ASTM F2312-03
(Terminology)Standard Terminology Relating to Tissue Engineered Medical Products
Standard Terminology Relating to Tissue Engineered Medical Products
SCOPE
1.1 This terminology defines basic terms and presents the relationships of the scientific fields related to Tissue Engineered Medical Products (TEMPs). Committee F04 has defined these terms for the specific purpose of unifying the language used in standards for TEMPs.
1.2 The terms and relationships defined here are limited to TEMPs. They do 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 The terms and nomenclature presented in this standard are for the specific purposes of unifying the language used in TEMP standards and are not intended for labeling of regulated medical products.
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 and health practices and determine the applicability of regulatory limitations prior to use.
General Information
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Standards Content (Sample)
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Designation:F2312–03
Standard Terminology Relating to
Tissue Engineered Medical Products
This standard is issued under the fixed designation F 2312; 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 (e) indicates an editorial change since the last revision or reapproval.
1. Scope 3. Significance and Use
1.1 This terminology defines basic terms and presents the 3.1 The need for standards regarding TEMPs has also
relationships of the scientific fields related to Tissue Engi- prompted a need for definitions. This terminology sets forth
neered Medical Products (TEMPs). Committee F04 has de- definitions of the most commonly used terms and specifies the
fined these terms for the specific purpose of unifying the relationship among the sciences and components applied in
language used in standards for TEMPs. tissue engineering to develop TEMPs. Use of these terms and
1.2 The terms and relationships defined here are limited to an understanding of these relationships will unify the ASTM
TEMPs. They do not apply to any medical products of human TEMPs standards with a common language such that the users
origin regulated by the U.S. Food and Drug Administration of these standards can understand and interpret the standards
under 21 CFR Parts 16 and 1270 and 21 CFR Parts 207, 807, more precisely.Terms specific to aTEMPstandard will also be
and 1271. defined within the respective standard as appropriate.
1.3 The terms and nomenclature presented in this standard 3.2 Defining Terms—Terms are defined with a broad scope
are for the specific purposes of unifying the language used in to encompass these new products known as TEMPs. For
TEMPstandards and are not intended for labeling of regulated instance, the definition for somatic cell therapy as stated in the
medical products. “Guidance for Human Somatic Cell Therapy and Gene
1.4 This standard does not purport to address all of the Therapy” (5) is recognized in this terminology. However, for
safety concerns, if any, associated with its use. It is the the purposes of TEMPs that contain cells, we have added the
responsibility of the user of this standard to establish appro- definition of “cell” which is much broader and not limited to
priate safety and health practices and determine the applica- the use of living cells.
bility of regulatory limitations prior to use. 3.3 Clinical Effects of TEMPs—The users of this terminol-
ogyshouldnotethattermsusedregardingtheclinicaleffectsof
2. Referenced Documents
TEMPs, for instance, “modify or modification” of the patient’s
2.1 ASTM Standards: condition, may also be interpreted to “enhance, augment,
F 2027 Guide for Characterization and Testing of Substrate
transform, alter, improve, or supplement.” Similarly, “repair”
Materials for Tissue-Engineered Medical Products may also serve to mean “restore.”
F 2311 Guide for Classification of Therapeutic Skin Substi-
3.4 The diagram in Fig. 1 shows the relationships of
tutes components of TEMPs and of the fields of science (for
2.2 Government Documents:
example, technologies and principles) used in tissue engineer-
21 CFR Parts 16 and 1270, Human Tissues, Intended for ing to createTEMPs. CertainTEMPs may be tissue engineered
Transplantation (July 29, 1997)
or produced in vitro by using specific components and sciences
21 CFR Parts 207, 807, and 1271, Human Cells, Tissues, to create an off-the-shelf TEMP for the users. Other TEMPs
and Cellular and Tissue-Based Products; Establishment
may by design require the users to place the components inside
Registration and Listing (January 19, 2001) the patient, (that is, in vivo) to rely upon the patient’s
regenerative potential to achieve the product’s primary in-
tended purpose. The expectation of a TEMPused for therapeu-
ThisterminologyisunderthejurisdictionofASTMCommitteeF04onMedical
tic clinical applications is to have a therapeutic effect, specifi-
and Surgical Materials and Devices and is the direct responsibility of Subcommittee
cally to repair, modify or regenerate the recipient’s cells,
F04.41 on Classification and Terminology for TEMPs.
Current edition approved Sept. 10, 2003. Published November 2003. tissues, and organs or their structure and function. Such a
For referenced ASTM standards, visit the ASTM website, www.astm.org, or
TEMPmay be used for human and non-human applications. In
contactASTM Customer Service at service@astm.org. ForAnnual Book ofASTM
Standards volume information, refer to the standard’s Document Summary page on
the ASTM website.
