下一步英文21CFR PART211(FDA的cGMP)

2021年1月19日发(作者：健身服务)
[Code of Federal Regulations]


[Revised as of April 1, 2010]

[CITE: 21CFR211]

[Title 21, Volume 4]
TITLE 21--FOOD AND DRUGS
CHAPTER I--FOOD AND DRUG ADMINISTRATION
DEPARTMENT OF HEALTH AND HUMAN SERVICES
SUBCHAPTER C--DRUGS: GENERAL


PART 211
CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED PHARMACEUTICALS


Subpart A--General Provisions

Sec. 211.1 Scope.
(a)
The
regulations
in
this
part
contain
the
minimum
current
good
manufacturing
practice
for
preparation
of
drug
products
for administration to humans or animals.
(b) The current good manufacturing practice regulations in this chapter as they pertain to drug products; in parts
600 through 680 of this chapter, as they pertain to drugs that are also biological products for human use; and in part
1271
of
this
chapter,
as
they
are
applicable
to
drugs
that
are
also
human
cells,
tissues,
and
cellular
and
tissue-based
products (HCT/Ps) and that are drugs (subject to review under an application submitted under section 505 of the act
or under a biological product license application under section 351 of the Public Health Service Act); supplement and
do not supersede the regulations in this part unless the regulations explicitly provide otherwise. In the event of
a conflict between applicable regulations in this part and in other parts of this chapter, or in parts 600 through
680 of this chapter, or in part 1271 of this chapter, the regulation specifically applicable to the drug product in
question shall supersede the more general.
(c)
Pending
consideration
of
a
proposed
exemption,
published
in
theFederal
Registerof
September
29,
1978,
the
requirements
in
this
part
shall
not
be
enforced
for
OTC
drug
products
if
the
products
and
all
their
ingredients
are
ordinarily
marketed
and consumed as human foods, and which products may also fall within the legal definition of drugs by virtue of their
intended
use.
Therefore,
until
further
notice,
regulations
under
part
110
of
this
chapter,
and
where
applicable,
parts
113 to 129 of this chapter, shall be applied in determining whether these OTC drug products that are also foods are
manufactured, processed, packed, or held under current good manufacturing practice.
Link to an amendment published at 74 FR 65431, Dec. 10, 2009.
[43 FR 45077, Sept. 29, 1978, as amended at 62 FR 66522, Dec. 19, 1997; 69 FR 29828, May 25, 2004]
Sec. 211.3 Definitions.
The definitions set forth in 210.3 of this chapter apply in this part.
Subpart B--Organization and Personnel

Sec. 211.22 Responsibilities of quality control unit.
(a) There shall be a quality control unit that shall have the responsibility and authority to approve or reject all
components,
drug
product
containers,
closures,
in-process
materials,
packaging
material,
labeling,
and
drug
products,
and the authority to review production records to assure that no errors have occurred or, if errors have occurred,
that they have been fully investigated. The quality control unit shall be responsible for approving or rejecting drug
products manufactured, processed, packed, or held under contract by another company.
(b)
Adequate
laboratory
facilities
for
the
testing
and
approval
(or
rejection)
of
components,
drug
product
containers,
closures,
packaging
materials,
in-process
materials,
and
drug
products
shall
be
available
to
the
quality
control
unit.
(c)
The
quality
control
unit
shall
have
the
responsibility
for
approving
or
rejecting
all
procedures
or
specifications
impacting on the identity, strength, quality, and purity of the drug product.
(d)
The
responsibilities
and
procedures
applicable
to
the
quality
control
unit
shall
be
in
writing;
such
written
procedures
shall be followed.
Sec. 211.25 Personnel qualifications.
(a) Each person engaged in the manufacture, processing, packing, or holding of a drug product shall have education,
training,
and
experience,
or
any
combination
thereof,
to
enable
that
person
to
perform
the
assigned
functions.
