ASTM F2847-17

Standard Practice for Reporting and Assessment of Residues on Single-Use Implants and Single-Use Sterile Instruments

SIGNIFICANCE AND USE
5.1 The quality and consequently the clinical performance of implants may be affected by residues. Residues may induce no tissue response, minor tissue irritations, or they may lead to local inflammation of tissues surrounding the implant which may lead to failure in short-term or long-term use. Residues may also cause harm at locations away from the implant. Residues may originate from manufacturing materials used in the course of processing or from the manufacturing environment, or may be the result of handling and packaging (1-3).10  
5.2 This practice shall be used to report the results of testing for residue. All residues cannot necessarily be detected. It suggests standard techniques that may be applied for analysis, and provides suggestions for how limit values may be set.  
5.3 Residues may be of inorganic, organic, or biological nature. They may exhibit as surface-bound substance, or as adsorbates (for example, electrostatically held), efflorescence, or mechanically held substances. Residues may be soluble in aqueous media, soluble in organic solvents, or may be insoluble particulates.  
5.4 Data generated in validation processes (that is, cleaning validation or sterility validation) may be used as results or as basis for setting acceptance criteria in the report.
SCOPE
1.1 The purpose of this practice is to describe how the cleanliness of single-use implants as manufactured shall be reported. This practice proposes how to approach the identification of critical compounds and suggests different analytical methods.  
1.2 The practice does not address substances which are intrinsic to the implant properties or design. In particular, it does not address substances released during implant resorption, implant coatings, or leachables by design.  
1.3 This practice does not address the cleanliness of implants which are re-processed, re-cleaned after unpacking for re-use in the hospital or by the manufacturer.  
1.4 This practice does not establish limit values for residues.  
1.5 This practice suggests appropriate test methods for the general specification of residues and residue requirements of implants and single-use sterile instruments. This practice may also be used to characterize semi-finished components for implants.  
1.6 The test methods suggested and described herein refer to established analytical methods and to existing standard methods for chemical, biochemical, or biological analysis.  
1.7 This practice is intended solely to provide guidance regarding suitable test methods and reporting conventions for residues, which may or may not affect implant biocompatibility. This practice does not suggest or recommend test methods for biocompatibility, which may be found in Practice F748 or in ISO 10993-1.  
1.8 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility of the user of this standard to establish appropriate safety, health, and environmental practices and determine the applicability of regulatory limitations prior to use.  
1.9 This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.

General Information

• Status: Published
• Publication Date: 14-Sep-2017
• ICS: 11.040.40 - Implants for surgery, prosthetics and orthotics
• Technical Committee: F04 - Medical and Surgical Materials and Devices
• Drafting Committee: F04.15 - Material Test Methods

Relations

• Replaces: ASTM F2847-10 - Standard Practice for Reporting and Assessment of Residues on Single Use Implants
• Effective Date: 15-Sep-2017
• Refers: ASTM E1504-11(2019) - Standard Practice for Reporting Mass Spectral Data in Secondary Ion Mass Spectrometry (SIMS)
• Effective Date: 01-Nov-2019
• Refers: ASTM E1635-06(2019) - Standard Practice for Reporting Imaging Data in Secondary Ion Mass Spectrometry (SIMS)
• Effective Date: 01-Nov-2019
• Refers: ASTM E996-19 - Standard Practice for Reporting Data in Auger Electron Spectroscopy and X-ray Photoelectron Spectroscopy
• Effective Date: 01-Apr-2019
• Refers: ASTM F561-19 - Standard Practice for Retrieval and Analysis of Medical Devices, and Associated Tissues and Fluids
• Effective Date: 01-Jan-2019
• Refers: ASTM G121-18 - Standard Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
• Effective Date: 01-Dec-2018
• Refers: ASTM E996-10(2018) - Standard Practice for Reporting Data in Auger Electron Spectroscopy and X-ray Photoelectron Spectroscopy
• Effective Date: 01-Nov-2018
• Refers: ASTM F2459-18 - Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis
• Effective Date: 01-Feb-2018
• Refers: ASTM F1877-16 - Standard Practice for Characterization of Particles
• Effective Date: 01-Oct-2016
• Refers: ASTM G136-03(2016) - Standard Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
• Effective Date: 01-May-2016
• Refers: ASTM G131-96(2016) - Standard Practice for Cleaning of Materials and Components by Ultrasonic Techniques
• Effective Date: 01-May-2016
• Refers: ASTM F748-16 - Standard Practice for Selecting Generic Biological Test Methods for Materials and Devices
• Effective Date: 01-Apr-2016
• Refers: ASTM F561-13 - Standard Practice for Retrieval and Analysis of Medical Devices, and Associated Tissues and Fluids
• Effective Date: 01-Sep-2013
• Refers: ASTM F2459-12 - Standard Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis
• Effective Date: 01-Mar-2012
• Refers: ASTM E1504-11 - Standard Practice for Reporting Mass Spectral Data in Secondary Ion Mass Spectrometry (SIMS)
• Effective Date: 01-Nov-2011

Overview

ASTM F2847-17, Standard Practice for Reporting and Assessment of Residues on Single-Use Implants and Single-Use Sterile Instruments, provides comprehensive guidelines for identifying, reporting, and assessing residues on single-use medical implants and sterile instruments. Developed by ASTM International, this standard outlines best practices to help manufacturers and laboratories ensure that medical devices are free from potentially harmful contamination that could impact patient safety or device performance. The standard addresses requirements for residue classification, selection of appropriate analytical methods, and the preparation of effective cleanliness reports essential for regulatory compliance and quality assurance.

