ASTM F2210-02(2010)
(Guide)Standard Guide for Processing Cells, Tissues, and Organs for Use in Tissue Engineered Medical Products (Withdrawn 2015)
Standard Guide for Processing Cells, Tissues, and Organs for Use in Tissue Engineered Medical Products (Withdrawn 2015)
SIGNIFICANCE AND USE
This guide describes the general product development criteria and analyses applicable to processing of cells, tissues, and organs used for the production of TEMPs. For the purposes of this guide, cells, tissues, and organs may be derived from any organism at any developmental stage and in any state of health. For example, this guide applies to stem, progenitor, somatic, and germline cells, as well as cells from specific tissue and organ types. This guide also applies to cells, tissues, and organs from healthy, diseased, or injured embryos to adults.
Cells, tissues, and organs may be combined with a scaffold and may contain locally or systemically acting biomolecules or a drug (medicinal) product. This type of TEMP would be a “combination product.”
SCOPE
1.1 This guide describes the processing, characterization, production, and quality assurance of cells, tissues, and organs used for Tissue Engineered Medical Products (TEMPs). It concerns aspects of processing activities for cells, tissues, and organs to be further processed. These aspects include: (1) cell, tissue, and organ processing (that is, facility, reagents, and procedures for receipt, inspection, and storage; tissue culture components, biological risk factors, and processing area), (2) donors (human and nonhuman) and screening, and (3) cell, tissue, and organ characterization and processing.
1.2 This guide does not apply to any medical products of human origin regulated by the U.S. Food and Drug Administration (FDA) under 21 CFR Parts 16 and 1270 (1) and 21 CFR Parts 207, 807, and 1271 (2).
1.3 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.
WITHDRAWN RATIONALE
This guide described the processing, characterization, production, and quality assurance of cells, tissues, and organs used for Tissue Engineered Medical Products (TEMPs).
Formerly under the jurisdiction of Committee F04 on Medical and Surgical Materials and Devices, this guide was withdrawn in September 2015. This standard is being withdrawn without replacement due to its limited use by industry.
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NOTICE: This standard has either been superseded and replaced by a new version or withdrawn.
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Designation: F2210 − 02(Reapproved 2010)
Standard Guide for
Processing Cells, Tissues, and Organs for Use in Tissue
Engineered Medical Products
This standard is issued under the fixed designation F2210; 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 namine or its derivatives (or any trivalent organic arsenic
compound) applicable to the prevention, treatment, or cure of
1.1 This guide describes the processing, characterization,
diseases or injuries of man.” (3)The term “analogous product”
production, and quality assurance of cells, tissues, and organs
is interpreted to encompass somatic cell and gene therapy (21
used for Tissue Engineered Medical Products (TEMPs). It
CFR 600.3 (h)). A biological product may be used as a
concerns aspects of processing activities for cells, tissues, and
component of a TEMP. For the purposes of TEMPs, these
organs to be further processed. These aspects include: (1) cell,
biological products may be of any origin (that is, organism),
tissue, and organ processing (that is, facility, reagents, and
tissue type, developmental stage, and may be living, non-
procedures for receipt, inspection, and storage; tissue culture
living, and genetically or otherwise modified.
components, biological risk factors, and processing area), (2)
donors (human and nonhuman) and screening, and (3) cell, 2.1.4 cell culture, n—the in vitro growth or maintenance of
cells.
tissue, and organ characterization and processing.
2.1.5 cell, n—“the smallest structural unit of an organism
1.2 This guide does not apply to any medical products of
that is capable of independent functioning, consisting of one or
human origin regulated by the U.S. Food and Drug Adminis-
more nuclei, cytoplasm, and various organelles, all surrounded
tration (FDA) under 21 CFR Parts 16 and 1270 (1) and 21
by a semipermeable cell membrane.” (4) Cells are highly
CFR Parts 207, 807, and 1271 (2).
variable and specialized in both structure and function, though
1.3 This standard does not purport to address all of the
all must at some stage synthesize proteins and nucleic acids,
safety concerns, if any, associated with its use. It is the
use energy, and reproduce.Acell or cells may be of any origin
responsibility of the user of this standard to establish appro-
(that is, organism), tissue type, developmental stage, and may
priate safety and health practices and determine the applica-
be living, non-living, and genetically or otherwise modified.
bility of regulatory requirements prior to use.
Cells may be used as a component of a TEMP.
