[Federal Register Volume 63, Number 213 (Wednesday, November 4, 1998)]
[Rules and Regulations]
[Pages 59463-59471]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: 98-29388]
=======================================================================
-----------------------------------------------------------------------
DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 211
[Docket No. 92N-0314]
Tamper-Evident Packaging Requirements for Over-the-Counter Human
Drug Products
AGENCY: Food and Drug Administration, HHS.
ACTION: Final rule.
-----------------------------------------------------------------------
SUMMARY: The Food and Drug Administration (FDA) is amending its
regulations on tamper-resistant packaging to require that all over-the-
counter (OTC) human drug products marketed in two-piece, hard gelatin
capsules be sealed using a tamper-evident technology; to change the
term ``tamper-resistant'' in the labeling of all OTC drug products to
``tamper-evident;'' and to specify that the required OTC drug product
labeling statement must refer to all packaging features used to comply
with the tamper-evident packaging requirements, including those on the
secondary package, the immediate container or closure, and any capsule
sealing technologies used. FDA is taking this action as a result of its
continuing review of the potential public health threat posed by
product tampering and to improve consumer protection by addressing
specific vulnerabilities in the OTC drug market.
DATES: Effective December 4, 1998.
Compliance dates: All two-piece, hard gelatin capsules subject to
the final rule that are initially introduced or initially delivered for
introduction into interstate commerce by November 4, 1999, must be
sealed in compliance with the requirements of the final rule.
OTC drug products that use the term ``tamper-resistant'' in their
labeling must change the term to ``tamper-evident'' by November 6,
2000.
FOR FURTHER INFORMATION CONTACT: Thomas C. Kuchenberg, Center for Drug
Evaluation and Research (HFD-7), Food and Drug Administration, 5600
Fishers Lane, Rockville, MD 20857, 301-594-5640.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of January 18, 1994 (59 FR 2542), FDA
proposed to amend the tamper-evident packaging requirements for OTC
drug products in Sec. 211.132 (21 CFR 211.132). This regulation, which
is intended to protect consumers from malicious tampering with OTC drug
products, was first codified in 1982 and amended in 1989.
The 1982 regulation (47 FR 50442, November 5, 1982) was issued in
response to a tampering incident in the Chicago area in which seven
people died after ingesting cyanide-laced Extra-Strength Tylenol
capsules. The regulation required, among other things, that any OTC
drug product (except a dermatologic, dentifrice, insulin, or lozenge
product) for retail sale be packaged in a ``tamper-resistant'' package,
so that a breach of the package would provide visible evidence to
consumers that tampering had occurred. Although the risk of tampering
was reduced significantly by this rule, the two-piece, hard gelatin
capsule remained vulnerable to tampering. Three deaths in 1986 were
associated with this dosage form. In response to the continued
susceptibility of two-piece, hard gelatin capsules, FDA amended
Sec. 211.132 (54 FR 5227, February 2, 1989) to require that OTC drug
products marketed in two-piece, hard gelatin capsules must be packaged
using at least two tamper-resistant packaging features, or with at
least one tamper-resistant packaging feature if a tamper-resistant
capsule seal was employed.
Despite these regulations, two-piece, hard gelatin capsules have
continued to be a target of malicious drug tampering. This dosage form
was implicated in a February 1991 tragedy, resulting in two deaths,
involving Sudafed capsules contaminated with cyanide. The Sudafed
package and dosage form met FDA's tamper-resistant standards, and there
were visible signs of tampering that were both numerous and
conspicuous. Based on investigations and discussions surrounding the
1991 tampering fatalities, as well as FDA's ongoing review of the
public health threat from OTC drug product tampering, the agency
initiated this rulemaking to reduce the potential for tampering with
vulnerable two-piece, hard gelatin capsules. The agency invited
comments from the public not only with respect to the proposed
amendments, but also on effective ways to educate consumers about OTC
drug product tampering issues and steps
[[Page 59464]]
consumers could take to reduce the threat from tampering. FDA also
invited comments on consumer behavior in buying and using OTC drug
products and how tamper-evident packaging and associated labeling
affect their behavior. The agency also requested comments on whether
additional regulatory changes, such as the establishment of performance
standards for tamper-evident packaging, may be necessary.
II. Highlights of the Final Rule
The final rule amends the current tamper-resistant packaging
requirements for OTC human drug products to further decrease the risks
posed by product tampering by: (1) Mandating the sealing of all OTC
two-piece, hard gelatin capsules; and (2) changing the terminology used
throughout the agency's regulatory program from ``tamper-resistant'' to
``tamper-evident'' to characterize more accurately the role of tamper-
evident packaging in protecting consumers.
The final rule requires that all OTC drug products marketed in two-
piece, hard gelatin capsules be sealed using a tamper-evident
technology, and that the packaging of the sealed capsules have a
minimum of one tamper-evident feature. This amends the current
requirement that a minimum of two tamper-resistant features be used for
this dosage form if the capsule is not sealed. The capsule sealing
requirement is necessary because two-piece hard gelatin capsules remain
vulnerable to malicious tampering.
The final rule changes the terminology used throughout FDA's
regulatory program from ``tamper-resistant'' to ``tamper-evident.'' The
words ``tamper-evident'' appropriately underscore the importance of
heightening consumer awareness to any evidence of tampering, rather
than implying that a particular package is difficult to breach or is
tamper-proof. Labeling is unacceptable if it implies that the product
is tamper resistant or tamper proof.
The final rule clarifies, in Sec. 211.132(c), that an OTC drug
product's labeling statement must identify all tamper-evident packaging
features used, including those on the secondary package, the immediate
container or closure, and any capsule sealing technologies used. This
clarification is necessary because some firms have interpreted the
regulation as requiring reference to the tamper-evident features only
on the outside of the package.