Key Topics

• Residue Types: Covers the identification and reporting of inorganic, organic, biological (including microbiological), and particulate residues.
• Sample Preparation and Analysis: Guidance on sample handling, extraction, and analysis, including both in-situ and extract-based approaches.
• Test Methods: Suggests established analytical techniques (e.g., ICP-OES, FTIR, TOC, GC-MS, SEM, XPS) for residue detection and quantification, tailored to different residue types.
• Reporting Requirements: Recommends standardized reporting formats, including key parameters such as detection limits, measurement results, acceptance criteria, and analytical methods used.
• Residue Classification: Urges residues to be classified and reported according to their nature (inorganic, organic, biological, particulate).
• Limit Values: Provides guidance on developing company-specific acceptance criteria for residue levels, though it does not set regulatory limit values.
• Validation and Quality Assurance: Addresses validation of analytical methods, manufacturing controls, risk-based approaches, and alignment with regulatory and industry benchmarks.

Applications

The practical value of ASTM F2847-17 lies in its application across the medical device industry, especially for manufacturers and quality assurance professionals involved with:

• Single-use Implants: Supports documentation and risk management for orthopedic, dental, cardiovascular, and other implants delivered for one-time use.
• Sterile Surgical Instruments: Ensures sterility and cleanliness of instruments to prevent patient harm and meet regulatory expectations.
• Product Qualification and Regulatory Submissions: Facilitates preparation of cleanliness reports required by regulatory authorities, contributing to faster product approvals and market entry.
• Process Validation: Assists manufacturers in setting up validated cleaning and sterilization processes, with data-driven criteria for residue acceptability.
• Supplier and Contract Manufacturer Oversight: Provides a common framework for cleanliness evaluation, streamlining communication between original equipment manufacturers and suppliers.

By following this standard, organizations can systematically identify, analyze, and minimize chemical, biological, and particulate contamination, thereby supporting patient safety and compliance with global regulatory requirements.

Related Standards

Several other ASTM standards and international guidelines are referenced in ASTM F2847-17, offering additional detail and harmonization for residue analysis and reporting. Key related documents include:

• ASTM E29: Practice for Using Significant Digits in Test Data
• ASTM E996: Practice for Reporting Data in Auger Electron and X-ray Photoelectron Spectroscopy
• ASTM F2459: Method for Extracting Residue from Metallic Medical Components
• ASTM F748: Practice for Selecting Generic Biological Test Methods (see also ISO 10993-1)
• ASTM F561, F1877, G121, G131, G136: Various guidance on specimen handling, cleaning, and surface analysis
• ISO 10993 Series: Biological evaluation of medical devices, particularly ISO 10993-1, -17, and -18
• ISO 11737-1: Determination of bioburden
• United States Pharmacopeia (USP) <85>, <161>, <231>, <232>, <233>: Testing protocols for endotoxin, elemental impurities, and organics
• AAMI ST72: Bacterial Endotoxins Testing

By integrating the recommendations and methods from ASTM F2847-17 and its related standards, medical device companies can strengthen cleanliness assessments and maintain high standards for product safety throughout the manufacturing and supply chain.

Keywords: residue analysis, cleanliness assessment, single-use medical implants, sterile instruments, ASTM F2847-17, standard reporting, medical device contamination, risk management, analytical methods, regulatory compliance.

Standards Content (Sample)

