[Federal Register Volume 71, Number 238 (Tuesday, December 12, 2006)]
[Proposed Rules]
[Pages 74474-74482]
From the Federal Register Online via the Government Publishing Office [www.gpo.gov]
[FR Doc No: E6-21019]
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DEPARTMENT OF HEALTH AND HUMAN SERVICES
Food and Drug Administration
21 CFR Part 201
[Docket No. 1998N-0337C]
RIN 0910-AD47
Over-the-Counter Human Drugs; Labeling Requirements; Proposed
Rule
AGENCY: Food and Drug Administration, HHS.
ACTION: Proposed rule.
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SUMMARY: The Food and Drug Administration (FDA) is proposing to amend
its final rule that established standardized format and content
requirements for the labeling of over-the-counter (OTC) drug products
(Drug Facts Rule, codified at 21 CFR 201.66). This amendment proposes a
definition and the option of alternative labeling requirements for
``convenience-size'' OTC drug packages.
DATES: Submit written comments by April 11, 2007; written comments on
FDA's economic impact determination by April 11, 2007. See section X of
this document for the proposed effective date of a final rule based on
this document.
ADDRESSES: You may submit comments, identified by Docket No. 1998N-
0337C and/RIN number 0910-AD47, by any of the following methods:
Electronic Submissions
Submit electronic comments in the following ways:
Federal eRulemaking Portal: http://www.regulations.gov.
Follow the instructions for submitting comments.
Agency Web site: http://www.fda.gov/dockets/ecomments.
Follow the instructions for submitting comments on the agency Web site.
Written Submissions
Submit written submissions in the following ways:
FAX: 301-827-6870.
Mail/Hand delivery/Courier [For paper, disk, or CD-ROM
submissions]: Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
To ensure more timely processing of comments, FDA is no longer
accepting comments submitted to the agency by e-mail. FDA encourages
you to continue to submit electronic comments by using the Federal
eRulemaking Portal or the agency Web site, as described in the
Electronic Submissions portion of this paragraph.
Instructions: All submissions received must include the agency name
and Docket No. and Regulatory Information Number (RIN) (if a RIN number
has been assigned) for this rulemaking. All comments received may be
posted without change to http://www.fda.gov/ohrms/dockets/default.htm,
including any personal information provided. For additional information
on submitting comments, see the ``Comments'' heading of the
SUPPLEMENTARY INFORMATION section of this document.
Docket: For access to the docket to read background documents or
comments received, go to http://www.fda.gov/ohrms/dockets/default.htm
and insert the docket number, found in brackets in the heading of this
document, into the ``Search'' box and follow the prompts and/or go to
the Division of Dockets Management (HFA-305), Food and Drug
Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852.
FOR FURTHER INFORMATION CONTACT: Gerald M. Rachanow or Cazemiro R.
Martin, Center for Drug Evaluation and Research, Food and Drug
Administration, 10903 New Hampshire Ave., Bldg. 22, rm. 5426, Silver
Spring, MD 20993-0002, 301-796-2090.
SUPPLEMENTARY INFORMATION:
I. Background
In the Federal Register of March 17, 1999 (64 FR 13254), FDA
published a final rule establishing standardized format and
standardized content requirements for the labeling of OTC drug products
(Drug Facts Rule). Those requirements are codified in 21 CFR 201.66.
Section 201.66(a) states that the content and format requirements
in Sec. 201.66 apply to the labeling of all OTC drug products. This
includes products marketed under a final OTC drug monograph, products
marketed under an approved new drug application (NDA) or abbreviated
new drug application (ANDA) under section 505 of the Federal Food,
Drug, and Cosmetic Act (the act) (21 U.S.C. 355), and products for
which there is no final OTC drug monograph or approved NDA/ANDA.
In the Drug Facts Rule and in subsequent notices, FDA provided
dates by which OTC drug products had to be in compliance with the new
labeling requirements. FDA provided a chart in the Drug Facts Rule (64
FR 13254 at 13274) that summarized the time periods within which the
various categories of marketed OTC drug products were required to
comply with the final rule. Unless otherwise stated,
[[Page 74475]]
all time periods in the chart began on the effective date of the final
rule. The chart was subsequently updated on June 20, 2000 (65 FR 38191
at 38193) and April 5, 2002 (67 FR 16304 at 16306 to 16307).
In the June 20, 2000, update, FDA clarified the applicable
compliance dates in situations where relabeling was required by both
the Drug Facts Rule and another rule. In the April 5, 2002, update, FDA
delayed the compliance dates for ``convenience-size'' OTC drug
products. Those products are the subject of this proposed rule.
A. Delay of Compliance Dates for ``Convenience-Size'' OTC Drug Products
FDA's delay notice of April 5, 2002, postponed the Drug Facts Rule
compliance dates for all ``convenience-size'' OTC drug product packages
that do the following: (1) Contain no more than two doses of an OTC
drug, and (2) because of their limited available labeling space, would
require more than 60 percent of the total surface area available to
bear labeling to meet the requirements set forth in Sec. 201.66(d)(1)
through (d)(9) and would therefore qualify for the labeling
modifications currently set forth in Sec. 201.66(d)(10). ``Dose'' was
defined in the delay notice as the maximum single-serving for an adult
(or a child for products marketed only for children) as specified in
the product's directions for use. (See 67 FR 16304 at 16306.)
FDA's delay does not include single- or double-dose OTC drug
packages that do not qualify for the labeling conditions in Sec.
201.66(d)(10) because they can accommodate the Drug Facts labeling
required in Sec. 201.66(d)(1) through (d)(9) using 60 percent or less
of their total surface area available to bear labeling. Examples of
such products include some enemas, disposable douche products, and
ipecac syrup products intended for emergency treatment use in
poisonings. (See 67 FR 16304 at 16306 to 16307.)
