Characterization of Ultrahigh 
Molecular Weight Polyethylene 
(UHMWPE) Used in Orthopedic 
Devices 
Guidance for Industry and Food and 
Drug Administration Staff 
Document issued on April 26, 2019. 
The draft of this document was issued on February 12, 2016. 
For questions regarding this document, contact the Division of Orthopedic Devices (DOD) at 
301-796-5650. 
U.S. Department of Health and Human Services 
Food and Drug Administration 
Center for Devices and Radiological Health  Contains Nonbinding Recommendations 
Preface 
Public Comment 
You may submit electronic comments and suggestions at any time for Agency consideration to 
https://www.regulations.gov . Submit written comments to the Dockets Management Staff, 
Food and Drug Administration, 5630 Fishers Lane, Room 1061, (HFA-305), Rockville, MD 
20852. Identify all comments with the docket number FDA-2016-D-0363. Comments may not 
be acted upon by the Agency until the document is next revised or updated. 
Additional Copies 
Additional copies are available from the Internet.  You may also send an e-mail request to 
CDRH-Guidance@fda.hhs.gov to receive a copy of the guidance.  Please use the document 
number 1300006 to identify the guidance you are requesting.  Contains Nonbinding Recommendations 
Table of Contents 
I. Introduction ........................................................................................................................... 1 
II. Scope .................................................................................................................................... 2 
III. Types of UHMWPE Materials Used in Implantable Orthopedic Devices ......................... 2 
A.  Conventional UHMWPE ............................................................................................... 2 
B.  Highly Crosslinked UHMWPE (HXLPE) ..................................................................... 3 
C.  Antioxidant Highly Crosslinked UHMWPE (AO-HXLPE) .......................................... 3 
D.  Non-Conventional UHMWPE ....................................................................................... 3 
IV. Material Processing and Characterization .......................................................................... 4 
A.  Conventional UHMWPE ............................................................................................... 4 
B.  Highly Crosslinked UHMWPE (HXLPE) ..................................................................... 5 
C.  Antioxidant Highly Crosslinked UHMWPE (AO-HXLPE) .......................................... 7 
D.  Non-Conventional UHMWPE ....................................................................................... 9 
V. Biocompatibility................................................................................................................... 9 
VI. Shelf Life and Packaging .................................................................................................. 11 
Appendix 1.  FDA-Recognized Standards Applicable to UHMWPE Evaluation .................. 13 
Appendix 2.  Summary of Characterization Information for Various UHMWPE Materials .15 Contains Nonbinding Recommendations 
Characterization of Ultrahigh 
Molecular Weight Polyethylene 
(UHMWPE) Used in Orthopedic 
Devices 
Guidance for Industry and 
Food and Drug Administration Staff 
This guidance represents the current thinking of the Food and Drug Administration (FDA 
or Agency) on this topic.  It does not establish any rights for any person and is not binding 
on FDA or the public. You can use an alternative approach if it satisfies the requirements 
of the applicable statutes and regulations. To discuss an alternative approach, contact the 
FDA staff or Office responsible for this guidance as listed on the title page. 
I. Introduction 
FDA has developed this guidance document for members of industry who submit and FDA 
staff who review testing of orthopedic devices using ultrahigh molecular weight polyethylene 
(UHMWPE) material. In this document, the terms you and your refer to members of 
industry, also known as sponsors, submitters, or applicants; and the terms we, us, and 
our refer to FDA. This guidance is intended to assist you in determining the appropriate 
information and testing to submit in Premarket Notifications (510(k)s), De Novo requests, 
Premarket Approval (PMA) applications, Humanitarian Device Exemptions (HDEs), and 
Investigational Device Exemptions (IDEs) for orthopedic devices that contain UHMWPE. 
This guidance addresses the characterization and testing of UHMWPE materials used in 
orthopedic devices. These materials include conventional UHMWPE, highly crosslinked 
UHMWPE, highly crosslinked UHMWPE containing antioxidants (e.g., -tocopherol (an 
isomer of vitamin E)), and non-conventional UHMWPE. This document outlines the 
information we recommend you include in a submission to FDA to characterize the 
UHMWPE material (e.g., material description, sterility, biocompatibility, mechanical 
properties, and chemical properties). 
Many standards are referenced in this document. For the current edition of the FDA-
recognized standard(s) referenced in this document, see the FDA Recognized Consensus 
1  Contains Nonbinding Recommendations 
Standards Database.1  A table of referenced FDA-recognized standards applicable to 
UHMWPE is provided in Appendix 1.  
