DSM Biomedical Calcium Phosphate Cement is indicated to fill bony voids or gaps of the skeletal system (i.e. extremities and pelvis). These defects may be surgically created from traumatic injury to the bone. The Calcium Phosphate Cement is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. The Calcium Phosphate Cement cured in situ provides an open void/gap filler that can augment provisional hardware (e.g. K-Wires, plates, screws) to help support bone fragments during the surgical procedure. The cured cement acts only as a temporary support media and is not intended to provide structural support during the healing process. The Calcium Phosphate Cement resorbs and is replaced by bone during the healing process.

Device Description

The DSM Calcium Phosphate Cement is a line extension to the current DSM Calcium Phosphate Cement product line, which introduces the 1cc size and a new packaging configuration. DSM Calcium Phosphate Cement is an injectable, sculptable, drillable, fast self-setting bone substitute. DSM Calcium Phosphate Cement is composed of calcium phosphate, which converts to hydroxyapatite in vivo, and bovine collagen powder. The device can also be used to augment provisional hardware to help support bone fragments during the surgical procedure. The cement is provided in a powder form and is packaged in a female luer syringe. An empty male luer syringe is provided to allow for syringe-to-syringe mixing of the powder with saline at the required powder-to-liquid ratio. DSM Calcium Phosphate Cement is supplied sterile by gamma irradiation and is non-pyrogenic.

AI/ML Overview

This document is a 510(k) premarket notification for the DSM Biomedical Calcium Phosphate Cement. It describes a line extension of an existing product, specifically a new 1cc size and packaging configuration. The submission aims to demonstrate substantial equivalence to the predicate device (DSM Biomedical Calcium Phosphate Cement, K173362).

Here's an analysis of the acceptance criteria and supporting studies based on the provided text:

1. Table of Acceptance Criteria and Reported Device Performance

Acceptance Criteria / Performance Metric	Subject Device (1cc DSM Biomedical Calcium Phosphate Cement) Reported Performance	Predicate Device (DSM Biomedical Calcium Phosphate Cement, K173362)
Indications for Use	To fill bony voids or gaps of the skeletal system (extremities and pelvis), surgically created or from traumatic injury. Not for intrinsic stability. Augments provisional hardware. Temporary support, resorbs and replaced by bone.	Identical Indications for Use
Material Composition	Calcium phosphate powder with bovine collagen mixed with saline to form hydroxyapatite	Calcium phosphate powder with bovine collagen mixed with saline, patient's blood, or patient's bone marrow aspirate to form hydroxyapatite
Form	Injectable, sculptable, drillable, and fast setting calcium phosphate cement that converts to hydroxyapatite	Injectable, sculptable, drillable, and fast setting calcium phosphate cement that converts to hydroxyapatite
Packaging	Powder pre-packaged in a female luer syringe, packaged with accessories to aid in mixing and delivery.	Powder prepackaged in a mixing and delivery syringe, packaged with accessories to aid in mixing and delivery.
Sterilization	Sterile by gamma irradiation (validated per ISO 11137-1 and ISO 11137-2).	Sterile by gamma irradiation
Reusable	Single Use Device	Single Use Device
Biocompatible	Yes (acceptance based on ISO 10993-1, -3, -5, -10, -11, -17, ISO 22442-2, -3, USP<85>)	Yes
Sizes Offered	1cc	5cc
Shelf Life	Confirmed by stability testing	Not specified in table, but generally implied for predicate.
Product Appearance	Met	Not explicitly stated, implied to be acceptable for predicate.
Handling	Met	Not explicitly stated, implied to be acceptable for predicate.
Injectability	Met	Not explicitly stated, implied to be acceptable for predicate.
Setting Time	Met	Not explicitly stated, implied to be acceptable for predicate.
Compressive Strength	Met	Not explicitly stated, implied to be acceptable for predicate.
X-ray Diffraction	Met	Not explicitly stated, implied to be acceptable for predicate.
Porosity	Met	Not explicitly stated, implied to be acceptable for predicate.
Anchor Pull Out Strength	Met	Not explicitly stated, implied to be acceptable for predicate.
Bacterial Endotoxins (BET)	Not more than 20 Endotoxin Units per device (met specifications per USP <85> and AAMI ANSI ST72: 2019)	Not explicitly stated, implied to be acceptable for predicate.
Packaging Integrity	Met requirements of ISO 11607-1	Not explicitly stated, implied to be acceptable for predicate.
New Bone Formation (animal study at 12 weeks)	5.8% ± 2%	6.3% ± 3.2%
Implant Material Remaining (animal study at 12 weeks)	84.2%	86.6%

