ASTM E3231-19
(Guide)Standard Guide for Cell Culture Growth Assessment of Single-Use Material
Standard Guide for Cell Culture Growth Assessment of Single-Use Material
SIGNIFICANCE AND USE
5.1 A risk-based approach must be used to determine the cell lines, test articles, and materials used for testing. An evaluation of relevant factors should be made to determine if a test article is representative of the intended use.
5.2 Cell culture compatibility should be assessed if the material is in direct contact with cell culture medium regardless of duration of contact. Test articles can be of a single material or assembled from a multitude of materials.
5.3 Two perspectives to single-use material cell culture compatibility assessments are the supplier and the end user perspectives. It is understood that the supplier may have better access to single-use materials and material manufacturing processes, while having limited access to representative cell lines. Supplier assessment of materials are best tested using cell lines available that have shown known material sensitivity. The end users may have more limited access to materials but access to more representative cell lines and processes. Therefore assessment of compatibility of material with a specific cell line in a process is best evaluated by the end user.
5.4 This guide outlines best practices to establish test procedures. Appendix X1 outlines an example test procedure for a commercially available CHO cell line.
SCOPE
1.1 This guide outlines best practices to consider when setting up a representative leachable test method to detect if a material is compatible with cell culture media or manufacturing processes. This guide does not replace or supersede cell growth tests like USP , USP (plastic/elastomeric materials), or ISO 10993 (medical device materials), that are used in assessing biological reactivity in humans. Polymeric materials that have passed these tests have been found to leach compounds under normal process conditions that can inhibit cell culture growth for some cell lines. See Refs (1-5).2 Test methods that are representative of the manufacturing conditions will help identify materials that are appropriate for use during manufacturing.
1.2 This guide may be relevant to biopharmaceutical manufacturing, cell-based therapeutics, vaccines, cell-based diagnostics, and other areas.
1.3 The values stated in SI units are to be regarded as standard. No other units of measurement are included in this standard.
1.4 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.
1.5 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
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: E3231 − 19
Standard Guide for
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Cell Culture Growth Assessment of Single-Use Material
This standard is issued under the fixed designation E3231; 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 2. Referenced Documents
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1.1 This guide outlines best practices to consider when 2.1 USP Documents:
USP <87> Biological Reactivity Tests, In Vitro
setting up a representative leachable test method to detect if a
material is compatible with cell culture media or manufactur- USP <88> Biological Reactivity Tests, In Vivo
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ing processes. This guide does not replace or supersede cell
2.2 ISO Documents:
growth tests like USP <87>, USP <88> (plastic/elastomeric
ISO 10993 Biological Evaluation of Medical Devices
materials), or ISO 10993 (medical device materials), that are
used in assessing biological reactivity in humans. Polymeric 3. Terminology
materials that have passed these tests have been found to leach
3.1 Definitions:
compounds under normal process conditions that can inhibit
3.1.1 bis(2,4-di-tert-butylphenyl)-phosphate (bDtBPP),
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cell culture growth for some cell lines. See Refs (1-5). Test
n—leachable compound known to inhibit cell growth (CAS #
methods that are representative of the manufacturing condi-
69284-93-1).
tions will help identify materials that are appropriate for use
3.1.2 dimethyl sulfoxide (DMSO), n—(CH3)2SO (CAS #
during manufacturing.
67-68-5).
1.2 This guide may be relevant to biopharmaceutical
3.1.3 test articles, n—the material being tested.
manufacturing, cell-based therapeutics, vaccines, cell-based
3.1.4 test media, n—cell culture media that has been used to
diagnostics, and other areas.
extract potential leachables from the test articles.
1.3 The values stated in SI units are to be regarded as
3.1.5 the gray (Gy), n—the SI unit for absorbed radiation
standard. No other units of measurement are included in this
dose, and defined as the absorption of one joule of energy, in
standard.
the form of ionizing radiation, per kilogram of matter, that is
one gray = 1 J/kg.
1.4 This standard does not purport to address all of the
safety concerns, if any, associated with its use. It is the
4. Summary of Guide
responsibility of the user of this standard to establish appro-
4.1 This guide outlines best practices to assess compatibility
priate safety, health, and environmental practices and deter-
of polymeric materials with animal cell cultures used in the
mine the applicability of regulatory limitations prior to use.
manufacture and processing of vaccine, gene, cell and protein
1.5 This international standard was developed in accor-
therapies reliant on cell-based processes. The best practices
dance with internationally recognized principles on standard-
may be used to reveal compatibility issues in a cell culture
ization established in the Decision on Principles for the
system that includes the cell culture medium, the cell line and
Development of International Standards, Guides and Recom-
the polymeric test articles that are under evaluation.
mendations issued by the World Trade Organization Technical
4.2 The guide starts with an overview of typical cell culture
Barriers to Trade (TBT) Committee.
compatibility studies and then outlines best practices for each
aspect of the study.
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This guide is under the jurisdiction of ASTM Committee E55 on Manufacture
of Pharmaceutical and Biopharmaceutical Products and is the direct responsibility of
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Subcommittee E55.07 on Single Use Systems. Available from U.S. Pharmacopeial Convention (USP), 12601 Twinbrook
Current edition approved Oct. 1, 2019. Published October 2019. DOI: 10.1520/ Pkwy., Rockville, MD 20852-1790, http://www.usp.org.
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E3231-19. Available from International Organization for Standardization (ISO), ISO
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The boldface numbers in parentheses refer to a list of references at the end of Central Secretariat, BIBC II, Chemin de Blandonnet 8, CP 401, 1214 Vernier,
this standard. Geneva, Switzerland, http://www.iso.org.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
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E3231 − 19
5. Significance and Use cell lines available that have shown known material sensitivity.
The end users may have more limited access to materials but
5.1 A risk-based approach must be used to determine the
access to more representative cell lines and processes. There-
ce
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