FDAs guidance documents, including this guidance, do not establish legally enforceable 
responsibilities. Instead, guidances describe the Agencys current thinking on a topic and 
should be viewed only as recommendations, unless specific regulatory or statutory 
requirements are cited. The use of the word should in Agency guidances means that 
something is suggested or recommended, but not required. 
II. Scope 
The recommendations in this document are applicable to class II and class III devices 
intended for orthopedic applications, including spinal devices, which contain UHMWPE.  
If you intend to submit an original IDE for an investigational device containing 
UHMWPE, we recommend you submit a Pre-Submission to the appropriate review 
division to determine what level of characterization is needed for the UHMWPE material. 
For more information on Pre-Submissions, see the FDA guidance document entitled, 
Requests for Feedback on Medical Device Submissions:  The Pre-Submission Program 
and Meetings with Food and Drug Administration Staff.2
This guidance document does not address nor discuss device-specific functional testing, 
such as impingement testing, wear testing, or interconnection strength testing. If you have 
any questions on these topics, refer to the recommendations in any applicable device-
specific guidance, when available, or contact the appropriate review division. 
III. Types of UHMWPE Materials Used in Implantable 
Orthopedic Devices 
The UHMWPE materials used in implantable orthopedic devices may be organized into four 
general categories: 1) conventional UHMWPE; 2) highly crosslinked UHMWPE; 3) 
antioxidant highly crosslinked UHMWPE; and 4) non-conventional UHMWPE. 
A.  Conventional UHMWPE 
Conventional UHMWPE originates from virgin resin powders or consolidated forms 
conforming to international consensus standard ASTM F648: Standard Specification for 
Ultra-High-Molecular-Weight Polyethylene Powder and Fabricated Form for Surgical 
Implants. According to section 5.1 of ASTM F2759: Standard Guide for Assessment of 
the Ultra High Molecular Weight Polyethylene (UHMWPE) Used in Orthopedic and 
Spinal Devices, fabricated forms of conventional UHMWPE are manufactured by 
                                                          
1 Available at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm. 
2 Available at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176. 
2 Contains Nonbinding Recommendations 
compression molding or ram extrusion and [have] not been intentionally cross-linked 
before terminal sterilization.3  
B.  Highly Crosslinked UHMWPE (HXLPE) 
HXLPE originates from virgin resin powders or consolidated forms conforming to 
ASTM F648. This material type includes UHMWPE that has been highly crosslinked by 
various methods. According to section 5.2 of ASTM F2759, fabricated forms of 
extensively radiation-crosslinked UHMWPE, a subset of HXLPE, are manufactured by 
compression molding or extrusion and irradiated with a dosage higher than 40 kGy of 
gamma or e-beam radiation for improved wear resistance.4
This material type may also include HXLPE that has been extensively crosslinked by 
methods other than ionizing radiation (e.g., peroxides, silane, high temperature exposure). 
C.    Antioxidant Highly Crosslinked UHMWPE (AO-HXLPE) 
AO-HXLPE material originates from virgin resin powders or consolidated forms 
conforming to ASTM F648 and/or ASTM F2695: Standard Specification for Ultra-High 
Molecular Weight Polyethylene Powder Blended with Alpha-Tocopherol (Vitamin E) and 
Fabricated Forms for Surgical Implant Applications. According to section 5.3 of ASTM 
F2759, Two stabilizing methods for the antioxidant UHMWPE form (Vitamin E-
stabilized or alpha-tocopherol) are blending or diffusing. The blending method has the 
Vitamin E mixed (blended) into the UHMWPE powder before consolidation and 
radiation cross-linking. The diffusing method has the Vitamin E diffusing into a 
consolidated UHMWPE form before or after radiation cross-linking. Also, antioxidant 
UHMWPE could potentially be used without any radiation cross-linking.5
D.  Non-Conventional UHMWPE 
Non-conventional UHMWPE is a polyethylene material other than the three material 
types discussed above. Examples may include, but are not limited to, materials that are 
made from lower molecular weight polyethylenes that may or may not be extensively 
crosslinked, porous polyethylenes, functionalized UHMWPE such as hyaluronic acid-
modified UHMWPE, or polyethylenes whose surfaces have been modified. These may or 
may not be stabilized with an antioxidant. 
