ASTM F3384-21

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:F3384 −21
Standard Specification for
Polydioxanone Polymer Resins for Surgical Implants
This standard is issued under the fixed designation F3384; 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 ties of fabricated forms of this resin should be evaluated
independently using appropriate test methods to ensure safety
1.1 Thisspecificationcoversvirginpolydioxanonehomopo-
and efficacy.
lymer resins intended for use in surgical implants.
1.7 Biocompatibility testing is not a requirement since this
1.2 Polydioxanone is commonly abbreviated as PDO, and is
specification is not intended to cover fabricated devices. While
alternatively referred to as poly(para dioxanone) or poly(ρ-
biocompatibility testing of resin may provide an early indica-
dioxanone) with the acronym PPD. Additionally, it may be
tion of potential safety, biocompatibility analysis of the final
referred to as PDS as it is the polymer of composition of PDS
finished device is required to determine safety and suitability
suture (Ethicon, Inc.), representing an early and widely used
for any implant device. Refer to Supplementary Requirement
application of polydioxanone polymer.
S1 of this standard and Guide F2902 for relevant biocompat-
1.3 This specification covers virgin polydioxanone resins ibility information.
able to be fully solvated at 30 °C by fluorinated solvents such
1.8 The values stated in SI units are to be regarded as
as hexafluoroisopropanol (HFIP) or hexafluoroacetone (HFA).
standard. No other units of measurement are included in this
standard.
1.4 Homopolymers of this composition are known to be
semi-crystalline. Within this specification, semi-crystallinity
1.9 This standard does not purport to address all of the
within the resin is defined by the presence of a DSC (differ-
safety concerns, if any, associated with its use. It is the
ential scanning calorimetry) crystalline endotherm peak upon
responsibility of the user of this standard to establish appro-
annealing between 105 and 115 °C. While the presence of a
priate safety, health, and environmental practices and deter-
crystalline endotherm indicates semi-crystallinity, the percent-
mine the applicability of regulatory limitations prior to use.
age and morphology of the crystalline phase are highly
1.10 This international standard was developed in accor-
dependent on processing, and in particular on the thermal
dance with internationally recognized principles on standard-
history of the material. Therefore, the thermal properties and
ization established in the Decision on Principles for the
percentcrystallinityofthevirginpolymerresin(withexception
Development of International Standards, Guides and Recom-
of melting temperature) are not necessarily indicative of final
mendations issued by the World Trade Organization Technical
product quality.
Barriers to Trade (TBT) Committee.
1.5 This specification addresses material characteristics of
2. Referenced Documents
the virgin polydioxanone-based resins intended for use in
2.1 ASTM Standards:
surgicalimplantsanddoesnotapplytopackagedandsterilized
D1505 Test Method for Density of Plastics by the Density-
finished implants fabricated from these materials, nor does it
Gradient Technique
address the characteristics of polydioxanone resins with com-
D2857 Practice for Dilute Solution Viscosity of Polymers
pounded materials such as dyes, polymeric or ceramic
D3418 Test Method for Transition Temperatures and En-
compounds, or any other additives.
