[Code of Federal Regulations]
[Title 21, Volume 8]
[Revised as of April 1, 2008]
From the U.S. Government Printing Office via GPO Access
[CITE: 21CFR1271.3]

[Page 719-722]
 
                        TITLE 21--FOOD AND DRUGS
 
CHAPTER I--FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN 
                          SERVICES (CONTINUED)
 
PART 1271_HUMAN CELLS, TISSUES, AND CELLULAR AND TISSUE-BASED
PRODUCTS--Table of Contents
 
                      Subpart A_General Provisions
 
Sec. 1271.3  How does FDA define important terms in this part?

    The following definitions apply only to this part:
    (a) Autologous use means the implantation, transplantation, 
infusion, or transfer of human cells or tissue back into the individual 
from whom the cells or tissue were recovered.
    (b) Establishment means a place of business under one management, at 
one general physical location, that engages in the manufacture of human 
cells, tissues, and cellular and tissue-based products. 
``Establishment'' includes:
    (1) Any individual, partnership, corporation, association, or other 
legal entity engaged in the manufacture of human cells, tissues, and 
cellular and tissue-based products; and
    (2) Facilities that engage in contract manufacturing services for a 
manufacturer of human cells, tissues, and cellular and tissue-based 
products.
    (c) Homologous use means the repair, reconstruction, replacement, or 
supplementation of a recipient's cells or tissues with an HCT/P that 
performs the same basic function or functions in the recipient as in the 
donor.
    (d) Human cells, tissues, or cellular or tissue-based products (HCT/
Ps) means articles containing or consisting of human cells or tissues 
that are intended for implantation, transplantation, infusion, or 
transfer into a human recipient. Examples of HCT/Ps include, but are not 
limited to, bone, ligament, skin, dura mater, heart valve, cornea, 
hematopoietic stem/progenitor cells derived from peripheral and cord 
blood, manipulated autologous chondrocytes, epithelial cells on a 
synthetic matrix, and semen or other reproductive tissue. The following 
articles are not considered HCT/Ps:
    (1) Vascularized human organs for transplantation;
    (2) Whole blood or blood components or blood derivative products 
subject to listing under parts 607 and 207 of this chapter, 
respectively;
    (3) Secreted or extracted human products, such as milk, collagen, 
and cell factors; except that semen is considered an HCT/P;
    (4) Minimally manipulated bone marrow for homologous use and not 
combined with another article (except for water, crystalloids, or a 
sterilizing, preserving, or storage agent, if the addition of the agent 
does not raise new clinical safety concerns with respect to the bone 
marrow);
    (5) Ancillary products used in the manufacture of HCT/P;
    (6) Cells, tissues, and organs derived from animals other than 
humans; and
    (7) In vitro diagnostic products as defined in Sec. 809.3(a) of 
this chapter.
    (8) Blood vessels recovered with an organ, as defined in 42 CFR 
121.2, that are intended for use in organ transplantation and labeled 
``For use in organ transplantation only.''
    (e) Manufacture means, but is not limited to, any or all steps in 
the recovery, processing, storage, labeling, packaging, or distribution 
of any human cell or tissue, and the screening or testing of the cell or 
tissue donor.
    (f) Minimal manipulation means:
    (1) For structural tissue, processing that does not alter the 
original relevant characteristics of the tissue relating to the tissue's 
utility for reconstruction, repair, or replacement; and
    (2) For cells or nonstructural tissues, processing that does not 
alter the relevant biological characteristics of cells or tissues.
    (g) Transfer means the placement of human reproductive cells or 
tissues into a human recipient.
    (h) Biohazard legend appears on the label as follows and is used to 
mark HCT/Ps that present a known or suspected relevant communicable 
disease risk.

