ASTM F1088-23

Standard Specification for Medical-Grade Beta-Tricalcium Phosphate Raw Material for Implantable Medical Devices

ABSTRACT
This specification covers chemical and crystallographic requirements for biocompatible beta-tricalcium phosphate for surgical implant applications. Elemental analysis for calcium and phosphorus will be consistent with the expected stoichiometry of beta-tricalcium phosphate. The calcium and phosphorus content shall be determined using a suitable method such X-ray fluorescence. A quantitative X-ray diffraction analysis shall indicate a minimum beta-tricalcium phosphate content of 95 % as determined using powder diffraction method. The analysis of other trace elements may be required, based on the conditions, apparatus, or environment. It is recommended that all metals or oxides present in concentrations equal or greater than 0.1 % be noted in material descriptions.
SCOPE
1.1 This specification covers chemical and crystallographic requirements for beta-tricalcium phosphate (β-TCP) raw materials intended for use in medical device applications. For a material to be identified as medical-grade beta-tricalcium phosphate, it must conform to this specification (see Appendix X1).  
1.2 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.3 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

General Information

• Status: Published
• Publication Date: 14-Apr-2023
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.13 - Ceramic Materials

Relations

• Refers: ASTM F748-16 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Apr-2016
• Refers: ASTM F748-06(2010) - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Jun-2010
• Refers: ASTM F981-04(2010) - Standard Practice for Assessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials on Muscle and Bone
• Effective Date: 01-Jun-2010
• Refers: ASTM F748-06 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Dec-2006
• Refers: ASTM F748-04 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-May-2004
• Refers: ASTM F981-04 - Standard Practice for Assessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials on Muscle and Bone
• Effective Date: 01-May-2004
• Refers: ASTM F981-99(2003) - Standard Practice for Assessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials on Muscle and Bone
• Effective Date: 01-Nov-2003
• Refers: ASTM F981-99 - Standard Practice for Assessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials on Muscle and Bone
• Effective Date: 10-May-1999
• Refers: ASTM F748-98 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 10-Aug-1998

Overview

ASTM F1088-23: Standard Specification for Medical-Grade Beta-Tricalcium Phosphate Raw Material for Implantable Medical Devices establishes the chemical and crystallographic requirements for biocompatible beta-tricalcium phosphate (β-TCP) intended for use in medical device applications. This standard ensures that β-TCP raw materials meet rigorous criteria for purity, consistency, and safety, supporting their effective use in surgical implants and other medical devices. Compliance with ASTM F1088-23 helps manufacturers demonstrate quality and regulatory alignment in the production of advanced ceramic materials for implantable devices.

Key Topics

• Chemical Composition: β-TCP raw materials must exhibit a calcium and phosphorus content consistent with the expected stoichiometry, verified through suitable analytical techniques such as X-ray fluorescence or USP <191> methods.
• Phase Purity: Quantitative X-ray diffraction analysis ensures β-TCP content is at least 95%, confirming material integrity for medical-grade application.
• Elemental Impurities: Detection and reporting of elemental impurities-using methods like ICP-MS or ICP-OES as specified in USP <233>-ensure compliance with recommended thresholds (e.g., USP <232>, ICH Q3D). All metals or oxides at concentrations of 0.1% or higher should be documented.
• Quality Management: Producers must maintain a documented quality system, referencing standards such as ASQ C1, ISO 9001, and ISO 13485 to ensure consistent manufacturing, compliance, and traceability.
• Certification: Each shipment of β-TCP must be accompanied by a certificate of compliance or analysis, detailing chemical composition, elemental analyses, lot number, supplier details, and conformity with referenced impurity limits.