The final rule replaces the term ``throat lozenge'' with
``lozenge'' in Sec. 211.132(a) and (b), thus slightly broadening the
exemption from, and narrowing the scope of, the rule.
Reflecting the change from tamper-resistant to tamper-evident, and
consistent with proposed Sec. 211.132(b), the final rule eliminates the
reference to ``aerosol product container.'' However, the reference to
``aerosol products'' in Sec. 211.132(c) was inadvertently omitted in
the proposed rule, and FDA has restored this language to make it clear
that no tamper-evident features are required for aerosol products. FDA
is also restoring the words ``materials or through commonly available''
in the explanation of the term ``distinctive by design'' in
Sec. 211.132(b). These words were inadvertently omitted in the proposed
rule.
The dates for compliance with the sealing requirement and
terminology change are 1 year and 2 years respectively from the date of
publication of this final rule in the Federal Register. In response to
comments, the final rule does not include a retail effective date as
proposed because of the expected high rate of manufacturer compliance
with the rule.
III. Comments on the Proposed Rule
A. General
FDA received 43 comments on the proposed rule, a substantial
majority of which were from the general public. The remaining comments
were from OTC drug manufacturers and packers, professional societies,
and organizations with special interests in consumer safety and product
packaging.
Many comments supported the requirement that two-piece, hard
gelatin capsules be sealed. One of these comments stated:
[U]nless two-piece, hard gelatin capsules used in OTC drug
products are required to be sealed, as FDA is proposing, it is just
a matter of time until another successful tampering incident
involving this dosage form occurs. Each publicized tampering
incident further erodes the public confidence in the safety of our
OTC drug supply.
However, some comments were less supportive, including one that
stated that:
[T]he amendment requiring two-piece, hard gelatin capsules be
sealed is unnecessary in light of the protections already required
under the present regulation. * * * [F]urther regulation will only
result in additional costs which will be borne by the consumer.
Furthermore, such changes cannot completely eliminate the dangers of
product tampering.
A significant majority of comments supported the change in
terminology from ``tamper-resistant'' to ``tamper-evident.'' These
comments concurred with the agency's position that the term ``tamper-
evident'' more accurately describes the role of packaging and other
features designed to decrease the risk of harm from tampering. A
typical comment on this issue stated that ``such a change imparts an
added degree of awareness to the consumer that no package design is
`tamper-proof'.'' Other comments were less supportive, saying that the
change in language would not substantially aid consumer awareness or
significantly reduce the threat of tampering harm.
B. Scope
Current Sec. 211.132 applies to manufacturers and packers who
package OTC drug products, except dermatologic, dentifrice, insulin, or
throat lozenge products. The final rule maintains the current scope,
except that it exempts all lozenge products rather than only throat
lozenges.
1. One comment stated that the agency should expand the scope of
the rule to include all OTC drug products, including dermatologics.
Dermatologic, dentifrice, and insulin products have been exempted
from the OTC tampering regulations since they were issued in 1982.
These product classes are exempted because of a lower probability of
tampering and in the case of dermatologic and dentifrice products, a
lower risk of severe consequences. Therefore the agency declines to
apply the regulation to these product classes in this rulemaking.
2. One comment asserted that FDA had not considered the effect of
the proposed rule on vitamins and other supplements sold in two-piece,
hard gelatin capsules and stated that the economic impact on dietary
supplement manufacturers and the public would be immense.
The scope of the regulation is limited to OTC drug products and is
not intended to cover products that are regulated as dietary
supplements.
C. Effectiveness of Sealing Requirement
Proposed Sec. 211.132(b)(2) stated that, in addition to an
acceptable tamper-evident packaging feature, any two-piece, hard
gelatin capsule covered by the OTC tamper-evident packaging rule must
be sealed using an acceptable tamper-evident technology.
3. Four comments asserted that if two-piece, hard gelatin capsules
were sealed, consumers would have a false sense of security that such
capsules are impenetrable.
The agency recognizes that an additional level of protection
against tampering may make consumers feel more secure about using OTC
drug products. However, the sealing requirement, along with the other
[[Page 59465]]
regulatory standards set forth in this final rule, will in fact add a
measure of protection against malicious tampering by making it more
difficult for a person to tamper with a product without leaving visible
evidence that tampering has occurred. Thus the heightened sense of
security may have some basis in fact. Because all packaging is
penetrable and no packaging or dosage form is tamper-proof, consumers
should be vigilant when buying and using OTC drug products. The change
in terminology from ``tamper-resistant'' to ``tamper-evident,'' in
combination with the agency's efforts to educate consumers about
tamper-evident packaging, is designed to alert consumers to examine OTC
drug product packaging for evidence of tampering.
4. Two comments claimed that consumers would not notice any
tampering with sealed capsules and, thus, would not be protected by
this requirement. Another comment stated that a breach in the tamper-
evident packaging feature would more likely be noticed than a breach of
a capsule seal.
The agency does not agree with the comments. However, a major
benefit of the capsule-sealing feature is that sealing makes it
virtually impossible for a tamperer to disturb the integrity of the
product and recombine the two parts of the capsule without leaving
conspicuous signs of entry. Although not all seals are visible in the
unbreached state, some seals have distinctive characteristics (e.g.,
color scheme) that make it less likely that a substituted capsule would
go unnoticed. Such signs of tampering with the product itself may be
more likely to be noticed than less obvious manifestations of tampering
left on certain tamper-evident packaging features such as container
mouth inner seals, film wrappers, and heat shrink bands or wrappers.
Some or all of these protective features could be removed by a tamperer
without leaving any signs of tampering to consumers unaware of the
packaging normally used. Thus, for the two-piece, hard gelatin capsule
dosage form, which has been particularly vulnerable to criminal
tampering, it is important to have the dual protection of a package
tamper-evident feature plus the capsule-sealing feature.
5. Three comments stated that the sealing requirement would be
ineffective in reducing the overall tampering risk because it only
addresses the vulnerability of one OTC drug product dosage form, the
two-piece, hard gelatin capsule, while other dosage forms go
unprotected.
