ASTM F2313-18

Standard Specification for Poly(glycolide) and Poly(glycolide-co-lactide) Resins for Surgical Implants with Mole Fractions Greater Than or Equal to 70 % Glycolide

ABSTRACT
This specification covers the material characteristics of virgin poly(glycolide) and poly(glycolide-co-lactide) resins with mole fractions within the specified range used in surgical implants. This does not cover packaged and sterilized finished implants fabricated from the same materials. Since some characteristics may be altered by processing techniques when used to produces a specific part or device, properties of fabricated forms of the resins should be evaluated independently using appropriate test methods. The identity of the poly(glycolide) homopolymer, poly(glycolide-co-lactide) copolymer, and poly(glycolide-co-lactide) polymer must be confirmed through nuclear magnetic resonance (NMR).
SCOPE
1.1 This specification covers both virgin poly(glycolide) homopolymer and poly(glycolide-co-lactide) copolymer resins intended for use in surgical implants. The poly(glycolide-colactide) copolymers covered by this specification possess nominal mole fractions greater than or equal to 70 % glycolide (65.3 % in mass fraction). This specification is also applicable to lactide-co-glycolide copolymers that possess glycolide segments sufficient in size to deliver potential for glycolide-based crystallization, thereby requiring fluorinated solvents for complete dissolution under room temperature conditions.  
1.2 Since poly(glycolide) is commonly abbreviated as PGA for poly(glycolic acid) and poly(lactide) is commonly abbreviated as PLA for poly(lactic acid), these polymers are commonly referred to as PGA, PLA, and PLA:PGA resins for the hydrolytic byproducts to which they respectively degrade. PLA is a term that carries no stereoisomeric specificity and therefore encompasses both the amorphous atactic/syndiotactic dl-lactide-based polymers and copolymers as well as the isotactic d-PLA and l-PLA moieties, each of which carries potential for crystallization.  
1.3 This specification is specifically not applicable to amorphous poly(lactide-co-glycolide) or poly(lactide)-based resins able to be fully solvated at 30°C by either methylene chloride (dichloromethane) or chloroform (trichloromethane), which are covered in Specification F2579 and typically possess molar glycolide levels of ~50 % or less. This specification is not applicable to lactide-based polymers or copolymers that possess isotactic polymeric segments sufficient in size to carry potential for lactide-based crystallization, which are covered by Specification F1925 and typically possess nominal mole fractions that equal or exceed 50 % l-lactide.  
1.4 This specification addresses material characteristics of both virgin poly(glycolide) and poly(>70 % glycolide-co-lactide) resins intended for use in surgical implants and does not apply to packaged and sterilized finished implants fabricated from these materials.  
1.5 As with any material, some characteristics may be altered by processing techniques (such as molding, extrusion, machining, assembly, sterilization, and so forth) required for the production of a specific part or device. Therefore, properties of fabricated forms of this resin should be evaluated independently using appropriate test methods to assure safety and efficacy.  
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.  
1.7 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.  
1.8 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-Dec-2018
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• ICS: 83.080.10 - Thermosetting materials
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.11 - Polymeric Materials

Relations

• Replaces: ASTM F2313-10 - Standard Specification for Poly(glycolide) and Poly(glycolide-co-lactide) Resins for Surgical Implants with Mole Fractions Greater Than or Equal to 70 % Glycolide
• Effective Date: 15-Dec-2018
• Refers: ASTM E1142-23b - Standard Terminology Relating to Thermophysical Properties
• Effective Date: 01-Oct-2023
• Refers: ASTM E473-23b - Standard Terminology Relating to Thermal Analysis and Rheology
• Effective Date: 01-Oct-2023
• Refers: ASTM D5296-19 - Standard Test Method for Molecular Weight Averages and Molecular Weight Distribution of Polystyrene by High Performance Size-Exclusion Chromatography
• Effective Date: 01-Nov-2019
• Refers: ASTM F2579-18 - Standard Specification for Amorphous Poly(lactide) and Poly(lactide-co-glycolide) Resins for Surgical Implants
• Effective Date: 15-Dec-2018
• Refers: ASTM D4603-18 - Standard Test Method for Determining Inherent Viscosity of Poly(Ethylene Terephthalate) (PET) by Glass Capillary Viscometer
• Effective Date: 01-May-2018
• Refers: ASTM F2902-16 - Standard Guide for Assessment of Absorbable Polymeric Implants
• Effective Date: 01-Dec-2016
• Refers: ASTM F2902-16e1 - Standard Guide for Assessment of Absorbable Polymeric Implants
• Effective Date: 01-Dec-2016
• Refers: ASTM F748-16 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Apr-2016
• Refers: ASTM E1142-15 - Standard Terminology Relating to Thermophysical Properties
• Effective Date: 01-May-2015
• Refers: ASTM E473-14 - Standard Terminology Relating to Thermal Analysis and Rheology
• Effective Date: 15-Aug-2014
• Refers: ASTM E1142-14b - Standard Terminology Relating to Thermophysical Properties
• Effective Date: 15-Aug-2014
• Refers: ASTM E2977-14 - Standard Practice for Measuring and Reporting Performance of Fourier-Transform Nuclear Magnetic Resonance (FT-NMR) Spectrometers for Liquid Samples
• Effective Date: 01-Aug-2014
• Refers: ASTM E1142-14a - Standard Terminology Relating to Thermophysical Properties
• Effective Date: 01-Apr-2014
• Refers: ASTM E1142-14 - Standard Terminology Relating to Thermophysical Properties
• Effective Date: 15-Feb-2014

Overview

ASTM F2313-18 sets the standard specification for virgin poly(glycolide) (PGA) and poly(glycolide-co-lactide) (PLGA) resins intended for use in surgical implants, specifically those with a glycolide mole fraction of 70% or greater. Developed by ASTM International, this standard focuses on the material characteristics-such as purity, chemical composition, and physical properties-of raw resins prior to their fabrication into finished medical devices. This specification is critical for ensuring the safety, quality, and performance of absorbable polymeric materials used in medical applications.