Applications

ASTM F1088-23 applies broadly across the medical device industry, particularly for:

• Surgical Implants: β-TCP is primarily used as a bone graft substitute due to its favorable biocompatibility and resorbability in physiological conditions, supporting new bone growth.
• Orthopedic Devices: The standard supports the use of β-TCP in orthopedic devices requiring bone replacement or repair, ensuring safe use through stringent material specifications.
• Dental and Craniofacial Implants: Its high purity and controlled impurity profile make β-TCP suitable for dental bone regeneration and craniofacial reconstruction.
• Custom and Advanced Ceramics: Manufacturers of advanced ceramic components used in diverse implantable medical devices rely on this standard for quality assurance and regulatory compliance.
• Material Qualification: Biomedical material developers use ASTM F1088-23 as a benchmark during qualification or certification processes for new or modified β-TCP raw materials.

Related Standards

Compliance with ASTM F1088-23 often requires adherence to additional related standards and regulatory documents, including:

• ASTM F748: Practice for selecting biological test methods for materials and devices.
• ASTM F981: Assessment of biomaterial compatibility for surgical implants.
• USP <191>, <232>, <233>: Identification and control of elemental impurities.
• ICH Q3D: Guidelines for elemental impurity assessment in pharmaceuticals, applied here for risk-based material assessment.
• ISO 10993-1: Biological evaluation of medical devices within a risk management system.
• ISO 9000 / ISO 9001: Quality management system fundamentals and requirements.
• ISO 13485: Quality management for medical device manufacturing.
• 21 CFR 820: US FDA quality system regulations for medical devices.

Practical Value

Adopting ASTM F1088-23 for medical-grade beta-tricalcium phosphate raw material ensures a high level of product safety, regulatory compliance, and market acceptance. By specifying detailed chemical and impurity criteria, the standard helps manufacturers and suppliers mitigate risks, assure biocompatibility, and consistently deliver raw materials suitable for sensitive implantable applications. This fosters trust among stakeholders while supporting innovation and safety in the medical device sector.

Keywords: beta-tricalcium phosphate, β-TCP, medical-grade ceramic, surgical implant material, ASTM F1088-23, calcium phosphate, implantable medical device, biocompatible ceramics, quality management, elemental impurities.

Standards Content (Sample)