It is true that consumer products other than two-piece, hard
gelatin capsules are vulnerable to tampering. For this reason, in
addition to the capsule sealing requirement, current Sec. 211.132
requires that all OTC drug products (except those specifically
exempted) be packaged using a tamper-evident feature. This final rule
maintains this requirement and proposes an extra measure of protection
for OTC two-piece, hard gelatin capsules which, as explained in the
preamble to the proposed rule, have been persistently implicated in the
most serious tampering incidents (59 FR 2542 at 2543). Thus the agency
believes the rule will reduce the overall tampering risk.
6. Two comments stated that the sealing requirement would not yield
a significant benefit because most OTC two-piece, hard gelatin capsule
drug products are already sealed.
While it is true that there are few two-piece, hard gelatin capsule
drug products currently marketed without a seal, the remaining unsealed
capsules may provide an attractive target for would-be tamperers. The
availability of unsealed OTC drug product capsules makes it relatively
easy for the tamperer to substitute them for other, sealed capsules
with a similar appearance. Thus, the universal sealing of two-piece,
hard gelatin capsule drug products will not only make products that are
presently unsealed safer, but will also bolster the effectiveness of
the sealing feature on currently sealed products by reducing
opportunities for substitution.
7. Several comments proposed alternative means of reducing the
threat of drug tampering. Some comments recommended that OTC drug
products marketed in two-piece, hard gelatin capsules be banned or
restricted to pharmacy counter sales.
FDA has considered these options and finds that a ban or
restriction on the sale of two-piece, hard gelatin capsule OTC drug
products is not warranted because the benefits of allowing the
continued OTC marketing of the dosage form outweigh the risks posed by
possible tampering. Consumers might mistakenly think that the threat of
tampering has been eliminated by such an action and thus be lulled into
a false sense of security. A complacent consumer may not remain
vigilant to signs of tampering with other dosage forms.
In addition, capsules are a valuable dosage form option for several
reasons: (1) Many consumers prefer capsules because they are easier to
swallow than some other dosage forms and this factor may increase
patient compliance with a drug regimen. (2) Some medicines cannot
easily be put in tablet form because of the detrimental effects of
tableting on the stability of the ingredients. (3) Capsules are less
susceptible than other dosage forms to damage during shipping. Uncoated
tablets may chip or break during shipping and, thus, may deliver less
than the recommended amounts of ingredients, possibly affecting the
product's efficacy. (4) Capsules contain fewer inactive ingredients
than some tablet and oral liquid formulations, thus lowering the risk
of allergic reactions. (5) Capsules are a preferred means of delivering
sustained-release medications. Capsules containing encapsulated beads
of active ingredients provide a means of delivering medications safely
over prolonged periods, thus enhancing patient compliance. (6) The
printing and color combinations that are possible with capsules aid
consumers and health professionals in distinguishing medicines. Product
distinction is important in aiding patient compliance with drug
regimens and in the effective handling of overdose cases (Ref. 1).
Because of the numerous advantages of capsules, the agency believes
that restricting two-piece, hard gelatin capsules to behind-the-counter
sales would be a disservice to consumers. If capsules were kept behind
the counter, consumers could not easily compare products. Also, because
behind-the-counter space is limited, the expense and inconvenience of
storing products might cause retail outlets to limit the number of OTC
capsule drug products they make available.
8. Comments suggested several other alternative methods of
protecting consumers against tampering, including requiring video
surveillance of areas where tamper-prone products are displayed, and
requiring that tamper-prone products have a holographic label to make
evidence of tampering more visible.
Although these suggestions have merit insofar as they would provide
an additional level of protection against tampering, FDA has determined
that sealing the capsules is the preferred alternative because it will
benefit the consuming public while keeping implementation costs low.
FDA encourages manufacturers to continue to use innovative tamper-
evident technologies to provide protection to the consumer and
encourages retail outlets to play a significant role in protecting the
consumer and apprehending tamperers. Retailers are encouraged, for
example, to train their employees to handle products properly to avoid
an accidental breach of the tamper-evident features and to play a role
in inspecting products for signs of tampering when working at the cash
register, placing
[[Page 59466]]
products on retail shelves, and otherwise handling products.
9. Two comments asserted that consumers accustomed to the use of
two package tamper-evident features on their OTC drug products may be
concerned if one of the familiar features is missing. As a result,
manufacturers would, in effect, be compelled to use two package tamper-
evident features in addition to the sealing feature.
FDA is not mandating that three tamper-evident features be used,
and the agency is not convinced that consumers will be alarmed by a
change in a product's tamper-evident features. Informative labeling
will help allay the anxiety that consumers may feel. Retailers will
also be able to explain the change in packaging to interested or
concerned customers.
D. Dates
10. Two comments opposed the proposed retail level effective date
for compliance with the sealing requirement. These comments
characterized the effective date as extraordinary, insupportable, and
unprecedented. The comments said that the retail effective date places
an undue burden on retailers to examine all of their products,
determine which products covered by the rule are out of compliance, and
return those products to the manufacturers. According to the comments,
the prospect of conducting these resource-intensive compliance checks
would likely lead retailers to return all products marketed in two-
piece, hard gelatin capsules rather than just those products that were,
in fact, out of compliance. The comments asserted that such a marketing
disruption is not justified in light of the negligible number of
unsealed capsules that would be on the market 2 years after the
publication of the final rule.
FDA has considered the benefits of a retail level effective date
and the burden that would be placed on retailers, and agrees that such
a condition is currently unwarranted. The agency expects that, because
no unsealed capsules may be initially introduced into interstate
commerce 1 year after publication of this final rule, a negligible
quantity of noncomplying products will remain on the market 2 years
after publication of the final rule. The agency bases this expectation
in part on the high level of compliance with the effective date of the
1982 tamper-resistant packaging rule. The agency has, accordingly,
removed the proposed retail level effective date from this final rule.