Key Topics

• Material Scope: Applies to unprocessed poly(glycolide) and poly(glycolide-co-lactide) resins, ensuring high glycolide content for crystallization potential. Not applicable to packaged/sterilized finished implants or lower glycolide-content resins.
• Chemical Identification: Requires thorough identification via methods such as nuclear magnetic resonance (NMR) and infrared spectroscopy to verify polymer type and copolymer ratios.
• Purity Requirements:
  • Residual Monomer: Must be ≤2.0% by mass to limit local acidity and degradation risks.
  • Residual Solvents and Catalysts: Limits imposed in line with ICH and USP guidelines to minimize toxicity and support biocompatibility.
  • Elemental Impurities: Requires reporting and compliance with established USP <232>/<233> and ICH Q3D guidelines for heavy metals.
• Physical Properties: Density must be determined according to ASTM methods, with optional assessments for thermal and crystalline characteristics to guide manufacturability and product performance.
• Quality Assurance: Emphasizes manufacturing controls per recognized quality management systems (e.g., ISO 13485, ISO 9001, 21 CFR 820) and detailed certification practices.

Applications

These resins provide critical base materials for a wide range of biodegradable surgical implants and medical devices. Typical applications include:

• Absorbable Sutures: High glycolide-content resins (PGA, PLGA) ensure strength and predictable hydrolysis, essential for safe wound closure.
• Orthopedic Implants: Screws, pins, and rods that gradually resorb, reducing the need for secondary surgeries.
• Tissue Engineering Scaffolds: Structural supports using PGA or PLGA to facilitate cell growth and natural tissue regeneration.
• Drug Delivery Systems: Biocompatible carrier matrices that degrade safely in physiological environments.

Compliance with ASTM F2313-18 helps manufacturers and medical device developers ensure that the raw polymers used in these applications are high quality, consistent, and suitable for the stringent demands of human implantation.

Related Standards

For comprehensive assurance and regulatory compliance, ASTM F2313-18 should be referenced alongside other relevant standards, including:

• ASTM F1925: Specification for semi-crystalline poly(lactide) polymer and copolymer resins for surgical implants.
• ASTM F2579: Covers amorphous poly(lactide) and poly(lactide-co-glycolide) resins with lower glycolide content.
• ASTM F748: Guidelines for selecting biological test methods.
• ASTM D1505, D2857, D3418: Methods for determining physical and chemical properties of plastics.
• ISO 10993: Biological evaluation of medical devices.
• USP <232>/<233>: Elemental impurities testing and reporting.
• ICH Q3C/Q3D: Guidelines for residual solvents and elemental impurities.

Manufacturers should ensure material and process validation per these standards to support safe, effective, and compliant biomedical products.

---

Keywords: poly(glycolide), poly(glycolide-co-lactide), surgical implant resins, ASTM F2313-18, biocompatible polymers, PGA, PLGA, medical device standards, absorbable implants, polymer quality, NMR identification, medical plastics.