Training
shall
be
in
the
particular
operations
that
the
employee
performs
and
in
current
good
manufacturing
practice
(including
the
current
good
manufacturing
practice
regulations
in
this
chapter
and
written
procedures
required
by
these
regulations)
as
they
relate
to
the
employee's
functions.
Training
in
current
good
manufacturing
practice
shall
be
conducted
by
qualified
individuals on a continuing basis and with sufficient frequency to assure that employees remain familiar with CGMP
requirements applicable to them.
(b) Each person responsible for supervising the manufacture, processing, packing, or holding of a drug product shall
have
the
education,
training,
and
experience,
or
any
combination
thereof,
to
perform
assigned
functions
in
such
a
manner
as
to
provide
assurance
that
the
drug
product
has
the
safety,
identity,
strength,
quality,
and
purity
that
it
purports
or is represented to possess.
(c) There shall be an adequate number of qualified personnel to perform and supervise the manufacture, processing,
packing, or holding of each drug product.
Sec. 211.28 Personnel responsibilities.
(a) Personnel engaged in the manufacture, processing, packing, or holding of a drug product shall wear clean clothing
appropriate for the duties they perform. Protective apparel, such as head, face, hand, and arm coverings, shall be
worn as necessary to protect drug products from contamination.
(b) Personnel shall practice good sanitation and health habits.
(c)
Only
personnel
authorized
by
supervisory
personnel
shall
enter
those
areas
of
the
buildings
and
facilities
designated
as limited-access areas.
(d)
Any
person
shown
at
any
time
(either
by
medical
examination
or
supervisory
observation)
to
have
an
apparent
illness
or
open
lesions
that
may
adversely
affect
the
safety
or
quality
of
drug
products
shall
be
excluded
from
direct
contact
with components, drug product containers, closures, in-process materials, and drug products until the condition is
corrected or determined by competent medical personnel not to jeopardize the safety or quality of drug products. All
personnel
shall
be
instructed
to
report
to
supervisory
personnel
any
health
conditions
that
may
have
an
adverse
effect
on drug products.
Sec. 211.34 Consultants.
Consultants
advising
on
the
manufacture,
processing,
packing,
or
holding
of
drug
products
shall
have
sufficient
education,
training, and experience, or any combination thereof, to advise on the subject for which they are retained. Records
shall
be
maintained
stating
the
name,
address,
and
qualifications
of
any
consultants
and
the
type
of
service
they
provide.
Subpart C--Buildings and Facilities

Sec. 211.42 Design and construction features.
(a) Any building or buildings used in the manufacture, processing, packing, or holding of a drug product shall be of
suitable size, construction and location to facilitate cleaning, maintenance, and proper operations.
(b)
Any
such
building
shall
have
adequate
space
for
the
orderly
placement
of
equipment
and
materials
to
prevent
mixups
between different components, drug product containers, closures, labeling, in-process materials, or drug products,
and
to
prevent
contamination.
The
flow
of
components,
drug
product
containers,
closures,
labeling,
in-process
materials,
and drug products through the building or buildings shall be designed to prevent contamination.
(c)
Operations
shall
be
performed
within
specifically
defined
areas
of
adequate
size.
There
shall
be
separate
or
defined
areas
or
such
other
control
systems
for
the
firm's
operations
as
are
necessary
to
prevent
contamination
or
mixups
during
the course of the following procedures:
(1) Receipt, identification, storage, and withholding from use of components, drug product containers, closures, and
labeling, pending the appropriate sampling, testing, or examination by the quality control unit before release for
manufacturing or packaging;
(2) Holding rejected components, drug product containers, closures, and labeling before disposition;
(3) Storage of released components, drug product containers, closures, and labeling;
(4) Storage of in-process materials;
(5) Manufacturing and processing operations;
(6) Packaging and labeling operations;
(7) Quarantine storage before release of drug products;
(8) Storage of drug products after release;
(9) Control and laboratory operations;
(10) Aseptic processing, which includes as appropriate:
(i) Floors, walls, and ceilings of smooth, hard surfaces that are easily cleanable;
(ii) Temperature and humidity controls;
(iii) An air supply filtered through high-efficiency particulate air filters under positive pressure, regardless of
whether flow is laminar or nonlaminar;
(iv) A system for monitoring environmental conditions;
(v) A system for cleaning and disinfecting the room and equipment to produce aseptic conditions;
(vi) A system for maintaining any equipment used to control the aseptic conditions.