3 4
AvailablefromU.S.GovernmentPrintingOfficeSuperintendentofDocuments, The boldface numbers in parentheses refer to this list of references at the end
732 N. Capitol St., NW, Mail Stop: SDE, Washington, DC 20401. of this standard.
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959, United States.
F2312–03
FIG. 1 Relationships of the Fields of Tissue Engineering to Tissue Engineered Medical Products
other applications, a TEMP may be used in diagnostic clinical injuries of man.” (6). The term analogous product is inter-
applications, or both, to achieve an investigative outcome of preted to encompass somatic cell and gene therapy (15).A
the function of the cells, tissues, and organs.
biological product may be used as a component of a TEMP.
For the purposes of TEMPs, these biological products may
4. Terminology
be of any origin (that is, organism), tissue type, develop-
mental stage, and may be living, non-living, and genetically
biological product, n—“any virus, therapeutic serum, toxin,
or otherwise modified.
antitoxin, vaccine, blood, blood component or derivative,
allergenicproduct,oranalogousproduct,orarsphenamineor biomaterial, n—“material intended to interface with biologi-
cal systems to treat, augment, replace or evaluate any tissue,
its derivatives (or any trivalent organic arsenic compound)
applicabletotheprevention,treatment,orcureofdiseasesor organ or function of the body,” (1). Biomaterials in their raw
F2312–03
or virgin form are known as substrates (Guide F 2027). device.” (9). The term “combination product” may apply to
Biomaterial substrates may be natural materials (Guide TEMPs.
F 2027), synthetic or combinations thereof. When biomate-
device, n—“an instrument, apparatus, implement, machine,
rial substrates are assembled into a construction they are
contrivance, implant, in vitro reagent, or other similar or
often referred to as scaffolds. A biomaterial (substrate and
related article. intended for use in the diagnosis of disease
scaffold) may be used as a component of a TEMP.
or other conditions, or in the cure, mitigation, treatment, or
biomolecule, n—a biologically active peptide, protein, carbo- prevention of disease, in man or other animals,. which does
not achieve its primary intended purposes through chemical
hydrate, vitamin, lipid, or nucleic acid produced by and
purified from naturally occurring or recombinant organisms, action within or on the body of man or other animals and
tissues or cell lines or synthetic analogs of such molecules. which is not dependent upon being metabolized for the
A biomolecule may be used as a component of a TEMP. achievement of its primary intended purposes.” Devices are
“intendedtoaffectthestructureoranyfunctionofthebody.”
biomolecule therapy, n—the use of biomolecules to repair,
(Section 201(h)(1) (10)). Device Criteria: “Aliquid, powder,
modify, or regenerate the recipient’s cells, tissues, or organs
or other similar formulation intended only to serve as a
or their structure and function, or both. Biomolecule therapy
component, part or accessory to a device with a primary
technologies can be applied in tissue engineering to generate
mode of action that is physical in nature” (11).Adevice may
TEMPs.
be used as a component of a TEMP.
cell, n—“the smallest structural unit of an organism that is
drug, n—“articles intended for use in the diagnosis, cure,
capable of independent functioning, consisting of one or
mitigation, treatment, or prevention of disease in man or
more nuclei, cytoplasm, and various organelles, all sur-
other animals.” Drugs are “intended to affect the structure or
rounded by a semipermeable cell membrane” (8). Cells are
any function of the body of man or other animals.” (Section
highly variable and specialized in both structure and func-
201(g)(1) (10)). Drug Criteria: “A liquid, powder, tablet or
tion, though all must at some stage synthesize proteins and
other similar formulation that achieves its primary intended
nucleic acids, use energy, and reproduce.Acell or cells may
purposethroughchemicalactionwithinoronthebody,orby
be of any origin (that is, organism), tissue type, develop-
being metabolized” (11). A drug may be used as a compo-
mental stage, and may be living, non-living, and genetically
nent of a TEMP.
or otherwise modified. Cells may be used as a component of
drug therapy, n—is the delivery of drug(s) that stimulate a
a TEMP.
specific physiologic (metabolic) response. Drug therapy
cell therapy, n—the administration of cells (any kind and
technologies can be applied in tissue engineering to generate
form) to repair, modify or regenerate the recipient’s cells,
TEMPs.
tissues, and organs or their structure and function, or both.
