Sec. 450.500 Tamper-Resistant Packaging Requirements for Certain Over-the-Counter (OTC)
Human Drug Products (CPG 7132a.17)
BACKGROUND:
*Requirements of the tamper-resistant packaging (TRP) regulations covering most OTC
products were published by FDA in the FEDERAL REGISTER of November 5, 1982.
The regulations require that all OTC human drug products (except dermatologics,
dentifrices, insulin and throat lozenges) (21 CFR 211.132), cosmetic liquid oral hygiene
products and vaginal products (21 CFR 700.25), and contact lens solutions and tablets used
to make these solutions (21 CFR 800.12) be packaged in tamper-resistant packaging.
The packaging must use an indicator or barrier to entry that is distinctive by design
(such as an aerosol container), or must employ an identifying characteristic (a pattern,
name, registered trademark, logo, or picture). Further, the regulations require a labeling
statement on the container (except ammonia inhalant in crushable glass ampules, aerosol
products, or containers of compressed medical oxygen) to alert the consumer to the
specific tamper-resistant feature(s) used. The labeling statement is also required to be
placed so that it will be unaffected if a TRP feature is breached or missing.
An amendment to the TRP regulations for OTC human drug products published as a final rule in the FEDERAL REGISTER on February 2, 1989. The new requirements (21 CFR 211.132(b)(1) and (2)) are:
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.
Manufacturers were given until February 2, 1990, to comply with the new requirements.
In addition, the Agency has re-evaluated currently available tamper-resistant packaging
technologies and concluded that some technologies as designed or applied are no longer
capable of meeting the requirements of the TRP regulations.
POLICY:
A. PACKAGING SYSTEMS
Manufacturers and packagers are free to use any packaging system as long as the
tamper-resistant standard in the regulations is met. The TRP requirements are intended to
assure that the product's packaging "can reasonably be expected to provide visible
evidence to consumers that tampering has occurred."
Examples of packaging technologies capable of meeting the TRP requirements are listed
below. The use of one of these packaging technologies does not, by itself, constitute
compliance with the requirements for a tamper-resistant package. Packaging features must
be properly designed and appropriately applied to be effective TRP.
1. FILM WRAPPERS. A transparent film is wrapped securely around the entire product
container. The film must be cut or torn to open the container and remove the product. A
tight "fit" of the film around the container must be achieved, e.g., by a
shrink-type process. A film wrapper sealed with overlapping end flaps must not be capable
of being opened and resealed without leaving visible evidence of entry.
The use of cellophane with overlapping end flaps is not effective as a tamper-resistant
feature because of the possibility that the end flaps can be opened and resealed without
leaving visible evidence of entry.
The film wrapper must employ an identifying characteristic that cannot be readily
duplicated. An identifying characteristic that is proprietary and different for each
product size is recommended.
Tinted wrappers are no longer acceptable as an identifying characteristic because of the possibility that their material or a facsimile may be available to the public.
2. BLISTER or STRIP PACKS. Dosage units (e.g., tablets or capsules) are individually
sealed in clear plastic or plastic compartments with foil or paper backing.
The individual compartment must be torn or broken to obtain the product. The backing
materials cannot be separated from the blisters or replaced without leaving visible
evidence of entry.
3. BUBBLE PACKS. The product and container are sealed in plastic and mounted in or on a
display card. The plastic must be torn or broken to remove the product. The backing
material cannot be separated from the plastic bubble or replaced without leaving visible
evidence of entry.
4. HEAT SHRINK BANDS OR WRAPPERS. A band or wrapper is securely applied to a portion of
the container, usually at the juncture of the cap and container. The band or wrapper is
heat shrunk to provide a tight fit. The band or wrapper must be cut or torn to open the
container and remove the product and cannot be worked off and reapplied without visible
damage. The use of a perforated tear strip can enhance tamper-resistance.
Cellulose wet shrink seals are not acceptable. The knowledge to remove and reapply
these seals without evidence of tampering is widespread.
The band or wrapper must employ an identifying characteristic that cannot be readily
duplicated. An identifying characteristic that is proprietary and different for each
product size is recommended.
Tinted bands or wrappers are no longer acceptable as an identifying characteristic
because of the possibility that their material or a facsimile may be available to the
public.
5. FOIL, PAPER, OR PLASTIC POUCHES. The product is enclosed in an individual pouch that
must be torn or broken to obtain the product. The end seams of the pouches cannot be
separated and resealed without showing visible evidence of entry.
6. CONTAINER MOUTH INNER SEALS. Paper, thermal plastic, plastic film, foil, or a
combination thereof, is sealed to the mouth of a container (e.g., bottle) under the cap.
The seal must be torn or broken to open the container and remove the product. The seal
cannot be removed and reapplied without leaving visible evidence of entry. Seals applied
by heat induction to plastic containers appear to offer a higher degree of
tamper-resistance than those that depend on an adhesive to create the bond.