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

Non-Clinical Bench Testing (Material, Mechanical, Physical): The document does not specify the exact sample sizes for each type of bench testing (e.g., injectability, setting time, compressive strength). It just states that "Material characterization and performance testing... was completed." The provenance is likely internal testing by DSM Biomedical.
Biocompatibility Testing: The number of samples for each biocompatibility test (Cytotoxicity, Sensitization, Irritation, Acute Systemic Toxicity, Genotoxicity, Subacute Systemic Toxicity, Pyrogenicity) is not specified. Provenance is likely contract labs performing testing according to ISO 10993 standards.
Performance Animal Testing: The test set used an "ovine critical sized femoral defect model." The number of animals in the DSM + saline group and the Hydroset predicate group is not explicitly stated, but the percentages imply multiple subjects, and statistical variations (e.g., "± 2%") would necessitate a reasonable sample size for statistical significance. This appears to be a prospective animal study specifically designed for this submission or product line.

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

Bench Testing: Ground truth for bench testing is established by recognized standards (FDA Guidance Document, ASTM F1185, USP <85>, AAMI ANSI ST72: 2019, ISO 11607-1, ISO 11137-1/2, ISO 10993 series, ISO 22442-2/3). Experts are likely engineers and scientists within DSM Biomedical or independent testing laboratories with expertise in these standards. Their specific number and qualifications are not detailed.
Animal Study: The animal study compared the device to a predicate and an empty defect control. The "ground truth" here is the biological response (new bone formation, implant remaining) observed in the ovine model. The evaluation of these outcomes would typically involve veterinary pathologists and/or histologists; however, their specific number and qualifications are not mentioned.

4. Adjudication Method for the Test Set

The document does not describe any specific adjudication method for human reviewers in a clinical context. The "adjudication" for bench and animal testing is inherent in the standardized methodologies and objective measurements.

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 MRMC comparative effectiveness study was mentioned. This device is a bone void filler, not an AI-powered diagnostic or assistive technology for human readers.

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

This question is irrelevant for the DSM Biomedical Calcium Phosphate Cement, as it is a medical device material/implant and not an algorithm or AI product.

7. The Type of Ground Truth Used

Bench Testing: Ground truth established through objective measurements against pre-defined performance specifications derived from recognized standards (ASTM, ISO, USP, FDA guidance).
Biocompatibility Testing: Ground truth established through biological response assays compared against established criteria for acceptable biocompatibility (based on ISO 10993 series).
Animal Study: Ground truth for "performance" (new bone formation, implant remaining) was established by histological and quantitative analysis of tissue samples from the ovine femoral defect model.

8. The Sample Size for the Training Set

This product is not an AI/ML algorithm requiring a training set. This question is not applicable.

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

This question is not applicable, as there is no training set for this device.

Summary

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March 21, 2023

Image /page/0/Picture/1 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which consists of the letters "FDA" in a blue square, followed by the words "U.S. FOOD & DRUG" in blue, with the word "ADMINISTRATION" underneath.

DSM Biomedical Diana Osgood Senior Regulatory Affairs Specialist 735 Pennsylvania Drive Exton, Pennsylvania 19431

Re: K230054

Trade/Device Name: DSM Biomedical Calcium Phosphate Cement Regulation Number: 21 CFR 888.3045 Regulation Name: Resorbable Calcium Salt Bone Void Filler Device Regulatory Class: Class II Product Code: MQV, OIS, Dated: January 6, 2023 Received: January 6, 2023

Dear Ms. Diana Osgood:

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. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. 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

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801); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4. Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.

Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.

For comprehensive regulatory information about mediation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).

Sincerely.

Sara S. Thompson -S

For

Laurence D. Coyne. Ph.D. Director DHT6C: Division of Restorative, Repair and Trauma Devices OHT6: Office of Orthopedic Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health

Enclosure

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Indications for Use

510(k) Number (if known) K230054

Device Name DSM Biomedical Calcium Phosphate Cement

Indications for Use (Describe)

Type of Use (Select one or both, as applicable)
☑ Prescription Use (Part 21 CFR 801 Subpart D)	☐ Over-The-Counter Use (21 CFR 801 Subpart C)

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Image /page/3/Picture/1 description: The image shows the logo for DSM, a global science-based company active in health, nutrition, and materials. The logo consists of a colorful abstract graphic on the left and the letters "DSM" in a bold, blue font on the right. The graphic is composed of overlapping, curved shapes in various colors, including blue, green, yellow, and purple, creating a sense of dynamism and innovation.

510(k) Summary

I. SUBMITTER

Submitter:	DSM Biomedical735 Pennsylvania DriveExton, PA 19341
Phone:	484-713-2100
Contact Person:	Diana Osgood
Date Prepared:	March 14, 2023

II. DEVICE

Trade Name:	DSM Biomedical Calcium Phosphate Cement
Common/Usual Name:	Bone Void Filler
Classification Name:	Resorbable Calcium Salt Bone Void Filler Device
Classification	21 CFR 880.3045
Regulation:
Device Class:	2
Device Code:	MQV: Filler, Bone Void, Calcium CompoundOIS: Calcium Salt Bone Void Filler, Drillable, Non-screwAugmentation
Advisory Panel:	Orthopedic

III. PREDICATE DEVICE

Substantial equivalence is claimed to the following device:

. DSM Biomedical Calcium Phosphate Cement, K173362

IV. DEVICE DESCRIPTION

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Image /page/4/Picture/1 description: The image shows the logo for DSM, a global science-based company. The logo consists of a colorful abstract graphic on the left and the letters "DSM" in bold blue font on the right. The graphic is composed of overlapping shapes in various colors, including blue, green, orange, and purple, creating a sense of dynamism and innovation. The overall design is modern and corporate, reflecting the company's focus on science and technology.

The DSM Calcium Phosphate Cement is a line extension to the current DSM Calcium Phosphate Cement product line, which introduces the 1cc size and a new packaging configuration. DSM Calcium Phosphate Cement is an injectable, sculptable, drillable, fast self-setting bone substitute. DSM Calcium Phosphate Cement is composed of calcium phosphate, which converts to hydroxyapatite in vivo, and bovine collagen powder. The device can also be used to augment provisional hardware to help support bone fragments during the surgical procedure. The cement is provided in a powder form and is packaged in a female luer syringe. An empty male luer syringe is provided to allow for syringeto-syringe mixing of the powder with saline at the required powder-to-liquid ratio. DSM Calcium Phosphate Cement is supplied sterile by gamma irradiation and is non-pyrogenic.

V. INDICATIONS FOR USE:

DSM Biomedical Calcium Phosphate Cement is indicated to fill bony voids or gaps of the skeletal system (i.e. extremities and pelvis). These defects may be surgically created, or osseous defects created from traumatic injury to the bone. The Calcium Phosphate Cement is indicated only for bony voids or gaps that are not intrinsic to the stability of the bony structure. The Calcium Phosphate Cement cured in situ provides an open void/gap filler that can augment provisional hardware (e.g. K-Wires, plates, screws) to help support bone fragments during the surgical procedure. The cured cement acts only as a temporary support media and is not intended to provide structural support during the healing process. The Calcium Phosphate Cement resorbs and is replaced by bone during the healing process.