B. Citizen Petition Requests Definition
FDA published the notice of delay for ``convenience-size'' OTC drug
product packages in response to a citizen petition (Ref. 1) submitted
by Lil' Drug Store Products, Inc. (Lil'). Lil' asked FDA to define
``convenience-size'' OTC drug products and to modify the labeling and
content requirements of the Drug Facts Rule with respect to such
products. Lil' proposed that ``convenience-size'' OTC drug products be
defined as packages sold to the public that contain one or two doses of
an OTC drug product. Lil' also proposed that ``dose'' be defined as a
manufacturer's recommended serving. In addition, Lil' requested that
FDA modify the requirements of Sec. 201.66 for these ``convenience-
size'' OTC drug products by permitting a reduced version of the OTC
Drug Facts labeling to appear on the external packaging of such
products, while requiring fully compliant Drug Facts labeling to appear
on the inside of the package through the use of package inserts or
inner-package printing. Lil' stated that, under its proposal, the
labeling on the external packaging would continue to include medically
relevant information, would be consistent with the retail environment
in which ``convenience-size'' OTC drug products are sold, and would
still adequately enable consumers to make the unique purchasing
decision associated with OTC drug use. Lil' described the
``convenience-size'' products that it sells as recognized, brand-name,
quality OTC drug products packaged in small doses and made available to
the consumer at his or her point of need.
Lil' stated that there were medical and policy rationales for its
request centering on the dosing limitations of ``convenience-size''
packages. Because such packages contain only one or two doses of an OTC
drug product, Lil' reasoned that it is acceptable and appropriate for
certain information required under the Drug Facts Rule to appear inside
the packages, either in a package insert or by inner-package printing.
Lil' proposed that the outer product labeling of a convenience-size
package still contain the complete ``Drug Facts'' title, active
ingredients, purpose, uses, and inactive ingredients, but that it be
allowed to abbreviate certain warnings and omit other required
information. Lil' also proposed adding the following statement in bold,
italic, seven-point Helvetica font: ``Please read complete Drug Facts
information inside prior to use.'' Lil' then proposed that the
remaining information required by the Drug Facts Rule, including
directions for use, certain warnings, and questions or comments, be
allowed to appear inside the package, and it provided supporting
reasons. (See section III.C of this document for a summary of Lil's
suggestions and reasoning.)
In its response (Ref. 2) to the Lil' citizen petition, FDA stated
that it had carefully reviewed the data and information in the petition
and agreed that some accommodation for ``convenience-size'' packages
might be appropriate. FDA stated that it intended to prepare, for
publication in a future issue of the Federal Register, a proposed rule
that would, if finalized, amend the Drug Facts Rule by defining
``convenience-size'' OTC drug packages and addressing Drug Facts
labeling requirements for such products. The proposed rule would also
provide all interested parties an opportunity to comment on the
viability, desirability, and impact of the proposed rule, and to
respond to specific questions posed by FDA.
II. The Basis for Optional Alternative Labeling for Convenience-Size
OTC Drug Packages
FDA believes, from a public health perspective, that convenience-
size OTC drug packages may not need to have all of the labeling
information required by the Drug Facts Rule on the outer package. This
belief is based on the reduced risks posed by the limited amount of the
active ingredient(s) contained in convenience-size packages,
particularly because most of these packages do not provide for
repetitive dosing. If a package contains only one or two doses of an
OTC drug product, FDA believes there is a significantly reduced
likelihood of an overdose occurring from consumption of the entire
contents of the package. Further, FDA believes there is a corresponding
reduction in the likelihood of other adverse side effects.
FDA also believes, as Lil' asserted in its petition, that many
consumers who purchase and use convenience-size packages of an OTC drug
product do so because they have an immediate need, often in a location
away from home, to take a dose or two of the product. These consumers
often purchase convenience size drug packages for immediate consumption
or other very short-term use and may not be as concerned at the time of
purchase about labeled statements regarding when to stop use of the
product and ask a doctor for assistance, overdose warnings, directions
for continued dosing, or storage information.
Lil' was also concerned that increasing the standardized size of
``convenience packages'' to comply with the Drug Facts Rule would
inhibit the sale of such packages from convenience stores and vending
machines, where space is limited and larger packages can not be
accommodated.
Thus, given the unique circumstances associated with the purchase
and use of ``convenience-size'' OTC drug products, FDA believes that
some modification of the current labeling requirements set forth under
Sec. 201.66(d)(10) can be achieved without jeopardizing the public
health or undermining the important goals of the act or the Drug Facts
Rule. FDA considers such a
[[Page 74476]]
modification to be especially important if failure to address this
issue means that ``convenience-size'' OTC drug products will no longer
be as available or accessible to consumers.
FDA has determined, however, that certain critical warnings (e.g.,
allergic reactions, do not use situations, drug/drug interactions,
risks associated with subsequent operation of a motor vehicle or
machinery) and other information (e.g., inactive ingredients) must
appear on the outer carton of convenience-size packages to allow
consumers to accurately assess certain potential risks associated with
the selection and use of the drug product at the time of purchase.
Further, FDA believes that complete product information should be
provided to consumers with ``convenience-size'' packages, regardless of
whether it is available at the point of purchase. For example,
information about repeat dosing need not appear on the outside carton
or wrapper of a ``convenience-size'' package, but it should appear on
the inside package labeling in an insert or in inner-package printing
for consumers who may purchase more than one package at a time.
Moreover, FDA strongly believes that the labeling modifications it
is proposing for convenience-size packages should be narrowly applied
and are not appropriate for packages of the same product that contain
more than two doses. FDA believes that consumers who buy packages
containing more than two doses customarily intend to take the product
over a longer period of time than consumers who buy convenience-size
packages. FDA believes that consumers who purchase packages with more
than two doses should have complete information available at the time
of purchase, so they can make fully informed decisions about prolonged
use of the product.
For the reasons stated previously, FDA is proposing to modify the
Drug Facts labeling requirements in Sec. 201.66 for convenience-size
OTC drug products as set forth in sections III.A, III.B, and III.C of
this document. FDA believes its proposal will help achieve an
appropriate balance between the consumer safety interests of the act
and the Drug Facts Rule and the desire to ensure continued access to
convenience-size OTC drug products in the marketplace.
III. FDA's Proposal
A. Definition of a Convenience-Size Package
FDA believes that the definition of a ``convenience-size'' OTC drug
package should be a function of both the number of doses contained in
the package and the size of the package. FDA's proposed definition of
convenience-size is set forth in proposed paragraph 201.66(d)(5). This
definition addresses the number of doses and the package size.