While FDA encourages manufacturers to revise OTC drug product
labeling to replace the term ``tamper-resistant'' with ``tamper-
evident'' as soon as possible, the agency recognizes that substantial
revision of OTC labeling may be required by a final rule based on the
proposed OTC labeling rule published in the Federal Register of
February 27, 1997 (62 FR 9024). A reasonable effort has been made to
coordinate implementation of the two rules and, following publication
of a final OTC labeling rule, FDA will consider whether to extend the
compliance date of the labeling changes provided by this regulation to
coincide with the effective date of the OTC labeling final rule. The
agency emphasizes that any such extension would apply only to the
labeling requirements and not to the sealing requirements of this rule.
All two-piece, hard gelatin capsules subject to this regulation that
are initially introduced or initially delivered for introduction into
interstate commerce must be sealed in compliance with this regulation
by the date provided in the ``Dates'' section of this document.
E. Effectiveness of Change in Terminology from ``Tamper-Resistant'' to
``Tamper-Evident''
FDA proposed to amend Sec. 211.132 by changing the term ``tamper-
resistant'' to ``tamper-evident.''
11. Fourteen comments, while agreeing with the proposed change,
stated that its effectiveness would depend on an education campaign to
bolster awareness of steps consumers can take to protect themselves.
The most common concerns expressed by comments opposed to the proposed
change were that consumers will not notice the change or that they will
not understand the distinction between ``tamper-resistant'' and
``tamper-evident.''
The agency recognizes that this change may go unnoticed by those
consumers who do not regularly read labels. It is nonetheless important
that labeling accurately and truthfully characterize the degree of
protection afforded by tamper-evident packaging. It is particularly
important that measures designed to discourage tampering do not convey
a false sense of security or reduce consumer vigilance. The agency
believes the term ``tamper-evident'' better indicates the need for
active consumer surveillance of protective packaging features. FDA
stated in the proposed rule and reiterates here that ``the term `tamper
evident' more accurately describes the role of packaging in reducing
the likelihood of harm from tampering, and emphasizes the necessity of
consumer involvement in the effectiveness of any packaging system
designed to meet the requirements of this regulation'' (59 FR 2542 at
2544). The role of consumer education in enhancing protection against
tampering is discussed in the response to comment 20 in section III.G
of this document.
12. Several comments suggested a requirement that the labeling
statement on tamper-evident features be printed in a more conspicuous
format (e.g., in bold face, underlined type, or contrasting colors).
The agency does not believe that such a requirement is necessary at
this time. While such labeling measures would no doubt attract some
consumers' attention initially, the agency believes that many other
factors must be weighed in a consideration of such a requirement.
First, such prominence of the tamper-evident message may distract
consumers from other labeling information, such as warnings and
directions for use, that may be equally important. Second, in light of
the crucial role of OTC drug products in our health care system,
consumers must not be discouraged from using OTC medications because of
an excessive emphasis on the tampering threat.
13. One comment stated that the term ``tamper-evident'' would not
convey the appropriate message, but rather would give consumers a false
sense that it would be ``glaringly obvious'' if a product's
antitampering feature had been breached. Another comment stated that
consumers are intelligent and do not interpret the term ``tamper-
resistant'' to mean ``tamper-proof.''
FDA does not agree that the term ``tamper-evident'' will mislead
the consumer or that the term ``tamper-resistant'' does not. While the
term ``tamper-resistant'' does not technically mean that a product is
tamper proof, the term focuses on the packaging technology itself and
can imply that it is difficult to breach an antitampering feature.
While it may not be difficult to breach some commonly used
antitampering features, it is difficult to breach a feature without
leaving visible signs of tampering. Such visible signs will only
protect consumers from tampering harm if they are aware that an
antitampering feature is breached or missing. The proposed change in
the terminology appropriately shifts the emphasis from the ability of
the feature itself to protect consumers to the ability of vigilant
consumers to protect themselves.
14. One comment asserted that the rule improperly shifts the burden
of preventing drug product tampering from the OTC industry to the
``unsuspecting sick and poor consumers.''
[[Page 59467]]
FDA does not agree. The proposed rule will require some
manufacturers of hard capsules to take additional steps to prevent
tampering by sealing two-piece, hard gelatin capsules. Nonetheless,
because it is impossible to make a tamper-proof package, the success of
an antitampering regulatory program necessarily depends in part on
consumers' attentiveness; consumers must take some responsibility for
protecting themselves. FDA-mandated tamper-evident features will allow
vigilant consumers to minimize their chances of being victimized by a
malicious tamperer. Ultimately, the best defense against tampering is
an awareness of the tamper-evident features and a careful inspection of
all products.
15. One comment stated that packages should, in fact, be required
to be tamper resistant.
FDA does not believe that such a requirement is practical. The
intent of tamper-evident packaging is to alert the consumer to signs of
tampering without making the package more difficult to open. Otherwise,
those who have difficulty opening packages, such as the elderly and
disabled, are more likely to avoid using products contained in such
packaging.
16. One comment requested clarification regarding the extent of the
regulation's restriction on the use of certain terms in OTC drug
product labeling.
It is not the intent of the regulation to mandate the use of the
specific term ``tamper-evident'' in labeling. Indeed, any words that
correctly characterize the role of packaging in reducing the likelihood
of harm from tampering (without an implication that a package or dosage
form is tamper resistant or tamper proof) and that place appropriate
emphasis on the importance of consumer involvement in their own
protection would be acceptable under the rule.
17. One comment recommended shortening the 2-year effective date
for implementing the labeling changes.
FDA does not agree that the proposed time for implementation of the
labeling change should be shortened. The agency determined that a 2-
year implementation is prudent because it achieves an expeditious
implementation while at the same time not unreasonably burdening
industry. Any burden to industry is minimized by a 2-year compliance
date because most product labels are routinely reprinted within an 18-
to 24-month period.