(d) Operations relating to the manufacture, processing, and packing of penicillin shall be performed in facilities
separate from those used for other drug products for human use.
[43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995]
Sec. 211.44 Lighting.
Adequate lighting shall be provided in all areas.
Sec. 211.46 Ventilation, air filtration, air heating and cooling.
(a) Adequate ventilation shall be provided.
(b)
Equipment
for
adequate
control
over
air
pressure,
micro-organisms,
dust,
humidity,
and
temperature
shall
be
provided
when appropriate for the manufacture, processing, packing, or holding of a drug product.
(c) Air filtration systems, including prefilters and particulate matter air filters, shall be used when appropriate
on air supplies to production areas. If air is recirculated to production areas, measures shall be taken to control
recirculation
of
dust
from
production.
In
areas
where
air
contamination
occurs
during
production,
there
shall
be
adequate
exhaust systems or other systems adequate to control contaminants.
(d)
Air-handling
systems
for
the
manufacture,
processing,
and packing
of
penicillin
shall
be
completely
separate
from
those for other drug products for human use.
Sec. 211.48 Plumbing.
(a)
Potable
water
shall
be
supplied
under
continuous
positive
pressure
in
a
plumbing
system
free
of
defects
that
could
contribute contamination to any drug product. Potable water shall meet the standards prescribed in the Environmental
Protection Agency's Primary Drinking Water Regulations set forth in 40 CFR part 141. Water not meeting such standards
shall not be permitted in the potable water system.
(b) Drains shall be of adequate size and, where connected directly to a sewer, shall be provided with an air break
or other mechanical device to prevent back-siphonage.
[43 FR 45077, Sept. 29, 1978, as amended at 48 FR 11426, Mar. 18, 1983]
Sec. 211.50 Sewage and refuse.
Sewage, trash, and other refuse in and from the building and immediate premises shall be disposed of in a safe and
sanitary manner.
Sec. 211.52 Washing and toilet facilities.
Adequate washing facilities shall be provided, including hot and cold water, soap or detergent, air driers or
single-service towels, and clean toilet facilities easily accesible to working areas.
Sec. 211.56 Sanitation.
(a) Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in
a clean and sanitary condition, Any such building shall be free of infestation by rodents, birds, insects, and other
vermin (other than laboratory animals). Trash and organic waste matter shall be held and disposed of in a timely and
sanitary manner.
(b)
There
shall
be
written
procedures
assigning
responsibility
for
sanitation
and describing
in
sufficient
detail
the
cleaning
schedules,
methods,
equipment,
and
materials
to
be
used
in
cleaning
the
buildings
and
facilities;
such
written
procedures shall be followed.
(c) There shall be written procedures for use of suitable rodenticides, insecticides, fungicides, fumigating agents,
and
cleaning
and
sanitizing
agents.
Such
written
procedures
shall
be
designed
to
prevent
the
contamination
of
equipment,
components,
drug
product
containers,
closures,
packaging,
labeling
materials,
or
drug
products
and
shall
be
followed.
Rodenticides,
insecticides,
and
fungicides
shall
not
be
used
unless
registered
and
used
in
accordance
with
the
Federal
Insecticide, Fungicide, and Rodenticide Act (7 U.S.C. 135).
(d)
Sanitation
procedures
shall
apply
to
work
performed
by
contractors
or
temporary
employees
as
well
as
work
performed
by full-time employees during the ordinary course of operations.
Sec. 211.58 Maintenance.
Any building used in the manufacture, processing, packing, or holding of a drug product shall be maintained in a good
state of repair.
Subpart D--Equipment

Sec. 211.63 Equipment design, size, and location.
