21
Code of Federal Regulations
Parts
211
Subpart
G-Packaging and Labeling Control
§
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Obsolete and outdated labels, labeling, and other packaging materials shall be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 printing of 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]
§ 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 utilized 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.
(f) Procedures shall be written describing in sufficient detail
the control procedures employed for the issuance of labeling; such written
procedures shall be followed.
[43 FR 45077, Sept. 29, 1978, as amended at 58 FR 41345, Aug. 3,
1993]
§ 211.130 Packaging and labeling operations.
There shall be written procedures designed to assure that correct
labels, labeling, and packaging materials are used for drug products; such
written procedures shall be followed. These procedures
shall incorporate the following features:
(a) Prevention of mixups and cross-contamination by physical or
spatial separation from operations on other drug products.
(b)
Identification and handling of filled drug product containers that are set
aside and held in unlabeled condition for future labeling operations to
preclude mislabeling of individual containers, lots, or portions of lots.
Identification need not be applied to each individual container but shall be
sufficient to determine name, strength, quantity of contents, and lot or
control number of each container.
(c)
Identification of the drug product with a lot or control number that permits
determination of the history of the manufacture and control of the batch.
(d)
Examination of packaging and labeling materials for suitability and correctness
before packaging operations, and documentation of such examination in the batch
production record.
(e)
Inspection of the packaging and labeling facilities immediately before use to
assure that all drug products have been removed from previous operations.
Inspection shall also be made to assure that packaging and labeling materials
not suitable for subsequent operations have been removed. Results of inspection
shall be documented in the batch production records.
[43
FR 45077, Sept. 29, 1978, as amended at 58 FR 41354, Aug. 3, 1993]
§
211.132 Tamper-resistant packaging requirements for over-the-counter (OTC)
human drug products.
(a)
General. The Food and Drug Administration has the authority under the
Federal Food, Drug, and Cosmetic Act (the act) to establish a uniform national
requirement for tamper-resistant packaging of OTC drug products that will
improve the security of OTC drug packaging and help assure the safety and effectiveness
of OTC drug products. An OTC drug product (except a dermatological, dentifrice,
insulin, or throat lozenge product) for retail sale that is not packaged in a
tamper-resistant package or that is not properly labeled under this section is
adulterated under section 501 of the act or misbranded under section 502 of the
act, or both.
(b)
Requirement for tamper-resistant package. Each manufacturer and packer
who packages an OTC drug product (except a dermatological, dentifrice, insulin,
or throat lozenge product) for retail sale shall package the product in a
tamper-resistant package, if this product is accessible to the public while
held for sale. A tamper-resistant package is one having one or more indicators
or barriers to entry which, if breached or missing, can reasonably be expected
to provide visible evidence to consumers that tampering has occurred. To reduce
the likelihood of successful tampering and to increase the likelihood that
consumers will discover if a product has been tampered with, the package is
required to be distinctive by design (e.g., an aerosol product container) or by
the use of one or more indicators or barriers to entry that employ an
identifying characteristic (e.g., a pattern, name, registered trademark, logo,
or picture). For purposes of this section, the term "distinctive by
design'' means the packaging cannot be duplicated with commonly available
materials or through commonly available processes. For purposes of this
section, the term "aerosol product'' means a product which depends upon
the power of a liquified or compressed gas to expel the contents from the
container. A tamper-resistant package may involve an immediate-container and
closure system or secondary container or carton system or any combination of
systems intended to provide a visual indication of package integrity. The
tamper- resistant feature shall be designed to and shall remain intact when handled
in a reasonable manner during manufacture, distribution, and retail display.
(1)
For two-piece, hard gelatin capsule products subject to this requirement, a
minimum of two tamper-resistant packaging features is required, unless the capsules
are sealed by a tamper- resistant technology.
(2)
For all other products subject to this requirement, including two-piece, hard
gelatin capsules that are sealed by a tamper- resistant technology, a minimum
of one tamper-resistant feature is required.