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:F2313 −18
Standard Specification for
Poly(glycolide) and Poly(glycolide-co-lactide) Resins for
Surgical Implants with Mole Fractions Greater Than or
Equal to 70% Glycolide
This standard is issued under the fixed designation F2313; 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 lactide) resins intended for use in surgical implants and does
not apply to packaged and sterilized finished implants fabri-
1.1 This specification covers both virgin poly(glycolide)
cated from these materials.
homopolymer and poly(glycolide-co-lactide) copolymer resins
intended for use in surgical implants. The poly(glycolide- 1.5 As with any material, some characteristics may be
colactide) copolymers covered by this specification possess altered by processing techniques (such as molding, extrusion,
nominal mole fractions greater than or equal to 70 % glycolide machining, assembly, sterilization, and so forth) required for
(65.3 % in mass fraction). This specification is also applicable the production of a specific part or device. Therefore, proper-
to lactide-co-glycolide copolymers that possess glycolide seg- ties of fabricated forms of this resin should be evaluated
ments sufficient in size to deliver potential for glycolide-based independently using appropriate test methods to assure safety
crystallization, thereby requiring fluorinated solvents for com- and efficacy.
plete dissolution under room temperature conditions.
1.6 The values stated in SI units are to be regarded as
1.2 Since poly(glycolide) is commonly abbreviated as PGA standard. No other units of measurement are included in this
for poly(glycolic acid) and poly(lactide) is commonly abbre- standard.
viated as PLA for poly(lactic acid), these polymers are com-
1.7 This standard does not purport to address all of the
monly referred to as PGA, PLA, and PLA:PGA resins for the
safety concerns, if any, associated with its use. It is the
hydrolyticbyproductstowhichtheyrespectivelydegrade.PLA
responsibility of the user of this standard to establish appro-
isatermthatcarriesnostereoisomericspecificityandtherefore
priate safety, health, and environmental practices and deter-
encompasses both the amorphous atactic/syndiotactic DL-
mine the applicability of regulatory limitations prior to use.
lactide-based polymers and copolymers as well as the isotactic
1.8 This international standard was developed in accor-
D-PLAand L-PLAmoieties, each of which carries potential for
dance with internationally recognized principles on standard-
crystallization.
ization established in the Decision on Principles for the
Development of International Standards, Guides and Recom-
1.3 This specification is specifically not applicable to amor-
mendations issued by the World Trade Organization Technical
phous poly(lactide-co-glycolide) or poly(lactide)-based resins
Barriers to Trade (TBT) Committee.
able to be fully solvated at 30°C by either methylene chloride
(dichloromethane) or chloroform (trichloromethane), which
2. Referenced Documents
are covered in Specification F2579 and typically possess molar
glycolide levels of ~50 % or less. This specification is not
2.1 ASTM Standards:
applicable to lactide-based polymers or copolymers that pos-
D1505 Test Method for Density of Plastics by the Density-
sess isotactic polymeric segments sufficient in size to carry
Gradient Technique
potential for lactide-based crystallization, which are covered
D2857 Practice for Dilute Solution Viscosity of Polymers
by Specification F1925 and typically possess nominal mole
D3418 Test Method for Transition Temperatures and En-
fractions that equal or exceed 50 % L-lactide.
thalpies of Fusion and Crystallization of Polymers by
Differential Scanning Calorimetry
1.4 This specification addresses material characteristics of
D5296 Test Method for Molecular Weight Averages and
both virgin poly(glycolide) and poly(>70 % glycolide-co-
Molecular Weight Distribution of Polystyrene by High
This specification is under the jurisdiction of ASTM Committee F04 on
Medical and Surgical Materials and Devicesand is the direct responsibility of
Subcommittee F04.11 on Polymeric Materials. For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Current edition approved Dec. 15, 2018. Published February 2019. Originally contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
approved in 2003. Last previous edition approved in 2010 as F2313 – 10. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/F2313-18. the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2313−18
Performance Size-Exclusion Chromatography 2.5 Other Documents/Websites:
D4603 Test Method for Determining Inherent Viscosity of ICH Q3C International Conference on Harmonisation of
Poly(Ethylene Terephthalate) (PET) by Glass Capillary Technical Requirements for Registration of Pharmaceuti-
Viscometer cals for Human Use, Quality Guideline: Impurities: Re-
E473 Terminology Relating to Thermal Analysis and Rhe- sidual Solvents
ology ICH Q3D International Conference on Harmonisation of
E793 Test Method for Enthalpies of Fusion and Crystalliza- Technical Requirements for Registration of Pharmaceuti-
tion by Differential Scanning Calorimetry cals for Human Use: Guideline for Elemental Impurities
E794 TestMethodforMeltingAndCrystallizationTempera- 21 CFR 820 Code of Federal Regulations,Title 21, Part 820,
tures By Thermal Analysis Quality System Regulation
E967 Test Method for Temperature Calibration of Differen- NIST Special Publication SP811 Guide for the Use of the
tial Scanning Calorimeters and Differential Thermal Ana- International System of Units (SI)
lyzers FDAGuidance “Use of International Standard ISO 10993-1,
E968 Practice for Heat Flow Calibration of Differential ‘Biological evaluation of medical devices – Part 1: Evalu-
Scanning Calorimeters ation and testing within a risk management process’ –
E1142 Terminology Relating to Thermophysical Properties Guidance for Industry and Food and DrugAdministration
E1252 Practice for General Techniques for Obtaining Infra- Staff
red Spectra for Qualitative Analysis
3. Terminology
E1356 Test Method for Assignment of the Glass Transition
Temperatures by Differential Scanning Calorimetry
3.1 Definitions:
E1994 Practice for Use of Process Oriented AOQL and
3.1.1 virgin polymer, n—the initially delivered form of a
LTPD Sampling Plans
polymer as synthesized from its monomers and prior to any
E2977 PracticeforMeasuringandReportingPerformanceof
processing or fabrication into a medical device.
Fourier-Transform Nuclear Magnetic Resonance (FT-
4. Materials and Manufacture
NMR) Spectrometers for Liquid Samples
F748 PracticeforSelectingGenericBiologicalTestMethods
4.1 All raw monomer components and other materials
for Materials and Devices
contacting either the raw monomer(s) or resin product shall be
F1925 SpecificationforSemi-CrystallinePoly(lactide)Poly-
of a quality suitable to allow for use of such resin in the
