ASTM F2211-02
(Classification)Standard Classification for Tissue Engineered Medical Products (TEMPs)
Standard Classification for Tissue Engineered Medical Products (TEMPs)
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 CDR Parts 16 and 1270 and 21 CFR Parts 207, 807, and 1271.
1.3 This standard does not purport to address specific components coverd 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 and health practices and determine the applicability of regulatory requirements prior to use.
General Information
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Standards Content (Sample)
NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Please contact ASTM International (www.astm.org) for the latest information.
Designation: F 2211 – 02
Standard Classification for
Tissue Engineered Medical Products (TEMPs)
This standard is issued under the fixed designation F 2211; 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 (ϵ) indicates an editorial change since the last revision or reapproval.
1. Scope 21 CFR Parts 16 and 1270 Human Tissues, Intended for
Transplantation
1.1 This classification outlines the aspects of tissue engi-
21CFRParts207,807,and1271 HumanCells,Tissues,and
neered medical products that will be developed as standards.
Cellular and Tissue-Based Products: Establishment Reg-
This classification excludes traditional transplantation of or-
istration and Listing
gans and tissues as well as transplantation of living cells alone
2.3 ISO Standard:
as cellular therapies.
ISO 10993 Biological Evaluation of Medical Devices
1.2 This classification does not apply to any medical prod-
ucts of human origin regulated by the U.S. Food and Drug
NOTE 1—International Standards:There are no known standards devel-
Administration under 21 CDR Parts 16 and 1270 and 21 CFR oped by the international community specifically for TEMPS; however,
ASTM International has an effort initiated in 1997 and several colleagues
Parts 207, 807, and 1271.
of the international community (IEC, CEN, ISO) have been coordinating
1.3 This standard does not purport to address specific
and contributing to the ASTM TEMPs standards. Also, the international
components coverd in other standards. Any safety areas asso-
community is in the process of formulating a direction for their standards
ciated with the medical product’s use will not be addressed in
and regulations for this area. Recently, several draft documents have been
this standard.This standard does not purport to address all of
circulated for input regarding code of practice for Products using Material
the safety concerns, if any, associated with its use. It is the
of Human Origin, from the U.K., EUCOMED position paper concerning
responsibility of the user of this standard to establish appro- the need for future regulation of human tissue products for Europe and
“Pre-clinical Safety Assessment of Tissue Engineered Medical Products
priate safety and health practices and determine the applica-
(TEMPs):AnInvestigationonAssaysandGuidelinesforBiocompatibility
bility of regulatory requirements prior to use.
Testing.”
2. Referenced Documents
3. Terminology
2.1 ASTM Standards:
3.1 tissue engineering, n—the application, in vivo and in
F 2027 Guide for Characterization and Testing of Substrate
vitro, of scientific principles and technologies to form tissue
Materials for Tissue-Engineered Medical Products
engineered medical products (TEMPs) used for medical treat-
F 2064 Guide for Characterization and Testing ofAlginates
ments and as diagnostics. The various technologies and prin-
as Starting Materials Intended for Use in Biomedical and
ciples are common practices and methods in engineering and
Tissue-Engineered Medical Products Application
biomedical sciences such as cell, gene, or drug therapy,
F 2103 Guide for Characterization and Testing of Chitosan
embryology or other forms of developmental biology, surgical
Salts as Starting Materials Intended for Use in Biomedical
methodsandtechnologiesusedtocreatetraditionaldevicesand
and Tissue-Engineered Medical Product Applications
biologics. Tissue engineering could be applied to create prod-
F 2131 Test Method for In Vitro Biological Activity of
ucts for non-human use as well.
Recombinant Human Bone Morphogenetic Protein-2
3.2 tissue engineered medical products (TEMPs),
(rhBMP-2) Using the W-20 Mouse Stromal Cell Line
n—medical products that repair, modify, or regenerate the
F 2150 Guide for Characterization and Testing of Biomate-
recipients’ cells, tissues, and organs, or their structure and
rial Scaffolds Used in Tissue-Engineered Medical Prod-
function, or combination thereof. TEMPs may achieve a
ucts
therapeutic potential from cells, biomolecules, scaffolds, and
2.2 Federal Documents:
other materials, and processed tissues and derivatives used in
US FDA CFR 21, Part 3 [3.2(e)] Product Jurisdiction
various combinations or alone. TEMPs are unique from con-
ventional organ transplants. TEMPs may be used in vivo or in
vitro for disease, injury, elective surgery, and as a diagnostic.