Equipment used in the manufacture, processing, packing, or holding of a drug product shall be of appropriate design,
adequate
size,
and
suitably
located
to
facilitate
operations
for
its
intended
use
and
for
its
cleaning
and
maintenance.
Sec. 211.65 Equipment construction.
(a) Equipment shall be constructed so that surfaces that contact components, in-process materials, or drug products
shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality, or purity of
the drug product beyond the official or other established requirements.
(b)
Any
substances
required
for
operation,
such
as
lubricants
or
coolants,
shall
not
come
into
contact
with
components,
drug
product
containers,
closures,
in-process
materials,
or
drug
products
so
as
to
alter
the
safety,
identity,
strength,
quality, or purity of the drug product beyond the official or other established requirements.
Sec. 211.67 Equipment cleaning and maintenance.
(a) Equipment and utensils shall be cleaned, maintained, and, as appropriate for the nature of the drug, sanitized
and/or
sterilized
at
appropriate
intervals
to
prevent
malfunctions
or
contamination
that
would
alter
the
safety,
identity,
strength, quality, or purity of the drug product beyond the official or other established requirements.
(b)
Written
procedures
shall
be
established
and
followed
for
cleaning
and
maintenance
of
equipment,
including
utensils,
used in the manufacture, processing, packing, or holding of a drug product. These procedures shall include, but are
not necessarily limited to, the following:
(1) Assignment of responsibility for cleaning and maintaining equipment;
(2) Maintenance and cleaning schedules, including, where appropriate, sanitizing schedules;
(3) A description in sufficient detail of the methods, equipment, and materials used in cleaning and maintenance
operations, and the methods of disassembling and reassembling equipment as necessary to assure proper cleaning and
maintenance;
(4) Removal or obliteration of previous batch identification;
(5) Protection of clean equipment from contamination prior to use;
(6) Inspection of equipment for cleanliness immediately before use.
(c) Records shall be kept of maintenance, cleaning, sanitizing, and inspection as specified in 211.180 and 211.182.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51931, Sept. 8, 2008]
Sec. 211.68 Automatic, mechanical, and electronic equipment.
(a)
Automatic,
mechanical,
or
electronic
equipment
or
other
types
of
equipment,
including
computers,
or
related
systems
that will perform a function satisfactorily, may be used in the manufacture, processing, packing, and holding of a
drug product. If such equipment is so used, it shall be routinely calibrated, inspected, or checked according to a
written program designed to assure proper performance. Written records of those calibration checks and inspections
shall be maintained.
(b)
Appropriate
controls
shall
be
exercised
over
computer
or
related
systems
to
assure
that
changes
in
master
production
and
control
records
or
other
records
are
instituted
only
by
authorized
personnel.
Input
to
and
output
from
the
computer
or related system of formulas or other records or data shall be checked for accuracy. The degree and frequency of
input/output
verification
shall
be
based
on
the
complexity
and
reliability
of
the
computer
or
related
system.
A
backup
file
of
data
entered
into
the
computer
or
related
system
shall
be
maintained
except
where
certain
data,
such
as
calculations
performed in connection with laboratory analysis, are eliminated by computerization or other automated processes. In
such instances a written record of the program shall be maintained along with appropriate validation data. Hard copy
or alternative systems, such as duplicates, tapes, or microfilm, designed to assure that backup data are exact and
complete and that it is secure from alteration, inadvertent erasures, or loss shall be maintained.
(c) Such automated equipment used for performance of operations addressed by 211.101(c) or (d), 211.103, 211.182, or
211.188(b)(11) can satisfy the requirements included in those sections relating to the performance of an operation
by one person and checking by another person if such equipment
is used in conformity with this section, and one person
checks that the equipment properly performed the operation.
[43 FR 45077, Sept. 29, 1978, as amended at 60 FR 4091, Jan. 20, 1995; 73 FR 51932, Sept. 8, 2008]
Sec. 211.72 Filters.
Filters for liquid filtration used in the manufacture, processing, or packing of injectable drug products intended
for
human
use
shall
not
release
fibers
into
such
products.
