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1271.270 Records. 1271.290 Tracking. 1271.320 Complaint file.

Subpart E-Additional Requirements for Establishments Described in & 1271.10

1271.22 How and where do I register and sub

mit an HCT/P list? 1271.25 What information is required for es

tablishment registration and HCT/P list

ing? 1271.26 When must I amend my establish

ment registration? 1271.27 Will FDA assign me a registration

number? 1271.37 Will establishment registrations and

HCT/P listings be available for inspection, and how do I request information on registrations and listings?

1271.330 Applicability. 1271.350 Reporting. 1271.370 Labeling.

Subpart F-Inspection and Enforcement of

Establishments Described in § 1271.10 1271.390 Applicability. 1271.400 Inspections. 1271.420 HCT/Ps offered for import. 1271.440 Orders of retention, recall, destruc

tion, and cessation of manufacturing. AUTHORITY: 42 U.S.C. 216, 243, 263a, 264, 271.

SOURCE: 66 FR 5466, Jan. 19, 2001, unless otherwise noted.

Subpart C-Donor Eligibility 1271.45 What requirements does this subpart

contain? 1271.47 What procedures must I establish

and maintain? 1271.50 How do I determine whether a donor

is eligible? 271.55 What records must accompany an

HCT/P after the donor-eligibility determination is complete; and what records

must I maintain? 1271.60 What quarantine and other require

ments apply before the donor-eligibility

determination is complete? 1271.65 How do I store an HCT/P from a

donor determined to be ineligible, and what uses of the HCT/P are not prohib

ited? 1271.75 How do I screen a donor? 1271.80 What are the general requirements

for donor testing? (271.85 What donor testing is required for

different types of cells and tissues? 271.90 Are there exceptions from the re

quirement of determining donor eligibility, and what labeling requirements

apply? Subpart D-Current Good Tissue Practice 271.145 Prevention of the introduction,

transmission, or spread of communicable

diseases. 271.150 Current good tissue practice re

quirements. 271.155 Exemptions and alternatives. 271.160 Establishment and maintenance of

a quality program. 271.170 Personnel. 271.180 Procedures. 271.190 Facilities. 271.195 Environmental control and moni

toring. 271.200 Equipment. 271.210 Supplies and reagents. 271.215 Recovery 271.220 Processing and process controls. 271.225 Process changes. 271.230 Process validation. 271.250 Labeling controls. 271.260 Storage. 271.265 Receipt, predistribution shipment,

and distribution of an HCT/P.

Subpart A-General Provisions $ 1271.1 What are the purpose and

scope of this part? (a) Purpose. The purpose of this part, in conjunction with 88 207.20(f), 210.1(c), 210.2, 807.20(d), and 820.1(a) of this chapter, is to create a unified registration and listing system for establishments that manufacture human cells, tissues, and cellular and tissue-based products (HCT/P's) and to establish donor-eligibility, current good tissue practice, and other procedures to prevent the introduction, transmission, and spread of communicable diseases by HCT/P's.

(b) Scope. (1) If you are an establishment that manufactures HCT/P's that are regulated solely under the authority of section 361 of the Public Health Service Act (the PHS Act), this part requires you to register and list your HCT/P's with the Food and Drug Administration's (FDA's) Center for Biologics Evaluation and Research and to comply with the other requirements contained in this part, whether or not the HCT/P enters into interstate commerce. Those HCT/P's that are regulated solely under the authority of section 361 of the PHS Act are described in $ 1271.10.

(2) If you are an establishment that manufactures HCT/P's that are regulated as drugs, devices and/or biological products under section 351 of the PHS Act and/or the Federal Food, Drug, and Cosmetic Act, $8 207.20(f) and

807.20(d) of this chapter require you to or other reproductive tissue. The folregister and list your HCT/P's fol- lowing articles are not considered HCT: lowing the procedures in subpart B of Ps: this part. Sections 210.1(c), 210.2, (1) Vascularized human organs for 211.1(b), and 820.1(a) of this chapter re- transplantation; quire you to comply with the donor-eli

(2) Whole blood or blood components gibility procedures in subpart C of this

or blood derivative products subject to part and the current good tissue prac

listing under parts 607 and 207 of this tice procedures in subpart D of this part, in addition to all other applicable

chapter, respectively;

(3) Secreted or extracted human regulations.

products, such as milk, collagen, and [66 FR 5466, Jan. 19, 2001, as amended at 69

cell factors; except that semen is conFR 29829, May 25, 2004)

sidered an HCT/P; $ 1271.3 How does FDA define impor

(4) Minimally manipulated bone martant terms in this part?

row for homologous use and not comThe following definitions apply only

bined with another article (except for to this part:

water, crystalloids, or a sterilizing, (a) Autologous use means the implan preserving, or storage agent, if the adtation, transplantation, infusion, or dition of the agent does not raise new transfer of human cells or tissue back clinical safety concerns with respect to into the individual from whom the the bone marrow); cells or tissue were recovered.