This international standard was developed in accordance with internationally recognized principles on standardization established in the Decision on Principles for the
Development of International Standards, Guides and Recommendations issued by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
Designation: F2847 − 17
Standard Practice for
Reporting and Assessment of Residues on Single-Use
Implants and Single-Use Sterile Instruments
This standard is issued under the fixed designation F2847; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope 1.9 This international standard was developed in accor-
dance with internationally recognized principles on standard-
1.1 The purpose of this practice is to describe how the
ization established in the Decision on Principles for the
cleanliness of single-use implants as manufactured shall be
Development of International Standards, Guides and Recom-
reported. This practice proposes how to approach the identifi-
mendations issued by the World Trade Organization Technical
cation of critical compounds and suggests different analytical
Barriers to Trade (TBT) Committee.
methods.
1.2 The practice does not address substances which are
2. Referenced Documents
intrinsic to the implant properties or design. In particular, it
2.1 ASTM Standards:
doesnotaddresssubstancesreleasedduringimplantresorption,
E29 Practice for Using Significant Digits in Test Data to
implant coatings, or leachables by design.
Determine Conformance with Specifications
1.3 This practice does not address the cleanliness of im-
E996 Practice for Reporting Data in Auger Electron Spec-
plants which are re-processed, re-cleaned after unpacking for
troscopy and X-ray Photoelectron Spectroscopy
re-use in the hospital or by the manufacturer.
E1078 Guide for Specimen Preparation and Mounting in
Surface Analysis
1.4 Thispracticedoesnotestablishlimitvaluesforresidues.
E1504 PracticeforReportingMassSpectralDatainSecond-
1.5 This practice suggests appropriate test methods for the
ary Ion Mass Spectrometry (SIMS)
general specification of residues and residue requirements of
E1635 Practice for Reporting Imaging Data in Secondary
implants and single-use sterile instruments. This practice may
Ion Mass Spectrometry (SIMS)
also be used to characterize semi-finished components for
E1829 Guide for Handling Specimens Prior to Surface
implants.
Analysis
1.6 Thetestmethodssuggestedanddescribedhereinreferto
F561 Practice for Retrieval and Analysis of Medical
established analytical methods and to existing standard meth-
Devices, and Associated Tissues and Fluids
ods for chemical, biochemical, or biological analysis.
F748 PracticeforSelectingGenericBiologicalTestMethods
for Materials and Devices
1.7 This practice is intended solely to provide guidance
F1251 Terminology Relating to Polymeric Biomaterials in
regarding suitable test methods and reporting conventions for
Medical and Surgical Devices (Withdrawn 2012)
residues, which may or may not affect implant biocompatibil-
F1877 Practice for Characterization of Particles
ity. This practice does not suggest or recommend test methods
F2459 Test Method for Extracting Residue from Metallic
for biocompatibility, which may be found in Practice F748 or
Medical Components and Quantifying via Gravimetric
in ISO 10993-1.
Analysis
1.8 This standard does not purport to address all of the
F2809 Terminology Relating to Medical and Surgical Mate-
safety concerns, if any, associated with its use. It is the
rials and Devices
responsibility of the user of this standard to establish appro-
G121 Practice for Preparation of Contaminated Test Cou-
priate safety, health, and environmental practices and deter-
pons for the Evaluation of Cleaning Agents
mine the applicability of regulatory limitations prior to use.
G131 PracticeforCleaningofMaterialsandComponentsby
1 2
ThispracticeisunderthejurisdictionofASTMCommitteeF04onMedicaland For referenced ASTM standards, visit the ASTM website, www.astm.org, or
Surgical Materials and Devices and is the direct responsibility of Subcommittee contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM
F04.15 on Material Test Methods. Standards volume information, refer to the standard’s Document Summary page on
Current edition approved Sept. 15, 2017. Published October 2017. Originally the ASTM website.
approved in 2010. Last previous edition approved in 2010 as F2847 – 10. DOI: The last approved version of this historical standard is referenced on
10.1520/F2847-17. www.astm.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2847 − 17
Ultrasonic Techniques 2.5 Association for the Advancement of Medical Instrumen-
G136 Practice for Determination of Soluble Residual Con- tation (AAMI) Document:
taminants in Materials by Ultrasonic Extraction AAMI ST72 Bacterial Endotoxins—Test Methodologies,
Routine Monitoring, and Alternatives to Batch Testing
2.2 ISO Standards:
2.6 Other References:
ISO 10993-1 Biological Evaluation of Medical Devices—
FDA Guidance for Industry Pyrogen and Endotoxins Test-
Part 1: Evaluation and Testing
ing: Questions and Answers, June 2012
ISO 10993-17 Biological Evaluation of Medical Devices—
8270C EPA Methodologies for GC-MS
Part 17: Establishment ofAllowable Limits for Leachable
Substances
3. Terminology
ISO 10993-18 Biological Evaluation of Medical Devices—
3.1 Unless provided otherwise in 3.2, terminology shall be
Part 18: Chemical Characterization of Materials
in conformance with Terminology F1251 and with Terminol-
ISO 11737-1 Sterilization of Medical Devices—
ogy F2809.
Microbiological Methods—Part 1: Determination of a
Population of Microorganisms on Products
3.2 Definitions:
ISO 17294-1 Water Quality—Application of Inductively
3.2.1 action value, n—the amount(s) of substance(s) toler-
Coupled Plasma Mass Spectrometry (ICP-MS)—Part 1:
ated at the surface of an implant by the manufacturer before it
General Guidelines
will interfere with the manufacturing process.
ISO 17294-2 Water Quality—Application of Inductively
3.2.2 exhaustive extraction, n—extraction until the cumula-
Coupled Plasma Mass Spectrometry (ICP-MS)—Part 2:
tive residue change is analytically insignificant or less than
Determination of Selected Elements Including Uranium
10 % of the initial extract.
Isotopes
3.2.3 limit value, n—the maximum allowable amount(s) of
2.3 United States Pharmacopeia (USP) Documents:
substance(s) at the surface of an implant not yet found to be
<85> Bacterial Endotoxin Test
harmful for the surrounding tissues and organs. Its value is
<161> Transfusion and Infusion Assemblies and Similar