TECHNOLOGICAL CHARACTERSTICS WITH THE VI. COMPARISON OF PREDICATE DEVICE

The DSM Calcium Phosphate Cement is a line extension of the currently cleared 5cc DSM CPC (predicate device, K173362). The 1cc device maintains the same formulation and indication for use as the 5cc device but will be packaged in a different configuration. The subject device is substantially

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Image /page/5/Picture/1 description: The image shows the logo for DSM, a global science-based company active in health, nutrition, and materials. The logo consists of a colorful abstract graphic on the left and the letters "DSM" in bold blue font on the right. The graphic is composed of overlapping curved shapes in various colors, including blue, green, orange, and purple, forming a circular design with a hexagonal space in the center.

equivalent in terms of indications for use, material composition, technological characteristics, and performance characteristics to the predicate device. The devices are compared in the table below.

Characteristic	1cc DSM Biomedical CalciumPhosphate Cement(Subject Device)	DSM Biomedical CalciumPhosphate Cement(K173362 Predicate Device)
Indications forUse	DSM Biomedical Calcium PhosphateCement is indicated to fill bony voidsor gaps of the skeletal system (i.e.,extremities and pelvis). These defectsmay be surgically created, or osseousdefects created from traumatic injury tothe bone. The Calcium PhosphateCement is indicated only for bony voidsor gaps that are not intrinsic to thestability of the bony structure. TheCalcium Phosphate Cement cured insitu provides an open void/gap fillerthat can augment provisional hardware(e.g., K-Wires, plates, screws) to helpsupport bone fragments during thesurgical procedure. The cured cementacts only as a temporary support mediaand is not intended to provide structuralsupport during the healing process.The Calcium Phosphate Cementresorbs and is replaced by bone duringthe healing process.	DSM Biomedical Calcium PhosphateCement is indicated to fill bony voidsor gaps of the skeletal system (i.e.,extremities and pelvis). These defectsmay be surgically created, or osseousdefects created from traumatic injury tothe bone. The Calcium PhosphateCement is indicated only for bony voidsor gaps that are not intrinsic to thestability of the bony structure. TheCalcium Phosphate Cement cured insitu provides an open void/gap fillerthat can augment provisional hardware(e.g., K-Wires, plates, screws) to helpsupport bone fragments during thesurgical procedure. The cured cementacts only as a temporary support mediaand is not intended to provide structuralsupport during the healing process.The Calcium Phosphate Cementresorbs and is replaced by bone duringthe healing process.
Material	Calcium phosphate powder withbovine collagen mixed with saline toform hydroxyapatite	Calcium phosphate powder withbovine collagen mixed with saline,patient's blood, or patient's bonemarrow aspirate to formhydroxyapatite
Form	Injectable, sculptable, drillable, andfast setting calcium phosphate cementthat converts to hydroxyapatite	Injectable, sculptable, drillable, andfast setting calcium phosphate cementthat converts to hydroxyapatite
Packaging	Powder pre-packaged in a female luersyringe, packaged with accessories to	Powder prepackaged in a mixing anddelivery syringe, packaged with
Characteristic	1cc DSM Biomedical CalciumPhosphate Cement(Subject Device)	DSM Biomedical CalciumPhosphate Cement(K173362 Predicate Device)
	aid in the mixing and delivery ofcement	accessories to aid in the mixing anddelivery of cement
Sterilization	Sterile by gamma irradiation	Sterile by gamma irradiation
Reusable	Single Use Device	Single Use Device
Biocompatible	Yes	Yes
Sizes Offered	1cc	5cc

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Image /page/6/Picture/1 description: The image shows the logo for DSM, a global science-based company active in health, nutrition, and materials. The logo consists of a colorful abstract graphic on the left and the letters "DSM" in blue on the right. The graphic is composed of overlapping curved shapes in various colors, including blue, green, yellow, and purple, arranged around a central hexagonal shape. The letters "DSM" are in a bold, sans-serif font and are positioned to the right of the graphic.

The DSM Calcium Phosphate Cement is a line extension to the current DSM CPC product line, which introduces the 1cc size and a new packaging configuration. DSM Biomedical Calcium Phosphate Cement and the predicate device have identical indications for use and are for use in the same target population. The subject and predicate devices are composed of the same materials and are the delivered in the same form. Both are sterilized by gamma irradiation and are for single use only. The additional size and new packaging of the subject device does not raise questions of substantial equivalence as verification testing confirms that the subject device meets the established design requirements.