mer and Copolymer Resins for Surgical Implants
manufacture of an implantable medical product. Such quality
F2579 Specification for Amorphous Poly(lactide) and
includes adequate control of particles and other potential
Poly(lactide-co-glycolide) Resins for Surgical Implants
contaminants that may affect either the toxicity of or the cell
F2902 Guide for Assessment of Absorbable Polymeric Im-
response to the as-implanted or degrading final product.
plants
4.2 All polymer manufacturing (including monomer
2.2 ANSI Standards:
handling, synthesis, pelletization/grinding and all subsequent
ANSI/ISO/ASQ 13485 Medical devices -- Quality manage-
steps) shall be undertaken under conditions suitable to allow
ment systems -- Requirements for regulatory purposes
for use of such resin in the manufacture of an implantable
ANSI/ISO/ASQ Q9000 Quality Management Systems; Fun-
medical product.
damentals and Vocabulary
ANSI/ISO/ASQ Q9001 Quality Management Systems; Re-
5. Chemical Composition
quirements
5.1 The poly(glycolide) polymers covered by this specifica-
2.3 ISO Standards:
tion shall be composed of glycolide or a combination of
ISO 10993 Biological Evaluation of Medical Devices
glycolide or lactide where the lactide content does not exceed
ISO 11357 Plastics—Differential Scanning Calorimetry
30 % mole fraction (34.7 % by mass fraction). To assure such
(DSC)
composition and the attainment of the desired properties, the
ISO 80000-9 Quantities and units -- Part 9: Physical chem-
following tests are to be conducted.
istry and molecular physics
5.2 Chemical Identification:
2.4 U. S. Pharmacopeia (USP) Standards:
5.2.1 The identity of the virgin polymer shall be confirmed
USP 232 United States Pharmacopeia: Elemental Impurities
1 13
either by infrared, H-NMR, or C-NMR spectroscopy.
– Limits
5.2.2 Infrared Identification:
USP 233 United States Pharmacopeia: Elemental Impurities
– Procedure
USP 788 United States Pharmacopeia: Particulate Matter in 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/
Injections
MEDIA423.pdf.
AvailablefromU.S.GovernmentPrintingOfficeSuperintendentofDocuments,
732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http://
Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St., www.access.gpo.gov.
4th Floor, New York, NY 10036, http://www.ansi.org. Available from National Institute of Standards and Technology (NIST), 100
Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville, Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, at http://physics.nist.gov/
MD 20852-1790, http://www.usp.org. cuu/Units/bibliography.html.
F2313−18
5.2.2.1 Identity of either poly(glycolide) homopolymer or but using hexafluoroisopropanol (HFIP) solvent and poly
poly(glycolide-co-lactide) copolymer may be confirmed methylmethacrylate (PMMA) calibration standards.
through an infrared spectrum exhibiting major absorption
NOTE2—Molarmasscalibrationstandards(forexample,polystyreneor
bands only at the wavelengths that appear in a suitable
polymethylmethacrylate) provide relative values only, and are not to be
reference spectrum. Analysis shall be conducted using infra-
confused with an absolute determination of a lactide-based polymer’s
molar mass.
redspectroscopymethodssimilartothosedescribedinPractice
E1252.Typical infrared transmission and absorbance reference
5.3.1.1 Determine the inherent viscosity of the polymer
spectraarepresentedforPGAhomopolymerinFig.1and90 %
either in hexafluoroisopropanol (HFIP) or hexafluoroacetone
PGA:10 % L-PLA copolymer in Fig. 2. While poly(glycolide-
sesquihydrate (HFAS) at 30°C using procedures similar to
co-lactide) copolymers will each have their own respective
those described in Practice D2857 and Test Method D4603.
spectrum that will vary in response to copolymer ratio, this
Determination at a lower temperature of 25°C is allowable,
analytic method typically lacks sensitivity sufficient for quan-
provided the utilized equipment delivers the required thermal
tification of copolymer ratio as specified in 7.1.2.
control and, if requested by the purchaser, an experimentally
5.2.2.2 Additional or variable spectral bands may be indica-
supported 30°C equivalent concentration-appropriate extrapo-
tive of sample crystallinity or either known or unknown
lated result is also reported within the supplied certification.
impurities, including residual monomer, solvents, and cata- Note that any incomplete sample dissolution, precipitation
lysts. Refer to limits specified in Table 1.
from solution, or the formation of gels will produce inconsis-
tency and variation in observed drop times.
5.2.3 Proton Nuclear Magnetic Resonance ( H-NMR) Iden-
tification:
NOTE 3—The IV test duration for each sample should be minimized to
5.2.3.1 Identity of either poly(glycolide) homopolymer or reduce risk of resin concentration changes due to evaporative loss of
solvent.
poly(glycolide-co-lactide) copolymer may be confirmed
through sample dissolution, H-NMR spectroscopy, and the
5.3.1.2 Inherent viscosity is determined utilizing the follow-
use of a suitable reference spectrum. Sample dissolution is in
ing:
either deuterated hexafluoroisopropanol (D-HFIP) or other
ln t/t v
~ !
o
substantially proton-free solvent able to fully solvate the
IV 5 (1)
w
specimen without inducing competing spectral bands.Analysis
or
shall be conducted using methods similar to those described in
Practice E2977. ln t/t
~ !
o
IV 5 (2)
C
5.2.3.2 Additional spectral bands may be indicative of
known or unknown impurities, including residual monomer,
where:
solvents, and catalysts (refer to limits specified in Table 1).
IV = inherent viscosity (at 30°C in dL/g),
5.2.4 Carbon-13 Nuclear Magnetic Resonance ( C-NMR)
t = efflux time in seconds for diluted solution,
Identification:
t = efflux time in seconds for source solvent,
o
5.2.4.1 Identity of either poly(glycolide) homopolymer or
w = mass of polymer being diluted (in grams),
poly(glycolide-co-lactide) copolymer may be confirmed in a v = dilution volume in deciliters (Note: 1 dL = 100 mL),
solid state through C-NMR spectroscopy and the use of a
and
C = concentration of dilute solution (w/v).
suitable reference spectrum.Analysis shall be conducted using
methods similar to those described in Practice E2977.
5.3.1.3 Resin concentration shall be 0.5 % w/v or less, with
5.2.4.2 Additional spectral bands may be indicative of
resin analyte concentrations of 0.1 % w/v (that is, 0.001 g/mL
known or unknown impurities, including residual solvents and
or 1 mg/mL) recommended. When reporting results, identify
catalysts. Refer to the limits specified in Table 1.
the solvent utilized, analyte concentration, and analysis tem-
perature.
5.3 Molar Mass:
5.4 Residual Monomer:
NOTE 1—The term molecular weight (abbreviated MW) is obsolete and
5.4.1 The virgin polymer shall have a combined total
should be replaced by the SI (Système Internationale) equivalent of either
residual monomer content less than or equal to 2.0 % in mass