                                                          
3 ASTM Standard F2759, 2011, Standard Guide for Assessment of the Ultra High Molecular Weight 
Polyethylene (UHMWPE) Used in Orthopedic and Spinal Devices, ASTM International, West Conshohocken, 
PA, 2011, DOI: 10.1520/F2759-11, www.astm.org. 
4 Ibid. 
5 Ibid. 
3 Contains Nonbinding Recommendations 
IV. Material Processing and Characterization
 
For all material types and submission types (510(k), De Novo, PMA, HDE, or IDE), FDA 
recommends that you provide the following general technical information regarding the 
UHMWPE material to establish the type of UHMWPE in use: 
  Starting resin (e.g., GUR 1020, GUR 1050); 
  Resin consolidation method (e.g., ram extrusion, compression molding); and 
  Terminal sterilization method.6 If radiation, type (e.g., gamma irradiation, electron beam) 
and delivered dose or equivalent measure should be provided, along with a description of 
the packaging and the environment in which it was packaged (e.g., barrier film, inert gas, 
vacuum). 
Depending on the type of UHMWPE, different mechanical and chemical characterization 
should be provided, as discussed in more detail below. This characterization information is 
summarized in Appendix 2. For information on recommended content and format of 
complete test reports for non-clinical bench performance testing in premarket submissions, 
refer to FDAs guidance, Recommended Content and Format of Non-Clinical Bench 
Performance Testing Information in Premarket Submissions.7 In cases where you believe 
the information or testing described in this document do not apply to your device, you should 
provide a rationale explaining why you believe the recommended information or testing are 
not applicable. 
A.  Conventional UHMWPE 
Material characteristics of conventional UHMWPE should conform to the specifications 
of ASTM F648 for both powder and fabricated forms, and we recommend that you 
include a declaration of conformity to ASTM F648, as appropriate, in your premarket 
submission.8 For orthopedic implants we recommend you consider the information 
summarized in Table 2 of ASTM F648, which identifies the material property 
specifications for conventional UHMWPE in fabricated form. Standard test methods 
typically used to assess these properties are also referenced in ASTM F648. You should 
provide the following material properties of your conventional UHMWPE in your 
regulatory submission to FDA: 
  Tensile properties (e.g., yield strength, ultimate tensile strength, and elongation at 
break); 
                                                          
6 Submission and Review of Sterility Information in Premarket Notification (510(k)) Submissions for Devices 
Labeled as Sterile, available at 
http://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm109897.p
df. 
7 Available at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM606051. 
8 For more information on the use of standards in premarket submissions, see Appropriate Use of Voluntary 
Consensus Standards in Premarket Submissions for Medical Devices 
(https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM077295). 
4 Contains Nonbinding Recommendations 
  Impact resistance (e.g., Izod); and 
  Density. 
  
If the material meets the specifications in ASTM F648, no additional information will 
typically be requested. However, if the materials properties are not within the 
specification range in the standard, then additional information should be provided to 
demonstrate that the device can perform as intended for its indicated use. 
We recommend that manufacturers refer to ASTM F2759 which provides general 
guidelines for physical, chemical, biocompatibility, mechanical, and preclinical 
assessments of UHMWPE in implantable orthopedic and spinal devices intended to 
replace a musculoskeletal joint. 
B.  Highly Crosslinked UHMWPE (HXLPE) 
HXLPE primarily differs from conventional UHMWPE in that extensively radiation-
crosslinked UHMWPE absorbs a relatively larger radiation dose and is then thermally 
processed. These differences alter the mechanical, physical, and chemical properties of 
the material, and these properties should be characterized. In addition to the information 
that is requested for conventional UHMWPE in Section IV.A, you should provide the 
following information in your regulatory submission to FDA: 
  Radiation type (e.g., gamma irradiation, electron beam) and delivered dose, inclusive 
of terminal sterilization, as measured by dosimeters or equivalent measures; 
  Percent crystallinity; 
  Melting temperature; 
  Trans-vinylene index throughout the sample; 
  Post-accelerated aging testing (e.g., oxidation index throughout the sample to 
compare pre- and post-aging properties and/or mechanical properties that demonstrate 
no adverse effect on performance); 
  Crosslink density; 
  Fatigue resistance crack propagation testing (K , Paris exponent, Paris 
inception
coefficient); 
  Free radical concentration; 
  Time, temperature, and rationale for all post-crosslinking thermal processing steps 
such as heating above the melt temperature of UHMWPE or annealing below the melt 
temperature (e.g., to reduce/eliminate free radicals, relieve internal stresses); and 
  Compression ratio of mechanical thermal processing steps. 