F. Listing of All Tamper-Evident Features
Proposed Sec. 211.132(c) clarified that the labeling statements on
all OTC drug products are required to identify all packaging features
used to comply with proposed Sec. 211.132(b)(1), not just the features
on the external package. These packaging features would include those
on the secondary package, the immediate container or closure, and any
capsule-sealing technologies used to meet the requirements of the
regulation.
18. Five of the seven comments raising the issue were in favor of
this proposed revision. One comment expressed reservations about the
lack of a requirement that the labeling on the inner package contain
information regarding tamper-evident features, stating that persons are
more likely to read the information on the inner labeling. The comment
suggested that the proposed rule should give manufacturers more
specific direction as to what information must be provided regarding
possible signs of tampering (e.g., directions to compare lot numbers of
blister packs with those on the box) and more specific guidance
regarding the requisite prominence with which such information must be
displayed.
The role of drug labeling is to effectively communicate
consequential information regarding the safe and effective use of a
drug. If the amount of information is too great, consumers may miss the
essential message. The agency believes that Sec. 211.132(c)(1) provides
sufficient guidance to ensure that the important safety message is
conveyed to consumers and that more specific direction to manufacturers
is unnecessary.
19. One comment stated that revised labeling is unwarranted because
consumers do not read the labeling and, thus, the reworded rule will
have no impact.
FDA is charged with protecting the public health, and package
labeling is one indispensable mechanism for conveying such information
as instructions for use, warnings, and signs of possible tampering.
Many consumers do read package labeling, and all consumers should have
the opportunity to avail themselves of such information.
G. Consumer Education Campaign
The proposal stated that consumer education and involvement are
important to help prevent malicious tampering, and discussed steps that
FDA has taken to inform consumers to be alert for drug product
tampering.
20. Nearly all of the comments stressed the need for a consumer
education campaign in conjunction with implementation of the new
tamper-evident requirements. Several comments cited the Sudafed
tampering incident, which resulted in two deaths despite numerous and
conspicuous signs of intrusion, as evidence that consumer education is
an indispensable element of an antitampering campaign. The comments
generally focused on two options for educating consumers: (1) A
widespread media campaign using such means of communication as public
service announcements, magazine advertisements, news articles, press
releases, signs placed where OTC drug products are sold, brochures, or
public workshops; and (2) a requirement for additional or stronger
warnings on OTC drug product labels about the risks from product
tampering.
While FDA encourages the drug industry to provide consumers as much
information as is feasible regarding tampering, the agency will not
mandate stronger tamper-evident messages on drug product labeling at
this time. As previously discussed, the agency believes that the
labeling requirements in this final rule provide necessary information
to consumers without the negative consequences that can result from
exaggerated emphasis on a single issue. Rather, FDA will focus its
efforts on disseminating information through public service
announcements, journal articles, store displays, flyers sent through
the mail or disseminated with the purchase of an OTC drug product, or
workshops aimed at specific target audiences. Messages will be aimed at
informing consumers about tamper-evident packaging, the need for
vigilance, and the safety of the OTC drug supply.
The extent of educational efforts undertaken depends, in large
part, on support from interested parties. FDA appreciates the
willingness of some professional societies to assist in the agency's
educational endeavors. The agency requests assistance from the drug
industry, professional organizations, consumer groups, and other
Government agencies in conveying an effective, consistent message to
consumers about drug tampering. Organizations, in coordination with
FDA, are encouraged to use their newsletters, magazines, or other
networking capacities to notify constituencies about the signs of drug
product tampering.
21. Comments advocating a media campaign emphasized the importance
of reaching a vast audience (e.g., through publication in a widely
circulated magazine or through prime time
[[Page 59468]]
television public service announcements).
FDA recognizes the importance of imparting the message about drug
tampering to as great a target audience as feasible. However, the
agency must conduct any educational campaign so that the increased
visibility of the tampering issue does not have the unintended effects
of stimulating tampering or creating undue anxiety about the threats
posed by tampering. In an effort to achieve this delicate balance, FDA
must carefully choose a clear and focused message and a method of
delivery to ensure that the message is perceived as intended.
H. Packaging Performance Standards
In the proposed rule FDA invited discussion on the possibility of
establishing performance standards for tamper-evident packaging.
Three comments urged FDA to adopt packaging performance standards
and two comments opposed such standards.
22. One comment in support of packaging performance standards
stated that FDA's current method of evaluating tamper evidence is not
objective and does not take into consideration all factors involved in
violating a package seal. Another comment expressed a different view,
stating that packaging performance standards are unnecessary because
packaging guidance already exists through this rule and FDA's
Compliance Policy Guide (CPG) 7132a.17 entitled ``Tamper-Resistant
Packaging Requirements for Certain Over-the-Counter (OTC) Human Drug
Products'' (Ref. 2). One comment that supported the use of packaging
performance standards stated that many aspects of packaging needed to
be improved if the packages are to provide adequate evidence of
tampering.
The agency has concluded that Sec. 211.132 and CPG 7132a.17 (which
the agency will amend to conform to this final rule) will provide
adequate guidance for a determination of whether a package meets the
tamper-evident requirement. FDA does not use a rigid checklist of
criteria to determine whether a package meets the tamper-evident
requirement. The agency deems a technology to be in compliance with the
regulation if the feature provides visible evidence to consumers that
tampering has occurred, as required by the tamper-evident packaging
regulation, and complies with the other regulatory requirements of
Sec. 211.132. Additional guidance on tamper-evident packaging is found
in CPG 7132a.17 that lists examples of packaging and sealing
technologies that are, and are not, capable of meeting tamper-evident
packaging requirements.
