ASTM F1185-23

Standard Specification for Composition of Medical-Grade Hydroxylapatite for Surgical Implants

ABSTRACT
This specification covers chemical and crystallographic requirements for hydroxylapatite intended for surgical implants. Elemental analysis for calcium and phosphorus will be consistent with the expected stoichiometry of hydroxylapatite. The calcium and phosphorus contents shall be determined using a suitable method such as ion chromatography. A quantitative X-ray diffraction analysis shall indicate a minimum hydroxylapatite content of 95 %. The concentration of trace elements such as arsenic, cadmium, mercury, and lead shall be determined for hydroxylapatite derived from natural resources. The analysis of other trace elements may be required, based on the conditions, apparatus, or environments specific to the manufacturing techniques and raw materials. Either inductively coupled plasma/mass spectroscopy (ICP/MS), atomic absorption (AAS), or the methods mentioned shall be used.
SCOPE
1.1 This specification covers chemical and crystallographic requirements for hydroxylapatite intended for surgical implants. For a material to be called medical-grade hydroxylapatite, it must conform to this specification. (See Appendix X1.)  
1.2 The biological response to hydroxylapatite in soft tissue and bone has been characterized by a history of clinical use (1-3)2 and by laboratory studies  (4-6).  
1.3 This specification includes powder, particulate, and forms intended for use as surgical implants, components of surgical implants, or as raw materials for manufacturing processes such as thermal spray coating, electrophoretic deposition, physical vapor deposition, and so forth.  
1.4 This specification specifically excludes hydroxylapatite coatings, amorphous calcium phosphate, ceramic-glasses, tribasic calcium phosphate, whitlockite, and alpha- and beta-tricalcium phosphate (see Specification F1088).  
1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.6 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.  
1.7 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 F1088-04a(2010) - Standard Specification for Beta-Tricalcium Phosphate for Surgical Implantation
• Effective Date: 01-Sep-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(2010) - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Jun-2010
• Refers: ASTM F2024-10 - Standard Practice for X-ray Diffraction Determination of Phase Content of Plasma-Sprayed Hydroxyapatite Coatings
• 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 F1088-04a - Standard Specification for Beta-Tricalcium Phosphate for Surgical Implantation
• 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 F1088-04ae1 - Standard Specification for Beta-Tricalcium Phosphate for Surgical Implantation
• Effective Date: 01-May-2004
• Refers: ASTM F1088-04 - Standard Specification for Beta-Tricalcium Phosphate for Surgical Implantation
• Effective Date: 01-Jan-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 F2024-00 - Standard Practice for X-ray Diffraction Determination of Phase Content of Plasma-Sprayed Hydroxyapatite Coatings (Withdrawn 2009)
• Effective Date: 10-May-2000
• 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 F1185-23 sets the international standard for the chemical and crystallographic composition of medical-grade hydroxylapatite intended for surgical implants. This specification provides clear requirements for ensuring the quality, purity, and safety of hydroxylapatite (HA) in a variety of medical applications, particularly as a component for surgical implants or as a raw material for advanced manufacturing processes.

Medical-grade hydroxylapatite is widely recognized for its compatibility with bone and soft tissue, making it a preferred material in orthopedic and dental implants. Compliance with ASTM F1185-23 ensures materials meet stringent criteria for composition, trace elements, and quality assurance, supporting long-term clinical success and patient safety.

Key Topics

• Chemical Composition: The standard mandates specific stoichiometric ratios for calcium and phosphorus, verified by appropriate analytical methods such as ion chromatography and X-ray diffraction.
• Purity Requirements: Medical-grade hydroxylapatite must demonstrate a minimum purity of at least 95% as determined by quantitative X-ray diffraction analysis.
• Elemental Impurities:
  • Trace elements including arsenic, cadmium, mercury, and lead are closely regulated, especially for HA derived from natural sources.
  • Maximum permissible concentrations are outlined, and advanced techniques like ICP/MS or AAS are prescribed for analysis.
  • Manufacturers must report concentrations and ensure conformity with Pharmacopeial and international guidance on elemental impurities.
• Material Exclusions: This specification excludes hydroxylapatite coatings, amorphous calcium phosphate, ceramic-glasses, tribasic calcium phosphate, whitlockite, alpha- and beta-tricalcium phosphate, ensuring clarity in materials allowable under this standard.
• Biocompatibility Guidance: Biological response to hydroxylapatite is supported by clinical and laboratory data. The standard references established methods for evaluating biocompatibility per ISO 10993-1 and relevant ASTM practices.
• Quality Systems: Manufacturers must implement robust quality management systems in line with global standards such as ISO 9001, ISO 13485, and 21 CFR 820.