established and defined by the manufacturer.
Medical Devices
3.2.4 model residue, n—a single substance or a mixture of
<232> Elemental Impurities – Limits
substances that reflect the process materials likely to be
<233> Elemental Impurities – Procedures
encountered and used during the manufacturing of the device.
<631> Chromatography
<643> Total Organic Carbon
3.2.5 residue, n—a substance present at the surface of an
<730> Plasma Spectrochemistry implant or embedded therein that is not explicitly recognized
<731> Loss on Drying
and defined as part of the implant specification (special
<851> Spectrophotometry and Light Scattering definition for residue analysis of surfaces). It includes process-
based residues as well as contamination by environmental
2.4 European Pharmacopoeia (PhEUR) Documents:
factors (adsorbates).
2.2.23 Atomic Absorption Spectrometry
2.2.24 Absorption Spectrophotometry, Infrared
3.2.6 single-use implant, n—a medical device which is
2.2.25 Absorption Spectrophotometry, Ultraviolet and Vis-
intendedtobeimplantedpermanentlyandthatisnotre-cleaned
ible
or re-worked for a second implantation after eventual removal.
2.2.28 Gas Chromatography
3.2.7 soiling, n—procedureofapplyingknownamountsofa
2.2.29 Liquid Chromatography
substance onto a medical device for determination of process
2.2.43 Mass Spectrometry
capability, that is, cleaning efficiency and extraction yields.
2.2.44 Total Organic Carbon in Water for Pharmaceutical
3.2.8 spiking, n—procedureofapplyingexactquantitiesofa
Use
substance to an analyte for instrumental calibration and deter-
2.2.48 Raman Spectrometry
mination reaction yield.
2.2.57 Inductively Coupled Plasma-Atomic Emission Spec-
3.2.9 surface area, n—the projected surface area of a part.
trometry
This area does not include the internal porosity of parts with
2.2.58 Inductively Coupled Plasma-Mass Spectrometry
Available from Association for the Advancement of Medical Instrumentation
Available fromAmerican National Standards Institute (ANSI), 25 W. 43rd St., (AAMI), 4301 North Fairfax Drive, Suite 301, Arlington, VA 22203, http://
4th Floor, New York, NY 10036, http://www.ansi.org. www.aami.org.
5 8
Available from U.S. Pharmacopeia (USP), 12601Twinbrook Pkwy., Rockville, Available from Food and Drug Administration (FDA), 5600 Fishers Ln.,
MD 20852-1790, http://www.usp.org. Rockville, MD 20857, http://www.fda.gov.
6 9
Available from European Directorate for the Quality of Medicines and Available from United States Environmental Protection Agency (EPA), Ariel
HealthCare (EDQM), 7 allee Kastner, CS 30026, F67081, Strasbourg, France, Rios Bldg., 1200 Pennsylvania Ave., NW, Washington, DC 20460, http://
http://www.edqm.eu/en/News-and-General-Information-43.html. www.epa.gov.
F2847 − 17
cancellous, porous, or wire structure. It does include factors or mechanically held substances. Residues may be soluble in
that correct for the estimated surface roughness. aqueous media, soluble in organic solvents, or may be in-
soluble particulates.
4. Summary of Practice
5.4 Data generated in validation processes (that is, cleaning
4.1 This practice describes how to report residues on im-
validation or sterility validation) may be used as results or as
plant surfaces and indicates useful and typical applicable
basis for setting acceptance criteria in the report.
analytical methods.
4.2 Application of the test methods contained within this 6. Reporting of Residues on Implants
practice does not guarantee clinical success of a finished
6.1 The reporting of cleanliness of implants shall include a
implant,butitwillhelptoensureconsistencyinitscleanliness.
table that lists at least sections on (1) the chemical categories,
(2) the results of validation studies or of routine analysis, (3)
5. Significance and Use
the acceptance criteria if applicable, (4) the detection limits of
5.1 The quality and consequently the clinical performance
the methods used, and (5) the methods of analysis (see Table
of implants may be affected by residues. Residues may induce
1).
no tissue response, minor tissue irritations, or they may lead to
6.2 Categories of Residues:
local inflammation of tissues surrounding the implant which
6.2.1 Residues shall be classified, as needed, according to
may lead to failure in short-term or long-term use. Residues
the common description and reported accordingly as (I)
may also cause harm at locations away from the implant.
inorganic,(II)organic,(III)biologic,(IV)microbiological,and
Residues may originate from manufacturing materials used in
(V) particulate residues.
the course of processing or from the manufacturing
6.2.2 In this practice, inorganic residues are referred to as
environment, or may be the result of handling and packaging
substances of all elements with the exception of carbon-
(1-3).
containing substances. Carbonates, carbides, graphite, or
5.2 Thispracticeshallbeusedtoreporttheresultsoftesting
graphite-like structures (for example, diamond-like coatings)
for residue. All residues cannot necessarily be detected. It
are traditionally listed as inorganic substances.
suggests standard techniques that may be applied for analysis,
6.2.3 In this practice, organic residues are referred to as
and provides suggestions for how limit values may be set.
synthetic and natural carbon-based substances, including both
5.3 Residues may be of inorganic, organic, or biological
small molecules with low molecular mass (for example,
nature. They may exhibit as surface-bound substance, or as
paraffin or low viscosity oil) and high molecular mass based
adsorbates (for example, electrostatically held), efflorescence,
synthetic polymers. Polysilanes and -oxanes are also consid-
ered organic residues.
6.2.3.1 In this practice, microbiologic residues are to be
The boldface numbers in parentheses refer to the list of references at the end
listedseparatelyanddifferentiatedasbioburdenandendotoxin.
of this standard.
TABLE 1 Suggested Table for Reporting of Residues
NOTE 1—The reported table shall reflect the mean value of all measurements of a product and the error, including the error of the method.
NOTE2—ThecolumnAppliedAnalyticalMethodexemplifiesmethodsandapplicablestandards.Theycanbereplacedbyanymethod/standardprotocol
suitable for the particular residues.
Results of Set Limit Applied Analytical
Categories Detection Limit
B
Analysis Values Methods
Inorganic [mass/implant] [mass/implant] [mass/implant] ICP-MS
[mass/surface area] [mass/surface area] [mass/surface area] (USP <233>,
ISO 17294-2)
Organic GC-MS
(PhEur 2.2.28,
EPA 8270C)
Biological e-spray MS