1. Number of Doses
FDA considers a limited number of doses as one of the key criteria
in any meaningful definition of ``convenience-size.'' FDA proposes that
the definition of ``convenience-size'' be limited to OTC drug packages
that contain no more than two doses of an OTC drug product. In the
notice of April 5, 2002, partial delay of compliance dates, FDA defined
a ``dose'' as the maximum single-serving for an adult (or a child for
products marketed only for children), as specified in the product's
directions for use (67 FR 16304 at 16306). FDA is including the same
definition in this proposal.
FDA has found that some currently marketed OTC convenience-size
drug products have directions for both adults and children. In most
cases, the child's dose is one-half the adult dose. For example, in
many products where the adult dose is two dosage units, the child's
dose is one dosage unit. FDA did not address this type of package in
the April 5, 2002, partial delay of compliance dates. For safety
reasons, FDA is proposing that, for products marketed with directions
for use for both adults and children, a ``dose'' be defined as the
maximum single serving based on the child's dose.
Those OTC drug monographs that provide directions for both children
and adults generally give manufacturers the flexibility to market the
OTC drug package to adults only, or to children only, or to both adults
and children, so long as the package labeling bears the warnings that
correspond to the age group(s) for whom the product is intended (see,
e.g., 21 CFR 341.74(c) and 341.80(c)). Therefore, FDA does not believe
that its proposed definition of ``dose'' will unduly hamper a
manufacturer's ability to market convenience size packages to adults,
but instead will provide a necessary safeguard against potential
overdose in children in those instances where such products are
marketed for children's use.
This proposed definition of ``dose'' would also apply to sample and
trial-size packages that contain only one or two dosage units of an OTC
drug. It would not apply to trial-size packages, or to any other small
package sizes, that contain more than two doses and are sold in a
retail setting.
2. Package Size
With respect to package size, FDA proposes that the definition of
convenience-size be limited to those packages that qualify for the
current labeling modification in Sec. 201.66(d)(10) but which, because
of their limited available labeling space, would require more than 60
percent of the total surface area available to bear labeling to meet
the requirements set forth in Sec. 201.66(d)(10). Thus, under the
proposed rule, one or two dose OTC drug packages that qualify for, and
can accommodate, the current labeling modifications provided in Sec.
201.66(d)(10) with 60 percent or less of their available labeling space
would not meet the definition of ``convenience-size'' package in
proposed Sec. 201.66(b)(5). Only those ``convenience-size'' OTC drug
packages that are so small that they cannot accommodate the modified
drug facts labeling in Sec. 201.66(d)(10) with 60 percent or less of
their available labeling space would be allowed to bear the optional
alternative labeling set forth in new Sec. 201.66(d)(11). We note that
there are many single-dose OTC products that are packaged in containers
that are too large to qualify for the modifications in Sec.
201.66(d)(10) (e.g., most enemas and disposable medicated douche
products).
FDA invites specific comment on the following issues:
1. Whether the definition of ``dose'' should be different from that
proposed and, if so, why. For those suggesting that the definition of
dose be either expanded or narrowed, please explain the precise
rationale for such a suggestion and explain how your proposed
definition could be implemented to be meaningfully limited;
2. Whether the criteria regarding package size in proposed Sec.
201.66(b)(5) should be different and, if so, why. For those suggesting
that the size criteria be either expanded or narrowed, please explain
the precise rationale for such a suggestion;
3. Whether there are any data or evidence to support Lil's
assertion that increasing package size to accommodate all of the
information currently required under Sec. 201.66(d)(10) will force
traditional OTC convenience-size drug products out of the retail
marketplace and/or reduce consumer access to such packages;
4. The relative public health risks associated with use of OTC
convenience-size drug packages and the types of labeling information
that must (or need not) be available at the point of
[[Page 74477]]
purchase to ensure the safe and effective use of such products;
5. How the proposed definition of ``dose'' (or any other suggested
definition of ``dose'') might apply to topical products and how it
might be possible to include OTC ``convenience-size'' topical drug
products within this proposed labeling modification;
6. Whether there are any data to support Lil's assertion that most
OTC convenience-size drug products are purchased for an immediate need
to take a dose or two of the drug (as opposed to repeat dosing); and
7. Whether there are reasons to oppose any labeling modification
for OTC convenience-size drug products. For those opposing any
modification to the Drug Facts Rule for OTC convenience-size packages,
please explain the precise rationale for your position and provide
evidence, if any, to support your concerns.
B. Exceptions to the Proposed Definition
For public health reasons, FDA proposes to exempt from the
definition of ``convenience-size'' several OTC drug products used for
poison treatment that are marketed in single-dose containers. These
include syrup of ipecac and activated charcoal. Syrup of ipecac is
limited by regulation (21 CFR 201.308(c)) to 1 fluid ounce (30
milliliter (mL)) packages for OTC sale. The usual dosage is one
tablespoon (15 mL) in persons over 1 year of age (Sec. 201.308(c)(3)).
FDA has proposed that the dosage be revised to 2 tablespoonsful (30 mL)
for adults and children 12 years of age and over and to 1 tablespoonful
(15 mL) for children 1 to under 12 years of age. (See proposed Sec.
357.54(d), 50 FR 2244 at 2261, January 15, 1985). Activated charcoal is
usually marketed in packages containing a minimum of one dose of 20
grams. (See proposed section 357.52(d)(1), 50 FR 2244 at 2261).
FDA considers it important that all of the labeling information for
these products be available to consumers at the time of purchase. FDA
also believes that, unlike most convenience-size OTC drug products,
poison treatments are not purchased for immediate use, but are often
acquired for subsequent access within the home in case of an emergency.
FDA is therefore concerned that if some of the important information
for using these products only appeared on a package insert and that
insert got separated from the package before the product was used, the
consumer would not have the necessary information at the time the
product was needed, possibly resulting in serious health consequences.
Those single dose OTC syrup of ipecac and activated charcoal packages
that qualify for the labeling modification in Sec. 201.66(d)(10) may
still be labeled according to the modifications set forth in that
section. However, for the reasons stated above, FDA proposes to exclude
them from the definition of ``convenience-size'' in Sec. 201.66(b)(5)
and the additional labeling modifications proposed in Sec.