FDA has considered the advantages and disadvantages of implementing
packaging performance standards and finds that the drawbacks of
requiring tamper-evident features to meet specific performance
standards outweigh the advantages of such a system. The agency's
current policy allows for flexibility in packaging technology and
encourages technical innovation to improve tamper evidence and enhance
packaging security.
The agency believes that the way to encourage improvements in
feature design is not to impose additional regulatory requirements, but
rather to set forth the general standard of tamper evidence and to
remain flexible with respect to use of alternative technologies. Use of
measurable performance standards might result in a premature ranking of
tamper-evident technologies, and FDA has concluded that the
establishment of performance standards for tamper-evident packaging is
not necessary at this time.
23. One comment expressed a concern that a tamper-evident feature
of a package may interfere with the package's child-resistant feature.
The agency wishes to clarify that the tamper-evident packaging rule
does not affect a manufacturer's responsibility to comply with other
applicable regulatory requirements, including the requirement of child-
resistant packaging issued by the Consumer Product Safety Commission
and found at 16 CFR 1700. The agency appreciates the comment's concern
and reiterates that the manufacturer must ensure that the tamper-
evident features of a package do not interfere with its child-resistant
features.
I. Economic Impact
As noted earlier, FDA requirements for OTC drug product packaging
to protect against drug tampering have been in effect since 1982. This
final rule clarifies the application of the current regulation, amends
the current regulation to require sealing of products marketed in two-
piece, hard gelatin capsules, and requires that the labeling of certain
products be modified to substitute the term ``tamper-evident'' for
``tamper-resistant.'' FDA estimated, in the proposed rule, that the
total one-time costs of the changes would be approximately $1.8 to $3
million to seal the few two-piece, hard gelatin capsule products that
are currently unsealed, and for other minor costs associated with a
change in the terminology used in the labeling of some products.
24. Some of the comments that specifically raised the issue of the
cost of sealing considered the cost reasonable. Other comments stated
that the sealing requirement is unduly burdensome and would result in
unwarranted increased costs to manufacturers and higher prices to
consumers.
An analysis of the costs of compliance with the new regulation is
only meaningful in the context of expected benefits. While the
important benefits that are expected to result from the sealing
requirement have been discussed, it is impossible to predict precisely
the number of lives that may be saved or injuries prevented by these
new requirements. Nevertheless, in view of the public health benefits
that can be reasonably expected from this added measure of consumer
protection, the costs of compliance with the sealing requirement are
relatively low.
25. Five comments stated that the cost of sealing all two-piece,
hard gelatin capsules would be much higher than FDA's estimate. The
comments questioned the premises on which the cost to industry estimate
of $1.8 to $3 million was based. One of these comments said that at
least 22 OTC drug products--not 12, as FDA estimated--are currently
marketed as unsealed two-piece, hard gelatin capsules. Another comment
said that, for companies with numerous OTC drug products offered in the
capsule dosage form, compliance with the proposed rule would require
the purchase of more than one hard gelatin capsule sealing machine,
which, in combination with the required parts for the sealing machine
and gelatin sealing solution, would total approximately $700,000. The
comment asserted that the eventual cost of compliance would be
substantially more because of additional costs for necessary
alterations to the manufacturing facility's encapsulating area.
FDA's original cost estimate assumed that each affected product
would require a separate gelatin capsule sealing and banding machine at
a cost of $250,000 per machine. Consequently, this calculation is not
inconsistent with the estimate of $700,000 for a company that
manufactures several affected products. FDA acknowledges that its
earlier estimate of 12 affected products may be too small and has
accepted the estimate that 22 products are currently marketed in
unsealed two-piece hard gelatin capsules. Using this higher figure, as
detailed in section VIII of this document, FDA has revised its
estimated compliance costs for this provision to $5.5 million.
[[Page 59469]]
26. Five comments expressed concern that the costs of compliance
would be passed on to consumers of OTC drug products in the form of
higher prices. One comment estimated that the cost passed on to the
consumer would be in the range of $1 to $2 per bottle. Another comment
estimated that the cost passed on to the consumer would be about 35 to
55 cents per 100-count bottle.
FDA realizes that a portion of the cost of compliance may be
passed on to consumers and the agency has revised its estimate of this
cost in section VIII of this document. In addition to the $250,000 cost
of a gelatin capsule sealing and banding machine, the cost of labeling
changes is expected to average $2,500 for each branded OTC drug and
$850 for each private label OTC drug. Individual companies control
product pricing and it is conceivable that the price of certain very
low volume drug products might be noticeably increased. However, given
the one-time impact of most of the costs of this rule, the safety
benefits, and the overall costs of drug product manufacturing, the
agency does not believe the price of many products will be
substantially affected.
27. One comment stated that tamper-evident packaging features would
be a cheaper, more effective alternative to sealing. The comment
provided no support for this theory.
As explained earlier, FDA believes that packaging requirements do
not effectively minimize the dangers posed by OTC drug product
tampering and that the sealing requirement is necessary to address the
continued vulnerability of two-piece, hard gelatin capsules.
28. Several comments stated that the cost of the labeling change to
eliminate terms such as ``tamper-resistant'' was unreasonably
burdensome.
In response to several comments, FDA reexamined the estimated cost
of proposed labeling changes and has revised the $5 to $6 million
estimate to $10 million. Even as revised, however, FDA disagrees that
the cost of the labeling change is unreasonably burdensome. The use of
terminology accurately characterizing the degree of protection offered
by tamper-resistant packaging is a cost effective step toward educating
consumers. The agency has further reduced the burden of the labeling
change to industry by giving manufacturers up to 2 years to make the
conversion.
IV. Legal Authority
FDA's revision of the tamper-resistant packaging requirements for
OTC drug products is authorized by the Federal Food, Drug, and Cosmetic
Act (the act). As discussed in the proposed rule (59 FR 2542 at 2545),
the agency is authorized to establish requirements for container and
package design that provide protection against intentional product
adulteration by tampering and to establish requirements for labeling
statements alerting consumers to tamper-evident features. (See also 47
FR 50442 at 50447, November 5, 1982, for additional discussion of the
legal authority for requirements related to drug product tampering.)