(PhEur 2.2.43)
Bioburden [CFU/implant] [CFU/implant] [CFU/implant] ISO 11737-1
A
Endotoxin [EU/implant] EU/implant [EU/implant] USP<85>
AAMI ST72
Particulate [mass/implant] [mass/implant] [mass/implant] SEM (internal protocol)
[mass/surface area] [mass/surface area] [mass/surface area] XPS (ASTM E996)
[Number/implant] [Number/ implant] [Number/implant]
2 2 2 2 2 2
or [cm /cm ] or [cm /cm ] or [cm /cm ]
[Atomic-%] [Atomic-%] [Atomic-%]
or [Molecular-%] or [Molecular-%] or [Molecular-%]
Visual Inspection [Optical observations] [Optical observations] [Optical observations] (internal protocol)
A
Limit value as defined for device types listed in FDA Guidance for Industry Pyrogen and Endotoxins Testing: Questions and Answers (June 2012) or in USP <161>
Transfusion and Infusion Assemblies and Similar Medical Devices.
B
Analytical methods indicated in the column are examples of possible methods only. Each producer is asked to justify in a rationale why a specific method and standard
are used.
F2847 − 17
It should be noted that for medical devices sold sterile, 7.4.1 Worst-case implants or test coupons (regarding sur-
bioburden testing is often part of sterilization validation and is face texture, machined features) and soiling with identified
monitoredonapredeterminedscheduleforthepurposeofdose worst-case manufacturing materials may be used to reduce the
audits or process control. number of process analyses.
7.4.2 Protocols shall be validated for surface texture(s) and
6.2.4 In this practice, particulate residues are referred to as
material insoluble in aqueous media or organic solvent, which material(s) being analyzed.
7.4.3 Worst-case soiling compounds or model residues shall
can be removed from the surface of an implant by physical
and/or chemical means without interfering with the integrity of be relevant regarding composition, amount applied, and incu-
bation conditions. A detailed procedure for preparing test
the implant surface. Even though particulates shall be reported
separately, they belong to one of the chemical classes men- coupons is found in Practice G121.
tioned above.
7.5 In case of extraction protocols, validation shall include
6.3 Reported Units: the determination of recovery yields and the resulting accuracy
ofthemethodandtheacceptancecriteriaforsuccessfultesting.
6.3.1 Results of inorganic and organic analysis shall be
reported as mass per implant or mass per surface area, or both
7.6 Each method of analysis shall be established with
(use SI units).
detection and quantification limits.
6.3.2 Results of biological analysis shall be reported in the
7.7 Quantification limits of methods shall be at least one
specificunitsperimplant,thatis,enumerationmethodssuchas
order of magnitude lower than the respective set limit values
colony forming unit (CFU), or enzymatic assays such as for
for robust data.
example, endotoxin units (EUs).
7.8 The reported precision shall be in accordance with
6.3.3 Results of particulate analysis shall be reported in
Practice E29.
mass per implant, mass per surface area, number per device,
number per surface area, atomic-%, or fraction per surface
7.9 Reports shall include the analytical laboratory, the
area. The size range of particulates considered in the analysis
analyst performing the test, protocol specifics (where more
(for example, based on filter pore sizes, capillaries, diffraction
than one option is possible in a standard method), and any
settings) shall be reported.
modifications from the standard protocol.
6.3.4 Results of surface analysis shall be reported as
atomic-%, molecular-%, or fraction per surface area.
8. Limit Values
6.4 Identification of Residues—Residues that have been
8.1 Determination of company internal acceptance criteria
identified shall be listed separately in the report if they are
for residues is required for quality assurance and review by
considered significant by the practitioner of this practice.
regulatory authorities.Arisk-based approach is appropriate for
considering where and how residues can be introduced and the
7. Quality Assurance
impact of existing controls such as validated cleaning and
passivation processes.
7.1 The cleanliness of the implant shall be determined using
the final product after packaging. Assessment can also be
8.2 The set value for a limit value be may be derived from
performed at various stages along the manufacturing process
historical and clinical analytical data, experience with the
for manufacturing control or validation. particular device or analogous devices, toxicological assess-
NOTE 1—Sterilization processes can affect the chemical and biological
ment based on acute local tissue reactions, or from data as
nature of residues. The manufacturer may elect to assess the residue
specified in other standards and guidance documents.
content before and after sterilization. In the case of bioburden, testing has
to be performed before sterilization. 8.3 Guides such as ISO 10993-17 may be helpful in
establishing limit values. Calculation of limit values based on
7.2 Each method of analysis shall be validated individually
classical toxicological calculations (TE, NOEL, dose base on
in the laboratory conducting the analysis.
body mass and exposure times) requires special attention.
7.3 The manufacturing process for the implant being ana-
Caution is advised in the use of such values since the
lyzed shall be reviewed regarding manufacturing materials
assessment is based on the whole organisms and not on the
used (for example, lubricants, emulsions, buffing compounds,
local effects that define the fate of the implant.
grit blast media, detergents, etc.). The listing of all manufac-
8.4 The quantitative and qualitative rationales for the ex-
turing materials will help to identify the appropriate analytical
trapolation or derivation of limit values shall be clearly
methods and facilitate toxicological and risk assessments.
documented.
7.4 It is recommended that analytical protocols be validated
8.5 Thelimitvaluereflectsamaximumnumberthatisnotto
directly on the implant or on test coupons with similar material
be exceeded in any case. It is not a mean value of separate
and surface properties by soiling with known amounts of
analyses, but it may be the value of a test group containing
manufacturing materials under conditions occurring in the
several devices in a single analysis.
implant processing. When working with model residues for
soiling, it is important to ensure that no unwanted chemical
9. Keywords
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...

