ASTM F2211-13(2021)
(Classification)Standard Classification for Tissue-Engineered Medical Products (TEMPs)
Standard Classification for Tissue-Engineered Medical Products (TEMPs)
SIGNIFICANCE AND USE
4.1 This classification outlines aspects of TEMPs which includes their individual components.
4.2 The categories outlined in this classification are intended to list, identify, and group the areas pertinent to tissue-engineered medical products. This classification will be used by the Tissue-Engineered Medical Products subcommittees for the organization of the development of standards for the field of tissue engineering, TEMPs, and protocols for their use. The development of products from the new tissue engineering technologies necessitates creation and implementation of new standards (1).5
4.3 Since interactions may occur among the components used in TEMPs, new standard descriptions, test methods, and practices are needed to aid the evaluation of these interactions. The degree of overall risk for any given TEMP is reflected by the number and types of tests required to demonstrate product safety and efficacy.
SCOPE
1.1 This classification outlines the aspects of tissue-engineered medical products that will be developed as standards. This classification excludes traditional transplantation of organs and tissues as well as transplantation of living cells alone as cellular therapies.
1.2 This classification does not apply to any medical products of human origin regulated by the U.S. Food and Drug Administration under 21 CFR Parts 16 and 1270 and 21 CFR Parts 207, 807, and 1271.
1.3 This standard does not purport to address specific components covered in other standards. Any safety areas associated with the medical product's use will not be addressed in this standard. 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.
1.4 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
Relations
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: F2211 −13 (Reapproved 2021)
Standard Classification for
Tissue-Engineered Medical Products (TEMPs)
This standard is issued under the fixed designation F2211; 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 F2103 Guide for Characterization and Testing of Chitosan
Salts as Starting Materials Intended for Use in Biomedical
1.1 This classification outlines the aspects of tissue-
and Tissue-Engineered Medical Product Applications
engineered medical products that will be developed as stan-
F2131 Test Method forIn Vitro Biological Activity of Re-
dards.This classification excludes traditional transplantation of
combinant Human Bone Morphogenetic Protein-2
organs and tissues as well as transplantation of living cells
(rhBMP-2) Using the W-20 Mouse Stromal Cell Line
alone as cellular therapies.
F2150 Guide for Characterization and Testing of Biomate-
1.2 This classification does not apply to any medical prod-
rial Scaffolds Used in Regenerative Medicine and Tissue-
ucts of human origin regulated by the U.S. Food and Drug
Engineered Medical Products
Administration under 21 CFR Parts 16 and 1270 and 21 CFR 3
2.2 Federal Documents:
Parts 207, 807, and 1271.
US FDA CFR 21, Part 3 (3.2(e)) Product Jurisdiction
1.3 This standard does not purport to address specific
21 CFR Parts 16 and 1270 Human Tissues, Intended for
components covered in other standards. Any safety areas
Transplantation
associatedwiththemedicalproduct’susewillnotbeaddressed
21 CFR Parts 207, 807, and 1271 Human Cells,Tissues, and
in this standard. This standard does not purport to address all
Cellular and Tissue-Based Products: Establishment Reg-
of the safety concerns, if any, associated with its use. It is the
istration and Listing
responsibility of the user of this standard to establish appro-
2.3 ISO Standard:
priate safety, health, and environmental practices and deter-
ISO 10993 Biological Evaluation of Medical Devices
mine the applicability of regulatory limitations prior to use.
3. Terminology
1.4 This international standard was developed in accor-
dance with internationally recognized principles on standard-
3.1 tissue engineering, n—the application, in vivo and in
ization established in the Decision on Principles for the
vitro, of scientific principles and technologies to form tissue-
Development of International Standards, Guides and Recom-
engineered medical products (TEMPs) used for medical treat-
mendations issued by the World Trade Organization Technical
ments and as diagnostics. The various technologies and prin-
Barriers to Trade (TBT) Committee.
ciples are common practices and methods in engineering and
biomedical sciences such as cell, gene, or drug therapy,
2. Referenced Documents
embryology or other forms of developmental biology, surgical
methods, and technologies used to create traditional devices
2.1 ASTM Standards:
and biologics. Tissue engineering could be applied to create
F2027 Guide for Characterization and Testing of Raw or
Starting Materials for Tissue-Engineered Medical Prod- products for non-human use as well.
ucts
3.2 tissue-engineered medical products (TEMPs),
F2064 Guide for Characterization and Testing of Alginates
n—medical products that repair, modify, or regenerate the
as Starting Materials Intended for Use in Biomedical and
recipients’ cells, tissues, and organs, or their structure and
Tissue Engineered Medical Product Applications
function, or combination thereof. TEMPs may achieve a
therapeutic potential from cells, biomolecules, scaffolds, and
other materials, and processed tissues and derivatives used in
This classification is under the jurisdiction of ASTM Committee F04 on
various combinations or alone. TEMPs are unique from con-
Medical and Surgical Materials and Devices and is the direct responsibility of
ventional organ transplants. TEMPs may be used in vivo or in
Subcommittee F04.41 on Classification and Terminology for TEMPs.
vitro for disease, injury, elective surgery, and as a diagnostic.