We recommend that characterization tests listed above be performed per the current 
FDA-recognized standards, ASTM F2759 and ASTM F2565: Standard Guide for 
Extensively Irradiation-Crosslinked Ultra-High Molecular Weight Polyethylene 
Fabricated Forms for Surgical Implant Applications, which reference standard test 
methods recommended to assess this information. 
5 Contains Nonbinding Recommendations 
If the measured values lie within an acceptable range, as determined by comparison to 
either another legally marketed device with the same intended use or literature, no 
additional information will typically be requested. However, if the materials properties 
lie outside the previously accepted range, then additional information should be provided 
to demonstrate that the device can perform as intended for its indicated use. 
For the characterization of properties that are also recommended for conventional 
UHMWPE, such as tensile properties, impact resistance, and density, we consider the 
minimum specifications set forth in ASTM F648 to be acceptable for highly crosslinked 
polyethylenes, which are outside the scope of that standard.  If the material meets the 
specifications of ASTM F648, no additional information will typically be requested to 
characterize these properties. However, if the materials properties do not meet these 
acceptance criteria, then additional information should be provided as recommended in 
the preceding paragraph.  
During the radiation crosslinking process, free radicals are produced, and the free radical 
concentration directly influences the oxidative stability of the material. As a result, post 
irradiation thermal treatment of the polymer is performed to reduce or eliminate the free 
radical concentration and to ensure the long term oxidative stability of the polyethylene.  
For materials thermally processed above or below the melt temperature, the free radical 
concentration should be determined. There currently is no standard test method for 
determining free radical concentration. Free radical concentration is typically assessed 
using electron paramagnetic resonance (EPR) spectroscopy, also known as electron spin 
resonance (ESR) spectroscopy. The test method you choose should be fully described and 
justified in your submission and the limit-of-detection of EPR/ESR measurements should 
be included in the test reports. We recommend that, in addition to supplying the measured 
concentration of free radicals, spectrographs showing the free radical spectra should also 
be provided. 
Some properties, such as wear, fatigue crack propagation resistance, and morphology of 
the fabricated form (i.e., consolidation quality, per Annex 2.1 of ASTM F648-14), are 
comparative in nature. No acceptance criteria are specified.  These properties should be 
evaluated in a manner that demonstrates that the device can perform as intended for its 
indicated use. 
Finally, device-specific impingement and/or fatigue studies should also be carried out on 
HXLPE in its final component design form factor to test locking mechanisms, posts, and 
other design features that may be sensitive to fatigue crack propagation. Refer to the 
recommendations in any applicable device-specific guidance document, when available, 
or contact the appropriate review division for comments on proposed testing. 
For UHMWPE that has been extensively crosslinked by methods other than ionizing 
radiation (e.g., peroxides, silane, high temperature exposure), additional tests may be 
requested depending on the crosslinking procedures, such as assessment of residual 
peroxide concentration and reaction by-products.  If a different crosslinking method is 
used, we recommend discussing your proposed procedures and any additional 
6 Contains Nonbinding Recommendations 
characterization assessments with the Agency prior to submission of a marketing 
application.  Please refer to the guidance Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug 
Administration Staff9 for more information on meetings with FDA staff. 
C.  Antioxidant Highly Crosslinked UHMWPE (AO-HXLPE) 
AO-HXLPE primarily differs from HXLPE in that an antioxidant (e.g., -tocopherol) is 
added either before or after exposure to radiation and the material is not thermally 
processed above its melting temperature. In addition to the information that is requested 
for conventional UHMWPE in Section IV.A, and HXLPE in Section IV.B., the following 
additional characterization information should be provided to address specific concerns 
raised by the addition of antioxidants: 
1.  Concentration and identification of antioxidant or other additives (in weight percent 
(wt. %) and parts per million (ppm) or as a Vitamin E index or equivalent).10
2.  Stability of antioxidant in the material.  It is possible that the added antioxidant may 
leach out over time due to loading and/or in vivo fluids that act as a solvent for the 
antioxidant. The loss of the antioxidant may undermine the materials oxidation 
resistance. This concern can be addressed by demonstrating adequate oxidation 
resistance following wear testing where the material is exposed to clinically relevant 
loads and solvents. 