Fiber-releasing
filters
may
be
used
when
it
is
not
possible
to manufacture such products without the use of these filters. If use of a fiber-releasing filter is necessary, an
additional nonfiber-releasing filter having a maximum nominal pore size rating of 0.2 micron (0.45 micron if the
manufacturing conditions so dictate) shall subsequently be used to reduce the content of particles in the injectable
drug product. The use of an asbestos-containing filter is prohibited.
[73 FR 51932, Sept. 8, 2008]
Subpart E--Control of Components and Drug Product Containers and Closures

Sec. 211.80 General requirements.
(a)
There
shall
be
written
procedures
describing
in
sufficient
detail
the
receipt,
identification,
storage,
handling,
sampling, testing, and approval or rejection of components and drug product containers and closures; such written
procedures shall be followed.
(b)
Components
and
drug
product
containers
and
closures
shall
at
all
times
be
handled
and
stored
in
a
manner
to
prevent
contamination.
(c)
Bagged
or
boxed
components
of
drug
product
containers,
or
closures
shall
be
stored
off
the
floor
and
suitably
spaced
to permit cleaning and inspection.
(d)
Each
container
or
grouping
of
containers
for
components
or
drug
product
containers,
or
closures
shall
be
identified
with a distinctive code for each lot in each shipment received. This code shall be used in recording the disposition
of each lot. Each lot shall be appropriately identified as to its status (i.e., quarantined, approved, or rejected).
Sec. 211.82 Receipt and storage of untested components, drug product containers, and closures.
(a)
Upon
receipt
and
before
acceptance,
each
container
or
grouping
of
containers
of
components,
drug
product
containers,
and closures shall be examined visually for appropriate labeling as to contents, container damage or broken seals,
and contamination.
(b) Components, drug product containers, and closures shall be stored under quarantine until they have been tested
or
examined,
whichever
is
appropriate,
and
released.
Storage
within
the
area
shall
conform
to
the
requirements
of
211.80.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]
Sec. 211.84 Testing and approval or rejection of components, drug product containers, and closures.
(a) Each lot of components, drug product containers, and closures shall be withheld from use until the lot has been
sampled, tested, or examined, as appropriate, and released for use by the quality control unit.
(b) Representative samples of each shipment of each lot shall be collected for testing or examination. The number of
containers to be sampled, and the amount of material to be taken from each container, shall be based upon appropriate
criteria such as statistical criteria for component variability, confidence levels, and degree of precision desired,
the past quality history of the supplier, and the quantity needed for analysis and reserve where required by 211.170.
(c) Samples shall be collected in accordance with the following procedures:
(1) The containers of components selected shall be cleaned when necessary in a manner to prevent introduction of
contaminants into the component.
(2)
The
containers
shall
be
opened,
sampled,
and
resealed
in
a
manner
designed
to
prevent
contamination
of
their
contents
and contamination of other components, drug product containers, or closures.
(3) Sterile equipment and aseptic sampling techniques shall be used when necessary.
(4)
If
it
is
necessary
to
sample
a
component
from
the
top,
middle,
and
bottom
of
its
container,
such
sample
subdivisions
shall not be composited for testing.
(5) Sample containers shall be identified so that the following information can be determined: name of the material
sampled, the lot number, the container from which the sample was taken, the date on which the sample was taken, and
the name of the person who collected the sample.
(6) Containers from which samples have been taken shall be marked to show that samples have been removed from them.
(d) Samples shall be examined and tested as follows:
(1) At least one test shall be conducted to verify the identity of each component of a drug product. Specific identity
tests, if they exist, shall be used.
(2) Each component shall be tested for conformity with all appropriate written specifications for purity, strength,
and quality. In lieu of such testing by the manufacturer, a report of analysis may be accepted from the supplier of
a component, provided that at least one specific identity test is conducted on such component by the manufacturer,
and
provided
that
the
manufacturer
establishes
the
reliability
of
the
supplier's
analyses
through
appropriate
validation
of the supplier's test results at appropriate intervals.