Current edition approved Sept. 15, 2021. Published September 2021. Originally
approved in 2002. Last previous edition approved in 2013 as F2211 – 13. DOI:
10.1520/F2211-13R21.
2 3
For referenced ASTM standards, visit the ASTM website, www.astm.org, or AvailablefromU.S.GovernmentPrintingOfficeSuperintendentofDocuments,
contact ASTM Customer Service at service@astm.org. For Annual Book of ASTM 732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401.
Standards volume information, refer to the standard’s Document Summary page on Available from International Organization for Standardization (ISO), 1 rue de
the ASTM website. Varembé, Case postale 56, CH-1211, Geneva 20, Switzerland.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2211 − 13 (2021)
3.3 For other definitions used in this classification, refer to referred to in the U.S. as a carrier often is an excipient in the
the terms developed by the subcommittee on tissue-engineered EU. In many cases, interactions occur among these combined
medical products terminology. materials to stimulate repair and regeneration of tissues and
3.3.1 Discussion—ASTM Committee F04 is continuing to organ function. The biological materials, cells, and cellular
refine definitions for tissue-engineered medical products products (therapeutic biomolecules) are often used to provide
(TEMPs) and related areas. A terminology standard for the biological message to initiate the repair function.
TEMPS will be published. Additionally, the three-dimensional material (natural or syn-
thetic biomaterials) may provide the architecture for the
3.4 For specific definitions related to specific standards,
structural support of the cells and repository for bioactive
refer to the general index and the individual standards.
substances. The interaction results in the integration of the
product with the patient, maintenance of the biological integ-
4. Significance and Use
rity of the product, and controlled signaling between the
4.1 This classification outlines aspects of TEMPs which
product and the patient’s cells. Synthetic biomaterials used in
includes their individual components.
the product can also have interactions and effects on the
4.2 The categories outlined in this classification are in-
product performance.
tended to list, identify, and group the areas pertinent to
6.2 Cells, that is, of autologous, allogeneic, xenogeneic
tissue-engineered medical products. This classification will be
origin or genetically modified cells of any species, may be
used by the Tissue-Engineered Medical Products subcommit-
components of theTEMP.The cells may be viable, inactivated,
tees for the organization of the development of standards for
ornonviable.Theymaybeembryonic,neonatal,adult,stem,or
the field of tissue engineering, TEMPs, and protocols for their
progenitor cells. As such, it is important to verify aspects of
use. The development of products from the new tissue engi-
TEMPproduction, that is, cell or tissue sourcing, procurement,
neering technologies necessitates creation and implementation
good tissue practices, facilities, storage, transportation, and
of new standards (1).
distribution. Other features of cells used for TEMPs may
4.3 Since interactions may occur among the components
include genotype and phenotype characterization and safety,
used in TEMPs, new standard descriptions, test methods, and
that is, absence of adventitious agents. When feasible, stan-
practices are needed to aid the evaluation of these interactions.
dardized methods should be provided.
The degree of overall risk for any given TEMP is reflected by
6.2.1 Other aspects of TEMPs with cells may be product
the number and types of tests required to demonstrate product
specific. Here, the TEMP developers may need to rely upon
safety and efficacy.
standards and methodologies appropriate for the cell type and
species. For instance, if the TEMP is comprised of non-human
5. Classification of Tissue-Engineered Medical Products
cells, the xenogeneic cell identity and safety and immunologi-
5.1 Aspects of TEMPs are classified according to the
cal responses must be considered. The use of cells from other
product components, site of action, therapeutic target, thera-
animal species presents additional issues and increased regu-
peutic effect, mode of action, duration of therapy, and lifetime
latory surveillance including those of ethics and public percep-
(see Fig. X2.1). TEMPs are composed of cells, biomolecules,
tion.