3.  Effect of antioxidant on the wear mechanism.  An antioxidant may affect the 
mechanism by which the material wears.  FDA recommends that you assess if the 
wear mechanism has been altered due to the addition of the antioxidant by 
characterizing the wear debris from wear testing of the new device per ASTM F1877: 
Standard Practice for Characterization of Particles.  In addition, wear testing under 
normal and abrasive wear conditions should be performed. An analysis of the wear 
rates and wear surfaces in terms of type and extent of damage modes should also be 
provided. The anticipated, or known, impact of the wear test results on device 
performance should be thoroughly discussed and supported with available literature 
and scientific rationale (e.g., comparison to the control, animal studies11).  
Alternatively, it may be possible to address this concern by supplying a scientific 
rationale comparing the antioxidant type, concentration, radiation dose, and radiation 
type (i.e., gamma or electron beam) to a legally-marketed, antioxidant-containing 
device with a similar intended use.  
                                                          
9 Available at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176. 
10 Oral E, Neils A, Muratoglu OK. 2014. High vitamin E content, impact resistant UHMWPE blend without 
loss of wear resistance. J Biomed Mater Res Part B 2015:103B:790797. 
11 FDA supports the principles of the 3Rs, to reduce, refine, and replace animal use in testing when feasible. 
We encourage sponsors to consult with us if it they wish to use a non-animal testing method they believe is 
suitable, adequate, validated, and feasible. We will consider if such an alternative method could be assessed for 
equivalency to an animal test method. 
7 Contains Nonbinding Recommendations 
We recommend contacting the appropriate review division for questions regarding 
device-specific wear testing.  
The following FDA-recognized standards may be helpful when performing wear 
testing: 
  ASTM F732: Standard Test Method for Wear Testing of Polymeric Materials 
Used in Total Joint Prostheses 
  ASTM F1714: Standard Guide for Gravimetric Wear Assessment of Prosthetic 
Hip Designs in Simulator Devices 
  ASTM F2423: Standard Guide for Functional, Kinematic, and Wear Assessment 
of Total Disc Prostheses 
  ISO 14242-1: Implants for surgery  Wear of total hip-joint prostheses- Part 1: 
Loading and displacement parameters for wear-testing machines and 
corresponding environmental conditions for test 
  ISO 14242-2: Implants for surgery  Wear of total hip-joint prostheses  Part 2: 
Methods of measurement 
  ISO 14242-3: Implants for surgery  Wear of total hip-joint prostheses  Part 3: 
Loading and displacement parameters for orbital bearing type wear testing 
machines and corresponding environmental conditions for test 
  ISO 14243-1: Implants for surgery  Wear of total knee-joint prostheses  Part 1: 
Loading and displacement parameters for wear-testing machines with load 
control and corresponding environmental conditions for test 
  ISO 14243-2: Implants for surgery  Wear of total knee-joint prostheses  Part 2: 
Methods of measurement 
  ISO 14243-3: Implants for surgery  Wear of total knee-joint prostheses  Part 3: 
Loading and displacement parameters for wear-testing machines with 
displacement control and corresponding environmental conditions for test 
  ISO 18192-1: Implants for surgery  Wear of total intervertebral spinal disc 
prostheses- Part 1: Loading and displacement parameters for wear testing and 
corresponding environmental conditions for test 
  ISO 18192-2: Implants for surgery  Wear of total intervertebral spinal disc 
prostheses  Part 2: Nucleus replacements 
4.  Effect of antioxidant on material consolidation.  When an antioxidant is added to the 
UHMWPE powder prior to consolidation, its presence may hinder powder 
consolidation. Therefore, FDA recommends that the morphology of the fabricated 
forms be assessed as described in Annex 2 of ASTM F648-14. 
5.  Biocompatibility should be evaluated per the recommendations in Section V, below. 
If additional concerns not discussed above are identified based on the material 
characterization, additional information such as preclinical or clinical data may be 
requested to mitigate these concerns. 
8 Contains Nonbinding Recommendations 
D.  Non-Conventional UHMWPE 
As non-conventional UHMWPE is not clearly defined, it is not possible to provide 
specific testing recommendations at this time. We encourage you to submit a Pre-
Submission with specific questions to be discussed for non-conventional UHMWPE 
devices. For additional information regarding the Pre-Submission process, refer to the 
Guidance for Industry and FDA Staff, Requests for Feedback on Medical Device 
Submissions: The Pre-Submission Program and Meetings with Food and Drug 
Administration Staff.12
In addition to the testing discussed above, we recommend you consider the following 
points: 
  Compression properties of the material; 
  Crystal size and structure; 
  Creep resistance; and 
  Durability of modified surface. 