thalpies of Fusion and Crystallization of Polymers by
1.6 As with any material, some characteristics may be
Differential Scanning Calorimetry
altered by processing techniques (such as molding, extrusion,
D4603 Test Method for Determining Inherent Viscosity of
machining, assembly, sterilization, and so forth) required for
Poly(Ethylene Terephthalate) (PET) by Glass Capillary
the production of a specific part or device. Therefore, proper-
Viscometer
D5296 Test Method for Molecular Weight Averages and
This specification is under the jurisdiction of ASTM Committee F04 on
Medical and Surgical Materials and Devices and is the direct responsibility of For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Subcommittee F04.11 on Polymeric Materials. contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
Current edition approved Dec. 1, 2021. Published December 2021. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/F3384-21. the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F3384−21
Molecular Weight Distribution of Polystyrene by High Title 21—Food and Drugs Services, Part 820—Quality
Performance Size-Exclusion Chromatography System Regulation
E473 Terminology Relating to Thermal Analysis and Rhe- 21 CFR 878.4840 Absorbable Polydioxanone Surgical
ology (PDS) Suture
E793 Test Method for Enthalpies of Fusion and Crystalliza- 21 CFR 74.3602 D&C Violet No. 2
tion by Differential Scanning Calorimetry FDAGuidanceDocument UseofInternationalStandardISO
E794 TestMethodforMeltingAndCrystallizationTempera- 10993-1, ‘Biological evaluation of medical devices – Part
tures By Thermal Analysis 1: Evaluation and testing within a risk management
E967 Test Method for Temperature Calibration of Differen- process’ – Guidance for Industry and Food and Drug
tial Scanning Calorimeters and Differential Thermal Ana- Administration Staff
lyzers USP United States Pharmacopeia, Edition 40
E968 Practice for Heat Flow Calibration of Differential USP <232> Elemental Impurities—Limits
Scanning Calorimeters USP <233> Elemental Impurities—Procedures
E1142 Terminology Relating to Thermophysical Properties USP <788> Particulate Contamination
E1252 Practice for General Techniques for Obtaining Infra- NIST Special Publication SP811 Guide for the Use of the
red Spectra for Qualitative Analysis International System of Units (SI)
E1356 Test Method for Assignment of the Glass Transition
3. Terminology
Temperatures by Differential Scanning Calorimetry
E1994 Practice for Use of Process Oriented AOQL and
3.1 Definitions:
LTPD Sampling Plans
3.1.1 virgin polymer, n—the initially delivered form of a
E2977 PracticeforMeasuringandReportingPerformanceof
polymer as synthesized from its monomers and prior to any
Fourier-Transform Nuclear Magnetic Resonance (FT-
processing or fabrication into a medical device.
NMR) Spectrometers for Liquid Samples
F748 PracticeforSelectingGenericBiologicalTestMethods 4. Materials and Manufacture
for Materials and Devices
4.1 All raw monomer components and other materials
F1925 SpecificationforSemi-CrystallinePoly(lactide)Poly-
contacting either the raw monomer(s) or resin product shall be
mer and Copolymer Resins for Surgical Implants
of a quality suitable to allow use of such resin in the
F2902 Guide for Assessment of Absorbable Polymeric Im-
manufacture of an implantable medical product. Such quality
plants
includes adequate control of particles and other potential
2.2 ANSI Standards:
contaminants that may affect either the toxicity of or the cell
ANSI/ISO/ASQ9000:2015 QualityManagementSystems—
response to the as-implanted or degrading final product.
Fundamentals and Vocabulary
4.2 All polymer manufacturing (including monomer
ANSI/ISO/ASQ9001:2015 QualityManagementSystems—
handling, synthesis, pelletization/grinding, and all subsequent
Requirements
handling) shall be undertaken under conditions suitable to
ANSI/ISO/ASQ 13485:2016 Medical Devices—Quality
allow use of such resin in the manufacture of an implantable
ManagementSystems—RequirementsforRegulatoryPur-
medical product.
poses
4.3 Any additional additives, as agreed upon by the manu-
2.3 Other Documents:
facturerandcustomer,shallbeofaqualitysuitabletoallowuse
ICH Q3C International Conference on Harmonisation of
in the manufacture of an implantable medical product. The
Technical Requirements for Registration of Pharmaceuti-
presence, analysis, and reporting related to any additives is
cals for Human Use, Quality Guideline: Impurities:
outside the scope of this standard specification.
Guideline for Residual Solvents
4.4 Guidancerelatedtotheuseofcolorants(coloradditives)
ICH Q3D International Conference on Harmonisation of
may be found through the US-FDA website: https://
Technical Requirements for Registration of Pharmaceuti-
www.fda.gov/ForIndustry/ColorAdditives.
cals for Human Use, Quality Guideline: Guideline for
Elemental Impurities
5. Chemical Composition
ISO 10993-1 Biological Evaluation of Medical Devices
ISO 11357 Plastics—Differential Scanning Calorimetry 5.1 To ensure the attainment of the desired properties, the
(DSC)
following tests shall be conducted with the requirements
ISO 80000-9 Quantities and Units—Part 9: Physical Chem- identified in Table 1.
istry and Molecular Physics
21 CFR 820 United States Code of Federal Regulations,
Available from U.S. Government Publishing Office (GPO), 732 N. Capitol St.,
NW, Washington, DC 20401, http://www.gpo.gov.
Available from U.S. Food and Drug Administration (FDA), 10903 New
Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St., Hampshire Ave., Silver Spring, MD 20993, http://www.fda.gov.
