21cfr1271

§ 1271.195

21 CFR Ch. I (4–1–06 Edition)

(c) Operations. You must divide a facility used in the manufacture of HCT/
Ps into separate or defined areas of
adequate size for each operation that
takes place in the facility, or you must
establish and maintain other control
systems to prevent improper labeling,
mix-ups,
contamination,
cross-contamination, and accidental exposure of
HCT/Ps
to
communicable
disease
agents.
(d) Procedures and records. (1) You
must establish and maintain procedures for facility cleaning and sanitation for the purpose of preventing the
introduction, transmission, or spread
of communicable disease. These procedures must assign responsibility for
sanitation and must describe in sufficient detail the cleaning methods to be
used and the schedule for cleaning the
facility.
(2) You must document, and maintain records of, all cleaning and sanitation activities performed to prevent
contamination of HCT/Ps. You must retain such records 3 years after their
creation.
§ 1271.195 Environmental control and
monitoring.
(a) Environmental control. Where environmental conditions could reasonably
be expected to cause contamination or
cross-contamination of HCT/Ps or
equipment, or accidental exposure of
HCT/Ps
to
communicable
disease
agents, you must adequately control
environmental conditions and provide
proper conditions for operations. Where
appropriate, you must provide for the
following control activities or systems:
(1) Temperature and humidity controls;
(2) Ventilation and air filtration;
(3) Cleaning and disinfecting of
rooms and equipment to ensure aseptic
processing operations; and
(4) Maintenance of equipment used to
control conditions necessary for aseptic processing operations.
(b) Inspections. You must inspect each
environmental control system periodically to verify that the system, including necessary equipment, is adequate
and functioning properly. You must
take appropriate corrective action as
necessary.

(c) Environmental monitoring. You
must monitor environmental conditions where environmental conditions
could reasonably be expected to cause
contamination or cross-contamination
of HCT/Ps or equipment, or accidental
exposure of HCT/Ps to communicable
disease agents. Where appropriate, you
must provide environmental monitoring for microorganisms.
(d) Records. You must document, and
maintain records of, environmental
control and monitoring activities.
§ 1271.200

Equipment.

(a) General. To prevent the introduction, transmission, or spread of communicable diseases, equipment used in
the manufacture of HCT/Ps must be of
appropriate design for its use and must
be suitably located and installed to facilitate operations, including cleaning
and maintenance. Any automated, mechanical, electronic, or other equipment used for inspection, measuring,
or testing in accordance with this part
must be capable of producing valid results. You must clean, sanitize, and
maintain equipment according to established schedules.
(b) Procedures and schedules. You
must establish and maintain procedures for cleaning, sanitizing, and
maintaining equipment to prevent
malfunctions, contamination or crosscontamination, accidental exposure of
HCT/Ps
to
communicable
disease
agents, and other events that could
reasonably be expected to result in the
introduction, transmission, or spread
of communicable diseases.
(c) Calibration of equipment. Where appropriate, you must routinely calibrate
according to established procedures
and schedules all automated, mechanical, electronic, or other equipment
used for inspection, measuring, and
testing in accordance with this part.
(d) Inspections. You must routinely
inspect equipment for cleanliness, sanitation, and calibration, and to ensure
adherence to applicable equipment
maintenance schedules.
(e) Records. You must document and
maintain records of all equipment
maintenance, cleaning, sanitizing, calibration, and other activities performed
in accordance with this section. You

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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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