This classification is under the jurisdiction of ASTM Committee F04 on
Medical and Surgical Materials and Devices and is the direct responsibility of
Subcommittee F04.41 on Classification and Terminology for TEMPs.
Current edition approved Nov. 10, 2002. Published February 2003. Available from International Organization for Standardization (ISO), 1 rue de
Annual ASTM Book of Standards, Vol 13.01. Varembé, Case postale 56, CH-1211, Geneva 20, Switzerland.
3 5
AvailablefromU.S.GovernmentPrintingOfficeSuperintendentofDocuments, Available from Rijksinstituut voor Volksgezondheid en Milieu, (National
732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401. Institute of Public Health and the Environment) The Netherlands.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Please contact ASTM International (www.astm.org) for the latest information.
F2211–02
3.3 For other definitions used in this classification, refer to product as having two active components. Also, what is
the terms developed by the subcommittee on tissue engineered referred to in the U.S. as a carrier often is an excipient in the
medical products terminology. EU. In many cases, interactions occur among these combined
3.3.1 Discussion—ASTM Committee F04 is continuing to materials to stimulate repair and regeneration of tissues and
refine definitions for tissue engineered medical products organ function. The biological materials, cells, and cellular
(TEMPs) and related areas. A terminology standard for products (therapeutic biomolecules) are often used to provide
TEMPS will be published. the biological message to initiate the repair function.Addition-
3.4 For specific definitions related to specific standards, ally, the three-dimensional material (natural or synthetic bio-
refer to the general index and the individual standards. materials) may provide the architecture for the structural
support of the cells and repository for bioactive substances.
4. Significance and Use
Theinteractionresultsintheintegrationoftheproductwiththe
4.1 This classification outlines aspects of TEMPs which patient, maintenance of the biological integrity of the product,
includes their individual components. and controlled signaling between the product and the patient’s
4.2 The categories outlined in this classification are in- cells. Synthetic biomaterials used in the product can also have
tended to list, identify, and group the areas pertinent to Tissue interactions and effects on the product performance.
Engineered Medical Products. This classification will be used
6.2 Cells (under jurisdiction of Subcommittee F04.45), that
by the Tissue Engineered Medical Products subcommittees for
is, of autologous, allogeneic, xenogeneic origin or genetically
the organization of the development of standards for the field
modified cells of any species, may be components of the
of tissue engineering, TEMPs, and protocols for their use. The
TEMP. The cells may be viable, inactivated, or nonviable.
development of products from the new tissue engineering
They may be embryonic, neonatal, adult, stem, or progenitor
technologies necessitates creation and implementation of new
cells. As such, it is important to verify aspects of TEMP
standards (1).
production, that is, cell or tissue sourcing, procurement, good
4.3 Since interactions may occur among the components
tissue practices, facilities, storage, transportation, and distribu-
used in TEMPs, new standard descriptions, test methods, and
tion. Other features of cells used for TEMPs may include
practices are needed to aid the evaluation of these interactions.
genotype and phenotype characterization and safety, that is,
The degree of overall risk for any given TEMP is reflected by
absence of adventitious agents. When feasible, standardized
the number and types of tests required to demonstrate product
methods should be provided.
safety and efficacy.