This document is not an ASTM standard and is intended only to provide the user of an ASTM standard an indication of what changes have been made to the previous version. Because
it may not be technically possible to adequately depict all changes accurately, ASTM recommends that users consult prior editions as appropriate. In all cases only the current version
of the standard as published by ASTM is to be considered the official document.
Designation: F2847 − 10 F2847 − 17
Standard Practice for
Reporting and Assessment of Residues on Single Use
ImplantsSingle-Use Implants and Single-Use Sterile
Instruments
This standard is issued under the fixed designation F2847; the number immediately following the designation indicates the year of
original adoption or, in the case of revision, the year of last revision. A number in parentheses indicates the year of last reapproval. A
superscript epsilon (´) indicates an editorial change since the last revision or reapproval.
1. Scope
1.1 The purpose of this practice is to describe how the cleanliness of single use single-use implants as manufactured shall be
reported. This practice proposes how to approach the identification of critical compounds and suggests different analytical methods.
1.2 The practice does not address substances which are intrinsic to the implant properties or design. In particular, it does not
address substances released during implant resorption, implant coatings, or leachables by design.
1.3 This practice does not address the cleanliness of implants which are re-processed, re-cleaned after unpacking for re-use in
the hospital or by the manufacturer.
1.4 This practice does not establish limit values for residues.
1.5 This practice suggests appropriate test methods for the general specification of residues and residue requirements of
implants. implants and single-use sterile instruments. This practice may also be used to characterize semi-finished components for
implants.
1.6 The test methods suggested and described herein refer to established analytical methods and to existing standard methods
for chemical, biochemical, or biological analysis.
1.7 This practice is intended solely to provide guidance regarding suitable test methods and reporting conventions for residues,
which may or may not affect implant biocompatibility. This practice does not suggest or recommend test methods for
biocompatibility, which may be found in Practice F748 or in ISO 10993-1.
1.8 This standard does not purport to address all of the safety concerns, if any, associated with its use. It is the responsibility
of the user of this standard to establish appropriate safety safety, health, and healthenvironmental practices and determine the
applicability of regulatory limitations prior to use.
1.9 This international standard was developed in accordance with internationally recognized principles on standardization
established in the Decision on Principles for the Development of International Standards, Guides and Recommendations issued
by the World Trade Organization Technical Barriers to Trade (TBT) Committee.
2. Referenced Documents
2.1 ASTM Standards:
E29 Practice for Using Significant Digits in Test Data to Determine Conformance with Specifications
E996 Practice for Reporting Data in Auger Electron Spectroscopy and X-ray Photoelectron Spectroscopy
E1078 Guide for Specimen Preparation and Mounting in Surface Analysis
E1504 Practice for Reporting Mass Spectral Data in Secondary Ion Mass Spectrometry (SIMS)
E1635 Practice for Reporting Imaging Data in Secondary Ion Mass Spectrometry (SIMS)
E1829 Guide for Handling Specimens Prior to Surface Analysis
F561 Practice for Retrieval and Analysis of Medical Devices, and Associated Tissues and Fluids
F748 Practice for Selecting Generic Biological Test Methods for Materials and Devices
This practice is under the jurisdiction of ASTM Committee F04 on Medical and Surgical Materials and Devices and is the direct responsibility of Subcommittee F04.15
on Material Test Methods.
Current edition approved Dec. 1, 2010Sept. 15, 2017. Published January 2011October 2017. Originally approved in 2010. Last previous edition approved in 2010 as
F2847 – 10. DOI: 10.1520/F2847–10.10.1520/F2847-17.
For referenced ASTM standards, visit the ASTM website, www.astm.org, or contact ASTM Customer Service at [e-mail]. For Annual Book of ASTM Standards
volume information, refer to the standard’s Document Summary page on the ASTM website.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2847 − 17
F1251 Terminology Relating to Polymeric Biomaterials in Medical and Surgical Devices (Withdrawn 2012)
F1877 Practice for Characterization of Particles
F2459 Test Method for Extracting Residue from Metallic Medical Components and Quantifying via Gravimetric Analysis
F2809 Terminology Relating to Medical and Surgical Materials and Devices
G121 Practice for Preparation of Contaminated Test Coupons for the Evaluation of Cleaning Agents
G131 Practice for Cleaning of Materials and Components by Ultrasonic Techniques
G136 Practice for Determination of Soluble Residual Contaminants in Materials by Ultrasonic Extraction
2.2 ISO Standards:
ISO 10993-1 Biological Evaluation of Medical Devices—Part 1: Evaluation and Testing
ISO 10993-17 Biological Evaluation of Medical Devices—Part 17: Establishment of Allowable Limits for Leachable Substances
ISO 10993-18 Biological Evaluation of Medical Devices—Part 18: Chemical Characterization of Materials
ISO 11737-1 Sterilization of Medical Devices—Microbiological Methods—Part 1: Determination of a Population of Microor-
ganisms on Products
ISO 17294-1 Water Quality—Application of Inductively Coupled Plasma Mass Spectrometry (ICP-MS)—Part 1: General
Guidelines
ISO 17294-2 Water Quality—Application of Inductively Coupled Plasma Mass Spectrometry (ICP-MS)—Part 2: Determination
of Selected Elements Including Uranium Isotopes
2.3 United States Pharmacopeia (USP) Document:Documents:
<85> Bacterial Endotoxin Test
<161> Transfusion and Infusion Assemblies and Similar Medical Devices
<232> Elemental Impurities – Limits
<233> Elemental Impurities – Procedures
<631> Chromatography
<643> Total Organic Carbon
<730> Plasma Spectrochemistry
<731> Loss on Drying
<851> Spectrophotometry and Light Scattering
2.4 European Pharmacopoeia (PhEUR) Documents:
2.2.23 Atomic Absorption Spectrometry
2.2.24 Absorption Spectrophotometry, Infrared
2.2.25 Absorption Spectrophotometry, Ultraviolet and Visible
2.2.28 Gas Chromatography
2.2.29 Liquid Chromatography
2.2.43 Mass Spectrometry
2.2.44 Total Organic Carbon in Water for Pharmaceutical Use
2.2.48 Raman Spectrometry
2.2.55 Peptide Mapping
2.2.57 Inductively Coupled Plasma-Atomic Emission Spectrometry
2.2.58 Inductively Coupled Plasma-Mass Spectrometry
2.5 Association for the Advancement of Medical Instrumentation (AAMI) Document:
AAMI ST72 Bacterial Endotoxins—Test Methodologies, Routine Monitoring, and Alternatives to Batch Testing
2.6 Other References:
FDA Guideline on Validation of the Limulus Amebocyte Lysate Test as an End-Product Endotoxin Test for Human and Animal