(5) Ancillary products used in the (b) Establishment means a place of manufacture of HCT/P; business under one management, at (6) Cells, tissues, and organs derived one general physical location, that en

from animals other than humans; and gages in the manufacture of human

(7) In vitro diagnostic products as decells, tissues, and cellular and tissue

fined in $ 809.3(a) of this chapter. based products. "Establishment" in

(e) Manufacture means, but is not limcludes:

ited to, any or all steps in the recov(1) Any individual, partnership, corporation, association, or other legal en

ery, processing, storage, labeling, packtity engaged in the manufacture of

aging, or distribution of any human human cells, tissues, and cellular and

cell or tissue, and the screening or tissue-based products; and

testing of the cell or tissue donor. (2) Facilities that engage in contract (f) Minimal manipulation means: manufacturing services for a manufac (1) For structural tissue, processing turer of human cells, tissues, and cel- that does not alter the original rellular and tissue-based products.

evant characteristics of the tissue re(c) Homologous use means the repair, lating to the tissue's utility for reconreconstruction, replacement, or sup struction, repair, or replacement; and plementation of a recipient's cells or (2) For cells or nonstructural tissues, tissues with an HCT P that performs

processing that does not alter the relthe same basic function or functions in

evant biological characteristics of cells the recipient as in the donor.

or tissues. (d) Human cells, tissues, or cellular or

(g) Transfer means the placement of tissue-based products (HCT Ps) means ar

human reproductive cells or tissues ticles containing or consisting of

into a human recipient. human cells or tissues that are intended for implantation, transplan

(h) Biohazard legend appears on the tation, infusion, or transfer into a

label as follows and is used to mark human recipient. Examples of HCT Ps

HCT Ps that present a known or susinclude but are not limited to. bone. pected relevant communicable disease ligament, skin, dura mater, heart risk. valve, cornea, hematopoietic stem progenitor cells derived from peripheral and cord blood, manipulated autologous chondrocytes, epithelial cells on a synthetic matrix, and semen

BIOHAZARD (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.

) 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.

(1) 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 $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 affin

ity relationship, and/or the primary treating physician).

(0) 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 CreutzfeldtJakob 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:

[graphic]

(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.

(2) 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,

eps to inactivate or remove adven- (3) The manufacture of the HCT/P tious agents, preservation for stor- does not involve the combination of ge, and removal from storage.

the cells or tissues with another arti(gg) Quality audit means a docu- cle, except for water, crystalloids, or a lented, independent inspection and re- sterilizing, preserving, or storage iew of an establishment's activities agent, provided that the addition of

lated to core CGTP requirements. water, crystalloids, or the sterilizing, he purpose of a quality audit is to preserving, or storage agent does not erify, by examination and evaluation raise new clinical safety concerns with f objective evidence, the degree of respect to the HCT/P; and ompliance with those aspects of the (4) Either: uality program under review.

(i) The HCT/P does not have a sys(hh) Quality program means an orga- temic effect and is not dependent upon ization's comprehensive system for the metabolic activity of living cells ianufacturing and tracking HCT/Ps in for its primary function; or ccordance with this part. A quality (ii) The HCT/P has a systemic effect rogram is designed to prevent, detect, or is dependent upon the metabolic acnd correct deficiencies that may lead tivity of living cells for its primary o circumstances that increase the risk function, and: f introduction, transmission, or (a) Is for autologous use; pread of communicable diseases.

(6) Is for allogeneic use in a first-de(ii) Recovery means obtaining from a gree or second-degree blood relative; or .uman donor cells or tissues that are

(c) Is for reproductive use. ntended for use in human implanta

(b) If you are a domestic or foreign ion, transplantation, infusion, or

establishment that manufactures an ransfer.

HCT/P described in paragraph (a) of (jj) Storage means holding HCT/Ps for

this section: uture processing and/or distribution

(1) You must register with FDA; (kk) Validation means confirmation

(2) You must submit to FDA a list of y examination and provision of objec

each HCT/P manufactured; and ive evidence that particular require

(3) You must comply with the other nents can consistently be fulfilled.

requirements contained in this part. Yalidation of a process, or process vali'ation, means establishing by objective (66 FR 5466, Jan. 19, 2001, as amended at 69 vidence that a process consistently FR 68681, Nov. 24, 2004) produces a result or HCT/P meeting its redetermined specifications.

$ 1271.15 Are there any exceptions

from the requirements of this part? (11) Verification means confirmation y examination and provision of objec (a) You are not required to comply ive evidence that specified require with the requirements of this part if nents have been fulfilled.

you are an establishment that uses

HCT/P's solely for nonclinical sci66 FR 5466, Jan. 19, 2001, as amended at 68 'R 3826, Jan. 27, 2004; 69 FR 29829, May 25,

entific or educational purposes. 004; 69 FR 68680, Nov. 24, 2004)

(b) You are not required to comply

with the requirements of this part if 1271.10 Are my HCT/P's regulated you are an establishment that removes

solely under section 361 of the PHS HCT/P's from an individual and imAct and the regulations in this part, plants such HCT/P's into the same indiand if so what must I do?

vidual during the same surgical proce(a) An HCT/P is regulated solely dure. inder section 361 of the PHS Act and (c) You are not required to comply he regulations in this part if it meets with the requirements of this part if 11 of the following criteria:

you are a carrier who accepts, receives, (1) The HCT/P is minimally manipu carries, or delivers HCT/P's in the ated;

usual course of business as a carrier. (2) The HCT/P is intended for homolo- (d) You are not required to comply sous use only, as reflected by the label- with the requirements of this part if ng, advertising, or other indications of you are an establishment that does not he manufacturer's objective intent; recover, screen, test, process, label,

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