ASTM F2902-16e1

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.
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Designation: F2902 − 16
Standard Guide for
Assessment of Absorbable Polymeric Implants
This standard is issued under the fixed designation F2902; 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.
ε NOTE—Editorial corrections were made throughout in May 2017.
1. Scope additional details.Additionally, some of the recommended test
methods may require modification to address the properties of
1.1 This guide describes general guidelines for the
a particular device, construct, or application.
chemical, physical, mechanical, biocompatibility, and preclini-
cal assessments of implantable synthetic polymeric absorbable 1.6 Adherence to all aspects of these guidelines is not
mandatory,inthatassessmentsandtestslistedwithinthisguide
devices. This guide also describes evaluation methods that are
potentially useful and should be considered when assessing are not necessarily relevant for all absorbable implant systems
and applications.
absorbable implants or implant components.
1.7 Absorbable polymers used as a matrix to control the in
1.2 The described evaluations may assist a manufacturer in
vivo release of bioactive agents (drugs, antimicrobials, and so
establishing the safety and effectiveness of an absorbable
forth) may be evaluated according to many of the methods
implantdevice.Thislistingofassessmentmethodsmayalsobe
described herein. However, additional test methods not cov-
utilized to assist in establishing substantial equivalence to an
ered by this guide will likely be needed to evaluate a bioactive
existing commercially marketed device. However, these poly-
agent’s composition, loading, release kinetics, safety, and
meric material-oriented guidelines do not necessarily reflect
efficacy.
the total needs for any particular implant application (for
example, orthopedic, cardiovascular, sutures, and dermal
1.8 Composites of absorbable polymers with ceramics
fillers), which may require additional and potentially essential
and/or metals may be evaluated according to many of the
application-specific evaluations.
methods described herein. However, additional test methods
not covered by this guide will likely be needed to evaluate the
1.3 This guide is intended to cover all forms of absorbable
composite’s other component(s).
polymeric components and devices, including solid (for
example, injection-molded) and porous (for example, fibrous)
1.9 The values stated in SI units are to be regarded as
forms. This guide is also intended to cover devices fabricated
standard. No other units of measurement are included in this
from amorphous and/or semi-crystalline absorbable polymer
standard.
systems.
1.10 This standard does not purport to address all of the
1.4 This guide has been generated with principal emphasis safety concerns, if any, associated with its use. It is the
on the evaluation of devices formed from synthetic polymers
responsibility of the user of this standard to establish appro-
that degrade in vivo primarily through hydrolysis (for example, priate safety and health practices and determine the applica-
α-hydroxy-polyesters). Evaluation methods suggested herein
bility of regulatory limitations prior to use.
may or may not be applicable to implants formed from 1.11 This international standard was developed in accor-
materials that, upon implantation, are substantially degraded
dance with internationally recognized principles on standard-
through other mechanisms (for example, enzymatically in- ization established in the Decision on Principles for the
duced degradation).
Development of International Standards, Guides and Recom-
mendations issued by the World Trade Organization Technical
1.5 This guide references and generally describes various
Barriers to Trade (TBT) Committee.
means to assess absorbable materials, components, and de-
vices. The user needs to refer to specific test methods for
2. Referenced Documents
2.1 ASTM Standards:
D570 Test Method for Water Absorption of Plastics
This guide is under the jurisdiction of ASTM Committee F04 on Medical and
Surgical Materials and Devices and 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. 1, 2016. Published January 2017. Originally contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM
approved in 2012. Last previous edition approved in 2012 as F2902 - 12. DOI: Standards volume information, refer to the standard’s Document Summary page on
10.1520/F2902-16E01. the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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F2902 − 16
D638 Test Method for Tensile Properties of Plastics E1570 Practice for Computed Tomographic (CT) Examina-
D695 Test Method for Compressive Properties of Rigid tion
E2207 Practice for Strain-Controlled Axial-Torsional Fa-
Plastics