relative molecular mass (M ), which reflects the dimensionless ratio of the
r
mass of a single molecule to an atomic mass unit [see ISO 880000-9], or fraction.
molar mass (M), which refers to the mass of a mole of a substance and is
5.4.1.1 Determinethemassfractionofresidualmonomerby
typically expressed as grams/mole. For polymers and other
gas chromatography, HPLC, H-NMR spectroscopy (using
macromolecules, use of the symbols M , M , and M continue, referring
w n z
D-HFIP or other substantially proton-free solvent able to fully
to mass-average molar mass, number-average molar mass, and z-average
solvate the specimen), or other suitably sensitive analytic
molar mass, respectively. For more information regarding proper utiliza-
tion of SI units, see NIST Special Publication SP811. method as agreed upon by the supplier and purchaser.
5.3.1 The molar mass of the virgin polymer shall be 5.5 Residual Solvents:
indicated by inherent viscosity (IV) in dilute solution. In 5.5.1 If any solvent is utilized in any resin manufacturing or
addition to (but not in place of) inherent viscosity, mass purification step, determine the residual levels of any utilized
average molar mass and molar mass distributions may be solvent(s) by gas chromatography or other suitable method as
determined by gel permeation chromatography (GPC) accord- agreed upon by the supplier and purchaser.Acceptable residual
ing to the general procedure described in Test Method D5296, levels of a particular solvent shall be reflective of toxicity, with
F2313−18
NOTE 1—Supplied example infra-red spectrum is of “Dexon Medical Suture (beige)” as acquired from the Hummel Polymer Library, available from:
Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.
FIG. 1Poly(glycolide) Resin Infrared Spectrum
F2313−18
NOTE 1—Supplied example infra-red spectrum is of “Vicryl Medical Suture (violet)” as acquired from the Hummel Polymer Library, available from:
Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.
FIG. 2Poly(90% glycolide-co-10% lactide) Resin Infrared Spectrum
F2313−18
TABLE 1 Physical/Chemical Property Requirements for Virgin Poly(glycolide) and Poly(glycolide-co-lactide) Resins
Individual Solvent
Total Total Solvent (Optional)
Residual(s) and Elemental Residual
Residual Combination Residual Copolymer
Analyte Applicable Impurities Catalyst
Monomer, Residual(s) Water Ratio
ICH Limit(s) (except catalyst) (in ppm)
(%) (in ppm) (%)
(in ppm)
Requirement #2.0 % <1000 ppm Report both for all #0.5 % Report compliance Report per USP ±3 % of target
A B C
(by mass) solvent(s) utilized (by mass) per USP <232> <233> (by mole)
A
Utilizing a moisture determination method agreed upon by the supplier and the purchaser.
B
See Section 5.6.3
C
See Section 5.7.1 and Note 4.
a maximum acceptable limit consistent with ICH Q3C. The TAL IMPURITIES – LIMITS (except catalyst). If any listed
detection limit for the chosen analytic method shall be ad- element (other than added catalyst) cannot be controlled to be
equate to assure compliance with the applicable ICH guideline
maintained within the described <232> limits, the resin does
and the determined residual(s) and applied concentration notconformwiththeUSP<232>ELEMENTALIMPURITIES
limit(s) shall be reported. If no ICH concentration guideline
– LIMITS (except catalyst) and the concentration (in ppm, in
has been established for a utilized solvent, an entry of “no ICH accordance with USP <233> or equivalent) of each uncon-
guidance available” shall be reported instead of a limit.
trolled element is to be both monitored and reported.
5.5.2 To minimize potential for toxic interaction of solvent
5.6.3.1 The Elemental Impurities thresholds for the Indi-
combinations, cumulative Total Solvent Combination Residu-
vidual Component Option of USP <232>, Table 3, provide
als shall be limited to 1000 ppm (refer to the limit specified in
specific elemental daily dosage limits for parenteral drug
Table1).ThislimithastheeffectofallowingICHQC3Quality
products. These daily Elemental Impurity limits (including
Guidelines when a single solvent system is utilized and less
those applied to catalyst concentrations) should be considered
than 1000 ppm when combinations of more than one solvent
as conservative thresholds for informational purposes only
are utilized (regardless of individual solvent toxicity).
when applied to absorbable implants. Proper application of
these limits should consider the amount of polymer in the final
5.6 Elemental Impurities:
5.6.1 The significance of Elemental Impurities within an implant product as well as its degradation and elemental
absorbablepolymerisultimatelydependentonthedimensional elution rate into the surrounding tissue.
characteristics of the final product and the rate of release of
5.6.4 For each element intentionally added as catalyst, the
those initially interstitial elements into the surrounding tissue
concentration (in ppm, in accordance with USP <233> or
and extracelluar fluid. Thus, any risk assessment of such
equivalent) shall be both monitored and reported.
impurities will be dependent on the final product design and
5.7 Residual Catalyst:
intended application. Consequently, this raw material (not final
5.7.1 Determine the elemental concentration of residual
device) standard provides for appropriate reporting of Elemen-
catalyst as described in USP <233>. If the utilized catalyst is
tal Impurities values, but does not mandate any specific
not measurable via USP <233>, suitable methods to both
performance requirements. More detailed and pharmaceutical
determine and report the catalyst residue shall be utilized.
oriented guidance regarding the appropriate means for both
monitoring and assessing relevant Elemental Impurities within
NOTE 4—The chemical nature and amount of residual catalyst can
afinalproductcanbefoundinUSPChapters<232>and<233>
significantlyaffectbothimplantbiocompatibilityandpolymerdegradation
andintheICHHARMONISEDGUIDELINEFORELEMEN-
during thermal processing. Since the resin supplier can provide the
TAL IMPURITIES - Q3D. purchaser with accurate information regarding both the chemical nature
and amount of added catalyst, reporting of actual added catalyst can be
5.6.2 DeterminetheconcentrationoftherespectiveElemen-
substituted for direct elemental testing.
tal Impurities within the absorbable polymer by utilizing a
method as described in Chapter <233> of the U.S. Pharmaco-
5.8 Residual Water (Optional):
peia. The specific 24 different Elemental Impurities of interest
5.8.1 Using an analytic method agreed upon by the supplier
are outlined in both USP <232> and in TableA.2.2 of the ICH
and purchaser, ascertain that the amount of residual moisture
HARMONISED GUIDELINE FOR ELEMENTAL IMPURI-
(water) within the resin is less than or equal to 0.5 % by mass.
TIES - Q3D (Dec 2014). Both of these documents include
Suitable methods include, but are not limited to, gravimetric
risk-based approaches toward the assessm
...