4th Floor, New York, NY 10036, http://www.ansi.org. Available from U.S. Pharmacopeial Convention (USP), 12601 Twinbrook
Available from ICH Seceretariat, c/o IFPMA, 30 rue de St-Jean, P.O. Box 758, Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
1211 Geneva 13, Switzerland. Available online at http://www.ich.org/LOB/media/ Available from National Institute of Standards and Technology (NIST), 100
MEDIA423.pdf. Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, http://www.nist.gov.
F3384−21
TABLE 1 Physical/Chemical Property Requirements for Virgin Polydioxanone Homopolymers
Individual Solvent
Total Solvent Elemental Melting
Total Residual Residual(s) and (Optional) Residual Residual Catalyst
Analyte Combination Impurities, Limits Temperature
Monomer, (%) Applicable ICH Water (%) (ppm)
Residual(s) (except catalyst) (°C)
Limit(s) (in ppm)
Report conformance
<0.5 % loss on Report both for all Report per USP
A
Requirement <2.0 % (by mass) #0.5 % (by mass) status per USP 105–115
C
drying solvent(s) utilized <233>
B
<232>
A
Utilizing a moisture determination method agreed upon by the supplier and purchaser.
B
See 5.6.3.
C
See 5.6.4 and X2.6.
5.2 Chemical Identification: 5.2.3.1 Identity of PDO may be confirmed through sample
5.2.1 The identity of the virgin polymer shall be confirmed dissolution, H-NMR spectroscopy, and the use of a suitable
1 13
either by infrared, H-NMR, or C-NMR spectroscopy. reference spectrum. Sample dissolution is in deuterated
5.2.2 Infrared Identification: hexafluoroisopropanol (d-HFIP) or other substantially proton-
5.2.2.1 Identity of polydioxanone homopolymer may be freesolventabletofullysolvatethespecimenwithoutinducing
confirmed through an infrared spectrum exhibiting major competing spectral bands. Analysis shall be conducted using
absorption bands only at the wavelengths that appear in a methodssimilartothosedescribedinPracticeE2977.Atypical
suitable reference spectrum.Analysis shall be conducted using H-NMR spectrum for PDO polymer is shown in Fig. 2.
infrared spectroscopy practices similar to those described in
5.2.3.2 Additional spectral bands may be indicative of
Practice E1252. A typical infrared transmission reference known or unknown impurities, including residual monomer,
spectrumforapolydioxanonehomopolymerisshowninFig.1.
solvents, and catalysts (refer to the limits specified in Table 1).
5.2.2.2 Additional or variable spectral bands may be indica- A typical H-NMR spectrum for PDO polymer containing
tive of sample crystallinity or either known or unknown
residual monomer is shown in Fig. 3.
impurities, including residual monomer, solvents, and catalysts
5.3 Molar Mass:
(refer to the limits specified in Table 1).
1 1
5.2.3 H-Nuclear Magnetic Resonance ( H-NMR): NOTE 1—The term molecular weight (abbreviated MW) is obsolete and
FIG. 1Example Polydioxanone Resin Infrared Spectrum
F3384−21
FIG. 2Example Polydioxanone Resin H-NMR Spectra
FIG. 3Example H-NMR Spectra of Polydioxanone Resin with Residual PDO Monomomer
should be replaced by the SI (Système Internationale) equivalent of either
ing to Test Method D5296, but using hexafluoroisopropanol
relative molecular mass (M ), which reflects the dimensionless ratio of the
r
(HFIP)orhexafluoroacetone(HFA)andappropriatecalibration
mass of a single molecule to an atomic mass unit (see ISO 31-8), or molar
standards.
mass (M), which refers to the mass of a mole of a substance and is
typically expressed as grams/mole. For polymers and other
NOTE2—Molarmasscalibrationstandards(forexample,polystyreneor
macromolecules, use of the symbols M ,M , and M continue, referring
w n z
polymethylmethacrylate) provide relative values only, and are not to be
to mass-average molar mass, number-average molar mass, and z-average
confused with an absolute determination of a dioxanone-based polymer’s
molar mass, respectively. For more information regarding proper utiliza-
molar mass.
tion of SI units, see NIST Special Publication SP811.
5.3.2 Determine the inherent viscosity of the polymer,
5.3.1 The molar mass of the virgin polymer shall be
preferentially in HFIP, at 30 °C using procedures similar to
indicated by inherent viscosity in dilute solution (IV). In
addition to inherent viscosity (but not in place of), mass those described in Practice D2857 and Test Method D4603.