tigue Testing with Thin-Walled Tubular Specimens
D732 Test Method for Shear Strength of Plastics by Punch
F99 Guide for Writing a Specification for Flexible Barrier
Tool
Rollstock Materials
D792 Test Methods for Density and Specific Gravity (Rela-
F316 Test Methods for Pore Size Characteristics of Mem-
tive Density) of Plastics by Displacement
brane Filters by Bubble Point and Mean Flow Pore Test
D1042 Test Method for Linear Dimensional Changes of
F748 PracticeforSelectingGenericBiologicalTestMethods
Plastics Caused by Exposure to Heat and Moisture
for Materials and Devices
D1922 Test Method for Propagation Tear Resistance of
F1249 Test Method for Water Vapor Transmission Rate
Plastic Film and Thin Sheeting by Pendulum Method
Through Plastic Film and Sheeting Using a Modulated
D2857 Practice for Dilute Solution Viscosity of Polymers
Infrared Sensor
D2990 Test Methods for Tensile, Compressive, and Flexural
F1635 Test Method for in vitro Degradation Testing of
Creep and Creep-Rupture of Plastics
HydrolyticallyDegradablePolymerResinsandFabricated
D3079 Test Method for Water Vapor Transmission of Flex-
Forms for Surgical Implants
ible Heat-Sealed Packages for Dry Products
F1925 SpecificationforSemi-CrystallinePoly(lactide)Poly-
D3164 Test Method for Strength Properties of Adhesively
mer and Copolymer Resins for Surgical Implants
Bonded Plastic Lap-Shear Sandwich Joints in Shear by
F1980 Guide for Accelerated Aging of Sterile Barrier Sys-
Tension Loading
tems for Medical Devices
D3418 Test Method for Transition Temperatures and En-
F1983 Practice forAssessment of Selected Tissue Effects of
thalpies of Fusion and Crystallization of Polymers by
Absorbable Biomaterials for Implant Applications
Differential Scanning Calorimetry
F2097 Guide for Design and Evaluation of Primary Flexible
D3420 Test Method for Pendulum Impact Resistance of
Packaging for Medical Products
Plastic Film
F2210 Guide for Processing Cells, Tissues, and Organs for
D3846 Test Method for In-Plane Shear Strength of Rein-
Use in Tissue Engineered Medical Products (Withdrawn
forced Plastics
2015)
D4404 Test Method for Determination of Pore Volume and
F2313 Specification for Poly(glycolide) and Poly(glycolide-
Pore Volume Distribution of Soil and Rock by Mercury
co-lactide) Resins for Surgical Implants with Mole Frac-
Intrusion Porosimetry tions Greater Than or Equal to 70 % Glycolide
D4603 Test Method for Determining Inherent Viscosity of F2450 Guide for Assessing Microstructure of Polymeric
Poly(Ethylene Terephthalate) (PET) by Glass Capillary Scaffolds for Use in Tissue-Engineered Medical Products
Viscometer F2477 Test Methods for in vitro Pulsatile Durability Testing
of Vascular Stents
D5225 Test Method for Measuring Solution Viscosity of
F2502 Specification andTest Methods forAbsorbable Plates
Polymers with a Differential Viscometer
and Screws for Internal Fixation Implants
D5296 Test Method for Molecular Weight Averages and
F2559 GuideforWritingaSpecificationforSterilizablePeel
Molecular Weight Distribution of Polystyrene by High
Pouches
Performance Size-Exclusion Chromatography
F2579 Specification for Amorphous Poly(lactide) and
D5748 Test Method for Protrusion Puncture Resistance of
Poly(lactide-co-glycolide) Resins for Surgical Implants
Stretch Wrap Film
F2791 Guide for Assessment of Surface Texture of Non-
E96/E96M Test Methods for Water Vapor Transmission of
Porous Biomaterials in Two Dimensions
Materials
2.2 ISO Standards:
E128 Test Method for Maximum Pore Diameter and Perme-
ISO 178 Plastics — Determination of flexural properties
ability of Rigid Porous Filters for Laboratory Use
ISO 180 Plastics — Determination of Izod impact strength
E328 Test Methods for Stress Relaxation for Materials and
ISO 527-1 Plastics — Determination of tensile properties —
Structures
Part 1: General principles
E398 Test Method for Water Vapor Transmission Rate of
ISO 527-2 Plastics — Determination of tensile properties —
Sheet Materials Using Dynamic Relative Humidity Mea-
Part 2:Test conditions for moulding and extrusion plastics
surement
ISO 527-3 Plastics — Determination of tensile properties —
E467 Practice for Verification of Constant Amplitude Dy-
Part 3: Test conditions for films and sheets
namic Forces in an Axial Fatigue Testing System
ISO 604 Plastics — Determination of compressive proper-
E793 Test Method for Enthalpies of Fusion and Crystalliza-
ties
tion by Differential Scanning Calorimetry
E794 Test MethodforMeltingAndCrystallizationTempera-
tures By Thermal Analysis
The last approved version of this historical standard is referenced on
E1356 Test Method for Assignment of the Glass Transition
www.astm.org.
Temperatures by Differential Scanning Calorimetry 4
Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St.,
E1441 Guide for Computed Tomography (CT) Imaging 4th Floor, New York, NY 10036, http://www.ansi.org.