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F1088 − 23
Standard Specification for
Medical-Grade Beta-Tricalcium Phosphate Raw Material for
Implantable Medical Devices
This standard is issued under the fixed designation F1088; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope ANSI/ISO/ASQ 9001 Quality Management Systems—
Requirements
1.1 This specification covers chemical and crystallographic
ANSI/ISO 10993-1 Biological Evaluation of Medical
requirements for beta-tricalcium phosphate (β-TCP) raw ma-
Devices—Part 1: Evaluation Within a Risk Management
terials intended for use in medical device applications. For a
System
material to be identified as medical-grade beta-tricalcium
ANSI/ISO/ASQ 13485 Medical Devices—Quality Manage-
phosphate, it must conform to this specification (see Appendix
ment Systems—Requirements for Regulatory Purposes
X1).
2.3 United States Pharmacopeia (USP) Documents:
1.2 This standard does not purport to address all of the
USP <191> Identification Tests for Calcium and Phosphate
safety concerns, if any, associated with its use. It is the
USP <232> Elemental Impurities—Limits
responsibility of the user of this standard to establish appro-
USP <233> Elemental Impurities—Procedure
priate safety, health, and environmental practices and deter-
2.4 ICH Document:
mine the applicability of regulatory limitations prior to use.
ICH Q3D International Conference on Harmonization of
1.3 This international standard was developed in accor-
Technical Requirements for Registration of Pharmaceuti-
dance with internationally recognized principles on standard-
cals for Human Use: Guideline for Elemental Impurities
ization established in the Decision on Principles for the
2.5 U.S. Code of Federal Regulations:
Development of International Standards, Guides and Recom-
21 CFR 820 Food and Drugs Services, Part 820—Quality
mendations issued by the World Trade Organization Technical
System Regulation
Barriers to Trade (TBT) Committee.
3. Chemical Requirements
2. Referenced Documents
3.1 Elemental analysis for calcium and phosphorus will be
2.1 ASTM Standards:
consistent with the expected stoichiometry of beta-tricalcium
F748 Practice for Selecting Generic Biological Test Methods
phosphate (Ca (PO ) . The calcium and phosphorus content
3 4 2
for Materials and Devices
shall be determined using a suitable method such as USP
F981 Practice for Assessment of Compatibility of Biomate-
<191> (see 2.3) or X-ray fluorescence.
rials for Surgical Implants with Respect to Effect of
3.2 A quantitative X-ray diffraction analysis shall indicate a
Materials on Muscle and Insertion into Bone
minimum beta-tricalcium phosphate content of 95 % as deter-
2.2 International Organization for Standardization Docu-
mined using Powder Diffraction File No. 550898 and a
ments:
8 9,10
method equivalent to Forman or Rietveld.
ANSI/ISO/ASQ 9000 Quality Management Systems—
3.3 Elemental Impurities:
Fundamentals and Vocabulary
Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,
This specification is under the jurisdiction of ASTM Committee F04 on MD 20852-1790, http://www.usp.org.
Medical and Surgical Materials and Devices and is the direct responsibility of Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758,
Subcommittee F04.13 on Ceramic Materials. 1211 Geneva 13, Switzerland. Available online at http://www.ich.org/LOB/media/
Current edition approved April 15, 2023. Published April 2023. Originally MEDIA423.pdf.
approved in 1987. Last previous edition approved in 2018 as F1088 – 18. DOI: Available from U.S. Government Publishing Office (GPO), 732 N. Capitol St.,
10.1520/F1088-23. NW, Washington, DC 20401, http://www.gpo.gov.
2 7
For referenced ASTM standards, visit the ASTM website, www.astm.org, or International Centre for Diffraction Data, 12 Campus Blvd, Newtown Square,
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM PA 19073-3273.
Standards volume information, refer to the standard’s Document Summary page on Forman, D. W. and Metsger, D. S., “The Determination of Phase Composition
the ASTM website. of Calcium Phosphate Ceramics by X-Ray Diffraction,” Transactions of the Seventh
Available from American National Standards Institute (ANSI), 25 W. 43rd St., Annual Meeting of the American Society for Bone and Mineral Research,
4th Floor, New York, NY 10036, http://www.ansi.org. Kelseyville, CA, 1985 p. 391.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F1088 − 23
3.3.1 The significance of elemental impurities within an 3.3.5.1 The elemental impurity content of β-TCP raw ma-
absorbable material is ultimately dependent on the dimensional terials used in implants with a successful clinical history may
characteristics of the final product and the rate of release of also be considered in setting limits for raw material specifica-
those initially interstitial elements into the surrounding tissue tions. For such data to be relevant, analyses shall be consistent