201.66(d)(11), regardless of package size.
Because there currently is no final monograph for OTC poison
treatment drug products, FDA does not know how many manufacturers,
repackers, and distributors of these products have attempted to develop
Drug Facts labeling for these products. FDA invites comment, especially
from companies that prepare labeling for these products, about how the
labeling proposed in Sec. 357.52 and 357.54 (50 FR 2244 at 2261) would
best fit on the immediate and outside containers when converted to the
new Drug Facts format. Interested parties are invited to submit draft
labeling in response to this proposed rule for FDA to evaluate. FDA
also invites specific comment on whether there are other OTC drug
products that should not be eligible for the proposed ``convenience-
size'' labeling format, even if such products otherwise meet the
definition set forth in proposed Sec. 201.66(b)(5).
C. Optional Alternative Labeling for Convenience-Size Packages:
Discussion
FDA agrees with Lil' that certain Drug Facts information must fully
appear on the outer product labeling of a convenience-size OTC drug
package, regardless of the size of that package. This information
includes the ``Drug Facts'' title, active and inactive ingredients,
purpose(s), use(s), certain warnings, and some of the other information
required by Sec. 201.66(c)(7). FDA considers this information an
essential part of Sec. 201.66 that must be available to all consumers
at the point of purchase. FDA also considers the warnings in Sec.
201.66(c)(5)(i), (c)(5)(ii), and (c)(5)(iii) essential information that
should appear in full on the outside of all OTC convenience-size
packages because these sections contain especially important warning
information that might influence a consumer's purchase decision at the
point of sale. Regarding the other applicable warnings and directions,
FDA has the following comments:
1. Section 201.66(c)(5)(iv): This section requires the warning
subheading ``Ask a doctor before use if you have'' and includes
warnings for certain pre-existing conditions and warnings for persons
experiencing certain symptoms. Lil' pointed out that the warnings under
this heading are those intended only for situations in which consumers
should not use the product until a doctor is consulted. Lil' contended
that the information, while important, becomes less so given the low
dosage being consumed and the unlikely negative side effects of such a
low dosage, and this information can be safely included inside the
outer carton of a convenience-size package.
FDA disagrees. Information under this subheading would include
disease conditions such as diabetes, glaucoma, high blood pressure,
heart disease, thyroid disease, and trouble urinating due to an
enlarged prostate gland. Consumers who have these conditions need to be
informed at the point of purchase that the product may have an
undesired effect because of the pre-existing condition(s). This
potential problem for an adverse side effect exists whether the
consumer is taking a single dose from a convenience-size or multiple
doses over time from a larger package.
2. Section 201.66(c)(5)(v): This section requires the warning
subheading ``Ask a doctor or pharmacist before use if you are'' and is
followed by all drug-drug and drug-food interaction warnings. Lil'
suggested this information need not appear on the outside of the carton
because there are generally no pharmacies located in the retail
environment in which most OTC convenience-size packages are sold.
FDA disagrees. FDA believes that this information must appear on
the outside of the carton to ensure it is accessible to consumers at
the point of purchase. For certain OTC drug products, the warnings
under this heading inform consumers not to take the product if they are
taking sedatives or tranquilizers. FDA believes that most consumers
will know if they are taking a sedative or tranquilizer and, thus, can
make the informed decision to avoid a product that has this warning,
even when the purchase occurs in a non-pharmacy outlet.
3. Section 201.66(c)(5)(vi): This section requires the warning
subheading ``When using this product'' and provides information on the
side effects that may occur and substances or machinery to avoid when
using the product. FDA believes, as Lil' suggested, that all
information about potential drowsiness, avoiding alcohol, and using
care when driving a motor vehicle or operating machinery must appear in
the external package labeling.
[[Page 74478]]
However, FDA acknowledges there may be other information that
appears under this subheading that could appear on the inside package
labeling of convenience-size packages without jeopardizing public
health or undermining the basic purpose of Sec. 201.66. Examples
include information about not using the product at certain times or
certain side effects that may occur (e.g., stomach discomfort, cramps).
FDA invites specific comments and suggestions, with supportive reasons,
about other information under this subheading that could appear on the
inside package labeling or should remain on the outside of the package.
4. Section 201.66(c)(5)(vii): This section requires the warning
subheading ``Stop use and ask a doctor if'' and provides information on
any signs of toxicity or other reactions that would necessitate
immediately discontinuing use of the product. Lil' stated that, based
on the dosing limitations of convenience-size packages, this
information could be adequately addressed inside the carton.
FDA generally agrees. Most of the signs of toxicity described in
this section are expected to occur when the product has been used for
more than one or two doses. However, for some products, this section
requires a specific warning about potential allergic reactions that
could occur even after one or two doses and informs consumers to seek
medical help right away. FDA believes this allergy warning information
describes a condition that may be serious and that could influence a
consumer's decision at the point of purchase. Therefore, FDA is
requiring that any warning information about allergic reactions
required under this subheading must continue to appear on the outside
package.
5. Section 201.66(c)(5)(viii): This section requires warnings that
do not fit within one of the paragraphs in Sec. 201.66(c)(5)(i)
through (c)(5)(vii), (c)(5)(ix), and (c)(5)(x). An example of such a
warning is ``* * * Do not puncture or incinerate. * * *'' for drugs in
dispensers pressurized by gaseous propellants set forth in 21 CFR
369.21. Lil' suggested that this section could be addressed case-by-
case using the same criteria as used for the other sections. FDA
believes that there is little labeling in this category that would
apply to convenience-size packages and that most, if not all, of the
information that would appear under this heading could appear on the
inside package labeling. There may be instances, perhaps in the future,
in which a warning required under this section should appear on the
outside Drug Facts label. FDA invites specific comment on which
warnings included in this category, if any, should be kept on the
outside package and how FDA should address the importance of future
warnings required under this section.
6. Section 201.66(c)(5)(ix): This section requires the pregnancy/
breast-feeding warning set forth in Sec. 201.63(a) and the third
trimester warning set forth in Sec. 201.63(e) or in certain approved
drug applications. Lil' acknowledged that this information should
continue to appear on the external package labeling. FDA concurs that
this information is needed at the point of purchase and must appear in
the outer package labeling.