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F2902 − 16
ISO 1628-1 Plastics — Determination of the viscosity of 21 CFR Part 820 Title 21 Food And Drug Administration,
polymers in dilute solution using capillary viscometers — Part 820—Quality System Regulation
Part 1: General principles 7
2.5 U. S. Pharmacopeia (USP) Standards:
ISO 1628-5 Plastics — Determination of the viscosity of
<232> Elemental Impurities – Limits
polymers in dilute solution using capillary viscometers —
<233> Elemental Impurities – Procedures
Part 5: Thermoplastic polyester (TP) homopolymers and
<724> Drug Release
copolymers
<905> Uniformity of Dosage Units
ISO 1805 Fishing nets — Determination of breaking load
<1207> Sterile Product Packaging—Integrity Evaluation
and knot breaking load of netting yarns
<1208> Sterility Testing—Validation of Isolator Systems
ISO2062 Textiles—Yarnsfrompackages—Determination
<1209> Sterilization—Chemical and Physiochemical Indi-
of single-end breaking force and elongation at break using
cators and Integrators
constant rate of extension (CRE) tester
<1211> Sterilization and Sterility Assurance of Compendial
ISO 6721-2 Plastics — Determination of dynamic mechani-
Articles
cal properties — Part 2: Torsion-pendulum method
2.6 NIST Document:
ISO 9000 Quality Management Systems—Fundamentals
NIST SP811 Special Publication SP811: Guide for the Use
and Vocabulary
of the International System of Units (SI)
ISO 9001 Quality Systems Management
ISO 10993 Biological Evaluation of Medical Devices
2.7 Other Documents:
ISO 11135 Sterilization of Health Care Products—Ethylene ICH Q3C International Conference on Harmonisation of
Oxide
Technical Requirements for Registration of Pharmaceuti-
ISO 11137 Sterilization of Health Care Products—Radiation cals for Human Use, Quality Guideline: Impurities: Re-
ISO 11607-1 Packaging for terminally sterilized medical
sidual Solvents
devices — Part 1: Requirements for materials, sterile
barrier systems and packaging systems.
3. Terminology
ISO 13485 Medical Devices—Quality Management
3.1 Definitions:
Systems—Requirements for Regulatory Purposes
3.1.1 absorbable, adj—in the body, an initially distinct
ISO 13781 Poly(L-lactide) Resins and Fabricated Forms for
foreign material or substance that either directly or through
Surgical Implants—In Vitro Degradation Testing
intended degradation can pass through or be metabolized or
ISO 13934-1 Textiles —Tensile properties of fabrics — Part
assimilated by cells and/or tissue.
1: Determination of maximum force and elongation at
maximum force using the strip method NOTE 1—See Appendix X4 for a discussion regarding the usage of
absorbable and other related terms.
ISO 14130 Fibre-reinforced plastic composites — Determi-
nation of apparent interlaminar shear strength by short-
3.1.2 bioactive agent, n—any molecular component in, on,
beam method
or with the interstices of a device that is intended to elicit a
ISO 15814 Implants for Surgery—Copolymers and Blends
desired tissue or cell response.
Based on Polylactide—In Vitro Degradation Testing
3.1.2.1 Discussion—Growthfactors,antibiotics,andantimi-
ISO/TS 12417 Cardiovascular Implants and Extracorporeal
crobials are typical examples of bioactive agents. Device
Systems—Vascular Device-Drug Combination Products
structural components or degradation products that evoke
ISO 80000–9 Quantities and units — Part 9: Physical
limited localized bioactivity are not included.
chemistry and molecular physics
3.1.3 plasticizer, n—substance incorporated into a material
2.3 AAMI Standards:
to increase its workability, flexibility, or distensibility.
AAMI STBK9–1 Sterilization—Part 1: Sterilization in
3.1.4 porogen, n—one or more added materials that, upon
Health Care Facilities
removal, produce voids that result in generation of a porous
AAMI STBK9–2 Sterilization—Part 2: Sterilization Equip-
structure.
ment
3.1.4.1 Discussion—The need for inclusion of a porogen is
AAMI STBK9–3 Sterilization—Part 3: Industrial Process
process dependent, with many porous structures able to be
AAMI TIR17 Compatibility of Materials Subject to Steril-
generatedwithouttheutilizationofporogens.Aporogencanbe
ization
a gas, liquid, or solid and can be either intentionally or
2.4 U. S. Code of Federal Regulations:
unintentionally added.
21CFRPart58 Title21FoodAndDrugAdministration,Part
58—GoodLaboratoryPracticeforNonclinicalLaboratory
Studies
Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville,
MD 20852-1790, http://www.usp.org.
5 8
Available from Association for the Advancement of Medical Instrumentation Available from National Institute of Standards and Technology (NIST), 100
(AAMI), 4301 N. Fairfax Dr., Suite 301, Arlington, VA 22203-1633, http:// Bureau Dr., Stop 1070, Gaithersburg, MD 20899-1070, http://www.nist.gov.
www.aami.org. Available from International Conference on Harmonisation of Technical
AvailablefromU.S.GovernmentPrintingOfficeSuperintendentofDocuments, Requirements for Registration of Pharmaceuticals for Human Use (ICH), ICH
732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401, http:// Secretariat, c/o IFPMA, 15 ch. Louis-Dunant, P.O. Box 195, 1211 Geneva 20,
www.access.gpo.gov. Switzerland, http://www.ich.org.