extracellular matrix, n—“(ECM), any material produced by
Cell therapy technologies can be applied in tissue engineer-
cells and excreted to the extracellular space within the
ing to generate TEMPs.
tissues. It takes the form of both ground substance and fibers
combination product, n—as defined in 21 CFR § 3.2(e), the
and is composed chiefly of fibrous elements, proteins in-
term combination product includes: (1)Aproduct comprised
volved in cell adhesion, and glycosaminoglycans and other
of two or more regulated components, that is, drug/device,
space-filling molecules. It serves as a scaffolding holding
biologic/device, drug/biologic, or drug/device/biologic, that
tissuestogetheranditsformandcompositionhelpdetermine
are physically, chemically, or otherwise combined or mixed
tissuecharacteristics.”(14)Extracellularmatrix,abiological
and produced as a single entity; (2) Two or more separate
material or tissue derivative, may be used as a component of
products packaged together in a single package or as a unit
a TEMP.
and comprised of drug and device products, device and
genetic material, n—is nucleic acid (either deoxyribonucleic
biological products, or biological and drug products; (3)A
acid or ribonucleic acid). Genetic material is also known as
drug, device, or biological product packaged separately that
DNA, RNA, genetic element, gene, factor, allele, operon,
according to its investigational plan or proposed labeling is
structural gene, regulator gene, operator gene, gene comple-
intended for use only with an approved individually speci-
ment, genome, genetic code, codon, anticodon, messenger
fied drug, device, or biological product where both are
RNA (mRNA), transfer RNA (tRNA), ribosomal extrachro-
requiredtoachievetheintendeduse,indication,oreffectand
mosomal genetic element, plasmagene, plasmid, transposon,
where upon approval of the proposed product the labeling of
gene mutation, gene sequence, exon, intron (modified ver-
the approved product would need to be changed, for ex-
sion, (12)). Genetic material may be used as a component of
ample, to reflect a change in intended use, dosage form,
a TEMP.
strength, route of administration, or significant change in
dose; or (4) Any investigational drug, device, or biological gene therapy, n—“is a medical intervention based on modifi-
product packaged separately that according to its proposed cation of the genetic material of living cells. Cells may be
labeling is for use only with another individually specified modified ex vivo for subsequent administration or may be
investigational drug, device, or biological product where altered in vivo by gene therapy products given directly to the
both are required to achieve the intended use, indication, or subject.When the genetic manipulation is performed ex vivo
effect.” Furthermore, “many somatic cell products adminis- on cells that are then administered to the patient, this is also
teredtopatientswill be combinations of a biological product atypeofsomaticcelltherapy.Thegeneticmanipulationmay
and a device or of a drug, a biological product, and a be intended to prevent, treat, cure, diagnose, or mitigate
F2312–03
disease or injuries in humans.” (9). Gene therapy technolo- the administration of autologous, allogeneic, or xenogeneic
giescanbeappliedintissueengineeringtogenerateTEMPs. cells that have been manipulated or altered ex vivo. Manu-
facture of products for somatic cell therapy involves the ex
gene therapy products, n—“are defined for the purpose of
vivo propagation, expansion, selection, or pharmacologic
this statement as products containing genetic material ad-
treatment of cells, or other alteration of their biological
ministeredtomodifyormanipulatetheexpressionofgenetic
characteristics.”(9).ForthepurposesofTEMPssomaticcell
material or to alter the biological properties of living cells.”
therapy technologies can be applied in tissue engineering to
(9).
generate TEMPs, for human and non-human use.
manufacture, v—“any or all steps in the recovery, screening,
testing, processing, storage, labeling, packaging or distribu- somatic cell therapy products, n—“are defined as autologous
tion of any human cellular or tissue-based product.” (16). (that is, self), allogeneic (that is, intra-species), or xenoge-
For TEMPs, manufacture is expanded to include production neic (that is, inter-species) cells that have been propagated,
of products in vitro or in vivo. TEMPs may also include the expanded, selected, pharmacologically treated, or otherwise
use of non-human cellular or tissue-based materials in any altered in biological characteristics ex vivo to be adminis-
manufacturing steps. tered to humans and applicable to the prevention, treatment,
cure, diagnosis, or mitigation of disease or injuries.” (9)
organ, n—a differentiated part of an organism that performs
Somatic cell therapy products may be used as a component
specific functions. Organs are biologic body parts, that after
of a TEMP.
embryonic and early fetal stages, are composed of the four
primary tissue types (that is, epithelial/mesothelial/
tissue, n—a grouping of cells and extracellular matrix that
endothelial, connective, muscular, and nervous tissues) that
collectively have a specific structure and function. Af
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