Applications

ASTM F1185-23 is integral to industries manufacturing:

• Surgical Implants: Including orthopedic and dental implants fabricated from or incorporating medical-grade hydroxylapatite.
• Component Manufacturing: For implants using HA in powder or particulate form.
• Surface Coatings: Utilizing HA as a raw material for thermal spray, electrophoretic deposition, and physical vapor deposition processes.
• Bone Grafts and Fillers: As a bioactive and osteoconductive material for bone repair and augmentation.

Conformance to this standard ensures:

• Product Consistency: Manufacturers can guarantee uniformity and reproducibility in the chemical and physical properties of HA.
• Safety and Regulatory Compliance: Meeting international regulatory expectations for implantable medical devices and raw materials.
• Trust in Clinical Outcomes: Healthcare providers, patients, and regulators can rely on documented material quality and biocompatibility.

Related Standards

For comprehensive compliance and best practices, users of ASTM F1185-23 should consult the following associated standards:

• ASTM F748 - Practice for Selecting Generic Biological Test Methods for Materials and Devices
• ASTM F981 - Practice for Assessment of Compatibility of Biomaterials for Surgical Implants
• ASTM F1088 - Specification for Medical-Grade Beta-Tricalcium Phosphate
• ASTM F2024 - X-ray Diffraction Determination of Phase Content of Plasma-Sprayed HA Coatings
• ISO 10993-1 - Biological Evaluation of Medical Devices
• ISO 9001 / ISO 13485 - Quality Management Systems for Medical Devices
• USP <232> and <233> - Guidelines for Elemental Impurities
• 21 CFR 820 - Quality System Regulation for Medical Devices

Conclusion

Implementing ASTM F1185-23 is essential for organizations producing or utilizing medical-grade hydroxylapatite for surgical implants. Following this standard assures high levels of purity, safety, and performance, reinforcing confidence in medical device manufacturing and supporting successful patient outcomes in orthopedic and dental surgery.

Keywords: medical-grade hydroxylapatite, ASTM F1185-23, surgical implants, chemical composition, elemental impurities, bioceramics, bone graft, quality management, orthopedic implants, biomaterial standard.