2. Terminology
2.1.6 combination product, n—“As defined in 21 CFR §
3.2(e), the term “combination product” includes: (1)Aproduct
2.1 Definitions of Terms Specific to This Standard:
comprised of two or more regulated components, that is,
2.1.1 allogeneic or allogenic, adj—cells, tissues, and organs
drug/device, biologic/device, drug/biologic, or drug/device/
in which the donor and recipient are genetically different
biologic, that are physically, chemically, or otherwise com-
individuals of the same species. Synonyms: allograft and
bined or mixed and produced as a single entity; (2) Two or
homograft.
more separate products packaged together in a single package
2.1.2 autologous, adj—cells, tissues, and organs in which
or as a unit and comprised of drug and device products, device
the donor and recipient is the same individual. Synonyms:
and biological products, or biological and drug products; (3)A
autogenous, autograft,or autotransfusion,a self-to-self graft.
drug, device, or biological product packaged separately that
2.1.3 biological product, n—“any virus, therapeutic serum,
according to its investigational plan or proposed labeling is
toxin, antitoxin, vaccine, blood, blood component or
intended for use only with an approved individually specified
derivative, allergenic product, or analogous product, or arsphe-
drug, device, or biological product where both are required to
achieve the intended use, indication, or effect and where upon
approval of the proposed product, the labeling of the approved
This guide is under the jurisdiction of ASTM Committee F04 on Medical and
product would need to be changed, for example, to reflect a
Surgical Materials and Devices and is the direct responsibility of Subcommittee
change in intended use, dosage form, strength, route of
F04.43 on Cells and Tissue Engineered Constructs for TEMPs.
Current edition approved Dec. 1, 2010. Published February 2011. Originally
administration, or significant change in dose; or (4) Any
approved in 2002. Last previous edition approved in 2002 as F2210 – 02. DOI:
investigational drug, device, or biological product packaged
10.1520/F2210-02R10.
separately that according to its proposed labeling is for use
The boldface numbers in parentheses refer to the list of references at the end of
this standard. only with another individually specified investigational drug,
Copyright © ASTM International, 100 Barr Harbor Drive, PO Box C700, West Conshohocken, PA 19428-2959. United States
F2210 − 02 (2010)
device, or biological product where both are required to 2.1.21 tissue,n—agroupingofcellsandextracellularmatrix
achieve the intended use, indication, or effect.” Furthermore, (that is, soluble and insoluble, fibrous and nonfibrous biologi-
“many somatic cell products administered to patients will be cal materials) that collectively have a specific structure and
combinations of a biological product and a device or of a drug, function.After embryonic and early fetal stages, there are four
a biological product, and a device.” (5)The term “combination primary tissues which may have various forms: (1) epithelium,
product” may apply to TEMPs. mesothelium, or endothelium, or combination thereof; (2)
connective tissues (for example, adipose, blood, bone, and
2.1.7 cross-contamination, n—the unintended presence of a
cartilage and loose connective tissue); (3) muscle tissue (that
cell or a material with another cell or material.
is, smooth, skeletal, cardiac); and (4) nerve tissue. Within a
2.1.8 disinfection, n—the destruction or reduction of patho-
differentiated organ, all four primary tissue types are repre-
genic and other kinds of microorganisms by thermal or
sented.Atissueanditsderivativesmaybeusedasacomponent
chemicalmeans(forexample,alcohol,antibiotics,germicides).
of a TEMP.
2.1.9 donor, n—a living or deceased organism who is the
2.1.22 transplantation, n—fortherapeuticpurposes,thepro-
source of cells or tissues, or both, for research or further
cessofimplantinginonepart,cells,tissue(s),ororgan(s)taken
processing for transplantation in accordance with established
from another part or from another individual. Transplantation
medical criteria and procedures.
in this sense is regulated by the U.S. Food and Drug Admin-
2.1.10 genetically modified, vt—referring to cells, tissues,
istration (FDA) under 21 CFR Parts 16 and 1270 (1) and 21
and organs of any origin that have an altered or modified
CFR Parts 207, 807, and 1271 (2).
genetic content.
2.1.23 xenogeneic or xenogenic, n—cells, tissues, and or-
2.1.11 implantation, n—the procedure of inserting materials
gans in which the donor and recipient belong to different
such as a cell(s), tissue(s), or organ(s) for therapeutic purposes.
species. Synonyms: xenogenous, heterogeneic,or heterolo-
Synonym: graft or grafting. TEMPs may be applied to a
gous.
recipient by implantation or grafting.
2.1.24 xenotransplantation, n—any procedure that involves
2.1.12 in-process control, n—monitoring and, if necessary,
the transplantation or infusion into a human recipient of either
adjustments performed to ensure that the process conforms to
(1) live cells, tissues, or organs from a nonhuman animal
its specification. The control of the environment or equipment
source or (2) human body fluids, cells, tissues, or organs that
may be part of in-process control.
have had ex vivo contact with live nonhuman cells, tissues, or
organs (24).
2.1.13 organ, n—a differentiated part of an organism that
performs specific functions. Organs are biologic body parts,
3. Significance and Use
thatafterembryonicandearlyfetalstages,arecomposedofthe
four primary tissue types (that is, epithelial/mesothelial/
3.1 This guide describes the general product development
endothelial, connective, muscular, and nervous tissues) that
criteria and analyses applicable to processing of cells, tissues,
form a specific structure. For example, the intestine aids
andorgansusedfortheproductionofTEMPs.Forthepurposes
digestionand,simplyput,itiscomposedofanepitheliallining,
of this guide, cells, tissues, and organs may be derived from
looseconnectivetissue,nervoustissue,andsmoothmuscle.An
any organism at any developmental stage and in any state of
organ and its derivatives may be used as a component of a
health. For example, this guide applies to stem, progenitor,
TEMP.
somatic,andgermlinecells,aswellascellsfromspecifictissue
2.1.14 processing, vt—any activity performed on cells, and organ types. This guide also applies to cells, tissues, and
organs from healthy, diseased, or injured embryos to adults.
tissues,andorgansotherthanrecovery,suchaspreparationand
preservation for storage and packaging.