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F2902 − 16
4. Significance and Use 5.1.2 Mode of Manufacture—Consideration should be made
toward the method of manufacture (e.g., injection molding
4.1 This guide is aimed at providing guidance for assess-
versus compression molding versus extrusion), which can
ments and evaluations to aid in preclinical research and
induce differing levels of thermal stress – potentially resulting
development of various absorbable components and devices.
in dissimilar degradation profiles within otherwise dimension-
4.2 This guide includes brief descriptions of various in-
ally identical devices.
tended uses, processing conditions, assessments, and both
5.2 Solvent Casting—Synthetic absorbable implants can be
qualitative and quantitative analyses for raw materials to
fabricated through dissolution in a solvent followed by casting
finished product components.
into a desired form. This process is typically utilized in the
4.3 The user is encouraged to utilize appropriateASTM and
formation of films, but other forms are possible.
other standards to conduct the physical, chemical, mechanical,
5.2.1 Compositional Purity—The purity of the solvent(s)
biocompatibility, and preclinical tests on absorbable materials,
utilized in the casting process must be known and of a grade
devicecomponents,ordevicespriortoassessmentinan in vivo
suitable for the intended application. The overall system (that
model.
is,incomingrawmaterialsandalldevicefabricationprocesses)
needs to maintain a level of particle control appropriate for the
4.4 Whenever an absorbable material is mixed or coated
intended application. It is important to note that the act of
with other substances (bioactive, polymeric, or otherwise), the
solvating a hydrolysable polymer inherently increases its chain
physical and degradation properties of the resulting composite
motion, thereby increasing its potential for reactivity. If any
may differ significantly from the base polymer. Thus, unless
chemically reactive moiety (such as water) is present in the
prior experience can justify otherwise, performance character-
solvent, degradation can increase significantly from the poly-
izations described herein should be conducted on the compos-
mer’s solid state condition. Consequently, the impact of actual
ite construct rather than on individual components.
processing conditions (for example, solution temperature,
4.5 Assessments of absorbable materials should be per-
moisture content) on the resulting product should be both
formed in accordance with the provisions of the FDA Good
understood and controlled.
Laboratories Practices Regulations 21 CFR 58, where feasible.
5.2.2 Chemical Compatibility—All components of a solvent
4.6 Studies to support regulatory approval for clinical or casting system need to possess a level of compatibility suitable
commercial use, or both, should conform to appropriate for the intended application. Examples of incompatibility
nationally adopted directives or guidelines, or both, for the include, but are not limited to, reactivity (unintended genera-
development of medical devices [for example, CE approval; tion of differing chemical moieties within the solution) and
US-FDAInvestigationalDeviceExemption(IDE),Pre-Market phase separation (unintended formation of colloids/
Approval (PMA), or 510K submission]. precipitates/particles that may be detrimental to overall bio-
compatibility and/or desired in vivo performance).
4.7 Assessments based upon data from physical, chemical,
5.2.3 Solvent Removal—The solvent casting process inher-
mechanical, biocompatibility, and preclinical testing models
ently includes a drying step to remove the major portion of the
are highly valuable but carry inherent limitations. Thus, the
solvent. Any remaining residual solvent will effectively tem-
clinical relevance of each assessment needs to be carefully
porarily plastisize the device, potentially affecting its initial
considered and the user is cautioned that pre-clinical evalua-
physical properties. In addition, residual solvent may pose
tions may not be predictive of human clinical performance.
biocompatibility-related issues, details of which are addressed
in Section 8.
5. Fabrication and Processing Related Features and
5.2.4 Dimensional Control—As with any forming process,
Considerations
casting dimensions (including thickness) shall be controlled
5.1 Thermal Processing—Synthetic absorbable implants are
within limits determined to be suitable for the intended
routinely fabricated through thermal means, with typical ex-
application.
amplesincludingextrusionandbothinjectionandcompression
5.3 Coating—Polymers with hydrolysable segments can be
molding. Extrusion is typically used to manufacture fibrous
applied to a device using various methods ranging from
forms(forexample,wovenorknittedmeshes,monofilamentor
dip-coating (aqueous or organic solvent) to vapor deposition.
braidedsutures,fibrousnonwovens),aswellasfilmsandtubes.
Injection molding typically includes screws, tacks, barbs, pins, 5.3.1 Physical Deposition Control—Coating
and bone anchors. Compression molding is a common method characteristics—including, but not limited to, density,
for fabrication of plates and panels. thickness, and/or bioactive agent loading—shall be controlled
within limits determined to be suitable for the intended
5.1.1 Thermal Degradation Control—The act of thermal
application.
processing can potentially degrade absorbable polymers. In
addition, any presence of moisture will introduce an additional 5.3.2 Compositional Purity—The purity of the coating itself
degradation mechanism, which will occur rapidly at elevated and any solvent(s) utilized in the coating process shall be
processing temperatures. Consequently, the impact of actual knownandofagradesuitablefortheintendedapplication.Any
processing conditions—including temperature, moisture, and aqueous-based solvent systems shall utilize water that meets
their variations—on the resulting product should be both USP Sterile Water for Injection requirements. Non-aqueous
understood and appropriately controlled. solvent systems need to maintain a level of particle control
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F2902 − 16
appropriate for the intended application. Additionally, Interna- 5.4.1.3 The plasticizer content in the finished as-formed
tional Conference on Harmonisation (ICH) based residual device must also be known, along with quantification of any
solvent limits—as described in Section 8 and in synthetic expected other components possessing toxicity and/or quanti-
absorbable resin Specifications F1925, F2579, and F2313— ties that may impact tissue response and/or display either local
or systemic toxicity.
