[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]


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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.

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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