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: F1185 − 23
Standard Specification for
Composition of Medical-Grade Hydroxylapatite for Surgical
Implants
This standard is issued under the fixed designation F1185; 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 2. Referenced Documents
2.1 ASTM Standards:
1.1 This specification covers chemical and crystallographic
requirements for hydroxylapatite intended for surgical im- F748 Practice for Selecting Generic Biological Test Methods
for Materials and Devices
plants. For a material to be called medical-grade
hydroxylapatite, it must conform to this specification. (See F981 Practice for Assessment of Compatibility of Biomate-
Appendix X1.) rials for Surgical Implants with Respect to Effect of
Materials on Muscle and Insertion into Bone
1.2 The biological response to hydroxylapatite in soft tissue
F1088 Specification for Medical-Grade Beta-Tricalcium
and bone has been characterized by a history of clinical use
2 Phosphate Raw Material for Implantable Medical Devices
(1-3) and by laboratory studies (4-6).
F2024 Practice for X-ray Diffraction Determination of Phase
1.3 This specification includes powder, particulate, and
Content of Plasma-Sprayed Hydroxyapatite Coatings
forms intended for use as surgical implants, components of
2.2 Code of Federal Regulations:
surgical implants, or as raw materials for manufacturing
Title 21 Part 820 Quality System Regulation
processes such as thermal spray coating, electrophoretic
2.3 National Formulary:
deposition, physical vapor deposition, and so forth.
Tribasic Calcium Phosphate
1.4 This specification specifically excludes hydroxylapatite
2.4 United States Pharmacopeia (USP) Documents:
coatings, amorphous calcium phosphate, ceramic-glasses,
USP <191> Identification Tests for Calcium and Phosphate
tribasic calcium phosphate, whitlockite, and alpha- and beta-
USP <232> Elemental Impurities—Limits
tricalcium phosphate (see Specification F1088).
USP <233> Elemental Impurities—Procedure
1.5 The values stated in SI units are to be regarded as
2.5 U.S. Geological Survey Method:
standard. No other units of measurement are included in this
Cadmium
standard.
2.6 ANSI/ISO Standards:
1.6 This standard does not purport to address all of the
ANSI/ISO/ASQ 9000 Quality Management Systems—
safety concerns, if any, associated with its use. It is the
Fundamentals and Vocabulary
responsibility of the user of this standard to establish appro-
ANSI/ISO/ASQ 9001 Quality Management Systems—
priate safety, health, and environmental practices and deter-
Requirements
mine the applicability of regulatory limitations prior to use.
1.7 This international standard was developed in accor-
dance with internationally recognized principles on standard-
ization established in the Decision on Principles for the
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
Development of International Standards, Guides and Recom-
Standards volume information, refer to the standard’s Document Summary page on
mendations issued by the World Trade Organization Technical
the ASTM website.
Barriers to Trade (TBT) Committee.
Available from U.S. Government Printing Office, N. Capitol and H St., NW,
Washington, DC 20402.
National Formulary XVI. Available from U.S. Pharmacopeia Convention, Inc.,
12601 Twinbrook Parkway, Rockville, MD 20852.
1 6
This specification is under the jurisdiction of ASTM Committee F04 on United States Pharmacopeia XXI. Available from U.S. Pharmacopeia
Medical and Surgical Materials and Devices and is the direct responsibility of Convention, Inc., 12601 Twinbrook Parkway, Rockville, MD 20852.
Subcommittee F04.13 on Ceramic Materials. Crock, J. G., Felichte, F. E., and Briggs, P. H., “Determination of Elements in
Current edition approved April 15, 2023. Published April 2023. Originally National Bureau of Standards Geological Reference Materials SRM 278 Obsidian
approved in 1988. Last previous edition approved in 2014 as F1185 – 03 (2014). and SRM 688 Basalt by Inductively Coupled Argon Plasma—Atomic Emission
DOI: 10.1520/F1185-23. Spectrometry,” Geostandards Newsletter, Vol 7, 1983, pp. 335–340.
2 8
The boldface numbers in parentheses refer to the list of references at the end of Available from American National Standards Institute (ANSI), 25 W. 43rd St.,
this specification. 4th Floor, New York, NY 10036, http://www.ansi.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F1185 − 23
ANSI/ISO 10993-1 Biological Evaluation of Medical Se, and Tl) may be excluded from the risk analysis due to their
Devices—Part 1: Evaluation Within a Risk Management low abundance and low potential for being co-isolated with
System
other materials.
ANSI/ISO/ASQ 13485 Medical Devices—Quality Manage-
4.3.2.1 Hydroxylapatite materials that are produced syn-