V. References
The following references have been placed on display in the Dockets
Management Branch (HFA-305), Food and Drug Administration, 5630 Fishers
Lane, rm. 1061, Rockville, MD 20852, and may be seen between 9 a.m. and
4 p.m, Monday through Friday.
1. The Nonprescription Drug Manufacturers Association, ``The
Sale of OTC Medicines in Capsule Form Should Not Be Banned or
Restricted,'' position statement, March 9, 1991.
2. FDA Compliance Policy Guide 7132a.17, ``Tamper Resistant
Packaging Requirements for Certain Over-the-Counter (OTC) Human Drug
Products,'' May 21, 1992. This document is also available at cost
from the National Technical Information Service (NTIS), U.S. Dept.
of Commerce, 5285 Port Royal Rd., Springfield, VA 22161, 703-487-
4650.
VI. Paperwork Reduction Act of 1995
FDA concludes that this final rule is not subject to review by the
Office of Management and Budget. Requiring manufacturers to use the
term ``tamper-evident'' in the labeling and to identify tamper-evident
features and capsule sealing technologies in the labeling is exempt
under 5 CFR 1320.3(c)(2) as a public disclosure of information
originally supplied by the Federal Government to the recipient for the
purpose of disclosure to the public.
VII. Environmental Impact
The agency has determined under 21 CFR 25.30(h) that this action is
of a type that does not individually or cumulatively have a significant
effect on the human environment. Therefore, neither an environmental
assessment nor an environmental impact statement is required.
VIII. Analysis of Impacts
FDA has examined the impact of the final rule under Executive Order
12866 and the Regulatory Flexibility Act (5 U.S.C. 601-612). Executive
Order 12866 directs agencies to assess all cost and benefits of
available regulatory alternatives and, when regulation is necessary, to
select regulatory approaches that maximize net benefits (including
potential economic, environmental, public health and safety, and other
advantages; distributive impacts; and equity). If an agency determines
that a rule has a significant economic impact on a substantial number
of small entities, the Regulatory Flexibility Act requires agencies to
analyze regulatory options that would minimize any significant impact
of a rule on small entities. Section 202 of the Unfunded Mandates
Reform Act (Pub. L. 104-4) requires that agencies prepare an assessment
of anticipated costs and benefits before proposing any rule that might
result in an expenditure by State, local and tribal governments, in the
aggregate, or by the private sector, of $100 million (adjusted annually
for inflation) in any year.
As discussed in this preamble, the regulatory history of measures
to reduce the risk of product tampering, the agency evaluation of
alternative control strategies suggested in response to comments, and
the revised implementation schedule demonstrate that this rule is
consistent with the principles set forth in the Executive Order and
these two statutes.
A. Executive Order 12866
FDA had estimated that the January 18, 1994 (59 FR 2542) proposed
rule to strengthen tamper-evident packaging requirements would impose
compliance costs of $3 million for sealing the two-piece hard gelatin
capsules. One comment to the proposed rule stated that at least 22
products are currently marketed in unsealed two-piece hard gelatin
capsules, not 12 products as FDA had estimated. Based on this comment,
FDA has revised its estimated compliance costs for this provision to
$5.5 million ($250,000 per capsule sealing machine x 22 products).
Compliance costs for relabeling OTC's containing the ``tamper-
resistant'' terminology with the ``tamper-evident'' terminology was
estimated at $5 to $6 million in the proposed rule. Based on
information from the Nonprescription Drug Manufacturers Association
(NDMA) indicating that these labels were routinely reprinted within an
18 to 24 month period, the incremental cost of this provision was
expected to be minimal. Several comments, however, stated that the cost
of the labeling change was unreasonably burdensome. FDA has reviewed
the latest data on label change costs and patterns and revised its
estimate of compliance costs for this provision. The agency estimates
that about 20 percent of OTC drug labels are reprinted over any 2-year
period, as shown by survey data from NDMA.
[[Page 59470]]
Further, FDA finds that branded OTC drugs have much higher per label
costs than do private label OTC drugs. Based on recent information, FDA
estimates that a minor label change would cost from $2,000 to $3,000
for each branded OTC drug. Private label costs for a minor change are
estimated to range from $500 to $1,200, or an average of $850 per OTC
drug.
FDA has also revised its estimate of the number of products (stock
keeping units or SKU's) that are subject to the labeling provisions of
the tamper-evident packaging. FDA estimates this number at about 62,000
SKU's (including both branded and private label SKU's). Whereas the
proposal estimated that 60 percent of the SKU's would be out of
compliance with the new rule, a very limited survey of OTC drug
products now shows a noncompliance rate of about 15 percent. Accounting
for all of the above factors, FDA estimates the compliance cost of the
labeling provision at $10 million. These costs, however, would be
mitigated to the extent that companies can coordinate this effort with
the forthcoming rule to standardize all OTC drug labels.
To summarize, the estimated total one-time costs of the final rule
are the sum of the $5.5 million to seal the capsule products that are
currently not sealed and the $10 million to change the labeling on the
products that currently use the ``tamper-resistant'' terminology. Total
one-time compliance costs, therefore, are estimated at $15.5 million.
The rule will not impose any other annual costs on the OTC drug
industry.
Because this final rule is not a significant regulatory action as
defined by Executive Order 12866, an additional assessment of the rule
under section 6 of the Executive Order is not necessary.
B. Regulatory Flexibility Act
According to the Regulatory Flexibility Act, the final rule should
include ``a succinct statement of the need for, and objectives of, the
rule.'' FDA is taking this action as a result of its continuing review
of the potential public health threat posed by product tampering and to
improve consumer protection by addressing specific vulnerabilities in
the OTC drug market.