tissues, and biomaterials, alone or in combination, which are
6.2.2 Other aspects ofTEMPs may require unique measures
designed, fabricated, and specified through the principles of
used by the TEMP developers and accepted by the regulatory
tissue engineering. The human body is composed of several
agencies for cell type specific characterizations, process and
organ systems that are coordinated to achieve the functions
test methods, and end-product use and performance. Since live
necessary for life. For the purposes of the ASTM Committee
cells may be used, the maintenance of their viability and
F04 TEMPs standard effort, ten organ and tissue systems have
genetic/phenotypic functional integrity should be addressed.
been classified. They are: integument, hematopoietic,
Microbiological safety is critical; thus the verified absence of
cardiovascular, musculoskeletal, respiratory, digestive,
adventitious agents must be addressed and methodologies
nervous, urinary, endocrine, and reproductive. (See X2.2 for
provided.
examples of each of the human systems.) Examples of product
6.2.3 Standards will be developed to identify general meth-
applications under development are given in X2.4.
ods of processing the cells, matrices, and tissue used for the
TEMPs; to preserve cells and tissues used for TEMPs; to
6. Components
enumerate cells of various kinds; to characterize cell and tissue
6.1 TEMPs are often combination products, as defined by viability; to identify general methods for vitro production and
the U.S. FDA21 CFR Part 3 (3.2(e)), Product Jurisdiction, that testingofTEMPs;and,tocharacterizegeneralfeaturesofcells.
incorporate attributes of at least two of the medical product
6.3 Syntheticornaturalbiomaterialsmaybeusedassupport
classifications, that is, a traditional biologic, device, or drug.
structures or delivery systems for therapeutic cells or biomol-
However, in other countries, the definition may be different.
ecules (2). Raw materials, referred to as substrates, may be
For example, the European Union (EU) defines a combination
formed or processed into scaffolds to provide load-bearing
product as having two active components. Also, what is
capacity, or a framework for tissue formation, or as a cell
contact surface coating. Control of substrate and scaffold
surface and bulk characteristics, toxicity, degradation, and
The boldface numbers in parentheses refer to the list of references at the end of
this standard. replacement rates require methods selection and protocol
F2211 − 13 (2021)
development. Specific naturally occurring biomaterials and biocompatibility of the product. Therefore, monitoring during
derivatives, which may be produced through various methods these critical phases of the product lifetime will be necessary.
and technologies, should be characterized first following sub- This in turn will impact the structural, mechanical, and
strate recommendations. Once processed into a scaffold, the functional properties and require appropriate testing methods
biocompatibility and the interactions with the other product and protocols.
components and the patient must be evaluated.
7.2 Imaging Modalities—Imaging modalities will include
6.3.1 Several naturally occurring materials are used for a
all forms of light microscopy (including spectral, fluorescent,
variety of TEMPs. Standards for characterization, sourcing,
and optical coherence tomography), electron microscopy, and
and test methods for alginate, chitosan, and collagen will be
imaging using other forms of energy. Standards for analyses
important for many TEMPs and are being developed.
that enable the relevant characterization of TEMPs (including
6.4 A biomolecule may be added to the product as an
digital image analysis) will also be developed.
individual component, the cells that are a product component
7.3 Mechanical Characterization—Mechanical character-
may produce them, or they may be elicited from the patient’s
ization will include all forms of bench-top testing for quanti-
tissue by product components. When biomolecules are added
fying mechanical properties (including compressive, tensile,
to or produced by the product to impact therapy, their identity,
burst pressure), and testing using novel test methods for
characterization, and function should be determined using
specific applications. Standards for analyses of the data and
specific standards and test methods. It is important to describe
calibration will also be referenced or developed de novo when
the biomolecule formulation and the formulation’s compatibil-
not otherwise available.
ity with the matrix. There may also be a need to control the
7.4 Biochemical Characterization—Biochemical character-
level of non-efficacious biomolecules, which may be antigenic
ization will include all forms of tests that determine the
or toxic.
activity, content, purity, or identity of any chemical constitu-
6.4.1 A test method for the in vitro bioassay of bone
ents.
morphogenetic protein-2 has been established (Test Method
F2131) to determine the component identity, potency, and
7.5 Gene Expression Profiling—Geneticsafetycanbemoni-
quantity. There is a need to establish bioactivity standards for
tored by methods of gene expression analysis and may become
other protein biomolecules that are components of TEMPs.
particularly important when xenogeneic materials are used.
6.4.2 Test methods to determine protein concentration, in-
cluding chromatographic purity methods for naturally occur-
8. Interactions
ring materials, are necessary due particularly to the variability
8.1 Characterization of the interactions among the product
of the sources for these materials.
components and the patient is the primary focus of the TEMPs
6.4.3 Dye-binding test methods for specific protein matrices
standards. The
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