VII. SUMMARY OF NON-CLINICAL TESTING TO SUPPORT SUBSTANTIAL EQUIVALENCE

The following performance data was provided in support of the substantial equivalence determination.

Mechanical and Physical Testing

Material characterization and performance testing of the DSM Biomedical Calcium Phosphate Cement was completed in accordance with the FDA Guidance Document, Resorbable Calcium Salt Bone Void Filler Device and ASTM F1185 Standard Specification for Composition of

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Image /page/7/Picture/1 description: The image shows the logo for DSM, a global science-based company. The logo consists of a colorful abstract graphic on the left and the letters "DSM" in bold blue font on the right. The graphic is composed of overlapping, curved shapes in shades of blue, green, yellow, and purple, creating a sense of movement and dynamism.

Hydroxylapatite for Surgical Implants. Bench testing included product appearance, handling, injectability, setting time, compressive strength, X-ray diffraction, porosity, and anchor pull out strength.

The Bacterial Endotoxins Test (BET) was conducted on the finished device to detect and quantify the presence of bacterial endotoxins using the gel-clot method. The device met endotoxin limit specifications according to FDA-recognized standards USP <85> Bacterial Endotoxins Test and AAMI ANSI ST72: 2019 Bacterial Endotoxins - Test methodologies, routine monitoring, and alternative to batch testing. The endotoxin limit is not more than 20 Endotoxin Units per device.

The packaging of the subject device was designed to meet the requirements of ISO 11607-1. The subject device is gamma sterilized and has been validated per ISO 11137-1 and ISO 11137-2. Stability testing on the device was performed and confirms the shelf life of the subject device.

Biocompatibility Testing

Biocompatibility testing was completed in accordance with the requirements of ISO 10993-1: 2018, Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing within a Risk Management Process for a permanent implant device with tissue/bone contact. Testing included the following biological effects:

Cytotoxicity per ISO 10993-5 .
Sensitization per ISO 10993-10 ●
Irritation per ISO 10993-10 .
Acute Systemic Toxicity per ISO 10993-11 ●
Genotoxicity per ISO 10993-3 .
Subacute Systemic Toxicity per ISO 10993-3 ●

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Image /page/8/Picture/1 description: The image shows the DSM company logo. On the left side of the logo, there is a colorful abstract design with blue, green, purple, and orange colors. On the right side of the logo, the company name "DSM" is written in bold blue letters.

Pyrogenicity testing per USP<85> and Rabbit Material Mediated Pyrogenicity per ISO 10993-11 have been completed to verify that the device is non-pyrogenic.

The bovine collagen is sourced in accordance with ISO 22442-2 and per FDA Guidance Document, Medical Devices Containing Materials Derived from Animal Sources (Except for In Vitro Diagnostic Devices).

Viral inactivation studies per ISO 22442-3 and a residual chemical assessment per ISO 10993-17 were conducted.

Results indicate that the device's biocompatibility profile is acceptable.

Performance Animal Testing

The performance of DSM Biomedical Calcium Phosphate Cement plus saline (DSM + Saline) was compared to Stryker Hydroset in an ovine critical sized femoral defect model. At the 12week timepoint, animal study data demonstrated new bone formation averages of 5.8% ±-2% in the DSM + saline group, 6.3% ±-3.2% in the Hydroset predicate group, and 24.3% ±-7.3% in the empty defect negative control group. Animal study data demonstrated that approximately 84.2% of implant material remained in the DSM + saline group, and 86.6% remained in the Hydroset predicate group 12 weeks following implantation. Clinical performance has not been evaluated.

VII. CONCLUSIONS

Pursuant to section 510(k), DSM Biomedical Calcium Phosphate Cement is substantially equivalent to the predicate device DSM Biomedical Calcium Phosphate Cement with regard to indication for use, technological characteristics (including principles of operation), and performance characteristics.

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.