ment Systems—Requirements for Regulatory Purposes
thetically from purified compounds should have significantly
lower and more consistent concentrations of elemental impu-
3. Terminology
rities compared to materials derived from natural sources. If
3.1 Definitions of Terms Specific to This Standard:
the manufacturer can demonstrate adequate process control,
3.1.1 hydroxylapatite—the chemical substance having the
sampling frequency for elemental impurities may be reduced.
empirical formula Ca (PO ) OH.
5 4 3
4.3.3 Except for intentionally added elements, assess the
obtained results for compliance with the Parenteral Concentra-
4. Chemical Requirements
tion limits described within the Individual Component Option
4.1 Elemental analysis for calcium and phosphorus shall be
of USP <232>, Table 3 (derived from ICH Q3D Option 1,
consistent with the expected stoichiometry of hydroxylapatite.
Table A.2.2). If all listed elements except for those that are
The calcium and phosphorus contents, or alternatively, the ratio
intentionally added can be assured to be maintained within the
of calcium to phosphorous, shall be determined using suitable
Parenteral Concentration Individual Component Option limits,
methods such as ion chromatography, X-ray fluorescence, or
the material “conforms” to USP <232>. If any listed element
X-ray diffraction (see USP <191>).
(other than those intentionally added) cannot be controlled to
4.2 A quantitative X-ray diffraction analysis shall indicate a
be maintained within the prescribed USP <232> limits, the
minimum hydroxylapatite content of 95 % as determined in
material does not conform with USP <232>.
accordance with Practice F2024. Analysis of relative peak
4.3.3.1 Report the concentration (in ppm, per USP <233> or
intensities shall be consistent with published data.
equivalent) of each element.
4.3.4 For each intentionally added element, the concentra-
4.3 Elemental Impurities:
tion (in ppm, per USP <233> or equivalent) shall be both
4.3.1 The significance of elemental impurities within an
monitored and reported.
absorbable material is ultimately dependent on the dimensional
characteristics of the final product and the rate of release of
4.3.5 The elemental impurities thresholds for the Individual
those initially interstitial elements into the surrounding tissue
Component Option of USP <232>, Table 3, provide specific
and extracelluar fluid. Thus, any risk assessment of such
elemental daily dosage limits for parenteral drug products.
impurities will be dependent on the final product design and
These daily elemental impurity limits (including those applied
intended application. Consequently, this standard provides for
to intentionally added elements) should be considered as
appropriate reporting of elemental impurities values, but does
conservative thresholds for informational purposes only when
not mandate any specific concentration requirements.
applied to absorbable implants. Proper application of these
Therefore, elemental impurity limits shall be as agreed upon
limits in setting raw material specifications should consider the
between the purchaser and the supplier. More detailed and
amount of hydroxylapatite in the final implant product as well
pharmaceutical-oriented guidance regarding the appropriate
as its degradation and elemental elution rate into the surround-
means for both monitoring and assessing relevant elemental
ing tissue.
impurities within a final product can be found in USP Chapters
4.3.5.1 The elemental impurity content of hydroxylapatite
<232> and <233> and ICH Q3D.
raw materials used in implants with a successful clinical
4.3.2 For each raw material lot, determine the concentra-
history may also be considered in setting limits for raw
tions of the respective elemental impurities within the hydroxy-
material specifications. For such data to be relevant, analyses
lapatite by utilizing inductively coupled plasma mass spectros-
shall be consistent with the methods of USP <233> and shall be
copy (ICP-MS) or inductively coupled plasma atomic or
conducted on raw material lots used for clinically released
optical emission spectroscopy (ICP-AES or ICP-OES) or an
product.
equivalent alternative method as described in USP Chapter
4.3.6 See X2.2 for additional information.
<233>. The specific 24 different elemental impurities of
4.3.7 The analysis of other trace elements may be required
interest are outlined in both USP <232> and in Table A.2.2 of
based on the conditions, apparatus, or environments specific to
ICH Q3D. Both of these documents include risk-based ap-
the manufacturing techniques and raw materials.
proaches toward the assessment and control of elemental
impurities. Per Section 4 of ICH Q3D, ten of the
...