Polystyrene foam container mouth seals applied with pressure sensitive adhesive are no
longer considered effective tamper-resistant features because they can be removed and
reapplied in their original state with no visible evidence of entry.
The Agency recognizes that technological innovations may produce foam seals that will
adhere to a container mouth in a manner that cannot be circumvented without visible
evidence of entry. Container mouth seals must employ an identifying characteristic that
cannot be readily duplicated. An identifying characteristic that is proprietary and
different for each product size is recommended.
7. TAPE SEALS. Tape seals relying on an adhesive to bond them to the package are not
capable of meeting the TRP requirements because they can be removed and reapplied with no
visible evidence of entry.
However, the Agency recognizes that technological innovations may produce adhesives which do not permit the removal and reapplication of tape seals. In addition, tape seals may contain a feature that makes it readily apparent if the seals have been removed and reapplied. Tape seals must employ an identifying characteristic that cannot be readily duplicated.
8. BREAKABLE CAPS. The container (e.g., bottle) is sealed by a plastic or metal cap
that either breaks away completely when removed from the container or leaves part of the
cap attached to the container. The cap, or a portion thereof, must be broken in order to
open the container and remove the product. The cap cannot be reapplied in its original
state.
9. SEALED METAL TUBES OR PLASTIC BLIND-END HEAT-SEALED TUBES. The bottom of the tube is heat sealed and the mouth or blind-end must be punctured to obtain the product. A tube with a crimped end is capable of meeting the definition of a tamper-resistant feature if the crimped end cannot be breached by unfolding and refolding without visible evidence of entry.
10 SEALED CARTONS. Paperboard cartons sealed by gluing the end flaps are not capable of
meting the TRP requirements. However, the Agency recognizes that technological advances
may provide sealed paperboard packages that meet the requirements of the TRP regulations.
11 AEROSOL CONTAINERS. Aerosol containers are believed to be inherently tamper-resistant because of their design. Direct printing of the label on the container (e.g., lithographing), is preferred to using a paper label which could be removed and substituted.
12 CANS (BOTH ALL-METAL AND COMPOSITE). Cans may be composed of all metal or composite
walls with metal tops and bottoms. The top and bottom of a composite can must be joined to
the can walls in such a manner that they cannot be pulled apart and reassembled without
visible evidence of entry. Rather than attaching a separate label, direct printing of the
label onto the can (e.g., lithographing ) is preferred.
B. CAPSULE SEALING TECHNOLOGIES
Technologies for sealing two-piece hard gelatin capsules are available that provide
evidence if the capsules have been tampered with after filling. Such sealing technologies
currently in use include sonic welding, banding, and sealing techniques employing solvents
and/or low temperature heating. These examples are not intended to rule out the
development and use of other capsule sealing technologies. Manufacturers may consult with
FDA if they are considering alternative capsule sealing processes.
Sealed capsules are not tamper-resistant packages. They are required to be contained within a package system that utilizes a minimum of one TRP feature.
C. TRP LABELING STATEMENT(S)
1. BOTTLE (CONTAINER) CAPS. In the past, some manufacturers have placed the TRP labeling statement on bottle caps. This practice is unacceptable in cases where it may be a simple matter to substitute another unlabeled bottle cap for the one with the tamper-resistant warning statement. Such an act could easily be accomplished without any apparent sign of tampering.
2. PACKAGE INSERTS. The practice of placing the TRP labeling statement solely on the
product's inserts is not acceptable. While package inserts may be a useful supplement for
consumer education purposes, they are not acceptable in lieu of label statements.
3. CARTON/CONTAINER (OUTER AND INNER). If the TRP feature is on an outer carton, the
inner container (e.g., bottle) needs to bear a statement alerting the consumer that the
bottle should be in a carton at the time of purchase. This policy applies only to
situations where the inner container is so labeled that such a container might reasonably
otherwise be displayed on the retail shelf without an outer carton.
4. IDENTIFYING CHARACTERISTIC. When a TRP feature is required to have an identifying characteristic, that characteristic needs to be referenced in the labeling statement (e.g., "imprinted" neck band). It is recommended that the labeling statement specifically identify the characteristic (e.g., imprinted with XYZ on the neck band).
5. TRP FEATURE(S). All required tamper-resistant features must be referenced in the
labeling statement. When two tamper-resistant packaging features are used for unsealed
two-piece hard gelatin capsules, both features must be referenced in the labeling
statement. If one tamper-resistant packaging feature plus sealed capsules are used, the
labeling statement must reference both the capsule seal and the tamper-resistant packaging
feature.
REGULATORY ACTION GUIDANCE:
The TRP requirements are part of the current good manufacturing practice (GMP)
regulations. Regulatory actions for deviations from these requirements should be handled
in the same manner as any other deviation from the GMP regulations.
*Material between asterisks is new or revised*
Issued: 3/1/88
Revised: 5/21/92