Determination at a lower temperature of 25 °C is allowable,
average molar mass and molar mass distributions may be
determined by gel permeation chromatography (GPC) accord- provided the utilized equipment delivers the required thermal
F3384−21
control and, if requested by the purchaser, an experimentally residuals shall be limited to <0.5 % loss on drying (refer to the
supported 30 °C equivalent concentration-appropriate extrapo- limit specified in Table 1). Individual limits for common
lated result is also reported within the supplied certification. If
processsolventsshallalsobeincluded,andthepresenceofany
the required sample of the subject polymer ratio does not fully one or more solvent may vary by manufacturer. This limit is
dissolve in HFIP, utilize HFA as the dissolution solvent. Note
based on the ICH Q3C quality guidelines for materials where
that any incomplete sample dissolution, precipitation from
Class 2 and Class 3 solvents may be present. Potential
solution, or the formation of gels will produce inconsistency
inclusionofalternativesolventsshouldbenotedandapplicable
and variation in observed drop times.
limits specified.
NOTE 3—The IV test duration for each sample should be minimized to
5.6 Elemental Impurities:
reduce the risk of resin concentration changes due to evaporative loss of
5.6.1 The significance of elemental impurities within an
solvent.
absorbablepolymerisultimatelydependentonthedimensional
5.3.3 Inherent viscosity is determined utilizing the follow-
characteristics of the final product and the rate of release of
ing:
those initially interstitial elements into the surrounding tissue
ln~t ⁄ t !v
and extracelluar fluid. Thus, any risk assessment of such
IV 5 (1)
W
impurities will be dependent on the final product design and
or intended application. Consequently, this raw material (not final
device) standard provides for appropriate reporting of elemen-
ln~t ⁄ t !
IV 5 (2)
tal impurities values, but does not mandate any specific
C
performance requirements. More detailed and pharmaceutical-
where:
oriented guidance regarding the appropriate means for both
IV = inherent viscosity (at 30 °C in dL/g), monitoring and assessing relevant elemental impurities within
t = efflux time in seconds for diluted solution,
afinalproductcanbefoundinUSPChapters<232>and<233>
t = efflux time in seconds for source solvent,
and in ICH Q3D.
W = mass of polymer being diluted (in grams),
5.6.2 Determine the concentration of the respective elemen-
v = dilution volume in deciliters (1 dL = 100 mL), and
tal impurities within the absorbable polymer by utilizing
C = concentration of dilute solution (w/v).
inductively coupled plasma mass spectroscopy (ICP-MS) or
5.3.4 Resin concentration shall be 0.5 % w⁄v or less. When
inductively coupled plasma atomic or optical emission spec-
reporting results identify the solvent utilized, analyte
troscopy (ICP-AES or ICP-OES) or an equivalent alternative
concentration, and analysis temperature.
method as described in Chapter <233> of the U.S. Pharmaco-
5.4 Residual Monomer:
peia. The specific 24 different elemental impurities of interest
5.4.1 The virgin polymer shall have a combined total are outlined in both USP <232> and in Table A.2.2 of ICH
residual monomer content ≤2.0 % in mass fraction.
Q3D. Both of these documents include risk-based approaches
Alternatively, a purchaser may require a monomer content toward the assessment and control of elemental impurities.
significantly less than 2 % to address processing and/or in-
5.6.3 Except for elements intentionally added as catalysts,
tended end-use requirements (see Supplementary Requirement
assess the obtained results for compliance with the parenteral
S1).
concentrationlimitsdescribedwithintheindividualcomponent
5.4.2 Determine the mass fraction of residual monomer by
option of USP<232>, Table 3 (derived from ICH Q3D Option
gas chromatography, HPLC, H-NMR spectroscopy (using
1,TableA.2.2). If all listed elements, except for those added as
deuteratedhexafluoroisopropanolorothersubstantiallyproton-
catalysts,canbeensuredtobemaintainedwithintheparenteral
free solvent able to fully solvate the specimen), or other
concentration individual component option limits, the resin
suitably sensitive analytic method as agreed upon by the
“conforms” to the USP <232> elemental impurities limits
supplier and purchaser.
(except catalyst). If any listed element (other than added
5.5 Residual Solvents: catalyst) cannot be controlled to be maintained within the
5.5.1 If any solvent is utilized
...