 20 mm length	2.0 to 10.0 cm3 total volume
Granule, ≤ 3 mm diameter	0.25, 0.5, and 1 gram

10. Intended Use

11. Comparison to Predicate Device

Bicera™ is substantially equivalent in design, function, and intended use to MBCPTM Bone Graft Substitute cleared as K032268 on December 11, 2003.

	Bicera™	MBCP™
Composition (wt%)	60% HAP and 40% β-TCP	60% HAP and 40% β-TCP
Porosity (%)	79.22 ± 1.04	70
Pore size (µm)	442.65 ± 80.31	450 ± 49
Ca/P	1.61	1.60 ± 0.02
Density (g/cm³)	0.64 ± 0.03	0.87 ± 0.04
Pore structure	Interconnected pores	Interconnected pores
Specific surface area (m²/g)	1.57	1.8 ± 0.1
Compressive strength (MPa)	1.80 ± 0.24	3.04 ± 0.79

Comparison of Technological Characteristics between Bicera™ and MBCPTM

12. Discussions of Non-Clinical Tests Performed for Determination of Substantial Equivalence are as follows

Assessments for biocompatibility evaluation are based on the final, to-be-implanted version of Bicera™. These assessments were conducted in accordance with the International Standard ISO 10993 part 4, 5, 6, 10, 11, ASTM F-1408-97, USP <85> version 34, <161> version 34 and the guideline provided by the FDA of the United

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K110949
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States. The test results for cytotoxicity, sensitization, irritation, acute systemic toxicity, and pyrogen assessments were considered acceptable. The result of the subcutaneous implantation study shows that Bicera™ has a good affinity with the surrounding tissue with no observations of inflammatory or adverse reaction. It can be concluded that Bicera™ has a substantially equivalent biocompatibility to that of MBCP™. Bicera™ is mainly composed of 60% of hydroxyapatite and 40% of ß-tri-calcium phosphate which is an osteoconductive material and has been widely applied in clinical application for years. In addition to these biocompatibility assessments, Bicera™ was compared to the predicate device in a long bone animal critical sized defect model. The results over time at multiple post-op evaluations demonstrate that Bicera™ was substantially equivalent to the predicate device with respect to resorption profile and new bone formation.

13. Discussion of Clinical Tests Performed

N/A

14. Conclusion

We have demonstrated that the Bicera™ is substantially equivalent to the predicate device,MBCP™ (K032268), based on physical and chemical characteristics as well as biocompatibility and animal implantation testing.

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DEPARTMENT OF HEALTH & HUMAN SERVICES

Image /page/4/Picture/1 description: The image shows the logo for the U.S. Department of Health & Human Services. The logo features a stylized eagle or bird symbol, 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.

Public Health Service

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

Wiltrom Corporation Limited % Mr. Yung-Chih Wu Plant Manager No. 221, Section 1, Chung Hsing Road Chutung Township, Hsinchu China (Taiwan) 31053

SEP 1 8 2012

Re: K110949

Trade/Device Name: Bicera™ Resorbable Bone Substitute Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable calcium salt bone void filler device Regulatory Class: Class II Product Code: MQV Dated: August 27, 2012 Received: August 28, 2012

Dear Mr. Wu:

We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. 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

ﻟﻢ -

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Page 2 - Mr. Yung-Chih Wu

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 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 go to http://www.fda.gov/AboutFDA/CentersOffices/CDRH/CDRHOffices/ucm115809.htm for the Center for Devices and Radiological Health's (CDRH's) Office of Compliance. 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 (800) 638-2041 or (301) 796-7100 or at its Internet address http://www.fda.gov/MedicalDevices/Resourcesfor You/Industry/default.htm.

Sincerely yours,

Erin Keith

Mark N. Melkerson Director Division of Surgical, Orthopedic and Restorative Devices Office of Device Evaluation Center for Devices and Radiological Health

Enclosure

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INDICATIONS FOR USE

510(k) Number (if known): K110949

Device Name:

Bicera™ Resorbable Bone Substitute

Indications For Use:

Prescription Use__X (Part 21 CFR 801 Subpart D) AND/OR

Over-The-Counter Use_ NO (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)

Yariv N. Eliazy

(Division Sign-Off) (Division Sign-On), Online Divisionative Devices

510(k) Number K110949

Regulation Number and Section

§ 888.3045 Resorbable calcium salt bone void filler device.

(a)
Identification. A resorbable calcium salt bone void filler device is a resorbable implant intended to fill bony voids or gaps of the extremities, spine, and pelvis that are caused by trauma or surgery and are not intrinsic to the stability of the bony structure.(b)
Classification. Class II (special controls). The special control for this device is the FDA guidance document entitled “Class II Special Controls Guidance: Resorbable Calcium Salt Bone Void Filler Device; Guidance for Industry and FDA.” See § 888.1(e) of this chapter for the availability of this guidance.