and extracelluar fluid. Thus, any risk assessment of such with the methods of USP <233> and shall be conducted on raw
impurities will be dependent on the final product design and material lots used for clinically released product.
intended application. Consequently, this raw material (not final
3.3.6 See X2.2 for additional information.
device) standard provides for appropriate reporting of elemen-
3.4 It is recommended that all metals or oxides present in
tal impurities values, but does not mandate any specific
concentrations equal or greater than 0.1 % be noted in material
concentration requirements. Therefore, elemental impurity lim-
descriptions.
its shall be as agreed upon between the purchaser and the
supplier. More detailed and pharmaceutical-oriented guidance
4. Guidance for Manufacturing Control and Quality
regarding the appropriate means for both monitoring and
Assurance
assessing relevant elemental impurities within a final product
4.1 Acceptable levels of manufacturing control are highly
can be found in USP Chapters <232> and <233> and ICH
desirable and apply to the manufacture of the β-TCP raw
Q3D.
material. Good manufacturing practice guidelines for achiev-
3.3.2 For each raw material lot, determine the concentration
ing acceptable levels of manufacturing quality control may be
of the respective elemental impurities within the beta-TCP by
found in:
utilizing inductively coupled plasma mass spectroscopy (ICP-
4.1.1 21 CFR 820—Identifies the requirements that govern
MS) or inductively coupled plasma atomic or optical emission
the methods used in, and the facilities and controls used for, the
spectroscopy (ICP-AES or ICP-OES) or an equivalent alterna-
design, manufacture, packaging, labeling, storage, installation,
tive method as described in USP Chapter <233>. The specific
and servicing of all finished devices intended for human use.
24 different elemental impurities of interest are outlined in both
4.1.2 ANSI/ISO/ASQ 9000—Provides fundamentals for
USP <232> and in Table A.2.2 of ICH Q3D. Both of these
quality management systems as described in the ISO 9000
documents include risk-based approaches toward the assess-
family (informative) and specifies quality management terms
ment and control of elemental impurities.
and their definitions (normative).
3.3.3 Except for intentionally added elements, assess the
4.1.3 ANSI/ISO/ASQ 9001—Presents requirements for a
obtained results for compliance with the Parenteral Concentra-
quality management system. The application of this specifica-
tion limits described within the Individual Component Option
tion can be used by an organization to demonstrate its
of USP <232>, Table 3 (derived from ICH Q3D Option 1,
capability to meet customer requirements for products and/or
Table A.2.2). If all listed element
...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F1088 − 18 F1088 − 23
Standard Specification for
Medical-Grade Beta-Tricalcium Phosphate for Surgical
ImplantationRaw Material for Implantable Medical Devices
This standard is issued under the fixed designation F1088; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 This specification covers chemical and crystallographic requirements for beta-tricalcium phosphate (β-TCP) for surgical
implant raw materials intended for use in medical device applications. For a material to be identified as medical-grade
beta-tricalcium phosphate, it must conform to this specification (see Appendix X1).
1.2 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of
regulatory limitations prior to use.
1.3 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
2. Referenced Documents
2.1 ASTM Standards:
F748 Practice for Selecting Generic Biological Test Methods for Materials and Devices
F981 Practice for Assessment of Compatibility of Biomaterials for Surgical Implants with Respect to Effect of Materials on
Muscle and Insertion into Bone
2.2 American Society for Quality (ASQ) Document:
C1 Specification of General Requirements for a Quality Program
2.2 International Organization for Standardization Document:Documents:
ANSI/ISO/ASQ 9000 Quality Management Systems—Fundamentals and Vocabulary
ANSI/ISO/ASQ 9001 Quality Management Systems—Requirements
ISOANSI/ISO 10993-1 Biological Evaluation of Medical Devices — Part Devices—Part 1: Evaluation Within a Risk
Management System
ANSI/ISO/ASQ 13485 Medical Devices—Quality Management Systems—Requirements for Regulatory Purposes
2.3 United States Pharmacopeia (USP) Documents:
USP <191> Identification Tests for Calcium and Phosphate
USP <232> United States Pharmacopeia: Elemental Impurities – LimitsElemental Impurities—Limits
USP <233> United States Pharmacopeia: Elemental Impurities – ProcedureElemental Impurities—Procedure
This specification is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee
F04.13 on Ceramic Materials.
Current edition approved Nov. 15, 2018April 15, 2023. Published January 2019April 2023. Originally approved in 1987. Last previous edition approved in 20102018 as