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: F2313 − 10 F2313 − 18
Standard Specification for
Poly(glycolide) and Poly(glycolide-co-lactide) Resins for
Surgical Implants with Mole Fractions Greater Than or
Equal to 70 % Glycolide
This standard is issued under the fixed designation F2313; 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 both virgin poly(glycolide) homopolymer and poly(glycolide-co-lactide) copolymer resins
intended for use in surgical implants. The poly(glycolide-co-lactide)poly(glycolide-colactide) copolymers covered by this
specification possess nominal mole fractions greater than or equal to 70 % glycolide (65.3 % 70 % glycolide (65.3 % in mass
fraction). This specification is also applicable to lactide-co-glycolide copolymers that possess glycolide segments sufficient in size
to deliver potential for glycolide based glycolide-based crystallization, thereby requiring fluorinated solvents for complete
dissolution under room temperature conditions.
1.2 Since poly(glycolide) is commonly abbreviated as PGA for poly(glycolic acid) and poly(lactide) is commonly abbreviated
as PLA for poly(lactic acid), these polymers are commonly referred to as PGA, PLA, and PLA:PGA resins for the hydrolytic
byproducts to which they respectively degrade. PLA is a term that carries no stereoisomeric specificity and therefore encompasses
both the amorphous atactic/syndiotactic DL-lactide-based polymers and copolymers as well as the isotactic D-PLA and L-PLA
moieties, each of which carries potential for crystallization.
1.3 This specification is specifically not applicable to amorphous poly(lactide-co-glycolide) or poly(lactide)-based resins able
to be fully solvated at 30°C by either methylene chloride (dichloromethane) or chloroform (trichloromethane), which are covered
in Specification F2579 and typically possess molar glycolide levels of ~50 % or less. This specification is not applicable to
lactide-based polymers or copolymers that possess isotactic polymeric segments sufficient in size to carry potential for
lactide-based crystallization, which are covered by Specification F1925 and typically possess nominal mole fractions that equal or
exceed 50 % L-lactide.
1.4 This specification addresses material characteristics of both virgin poly(glycolide) and poly(>70 % glycolide-co-lactide)
resins intended for use in surgical implants and does not apply to packaged and sterilized finished implants fabricated from these
materials.
1.5 As with any material, some characteristics may be altered by processing techniques (such as molding, extrusion, machining,
assembly, sterilization, etc.) and so forth) required for the production of a specific part or device. Therefore, properties of fabricated
forms of this resin should be evaluated independently using appropriate test methods to assure safety and efficacy.
1.6 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.7 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 safety, health, and healthenvironmental practices and determine the
applicability of regulatory limitations prior to use.
1.8 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.
This specification is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devicesand is the direct responsibility of Subcommittee
F04.11 on Polymeric Materials.
Current edition approved Dec. 1, 2010Dec. 15, 2018. Published January 2011February 2019. Originally approved in 2003. Last previous edition approved in 20082010
ε1
as F2313 – 08F2313 – 10. . DOI: 10.1520/F2313-10.10.1520/F2313-18.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2313 − 18
2. Referenced Documents
2.1 ASTM Standards:
D1505 Test Method for Density of Plastics by the Density-Gradient Technique
D2857 Practice for Dilute Solution Viscosity of Polymers
D3418 Test Method for Transition Temperatures and Enthalpies of Fusion and Crystallization of Polymers by Differential
Scanning Calorimetry
D5296 Test Method for Molecular Weight Averages and Molecular Weight Distribution of Polystyrene by High Performance
Size-Exclusion Chromatography
D4603 Test Method for Determining Inherent Viscosity of Poly(Ethylene Terephthalate) (PET) by Glass Capillary Viscometer
E386 Practice for Data Presentation Relating to High-Resolution Nuclear Magnetic Resonance (NMR) Spectroscopy
(Withdrawn 2015)
E473 Terminology Relating to Thermal Analysis and Rheology
E793 Test Method for Enthalpies of Fusion and Crystallization by Differential Scanning Calorimetry
E794 Test Method for Melting And Crystallization Temperatures By Thermal Analysis
E967 Test Method for Temperature Calibration of Differential Scanning Calorimeters and Differential Thermal Analyzers
E968 Practice for Heat Flow Calibration of Differential Scanning Calorimeters
E1142 Terminology Relating to Thermophysical Properties
E1252 Practice for General Techniques for Obtaining Infrared Spectra for Qualitative Analysis
E1356 Test Method for Assignment of the Glass Transition Temperatures by Differential Scanning Calorimetry
E1994 Practice for Use of Process Oriented AOQL and LTPD Sampling Plans
E2977 Practice for Measuring and Reporting Performance of Fourier-Transform Nuclear Magnetic Resonance (FT-NMR)
Spectrometers for Liquid Samples
F748 Practice for Selecting Generic Biological Test Methods for Materials and Devices
F1925 Specification for Semi-Crystalline Poly(lactide) Polymer and Copolymer Resins for Surgical Implants
F2579 Specification for Amorphous Poly(lactide) and Poly(lactide-co-glycolide) Resins for Surgical Implants
F2902 Guide for Assessment of Absorbable Polymeric Implants
2.2 ANSI Standards:
ANSI/ISO/ASQ 13485 Medical devices -- Quality management systems -- Requirements for regulatory purposes
ANSI/ISO/ASQ Q9000 Quality Management Systems; Fundamentals and Vocabulary
ANSI/ISO/ASQ Q9001 Quality Management Systems; Requirements
2.3 ISO Standards:
ISO 31–8 Physical Chemistry and Molecular Physics—Part 8: Quantities and Units
ISO 10993 Biological Evaluation of Medical Devices
ISO 11357 Plastics—Differential Scanning Calorimetry (DSC)
ISO 80000-9 Quantities and units -- Part 9: Physical chemistry and molecular physics
2.4 U. S. Pharmacopeia (USP) Standard:Standards:
USP30/NF25USP 232 United States Pharmacopeia (USP),Pharmacopeia: Elemental May 2, 2007Impurities – Limits
USP 233 United States Pharmacopeia: Elemental Impurities – Procedure
USP 788 United States Pharmacopeia: Particulate Matter in Injections
2.5 Other Documents/Websites:
ICH Q3C(R3)Q3C International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals
for Human Use, Quality Guideline: Impurities: Residual Solvents
ICH Q3D International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human
Use: Guideline for Elemental Impurities
21 CFR 820 Code of Federal Regulations, Title 21, Part 820, Quality System Regulation
NIST Special Publication SP811 Guide for the Use of the International System of Units (SI)
FDA Guidance “Use of International Standard ISO 10993-1, ‘Biological evaluation of medical devices – Part 1: Evaluation and
testing within a risk management process’ – Guidance for Industry and Food and Drug Administration Staff
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.