If additional concerns are identified based on the material characterization, additional 
information such as additional preclinical or clinical data may be requested to mitigate 
these concerns. 
V. Biocompatibility 
UHMWPE materials used in implantable orthopedic devices are patient-contacting materials, 
which, when used for their intended purpose (i.e., contact type and duration), may induce a 
harmful biological response. 
You should determine the biocompatibility of all patient-contacting materials present in your 
device.  If the subject device uses the identical UHMWPE materials and manufacturing 
processes as a legally marketed device with a history of safe use, you may reference previous 
testing experience or literature, if appropriate. 
If you are unable to identify a legally marketed device with similar location/duration of 
contact and intended use that uses the same materials and manufacturing processes as used in 
your device, we recommend you conduct and provide a biocompatibility risk assessment. 
The assessment should explain the relationship between the identified biocompatibility risks, 
the information available to mitigate the identified risks, and any knowledge gaps that 
remain. You should then identify any biocompatibility testing or other evaluations that were 
conducted to mitigate any remaining risks. If your biocompatibility assessment relies on 
                                                          
12 Available at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM311176. 
9 Contains Nonbinding Recommendations 
information regarding the raw material in a device Master File (MAF), we recommend that 
you include a Letter of Authorization (LOA) for the relevant Master File, and ensure that you 
address the subsequent processing, cleaning, and sterilization steps to address the 
biocompatibility of the final sterilized device.   In addition, you may declare conformity to a 
recognized material consensus standard, if applicable. 
We recommend that you follow FDAs guidance Use of International Standard ISO 10993-
1, Biological evaluation of medical devices  Part 1: Evaluation and testing within a risk 
management process13 (referred to as CDRHs 2016 Biocompatibility Guidance), which 
identifies the type of biocompatibility assessments that should be considered and 
recommendations regarding how to conduct related tests, if applicable. 
Per ISO 10993-1 and Attachment A of CDRHs 2016 Biocompatibility Guidance, most 
orthopedic devices that incorporate UHMWPE are considered implant devices in contact 
with tissue/bone for a permanent contact duration. Therefore, the following endpoints should 
be addressed in your biocompatibility evaluation:  
  Cytotoxicity; 
  Sensitization; 
  Irritation or Intracutaneous Reactivity; 
  Acute Systemic Toxicity; 
  Material-Mediated Pyrogenicity; 
  Subchronic toxicity (Sub-acute toxicity); 
  Genotoxicity (We recommend that both mutagenicity and clastogenicity be assessed.); 
  Implantation; 
  Chronic Toxicity; and 
  Carcinogenicity. 
For device-specific, patient-contacting device instrumentation in contact with tissue/bone for 
a temporary contact duration, the following endpoints should be addressed in your 
biocompatibility evaluation: 
  Cytotoxicity; 
  Sensitization; 
  Irritation or Intracutaneous Reactivity; 
  Acute Systemic Toxicity; and 
  Material-Mediated Pyrogenicity. 
The following additional considerations are recommended for components made from 
UHMWPE materials containing antioxidants: 
                                                          
13 Available at 
https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/UCM348890. 
10 Contains Nonbinding Recommendations 
  The addition of antioxidants raises concerns regarding the biocompatibility of the 
antioxidant itself and the biocompatibility of radiation-induced degradation products. The 
second concern generally applies to materials that contain the antioxidant and have been 
exposed to radiation (i.e., AO-HXLPE, or possibly Non-Conventional UHMWPE). For 
tissue/bone contacting, permanently implanted devices, FDA recommends that you 
submit a biocompatibility evaluation as per CDRHs 2016 Biocompatibility Guidance, 
referenced above. 
  Wear debris is an important consideration for any UHMWPE-containing, articulating 
device component.  Therefore, the bodys response to any antioxidant and associated 
degradation products leached from the wear debris should be assessed. This may be 
accomplished via injecting wear particles from the wear simulator or other representative 
particles into an appropriate animal model. The results of the test should be compared to 
a control. We encourage you to submit a Pre-Submission with a testing protocol for 
review prior to initiating animal testing. As an alternative to the animal testing, it may be 
possible to demonstrate that the wear debris generated has similar size/number/shape of 
particles as other similar, legally marketed devices, and the antioxidant and its 
degradation products are not bioavailable. 