7. Section 201.66(c)(5)(x): This section requires the warning to
``Keep out of reach of children'' and the accidental overdose/ingestion
warnings set forth in Sec. 330.1(g). Lil' provided a number of reasons
why this information could appear inside the package. Lil' stated that
convenience-size OTC products are usually not purchased, taken home,
and stored. Instead, said Lil', they are usually consumed shortly after
purchase to satisfy a consumer's immediate need. Lil' added that it is
not industry practice to sell OTC drug products to children, which
reduces the likelihood of a child possessing a convenience-size
package. Finally, Lil' asserted an overdose is extremely unlikely given
the dosing limitations in a ``convenience-size'' package.
FDA agrees. Under Sec. 330.1(g), FDA has authority to grant an
exemption from these warnings where appropriate upon petition. FDA is
not inclined to use this authority to exempt convenience-size products
from these warnings altogether. However, we are proposing to allow
these warnings to appear inside OTC convenience-size packages on either
an insert or inner-package labeling.
8. Section 201.66(c)(6): This section requires the Drug Facts
labeling to include the directions for use described in an applicable
OTC drug monograph or approved drug application. The regulations in 21
CFR 201.5 describe adequate directions for use for drugs as
``directions under which the layman can use a drug safely and for the
purposes for which it is intended.'' Directions can include: Uses of
the drug; quantity of the dose (based on age); frequency, duration,
time, and route or method of administration; preparation for use (i.e.,
shaking, dilution).
Lil' stated that, for one- or two-dose products, having the
directions for use at the point of purchase is less important because
of the following:
The package will not contain enough product for continued
dosing and overdose, and
The consumer's likely intent is to take the product
immediately.
FDA believes that for all OTC drugs, including convenience-size
packages, it is preferable for all of the directions information to
appear in one location to best inform consumers how to use the product.
Because the directions may be lengthy, FDA is proposing that this
information appear in full on the inside package labeling for OTC
convenience-size drug products. However, FDA believes that it is
important to inform consumers that the directions are inside the
package. In addition, FDA believes that it is also important to inform
consumers at the point of purchase that the product is not intended for
use in certain age groups. Therefore, FDA is proposing that the
following information appear in the outer package labeling in 7-point
bold type size under the heading Directions: ``See inside for
directions. This product is not for children under [insert appropriate
age] without asking a doctor.'' FDA believes this approach strikes a
balance between package size and the need for information about age
limitations at the point of purchase. This will also enable consumers
to make appropriate purchase decisions at the point of purchase and use
OTC convenience-size packages safely for their intended purposes.
9. Section 201.66(c)(7): This section requires, under the heading
``Other information,'' additional information that is not included
under Sec. 201.66(c)(2) through (c)(9), but which is required by or is
made optional under an applicable OTC drug monograph, other OTC drug
regulation, or is included in the labeling of an approved drug
application. Examples include: (1) Required information about certain
ingredients in OTC drug products (e.g., sodium in Sec. 201.64(c)), (2)
phenylalanine/aspartame content required by Sec. 201.21(b), if
applicable, and (3) additional information authorized to appear under
this heading, such as the storage temperature and tamper evident
statement. Lil' suggested that any reference to sodium, aspartame, or
other special ingredients still appear on the outer labeling, while all
other statements in this section appear on the inside package labeling.
Lil' noted that the contents of convenience-size packages are
customarily consumed upon purchase, lessening the need for storage and
temperature warnings.
FDA agrees with Lil', except for the location of the tamper evident
statement. The regulations in 21 CFR
[[Page 74479]]
211.132(c) require the tamper-evident statement to be prominently
placed on the package in such a manner that it will be unaffected if
the tamper-evident feature of the package is breached or missing. To
meet this requirement, FDA has determined that the tamper-evident
statement must appear on the outer package labeling. However, the
tamper-evident statement is not required to appear within the Drug
Facts portion of the labeling and may appear elsewhere on the outer
packaging.
10. Section 201.66(c)(9): This section requires the heading
``Questions or Comments,'' followed by the telephone number of a source
to answer questions on the product. Lil' stated that, presumably, this
section is related to questions and comments about continued
consumption of a product. Given the one- and two-dose limitation and
the consumer's usual intent for immediate consumption of the product,
Lil' contended that this section may be adequately presented inside the
package. FDA agrees that this information may appear on the inside
labeling of the package.
D. Package Inserts and Inner-Labeling
FDA is also considering different ways to present the Drug Facts
labeling inside the package. Currently, FDA favors the following
options: (1) A package insert that contains complete Drug Facts
labeling in accord with Sec. 201.66(d)(1) through (d)(9), including
all the information exempted from the outside labeling under proposed
Sec. 201.66(b)(5) and (d)(11); or (2) permitting the Drug Facts
labeling that is not required to appear on the outside container or
wrapper to be printed on the inside of the outer container or wrapper
in the required Drug Facts order. FDA believes the package insert
containing the complete Drug Facts labeling is the preferred approach
because it will be complete and less confusing to consumers. However,
FDA is aware that information can be printed on the inside of cardboard
and other containers, and Lil' mentioned inner-package printing as a
possible approach. FDA's major concern about labeling appearing on the
inside of the outer container or wrapper is whether consumers can (or
will) open the package without tearing the part that contains the
labeling, and the ease with which the information can be read once the
outer container or wrapper is opened. FDA believes if this second
option is allowed, it should be conditioned upon the package having an
easy way to be opened (e.g., a pull tab), so that when the package is
opened, the inside labeling information is readily exposed and can be
easily read. FDA invites specific comment on the comparative costs of
these methods of providing labeling inside the outer container, and
whether there are packaging techniques readily available that would
allow for these convenience-size packages to be easily opened without
tearing the part of the package that contains labeling information. FDA
also invites comment on other ways that Drug Facts labeling information
could be presented inside a convenience-size package and comparative
costs with the two methods discussed above.
E. Information Available on the Outside Container or Wrapper
FDA discusses in section II of this document its basis for
proposing to modify labeling for convenience-size OTC drug packages.