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 Printing Office Superintendent of Documents, 732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http://
www.access.gpo.gov.
Available from National Institute of Standards and Technology (NIST), 100 Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, at http://physics.nist.gov/cuu/Units/
bibliography.html.
F2313 − 18
3. Terminology
3.1 Definitions:
3.1.1 virgin polymer, n—the initially delivered form of a polymer as synthesized from its monomers and prior to any processing
or fabrication into a medical device.
4. Materials and Manufacture
4.1 All raw monomer components and other materials contacting either the raw monomer(s) or resin product shall be of a
quality suitable to allow for use of such resin in the manufacture of an implantable medical product. Such quality includes adequate
control of particles and other potential contaminants that may affect either the toxicity of or the cell response to the as-implanted
or degrading final product.
4.2 All polymer manufacturing (including monomer handling, synthesis, pelletization/grinding and all subsequent steps) shall
be undertaken under conditions suitable to allow for use of such resin in the manufacture of an implantable medical product.
5. Chemical Composition
5.1 The poly(glycolide) polymers covered by this specification shall be composed of glycolide or a combination of glycolide
or lactide where the lactide content does not exceed 30 % mole fraction (34.7 % by mass fraction). To assure such composition
and the attainment of the desired properties, the following tests are to be conducted.
5.2 Chemical Identification:
1 13
5.2.1 The identity of the virgin polymer shall be confirmed either by infrared, H-NMR, or C-NMR spectroscopy.
5.2.2 Infrared Identification:
5.2.2.1 Identity of either poly(glycolide) homopolymer or poly(glycolide-co-lactide) copolymer may be confirmed through an
infrared spectrum exhibiting major absorption bands only at the wavelengths that appear in a suitable reference spectrum. Analysis
shall be conducted using infra-red spectroscopy practicesmethods similar to those described in Practice E1252. Typical infrared
transmission and absorbance reference spectra are presented for PGA homopolymer in Fig. 1 and 90 % PGA:10 % L-PLA
copolymer in Fig. 2. While poly(glycolide-co-lactide) copolymers will each have their own respective spectrum that will vary in
response to copolymer ratio, this analytic method typically lacks sensitivity sufficient for quantification of copolymer ratio as
specified in 7.1.2.
5.2.2.2 Additional or variable spectral bands may be indicative of sample crystallinity or either known or unknown impurities,
including residual monomer, solvents, and catalysts (refercatalysts. Refer to limits specified in Table 1).
5.2.3 Proton Nuclear Magnetic Resonance ( H-NMR) Identification:
5.2.3.1 Identity of either poly(glycolide) homopolymer or poly(glycolide-co-lactide) copolymer may be confirmed through
sample dissolution, H-NMR spectroscopy, and the use of a suitable reference spectrum. Sample dissolution is in either deuterated
hexafluoroisopropanol (D-HFIP) or other substantially proton-free solvent able to fully solvate the specimen without inducing
competing spectral bands. Analysis shall be conducted using practicesmethods similar to those described in Practice E386E2977.
5.2.3.2 Additional spectral bands may be indicative of known or unknown impurities, including residual monomer, solvents, and
catalysts (refer to limits specified in Table 1).
5.2.4 Carbon-13 Nuclear Magnetic Resonance ( C-NMR) Identification:
5.2.4.1 Identity of either poly(glycolide) homopolymer or poly(glycolide-co-lactide) copolymer may be confirmed in a solid
state through C-NMR spectroscopy and the use of a suitable reference spectrum. Analysis shall be conducted using
practicesmethods similar to those described in Practice E386E2977.
5.2.4.2 Additional spectral bands may be indicative of known or unknown impurities, including residual solvents and catalysts
(refercatalysts. Refer to the limits specified in Table 1).
5.3 Molar Mass:
NOTE 1—The term molecular weight (abbreviated MW) is obsolete and should be replaced by the SI (Système Internationale) equivalent of either
relative molecular mass (M ), which reflects the dimensionless ratio of the mass of a single molecule to an atomic mass unit [see ISO 31-8],880000-9],
r
or molar mass (M), which refers to the mass of a mole of a substance and is typically expressed as grams/mole. For polymers and other macromolecules,
use of the symbols M , M , and M continue, referring to mass-average molar mass, number-average molar mass, and z-average molar mass, respectively.
w n z
For more information regarding proper utilization of SI units, see NIST Special Publication SP811.
5.3.1 The molar mass of the virgin polymer shall be indicated by inherent viscosity (IV) in dilute solution (IV). solution. In
addition to inherent viscosity (but not in place of), of) inherent viscosity, mass average molar mass and molar mass distributions
may be determined by gel permeation chromatography (GPC) according to the general procedure described in Test Method D5296,
but using hexafluoroisopropanol (HFIP) solvent and poly methylmethacrylate (PMMA) calibration standards.
NOTE 2—Molar mass calibration standards (for example, polystyrene or polymethylmethacrylate) provide relative values only, and are not to be
confused with an absolute determination of a lactide-based polymer’s molar mass.
5.3.1.1 Determine the inherent viscosity of the polymer either in hexafluoroisopropanol (HFIP) or hexafluoroacetone
sesquihydrate (HFAS) at 30°C using procedures similar to those described in Practice D2857 and Test Method D4603.
Determination at a lower temperature of 25°C is allowable, provided the utilized equipment delivers the required thermal control
F2313 − 18
NOTE 1—Supplied example infra-red spectrum is of “Dexon Medical Suture (beige)” as acquired from the Hummel Polymer Library, available from:
Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.
FIG. 1 Poly(glycolide) Resin Infrared Spectrum
F2313 − 18
NOTE 1—Supplied example infra-red spectrum is of “Vicryl Medical Suture (violet)” as acquired from the Hummel Polymer Library, available from:
Thermo Nicolet Corporation, 5225 Verona Road, Madison, WI 53711-4495, USA.
FIG. 2 Poly(90 % glycolide-co-10 % lactide) Resin Infrared Spectrum
F2313 − 18
TABLE 1 Physical/Chemical Property Requirements for Virgin Poly(glycolide) and Poly(glycolide-co-lactide) Resins
Individual Solvent
Total Total Solvent (Optional) (Optional)
Residual(s) and Heavy
Residual Combination Residual Residual Copolymer
Analyte Applicable Metals,
Monomer, Residual(s) Water Catalyst Ratio
ICH Limit(s) (ppm as Pb)
(%) (in ppm) (%) (in ppm)
(in ppm)
Requirement #2.0 % <1000 ppm Report both for all #0.5 % #10 ppm #100 ppm Sn ±3 % of target
A
(by mass) solvent(s) utilized (by mass) (minus Sn) (by mole)
TABLE 1 Physical/Chemical Property Requirements for Virgin Poly(glycolide) and Poly(glycolide-co-lactide) Resins
Individual Solvent
Total Total Solvent (Optional)
Residual(s) and Elemental Residual
Residual Combination Residual Copolymer
Analyte Applicable Impurities Catalyst
Monomer, Residual(s) Water Ratio