need to be met. Devices are to be characterized by analytic
detection limits sufficient to assure that total solvent residuals 5.4.2 Porogens—Porogens are one or more added materials
that, upon their removal, produce voids that result in a porous
are maintained below ICH guidelines.
structure. A porogen can be a gas, liquid, or solid and can be
5.4 Additives—In the context of this guide, an additive is
either intentionally or unintentionally added. The need for
any substance that is intentionally added to the implant,
inclusionofaporogenisprocess-dependent,withmanyporous
regardless as to whether or not it is removed during subsequent
structures able to be generated without the utilization of
processing. As a result, additives needing consideration can
porogens. Any porogen needs to deliver the desired pore
range broadly from processing aids (for example, mold release
characteristics, which typically includes porosity, presence of
agents) to fillers to pharmaceuticals. Since in vivo release is
open/closed cells, pore size, and so forth. Characterization of a
categorically inherent to absorbability, a thorough understand-
porogen raw material should, at minimum, include:
ing of any additive’s biological/toxicological properties is
5.4.2.1 Dimensions—Provide some relevant measure of the
essential to implant design.Also worthy of consideration is the
porogen’s size distribution.
impact expected additive concentration(s) may impart on
5.4.2.2 Chemical Composition—Assay the basic composi-
manufacturing processes and/or the physical properties of the
tion of the porogen and quantify any expected other compo-
polymeric device itself.
nents (due to raw material sources and/or processing methods;
5.4.1 Plasticizers—In the context of this guide, plasticiza-
for example, reactive chemical byproducts, trace metals/
tion can be imparted by anything added to a macromolecular
catalysts). Quantification of each expected other component is
device or component that swells and/or solvates its polymeric
to be undertaken at an analytic level that assures that the tissue
structure to effectively lower its glass transition temperature
response in the final porous product will be suitable for the
(Tg). Almost any low molar mass molecule able to penetrate
intended application. Low or non-toxic materials may need
the polymeric structure—including solvents, water, and bioac-
no-to-minimal monitoring, depending on extraction efficiency
tive agents—carries potential to impart a plasticization effect.
and expected residual levels within the formed porous device.
Thus, plasticizer should be perceived as a descriptive term that
Higher toxicity materials will require elevated awareness and
is not limited solely to the class of chemicals commonly added
monitoring, the extent of which will depend on extraction
to modify/affect the mechanical properties of the polymer
efficiency and expected residual levels within the formed
and/or device.
porous device.
5.4.2.3 Characterization of Formed Porous Device—The
5.4.1.1 Any material used to plasticize absorbable polymers
will, upon polymer absorption, inherently be released into the porecharacteristicsoftheformeddeviceshouldbeassessedby
body. While local toxicity would be addressed through the appropriate means as summarized in Guide F2450.
Additionally, any remaining residual porogen(s) or other com-
implant’s histological response, systemic toxicity of any plas-
ticizer should be fully understood (for example, excretion, ponents that display either local or systemic toxicity or have
the potential to adversely impact tissue response or device
concentrationinorgans,andsoforth).Ifadequatetoxicological
information is unavailable for the utilized placticizer(s), such performance should be quantified.Also, it should be noted that
addition/elimination of porosity to/from a material can influ-
data must be generated. Additionally, the purity of the raw
material plasticizer must be known and of a grade suitable for ence the local tissue response - so additional studies to
understand the impact of porosity changes may be needed.
the intended application.
5.4.3 Bioactive Agents—Bioactive agents are typically con-
5.4.1.2 The chemical composition of the plasticizer raw
sidered to be pharmaceuticals, growth factors, antibiotics, or
material shall be determined by means of an assay of the basic
antimicrobials. Additionally, cells or specific cell surface/
composition and a quantification of any expected other com-
growth factor antigens may be components of the device. If a
ponents (due to raw material sources and/or processing meth-
bioactive substance is to be released from a device or a device
ods; for example, reactive chemical byproducts, trace metals/
component, the release profile should be characterized.
catalysts). Quantification of each expected other component is
5.4.3.1 Controlled Release—Any controlled release of a
to be undertaken at an analytic level that brings assurance that
bioactive agent or substance from an absorbable device (be it
tissue response in the final product will be suitable for the
from the bulk or a coating, or both) needs to be sufficiently
intended application. Low or non-toxic materials may need
understoodandcharacterizedtoassurethattheeffectivedosage
no-to-minimal monitoring, depending on extraction efficiency
into the surrounding tissue is both safe (that is, below toxic
and expected residual levels within the formed device. Higher
levels) and accomplishes the design goal.
toxicity materials will require elevated awareness and
monitoring, dependent on extraction efficiency expected re-
NOTE 2—See X1.1 for more information on appropriately characteriz-
sidual levels within the formed device. ing the controlled release of bioactive agents, drugs/pharmaceuticals,
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F2902 − 16
antimicrobials, or cells, or combination thereof.