[[Page 720]]

[GRAPHIC] [TIFF OMITTED] TR25MY04.000

    (i) Blood component means a product containing a part of human blood 
separated by physical or mechanical means.
    (j) Colloid means:
    (1) A protein or polysaccharide solution, such as albumin, dextran, 
or hetastarch, that can be used to increase or maintain osmotic 
(oncotic) pressure in the intravascular compartment; or
    (2) Blood components such as plasma and platelets.
    (k) Crystalloid means an isotonic salt and/or glucose solution used 
for electrolyte replacement or to increase intravascular volume, such as 
saline solution, Ringer's lactate solution, or 5 percent dextrose in 
water.
    (l) Directed reproductive donor means a donor of reproductive cells 
or tissue (including semen, oocytes, and embryos to which the donor 
contributed the spermatozoa or oocyte) to a specific recipient, and who 
knows and is known by the recipient before donation. The term directed 
reproductive donor does not include a sexually intimate partner under 
Sec. 1271.90.
    (m) Donor means a person, living or dead, who is the source of cells 
or tissue for an HCT/P.
    (n) Donor medical history interview means a documented dialog about 
the donor's medical history and relevant social behavior, including 
activities, behaviors, and descriptions considered to increase the 
donor's relevant communicable disease risk:
    (1) With the donor, if the donor is living and able to participate 
in the interview, or
    (2) If not, with an individual or individuals able to provide the 
information sought in the interview (e.g., the donor's next-of-kin, the 
nearest available relative, a member of the donor's household, an 
individual with an affinity relationship, and/or the primary treating 
physician).
    (o) Physical assessment of a cadaveric donor means a limited autopsy 
or recent antemortem or postmortem physical examination of the donor to 
assess for signs of a relevant communicable disease and for signs 
suggestive of any risk factor for a relevant communicable disease.
    (p) Plasma dilution means a decrease in the concentration of the 
donor's plasma proteins and circulating antigens or antibodies resulting 
from the transfusion of blood or blood components and/or infusion of 
fluids.
    (q) Quarantine means the storage or identification of an HCT/P, to 
prevent improper release, in a physically separate area clearly 
identified for such use, or through use of other procedures, such as 
automated designation.
    (r) Relevant communicable disease agent or disease means:
    (1)(i) For all human cells and tissues, a communicable disease or 
disease agent listed as follows:
    (A) Human immunodeficiency virus, types 1 and 2;
    (B) Hepatitis B virus;
    (C) Hepatitis C virus;
    (D) Human transmissible spongiform encephalopathy, including 
Creutzfeldt-Jakob disease; and
    (E) Treponema pallidum.
    (ii) For viable, leukocyte-rich cells and tissues, a cell-associated 
disease agent or disease listed as follows:
    (A) Human T-lymphotropic virus, type I; and
    (B) Human T-lymphotropic virus, type II.
    (iii) For reproductive cells or tissues, a disease agent or disease 
of the genitourinary tract listed as follows:
    (A) Chlamydia trachomatis; and
    (B) Neisseria gonorrhea.
    (2) A disease agent or disease not listed in paragraph (r)(1) of 
this section:
    (i) For which there may be a risk of transmission by an HCT/P, 
either to the recipient of the HCT/P or to those people who may handle 
or otherwise come in contact with it, such as medical personnel, because 
the disease agent or disease:
    (A) Is potentially transmissible by an HCT/P and
    (B) Either of the following applies:

[[Page 721]]