VI. Shelf Life and Packaging 
Shelf-life testing is conducted to support the proposed expiration date through evaluation of 
the package integrity for maintaining device sterility and evaluation of any changes to device 
performance or functionality. 
With respect to package integrity for maintaining device sterility, you should provide a 
description of the packaging, including how it will maintain the devices sterility. Depending 
on submission type, you should also provide the protocol(s) used for your package integrity 
testing, the results of the testing, and the conclusions drawn from your results.   FDA 
recommends that package integrity test methods include simulated distribution and 
associated package integrity, as well as simulated (and/or real-time) aging and associated seal 
strength testing, to validate package integrity and shelf life claims. We recommend you 
follow the methods described in the FDA-recognized series of consensus standards ISO 
11607-1: Packaging for terminally sterilized medical devices  Part 1: Requirements for 
materials, sterile barrier systems and packaging systems, and ISO 11607-2: Packaging for 
terminally sterilized medical devices  Part 2: Validation requirements for forming, sealing 
and assembly processes. 
The mechanical properties of UHMWPE that contains unstable free radicals may degrade if 
the product is exposed to air during shelf storage. In addition, the shelf life of UHMWPE that 
has been irradiated and packaged in an inert environment may be limited by the integrity of 
the packaging material. Therefore, FDA recommends that the stability of UHMWPE 
materials used in implantable devices be assessed for the duration of their specified shelf life. 
With respect to evaluating the effects of aging on device performance or functionality, shelf 
life studies should evaluate the critical device properties to ensure that it will perform 
adequately and consistently during the entire proposed shelf life. To evaluate device 
11 Contains Nonbinding Recommendations 
functionality, we recommend that you assess each of the relevant bench tests described in 
Section IV and repeat all tests that evaluate design components or characteristics that are 
potentially affected by aging. 
If you intend to extend the shelf-life of the device after initial approval, we recommend that 
you provide the methods or protocol(s) to support the extension in the original submission. 
We recommend devices undergo real-time aging to determine definitively the effects of 
aging on the maintenance of sterility and device performance. If you use devices subjected to 
accelerated aging, we recommend that you specify the way in which the device was aged and 
develop a rationale to explain how the results of shelf life testing based on accelerated aging 
are representative of the results if the device were aged in real time. We recommend that you 
age your devices as per the currently FDA-recognized version of ASTM F1980: Standard 
Guide for Accelerated Aging of Sterile Barrier Systems for Medical Devices and specify the 
environmental parameters established to attain the expiration date. Testing of real-time aged 
devices can be conducted in parallel with submission review, with results documented to file 
in the design history file (i.e., complete test reports do not need to be submitted to FDA). 
12 Contains Nonbinding Recommendations 
Appendix 1.  FDARecognized Standards Applicable to 
UHMWPE Evaluation
Standard Number  Standard Title 
ASTM E647  Standard Test Method for Measurement of Fatigue Crack Growth Rates 
Standard Specification for Ultra-High-Molecular-Weight Polyethylene Powder and 
ASTM F648 
Fabricated Form for Surgical Implants 
Standard Test Method for Wear Testing of Polymeric Materials Used in Total Joint 
ASTM F732 
Prostheses 
Standard Guide for Gravimetric Wear Assessment of Prosthetic Hip Designs in Simulator 
ASTM F1714 
Devices 
ASTM F1877  Standard Practice for Characterization of Particles 
Standard Practice for Accelerated Aging of Ultra-High Molecular Weight Polyethylene after 
ASTM F2003 
Gamma Irradiation in Air 
Standard Guide for Evaluating the Extent of Oxidation in Polyethylene Fabricated Forms 
ASTM F2102 
Intended for Surgical Implants 
Standard Test Method for In Situ Determination of Network Parameters of Crosslinked Ultra 