ICH Limit(s) (except catalyst) (in ppm)
(%) (in ppm) (%)
(in ppm)
Requirement #2.0 % <1000 ppm Report both for all #0.5 % Report compliance Report per USP ±3 % of target
A B C
(by mass) solvent(s) utilized (by mass) per USP <232> <233> (by mole)
A
Utilizing a moisture determination method agreed upon by the supplier and the purchaser.
B
See Section 5.6.3
C
See Section 5.7.1 and Note 4.
and, if requested by the purchaser, an experimentally supported 30°C equivalent concentration-appropriate extrapolated result is
also reported within the supplied certification. Note that any incomplete sample dissolution, precipitation from solution, or the
formation of gels will produce inconsistency and variation in observed drop times.
NOTE 3—The IV test duration for each sample should be minimized to reduce risk of resin concentration changes due to evaporative loss of solvent.
5.3.1.2 Inherent viscosity is determined utilizing the following:
ln t/t v
~ !
o
IV 5 (1)
w
or
ln t/t
~ !
o
IV 5 (2)
C
where:
IV = inherent viscosity (at 30°C in dL/g),
t = efflux time in seconds for diluted solution,
t = efflux time in seconds for source solvent,
o
w = mass of polymer being diluted (in grams),
v = dilution volume in deciliters (Note: 1 dL = 100 mL), and
C = concentration of dilute solution (w/v).
5.3.1.3 Resin concentration shall be 0.5 % w/v or less, with resin analyte concentrations of 0.1 % w/v (that is, 0.001 g/mL or
1 mg/mL) recommended. When reporting results, identify the solvent utilized, analyte concentration, and analysis temperature.
5.4 Residual Monomer:
5.4.1 The virgin polymer shall have a combined total residual monomer content less than or equal to 2.0 % in mass fraction.
5.4.1.1 Determine the mass fraction of residual monomer by gas chromatography, HPLC, H-NMR spectroscopy (using
D-HFIP or other substantially proton-free solvent able to fully solvate the specimen), or other suitably sensitive analytic method
as agreed upon by the supplier and purchaser.
5.5 Residual Solvents:
5.5.1 If any solvent is utilized in any resin manufacturing or purification step, determine the residual levels of any utilized
solvent(s) by gas chromatography or other suitable method as agreed upon by the supplier and purchaser. Acceptable residual levels
of a particular solvent shall be reflective of toxicity, with a maximum acceptable limit consistent with ICH Q3C(R3).Q3C. The
detection limit for the chosen analytic method mustshall be adequate to assure compliance with the applicable ICH guideline and
the determined residual(s) and applied concentration limit(s) shall be reported. If no ICH concentration guideline has been
established for a utilized solvent, an entry of “no ICH guidance available” shall be reported in lieu instead of a limit.
5.5.2 To minimize potential for toxic interaction of solvent combinations, cumulative Total Solvent Combination Residuals shall
be limited to 1000 ppm (refer to the limit specified in Table 1). This limit carrieshas the effect of allowing ICH QC3 Quality
Guidelines when a single solvent system is utilized and less than 1000 ppm when combinations of more than one solvent are
utilized (regardless of individual solvent toxicity).
5.6 Heavy Metals:Elemental Impurities:
F2313 − 18
5.6.1 The significance of Elemental Impurities within an absorbable polymer 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. 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 in the ICH HARMONISED GUIDELINE FOR ELEMENTAL IMPURITIES - Q3D.
5.6.2 Determine residual Heavy Metals per Method II, Chapter 231 of U. S. Pharmacopeia (USP30/NF25). the concentration
of the respective Elemental Impurities within the absorbable polymer by utilizing a method as described in Chapter <233> of the
U.S. Pharmacopeia. The specific 24 different Elemental Impurities of interest are outlined in both USP <232> and in Table A.2.2
of the ICH HARMONISED GUIDELINE FOR ELEMENTAL IMPURITIES - Q3D (Dec 2014). Both of these documents include
risk-based approaches toward the assessment and control of elemental impurities.
5.6.3 Heavy metals generally refers to divalent cations of the elements cadmium (Cd), copper (Cu), mercury (Hg), and lead
(Pb), to the trivalent cations of antimony (Sb), arsenic (As), and bismuth (Bi), and to tetravalent (stannic) tin (SnExcept for
4+
elements intentionally added as catalysts, assess the obtained results for compliance ) that form complexes with sulfide under
slightly acidic conditions.with the Parenteral Concentration limits described Since stannous tin (Snwithin the Individual
2+
Component ) can also form tin (II) sulfide and therefore can potentially influence test results, the excess amount ascertained by
alternative analytic means to be directly attributable to both stannic and stannous tin may be ignored, provided that the cumulative
lead (Pb) equivalent total of the remaining listed heavy metals elements determined through the same alternative analytic means
(see discussion and calculations Option of USP <232>, Table 3 (derived from ICH-Q3D Option 1, Table A.2.2). If all listed
elements, except for those added as catalysts, can be assured to be maintained within the Parenteral Concentration - Individual
Component Option limits, the resin “complies” with the USP <232> ELEMENTAL IMPURITIES – LIMITS (except catalyst). If
any listed element (other than added catalyst) cannot be controlled to be maintained within the described <232> limits, the resin
does not conform with the USP <232> ELEMENTAL IMPURITIES – LIMITS (except catalyst) and the concentration (in ppm,
in X2.5) remains below a 10 ppm as lead (Pb) limit.accordance with USP <233> or equivalent) of each uncontrolled element is
to be both monitored and reported.
5.6.3.1 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
catalyst concentrations) should be considered as conservative thresholds for informational purposes only when applied to
absorbable implants. Proper application of these limits should consider the amount of polymer in the final implant product as well
as its degradation and elemental elution rate into the surrounding tissue.
5.6.4 For each element intentionally added as catalyst, the concentration (in ppm, in accordance with USP <233> or equivalent)
shall be both monitored and reported.
5.7 Residual Catalyst (Optional): Catalyst:
5.7.1 Determine the amount of residual tin (Sn) and each of the above listed heavy metal elements by atomic absorption/
emission (AA) spectroscopy or inductively coupled plasma (ICP) spectroscopy. If a catalyst other than tin is utilized, elemental
concentration of residual catalyst as described in USP <233>. If the utilized catalyst is not measurable via USP <233>, suitable
methods to both determine and report the catalyst residue shall be utilized.
NOTE 4—The chemical nature and amount of residual catalyst can significantly affect both implant biocompatibility and polymer degradation during
thermal processing. Since the resin supplier can provide the purchaser with accurate information regarding both the chemical nature and amount of added
catalyst, direct testing for residual catalyst is listed here as optional.reporting of actual added catalyst can be substituted for direct elemental testing.
5.8 Resid
...