3.2 Cells, tissues, and organs may be combined with a
2.1.15 processing materials, n—any item or material that is scaffoldandmaycontainlocallyorsystemicallyactingbiomol-
not a component of the TEMP and is in contact with the cells,
eculesoradrug(medicinal)product.ThistypeofTEMPwould
tissues, and organs during processing. be a “combination product.”
2.1.16 recipient, n—the individual or organism into whom
4. Facility, Reagents, and Procedures
materials are grafted or implanted.
4.1 Facility:
2.1.17 recovery, n—the obtaining of cells or tissues which
4.1.1 Receipt, Inspection, and Storage—Facility issues in-
may be used for the production of TEMPs.
cluding establishment of clean room classifications, training of
2.1.18 reprocessing, vt—the reworking of cells, tissues, and
personnel, environmental monitoring, sampling plans, and
organs of unacceptable quality from a defined stage of
limits should comply with current good manufacturing prac-
processing, so that the quality may be rendered acceptable by
tices (cGMP) (6, 7) and AATB standard for tissue banking
one or more additional operations.
related to good tissue practices (cGTP) (8). The FDA has
2.1.19 stem cells, n—progenitor cells capable of self-
proposed a new regulation on current good tissue practice
replication, proliferation, and differentiation.
(GTP) which, if finalized, would also be applicable, for
2.1.20 syngeneic, n—cells, tissues, and organs in which the example, FDA 21 CFR 1271 (9). All regions should be
donor has an unreactive genotype with the recipient. Syn- qualifiedusingarationaleandscientificallysoundqualification
onyms: syngraft, isograft, isogeneic,or isogenic. program that includes: (1) information on traceability, (2)
F2210 − 02 (2010)
assessment of risks for each material, and (3) the specific 4.3.2 Processing Area—Guidelines for the processing area
characterization tests. Guidelines for the storage of materials must be followed to demonstrate qualified procedures and
for processing can be found in FDA21CFR 820 (6) as well as equipment which are able to keep contamination below a
in GMP guidelines for shelf-life (2, 8). specified level (19, 25-27).
4.3.2.1 Environmental Monitoring Controls—
4.2 Reagents:
Environmental controls typically include establishing and
4.2.1 Tissue Culture Components—All media and reagents
maintaining clean room classifications at appropriate baseline
usedforthegrowthormaintenanceofcells,tissues,andorgans
levels through scheduled monitoring (28). cGMP guidelines
should be manufactured under cGMP guidelines or be pur-
should attempt to meet Class 100 requirements for critical
chased from an organization that meets the guidelines (6).
aseptic processing operations (6, 19). The adequacy of the
Ideally, all media and reagents should be of non-animal origin
clean room environment is monitored by close microbiological
orcontainnocomponentsofanimalorigin (10)tominimizethe
surveillance of air, water, surfaces, clean room, and personnel.
opportunity for virus or prion contamination and transmission.
Routine environmental monitoring with established alert levels
At the minimum, one should utilize media and reagents from
can provide early warning on the adequacy of cleaning and
organizations that have applied stringent sourcing controls and
sanitization procedures before action levels are exceeded. In
have validated terminal processes to minimize the risk of
addition to the environmental monitoring of the production
infection (11) It would be even more ideal, when working with
area, products can be monitored for microbiological control
animal cells, tissues, or derivatives, to obtain these biological
during critical manufacturing steps (19, 26, 29, 30).
materials from special breeding facilities (for instance, closed
4.3.2.2 Preventive Maintenance Procedures and Routine
pathogen-free herds) and to include control ancestors.
Calibration—Preventive maintenance procedures and calibra-
4.2.1.1 Basal Culture Media and Supplements—Guidelines
tion should be performed on equipment at scheduled intervals.
for sterile drug products produced by aseptic processing are
Calibrations, where appropriate, should be against traceable
published by CBER, 6/87 (12). Additional information con-
standards, for instance U.S. National Institute of Standards and
cerning the use of basal media, supplements, recombinant,
Technology (NIST) standards.
animal origin, non-animal origin, enzymes, feeder cells, sub-
4.4 Donor Screening:
strates (two or three dimensional; exogenous versus
4.4.1 Human Sources—General donor suitability which
endogenous), animal derived, non-animal derived, and other
covers aspects of testing for diseases (microbial and viral) and
components of animal origin can be can be found in Brown et
general safety can be completed by the manufacturer with
al. (10). Validation of aseptic filling for solution drug products
validated tests methods or by CLIAcertified testing laboratory
is published by the PDA, 1980 (13). Quality assurance mea-
(6). If using autologous donors, screening and testing of donor
sures for acceptance of all components, including media,
materials intended for transplantation is recommended and
serum, and other additives should include records detailing
mandatory for allogeneic s
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