    (1) The disease agent or disease has sufficient incidence and/or 
prevalence to affect the potential donor population, or
    (2) The disease agent or disease may have been released accidentally 
or intentionally in a manner that could place potential donors at risk 
of infection;
    (ii) That could be fatal or life-threatening, could result in 
permanent impairment of a body function or permanent damage to body 
structure, or could necessitate medical or surgical intervention to 
preclude permanent impairment of body function or permanent damage to a 
body structure; and
    (iii) For which appropriate screening measures have been developed 
and/or an appropriate screening test for donor specimens has been 
licensed, approved, or cleared for such use by FDA and is available.
    (s) Relevant medical records means a collection of documents that 
includes a current donor medical history interview; a current report of 
the physical assessment of a cadaveric donor or the physical examination 
of a living donor; and, if available, the following:
    (1) Laboratory test results (other than results of testing for 
relevant communicable disease agents required under this subpart);
    (2) Medical records;
    (3) Coroner and autopsy reports; and
    (4) Records or other information received from any source pertaining 
to risk factors for relevant communicable disease (e.g., social 
behavior, clinical signs and symptoms of relevant communicable disease, 
and treatments related to medical conditions suggestive of risk for 
relevant communicable disease).
    (t) Responsible person means a person who is authorized to perform 
designated functions for which he or she is trained and qualified.
    (u) Urgent medical need means that no comparable HCT/P is available 
and the recipient is likely to suffer death or serious morbidity without 
the HCT/P.
    (v) Act means the Federal Food, Drug, and Cosmetic Act.
    (w) PHS Act means the Public Health Service Act.
    (x) FDA means the Food and Drug Administration.
    (y) Adverse reaction means a noxious and unintended response to any 
HCT/P for which there is a reasonable possibility that the HCT/P caused 
the response.
    (z) Available for distribution means that the HCT/P has been 
determined to meet all release criteria.
    (aa) Complaint means any written, oral, or electronic communication 
about a distributed HCT/P that alleges:
    (1) That an HCT/P has transmitted or may have transmitted a 
communicable disease to the recipient of the HCT/P; or
    (2) Any other problem with an HCT/P relating to the potential for 
transmission of communicable disease, such as the failure to comply with 
current good tissue practice.
    (bb) Distribution means any conveyance or shipment (including 
importation and exportation) of an HCT/P that has been determined to 
meet all release criteria, whether or not such conveyance or shipment is 
entirely intrastate. If an entity does not take physical possession of 
an HCT/P, the entity is not considered a distributor.
    (cc) Establish and maintain means define, document (in writing or 
electronically), and implement; then follow, review, and, as needed, 
revise on an ongoing basis.
    (dd) HCT/P deviation means an event:
    (1) That represents a deviation from applicable regulations in this 
part or from applicable standards or established specifications that 
relate to the prevention of communicable disease transmission or HCT/P 
contamination; or
    (2) That is an unexpected or unforeseeable event that may relate to 
the transmission or potential transmission of a communicable disease or 
may lead to HCT/P contamination.
    (ee) Importer of record means the person, establishment, or its 
representative responsible for making entry of imported goods in 
accordance with all laws affecting such importation.
    (ff) Processing means any activity performed on an HCT/P, other than 
recovery, donor screening, donor testing, storage, labeling, packaging, 
or distribution, such as testing for microorganisms, preparation, 
sterilization,

[[Page 722]]

steps to inactivate or remove adventitious agents, preservation for 
storage, and removal from storage.
    (gg) Quality audit means a documented, independent inspection and 
review of an establishment's activities related to core CGTP 
requirements. The purpose of a quality audit is to verify, by 
examination and evaluation of objective evidence, the degree of 
compliance with those aspects of the quality program under review.
    (hh) Quality program means an organization's comprehensive system 
for manufacturing and tracking HCT/Ps in accordance with this part. A 
quality program is designed to prevent, detect, and correct deficiencies 
that may lead to circumstances that increase the risk of introduction, 
transmission, or spread of communicable diseases.
    (ii) Recovery means obtaining from a human donor cells or tissues 
that are intended for use in human implantation, transplantation, 
infusion, or transfer.
    (jj) Storage means holding HCT/Ps for future processing and/or 
distribution.
    (kk) Validation means confirmation by examination and provision of 
objective evidence that particular requirements can consistently be 
fulfilled. Validation of a process, or process validation, means 
establishing by objective evidence that a process consistently produces 
a result or HCT/P meeting its predetermined specifications.
    (ll) Verification means confirmation by examination and provision of 
objective evidence that specified requirements have been fulfilled.

[66 FR 5466, Jan. 19, 2001, as amended at 68 FR 3826, Jan. 27, 2004; 69 
FR 29829, May 25, 2004; 69 FR 68680, Nov. 24, 2004]