F1088 – 04aF1088 – 18.(2010). DOI: 10.1520/F1088-18. 10.1520/F1088-23.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F1088 − 23
2.4 ICH Document:
ICH Q3D International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for
Human Use: Guideline for Elemental Impurities
2.5 U.S. Code of Federal Regulations:
21 CFR 820 Food and Drugs Services, Part 820—Quality System Regulation
3. Chemical Requirements
3.1 Elemental analysis for calcium and phosphorus will be consistent with the expected stoichiometry of beta-tricalcium phosphate
(Ca (PO ) . The calcium and phosphorus content shall be determined using a suitable method such as USP <191> (see 2.42.3) or
3 4 2
X-ray fluorescence.
3.2 A quantitative X-ray diffraction analysis shall indicate a minimum beta-tricalcium phosphate content of 95 % as determined
7 8 9,10
using Powder Diffraction File #550898No. 550898 and a method equivalent to Forman or Rietveld.
3.3 Elemental Impurities:
3.3.1 The significance of elemental impurities within an absorbable material is ultimately dependent on the dimensional
characteristics of the final product and the rate of release of those initially interstitial elements into the surrounding tissue and
extracelluar fluid. Thus, any risk assessment of such impurities will be dependent on the final product design and intended
application. Consequently, this raw material (not final device) standard provides for appropriate reporting of elemental impurities
values, but does not mandate any specific performance requirements. concentration requirements. Therefore, elemental impurity
limits shall be as agreed upon between the purchaser and the supplier. More detailed and pharmaceutical-oriented guidance
regarding the appropriate means for both monitoring and assessing relevant elemental impurities within a final product can be
found in USP Chapters <232> and <233> and ICH Q3D.
3.3.2 Determine For each raw material lot, determine the concentration of the respective elemental impurities within the beta-TCP
by utilizing inductively coupled plasma mass spectroscopy (ICP-MS) or inductively coupled plasma atomic or optical emission
spectroscopy (ICP-AES or ICP-OES) or an equivalent alternative method as described in USP Chapter <233>. The specific 24
different elemental impurities of interest are outlined in both USP <232> and in Table A.2.2 of ICH Q3D. Both of these documents
include risk-based approaches toward the assessment and control of elemental impurities.
3.3.3 Except for intentionally added elements, assess the obtained results for compliance with the Parenteral Concentration limits
described within the Individual Component Option of USP <232>, Table 3 (derived from ICH Q3D Option 1, Table A.2.2). If all
listed elements except for those that are intentionally added can be assured to be maintained within the Parenteral Concentration
– Individual Component Option limits, the material “conforms” to USP <232>. If any listed element (other than those intentionally
added) cannot be controlled to be maintained within the prescribed USP <232> limits, the material does not conform with USP
<232> and the concentration (in ppm, per USP <233> or equivalent) of each uncontrolled element shall be both monitored and
reported.<232>.
3.3.3.1 Report the concentration (in ppm, per USP <233> or equivalent) of each element.
3.3.4 For each intentionally added element, the concentration (in ppm, per USP <233> or equivalent) shall be both monitored and
reported.
3.3.5 The elemental impurities thresholds for the Individual Component Option of USP <232>, Table 3, provide specific
elemental daily dosage limits for parenteral drug products. These daily elemental impurity limits (including those applied to
intentionally added elements) should be considered as conservative thresholds for informational purposes only when applied to
Available from ICH Secretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758, 1211 Geneva 13, Switzerland. Available online at http://www.ich.org/LOB/media/
MEDIA423.pdf.
Available from U.S. Government Publishing Office (GPO), 732 N. Capitol St., NW, Washington, DC 20401, http://www.gpo.gov.
International Centre for Diffraction Data, 12 Campus Blvd, Newtown Square, PA 19073-3273.
Forman, D. W. and Metsger, D. S., “The“The Determination of Phase Composition of Calcium Phosphate Ceramics by X-Ray Diffraction Determination of Phase
Composition of Calcium Phosphate Ceramics by X-Ray Diffraction,” ,” Transactions of the Seventh Annual Meeting of the American Society for Bone and Mineral Research,
Kelseyville, CA, 1985 p. 391.
Jackson, L. E., Barralet, J. E., and Wright, A. J., “Rietveld“Rietveld Analysis in Sintering Studies of Ca-Deficient Hydrxyapatite Analysis in Sintering Studies of
Ca-Deficient Hydrxyapatite,”,” Bioceramics 16, Key Engineering Materials, Vols 254-256254–256, 2004, pp.297–300.
Rietveld, H. M., Acta Crystallogr., Vol 22, 1967, p. 151.
F1088 −
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