(c)
Labeling. Each retail package of an OTC drug product covered by this
section, except ammonia inhalant in crushable glass ampules, aerosol products
as defined in paragraph (b) of this section, or containers of compressed
medical oxygen, is required to bear a statement that is prominently placed so
that consumers are alerted to the specific tamper-resistant feature of the package.
The labeling statement is also required to be so placed that it will be
unaffected if the tamper-resistant feature of the package is breached or
missing. If the tamper-resistant feature chosen to meet the requirement in
paragraph (b) of this section is one that uses an identifying characteristic,
that characteristic is required to be referred to in the labeling statement.
For example, the labeling statement on a bottle with a shrink band could say
"For your protection, this bottle has an imprinted seal around the neck.''
(d)
Request for exemptions from packaging and labeling requirements. A
manufacturer or packer may request an exemption from the packaging and labeling
requirements of this section. A request for an exemption is required to be
submitted in the form of a citizen petition under § 10.30 of this chapter and
should be clearly identified on the envelope as a "Request for Exemption
from Tamper-Resistant Rule.'' The petition is required to contain the
following:
(1)
The name of the drug product or, if the petition seeks an exemption for a drug
class, the name of the drug class, and a list of products within that class.
(2)
The reasons that the drug product's compliance with the tamper-resistant
packaging or labeling requirements of this section is unnecessary or cannot be
achieved.
(3)
A description of alternative steps that are available, or that the petitioner
has already taken, to reduce the likelihood that the product or drug class will
be the subject of malicious adulteration.
(4)
Other information justifying an exemption.
(e)
OTC drug products subject to approved new drug applications. Holders of
approved new drug applications for OTC drug products are required under §
314.70 of this chapter to provide the agency with notification of changes in
packaging and labeling to comply with the requirements of this section. Changes
in packaging and labeling required by this regulation may be made before FDA
approval, as provided under § 314.70(c) of this chapter. Manufacturing changes
by which capsules are to be sealed require prior FDA approval under § 314.70(b)
of this chapter.
(f)
Poison Prevention Packaging Act of 1970. This section does not affect
any requirements for "special packaging'' as defined under § 310.3(l) of
this chapter and required under the Poison
Prevention
Packaging Act of 1970.
(Approved
by the Office of Management and Budget under OMB control number 0910-0149)
[54
FR 5228, Feb. 2, 1989]
§
211.134 Drug product inspection.
(a)
Packaged and labeled products shall be examined during finishing operations to
provide assurance that containers and packages in the lot have the correct
label.
(b)
A representative sample of units shall be collected at the completion of
finishing operations and shall be visually examined for correct labeling.
(c)
Results of these examinations shall be recorded in the batch production or
control records.
§ 211.137 Expiration dating.
(a) To assure that a drug product meets applicable standards of
identity, strength, quality, and purity at the time of use, it shall bear an
expiration date determined by appropriate stability testing described in § 211.166.
(b) Expiration dates shall be related to any storage conditions
stated on the labeling, as determined by stability studies described in §211.166.
(c) If the drug product is to be reconstituted at the time of
dispensing, its labeling shall bear expiration information for both the reconstituted
and unreconstituted drug products.
(d) Expiration dates shall appear on labeling in accordance with
the requirements of § 201.17 of this chapter.
(e) Homeopathic drug products shall be exempt from the
requirements of this section.
(f) Allergenic extracts that are labeled "No U.S. Standard of
Potency'' are exempt from the
requirements of this section.
(g) New drug products for investigational use are exempt from the
requirements of this section,
provided that they meet appropriate standards or specifications as
demonstrated by stability studies during their use in clinical investigations.
Where new drug products for investigational use are to be reconstituted at the
time of dispensing, their labeling shall bear expiration information for the
reconstituted drug product.
(h) Pending consideration of a proposed exemption, published in
the Federal Register of September 29, 1978, the requirements in this section
shall not be enforced for human OTC drug products if their labeling does not
bear dosage limitations and they are stable for at least 3 years as supported
by appropriate stability data.
[43 FR 45077, Sept. 29, 1978, as amended at 46 FR 56412, Nov. 17,
1981; 60 FR 4091, Jan. 20,
1995]
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