(3) Containers and closures shall be tested for conformity with all appropriate written specifications. In lieu of
such testing by the manufacturer, a certificate of testing may be accepted from the supplier, provided that at least
a
visual
identification
is
conducted
on
such
containers/closures
by
the
manufacturer
and
provided
that
the
manufacturer
establishes
the
reliability
of
the
supplier's
test
results
through
appropriate
validation
of
the
supplier's
test
results
at appropriate intervals.
(4) When appropriate, components shall be microscopically examined.
(5) Each lot of a component, drug product container, or closure that is liable to contamination with filth, insect
infestation,
or
other
extraneous
adulterant
shall
be
examined
against
established
specifications
for
such
contamination.
(6) Each lot of a component, drug product container, or closure with potential for microbiological contamination that
is objectionable in view of its intended use shall be subjected to microbiological tests before use.
(e) Any lot of components, drug product containers, or closures that meets the appropriate written specifications of
identity,
strength,
quality,
and
purity
and
related
tests
under
paragraph
(d)
of
this
section
may
be
approved
and
released
for use. Any lot of such material that does not meet such specifications shall be rejected.
[43 FR 45077, Sept. 29, 1978, as amended at 63 FR 14356, Mar. 25, 1998; 73 FR 51932, Sept. 8, 2008]
Sec. 211.86 Use of approved components, drug product containers, and closures.
Components, drug product containers, and closures approved for use shall be rotated so that the oldest approved stock
is used first. Deviation from this requirement is permitted if such deviation is temporary and appropriate.
Sec. 211.87 Retesting of approved components, drug product containers, and closures.
Components,
drug
product
containers,
and
closures
shall
be
retested
or
reexamined,
as
appropriate,
for
identity,
strength,
quality,
and
purity
and
approved
or
rejected
by
the
quality
control
unit
in
accordance
with
211.84
as
necessary,
e.g.,
after
storage
for
long
periods
or
after
exposure
to
air,
heat
or
other
conditions
that
might
adversely
affect
the
component,
drug product container, or closure.
Sec. 211.89 Rejected components, drug product containers, and closures.
Rejected
components,
drug
product
containers,
and
closures
shall
be
identified
and
controlled
under
a
quarantine
system
designed to prevent their use in manufacturing or processing operations for which they are unsuitable.
Sec. 211.94 Drug product containers and closures.
(a) Drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety,
identity, strength, quality, or purity of the drug beyond the official or established requirements.
(b) Container closure systems shall provide adequate protection against foreseeable external factors in storage and
use that can cause deterioration or contamination of the drug product.
(c) Drug product containers and closures shall be clean and, where indicated by the nature of the drug, sterilized
and
processed
to
remove
pyrogenic
properties
to
assure
that
they
are
suitable
for
their
intended
use.
Such
depyrogenation
processes shall be validated.
(d) Standards or specifications, methods of testing, and, where indicated, methods of cleaning, sterilizing, and
processing to remove pyrogenic properties shall be written and followed for drug product containers and closures.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]
Subpart F-- Production and Process Controls

Sec. 211.100 Written procedures; deviations.
(a) There shall be written procedures for production and process control designed to assure that the drug products
have the identity, strength, quality, and purity they purport or are represented to possess. Such procedures shall
include
all
requirements
in
this
subpart.
These
written
procedures,
including
any
changes,
shall
be
drafted,
reviewed,
and approved by the appropriate organizational units and reviewed and approved by the quality control unit.
(b) Written production and process control procedures shall be followed in the execution of the various production
and
process
control
functions
and
shall
be
documented
at
the
time
of
performance.
Any
deviation
from
the
written
procedures
shall be recorded and justified.
Sec. 211.101 Charge-in of components.
Written
production
and
control
procedures
shall
include
the
following,
which
are
designed
to
assure
that
the
drug
products
produced have the identity, strength, quality, and purity they purport or are represented to possess:
(a) The batch shall be formulated with the intent to provide not less than 100 percent of the labeled or established
amount of active ingredient.