fabricated absorbable device be specified. Factors that should
be considered for inclusion within the specification can be
5.5 Post-formation Thermal Processing—Fabricated forms
found in Specifications F1925, F2313, and F2579. Additional
typically undergo at least one or more thermal processes,
items for consideration can be found in Table 1—Sections A
which may include thermally induced annealing, crosslinking,
and B of this guide.
solvent extraction, and so forth.Any thermal processing of the
6.1.3 Physical Description Properties Characterization—It
fabricated form (including cooling/quenching processes)
is recommended that the physical properties of a fabricated
should be documented and the mechanical, physical, and
absorbable device be specified. Factors that should be consid-
chemical effects assessed.
ered for inclusion within the specification can be found in
5.6 Work in Progress—Since hydrolysable polymers can be
Table 1—Sections C, D, and E.
affected by atmospheric moisture, the effects of such exposure
6.1.4 Thermal Properties Characterization—It is recom-
during manufacture and prior to final packaging need to be
mended that the thermal properties of a fabricated absorbable
both understood and controlled to a level that assures device
device be specified. Factors that should be considered for
performance. Device susceptibility to such exposure can be a
inclusion within the specification can be found in Table
function of multiple variables, which may include processing/
1—Section F.
storage humidity(ies) and temperature(s), polymer/device
6.2 Mechanical/Performance Properties—The objective of
moisture uptake, device degradation rate, etc. Particular pre-
any mechanical characterization is to adopt relevant evaluation
caution should be directed toward devices that are fragile
methods that approximate the expected clinical loading of the
and/or temperature-sensitive.
device (for example, don’t rely solely on tensile testing when
5.7 Sterilization Processing—A summary of sterilization
clinical loading is in shear). Besides understanding and mod-
methods and standards is presented in 7.2. However, it is
eling normal service conditions, mechanical characterizations
important to emphasize that sterilization is a manufacturing
should assess the worst-case clinical failure mode and then
process that can have significant impact on an absorbable
evaluate device performance under similar conditions. Worst
implant system’s material or (if present) bioactive agent
case failure may be the result of numerous combined factors,
properties.Thus,evaluationsconsideredtoberepresentativeof
which can include materials composition, physiological fluids
actual performance in vivo and/or finished product shall be
and temperatures, effects of clinical placement, and in vivo
conducted on devices or test specimens that have been steril-
loading conditions. However, the user is cautioned that such
ized by means that approximate the intended commercial
pre-clinical testing does not, in itself, assure suitability to a
method.
particular application and may not be predictive of human
clinical performance. Mechanical properties that should be
6. Device Characterizations/Assessments
considered for inclusion within a specification can be found in
NOTE 3—Sterilization of absorbable polymeric materials should be
Table 2—Sections A to F.
expected to cause changes in molar mass or structure, or both. This can
affect the initial mechanical and physical properties of a material or
6.2.1 Initial Characteristics/Properties—Characterize the
device, as well as its subsequent rate of degradation. Therefore, if a test is
relevantinitial(thatis,as-manufactured)mechanicalproperties
intended to be representative of actual performance in vivo and/or finished
of the device. The initial dimensional and net mechanical
product, assess the test absorbable polymeric material in a form that is
characteristics of the device will need to reflect the intended
representative of a product produced under standard manufacturing
applicationandtheresultingdesign.Anexampleofmechanical
conditions and ready for sale.
characterizations appropriate for absorbable implants designed
6.1 Compositional Properties:
towardaspecificfunctioncanbefoundinSpecificationF2502.
6.1.1 Raw Material Characterization—It is recommended
However, each different absorbable application or design
thattherequiredcharacteristicsofallincomingrawmaterialbe
approach will likely require appropriate variations in the
specified, including absorbable resin. Factors that should be
applied assessment method(s).
considered for inclusion within specifications for hydrolysable
6.2.2 Hydrolytic Degradation Properties (Degradation
polyesters can be found in Specifications F1925, F2313, and
Profiling/Modeling)—Characterize the loss of relevant me-
F2579, which typically include a means for monitoring molar
chanical properties of the device over time under conditions
mass (M) — such as via inherent viscosity or size exclusion
that are representative of expected in vivo service conditions.
chromatography (SEC) [also known as gel permeation chro-
Once conditioned for a clinically relevant time interval, evalu-
matography (GPC)].
ations may include destructive mechanical testing or testing
NOTE 4—The term molecular weight (abbreviated MW) is obsolete and
untilfailure(inthecaseofstaticorcyclicloadingevaluations).
should be replaced by the SI (Système Internationale) equivalent of either
Depending on the indicated use of a device, clinical relevance
relative molecular mass (Mr), which reflects the dimensionless ratio of the
may indicate the need for one or more of the following
mass of a single molecule to an atomic mass unit (see ISO 80000-9), or
conditioning methods.