Parenteral Drugs, Biological Products, and Medical Device, 1987Guidance for Industry Pyrogen and Endotoxins Testing:
Questions and Answers, June 2012
200.7 EPA Methodologies for ICP
8270C EPA Methodologies for GC-MS
3. Terminology
3.1 Unless provided otherwise in 3.2, terminology shall be in conformance with Terminology F1251 and with Terminology
F2809.
The last approved version of this historical standard is referenced on www.astm.org.
Available from American National Standards Institute (ANSI), 25 W. 43rd St., 4th Floor, New York, NY 10036, http://www.ansi.org.
Available from U.S. Pharmacopeia (USP), 12601 Twinbrook Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
Available from European Directorate for the Quality of Medicines and HealthCare (EDQM), 7 allee Kastner, CS 30026, F67081, Strasbourg, France, http://www.edqm.eu/
en/News-and-General-Information-43.html.
Available from Association for the Advancement of Medical Instrumentation (AAMI), 4301 North Fairfax Drive, Suite 301, Arlington, VA 22203, http://www.aami.org.
Available from Food and Drug Administration (FDA), 5600 Fishers Ln., Rockville, MD 20857, http://www.fda.gov.
Available from United States Environmental Protection Agency (EPA), Ariel Rios Bldg., 1200 Pennsylvania Ave., NW, Washington, DC 20460, http://www.epa.gov.
F2847 − 17
3.2 Definitions:
3.2.1 action value, n—the amount(s) of substance(s) tolerated at the surface of an implant by the manufacturer before it will
interfere with the manufacturing process.
3.2.2 exhaustive extraction, n—extraction until the cumulative residue change is analytically insignificant or less than 10 % of
the initial extract.
3.2.3 limit value, n—the maximum allowable amount(s) of substance(s) at the surface of an implant not yet found to be harmful
for the surrounding tissues and organs. Its value is established and defined by the manufacturer.
3.2.4 model residue, n—a single substance or a mixture of substances that reflect the process materials likely to be encountered
and used during the manufacturing of the device.
3.2.5 residue, n—a substance present at the surface of an implant or embedded therein that is not explicitly recognized and
defined as part of the implant specification (special definition for residue analysis of surfaces). It includes process-based residues
as well as contamination by environmental factors (adsorbates).
3.2.6 single use single-use implant, n—a medical device which is intended use is to be implanted permanently and that is not
re-cleaned or re-worked for a second implantation after eventual removal.
3.2.7 soiling, n—procedure of applying known amounts of a substance onto a medical device for determination of process
capability, that is, cleaning efficiency and extraction yields.
3.2.8 spiking, n—procedure of applying exact quantities of a substance to an analyte for instrumental calibration and
determination reaction yield.
3.2.9 surface area, n—the projected surface area of a part. This area does not include the internal porosity of parts with
cancellous, porous, or wire structure. It does include factors that correct for the estimated surface roughness.
4. Summary of Practice
4.1 This practice describes how to report residues on implant surfaces and indicates useful and typical applicable analytical
methods.
4.2 Application of the test methods contained within this practice does not guarantee clinical success of a finished implant, but
it will help to ensure consistency in its cleanliness.
5. Significance and Use
5.1 The quality and consequently the clinical performance of implants may be affected by residues. Residues may induce no
tissue response, minor tissue irritations, or they may lead to local inflammation of tissues surrounding the implant which may lead
to failure in short-term or long-term use. Residues may also cause harm at locations away from the implant. Residues may originate
from manufacturing materials used in the course of processing, or processing or from the manufacturing environment, or may be
the result of handling and packaging (1-3).
5.2 This practice shall be used to report the results of testing for residue. All residues cannot necessarily be detected. It suggests
standard techniques that may be applied for analysis, and provides suggestions for how limit values may be set.
5.3 Residues may be of inorganic, organic, or biological nature. They may exhibit as surface bound surface-bound substance,
or as an adsorbate adsorbates (for example, electrostatically held), an efflorescence, or a mechanically held substance.substances.
Residues may be soluble in aqueous media, soluble in organic solvents, or may be insoluble particulates.
5.4 Data generated in validation processes, thatprocesses (that is, cleaning validation or sterility validationvalidation) may be
used as results or as basis for setting acceptance criteria in the report.
6. Reporting of Residues on Implants
6.1 The reporting of cleanliness of implants shall include a table that lists at least sections on (1) the chemical categories, (2)
the results of validation studies or of routine analysis, (3) the acceptance criteria if applicable, (4) the detection limits of the
methods used, and (5) the methods of analysis (see Table 1).
6.2 Categories of Residues:
6.2.1 Residues shall be classified, as needed, according to the common description and reported accordingly as (I) inorganic,
(II) organic, (III) biologic, (IV) microbiological, and (V) particulate residues.
6.2.2 In this practice, inorganic residues are referred to as substances of all elements with the exception of carbon-containing
substances. Carbonates, graphite carbides, graphite, or graphite-like structures (for example, diamond like diamond-like coatings)
are traditionally listed as inorganic substances.
The boldface numbers in parentheses refer to the list of references at the end of this standard.
F2847 − 17
TABLE 1 Suggested Table for Reporting of Residues
NOTE 1—The reported table shall reflect the mean value of all measurements of a product and the error, including the error of the method.
NOTE 2—The column Applied Analytical Method exemplifies methods and applicable standards. They can be replaced by any method/standard protocol
suitable for the particular residues.
Results of Set Limit Applied Analytical
Categories Detection Limit
B
Analysis Values Methods
Inorganic [mass/implant] [mass/implant] [mass/implant] ICP-OES
[mass/surface area] [mass/surface area] [mass/surface area] (PhEur 2.2.57)
Inorganic [mass/implant] [mass/implant]
[mass/surface area] [mass/surface
Organic
Biological e-spray MS
(PhEur 2.2.43)
Bioburden [CFU/implant] [CFU/implant] [CFU/implant] ISO 11737-1
A
Endotoxin [EU/implant] EU/implant [EU/implant] USP<85>
AAMI ST72
Particulate [mass/implant] [mass/implant] [mass/implant] SEM (internal protocol)
[mass/surface area] [mass/surface area] [mass/surface area] XPS (ASTM E996)
[Number/implant] [Number/ implant] [Number/implant]
2 2 2 2 2 2
or [cm /cm ] or [cm /cm ] or [cm /cm ]
[Atomic-%] [Atomic-%] [Atomic-%]
or [Molecular-%] or [Molecular-%] or [Molecular-%]