(b)
Components
for
drug
product
manufacturing
shall
be
weighed,
measured,
or
subdivided
as
appropriate.
If
a
component
is
removed
from
the
original
container
to
another,
the
new
container
shall
be
identified
with
the
following
information:
(1) Component name or item code;
(2) Receiving or control number;
(3) Weight or measure in new container;
(4) Batch for which component was dispensed, including its product name, strength, and lot number.
(c) Weighing, measuring, or subdividing operations for components shall be adequately supervised. Each container of
component dispensed to manufacturing shall be examined by a second person to assure that:
(1) The component was released by the quality control unit;
(2) The weight or measure is correct as stated in the batch production records;
(3) The containers are properly identified. If the weighing, measuring, or subdividing operations are performed by
automated equipment under 211.68, only one person is needed to assure paragraphs (c)(1), (c)(2), and (c)(3) of this
section.
(d)
Each
component
shall
either
be
added
to
the
batch
by
one
person
and
verified
by
a
second
person
or,
if
the
components
are added by automated equipment under 211.68, only verified by one person.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]
Sec. 211.103 Calculation of yield.
Actual yields and percentages of theoretical yield shall be determined at the conclusion of each appropriate phase
of manufacturing, processing, packaging, or holding of the drug product. Such calculations shall either be performed
by one person and independently verified by a second person, or, if the yield is calculated by automated equipment
under 211.68, be independently verified by one person.
[73 FR 51932, Sept. 8, 2008]
Sec. 211.105 Equipment identification.
(a)
All
compounding
and
storage
containers,
processing
lines,
and
major
equipment
used
during
the
production
of
a
batch
of a drug product shall be properly identified at all times to indicate their contents and, when necessary, the phase
of processing of the batch.
(b) Major equipment shall be identified by a distinctive identification number or code that shall be recorded in the
batch production record to show the specific equipment used in the manufacture of each batch of a drug product. In
cases where only one of a particular type of equipment exists in a manufacturing facility, the name of the equipment
may be used in lieu of a distinctive identification number or code.
Sec. 211.110 Sampling and testing of in- process materials and drug products.
(a) To assure batch uniformity and integrity of drug products, written procedures shall be established and followed
that
describe
the
in- process
controls,
and
tests,
or
examinations
to
be
conducted
on
appropriate
samples
of
in- process
materials
of
each
batch.
Such
control
procedures
shall
be
established
to
monitor
the
output
and
to
validate
the
performance
of
those
manufacturing
processes
that
may
be
responsible
for
causing
variability
in
the
characteristics
of
in-process
material and the drug product. Such control procedures shall include, but are not limited to, the following, where
appropriate:
(1) Tablet or capsule weight variation;
(2) Disintegration time;
(3) Adequacy of mixing to assure uniformity and homogeneity;
(4) Dissolution time and rate;
(5) Clarity, completeness, or pH of solutions.
(6) Bioburden testing.
(b)
Valid
in-process
specifications
for
such
characteristics
shall
be
consistent
with
drug
product
final
specifications
and shall be derived from previous acceptable process average and process variability estimates where possible and
determined
by
the
application
of
suitable
statistical
procedures
where
appropriate.
Examination
and
testing
of
samples
shall assure that the drug product and in-process material conform to specifications.
(c) In-process materials shall be tested for identity, strength, quality, and purity as appropriate, and approved or
rejected
by
the
quality
control
unit,
during
the
production
process,
e.g.,
at
commencement
or
completion
of
significant
phases or after storage for long periods.
(d) Rejected in-process materials shall be identified and controlled under a quarantine system designed to prevent
their use in manufacturing or processing operations for which they are unsuitable.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]
Sec. 211.111 Time limitations on production.
When
appropriate,
time
limits
for
the
completion
of
each
phase
of
production
shall
be
established
to
assure
the
quality
of the drug product. Deviation from established time limits may be acceptable if such deviation does not compromise
the quality of the drug product. Such deviation shall be justified and documented.
Sec. 211.113 Control of microbiological contamination.