FDA believes that convenience-size OTC drug packages, as defined by
limited dose and container size in section III of this document, can
adequately meet public health needs without presenting on the outer
package all of the information required by the Drug Facts Rule. FDA
does not believe that such modifications can be justified for larger
packages, which contain enough medication for repetitive dosing and/or
have sufficient available labeling space to bear all of the information
required under the Drug Facts Rule. FDA is seeking feedback about
whether the information proposed for the outer package, and available
at the time of purchase, is adequate to support safe and effective use
of the dose of medication to be allowed in a convenience-size OTC drug
package. FDA is seeking comment on whether there should be an
additional requirement that provides for full product information to be
available at the point of purchase (e.g., a shelf-talker or extender,
or a tear-off Drug Facts information sheet) if some of the Drug Facts
information is not available on the outer package.
F. Summary of Optional Alternative Labeling for Convenience-Size
Packages
In summary, based on the previous discussion, it is FDA's view that
as much of the Drug Facts labeling as possible should appear on the
outside container or wrapper of convenience-size packages and be
available to consumers at the point of purchase. FDA recommends that,
when possible, manufacturers of convenience-size OTC drug packages as
described in proposed Sec. 201.66(b)(5) try to fit all of the Drug
Facts labeling on the outer container or wrapper using the modified
format currently available in Sec. 201.66(d)(10). However, given the
unique status of convenience-size OTC drug products--including the
reduced risks associated with their limited contents, the ``size
sensitive'' retail setting in which they are sold, and the fact that
many are purchased for immediate consumption--FDA is proposing to allow
certain Drug Facts information to appear inside a convenience-size OTC
drug package. Accordingly, FDA is proposing a new Sec. 201.66(d)(11)
(existing Sec. 201.66(d)(11) is being redesignated as Sec.
201.66(d)(12)) to state that OTC drug products that meet the
convenience-size package definition in Sec. 201.66(b)(5) may use an
optional alternative version of the Drug Facts labeling in which
certain information otherwise required to appear on the outside wrapper
or container of an OTC drug product under Sec. 201.66(c)(5)(vi),
(c)(5)(vii), (c)(5)(viii), (c)(5)(x), (c)(6), (c)(7), and (c)(9) may
appear inside the package. FDA further proposes, under Sec.
201.66(d)(11), that the Drug Facts labeling on the outside container or
wrapper contain the statement ``See information inside before using,''
in bold italic type no smaller than 7-point size. This statement would
appear either immediately after and on the same line as the ``Drug
Facts'' title, or immediately beneath the ``Drug Facts'' title and
above the horizontal hairline that would otherwise immediately follow
the ``Drug Facts'' title. FDA is also proposing that the following
information appear in the outer package labeling in 7-point bold type
size under the heading Directions: ``See inside for directions. This
product is not for children under [insert appropriate age] without
asking a doctor.'' FDA invites specific comment on this wording and
format and other wording or formats that would convey the same message.
FDA is also considering different ways to present the exempted Drug
Facts labeling inside the OTC drug package. Currently, FDA favors the
following options: (1) A package insert that contains complete Drug
Facts labeling in accord with Sec. 201.66(d)(1) through (d)(9),
including all the information exempted from the outside labeling under
proposed Sec. 201.66(b)(5) and (d)(11); or (2) permitting the Drug
Facts labeling that is not required to appear on the outside container
or wrapper to be printed on the inside of the outer container or
wrapper in the required Drug Facts order.
IV. Legal Authority
This rule, if finalized, would not require OTC drug product
labeling to bear new kinds of information. Rather, the rule would
modify the format of the current OTC Drug Facts labeling to
[[Page 74480]]
accommodate the unique circumstances associated with the packaging,
marketing, purchase, and use of ``convenience size'' OTC drug packages.
FDA's legal authority to modify Sec. 201.66 arises from the same
authority under which FDA initially issued the regulation, including 21
CFR parts 201, 301, 502, 505, 507, and 701 of the act. This authority
is described in detail in the Federal Register of February 27, 1997 (62
FR 9042 through 9043).
V. Analysis of Impacts
The economic impact of the Drug Facts Rule was discussed in the
final rule (64 FR 13254 at 13276). That discussion included estimates
of the increased costs for small package products that could not fit
the new Drug Facts labeling to enlarge the package or to use other
labeling techniques (e.g., risers) to fit the information. FDA
estimated that 6.4 percent of all shelf-keeping units (SKUs) had labels
that either would not fit or were indeterminate (too close to call)
and, thus, might require a new packaging configuration to accommodate
the new format (64 FR 13254 at 13283). Convenience size packages were
included in the estimate, as well as other small package sizes. The
Consumer Healthcare Products Association has stated that ``convenience-
sizes'' represent less than 1 percent of the retail market (Ref. 3).
FDA has examined the impacts of the proposed rule under Executive
Order 12866, the Regulatory Flexibility Act (5 U.S.C. 601-612), and the
Unfunded Mandates Reform Act of 1995 (Public Law 104-4). Executive
Order 12866 directs agencies to assess all costs 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). Under the Regulatory
Flexibility Act, if a rule has a significant economic impact on a
substantial number of small entities, FDA must analyze regulatory
options that would minimize any significant impact of the rule on small
entities.
Section 202(a) of the Unfunded Mandates Reform Act requires that
agencies prepare a written statement of anticipated costs and benefits
before proposing any rule that may result in an expenditure in any one
year by State, local, and tribal governments, in the aggregate, or by
the private sector, of $100 million (adjusted annually for inflation).
FDA has concluded that this proposed rule is consistent with the
principles set out in Executive Order 12866 and in these two statutes.
This proposed rule is not a significant regulatory action as defined by
the Executive order and so is not subject to review under the Executive
order. As discussed in this section, FDA has determined that this
proposed rule will not have a significant economic impact on a
substantial number of small entities. The Unfunded Mandates Reform Act
does not require FDA to prepare a statement of costs and benefits for
this proposed rule, because the proposed rule is not expected to result
in any 1-year expenditure that would exceed $100 million adjusted for
inflation. The current threshold after adjustment for inflation is $115
million, using the most current (2003) Implicit Price Deflator for the
Gross Domestic Product.
