21cfr1271

Food and Drug Administration, HHS

§ 1271.230

must display records of recent maintenance, cleaning, sanitizing, calibration, and other activities on or near
each piece of equipment, or make the
records readily available to the individuals responsible for performing
these activities and to the personnel
using the equipment. You must maintain records of the use of each piece of
equipment, including the identification
of each HCT/P manufactured with that
equipment.
§ 1271.210

Supplies and reagents.

(a) Verification. You must not use
supplies and reagents until they have
been verified to meet specifications designed to prevent circumstances that
increase the risk of the introduction,
transmission, or spread of communicable diseases. Verification may be
accomplished by the establishment
that uses the supply or reagent, or by
the vendor of the supply or reagent.
(b) Reagents. Reagents used in processing and preservation of HCT/Ps
must be sterile, where appropriate.
(c) In-house reagents. You must validate and/or verify the processes used
for production of in-house reagents.
(d) Records. You must maintain the
following records pertaining to supplies
and reagents:
(1) Records of the receipt of each supply or reagent, including the type,
quantity, manufacturer, lot number,
date of receipt, and expiration date;
(2) Records of the verification of each
supply or reagent, including test results or, in the case of vendor
verification, a certificate of analysis
from the vendor; and
(3) Records of the lot of supply or reagent used in the manufacture of each
HCT/P.
§ 1271.215

Recovery.

If you are an establishment that recovers HCT/Ps, you must recover each
HCT/P in a way that does not cause
contamination or cross-contamination
during recovery, or otherwise increase
the risk of the introduction, transmission, or spread of communicable
disease through the use of the HCT/P.

§ 1271.220
trols.

Processing and process con-

(a) General. If you are an establishment that processes HCT/Ps, you must
process each HCT/P in a way that does
not cause contamination or cross-contamination during processing, and that
prevents
the
introduction,
transmission, or spread of communicable
disease through the use of the HCT/P.
(b) Pooling. Human cells or tissue
from two or more donors must not be
pooled (placed in physical contact or
mixed in a single receptacle) during
manufacturing.
(c) In-process control and testing. You
must ensure that specified requirements, consistent with paragraph (a) of
this section, for in-process controls are
met, and that each in-process HCT/P is
controlled until the required inspection and tests or other verification activities have been completed, or necessary approvals are received and documented. Sampling of in-process HCT/Ps
must be representative of the material
to be evaluated.
(d) Dura mater. (1) When there is a
published validated process that reduces
the
risk
of
transmissible
spongiform encephalopathy, you must
use this process for dura mater (or an
equivalent process that you have validated), unless following this process
adversely affects the clinical utility of
the dura mater.
(2) When you use a published validated process, you must verify such a
process in your establishment.
§ 1271.225

Process changes.

Any change to a process must be
verified or validated in accordance
with § 1271.230, to ensure that the
change does not create an adverse impact elsewhere in the operation, and
must be approved before implementation by a responsible person with appropriate knowledge and background.
You must communicate approved
changes to the appropriate personnel in
a timely manner.
§ 1271.230

Process validation.

(a) General. Where the results of processing described in § 1271.220 cannot be
fully verified by subsequent inspection

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§ 1271.250

21 CFR Ch. I (4–1–06 Edition)

and tests, you must validate and approve the process according to established procedures. The validation activities and results must be documented, including the date and signature of the individual(s) approving the
validation.
(b) Written representation. Any written representation that your processing methods reduce the risk of
transmission of communicable disease
by an HCT/P, including but not limited
to, a representation of sterility or
pathogen inactivation of an HCT/P,
must be based on a fully verified or
validated process.
(c) Changes. When changes to a validated process subject to paragraph (a)
of this section occur, you must review
and evaluate the process and perform
revalidation where appropriate. You
must document these activities.

(1) HCT/P type;
(2) Processing, including the method
of preservation;
(3) Storage conditions; and
(4) Packaging.
(d) Corrective action. You must take
and document corrective action whenever proper storage conditions are not
met.
(e) Acceptable temperature limits. You
must establish acceptable temperature
limits for storage of HCT/Ps at each
step of the manufacturing process to
inhibit the growth of infectious agents.
You must maintain and record storage
temperatures for HCT/Ps. You must periodically review recorded temperatures to ensure that temperatures have
been within acceptable limits.

§ 1271.250 Labeling controls.
(a) General. You must establish and
maintain procedures to control the labeling of HCT/Ps. You must design
these procedures to ensure proper HCT/
P identification and to prevent mixups.
(b) Verification. Procedures must include verification of label accuracy,
legibility, and integrity.
(c) Labeling requirements. Procedures
must ensure that each HCT/P is labeled
in accordance with all applicable labeling requirements, including those in
§§ 1271.55,
1271.60,
1271.65,
1271.90,
1271.290, and 1271.370, and that each
HCT/P made available for distribution
is accompanied by documentation of
the donor eligibility determination as
required under § 1271.55.

(a) Receipt. You must evaluate each
incoming HCT/P for the presence and
significance of microorganisms and inspect for damage and contamination.
You must determine whether to accept,
reject, or place in quarantine each incoming HCT/P, based upon pre-established criteria designed to prevent
communicable disease transmission.
(b) Predistribution shipment. If you
ship an HCT/P within your establishment or between establishments (e.g.,
procurer to processor) and the HCT/P is
not available for distribution as described in paragraph (c) of this section,
you must first determine and document whether pre-established criteria
designed to prevent communicable disease transmission have been met, and
you must ship the HCT/P in quarantine.
(c) Availability for distribution. (1) Before making an HCT/P available for
distribution, you must review manufacturing and tracking records pertaining to the HCT/P, and, on the basis
of that record review, you must verify
and document that the release criteria
have been met. A responsible person
must document and date the determination that an HCT/P is available
for distribution.
(2) You must not make available for
distribution an HCT/P that is in quarantine, is contaminated, is recovered
from a donor who has been determined

§ 1271.260 Storage.
(a) Control of storage areas. You must
control your storage areas and stock
rooms to prevent:
(1) Mix-ups, contamination, and
cross-contamination of HCT/Ps, supplies, and reagents, and
(2) An HCT/P from being improperly
made available for distribution.
(b) Temperature. You must store HCT/
Ps at an appropriate temperature.
(c) Expiration date. Where appropriate, you must assign an expiration
date to each HCT/P based on the following factors:

§ 1271.265 Receipt,
predistribution
shipment, and distribution of an
HCT/P.

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