(a) Appropriate written procedures, designed to prevent objectionable microorganisms in drug products not required
to be sterile, shall be established and followed.
(b) Appropriate written procedures, designed to prevent microbiological contamination of drug products purporting to
be
sterile,
shall
be
established
and
followed.
Such
procedures
shall
include
validation
of
all
aseptic
and
sterilization
processes.
[43 FR 45077, Sept. 29, 1978, as amended at 73 FR 51932, Sept. 8, 2008]
Sec. 211.115 Reprocessing.
(a) Written procedures shall be established and followed prescribing a system for reprocessing batches that do not
conform to standards or specifications and the steps to be taken to insure that the reprocessed batches will conform
with all established standards, specifications, and characteristics.
(b) Reprocessing shall not be performed without the review and approval of the quality control unit.
Subpart G--Packaging and Labeling Control

Sec. 211.122 Materials examination and usage criteria.
(a)
There
shall
be
written
procedures
describing
in
sufficient
detail
the
receipt,
identification,
storage,
handling,
sampling,
examination,
and/or
testing
of
labeling
and
packaging
materials;
such
written
procedures
shall
be
followed.
Labeling and packaging materials shall be representatively sampled, and examined or tested upon receipt and before
use in packaging or labeling of a drug product.
(b) Any labeling or packaging materials meeting appropriate written specifications may be approved and released for
use. Any labeling or packaging materials that do not meet such specifications shall be rejected to prevent their use
in operations for which they are unsuitable.
(c)
Records
shall
be
maintained
for
each
shipment
received
of
each
different
labeling
and
packaging
material
indicating
receipt, examination or testing, and whether accepted or rejected.
(d)
Labels
and
other
labeling
materials
for
each
different
drug
product,
strength,
dosage
form,
or
quantity
of
contents
shall be stored separately with suitable identification. Access to the storage area shall be limited to authorized
personnel.
(e) Obsolete and outdated labels, labeling, and other packaging materials shall be destroyed.
(f) Use of gang-printed labeling for different drug products, or different strengths or net contents of the same drug
product, is prohibited unless the labeling from gang-printed sheets is adequately differentiated by size, shape, or
color.
(g) If cut labeling is used, packaging and labeling operations shall include one of the following special control
procedures:
(1) Dedication of labeling and packaging lines to each different strength of each different drug product;
(2)
Use
of
appropriate
electronic
or
electromechanical
equipment
to
conduct
a
100-percent
examination
for
correct
labeling
during or after completion of finishing operations; or
(3) Use of visual inspection to conduct a 100-percent examination for correct labeling during or after completion of
finishing operations for hand-applied labeling. Such examination shall be performed by one person and independently
verified by a second person.
(h) Printing devices on, or associated with, manufacturing lines used to imprint labeling upon the drug product unit
label
or
case
shall
be
monitored
to
assure
that
all
imprinting
conforms
to
the
print
specified
in
the
batch
production
record.
[43 FR 45077, Sept. 29, 1978, as amended at 58 FR 41353, Aug. 3, 1993]
Sec. 211.125 Labeling issuance.
(a) Strict control shall be exercised over labeling issued for use in drug product labeling operations.
(b)
Labeling
materials
issued
for
a
batch
shall
be
carefully
examined
for
identity
and
conformity
to
the
labeling
specified
in the master or batch production records.
(c) Procedures shall be used to reconcile the quantities of labeling issued, used, and returned, and shall require
evaluation of discrepancies found between the quantity of drug product finished and the quantity of labeling issued
when
such
discrepancies
are
outside
narrow
preset
limits
based
on
historical
operating
data.
Such
discrepancies
shall
be
investigated
in
accordance
with
211.192.
Labeling
reconciliation
is
waived
for
cut
or
roll
labeling
if
a
100-percent
examination for correct labeling is performed in accordance with 211.122(g)(2).
(d) All excess labeling bearing lot or control numbers shall be destroyed.
(e) Returned labeling shall be maintained and stored in a manner to prevent mixups and provide proper identification.