The purpose of this proposed rule is to define OTC ``convenience-
size'' drug products and to provide Drug Facts labeling alternatives
for these products that would enable manufacturers, repackers, or
distributors to provide certain labeling information on the inside of
the package, either in a package insert or by internal package
printing. This alternative approach would apply only to packages that
meet the proposed package size and dose limitations. The economic
impact for relabeling OTC drug products was previously addressed in the
final rule. This proposed rule provides an alternative labeling
approach to accommodate the Drug Facts labeling requirements.
In the final rule (64 FR 13254 at 13283), FDA estimated 4.5 percent
of all OTC drug SKUs may require increased package sizes to accommodate
the new Drug Facts format. The one-time cost to industry was about
$38.1 million and the annually recurring costs were estimated to be
$11.5 million for the added package and label materials (64 FR 13254 at
13284). The cost analysis included a number of alternative package
configurations, including adding an outer carton, a fifth panel (a back
panel), enlarging the package, and adding a peel-back or two-ply label
using existing or retooled packaging lines. Package inserts or double-
sided printing were not considered in that analysis. In some
circumstances these two alternatives could be less costly than the
others included in the analysis. This proposed rule allows
manufacturers additional flexibility to choose the least costly
packaging alternative to meet their marketing requirements but would
probably have little effect on the overall cost of relabeling. In the
original analysis FDA did not identify which of the small package sizes
that could not accommodate the Drug Facts format would be considered
convenience sized packages. As such, we cannot breakout the estimated
costs from the Drug Facts Rule (64 FR 13254 at 13276 to 13285) that
applied to convenience-sized packaged products.
Because this proposed rule does not mandate changes to packaging,
but increases manufacturers choice of package configurations FDA
certifies that this proposed rule will not have a significant economic
impact on a substantial number of small entities. No further analysis
is required.
VI. Paperwork Reduction Act of 1995
FDA tentatively concludes that the proposed labeling requirements
in this document are not subject to review by the Office of Management
and Budget because they do not constitute a ``collection of
information'' under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501
et seq.). Rather, the proposed labeling requirements are a ``public
disclosure of information originally supplied by the Federal government
to the recipient for the purpose of disclosure to the public'' (5 CFR
1320.3(c)(2)).
VII. Environmental Impact
FDA has determined under 21 CFR 25.31(a) 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. Federalism
FDA has analyzed this proposed rule in accordance with the
principles set forth in Executive Order 13132. FDA has determined that
the proposed rule, if finalized as proposed, would have a pre-emptive
effect on State law. Section 4(a) of the Executive Order requires
agencies to ``construe * * * a Federal statute to preempt State law
only where the statute contains an express preemption provision or
there is some other clear evidence that the Congress intended
preemption of State law, or where the exercise of State authority
conflicts with the exercise of Federal authority under the Federal
statute.'' Section 751 of the act (21 U.S.C. 379r) is an express pre-
emption provision. Section 751(a) of the act provides that: ``* * * no
State or political subdivision of a State may establish or continue in
effect any requirement-- * * * (1) that relates to the regulation of a
drug that
[[Page 74481]]
is not subject to the requirements of section 503(b)(1) or
503(f)(1)(A); and (2) that is different from or in addition to, or that
is otherwise not identical with, a requirement under this Act, the
Poison Prevention Packaging Act of 1970 (15 U.S.C. 1471 et seq.), or
the Fair Packaging and Labeling Act (15 U.S.C. 1451 et seq.). * * *''
Currently, this provision operates to pre-empt States from imposing
requirements related to the regulation of nonprescription drug
products. (See section 751(b), (c), (d), and (e) of the act for the
scope of the express pre-emption provision, the exemption procedures,
and the exceptions to the provision.) This proposed rule, if finalized
as proposed, would amend the format and content requirements for the
labeling for OTC convenience size drug packages. Although any final
rule would have a pre-emptive effect, in that it would preclude States
from issuing requirements related to the labeling of OTC convenience
size drug products that are different from or in addition to, or not
otherwise identical with a requirement in the final rule, this
preemptive effect is consistent with what Congress set forth in section
751 of the act. Section 751(a) of the act displaces both State
legislative requirements and State common law duties. FDA also notes
that even where the express pre-emption provision is not applicable,
implied preemption may arise (See Geier v. American Honda Co., 529 US
861 (2000)).
FDA believes that the pre-emptive effect of the proposed rule, if
finalized as proposed, would be consistent with Executive Order 13132.
Section 4(e) of the Executive order provides that ``when an agency
proposes to act through adjudication or rulemaking to preempt State
law, the agency shall provide all affected State and local officials
notice and an opportunity for appropriate participation in the
proceedings.'' FDA is providing an opportunity for State and local
officials to comment on this rulemaking.
IX. Request for Comments
Interested persons may submit to the Division of Dockets Management
(see ADDRESSES) written or electronic comments regarding this document
and FDA's economic impact determination. Three copies of all written
comments are to be submitted. Individuals submitting written comments
or anyone submitting electronic comments may submit one copy. Comments
are to be identified with the docket number found in brackets in the
heading of this document and may be accompanied by a supporting
memorandum or brief. Received comments may be seen in the Division of
Dockets Management between 9 a.m. and 4 p.m., Monday through Friday.
X. Proposed Effective Date
FDA is proposing that any final rule that may issue based on this
proposal for OTC convenience-size drug products become effective 18
months after its date of publication in the Federal Register. FDA is
proposing that the compliance date for OTC convenience-size drug
products with annual sales less than $25,000 would be 24 months after
the date of publication in the Federal Register. The compliance date
for all other OTC convenience-size drug products would be 18 months
after the date of publication in the Federal Register.
XI. References
The following references are on display in the Division of Dockets
Management (see ADDRESSES) and may be seen by interested persons
between 9 a.m. and 4 p.m., Monday through Friday.
1. Comment No. CP1, Docket Number 2001P-0207.
2. Letter from S. Galson, FDA, to J. M. Nikrant, Lil' Drug Store
Products, Inc., coded LET 1, Docket Number 2001P-0207.
3. Letter from R. W. Soller, CHPA, to C. Ganley, FDA, dated October
3, 2000, Docket Number 1998N-0337.