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
NOTE 5—Hydrolytic environments that are intended to mimic in vivo
macromolecules, use of the symbols Mw, Mn, and Mz continue, referring
conditions typically include buffered saline-based water baths. In such
to mass-average molar mass, number-average molar mass, and z-average
baths, attention toward buffer capacity and careful monitoring and
molar mass, respectively. For more information regarding proper utiliza-
maintenance of pH throughout the evaluation is essential for proper
tion of SI units, see NIST SP811.
hydrolytic evaluation of a hydrolysable device.
6.1.2 Chemical Properties Characterization (Fabricated
NOTE 6—Since loss of mechanical properties within an absorbable
Device)—It is recommended that the chemical properties of a polymeric device is typically the result of chain scission, concurrent
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TABLE 1 Chemical and Physical Properties
Property, Behavior, or Characteristics Applicable Issues/Design Considerations Potentially Relevant Analyses,
Characterizations, and Test Methods
A—Chemical Composition Main Ingredients: NMR
Polymers (incl copolymer ratio), GC
Chain extenders, HPLC
Cross-linking agents, Residual Ignition
Coating composition, AA
Plasticizer(s)/processing aids ICP
IR
Purity/Trace Elements: GPC
Catalysts Karl-Fischer Titration
Low Mw components (water solvent, monomers, oligomers) Polarimeter (optical rotation
Stereoregularity and Optical Purity
B—Molecular Structure Polymer Blending NMR
Crosslinking
Copolymer block/branch length IR
Copolymer conversion efficiency Solubility
Mn, Mw, Polydispersity, MWD Swelling
GPC/SEC – ASTM D5296
Inherent Viscosity:
 ASTM D4603
 ISO 1628-5
 ASTM D2857
 ASTM D5225
 ISO 1628–1
 NOTE— Choice of solvent and tem-
perature should be reported (see F1925,
F2313, and/or F2579 for more detail on IV
testing of absorbable polymers and related
reporting requirements).
C—Morphology (Supermolecular Structure) % Crystallinity X-ray diffraction
Phases (Types, amount, and orientation) DSC
DTA
Optical Microscopy
Birefringence
X-ray diffraction
Draw ratio
D—Composite Structure Laminate Structure: Scanning Electron Microscopy (SEM)
Ply thickness and orientation Optical Microscopy
Ply orientation and stacking sequence (incl symmetry) Micro-CT
Reinforcement: Porosimetry
Location within part Transmission Electron Microscopy (TEM)
3D orientation
Volume or weight fraction
Contacts/cross-overs, homogeneity
Cross-section shape
Fiber—twist and denier
Weave—types, ends/mm
Coatings—number and thickness of each layer
Voids:
Mean Vol %
Interconnections
Depth and Profile
E—Physical Properties Water Absorption ASTM D570
Dimensional Changes ASTM D1042
Density (mass and volume) (smallest and largest device sizes) ASTM D792
Porosity Distribution ASTM F2450
Surface Area: Porosimetry (ASTM D4404)
(smallest and largest device sizes)—determined by overall Porometry (ASTM E128, F316
external dimensions, not intended to include internal surfaces ASTM F2791
with microporous structures
Surface Characteristics—(Texture, patterns, roughness, and
so forth)
F—Thermal Properties Glass Transition Temperature ASTM D3418
Crystallization Temperature ASTM E793
Melting Temperature ASTM E794
ASTM E1356
monitoring of molar mass should be considered since measurable loss can be expected prior to any detectable degradation of mechanical properties.
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TABLE 2 Mechanical, Degradation, and Performance Properties
Property/Behavior Applicable Issues/Design Considerations Potentially Relevant Analyses, Characterizations, and Test Methods
A—Cyclic Fatigue Fracture, Deformation, Wear, and ASTM E467 (Axial Fatigue)
Loosening ASTM F2477 (Pulsatile Durability)
ASTM E2207 (Strain-Controlled Axial-Torsional Fatigue)
B—Static Strength and Stiffness Fracture/Loosening under Anticipated Load- ASTM D638, D695—Tensile/compressive properties
ing (for example, shear) ISO 527-1, ISO 527-2, ISO 527-3, ISO 604, ISO 2062, ISO 13934-1 —Tensile/
Compressive Properties
ASTM F2502—Torque (for example, screws); Shear (for example, pins)
in-vitro mechanical testing under analogous loading conditions
ISO 178 - Flexural properties
ISO 180 - Izod impact strength
ISO 14130 – Shear Strength
 ASTM D732
 ASTM D3846
 ISO 1805
 ISO 6721-2
 ASTM D1922
 ASTM D5748
 ASTM D3420
 ASTM D3164
C—Stress Concentrations, Re- Determine the potential presence and loca- Geometric Characterization and Measurement (for example, fillet and corner radii)—
sidual Stresses tion of high stresses and their effect(s) on SEM, etc.
the performance of the device Note—SEM does not provide information on stress, but can be used to help
understand/bound the radii of sharp corners, etc., and do bounding analyses
on stress concentrations, etc.