FDA accepts the industry estimate of 22 products currently marketed
in two-piece hard gelatin capsules. FDA does not have a definitive
estimate of the percentage of these companies that may be small. The
Small Business Administration (SBA) defines small pharmaceutical
manufacturers as those having less than 750 employees. It is likely,
however, that many of these firms will not be small. FDA estimates
that, at a maximum, only 2 of the original 12 products identified by
FDA were made by a small manufacturer. Using the same ratio (2:12), a
low-end range estimate of about 4 of the 22 affected products would be
made by a small manufacturer. A high-end estimate of 12 was developed
by assuming that all of the 10 products not previously accounted for
(22 - 12 = 10) are made by different small manufacturers. The final
estimate, therefore, is a range of 4 to 12 products from small
manufacturers that are marketed in two-piece hard gelatin capsules.
These small businesses are expected to incur average one-time
compliance costs of $150,000 to $250,000 for purchasing the capsule
sealing machinery if it is not already available. Other firms may
choose to contract out the manufacturing process for these products.
Further, the proposed rule estimated that about 780 products
(including different sizes and strengths) would be affected by the
labeling provisions of this rule. Using more recent data, FDA revised
its estimate of the number of product SKU's in need of relabeling to
about 9,300. Due to the 2-year phase-in period for ``tamper-evident''
labeling, FDA expects only about 7,450 of these SKU's to be affected
outside of their normal reprinting patterns. FDA does not have a good
estimate of the number of small companies that would have to relabel
their products. It can be assumed, however, that each small company has
very few SKU's, as the large companies and a small number of large
private labelers market numerous SKU's. As noted previously, each
affected SKU is estimated to incur a one-time relabeling cost of either
$850 or $2,500.
FDA attempted to minimize the burden of this rule on manufacturers
by granting them 2 years after final publication to comply with the
labeling provisions. Also, FDA has not included any new reporting or
recordkeeping requirements. After review of the comments, FDA has
revised the final rule even further. The proposed rule would have
created a 2-year effective date at the retail level. Comments to the
proposed rule claimed that it would require burdensome compliance
checks by retailers in order to check for a negligible quantity of
noncomplying products. In response to these comments, FDA has chosen an
alternative policy that does not include a retail effective date.
Several other alternatives were considered. Comments suggested a
requirement that: (1) Two-piece capsules be kept behind the counter,
(2) video surveillance be provided for retail space where OTC drug
products are sold, (3) holographic labels be used on OTC drugs, (4)
bold print or contrasting colors be used to further illuminate the
tamper-evident warning on OTC drugs and (5) packaging performance
standards be developed and applied to tamper-evident OTC drug
packaging. FDA considered these alternatives and determined that the
additional compliance costs they would create cannot be justified by
the small amount of increased awareness of tamper-evident packaging
they would offer.
C. Unfunded Mandates Reform Act
FDA concludes that this regulation will not result in expenditure
of $100 million by State, local or tribal governments, in the
aggregate, or by the private sector, in any 1 year. Therefore, under
the Unfunded Mandates Reform Act, no further analysis is required.
List of Subjects in 21 CFR Part 211
Drugs, Labeling, Laboratories, Packaging and containers,
Prescription drugs, Reporting and recordkeeping requirements,
Warehouses.
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, 21 CFR part
211 is amended as follows:
PART 211--CURRENT GOOD MANUFACTURING PRACTICE FOR FINISHED
PHARMACEUTICALS
1. The authority citation for 21 CFR part 211 continues to read as
follows:
Authority: 21 U.S.C. 321, 351, 352, 355, 357, 360b, 371, 374.
2. Section 211.132 is amended by revising the section heading, by
removing in paragraph (a) the word ``throat'', by removing in
paragraphs (a) and (d)(2) the words ``tamper-resistant'' and adding in
their place the words ``tamper-evident'', and by revising paragraphs
(b) and (c), and the second sentence in the introductory text of
paragraph (d) to read as follows:
Sec. 211.132 Tamper-evident packaging requirements for over-the-
counter (OTC) human drug products.
* * * * *
(b) Requirements for tamper-evident package. (1) Each manufacturer
and packer who packages an OTC drug product (except a dermatological,
dentifrice, insulin, or lozenge product) for retail sale shall package
the product in a tamper-evident package, if this product is accessible
to the public while held for sale. A tamper-evident package
[[Page 59471]]
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 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. A tamper-
evident 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-evident feature shall be designed to and shall remain intact
when handled in a reasonable manner during manufacture, distribution,
and retail display.
(2) In addition to the tamper-evident packaging feature described
in paragraph (b)(1) of this section, any two-piece, hard gelatin
capsule covered by this section must be sealed using an acceptable
tamper-evident technology.
(c) Labeling. (1) In order to alert consumers to the specific
tamper-evident feature(s) used, each retail package of an OTC drug
product covered by this section (except ammonia inhalant in crushable
glass ampules, containers of compressed medical oxygen, or aerosol
products that depend upon the power of a liquefied or compressed gas to
expel the contents from the container) is required to bear a statement
that:
(i) Identifies all tamper-evident feature(s) and any capsule
sealing technologies used to comply with paragraph (b) of this section;
(ii) Is prominently placed on the package; and
(iii) Is so placed that it will be unaffected if the tamper-evident
feature of the package is breached or missing.
(2) If the tamper-evident feature chosen to meet the requirements
in paragraph (b) of this section 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) * * * A request for an exemption is required to be submitted in
the form of a citizen petition under Sec. 10.30 of this chapter and
should be clearly identified on the envelope as a ``Request for
Exemption from the Tamper-Evident Packaging Rule.'' * * *
* * * * *
Dated: October 28, 1998.
William B. Schultz,
Deputy Commissioner for Policy
[FR Doc. 98-29388 Filed 11-3-98; 8:45 am]
BILLING CODE 4160-01-F