List of Subjects in 21 CFR Part 201
Drugs, Labeling, Reporting and recordkeeping requirements.
0
Therefore, under the Federal Food, Drug, and Cosmetic Act and under
authority delegated to the Commissioner of Food and Drugs, it is
proposed that 21 CFR part 201 be amended as follows:
PART 201--LABELING
0
1. The authority citation for 21 CFR part 201 continues to read as
follows:
Authority: 21 U.S.C. 321, 331, 351, 352, 353, 355, 358, 360,
360b, 360gg-360ss, 371, 374, 379e; 42 U.S.C. 216, 241, 262, 264.
0
2. Section 201.66 is amended by redesignating paragraphs (b)(5) through
(b)(12) as paragraphs (b)(7) through (b)(14), respectively, and by
redesignating paragraph (d)(11) as paragraph (d)(12), and by adding new
paragraphs (b)(5), (b)(6), and (d)(11) to read as follows:
Sec. 201.66 Format and content requirements for over-the-counter
(OTC) drug product labeling.
* * * * *
(b) * * *
(5) Convenience-size package means a package containing no more
than two doses, as defined in paragraph (b)(6) of this section, of an
OTC drug product that, because of its limited available labeling space,
both qualifies for the modified labeling set forth in paragraph (d)(10)
of this section and would require more than 60 percent of its total
surface area available to bear labeling to meet the labeling
requirements set forth in paragraph (d)(10). This definition does not
include OTC drug packages that contain ipecac syrup or activated
charcoal.
(6) Dose means a maximum single-serving for an adult (or child for
products marketed only for children) as specified in the product's
directions for use. For products marketed with directions for use for
both adults and children, dose means a maximum single serving for a
child as specified in the product's direction for use.
* * * * *
(d) * * *
(11) Convenience-size packages. The labeling of products that meet
the convenience-size package definition in paragraph (b)(5) of this
section shall appear in accord with either paragraph (d)(10) or
paragraph (d)(11)(i) of this section.
(i) The outside container or wrapper of an OTC convenience-size
drug product labeled under this section shall comply in all respects
with paragraph (d)(10) of this section, except as modified by
paragraphs (d)(11)(i)(A) through (d)(11)(i)(G) and paragraph
(d)(11)(ii) of this section.
(A) All information required by paragraph (c)(5)(vi) of this
section, including the statement ``do not use more than directed,'' may
appear on the inside of the OTC drug package in accord with paragraph
(d)(11)(ii) of this section, except any information about potential
drowsiness, avoiding alcohol, and using caution when driving a motor
vehicle or operating machinery, which shall appear on the outside
container or wrapper in accord with paragraph (d)(10) of this section.
(B) All information required by paragraph (c)(5)(vii) of this
section may appear on the inside of the OTC drug package in accord with
paragraph (d)(11)(ii) of this section, except any information about a
potential allergic reaction, which shall appear on the outside
container or wrapper in accord with paragraph (d)(10) of this section.
(C) All information required by paragraph (c)(5)(x) of this
section, including the statement ``Keep out of reach of children'' and
the accidental overdose/ingestion warnings set forth
[[Page 74482]]
under Sec. 330.1(g) of this chapter, may appear on the inside of the
OTC drug package in accord with paragraph (d)(11)(ii) of this section.
(D) All information required by paragraph (c)(6) of this section
may appear on the inside of the OTC drug package in accord with
paragraph (d)(11)(ii) of this section. If any such information is
placed inside the package, the outside container or wrapper shall state
the following in bold italic type no smaller than 7-point under the
heading ``Directions'': ``See inside for directions. This product is
not for children under [insert appropriate age] without asking a
doctor.''
(E) All information required by paragraph (c)(7) of this section
may appear on the inside of the OTC drug package in accord with
paragraph (d)(11)(ii) of this section, except: the tamper evident
statement required by Sec. 211.132(c), which must appear on the
outside container or wrapper, but need not necessarily appear in the
Drug Facts box or similar enclosure; andall information required by
paragraphs (c)(7)(i) and (c)(7)(ii) of this section, which shall appear
on the outside container or wrapper in accord with paragraph (d)(10) of
this section.
(F) All information required by or authorized under paragraph
(c)(9) of this section may appear on the inside of the OTC drug package
in accord with paragraph (d)(11)(ii) of this section.
(G) In the event that any information is placed inside an OTC drug
package under the authority of paragraphs (d)(11)(i)(A) through
(d)(11)(i)(G), the outside container or wrapper of that package shall
state the following in bold italic type no smaller than 7-point: ``See
information inside before using.'' This statement shall appear either
immediately after and on the same line as the ``Drug Facts'' title or
immediately beneath the ``Drug Facts'' title and above the horizontal
hairline that would otherwise immediately follow this title.
(ii) Any and all labeling included inside any OTC drug package or
wrapper to comply with any provision of paragraph (d)(11)(i) of this
section shall appear in one and only one of the following ways:
(A) In a package insert that contains the complete Drug Facts
labeling as defined in paragraph (b)(12) of this section printed in
accordance with the specifications in paragraphs (d)(1) through (d)(9)
of this section, regardless of whether some of this information also
appears on the outside container or wrapper; or
(B) All Drug Facts labeling as defined in paragraph (b)(12) of this
section that does not appear on the outside container or wrapper shall
be printed on the inside of the outside container or wrapper in the
order listed in paragraph (d)(11) of this section and shall appear in
accordance with the specifications in paragraphs (d)(1) through (d)(9)
or in paragraph (d)(10). The title ``Drug Facts (continued)'' shall
appear at the top of each subsequent panel containing such information.
When any Drug Facts labeling is printed on the inside of the outside
container or wrapper, the container or wrapper shall have an easy way
to be opened (e.g., a pull tab or something similar) so that the
package or wrapper on which the information is printed is unlikely to
be torn or destroyed, and the labeling information is readily exposed
and can be easily read.
Dated: November 20, 2006.
Jeffrey Shuren,
Assistant Commissioner for Policy.
[FR Doc. E6-21019 Filed 12-11-06; 8:45 am]
BILLING CODE 4160-01-S