Stress Analysis
Finite Element Analysis (FEA)
Mechanical Testing
D—Viscoelasticity Loosening Creep, ASTM D2990
(time-dependent deformation or Stress Relaxation, ASTM E328
relaxation)
E—Wear and Degradation Effect of Sterilization ASTM F1635, F2502, ISO 13781
Significant effects from implant contact with Characterization of aged/degraded samples, including: mechanical properties;
other materials reasonably expected within microstructure, weight loss, molar mass (molecular weight), Tg, crystallinity, dimen-
a clinical use setting sional
Shelf-life stability (for example, swelling, stretching)
Strength retention after cyclic loading in Note—use sterilized samples for all evaluations or demonstrate no significant
37°C buffered saline effect on all properties
Fracture/loosening
F—Biocompatibility Compatibility of Bulk Material; ISO 10993
Compatibility of Particles and Degradation ASTM F748
Products (Synovitis—see Appendix X2) Elemental Impurities – Limits <232>
Metabolic pathways Elemental Impurities – Procedures <233>
G—Preclinical Localized inflammatory response; histologi- in vivo
(in vivo) Evaluations cal resolution of absorbable component(s) ASTM F1983
ISO 10993–6
X-ray, microCT (ASTM E1441, E1570), ultrasound, OCT, MRI, and others
Post-retrieval
Optical microscopy
SEM
histology
6.2.2.1 Mechanically Unloaded Hydrolytic Evaluation— use includes loading, hydrolytic aging alone can NOT be
Conditioning of a hydrolysable device under mechanically considered as sufficient to fully characterize the device.
unchallenged hydrolytic conditions at 37°C in water or buff- 6.2.2.2 Mechanically Loaded Hydrolytic Evaluation—The
eredsalineisdescribedinTestMethodF1635.Additionalmore objective of loading is to approximate (at 37°C in buffered
specific polymer-related guidance may be found in ISO 13781 saline) the actual expected device service conditions so as to
and ISO 15814. While testing of unloaded specimens is a better understand potential physicochemical changes that may
common means to obtain a first approximation of the degra- occur. Such testing can be considered as necessary if clinically
dation profile of an absorbable material or device, it does not relevant device loading can reasonably be expected under in
necessarily represent actual in vivo service conditions, which vivo service conditions. Whenever possible, mechanical evalu-
can include mechanical loading in a variety of forms (for ation of an implant should include loading that is comparable
example, static tensile, cyclic tensile, shear, bending, torsion, to expected in vivo service conditions, with test specimens
andsoforth).Iftheperformanceofadeviceunderitsindicated loaded in a meaningful manner that—as closely as practical—
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F2902 − 16
represents in vivo conditions, both in magnitude and in type of 7. Packaging, Sterility, Shelf-Life, and Labeling
loading. Clinically relevant cyclic load tests may include
7.1 Packaging—Suitability of a device for intended use
testing to failure or for a specified number of cycles followed
typically includes its provision within a sterile package suffi-
by testing to evaluate physicochemical properties.
ciently durable to adequately protect that sterility during
(1) Physiochemical Changes—When assessing hydrolytic
normal handling and storage. With an absorbable product
degradation under a mechanical load, consideration should be
where a device’s physical, mechanical, and chemical charac-
given to the potential significance of any alterations to the
teristics are additionally susceptible to hydrolytic degradation,
chemical or physical properties, or both, of the polymeric
maintenance of the device’s critical performance must also
device, the scope of which includes cracking or crazing,
include reliable ongoing control and/or removal of moisture
accelerated local degradation (for example, in regions of stress
from both the product and package interior. Therefore, pack-
concentration), extension, swelling, fracture, and so forth.
aging for devices fabricated from hydrolysable polymers must
(2) Creep, Relaxation, and Fatigue—Whenassessingpoly-
be designed so that any moisture ingress is controlled. Control
mer degradation under load, it may be necessary to consider
can be facilitated through utilization of moisture-resistant
and monitor creep, relaxation, and/or fatigue, any combination
materials (for example, foil-lined packaging) and desiccants.
of which may be significant. Fatigue is crack initiation and
However, regardless of design, no package can inherently be
growth due to imposition of repeated or cyclic stresses. Creep
assumed to be moisture-proof. Consequently, some level of
is time-dependent deformation under imposed stresses (con-
package desiccation should be considered.
stant or cyclic) and is frequently observed in viscoelastic
7.1.1 Package Components—Moisture vapor transmission
materials(forexample,plastics),especiallyastemperaturesare
rates for the various available packaging materials, sealing
elevated. Creep is also known as cold flow when it occurs at
layers, and desiccant capacity all need to be considered in the
room temperature. Creep rate is dependent on factors such as
package design.
temperature, thermal history, degree of crystallinity, and both
7.1.2 Package Sealing—Particular attention should be di-
the presence and extent of filler material(s). Creep testing is
rected toward both thoroughness and consistency in executing
typically conducted under constant load. Relaxation is similar the package sealing process, along with comprehensive assess-
to creep, dependent on many of the same factors, but is
ment of the moisture-vapor transmission occurring through the
measured as the time-dependent reduction in stress under plane of that sealing layer.
imposed deformation. Additional information regarding the
7.1.3 Moisture Vapor Specific Test Methods for Consider-
measurement an
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