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: F1185 − 03 (Reapproved 2014) F1185 − 23
Standard Specification for
Composition of Medical-Grade Hydroxylapatite for Surgical
Implants
This standard is issued under the fixed designation F1185; 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 hydroxylapatite intended for surgical implants. For
a material to be called medical-grade hydroxylapatite, it must conform to this specification. (See Appendix X1.)
1.2 The biological response to hydroxylapatite in soft tissue and bone has been characterized by a history of clinical use (1-3)
and by laboratory studies (4-6).
1.3 This specification includes powder, particulate, and forms intended for use as surgical implants, components of surgical
implants, or as raw materials for manufacturing processes such as thermal spray coating, electrophoretic deposition, physical vapor
deposition, and so forth.
1.4 This specification specifically excludes hydroxylapatite coatings, amorphous calcium phosphate, ceramic-glasses, tribasic
calcium phosphate, whitlockite, and alpha- and beta-tricalcium phosphate. (Seephosphate (see Specification F1088.)).
1.5 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.6 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 and healthsafety, health, and environmental practices and determine
the applicability of regulatory limitations prior to use.
1.7 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
F1088 Specification for Medical-Grade Beta-Tricalcium Phosphate Raw Material for Implantable Medical Devices
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 March 1, 2014April 15, 2023. Published March 2014April 2023. Originally approved in 1988. Last previous edition approved in 20092014 as
F1185F1185 – 03 (2014). – 03 (2009). DOI: 10.1520/F1185-03R14.DOI: 10.1520/F1185-23.
The boldface numbers in parentheses refer to the list of references at the end of this specification.
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.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F1185 − 23
F2024 Practice for X-ray Diffraction Determination of Phase Content of Plasma-Sprayed Hydroxyapatite Coatings
2.2 Code of Federal Regulations:
Title 21,21 Part 820 Part 820.Quality System Regulation
2.3 National Formulary:
Tribasic Calcium Phosphate
2.4 United States Pharmacopeia:Pharmacopeia (USP) Documents:
Identification Tests for Calcium and Phosphate USP <191> Identification Tests for Calcium and Phosphate
Lead < 251>USP <232> Elemental Impurities—Limits
Mercury <261>USP <233> Elemental Impurities—Procedure
Arsenic <211>
Heavy Metals <231> Method 1
2.5 U. S. U.S. Geological Survey Method:
Cadmium
2.6 American Society for Quality:ANSI/ISO Standards:
ANSI/ISO/ASQ 9000 Quality Management Systems—Fundamentals and Vocabulary
ANSI/ISO/ASQ 9001 Quality Management Systems—Requirements
C1ANSI/ISO 10993-1 Specification of General Requirements for a Quality ProgramBiological Evaluation of Medical
Devices—Part 1: Evaluation Within a Risk Management System
ANSI/ISO/ASQ 13485 Medical Devices—Quality Management Systems—Requirements for Regulatory Purposes
3. Terminology
3.1 Definitions of Terms Specific to This Standard:
3.1.1 hydroxylapatite—the chemical substance having the empirical formula Ca (PO ) OH.
5 4 3
4. Chemical Requirements
4.1 Elemental analysis for calcium and phosphorus willshall be consistent with the expected stoichiometry of hydroxylapatite. The
calcium and phosphorus contents contents, or alternatively, the ratio of calcium to phosphorous, shall be determined using a
suitable methodmethods such as ion chromatography.chromatography, X-ray fluorescence, or X-ray diffraction (see USP <191>).
4.2 A quantitative X-ray diffraction analysis shall indicate a minimum hydroxylapatite content of 95 % as determined in
accordance with Practice F2024. Analysis of relative peak intensities shall be consistent with published data.
4.3 For hydroxylapatite derived from natural sources, the concentration of trace elements shall be limited as follows:
Element ppm, max
As 3
Cd 5
Hg 5
Pb 30
Elemental Impurities:
Either inductively coupled plasma/mass spectroscopy (ICP/MS), atomic absorption (AAS), or the methods listed in 2.4 and 2.5
shall be used.
4.3.1 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
Available from U.S. Government Printing Office, N. Capitol and H St., NW, Washington, DC 20402.
National Formulary XVI. Available from U.S. Pharmacopeia Convention, Inc., 12601 Twinbrook Parkway, Rockville, MD 20852.
United States Pharmacopeia XXI. Available from U.S. Pharmacopeia Convention, Inc., 12601 Twinbrook Parkway, Rockville, MD 20852.
Crock, J. G., Felichte, F. E., and Briggs, P. H., “Determination of Elements in National Bureau of Standards Geological Reference Materials SRM 278 Obsidian and SRM
688 Basalt by Inductively Coupled Argon Plasma—Atomic Emission Spectrometry,” Geostandards Newsletter, Vol 7, 1983, pp. 335-340.335–340.
Available from American Society for Quality (ASQ), 600 N. Plankinton Ave., Milwaukee, WI 53203, http://www.asq.org.National Standards Institute (ANSI), 25 W. 43rd
St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Chemical Abstracts Service Registry Number [1306-06-5].
The Joint Committee on Powdered Diffraction Standards has established a Powder Diffraction File. The Committee operates on an international basis and cooperates
closely with the Data Commission of the International Union of Crystallography and ASTM (American Society for Testing and Materials). Hydroxylapatite data can be found
on file card number 9-432 and is available from the Joint Committee on Powder Diffraction Standards, 1600 Park Lane, Swarthmore, PA 19081.
F1185 − 23
application. Consequently, this standard provides for appropriate reporting of elemental impurities values, but does not mandate
any specific 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.
4.3.2 For each raw material lot, determine the concentrations of the respective elemental impurities within the hydroxylapatite 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. Per Section 4 of ICH Q3D, ten of the
24 elements of interest (Class 2B elements, Ag, Au, Ir, Os, Pd, Pt, Rh, Ru, Se, and Tl) may be excluded from the risk analysis due
to their low abundance and low potential for being co-isolated with other materials.
4.3.2.1 Hydroxylapatite materials that are produced synthetically from purified compounds should have significantly lower and
more consistent concentrations of elemental impurities compared to materials derived from natural sources. If the manufacturer
can demonstrate adequate process control, sampling frequency for elemental impurities may be reduced.
4.3.3 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>.
4.3.3.1 Report the concentration (in ppm, per USP <233> or equivalent) of each element.
4.3.4 For each intentionally added element, the concentration (in ppm, per USP <233> or equivalent) shall be both monitored and
reported.
4.3.5 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 absorbable
implants. Proper application of these limits in setting raw material specifications should consider the amount of hydroxylapatite
in the final implant product as well as its degradation and elemental elution rate into the surrounding tissue.
4.3.5.1 The elemental impurity content of hydroxylapatite raw materials used in implants with a successful clinical history may
also be considered in setting limits for raw material speci
...