6.2.1 Other aspects of TEMPs with cells may be product
specific. Here, the TEMP developers may need to rely upon
5. Classification of Tissue Engineered Medical Products
standards and methodologies appropriate for the cell type and
5.1 Aspects of TEMPs are classified according to the
species. For instance, if the TEMP is comprised of non-human
product components, site of action, therapeutic target, thera-
cells, the xenogeneic cell identity and safety and immunologi-
peutic effect, mode of action, duration of therapy, and lifetime
cal responses must be considered. The use of cells from other
(see Fig. X2.1). TEMPs are composed of cells, biomolecules,
animal species presents additional issues and increased regu-
tissues, and biomaterials, alone or in combination, which are
latory surveillance including those of ethics and public percep-
designed, fabricated, and specified through the principles of
tion.
tissue engineering. The human body is composed of several
6.2.2 Other aspects ofTEMPs may require unique measures
organ systems that are coordinated to achieve the functions
used by the TEMP developers and accepted by the regulatory
necessary for life. For the purposes of the ASTM Committee
agencies for cell type specific characterizations, process and
F04 TEMPs standard effort, 10 organ and tissue systems have
test methods, and end-product use and performance. Since live
been classified. They are: Integument, Hematopoietic, Cardio-
cells may be used, the maintenance of their viability, and
vascular, Musculoskeletal, Respiratory, Digestive, Nervous,
genetic/phenotypic functional integrity should be addressed.
Urinary, Endocrine, and Reproductive. (See X2.3 for examples
Microbiological safety is critical, thus the verified absence of
of each of the human systems). Examples of product applica-
adventitious agents must be addressed and methodologies
tions under development are given in X2.5.
provided.
6.2.3 Standards will be developed to identify general meth-
6. Components
ods of processing the cells, matrices, and tissue used for the
6.1 TEMPs are often combination products, as defined by
TEMPs; to preserve cells and tissues used for TEMPs; to
the U.S. FDA21 CFR Part 3 [3.2(e)], Product Jurisdiction, that
enumerate cells of various kinds; to characterize cell and tissue
incorporate attributes of at least two of the medical product
viability; to identify general methods for vitro production and
classifications, that is, a traditional biologic, device, or drug.
testingofTEMPs;and,tocharacterizegeneralfeaturesofcells.
However, in other countries, the definition may be different.
6.3 Synthetic or natural biomaterials (under jurisdiction of
For example, the European Union (EU) defines a combination
Subcommittee F04.43) may be used as support structures or
delivery systems for therapeutic cells or biomolecules(3). Raw
materials,referredtoassubstrates,maybeformedorprocessed
The boldface numbers in parentheses refer to the list of references at the end of
this standard. into scaffolds to provide load-bearing capacity, or a framework
NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
Please contact ASTM International (www.astm.org) for the latest information.
F2211–02
for tissue formation, or as a cell contact surface coating. designed to degrade and be replaced by the host tissue. The
Control of substrate and scaffold surface and bulk characteris- balance in the biodegradation and replacement rates will be
tics, toxicity, degradation, and replacement rates require meth- influenced by the characteristics of the materials in the product
ods selection and protocol development. Specific naturally- and host response to the product, which also relates to the
occurring biomaterials and derivatives, which may be biocompatibility of the product. Therefore, monitoring during
produced through various methods and technologies, should be these critical phases of the product lifetime will be necessary.
characterized first following substrate recommendations. Once This in turn will impact the structural, mechanical and func-
processed into a scaffold, the biocompatibility and the interac- tional properties and require appropriate testing methods and
tions with the other product components and the patient must protocols.
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 ofTEMPs. Standards for characterization, sourcing and and optical coherence tomography), electron microscopy, 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 (under jurisdiction of Subcommittee digital image analysis) will also be developed.
F04.44) may be added to the product as an individual compo- 7.3 Mechanical Characterization—Mechanical character-
nent,thecellsthatareaproductcomponentmayproducethem, ization will include all forms of bench-top testing for quanti-
or they may be elicited from the patient’s tissue by product fying mechanical properties (including compressive, tensile,
components. When biomolecules are added to or produced by burst pressure), and testing using novel test methods for
the product to impact therapy, their identity, characterization, specific applications. Standards for analyses of the data and
andfunctionshouldbedeterminedusingspecificstandardsand calibration will also be referenced or developed de novo when
test methods. It is important to describe the biomolecule not otherwise available.
formulation and the formulation’s compatibility with the ma- 7.4 Biochemical Characterization—Biochemical character-
trix. There may also be a need to control the level of ization will include all forms of tests that determine the
non-efficacious biomolecules, which may be antigenic 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.
morpho
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