ASTM F2214 
High Molecular Weight Polyethylene (UHMWPE) 
Standard Test Method for Evaluating Trans-Vinylene Yield in Irradiated Ultra-High 
ASTM F2381  Molecular-Weight Polyethylene Fabricated Forms Intended for Surgical Implants by Infrared 
Spectroscopy 
ASTM F2423  Standard Guide for Functional, Kinematic, and Wear Assessment of Total Disc Prostheses 
Standard Guide for Extensively Irradiation-Crosslinked Ultra-High Molecular Weight 
ASTM F2565 
Polyethylene Fabricated Forms for Surgical Implant Applications 
Standard Test Method for Measurement of Enthalpy of Fusion, Percent Crystallinity, and 
ASTM F2625  Melting Point of Ultra-High-Molecular Weight Polyethylene by Means  of Differential 
Scanning Calorimetry 
Standard Specification for Ultra-High Molecular Weight Polyethylene Powder Blended with 
ASTM F2695 
Alpha-Tocopherol (Vitamin E) and Fabricated Forms for Surgical Implant Applications 
Standard Guide for Assessment of the Ultra High Molecular Weight Polyethylene 
ASTM F2759 
(UHMWPE) Used in Orthopedic and Spinal Devices 
ISO 5834-1  Implants for surgery  Ultra-high-molecular-weight polyethylene  Part 1:  Powder form 
Implants for surgery  Ultra-high-molecular-weight polyethylene  Part 3:  Accelerated 
ISO 5834-3 
ageing methods 
Implants for surgery  Ultra-high-molecular-weight polyethylene  Part 4:  Oxidation index 
ISO 5834-4 
measurement method 
Implants for surgery  Ultra-high-molecular-weight polyethylene  Part 5:  Morphology 
ISO-5834-5 
assessment method 
Implants for surgery  Wear of total hip-joint prostheses  Part 1: Loading and displacement 
ISO 14242-1 
parameters for wear-testing machines and corresponding environmental conditions for test 
ISO 14242-2  Implants for surgery  Wear of total hip-joint prostheses  Part 2: Methods of measurement 
Implants for surgery  Wear of total hip-joint prostheses  Part 3: Loading and displacement 
ISO 14242-3  parameters for orbital bearing type wear testing machines and corresponding environmental 
conditions for test 
13 Contains Nonbinding Recommendations 
Implants for surgery  Wear of total knee-joint prostheses  Part 1: Loading and displacement 
ISO 14243-1  parameters for wear-testing machines with load control and corresponding environmental 
conditions for test 
ISO 14243-2  Implants for surgery  Wear of total knee-joint prostheses  Part 2: Methods of measurement 
Implants for surgery  Wear of total knee-joint prostheses  Part 3: Loading and displacement 
ISO 14243-3  parameters for wear-testing machines with displacement control and corresponding 
environmental conditions for test 
Implants for surgery  Wear of total intervertebral spinal disc prostheses  Part 1: Loading 
ISO 18192-1  and displacement parameters for wear testing and corresponding environmental conditions for 
test 
Implants for surgery  Wear of total intervertebral spinal disc prostheses  Part 2: Nucleus 
ISO 18192-2 
replacements 
Biological evaluation of medical devices  Part 1: Evaluation and testing within a risk 
ISO 10993-1 
management process 
Refer to FDAs consensus standards database 
(https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfStandards/search.cfm) to identify the most current 
version of the standard recognized by FDA, as well as the extent of recognition. 
14 Contains Nonbinding Recommendations 
Appendix 2.  Summary of Characterization Information 
for Various UHMWPE Materials14 
AO- Non-
Property  Conventional  HXLPE  Relevant Standards 
HXLPE  Conventional 
Tensile Properties  X  X  X  X  ASTM F648, 
ASTM F2759 
Crystallinity, 
ASTM F2625, 
Melting  X  X  X* 
ASTM F2759 
Temperature 
Impact Resistance  X  X  X  X  ASTM F648, ASTM 
F2565, ASTM F2759 
Trans-vinylene  ASTM F2381, ASTM 
X  X  X* 
index  F2625, ASTM F2759 
Post-accelerated 
Aging; Maximum 
ASTM F2003, ASTM 
Oxidation Index,  X  X  X* 
2102, ASTM F2759 
and/or Mechanical 
Properties 
Density  X  X  X  X  ASTM F648 
Crosslink Density  X  X  X*  N/A 
ASTM F2565, 
Fatigue Resistance  X  X  X 
ASTM F2759 
Free Radical 
X  X  X*  N/A 
Concentration 
Morphology  ASTM F648 (Annex 2) 
X  X* 
Testing 
* As applicable. 
                                                          
14 Note that this table is not all-inclusive. Refer to the main body of this guidance document for additional 
information that should be provided to characterize the material. 
15