Visual Inspection [Optical observations] [Optical observations] [Optical observations] (internal protocol)
A
LimitLimit value as defined for device types listed in FDA Guidance for Industry and Guideline on Validation of the Limulus Amebocyte Lysate Test as an End-Product
Endotoxin Text for Human and Animal Parenteral Drugs, Biological Products, and Medical Devices (December 1987).Pyrogen and Endotoxins Testing: Questions and
Answers (June 2012) or in USP <161> Transfusion and Infusion Assemblies and Similar Medical Devices.
B
Analytical methods indicated in the column are examples of possible methods only. Each producer is asked to justify in a rationale why a specific method and standard
are used.
6.2.3 In this practice, organic residues are referred to as synthetic and natural carbon-based substances. It includes substances,
including both small molecules with low molecular mass (for example, paraffin or low viscosity oil) and high molecular mass based
synthetic polymers. Polysilanes and -oxanes are also considered organic residues.
6.2.3.1 In this practice, microbiologic residues are to be listed separately and differentiated as bioburden and endotoxin. It
should be noted that for medical devices sold sterile, bioburden testing is often part of sterilization validation and is monitored on
a predetermined schedule for the purpose of dose audits or process control.
6.2.4 In this practice, particulate residues are referred to as material insoluble in aqueous media or organic solvent, which can
be removed from the surface of an implant by physical-chemical physical and/or chemical means without interfering with the
integrity of the implant surface. Even though particulates shall be reported separately, they belong to one of the chemical classes
mentioned above.
6.3 Reported Units:
6.3.1 Results of inorganic and organic analysis shall be reported as mass per implant and/oror mass per surface area area, or
both (use SI units).
6.3.2 Results of biological analysis shall be reported in the specific units per implant, that is, enumeration methods such as
colony forming unit (CFU), or enzymatic assays such as for example, endotoxin units (EU).(EUs).
6.3.3 Results of particulate analysis shall be reported in mass per implant, mass per surface area, number per device, number
per surface area, or atomic-%, or fraction per surface area. The size range of particulates considered in the analysis (for example,
based on filter pore sizes, capillaries, diffraction settings) shall be reported.
6.3.4 Results of surface analysis shall be reported as atomic-%, molecular-%, or fraction per surface area.
6.4 Identification of Residues—Residues that have been identified shall be listed separately in the report if they are considered
significant by the practitioner of this practice.
7. Quality Assurance
7.1 The cleanliness of the implant shall be determined using the final product after packaging. Assessment can also be
performed at various stages along the manufacturing process for manufacturing control or validation.
NOTE 1—Sterilization processes can affect the chemical and biological nature of residues. The manufacturer may elect to assess the residue content
before and after sterilization. In the case of bioburden, testing has to be performed before sterilization.
7.2 Each method of analysis shall be validated individually in the laboratory conducting the analysis.
7.3 The manufacturing process for the implant being analyzed shall be reviewed regarding manufacturing materials used,
forused (for example, lubricants, emulsions, buffing compounds, grit blast media, detergents, etc.etc.). The listing of all
manufacturing materials will help to identify the appropriate analytical methods and facilitate toxicological and risk assessments.
F2847 − 17
7.4 It is recommended that analytical protocols be validated directly on the implant or on test coupons with similar material and
surface properties by soiling with known amounts of manufacturing materials under conditions occurring in the implant processing.
When working with model residues for soiling, it is important to assureensure that no unwanted chemical cross reactions occur.
The use of spikes in eluates for quality control reasons should be also considered with certain test methods (4, 5).
7.4.1 Worst-case implants or test coupons (regarding surface texture, machined features) and soiling with identified worst case
worst-case manufacturing materials may be used to reduce the number of process analyses.
7.4.2 Protocols shall be validated for surface texture(s) and material(s) being analyzed.
7.4.3 Worst cast Worst-case soiling compounds or model residues shall be relevant regarding composition, amount applied, and
incubation conditions. A detailed procedure for preparing test coupons is found in Practice G121.
7.5 In case of extraction protocols, validation shall include the determination of recovery yields and the resulting accuracy of
the method and the acceptance criteria for successful testing.
7.6 Each method of analysis shall be established with detection and quantification limits.
7.7 Quantification limits of methods shall be at least one order of magnitude lower than the respective set limit values for robust
data.
7.8 The reported precision shall be in accordance with Practice E29.
7.9 Reports shall include the analytical laboratory, the analyst performing the test, protocol specifics (where more than one
option is possible in a standard method), and any modifications from the standard protocol.
8. Limit Values
8.1 Determination of company internal acceptance criteria for residues is required for quality assurance and review by
regulatory authorities. A risk-based approach is appropriate for considering where and how residues can be introduced and the
impact of existing controls such as validated cleaning and passivation processes.
8.2 The set value for a limit value be may be derived from historical and clinical analytical data, experience with the particular
device or analogous devices, toxicological assessment based on acute local tissue reactions, or from data as specified in other
standards and guidance documents.
8.3 Guides such as ISO 10993-17 may be helpful in establishing limit values. Calculation of limit values based on classical
toxicological calculations (TE, NOEL, dose base on body mass and exposure times) requires special attention. Caution is advised
in the use of such values since the assessment is based on the whole organisms and not on the local effecteffects that define the
fate of the implant.
8.4 The quantitative and qualitative rationales for the extrapolation or derivation of limit values shall be clearly documented.
8.5 The limit value reflects a maximum number that is not to be exceeded in any case. It is not a mean value of separate analyses,
but it may be the value of a test group containing several devices in a single analysis.
9. Keywords
9.1 analysis; cleanliness; contamination; limit value; residues
ANNEX
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